Search results for: Salmonella infection

Authors: Mahbuba Rahman, Sabri Boughorbel, Scott Presnell, Charlie Quinn, Darawan Rinchai, Damien Chaussabel, Nico Marr

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Collections of large-scale datasets made available in public repositories can be used to identify and fill gaps in biomedical knowledge. But first, these data need to be made readily accessible to researchers for analysis and interpretation. Here a collection of transcriptome datasets was made available to investigate the functional programming of human hematopoietic cells in early life. Thirty two datasets were retrieved from the NCBI Gene Expression Omnibus (GEO) and loaded in a custom, interactive web application called the Gene Expression browser (GXB), designed for visualization and query of integrated large-scale data. Multiple sample groupings and gene rank lists were created based on the study design and variables in each dataset. Web links to customized graphical views can be generated by users and subsequently be used to graphically present data in manuscripts for publication. The GXB tool also enables browsing of a single gene across datasets, which can provide information on the role of a given molecule across biological systems. The dataset collection is available online. As a proof-of-principle, one of the datasets (GSE25087) was re-analyzed to identify genes that are differentially expressed by regulatory T cells in early life. Re-analysis of this dataset and a cross-study comparison using multiple other datasets in the above mentioned collection revealed that PMCH, a gene encoding a precursor of melanin-concentrating hormone (MCH), a cyclic neuropeptide, is highly expressed in a variety of other hematopoietic cell types, including neonatal erythroid cells as well as plasmacytoid dendritic cells upon viral infection. Our findings suggest an as yet unrecognized role of MCH in immune regulation, thereby highlighting the unique potential of the curated dataset collection and systems biology approach to generate new hypotheses which can be tested in future mechanistic studies.

Keywords: early-life, GEO datasets, PMCH, interactive query, systems biology

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Authors: Farida Azzouz-Olden, Arthur G. Hunt, Gloria Degrandi-Hoffman

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Bees are confronting several environmental challenges, including the intermingled effects of malnutrition and disease. Intuitively, pollen is the healthiest nutritional choice; however, commercial substitutes, such as BeePro and MegaBee, are widely used. Herein we examined how feeding natural and artificial diets shapes transcription in the abdomen of the honey bee, and how transcription shifts in combination with Nosema parasitism. Gene ontology enrichment revealed that, compared with poor diet (carbohydrates (C)), bees fed pollen (P > C), BeePro (B > C), and MegaBee (M > C) showed a broad upregulation of metabolic processes, especially lipids; however, pollen feeding promoted more functions and superior proteolysis. The superiority of the pollen diet was also evident through the remarkable overexpression of vitellogenin in bees fed pollen instead of MegaBee or BeePro. Upregulation of bioprocesses under carbohydrates feeding compared to pollen (C > P) provided a clear poor nutritional status, uncovering stark expression changes that were slight or absent relatively to BeePro (C > B) or MegaBee (C > M). Poor diet feeding (C > P) induced starvation response genes and hippo signaling pathway, while it repressed growth through different mechanisms. Carbohydrate feeding (C > P) also elicited ‘adult behavior’, and developmental processes suggesting transition to foraging. Finally, it altered the ‘circadian rhythm’, reflecting the role of this mechanism in the adaptation to nutritional stress in mammals. Nosema-infected bees fed pollen compared to carbohydrates (PN > CN) upheld certain bioprocesses of uninfected bees (P > C). Poor nutritional status was more apparent against pollen (CN > PN) than BeePro (CN > BN) or MegaBee (CN > MN). Nosema accentuated the effects of malnutrition since more starvation-response genes and stress response mechanisms were upregulated in CN > PN compared to C > P. The bioprocess ‘Macromolecular complex assembly’ was also enriched in CN > PN, and involved genes associated with human HIV and/or influenza, thus providing potential candidates for bee-Nosema interactions. Finally, the enzyme Duox emerged as essential for guts defense in bees, similarly to Drosophila. These results provide evidence of the superior nutritional status of bees fed pollen instead of artificial substitutes in terms of overall health, even in the presence of a pathogen.

