Search results for: herbal drug of depression

Authors: Eitedal Daoud, Reda M.Daoud, Khaled Abdel-Wahhab, Maha M.Saber, Lobna Saber

Abstract:

Background: Cis-platin is a widely used chemotherapeutic drug to treat many malignant disorders including head and neck malignancies. Oto-nephrotxicity is an important and dose - limiting side effect of cis - platin therapy. Nowadays, more attention had been paid to oto-toxicity caused with cis-platin. Aim of the Work: This study was designed to investigate the potential protective effect of Whey protein (WP) against cis-platin induced ototoxicity compared to the effect of N-acetylcysteine (NAC) in rats. Methodology: Male albino rats were randomly divided into 6 groups: untreated rats (control), rats orally treated with whey protein (1g/kg b.w/day) for seven executive days, rats treated orally with N-acetylcysteine (500 mg/kgb.w /day) for seven executive days, rates intoxicated intraperitoneal (ip) with cis- platin (10 mg/kgb.w. once), rats treated with whey protein (1g/kgb.w./day) for seven executive days) followed by one injection (ip) of cis-platin(10 mg/kg b.w.) one hour after the last oral administration of whey protein, rats treated with N- acetylcysteine (for seven executive days followed by one injection (ip) of cis-platin (10 mg/kgb.w) one hour after the last oral administration of N-acetylcysteine. The organ of Corti, the stria vascularis and spiral ganglia were visualized by light microscopy at different magnifications. Results: Cis-platin intoxicated animals showed a significant decrease in serum level of total antioxidant capacity (TAC),with inhibition in the activity of serum glutathione-s transferase(GST) and paraoxonnase-1 (PON-1) in comparison with control. Group treated with either NAC or WP with cis-platin showed significant elevation in the activity of both GST & PON-1 with increased serum level of TAC when compared with cis-platin intoxicated rats. Animals treated with NAC or WP with cis-platin compared to those treated with cis-platin alone showed marked degree of improvement towards control rats as there was significant drop in the serum level of cortecosterone, nitric oxide (NO), and melandialdehyde (MDA).Histopathologic, in NAC pretreated group there was no changes in stria vascularis or spiral ganglia. In group pretreated with WP, there was no histopathologic alteration detected in the organ of Corti and Reissers membrane but oedema and haemorrhage were founded in the stria vascularis in small focal manner. Conclusion: Our finding showed that Whey protein is a natural dietary supplement product proved its ability of protection of anti-oxidant system and the cochlea against cis-platin induced ototoxicity.

Keywords: anti-oxidant, cis-platin, N-acetylcysteine, ototoxicity, whey protein

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Authors: L. Sudbury-Riley, P. Hunter-Jones, L. Menzies, M. Pyrah, H. Knight

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Just as manufacturing firms aim for zero defects, service providers strive to avoid service failures where customer expectations are not met. However, because services comprise unique human interactions, service failures are almost inevitable. Consequently, firms focus on service recovery strategies to fix problems and retain their customers for the future. Because a hospice offers care to terminally ill patients, it may not get the opportunity to correct a service failure. This situation makes the identification of what hospice users really need and want, and to ascertain perceptions of the hospice’s service delivery from the user’s perspective, even more important than for other service providers. A well-documented and fundamental barrier to improving end-of-life care is a lack of service quality measurement tools that capture the experiences of user’s from their own perspective. In palliative care, many quantitative measures are used and these focus on issues such as how quickly patients are assessed, whether they receive information leaflets, whether a discussion about their emotional needs is documented, and so on. Consequently, quality of service from the user’s perspective is overlooked. The current study was designed to overcome these limitations by adapting service blueprinting - never before used in the hospice sector - in order to undertake a ‘deep-dive’ to examine the impact of hospice services upon different users. Service blueprinting is a customer-focused approach for service innovation and improvement, where the ‘onstage’ visible service user and provider interactions must be supported by the ‘backstage’ employee actions and support processes. The study was conducted in conjunction with East Cheshire Hospice in England. The Hospice provides specialist palliative care for patients with progressive life-limiting illnesses, offering services to patients, carers and families via inpatient and outpatient units. Using service blueprinting to identify every service touchpoint, in-depth qualitative interviews with 38 in-patients, outpatients, visitors and bereaved families enabled a ‘deep-dive’ to uncover perceptions of the whole service experience among these diverse users. Interviews were recorded and transcribed, and thematic analysis of over 104,000 words of data revealed many excellent aspects of Hospice service. Staff frequently exceed people’s expectations. Striking gratifying comparisons to hospitals emerged. The Hospice makes people feel safe. Nevertheless, the technique uncovered many areas for improvement, including serendipity of referrals processes, the need for better communications with external agencies, improvements amid the daunting arrival and admissions process, a desperate need for more depression counselling, clarity of communication pertaining to actual end of life, and shortcomings in systems dealing with bereaved families. The study reveals that the adapted service blueprinting tool has major advantages of alternative quantitative evaluation techniques, including uncovering the complex nature of service user’s experiences in health-care service systems, highlighting more fully the interconnected configurations within the system and making greater sense of the impact of the service upon different service users. Unlike other tools, this in-depth examination reveals areas for improvement, many of which have already been implemented by the Hospice. The technique has potential to improve experiences of palliative and end-of-life care among patients and their families.

Keywords: hospices, end-of-life-care, service blueprinting, service delivery

Procedia PDF Downloads 177

Authors: Wiesława Klimek-Piotrowska, Mateusz K. Hołda, Mateusz Koziej, Katarzyna Piątek, Jakub Hołda

Abstract:

Introduction: The coronary sinus venous system (CSVS), which has always been overshadowed by the coronary arterial tree, has recently begun to attract more attention. Since it is a target for clinicians the knowledge of its anatomy is essential. Cardiac resynchronization therapy, catheter ablation of cardiac arrhythmias, defibrillation, perfusion therapy, mitral valve annuloplasty, targeted drug delivery, and retrograde cardioplegia administration are commonly used therapeutic methods involving the CSVS. The great variability in the course of coronary veins and tributaries makes the diagnostic and therapeutic processes difficult. Our aim was to investigate detailed anatomy of most common clinically used CSVS`s structures: the coronary sinus with its ostium, great cardiac vein, posterior vein of the left ventricle, middle cardiac vein and oblique vein of the left atrium. Methodology: This is a prospective study of 70 randomly selected autopsied hearts dissected from adult humans (Caucasian) aged 50.1±17.6 years old (24.3% females) with BMI=27.6±6.7 kg/m2. The morphology of the CSVS was assessed as well as its precise measurements were performed. Results: The coronary sinus (CS) with its ostium was present in all hearts. The mean CS ostium diameter was 9.9±2.5mm. Considered ostium was covered by its valve in 87.1% with mean valve height amounted 5.1±3.1mm. The mean percentage coverage of the CS ostium by the valve was 56%. The Vieussens valve was present in 71.4% and was unicuspid in 70%, bicuspid in 26% and tricuspid in 4% of hearts. The great cardiac vein was present in all cases. The oblique vein of the left atrium was observed in 84.3% of hearts with mean length amounted 20.2±9.3mm and mean ostium diameter 1.4±0.9mm. The average length of the CS (from the CS ostium to the Vieussens valve) was 31.1±9.5mm or (from the CS ostium to the ostium of the oblique vein of the left atrium) 28.9±10.1mm and both were correlated with the heart weight (r=0.47; p=0.00 and r=0.38; p=0.006 respectively). In 90.5% the ostium of the oblique vein of the left atrium was located proximally to the Vieussens valve, in remaining cases was distally. The middle cardiac vein was present in all hearts and its valve was noticed in more than half of all the cases (52.9%). The posterior vein of the left ventricle was observed in 91.4% of cases. Conclusions: The CSVS is vastly variable and none of basic hearts parameters is a good predictor of its morphology. The Vieussens valve could be a significant obstacle during CS cannulation. Caution should be exercised in this area to avoid coronary sinus perforation. Because of the higher incidence of the presence of the oblique vein of the left atrium than the Vieussens valve, the vein orifice is more useful in determining the CS length.

Keywords: cardiac resynchronization therapy, coronary sinus, Thebesian valve, Vieussens valve

Procedia PDF Downloads 282

Authors: M. M. Essa, S. Subash, M. Akbar, S. Al-Adawi, A. Al-Asmi, G. J. Guillemein

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Transgenic (tg) mice which contain an amyloid precursor protein (APP) gene mutation, develop extracellular amyloid beta (Aβ) deposition in the brain, and severe memory and behavioral deficits with age. These mice serve as an important animal model for testing the efficacy of novel drug candidates for the treatment and management of symptoms of Alzheimer's disease (AD). Several reports have suggested that oxidative stress is the underlying cause of Aβ neurotoxicity in AD. Date palm fruits contain very high levels of antioxidants and several medicinal properties that may be useful for improving the quality of life in AD patients. In this study, we investigated the effect of dietary supplementation of Omani date palm fruits on the memory, anxiety and learning skills along with inflammation in an AD mouse model containing the double Swedish APP mutation (APPsw/Tg2576). The experimental groups of APP-transgenic mice from the age of 4 months were fed custom-mix diets (pellets) containing 2% and 4% Date palm fruits. We assessed spatial memory and learning ability, psychomotor coordination, and anxiety-related behavior in Tg and wild-type mice at the age of 4-5 months and 18-19 months using the Morris water maze test, rota rod test, elevated plus maze test, and open field test. Further, inflammatory parameters also analyzed. APPsw/Tg2576 mice that were fed a standard chow diet without dates showed significant memory deficits, increased anxiety-related behavior, and severe impairment in spatial learning ability, position discrimination learning ability and motor coordination along with increased inflammation compared to the wild type mice on the same diet, at the age of 18-19 months In contrast, PPsw/Tg2576 mice that were fed a diet containing 2% and 4% dates showed a significant improvements in memory, learning, locomotor function, and anxiety with reduced inflammatory markers compared to APPsw/Tg2576 mice fed the standard chow diet. Our results suggest that dietary supplementation with dates may slow the progression of cognitive and behavioral impairments in AD. The exact mechanism is still unclear and further extensive research needed.

Keywords: Alzheimer's disease, date palm fruits, Oman, cognitive decline, memory loss, anxiety, inflammation

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Authors: Sanjay Singh, Parameswara Rao Vuddanda

Abstract:

The aim of the present study is study the factual benefit of nano size and surface coating of p-gp efflux inhibitor on enhancement of bioavailability of Berberine chloride (BBR); a p-gp substrate. In addition, 28 days sub acute oral toxicity study was also conducted to assess the toxicity of the formulation on chronic administration. BBR loaded polymeric nanoparticles (BBR-NP) were prepared by nanoprecipitation method. BBR NP were surface coated (BBR-SCNP) with the 1 % w/v of vitamin E TPGS. For bioavailability study, total five groups (n=6) of rat were treated as follows first; pure BBR, second; physical mixture of BBR, carrier and vitamin E TPGS, third; BBR-NP, fourth; BBR-SCNP and fifth; BBR and verapamil (widely used p-gp inhibitor). Blood was withdrawn at pre-set timing points in 24 hrs study and drug was quantified by HPLC method. In oral chronic toxicity study, total four groups (n=6) were treated as follows first (control); water, second; pure BBR, third; BBR surface coated nanoparticles and fourth; placebo BBR surface coated nanoparticles. Biochemical levels of liver (AST, ALP and ALT) and kidney (serum urea and creatinine) along with their histopathological studies were also examined (0-28 days). The AUC of BBR-SCNP was significantly 3.5 folds higher compared to all other groups. The AUC of BBR-NP was 3.23 and 1.52 folds higher compared to BBR solution and BBR with verapamil group, respectively. The physical mixture treated group showed slightly higher AUC than BBR solution treated group but significantly low compared to other groups. It indicates that encapsulation of BBR in nanosize form can circumvent P-gp efflux effect. BBR-NP showed pharmacokinetic parameters (Cmax and AUC) which are near to BBR-SCNP. However, the difference in values of T1/2 and clearance indicate that surface coating with vitamin E TPGS not only avoids the P-gp efflux at its absorption site (intestine) but also at organs which are responsible for metabolism and excretion (kidney and liver). It may be the reason for observed decrease in clearance of BBR-SCNP. No toxicity signs were observed either in biochemical or histopathological examination of liver and kidney during toxicity studies. The results indicate that administration of BBR in surface coated nanoformulation would be beneficial for enhancement of its bioavailability and longer retention in systemic circulation. Further, sub acute oral dose toxicity studies for 28 days such as evaluation of intestine, liver and kidney histopathology and biochemical estimations indicated that BBR-SCNP developed were safe for long use.

Keywords: bioavailability, berberine nanoparticles, p-gp efflux inhibitor, nanoprecipitation method

Procedia PDF Downloads 369

Authors: A. H. Taghdisi, M. Mirmohammadi, S. Kamali

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Evening primrose (Oenothera biennis L.) is a biennial and herbaceous and one of the most important species of medicinal plants in the world. due to the production of unsaturated fatty acids such as linoleic acid, alpha-linolenic acid, etc. in its seeds and roots, and compounds such as kaempferol in its leaves, Evening primrose has important medicinal efficiency such as reducing premenstrual problems, acceleration of wound healing, inhibiting platelet aggregation, sedation of cardiovascular diseases, and treatment of viral infections. The sap of the plant is used to treat warts, and the plant itself is used as a charm against mental and spiritual diseases and poisonous animals. Its leaves have significant antibacterial activity against yellow staphylococci. It is also used in the treatment of poisoning, especially the toxication caused by the consumption of alcoholic beverages, in the treatment of arteriosclerosis and diseases caused by liver cell insufficiency. Low germination and production speed are the problems of evening primrose growth and propagation. In the present study, extracts were obtained from four components (flowers, stems, seeds, leaves) of the evening primrose plant using the Soxhlet apparatus. To measure the antibacterial properties against MDR bacteria, microbial methods, including dilution, cultivation on a plate containing nutrient agar culture medium, and disc diffusion in agar, were performed using Staphylococcus aureus and Escherichia coli bacteria on all four extracts. The maximum antibacterial activity related to the dilution method was obtained in all extracts. In the plate culture method, antibacterial activity was obtained for all extracts in the nutrient agar medium. The maximum diameter of the non-growth halo was obtained in the disc diffusion method in agar in the leaf extract. The statistical analysis of the microbial part was done by one-way ANOVA test (SPSS). By comparing the amount of omega-3 in extracts of Iranian and foreign oils available in the market and the extracts extracted from evening primrose plant samples with gas chromatography, it is shown that the stem extract had the most omega-3 (oleic acid) and compared to the extract of the mentioned oils, it had the highest amount of omega-3 overall. Also, the amount of omega-3 in the extract of Iranian oils was much higher than in the extract of foreign oils. It should be noted that the extract of foreign oils had a more complete composition of omega-3 than the extract of Iranian oils.

Keywords: antibacterial activity, MDR bacteria, evening primrose, omega-3

Procedia PDF Downloads 81

Authors: Maneesha Pahlani, Najmin Sultana

Abstract:

A hospital is one of the most suitable places for acquiring an infection because it harbors a high population of virulent strains of microorganisms that may be resistant to antibiotics, especially the prevalence of Methicillin-Resistant Staphylococcus Aureus (MRSA) infections. The hospital-acquired infection has become a global challenge. In developed countries, healthcare-associated infections occur in 5-15% of hospitalized clients, affecting 9-37% of those admitted to intensive care units (ICU). A non-experimental descriptive study was conducted among 50 nursing officers working in a selected hospital in Bangalore to assess the nursing officers’ level of knowledge regarding the prevention and management of MRSA infections and to associate the pre-test knowledge mean scores of nursing officers with selected socio-demographic variables. Data was collected using a structured questionnaire consisting of socio-demographic data and a structured questionnaire on knowledge regarding the prevention and management of MRSA infections. The data was analyzed in terms of frequencies and percentages for the analysis of demographic variables and computing chi-square to determine the association between knowledge means scores and selected demographic variables. The study findings revealed that the nursing officer had an overall good level of knowledge (63.05%) regarding the prevention and management of MRSA infections, and there is no significant association found between the level of knowledge mean scores for prevention and management of MRSA infection with the selected socio-demographic variables. However, the categorization of knowledge items showed that the nursing officer must thoroughly receive education on correct guidance and information regarding MRSA infection control policy, including measures and practices on hygiene precautions and information regarding antibiotic resistance for effective nursing care to patients with MRSA infections. The conclusions drawn from the study findings showed that it is necessary that the nursing officer thoroughly receive education on correct guidance and information regarding MRSA infection control policy, including measures and practices on hygiene precautions and information regarding antibiotic resistance to provide effective nursing care to patients with MRSA infection as they constantly care for the patient who can be at risk for multi-drug resistance organisms to reduce the risk of MRSA infection in hospital care settings as well community settings.

Keywords: MRSA, nursing officers, knowledge, preventive and management

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Authors: Ana Carolina Kogawa, Selma Gutierrez Antonio, Hérida Regina Nunes Salgado

Abstract:

Rifaximin is an oral antimicrobial, gut - selective and not systemic with adverse effects compared to placebo. It is used for the treatment of hepatic encephalopathy, travelers diarrhea, irritable bowel syndrome, Clostridium difficile, ulcerative colitis and acute diarrhea. The crystalline form present in the rifaximin with minimal systemic absorption is α, being the amorphous form significantly different. Regulators are increasingly attention to polymorphisms. Polymorphs can change the form by altering the drug characteristics compromising the effectiveness and safety of the finished product. International Conference on Harmonization issued the ICH Guidance Q6A, which aim to improve the control of polymorphism in new and existing pharmaceuticals. The objective of this study was to obtain polymorphic forms of rifaximin employing recrystallization processes and characterize them by thermal analysis (thermogravimetry - TG and differential scanning calorimetry - DSC), X-ray diffraction, scanning electron microscopy and solubility test. Six polymorphic forms of rifaximin, designated I to VI were obtained by the crystallization process by evaporation of the solvent. The profiles of the TG curves obtained from polymorphic forms of rifaximin are similar to rifaximin and each other, however, the DTG are different, indicating different thermal behaviors. Melting temperature values of all the polymorphic forms were greater to that shown by the rifaximin, indicating the higher thermal stability of the obtained forms. The comparison of the diffractograms of the polymorphic forms of rifaximin with rifaximin α, β and γ constant in patent indicate that forms III, V and VI are formed by mixing polymorph β and α and form III is formed by polymorph β. The polymorphic form I is formed by polymorph β, but with a significant amount of amorphous material. Already, the polymorphic form II consists of polymorph γ, amorphous. In scanning electron microscope is possible to observe the heterogeneity of morphological characteristics of crystals of polymorphic forms among themselves and with rifaximin. The solubility of forms I and II was greater than the solubility of rifaximin, already, forms III, IV and V presented lower solubility than of rifaximin. Similarly, the bioavailability of the amorphous form of rifaximin is considered significantly higher than the form α, the polymorphic forms obtained in this work can not guarantee the excellent tolerability of the reference medicine. Therefore, studies like these are extremely important and they point to the need for greater requirements by the regulatory agencies competent about polymorphs analysis of the raw materials used in the manufacture of medicines marketed globally. These analyzes are not required in the majority of official compendia. Partnerships between industries, research centers and universities would be a viable way to consolidate researches in this area and contribute to improving the quality of solid drugs.