Keywords: honeybee, immunity, Nosema, nutrition, RNA-seq

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Authors: Emma O’ Keeffe, Helen Hughes, Peter McLoughlin, Shiau Pin Tan, Nick McCarthy

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Biosecurity is emerging as one of the most important issues facing the agricultural and forestry community. This is as a result of increased invasion from new pests and diseases with the main protocol for dealing with these species being the use of synthetic pesticides. However, these chemicals have been shown to exhibit negative effects on the environment. Seaweeds represent a vast untapped resource of bio-molecules with a broad range of biological activities including pesticidal. This project investigated both the antifungal and antibacterial activity of seaweed species against two problematic root rot fungi, Armillaria mellea and Heterobasidion annosum and ten quarantine bacterial plant pathogens including Xanthomonas arboricola, Xanthomonas fragariae, and Erwinia amylovora. Four seaweed species were harvested from the South-East coast of Ireland including brown, red and green varieties. The powdered seaweeds were extracted using four different solvents by liquid extraction. The poisoned food technique was employed to establish the antifungal efficacy, and the standard disc diffusion assay was used to assess the antibacterial properties of the seaweed extracts. It was found that extracts of the green seaweed exhibited antifungal activity against H. annosum, with approximately 50% inhibition compared to the negative control. The protectant activities of the active extracts were evaluated on disks of Picea sitchensis, a plant species sensitive to infection from H. annosum and compared to the standard chemical control product urea. The crude extracts exhibited very similar activity to the 10% and 20% w/v concentrations of urea, demonstrating the ability of seaweed extracts to compete with commercially available products. Antibacterial activity was exhibited by a number of seaweed extracts with the red seaweed illustrating the strongest activity, with a zone of inhibition of 15.83 ± 0.41 mm exhibited against X. arboricola whilst the positive control (10 μg/disk of chloramphenicol) had a zone of 26.5 ± 0.71 mm. These results highlight the potential application of seaweed extracts in the forestry and agricultural industries for use as biopesticides. Further work is now required to identify the bioactive molecules that are responsible for this antifungal and antibacterial activity in the seaweed extracts, including toxicity studies to ensure the extracts are non-toxic to plants and humans.

Keywords: antibacterial, antifungal, biopesticides, seaweeds

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Authors: Yi-Hao Pai, Wen-Feng Chen

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The planting area of Pomelo in Hualien, Taiwan amounts to thousands of hectares. Especially in the blooming season of Pomelo, it is an important producing area for Pomelo honey, and it is also a good test field for promoting the "Under-forest Economy". However, in the current Pomelo garden planting and management operations, the large amount of agricultural waste generated by the pruning of the branches causes environmental sanitation concerns, which can lead to the hiding of pests or the infection of the Pomelo tree, and indirectly increase the health risks of bees. Therefore, how to deal with the pruning of the branches and avoid open burning is a topic of social concern in recent years. In this research, afeasibility study evaluating energy conversion efficiency through agricultural waste gasification from the Pomelo garden, Taiwan, is demonstrated. we used a high-temperature gasifier to convert the pruning of the branches into syngas and biochar. In terms of syngas composition and calorific value assessment, we use the biogas monitoring system for analysis. Then, we used Raman spectroscopy and electron microscopy (EM) to diagnose the microstructure and surface morphology of biochar. The results indicate that the 1 ton of pruning of the branches can produce 1797.03m3 of syngas, corresponding to a calorific value of 9.1MJ/m3. The main components of the gas include CH4, H2, CO, and CO2, and the corresponding gas composition ratio is 16.8%, 7.1%, 13.7%, and 24.5%. Through the biomass syngas generator with a conversion efficiency of 30% for power generation, a total of 1,358kWh can be obtained per ton of pruning of the branches. In the research of biochar, its main characteristics in Raman spectroscopy are G bands and D bands. The first-order G and D bands are at 1580 and 1350 cm⁻¹, respectively. The G bands originates from the in-plane tangential stretching of the C−C bonds in the graphitic structure, and theD band corresponds to scattering from local defects or disorders present in carbon. The area ratio of D and G peaks (D/G) increases with the decrease of reaction temperature. The larger the D/G, the higher the defect concentration and the higher the porosity. This result is consistent with the microstructure displayed by SEM. The study is expected to be able to reuse agricultural waste and promote the development of agricultural and green energy circular economy.