Keywords: electronic microscopy, polymorphism, rifaximin, solubility, X-ray diffraction

Procedia PDF Downloads 640

Authors: Hayley Lawrence, Nabi Shah, Sarah Dyer

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Aims: Lumbar punctures are a common bedside procedure performed in acute medicine. Published guidance exists on the standardised documentation of invasive procedures in order to reduce the risk of complications. The audit aim was to assess current standards of documentation in accordance with both the GMC and the National Standards for Invasive Procedures guidelines. A second cycle was conducted after introducing a standardised sticker created using current guidelines. This would assess whether the sticker improved documentation, aiming for 100% standard in each step of the procedure. Methods: An initial prospective audit of current practice was conducted over a 3-month period. Patients were identified by their presenting complaints and by colleagues assessing acute medical patients. Initial findings were presented locally, and a further prospective audit was conducted following the implementation of a standardised sticker. Results: 19 lumbar punctures were included in the first cycle and 13 procedures in the second. Pre-procedure documentation was collected for each cycle, whereby documentation of ‘Indication’ improved from 5.3% to 84.6%, ‘Consent’ from 84.2% to 100%, ‘Coagulopathy’ from 0% to 61.5%, ‘Drug Chart checked’ from 0% to 100%, ‘Position of patient’ from 26.3% to 100% and use of ‘Aseptic Technique’ from 83.3% to 100% from the first to the second cycle respectively. ‘Level of Doctor’ and ‘Supervision’ decreased from 53% to 31% and 53% to 46%, respectively, in the second cycle. Documentation of the procedure itself also demonstrated improvements, with ‘Level of Insertion’ 15.8% to 100%, ‘Name of Antiseptic Used’ 11.1% to 69.2%, ‘Local Anaesthetic Used’ 26.3% to 53.8%, ‘Needle Gauge’ 42.1% to 76.9%, ‘Number of Attempts’ 78.9% to 100% and ‘Traumatic/Atraumatic’ procedure 26.3% to 92.3%, respectively. A similar number of opening pressures were documented in each cycle at 57.9% and 53.8%, respectively, but its documentation was deemed ‘Not Applicable’ in a higher number of patients in the second cycle. Post-procedure documentation improved, with ‘Number of Samples obtained’ increasing from 52.6% to 92.3% and documentation of ‘Immediate Complications’ increasing from 78.9% to 100%. ‘Dressing Applied’ was poorly documented in the first cycle at 16.7%. This was not included on the standardised sticker, resulting in 0% documentation in the second cycle. Documentation of Clinicians’ Name and Bleep reduced from 63.2% to 15.4%, but when the name only was analysed, this increased to 84.6%. Conclusions: Standardised stickers for lumbar punctures do improve documentation and hence should result in improved patient safety. There is still room for improvement to reach 100% standard in each area, especially with respect to the clinician’s name and contact details being documented. Final adjustments will be made to the sticker before being included in a lumbar puncture kit, which will be made readily available in the acute medical wards. Future audits could be extended to include other common bedside procedures performed in acute medicine to ensure documentation of all these procedures reaches 100% standard.

Keywords: invasive procedure, lumbar puncture, medical record keeping, procedure checklist, procedure documentation, standardised documentation

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Authors: Najmin Sultana, Maneesha Pahlani

Abstract:

A hospital is one of the most suitable places for acquiring an infection because it harbors a high population of virulent strains of microorganisms that may be resistant to antibiotics, especially the prevalence of Methicillin-Resistant Staphylococcus Aureus (MRSA) infections. The hospital-acquired infection has become a global challenge. In developed countries, healthcare-associated infections occur in 5-15% of hospitalized clients, affecting 9-37% of those admitted to intensive care units (ICU). A non-experimental descriptive study was conducted among 50 nursing officers working in a selected hospital in bengaluru to assess the nursing officers’ level of knowledge regarding the prevention and management of MRSA infections and to associate the pre-test knowledge mean scores of nursing officers with selected socio-demographic variables. Data was collected using a structured questionnaire consisting of socio-demographic data and a structured questionnaire on knowledge regarding the prevention and management of MRSA infections. The data was analyzed in terms of frequencies and percentages for the analysis of demographic variables and computing chi-square to determine the association between knowledge means scores and selected demographic variables. The study findings revealed that the nursing officer had an overall good level of knowledge (63.05%) regarding the prevention and management of MRSA infections, and there is no significant association found between the level of knowledge mean scores for prevention and management of MRSA infection with the selected socio-demographic variables. However, the categorization of knowledge items showed that the nursing officer must thoroughly receive education on correct guidance and information regarding MRSA infection control policy, including measures and practices on hygiene precautions and information regarding antibiotic resistance for effective nursing care to patients with MRSA infections. The conclusions drawn from the study findings showed that it is necessary that the nursing officer thoroughly receive education on correct guidance and information regarding MRSA infection control policy, including measures and practices on hygiene precautions and information regarding antibiotic resistance to provide effective nursing care to patients with MRSA infection as they constantly care for the patient who can be at risk for multi-drug resistance organisms to reduce the risk of MRSA infection in hospital care settings as well community settings.

Keywords: MRSA, knowledge, nursing officers', prevention and management

Procedia PDF Downloads 44

Authors: H. Pegram, R. Stevens, L. De Girolamo

Abstract:

Aligned electrospun nanofibres act as effective neuronal and glial cell scaffolds that can be layered to contain multiple sheets harboring different cell populations. This allows personalised biofunctional prostheses to be manufactured with both acellular and cellularised layers for the treatment of spinal cord injury. Additionally, the manufacturing route may be configured to produce in-vitro 3D cell based model of spinal cord injury to aid drug development and enhance prosthesis performance. The goal of this investigation was to optimise the multi-layer scaffold design parameters for prosthesis manufacture, to enable the development of multi-layer patient specific implant therapies. The work has also focused on the fabricating aligned nanofibre scaffolds that promote in-vitro neuronal and glial cell population growth, cell-to-cell interaction and long-term survival following trauma to mimic an in-vivo spinal cord lesion. The approach has established reproducible lesions and has identified markers of trauma and regeneration marked by effective neuronal migration across the lesion with glial support. The investigation has advanced the development of an in-vitro model of traumatic spinal cord injury and has identified a route to manufacture prostheses which target the repair spinal cord injury. Evidence collated to investigate the multi-layer concept suggests that physical cues provided by nanofibres provide both a natural extra-cellular matrix (ECM) like environment and controls cell proliferation and migration. Specifically, aligned nanofibre layers act as a guidance system for migrating and elongating neurons. On a larger scale, material type in multi-layer systems also has an influence in inter-layer migration as cell types favour different material types. Results have shown that layering nanofibre membranes create a multi-level scaffold system which can enhance or prohibit cell migration between layers. It is hypothesised that modifying nanofibre layer material permits control over neuronal/glial cell migration. Using this concept, layering of neuronal and glial cells has become possible, in the context of tissue engineering and also modelling in-vitro induced lesions.