Keywords: agricultural waste, gasification, energy conversion, pomelo garden

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Authors: Alaa T. Ali, Nevine H. Kheir El Din, Ehab S. Abdelhamid, Ahmed E. Amr

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Objective: Severe alveolar bone resorption is usually associated with a deficient amount of soft tissues. soft tissue expansion is introduced to provide an adequate amount of soft tissue over the grafted area. This study aimed to assess the efficacy of sub-periosteal self-inflating osmotic tissue expanders used as preparatory surgery before horizontal alveolar ridge augmentation using autogenous onlay block bone graft. Methods: A prospective randomized controlled clinical trial was performed. Sixteen partially edentulous patients demanding horizontal bone augmentation in the anterior maxilla were randomly assigned to horizontal ridge augmentation with autogenous bone block grafts harvested from the mandibular symphysis. For the test group, soft tissue expanders were placed sub-periosteally before horizontal ridge augmentation. Impressions were taken before and after STE, and the cast models were optically scanned and superimposed to be used for volumetric analysis. Horizontal ridge augmentation was carried out after STE completion. For the control group, a periosteal releasing incision was performed during bone augmentation procedures. Implants were placed in both groups at re-entry surgery after six months period. A core biopsy was taken. Histomorphometric assessment for newly formed bone surface area, mature collagen area fraction, the osteoblasts count, and blood vessel count were performed. The change in alveolar ridge width was evaluated through bone caliper and CBCT. Results: Soft tissue expander successfully provides a Surplus amount of soft tissues in 5 out of 8 patients in the test group. Complications during the expansion period were perforation through oral mucosa occurred in two patients. Infection occurred in one patient. The mean soft tissue volume gain was 393.9 ± 322mm. After 6 months. The mean horizontal bone gains for the test and control groups were 3.14 mm and 3.69 mm, respectively. Conclusion: STE with a sub-periosteal approach is an applicable method to achieve an additional soft tissue and to reduce bone block graft exposure and wound dehiscence.

Keywords: soft tissue expander, ridge augmentation, block graft, symphysis bone block

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Authors: Don Anushka Sandaruwan Elvitigala, P. D. S. U. Wickramasinghe, Jehee Lee

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Cystatins are a large superfamily of proteins which act as reversible inhibitors of cysteine proteases. Papain proteases and cysteine cathepsins are predominant substrates of cystatins. Cystatin superfamily can be further clustered into three groups as Stefins, Cystatins, and Kininogens. Among them, stefines are also known as family 1 cystatins which harbors cystatin Bs and cystatin As. In this study, a homologue of family one cystatins more close to cystatin Bs was identified from Korean black rockfish (Sebastes schlegeli) using a prior constructed cDNA (complementary deoxyribonucleic acid) database and designated as RfCyt1. The full-length cDNA of RfCyt1 consisted of 573 bp, with a coding region of 294 bp. It comprised a 5´-untranslated region (UTR) of 55 bp, and 3´-UTR of 263 bp. The coding sequence encodes a polypeptide consisting of 97 amino acids with a predicted molecular weight of 11kDa and theoretical isoelectric point of 6.3. The RfCyt1 shared homology with other teleosts and vertebrate species and consisted conserved features of cystatin family signature including single cystatin-like domain, cysteine protease inhibitory signature of pentapeptide (QXVXG) consensus sequence and N-terminal two conserved neighboring glycine (⁸GG⁹) residues. As expected, phylogenetic reconstruction developed using the neighbor-joining method showed that RfCyt1 is clustered with the cystatin family 1 members, in which more closely with its teleostan orthologues. An SYBR Green qPCR (quantitative polymerase chain reaction) assay was performed to quantify the RfCytB transcripts in different tissues in healthy and immune stimulated fish. RfCyt1 was ubiquitously expressed in all tissue types of healthy animals with gill and spleen being the highest. Temporal expression of RfCyt1 displayed significant up-regulation upon infection with Aeromonas salmonicida. Recombinantly expressed RfCyt1 showed concentration-dependent papain inhibitory activity. Collectively these findings evidence for detectable protease inhibitory and immunity relevant roles of RfCyt1 in Sebastes schlegeli.