Keywords: electrospinning, layering, lesion, modeling, nanofibre

Procedia PDF Downloads 118

Authors: Bryana Woodard, Monica Mitchell, Kasey Harry, Ebony Washington, Megan Harris, Marcia Boyd, Regina Lynch, Daphene Baines, Surbi Bankar

Abstract:

Introduction: African Americans experience mental health illnesses (i.e., depression, anxiety, etc.) at higher rates than their white counterparts. Despite this, they utilize mental health resources less and have lower mental health literacy, perhaps due to cultural barriers- including but not limited to mistrust. Research acknowledges African Americans’ close ties to community networks, identifying these linkages as key to establishing comfort and trust. Similarly, the church has historically been a space that creates unity and community among African Americans. Studies show that longstanding academic-community partnerships with organizations, such as churches and faith-based entities, have the capability to effectively address health and mental health barriers and needs in African Americans. The importance of implementing faith-based approaches is supported in the literature, however few empirical studies exist. This project describes the First Ladies for Health and Cincinnati Children's Hospital Medical Center (CCHMC) Partnership (FLFH-CCHMC Partnership) and the implementation and assessment of an annual Mental Health Symposium, the overall aim of which was to increase mental health awareness and decrease stigma in African American communities. Methods: The specific goals of the FLFH Mental Health Symposium were to (1) Collaborate with trusted partners to build trust with community participants; (2) Increase mental health literacy and decrease mental health stigma; (3) Understand the barriers to improving mental health and improving trust; (4) Assess the short-term outcomes two months following the symposium. Data were collected through post-event and follow-up surveys using a mixed methods approach. Results: More than 100 participants attended each year with over 350 total participants over three years. 98.7% of participants were African American, 86.67% female, 11.6% male, and 11.6% LGBTQ+/non-binary; 10.5% of participants were teens, with the remainder aged 20 to 80 plus. The event was successful in achieving its goals: (1a) Eleven different speakers from 8 community and church organizations presented; (1b) 93% of participants rated the overall symposium as very good or excellent (2a) Mental health literacy significantly increased each year with over 90% of participants reporting improvement in their “understanding” and “awareness of mental health (2b) Participants 'personal stigma surrounding mental health illness decreased each year with 92.3% of participants reporting changes in their “willingness to talk about and share” mental health challenges; (3) Barriers to mental health care were identified and included social stigma, lack of trust, and the cost of care. Data were used to develop priorities and an action plan for the FLFH-CCHMC Mental Health Partnership; (4) Follow-up data showed that participants sustained benefits of the FLFH Symposium and took actionable steps (e.g., meditation, referrals, etc.). Additional quantitative and qualitative data will be shared. Conclusions: Lower rates of mental health literacy and higher rates of stigma among participants in this initiative demonstrate the importance of mental health providers building trust and partnerships in communities. Working with faith-based entities provides an opportunity to mitigate and address mental health equity in African American communities.

Keywords: community psychology, faith-based, african-american, culturally competent care, mental health equity

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Authors: J. Yan, B. Pieper, B. Bucsky, H. H. Sievers, B. Nasseri, S. A. Mohamed

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In order to optimize the efficacy of medications, the regular follow-up with long-term continuous monitoring of heart rhythmic patterns has been facilitated since clinical introduction of cardiac implantable electronic monitoring devices (CIMD). Extensive analysis of rhythmic circadian properties is capable to disclose the distributions of arrhythmic events, which may support appropriate medication according rate-/rhythm-control strategy and minimize consequent afflictions. 348 patients (69 ± 0.5ys, male 61.8%) with predisposed atrial fibrillation (AF), undergoing primary ablating therapies combined to coronary or valve operations and secondary implantation of CIMDs, were involved and divided into 3 groups such as PAAF (paroxysmal AF) (n=99, male 68.7%), PEAF (persistent AF) (n=94, male 62.8%), and LSPEAF (long-standing persistent AF) (n=155, male 56.8%). All patients participated in three-year ambulant follow-up (3, 6, 9, 12, 18, 24, 30 and 36 months). Burdens of atrial fibrillation recurrence were assessed using cardiac monitor devices, whereby attacks frequencies and their circadian patterns were systemically analyzed. Anticoagulants and regular anti-arrhythmic medications were evaluated and the last were listed in terms of anti-rate and anti-rhythm regimens. Patients in the PEAF-group showed the least AF-burden after surgical ablating procedures compared to both of the other subtypes (p < 0.05). The AF-recurrences predominantly performed such attacks’ property as shorter than one hour, namely within 10 minutes (p < 0.05), regardless of AF-subtypes. Concerning circadian distribution of the recurrence attacks, frequent AF-attacks were mostly recorded in the morning in the PAAF-group (p < 0.05), while the patients with predisposed PEAF complained less attack-induced discomforts in the latter half of the night and the ones with LSPEAF only if they were not physically active after primary surgical ablations. Different AF-subtypes presented distinct therapeutic efficacies after appropriate surgical ablating procedures and recurrence properties in sense of circadian distribution. An optimization of medical regimen and drug dosages to maintain the therapeutic success needs more attention to detailed assessment of the long-term follow-up. Rate-control strategy plays a much more important role than rhythm-control in the ongoing follow-up examinations.

Keywords: atrial fibrillation, CIMD, MAZE, rate-control, rhythm-control, rhythm patterns

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Authors: Kanika Gupta, Ashok Kumar

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Biofilms are dense, highly hydrated cell clusters that are irreversibly attached to a substratum, to an interface or to each other, and are embedded in a self-produced gelatinous matrix composed of extracellular polymeric substances. Research in biofilm field has become very significant, as biofilm has shown high mechanical resilience and resistance to antibiotic treatment and constituted as a significant problem in both healthcare and other industry related to microorganisms. The massive information both stated and hidden in the biofilm literature are growing exponentially therefore it is not possible for researchers and practitioners to automatically extract and relate information from different written resources. So, the current work proposes and discusses the use of text mining techniques for the extraction of information from biofilm literature corpora containing 34306 documents. It is very difficult and expensive to obtain annotated material for biomedical literature as the literature is unstructured i.e. free-text. Therefore, we considered unsupervised approach, where no annotated training is necessary and using this approach we developed a system that will classify the text on the basis of growth and development, drug effects, radiation effects, classification and physiology of biofilms. For this, a two-step structure was used where the first step is to extract keywords from the biofilm literature using a metathesaurus and standard natural language processing tools like Rapid Miner_v5.3 and the second step is to discover relations between the genes extracted from the whole set of biofilm literature using pubmed.mineR_v1.0.11. We used unsupervised approach, which is the machine learning task of inferring a function to describe hidden structure from 'unlabeled' data, in the above-extracted datasets to develop classifiers using WinPython-64 bit_v3.5.4.0Qt5 and R studio_v0.99.467 packages which will automatically classify the text by using the mentioned sets. The developed classifiers were tested on a large data set of biofilm literature which showed that the unsupervised approach proposed is promising as well as suited for a semi-automatic labeling of the extracted relations. The entire information was stored in the relational database which was hosted locally on the server. The generated biofilm vocabulary and genes relations will be significant for researchers dealing with biofilm research, making their search easy and efficient as the keywords and genes could be directly mapped with the documents used for database development.

Keywords: biofilms literature, classifiers development, text mining, unsupervised learning approach, unstructured data, relational database

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Authors: Jae-Hyeon Kim, Michael Lee

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Intrinsic and acquired resistance limits the therapeutic benefits of oncogenic BRAF inhibitors in melanoma. MicroRNAs (miRNA) regulate the expression of target mRNAs by repressing their translation. Thus, we investigated miRNA expression patterns in melanoma cell lines to identify candidate biomarkers for acquired resistance to BRAF inhibitor. Here, we used Affymetrix miRNA V3.0 microarray profiling platform to compare miRNA expression levels in three cell lines containing BRAF inhibitor-sensitive A375P BRAF V600E cells, their BRAF inhibitor-resistant counterparts (A375P/Mdr), and SK-MEL-2 BRAF-WT cells with intrinsic resistance to BRAF inhibitor. The miRNAs with at least a two-fold change in expression between BRAF inhibitor-sensitive and –resistant cell lines, were identified as differentially expressed. Averaged intensity measurements identified 138 and 217 miRNAs that were differentially expressed by 2 fold or more between: 1) A375P and A375P/Mdr; 2) A375P and SK-MEL-2, respectively. The hierarchical clustering revealed differences in miRNA expression profiles between BRAF inhibitor-sensitive and –resistant cell lines for miRNAs involved in intrinsic and acquired resistance to BRAF inhibitor. In particular, 43 miRNAs were identified whose expression was consistently altered in two BRAF inhibitor-resistant cell lines, regardless of intrinsic and acquired resistance. Twenty five miRNAs were consistently upregulated and 18 downregulated more than 2-fold. Although some discrepancies were detected when miRNA microarray data were compared with qPCR-measured expression levels, qRT-PCR for five miRNAs (miR-3617, miR-92a1, miR-1246, miR-1936-3p, and miR-17-3p) results showed excellent agreement with microarray experiments. To further investigate cellular functions of miRNAs, we examined effects on cell proliferation. Synthetic oligonucleotide miRNA mimics were transfected into three cell lines, and proliferation was quantified using a colorimetric assay. Of the 5 miRNAs tested, only miR-1246 altered cell proliferation of A375P/Mdr cells. The transfection of miR-1246 mimic strongly conferred PLX-4720 resistance to A375P/Mdr cells, implying that miR-1246 upregulation confers acquired resistance to BRAF inhibition. We also found that PLX-4720 caused much greater G2/M arrest in A375P/Mdr cells transfected with miR-1246mimic than that seen in scrambled RNA-transfected cells. Additionally, miR-1246 mimic partially caused a resistance to autophagy induction by PLX-4720. These results indicate that autophagy does play an essential death-promoting role inPLX-4720-induced cell death. Taken together, these results suggest that miRNA expression profiling in melanoma cells can provide valuable information for a network of BRAF inhibitor resistance-associated miRNAs.