Keywords: Sebastes schlegeli, family 1 cystatin, immune stimulation, expressional modulation

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Authors: Sinethemba Yakobi, Lindiwe Zuma, Ofentse Pooe

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Gonococcal infections present a notable public health issue, and the major approach for treatment involves using β-lactam antibiotics that specifically target penicillin-binding protein 2 (PBP2) in Neisseria gonorrhoeae. This study examines the influence of flavonoids, namely rutin, on the structural changes of PBP2 in both penicillin-resistant (FA6140) and penicillin-susceptible (FA19) strains. The research clarifies the structural effects of particular mutations, such as inserting an aspartate residue at position 345 (Asp-345a) in the PBP2 protein. The strain FA6140, which is resistant to penicillin, shows specific changes that lead to a decrease in penicillin binding. These mutations, namely P551S and F504L, significantly impact the pace at which acylation occurs and the stability of the strain under high temperatures. Molecular docking analyses investigate the antibacterial activities of rutin and other phytocompounds, emphasizing its exceptional binding affinity and potential as an inhibitor of PBP2. Quercetin and protocatechuic acid have encouraging antibacterial effectiveness, with quercetin displaying characteristics similar to those of drugs. Molecular dynamics simulations offer a detailed comprehension of the interactions between flavonoids and PBP2, highlighting rutin's exceptional antioxidant effects and strong affinity for the substrate binding site. The study's wider ramifications pertain to the pressing requirement for antiviral treatments in the context of the ongoing COVID-19 epidemic. Flavonoids have a strong affinity for binding to PBP2, indicating their potential as inhibitors to impair cell wall formation in N. gonorrhoeae. Ultimately, this study provides extensive knowledge on the interactions between proteins and ligands, the dynamics of the structure, and the ability of flavonoids to combat penicillin-resistant N. gonorrhoeae bacteria. The verified simulation outcomes establish a basis for creating potent inhibitors and medicinal therapies to combat infectious illnesses.

Keywords: phytochemicals, penicillin-binding protein 2, gonococcal infection, ligand-protein interaction, binding energy, neisseria gonorrhoeae FA19, neisseria gonorrhoeae FA6140, flavonoids

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Authors: Yik Sin Chan, Nam Weng Sit, Fook Yee Chye, van Ofwegen Leen, de Voogd Nicole, Kong Soo Khoo

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Chikungunya fever is an arboviral disease transmitted by the Aedes mosquitoes. It has resulted in epidemics of the disease in tropical countries in the Indian Ocean and South East Asian regions. The recent spread of this disease to the temperate countries such as France and Italy, coupled with the absence of vaccines and effective antiviral drugs make chikungunya fever a worldwide health threat. This study aims to investigate the anti-chikungunya virus activity of selected marine organism samples collected from Malaysian coastal areas, including seaweeds (Caulerpa racemosa, Caulerpa sertularioides and Kappaphycus alvarezii), a soft coral (Lobophytum microlobulatum) and a sponge (Spheciospongia vagabunda). Following lyophilization (oven drying at 40C for K. alvarezii) and grinding to powder form, each sample was subjected to sequential solvent extraction using hexane, chloroform, ethyl acetate, ethanol, methanol and distilled water in order to extract bioactive compounds. The antiviral activity was evaluated using monkey kidney epithelial (Vero) cells infected with the virus (multiplicity of infection=1). The cell viability was determined by Neutral Red uptake assay. 70% of the 30 extracts showed weak inhibitory activity with cell viability ≤30%. Seven of the extracts exhibited moderate inhibitory activity (cell viability: 31%-69%). These were the chloroform, ethyl acetate, ethanol and methanol extracts of C. racemosa; chloroform and ethyl acetate extracts of L. microlobulatum; and the chloroform extract of C. sertularioides. Only the hexane and ethanol extracts of L. microlobulatum showed strong inhibitory activity against the virus, resulting in cell viabilities (mean±SD; n=3) of 73.3±2.6% and 79.2±0.9%, respectively. The corresponding mean 50% effective concentrations (EC50) for the extracts were 14.2±0.2 and 115.3±1.2 µg/mL, respectively. The ethanol extract of the soft coral L. microlobulatum appears to hold the most promise for further characterization of active principles as it possessed greater selectivity index (SI>5.6) compared to the hexane extract (SI=2.1).