Keywords: microRNA, BRAF inhibitor, drug resistance, autophagy

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Authors: Rachid Essamoud, Abdelkrim Afenzar, Ahmed Belqadi

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During the Early Mesozoic, the northwestern part of the African continent was affected by initial fracturing associated with the early stages of the opening of the Central Atlantic (Atlantic Rift). During this rifting phase, the Moroccan Meseta experienced an extensive tectonic regime. This extension favored the formation of a set of rift-type basins, including the Mohammedia-Benslimane-ElGara-Berrechid basin. Thus, it is essential to know the nature of the deposits in this basin and their evolution over time as well as their relationship with the basaltic effusion of the Central Atlantic Magmatic Province (CAMP). These deposits are subdivided into two large series: The Lower clay-salt series attributed to the Triassic and the Upper clay-salt series attributed to the Liassic. The two series are separated by the Upper Triassic-Lower Liassic basaltic complex. The detailed sedimentological analysis made it possible to characterize four mega-sequences, fifteen types of facies and eight architectural elements and facies associations in the Triassic series. A progressive decrease observed in paleo-slope over time led to the evolution of the paleoenvironment from a proximal system of alluvial fans to a braided fluvial style, then to an anastomosed system. These environments eventually evolved into an alluvial plain associated with a coastal plain where playa lakes, mudflats and lagoons had developed. The pure and massive halitic facies at the top of the series probably indicate an evolution of the depositional environment towards a shallow subtidal environment. The presence of these evaporites indicates a climate that favored their precipitation, in this case, a fairly hot and humid climate. The sedimentological analysis of the supra-basaltic part shows that during the Lower Liassic, the paleopente after basaltic effusion remained weak with distal environments. The faciological analysis revealed the presence of four major sandstone, silty, clayey and evaporitic lithofacies organized in two mega-sequences: the sedimentation of the first rock-salt mega-sequence took place in a brine depression system free, followed by saline mudflats under continental influences. The upper clay mega-sequence displays facies documenting sea level fluctuations from the final transgression of the Tethys or the opening Atlantic. Saliferous sedimentation is therefore favored from the Upper Triassic, but experienced a sudden rupture by the emission of basaltic flows which are interstratified in the azoic salt clays of very shallow seas. This basaltic emission which belongs to the CAMP would come from a fissural volcanism probably carried out through transfer faults located in the NW and SE of the basin. Their emplacement is probably subaquatic to subaerial. From a chronological and paleogeographic point of view, this main volcanism, dated between the Upper Triassic and the Lower Liassic (180-200 MA), is linked to the fragmentation of Pangea and managed by a progressive expansion triggered in the West in close relation with the initial phases of Central Atlantic rifting and seems to coincide with the major mass extinction at the Triassic-Jurassic boundary.

Keywords: Basalt, CAMP, Liassic, sedimentology, Triassic, Morocco

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Authors: Paresh Patel, Priya Patel, Vaidehi Sorathiya, Navin Sheth

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The aim of present work was to fabricate Salmeterol Xinafoate (SX) metered dose inhaler (MDI) for asthma and to evaluate the SX loaded solid lipid nanoparticles (SLNs) for pulmonary delivery. Solid lipid nanoparticles can be used to deliver particles to the lungs via MDI. A modified solvent emulsification diffusion technique was used to prepare Salmeterol Xinafoate loaded solid lipid nanoparticles by using compritol 888 ATO as lipid, tween 80 as surfactant, D-mannitol as cryoprotecting agent and L-leucine was used to improve aerosolization behaviour. Box-Behnken design was applied with 17 runs. 3-D surface response plots and contour plots were drawn and optimized formulation was selected based on minimum particle size and maximum % EE. % yield, in vitro diffusion study, scanning electron microscopy, X-ray diffraction, DSC, FTIR also characterized. Particle size, zeta potential analyzed by Zetatrac particle size analyzer and aerodynamic properties was carried out by cascade impactor. Pre convulsion time was examined for control group, treatment group and compare with marketed group. MDI was evaluated for leakage test, flammability test, spray test and content per puff. By experimental design, particle size and % EE found to be in range between 119-337 nm and 62.04-76.77% by solvent emulsification diffusion technique. Morphologically, particles have spherical shape and uniform distribution. DSC & FTIR study showed that no interaction between drug and excipients. Zeta potential shows good stability of SLNs. % respirable fraction found to be 52.78% indicating reach to the deep part of lung such as alveoli. Animal study showed that fabricated MDI protect the lungs against histamine induced bronchospasm in guinea pigs. MDI showed sphericity of particle in spray pattern, 96.34% content per puff and non-flammable. SLNs prepared by Solvent emulsification diffusion technique provide desirable size for deposition into the alveoli. This delivery platform opens up a wide range of treatment application of pulmonary disease like asthma via solid lipid nanoparticles.

Keywords: salmeterol xinafoate, solid lipid nanoparticles, box-behnken design, solvent emulsification diffusion technique, pulmonary delivery

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Authors: S. G. Vasantharaju, Viswanath Guptha, Raghavendra Shetty

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Introduction: Aminophylline is a methylxanthine derivative belonging to the class bronchodilator. From the literature survey, reported methods reveals the solid phase extraction and liquid liquid extraction which is highly variable, time consuming, costly and laborious analysis. Present work aims to develop a simple, highly sensitive, precise and accurate high-performance liquid chromatography method for the quantification of Aminophylline in rat plasma samples which can be utilized for preclinical studies. Method: Reverse Phase high-performance liquid chromatography method. Results: Selectivity: Aminophylline and the internal standard were well separated from the co-eluted components and there was no interference from the endogenous material at the retention time of analyte and the internal standard. The LLOQ measurable with acceptable accuracy and precision for the analyte was 0.5 µg/mL. Linearity: The developed and validated method is linear over the range of 0.5-40.0 µg/mL. The coefficient of determination was found to be greater than 0.9967, indicating the linearity of this method. Accuracy and precision: The accuracy and precision values for intra and inter day studies at low, medium and high quality control samples concentrations of aminophylline in the plasma were within the acceptable limits Extraction recovery: The method produced consistent extraction recovery at all 3 QC levels. The mean extraction recovery of aminophylline was 93.57 ± 1.28% while that of internal standard was 90.70 ± 1.30%. Stability: The results show that aminophylline is stable in rat plasma under the studied stability conditions and that it is also stable for about 30 days when stored at -80˚C. Pharmacokinetic studies: The method was successfully applied to the quantitative estimation of aminophylline rat plasma following its oral administration to rats. Discussion: Preclinical studies require a rapid and sensitive method for estimating the drug concentration in the rat plasma. The method described in our article includes a simple protein precipitation extraction technique with ultraviolet detection for quantification. The present method is simple and robust for fast high-throughput sample analysis with less analysis cost for analyzing aminophylline in biological samples. In this proposed method, no interfering peaks were observed at the elution times of aminophylline and the internal standard. The method also had sufficient selectivity, specificity, precision and accuracy over the concentration range of 0.5 - 40.0 µg/mL. An isocratic separation technique was used underlining the simplicity of the presented method.

Keywords: Aminophyllin, preclinical pharmacokinetics, rat plasma, RPHPLC

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Authors: Caroline Seo, Jennifer Stephens, Kirstin H. Heinrich

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Background: Clostridiodes (formerly Clostridium) difficile infection (CDI) is an anaerobic, spore-forming bacterium with manifestations including diarrhea, pseudomembranous colitis and toxic megacolon. Despite general understanding that CDI may be associated with marked burden on patients’ health, there has been limited information available on the humanistic burden of CDI. The objective of this literature review was to summarize the published data on the humanistic burden of CDI globally, in order to better inform future research efforts and increase awareness of the patient perspective in this disease. Methods: A comprehensive literature review of the past 15 years (2002-2017) was conducted using MEDLINE, Embase and Cumulative Index of Nursing and Allied Health Literature. Additional searches were conducted from conference proceedings (2015-2017). Articles selected were studies specifically designed to examine the humanistic burden of illness associated with adult patients with CDI. Results: Of 3,325 articles or abstracts identified, 33 remained after screening and full text review. Sixty percent (60%) were published in 2016 or 2017. Data from the United States or Western Europe were most common. Data from Brazil, Canada, China and Spain also exist. Thirteen (13) studies used validated patient-reported outcomes instruments, mostly EQ-5D utility and SF-36 generic instruments. Three (3) studies used CDI-specific instruments (CDiff32, CDI-DaySyms). The burden of CDI impacts patients in multiple health-related quality of life (HRQOL) domains. SF-36 domains with the largest decrements compared to other GI diarrheal diseases (IBS-D and Crohn’s) were role physical, physical functioning, vitality, social functioning, and role emotional. Reported EQ-5D utilities for CDI ranged from 0.35-0.42 compared to 0.65 in Crohn’s and 0.72 in IBS-D. The majority of papers addressed physical functioning and mental health domains (67% for both). Across various studies patients reported weakness, lack of appetite, sleep disturbance, functional dependence, and decreased activities of daily lives due to the continuous diarrhea. Due to lack of control over this infection, CDI also impacts the psychological and emotional quality of life of the patients. Patients reported feelings of fear, anxiety, frustration, depression, and embarrassment. Additionally, the type of disease (primary vs. recurrent) may impact mental health. One study indicated that there is a decrement in SF-36 mental scores in patients with recurrent CDI, in comparison to patients with primary CDI. Other domains highlighted by these studies include pain (27%), social isolation (27%), vitality and fatigue (24%), self-care (9%), and caregiver burden (0%). Two studies addressed work productivity, with 1 of these studies reporting that CDI patients had the highest work productivity and activity impairment scores among the gastrointestinal diseases. No study specifically included caregiver self-report. However, 3 studies did provide mention of patients’ worry on how their diagnosis of CDI would impact family, caregivers, and/or friends. Conclusions: Despite being a serious public health issue there has been a paucity of research on the HRQOL among those with CDI. While progress is being made, gaps exist in understanding the burden on patients, caregivers, and families. Future research is warranted to aid understanding of the CDI patient perspective.

Keywords: burden, Clostridiodes, difficile, humanistic, infection

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Authors: N. Khursheed, M. Fatima, S. Jamal, A. Raza, S. Rattani, Q. Ahsan, A. Rasheed, M. Jawed

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Introduction: Antibiotics are among the commonly prescribed medicines to treat bacterial infections. Their misuse intensifies resistance, and overuse incurs heavy losses to the healthcare system in terms of increased treatment costs and enhanced disease burden. Studies show that 40% of empirically used antibiotics are irrationally utilized. The objective of this study was to evaluate prescribing pattern of antibiotics at six public sector tertiary care hospitals across Pakistan. Methods: A multicenter cross-sectional point prevalence survey (PPS) was conducted in selected wards of six public sector tertiary care hospitals in Pakistan as part of the Clinical Engagement program by Fleming Fund Country Grant Pakistan in collaboration with Indus Hospital & Health Network (IHHN) from February to March 2021, these included Jinnah Postgraduate Medical Center and Dr. Ruth K. M. Pfau Civil Hospital from Karachi, Sheikh Zayed Hospital Lahore, Nishtar Medical University Hospital Multan, Medical Teaching Institute Hayatabad Medical Complex Peshawar, and Provincial Headquarters Hospital Gilgit. WHO PPS methodology was used for data collection (Hospital, ward, and patient level data was collected). Data was entered into the open-source Kobo Collect application and was analyzed using SPSS (version 22.0). Findings: Medical records of 837 in-patients were surveyed, of which the prevalence of antibiotics use was 78.5%. The most commonly prescribed antimicrobial was Ceftriaxone (21.7%) which is categorized in the Watch group of WHO AWaRe Classification, followed by Metronidazole (17.3%), Cefoperazone/Sulbactam (8.4%), Co-Amoxiclav (6.3%) and Piperacillin/Tazobactam (5.9%). The antibiotics were prescribed largely for surgical prophylaxis (36.7%), followed by community-acquired infections (24.7%). One antibiotic was prescribed to 46.7%, two to 39.9%, and three or more to 12.5 %. Two of six (30%) hospitals had functional drug and therapeutic committees, three (50%) had infection prevention and control committees, and one facility had an antibiotic formulary. Conclusion: Findings demonstrate high consumption of broad-spectrum antimicrobials and emphasizes the importance of expanding the antimicrobial stewardship program. Mentoring clinical teams will help to rationalize antimicrobial use.

Keywords: antimicrobial resistance, antimicrobial stewardship, point prevalence survey, antibiotics

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Authors: Manohar Salla, Mark S. Butler, Ruby Pelingon, Geraldine Kaeslin, Daniel E. Croker, Janet C. Reid, Jong Min Baek, Paul V. Bernhardt, Elizabeth M. J. Gillam, Matthew A. Cooper, Avril A. B. Robertson

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MCC950 is a potent and selective inhibitor of the NOD-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome that shows early promise for treatment of inflammatory diseases. The identification of major metabolites of lead molecule is an important step during drug development process. It provides an information about the metabolically labile sites in the molecule and thereby helping medicinal chemists to design metabolically stable molecules. To identify major metabolites of MCC950, the compound was incubated with human liver microsomes and subsequent analysis by (+)- and (−)-QTOF-ESI-MS/MS revealed a major metabolite formed due to hydroxylation on 1,2,3,5,6,7-hexahydro-s-indacene moiety of MCC950. This major metabolite can lose two water molecules and three possible regioisomers were synthesized. Co-elution of major metabolite with each of the synthesized compounds using HPLC-ESI-SRM-MS/MS revealed the structure of the metabolite (±) N-((1-hydroxy-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-4-(2-hydroxypropan-2-yl)furan-2-sulfonamide. Subsequent synthesis of individual enantiomers and coelution in HPLC-ESI-SRM-MS/MS using a chiral column revealed the metabolite was R-(+)- N-((1-hydroxy-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-4-(2-hydroxypropan-2-yl)furan-2-sulfonamide. To study the possible cytochrome P450 enzyme(s) responsible for the formation of major metabolite, MCC950 was incubated with a panel of cytochrome P450 enzymes. The result indicated that CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2C18, CYP2C19, CYP2J2 and CYP3A4 are most likely responsible for the formation of the major metabolite. The biological activity of the major metabolite and the other synthesized regioisomers was also investigated by screening for for NLRP3 inflammasome inhibitory activity and cytotoxicity. The major metabolite had 170-fold less inhibitory activity (IC50-1238 nM) than MCC950 (IC50-7.5 nM). Interestingly, one regioisomer had shown nanomolar inhibitory activity (IC50-232 nM). However, no evidence of cytotoxicity was observed with any of these synthesized compounds when tested in human embryonic kidney 293 cells (HEK293) and human liver hepatocellular carcinoma G2 cells (HepG2). These key findings give an insight into the SAR of the hexahydroindacene moiety of MCC950 and reveal a metabolic soft spot which could be blocked by chemical modification.

Keywords: Cytochrome P450, inflammasome, MCC950, metabolite, microsome, NLRP3

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Authors: Lewis Mehl-Madrona, Barbara Mainguy, Patrick McFarlane

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Introduction: There are many risk factors for attempting suicide, including young age, “minority stress,” which would include Transgender and Gender Diverse orientations (TGD). The rate of TGD youths for suicide attempts is 3 times higher than heterosexual cis-gender youth. Half of TGD youth have seriously contemplated taking their own lives; of those, about half attempted suicide; and 18% of the TGD teenagers reported suicidal thoughts linked to their gender identity. Native American TGD have a six times higher suicide attempt rate. Conventional mental health has not generally helped these individuals. Stigma and discrimination contribute to healthcare disparities. Storytelling plays a crucial role in the development of human culture and individual identities. Sharing narrative artwork, creative writing, and personal stories allow people to build trust and to share their vulnerabilities. This helps people become aware of themselves in relation to others and gain a sense of comfort that their stories are similar; they may also be transformed in the process. Art provides a means to reach people who are otherwise difficult to engage in services. Methods: TGD individuals are recruited through a snowballing procedure. Following a life story interview, participants complete a scale of gender dysphoria, identification with conventional masculinity, patient-reported anxiety, and depression measure, and a quality-of-life scale. The interview completes the Columbia Suicide Scale. Following this, an artist and a therapist works with the participant to create a story related to their gender identity using the six-part story method. This story is then rendered to an artists’ book, which combines narrative with art (drawings, collage, computer images, etc.) and can take the form of a graphic novella, a zine, or a comic book. The pages can range from plain to ornate, as can the covers. Participants describe their process of making the books as the work unfolds and then participate in an exit interview at the completion of their book, remarking on what has changed for them and how the process affected them. Results: Preliminary results show high levels of suicidal thoughts among this population, as expected. Participants participate enthusiastically in the life story interview process and in the construction of a story related to gender identity. They enthusiastically participate in the studio process of putting their story into the form of a graphic novel, zine, or comic book. Participants reported feeling more comfortable with their TGD identity after the process and more able to resist negative judgments of family members and society. Suicidal thoughts diminish, and participants reported improved emotional wellbeing. Quantitative analysis of questionnaire data is underway Conclusions: A process in which narrative therapy is combined with art therapy shows promise for attracting and helping TGD individuals to reduce their risk for suicide without the stigma of going for mental health treatment. This process can be done outside of conventional mental health settings, on college and University campuses. This can provide an exciting alternative pathway for minority stressed and stigmatized individuals to engage in reflective, psychotherapeutic work without the trappings of psychotherapy or mental health treatment.

Keywords: minority stress, narrative process, artists' books, life story interview

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Authors: Abeer Y. Ibrahim, Faten M. Ibrahim, Samah A. El-Newary, Saber F. Hendawy

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Objective: Appreciation of in-vitro anti-inflammatory and antioxidant characters of Vitex agnus-castus berries alcoholic extract and fractions, as well as in-vivo antitumor ability of alcoholic extract and chloroform fraction against Ehrlich ascites carcinoma is the aim of this study. Material and methods: Antioxidant properties of crude alcoholic extract of vitex berries as well as petroleum ether, chloroform, ethyl acetate and butanol fractions were evaluated, in-vitro assessments, as compared with standard materials, l-ascorbic acid (vitamin C) and butylated hydroxyl toluene(BHT). The anti-inflammatory activity was investigated in cyclooxygenase (COX)-1 and COX-2 inhibition assays. Moreover, in-vivo antitumor effect of vitex berries alcoholic and chloroform extracts were evaluated using Ehrlich ascites carcinoma model. Data were presented as mean±SE, and data were analyzed by one-way analysis of variance test. Results and conclusion: Berries crude extract showed potent antioxidant activity followed with its fractions ethyl acetate and chloroform as compared with standard (V.C and BHT). Ethyl acetate fraction showed good reduction capability, metal ion chelation, hydrogen peroxide scavenging, nitric oxide scavenging and superoxide anion scavenging. Meanwhile, chloroform fraction produced the highest free radical scavenging activity and total antioxidant capacity. In respectable of lipid peroxidation inhibition, crude alcoholic extract and its fractions cleared weak inhibition in comparing with standard materials. Anti-inflammatory activity of V. agnus-castus berries chloroform fraction of vitex was best COX-2 inhibitor (IC₅₀, 135.41 µg/ ml) as compared to vitex alcoholic extract or ethyl acetate fraction with weak inhibitory effect on COX-1 (IC50, 778.432 µg/ ml), where the lowest effect on COX-1 was recorded with alcoholic extract. Alcoholic extract and its fractions showed weak COX-1 inhibition activity, whereas COX-2 was inhibited (100%), compared with celecoxib drug (72% at 1000ppm). The crude alcoholic and chloroform extracts of V. agnus-castus barries significantly reduced the viable Ehrlich cell count and increased nonviable count with amelioration of all hematological parameters. This amelioration was reflected on increasing median survival time and significant increase (P < 0.05) in lifespan.

Keywords: anti-inflammatory, antioxidants, ehrlich ascites carcinoma, Vitex agnus-castus

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Authors: Eman Ghoneim

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The Arabian deserts include some of the driest areas on Earth. Yet, its landforms reserved a record of past wet climates. During humid phases, the desert was green and contained permanent rivers, inland deltas and lakes. Some of their water would have seeped and replenished the groundwater aquifers. When the wet periods came to an end, several thousand years ago, the entire region transformed into an extended band of desert and its original fluvial surface was totally covered by windblown sand. In this work, radar and thermal infrared images were used to reveal numerous hidden surface/subsurface features. Radar long wavelength has the unique ability to penetrate surface dry sands and uncover buried subsurface terrain. Thermal infrared also proven to be capable of spotting cooler moist areas particularly in hot dry surfaces. Integrating Radarsat images and GIS revealed several previously unknown paleoriver and lake basins in the region. One of these systems, known as the Kufrah, is the largest yet identified river basin in the Eastern Sahara. This river basin, which straddles the border between Egypt and Libya, flowed north parallel to the adjacent Nile River with an extensive drainage area of 235,500 km2 and massive valley width of 30 km in some parts. This river was most probably served as a spillway for an overflow from Megalake Chad to the Mediterranean Sea and, thus, may have acted as a natural water corridor used by human ancestors to migrate northward across the Sahara. The Gilf-Kebir is another large paleoriver system located just east of Kufrah and emanates from the Gilf Plateau in Egypt. Both river systems terminate with vast inland deltas at the southern margin of the Great Sand Sea. The trends of their distributary channels indicate that both rivers drained to a topographic depression that was periodically occupied by a massive lake. During dry climates, the lake dried up and roofed by sand deposits, which is today forming the Great Sand Sea. The enormity of the lake basin provides explanation as to why continuous extraction of groundwater in this area is possible. A similar lake basin, delimited by former shorelines, was detected by radar space data just across the border of Sudan. This lake, called the Northern Darfur Megalake, has a massive size of 30,750 km2. These former lakes and rivers could potentially hold vast reservoirs of groundwater, oil and natural gas at depth. Similar to radar data, thermal infrared images were proven to be useful in detecting potential locations of subsurface water accumulation in desert regions. Analysis of both Aster and daily MODIS thermal channels reveal several subsurface cool moist patches in the sandy desert of the Arabian Peninsula. Analysis indicated that such evaporative cooling anomalies were resulted from the subsurface transmission of the Monsoonal rainfall from the mountains to the adjacent plain. Drilling a number of wells in several locations proved the presence of productive water aquifers confirming the validity of the used data and the adopted approaches for water exploration in dry regions.

Keywords: radarsat, SRTM, MODIS, thermal infrared, near-surface water, ancient rivers, desert, Sahara, Arabian peninsula

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Authors: K. Graniczkowska, N. Beloglazova, S. De Saeger

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The threat of synthetic drugs is one of the most significant current drug problems worldwide. The use of drugs of abuse has increased dramatically during the past three decades. Among others, Amphetamine-Type Stimulants (ATS) are globally the second most widely used drugs after cannabis, exceeding the use of cocaine and heroin. ATS are potent central nervous system (CNS) stimulants, capable of inducing euphoric static similar to cocaine. Recreational use of ATS is widespread, even though warnings of irreversible damage of the CNS were reported. ATS pose a big problem and their production contributes to the pollution of the environment by discharging big volumes of liquid waste to sewage system. Therefore, there is a demand to develop robust and sensitive sensors that can detect ATS and their intermediates in environmental water samples. A rapid and simple test is required. Analysis of environmental water samples (which sometimes can be a harsh environment) using antibody-based tests cannot be applied. Therefore, molecular imprinted polymers (MIPs), which are known as synthetic antibodies, have been chosen for that approach. MIPs are characterized with a high mechanical and thermal stability, show chemical resistance in a broad pH range and various organic or aqueous solvents. These properties make them the preferred type of receptors for application in the harsh conditions imposed by environmental samples. To the best of our knowledge, there are no existing MIPs-based sensors toward amphetamine and its intermediates. Also not many commercial MIPs for this application are available. Therefore, the aim of this study was to compare different techniques to obtain MIPs with high specificity towards ATS and characterize them for following use in a sensing unit. MIPs against amphetamine and its intermediates were synthesized using a few different techniques, such as electro-, thermo- and UV-initiated polymerization. Different monomers, cross linkers and initiators, in various ratios, were tested to obtain the best sensitivity and polymers properties. Subsequently, specificity and selectivity were compared with commercially available MIPs against amphetamine. Different linkers, such as lipoic acid, 3-mercaptopioponic acid and tyramine were examined, in combination with several immobilization techniques, to select the best procedure for attaching particles on sensor surface. Performed experiments allowed choosing an optimal method for the intended sensor application. Stability of MIPs in extreme conditions, such as highly acidic or basic was determined. Obtained results led to the conclusion about MIPs based sensor applicability in sewage system testing.

Keywords: amphetamine type stimulants, environment, molecular imprinted polymers, MIPs, sensor

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Authors: R. Zhankina, U. Zhanbyrbekuly, A. Tamadon, M. Askarov, R. Sherkhanov, D. Akhmetov, D. Saipiyeva, N. Keulimzhaev

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Male infertility affects about 15% of couples of reproductive age. Approximately 10–15% have azoospermia who have previously been diagnosed with male infertility. Azoospermia is regarded as the absence of spermatozoa in the ejaculate and is found in 10-15% of infertile men. Non-obstructive azoospermia is considered a cause of male infertility that is not amenable to drug therapy. Patients with non-obstructive azoospermia are unable to have their "own" children and have only options for adoption or use of donor sperm. Advances in assisted reproductive technologies such as intracytoplasmic sperm injection in vitro fertilization have significantly changed the management of patients with non-obstructive azoospermia. Advances in biotechnology have increased the options for treating patients with non-obstructive azoospermia. Mesenchymal stem cell therapy has been recognized as a new option for infertility treatment. Material and methods of the study: After obtaining informed consent, 5 patients diagnosed with non-obstructive azoospermia were included in an open, non-randomized study. The age of the patients ranged from 24 to 35 years. The examination was carried out before the start of treatment, which included biochemical blood tests, hormonal profile levels (luteinizing hormone, follicle-stimulating hormone, testosterone, prolactin, inhibin B); tests for tumor markers; genetic research. All studies were carried out in compliance with the requirements of Protocol No. 8 dated 06/09/20, approved by the Local Ethical Commission of NJSC "Astana Medical University". The control examination of patients was carried out after 6 months, by re-taking the program and hormonal profile (testosterone, luteinizing hormone, follicle-stimulating hormone, prolactin, inhibin B). Before micro-TESE of the testis, all 5 patients underwent myeloexfusion in the operating room. During the micro-TESE, autotransplantation of mesenchymal stem cells into the testicular network, previously cultured in a cell technology laboratory for 2 weeks, was performed. Results of the study: in all patients, the levels of total testosterone increased, the level of follicle-stimulating hormone decreased, the levels of luteinizing hormone returned to normal, the level of inhibin B increased. IVF with a positive result; another patient (20%) had spermatogenesis cells. Non-obstructive azoospermia and mesenchymal stem cells Conclusions: The positive results of this work serve as the basis for the application of a new cellular therapeutic approach for the treatment of non-obstructive azoospermia using mesenchymal stem cells.

Keywords: cell therapy, regenerative medicine, male infertility, mesenchymal stem cells

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Authors: Emma Plante, Charles Ekwunwa, Diego Illanes

Abstract:

Introduction: Serum Sickness-Like Reaction (SSLR) is an inflammatory immune response characterized by a rash, polyarthralgias, and fever. SSLR usually occurs in response to a new medication (most commonly antibiotics, anticonvulsants, or antiinflammatory agents) and is believed to involve the formation of drug-specific immune complexes. Here we present a case of a 16-year-old female patient who developed an SSLR in response to the D-mannose-containing over-the-counter supplement, Uqora, used to promote bladder health. Methodology: The methodology for this study included a thorough literature search for other cases of SSLR associated with D-Mannose containing products. Data collection was performed through a review of the patient’s medical record, including history, physical examination, relevant laboratory results, and treatment plan. Findings: A 16-year-old female with a history of overactive bladder and anemia presented with a diffuse urticarial rash, headaches, joint pain, and swelling for three days. Her medications included oral contraceptive pills, iron, mirabegron, UQora, and a probiotic. Physical examination revealed a diffuse urticarial rash, and her musculoskeletal exam revealed swelling and tenderness in her wrists. Her CBC, basic metabolic panel, liver function panel, lyme titers, and urinalysis were all within normal limits. The patient was referred to an allergist, who diagnosed her with SSLR. All medications were discontinued, and she was treated with a 7-day course of prednisone and cetirizine. Her symptoms resolved, and her medications were slowly resumed sequentially over several months. However, UQora triggered a recurrence of her symptoms, and it was identified as the culprit medication. Consequently, UQora was permanently discontinued, and the patient has remained symptom-free. Conclusion: This case report describes the first documented case of SSLR caused by UQora (active ingredient D-mannose). D-Mannose is a monosaccharide found in many plants and fruits, and it is commonly used to prevent urinary tract infections. While the clinical features and timeline, in this case, were typical of SSLR, UQora as the trigger was highly unusual. Clinicians should be aware of the diverse triggers of SSLR and the importance of prompt identification and management to enhance patient safety. It is possible D-mannose was not the trigger, and further research is necessary to better understand the potential therapeutic applications of D-mannose, as well as the potential risks and interactions.

Keywords: serum sickness-like reaction, d-mannose, hypersensitivity reaction, urticaria

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Authors: Victoria Eugenia Garnacho-Garnacho, Elena Sonsoles Rodriguez-Lopez, Raquel Delgado-Delgado, Alvaro Otero-Campos, Jesus Guodemar-Perez, Angelo Michelle Vagali, Juan Pablo Hervas-Perez

Abstract:

Asthma is a heterogeneous disease which has always had a drug treatment. Osteopathic treatment that we propose is aimed, seen through a dorsal manipulation (Dog Technic D1-D4) and a technique for diaphragm (Longitudinal Stroke) forced expiratory flow in spirometry changes there are in particular that there is an increase in the volumes of the Peak Flow and Post intervention and effort and that the application of these two techniques together is more powerful if we applied only a Longitudinal (Stroke). Also rating if this type of treatment will have repercussions on breathlessness, a very common symptom in asthma. And finally to investigate if provided vertebra pain decreased after a manipulation. Methods—Participants were recruited between students and professors of the University, aged 18-65, patients (n = 18) were assigned randomly to one of the two groups, group 1 (longitudinal Stroke and manipulation dorsal Dog Technic) and group 2 (diaphragmatic technique, Longitudinal Stroke). The statistical analysis is characterized by the comparison of the main indicator of obstruction of via area PEF (peak expiratory flow) in various situations through the peak flow meter Datospir Peak-10. The measurements were carried out in four phases: at rest, after the stress test, after the treatment, after treatment and the stress test. After each stress test was evaluated, through the Borg scale, the level of Dyspnea on each patient, regardless of the group. In Group 1 in addition to these parameters was calculated using an algometer spinous pain before and after the manipulation. All data were taken at the minute. Results—12 Group 1 (Dog Technic and Longitudinal Stroke) patients responded positively to treatment, there was an increase of 5.1% and 6.1% of the post-treatment PEF and post-treatment, and effort. The results of the scale of Borg by which we measure the level of Dyspnea were positive, a 54.95%, patients noted an improvement in breathing. In addition was confirmed through the means of both groups group 1 in which two techniques were applied was 34.05% more effective than group 2 in which applied only a. After handling pain fell by 38% of the cases. Conclusions—The impact of the technique of Dog-Technic for D1-D4 and the Longitudinal Stroke technique for diaphragm in the volumes of peak expiratory flow (PEF) in asthmatic patients were positive, there was a change of the PEF Post intervention and post-treatment, and effort and showed the most effective group in which only a technique was applied. Furthermore this type of treatment decreased facilitated vertebrae pain and was efficient in the improvement of Dyspnea and the general well-being of the patient.

Keywords: ANS, asthma, manipulation, manual therapy, osteopathic

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Authors: Santi Maneewatchararangsri, Wanpen Chaicumpa, Patcharin Saengjaruk, Urai Chaisri

Abstract:

Leptospirosis is a globally neglected disease that continues to be a significant public health and veterinary burden, with millions of cases reported each year. Early and accurate differential diagnosis of leptospirosis from other febrile illnesses and the development of a broad spectrum of leptospirosis vaccines are needed. The LipL32 outer membrane lipoprotein is a member of Leptospira adhesive matrices and has been found to exert hemolytic activity to erythrocytes in vitro. Therefore, LipL32 is regarded as a potential target for diagnosis, broad-spectrum leptospirosis vaccines, and for passive immunotherapy. In this study, we established LipL32-specific mouse monoclonal antibodies, mAbLPF1 and mAbLPF2, and their respective mouse- and humanized-engineered single chain variable fragment (ScFv). Their antibodies’ neutralizing activities against Leptospira-mediated hemolysis in vitro, and the therapeutic efficacy of mAbs against heterologous Leptospira infected hamsters were demonstrated. The epitope peptide of mAb LPF1 was mapped to a non-contiguous carboxy-terminal β-turn and amphipathic α-helix of LipL32 structure contributing to phospholipid/host cell adhesion and membrane insertion. We found that the mAbLPF2 epitope was located on the interacting loop of peptide binding groove of the LipL32 molecule responsible for interactions with host constituents. Epitope sequences are highly conserved among Leptospira spp. and are absent from the LipL32 superfamily of other microorganisms. Both epitopes are surface-exposed, readily accessible by mAbs, and immunogenic. However, they are less dominant when revealed by LipL32-specific immunoglobulins from leptospirosis-patient sera and rabbit hyperimmune serum raised by whole Leptospira. Our study also demonstrated an adhesion inhibitory activity of LipL32 protein to host membrane components and cells mediated by mAbs as well as an anti-hemolytic activity of the respective antibodies. The therapeutic antibodies, particularly the humanized-ScFv, have a potential for further development as non-drug therapeutic agent for human leptospirosis, especially in subjects allergic to antibiotics. The epitope peptides recognized by two therapeutic mAbs have potential use as tools for structure-function studies. Finally, protective peptides may be used as a target for epitope-based vaccines for control of leptospirosis.

Keywords: leptospira lipl32-specific antibodies, therapeutic epitopes, epitopes characterization, immunotherapy

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Authors: Uwizera Egide

Abstract:

Introduction: Dermatological conditions are one of the most burdensome diseases in our health system. Global studies suggest that around 1 in 3 people gets a skin disease at a certain point in their life, though this does not necessarily guarantee the urge to consult. For a high-ranking disease, it is surprising how there is not enough data to support its effect on the economy and the general health system impact. It is for that reason that this study’s aim is to identify the burden of dermatological conditions in Rwanda so as to have a general picture of what our population is going through in regards to dermatological conditions. Methods: We used a cross sectional retrospective study. Data were obtained from patient’s information recorded in an open clinic at CHUB in a period of six months from July to December of the year 2021. Results: The study had a total of 4600 patients who attended dermatology service in a period of six months from July to December of the year 2021. We found a list of 102 dermatological diseases that presented at variable rates. The most prevalent disease was atopic dermatitis, at a rate of 23%. About 90% of presented conditions had only one choice of treatment from the hospital pharmacy. Most patients who presented were between 18-35 years old and with a predominance of the female gender; the level of education was either secondary or University Degree in our study, 65.4% of patients who presented were female; the majority, around 45% were between 18-35 years old, mostly being single 56%. The majority came from Southern province as it is the location of the hospital. The insurance mostly used was community-based health insurance with 63.8%, followed by RSSB with 18.5%, MS/UR, and other private insurances. The frequency of group drugs prescribed among all dermatological medications, steroids were the most commonly given medications at a rate of 39%, followed by emollients, antibiotics, and antifungal. The drugs prescribed were mostly available in the pharmacy of CHUB, with 60% and 40% being found in pharmacies outside the hospital. Conclusion: Dermatological conditions are prevalent in all age groups and distributed through all socioeconomic classes. About 9.2% of patient who consulted CHUB in 2021 presented one Dermatological condition of which 40 % of prescribed medications is never found in Hospital urging a need to buy medication in private pharmacies with more expenses and a risk of not complying on prescribed medication if in case they can’t afford paying them outside the CHUB. This finding urges a need to avail all essential dermatological drugs in hospital pharmacies to allow our patients to get them for the proper compliance of prescribed drugs in the management of skin diseases.

Keywords: atopic dermatitis, CHUB (centre hopitalier univerisitaire de butare), dermatological condition, fungal infections

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