Keywords: antiviral, seaweed, sponge, soft coral, vero cell

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Authors: Katerina H. Takova, Ivan N. Minkov, Gergana G. Zahmanova

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Molecular farming is the production of recombinant proteins in plants with the aim to use the protein as a purified product, crude extract or directly in the planta. Plants gain more attention as expression systems compared to other ones due to the cost effective production of pharmaceutically important proteins, appropriate post-translational modifications, assembly of complex proteins, absence of human pathogens to name a few. In addition, transient expression in plant leaves enables production of recombinant proteins within few weeks. Hepatitis E virus (HEV) is a causative agent of acute hepatitis. HEV causes epidemics in developing countries and is primarily transmitted through the fecal-oral route. Presently, all efforts for development of Hepatitis E vaccine are focused on the Open Read Frame 2 (ORF2) capsid protein as it contains epitopes that can induce neutralizing antibodies. For our purpose, we used the CMPV-based vector-pEAQ-HT for transient expression of HEV ORF2 in Nicotiana benthamina. Different molecular analysis (Western blot and ELISA) showed that HEV ORF2 capsid protein was expressed in plant tissue in high-yield up to 1g/kg of fresh leaf tissue. Electron microscopy showed that the capsid protein spontaneously assembled in low abundance virus-like particles (VLPs), which are highly immunogenic structures and suitable for vaccine development. The expressed protein was recognized by both human and swine HEV positive sera and can be used as a diagnostic reagent for the detection of HEV infection. Production of HEV capsid protein in plants is a promising technology for further HEV vaccine investigations. Here, we reported for a rapid high-yield transient expression of a recombinant protein in plants suitable for vaccine production as well as a diagnostic reagent. Acknowledgments -The authors’ research on HEV is supported with grants from the Project PlantaSYST under the Widening Program, H2020 as well as under the UK Biotechnological and Biological Sciences Research Council (BBSRC) Institute Strategic Programme Grant ‘Understanding and Exploiting Plant and Microbial Secondary Metabolism’ (BB/J004596/1). The authors want to thank Prof. George Lomonossoff (JIC, Norwich, UK) for his contribution.

Keywords: hepatitis E virus, plant molecular farming, transient expression, vaccines

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Authors: S. D. Kadir

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Background: Antibiotics have always been at the centrum of the revolution of modern microbiology. Micro-organisms and its pathogenicity, resistant organisms, inappropriate or over usage of various types of antibiotic agents are fuelled multidrug-resistant pathogenic organisms. Our present time review report mainly focuses on the therapeutic condition of antibiotic resistance and the possible roots behind the development of antibiotic resistance in Bangladesh in 2019. Methodology: The systemic review has progressed through a series of research analyses on various manuscripts published on Google Scholar, PubMed, Research Gate, and collected relevant information from established popular healthcare and diagnostic center and its subdivisions all over Bangladesh. Our research analysis on the possible assurance of antibiotic resistance been ensured by the selective medical reports and on random assay on the extent of individual antibiotic in 2019. Results: 5 research articles, 50 medical report summary, and around 5 patients have been interviewed while going through the estimation process. We have prioritized research articles where the research analysis been performed by the appropriate use of the Kirby-Bauer method. Kirby-Bauer technique is preferred as it provides greater efficiency, ensures lower performance expenditure, and supplies greater convenience and simplification in the application. In most of the reviews, clinical and laboratory standards institute guidelines were strictly followed. Most of our reports indicate significant resistance shown by the Beta-lactam drugs. Specifically by the derivatives of Penicillin's, Cephalosporin's (rare use of the first generation Cephalosporin and overuse of the second and third generation of Cephalosporin and misuse of the fourth generation of Cephalosporin), which are responsible for almost 67 percent of the bacterial resistance. Moreover, approximately 20 percent of the resistance was due to the fact of drug pumping from the bacterial cell by tetracycline and sulphonamides and their derivatives. Conclusion: 90 percent of the approximate antibiotic resistance is due to the usage of relative and true broad-spectrum antibiotics. The environment has been created by the following circumstances where; the excessive usage of broad-spectrum antibiotics had led to a condition where the disruption of native bacteria and a series of anti-microbial resistance causing a disturbance of the surrounding environments in medium, leading to a state of super-infection.

Keywords: antibiotics, antibiotic resistance, Kirby Bauer method, microbiology

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Authors: Raphael Udeh, Luis García De Guadiana Romualdo, Xenia Dolje-Gore

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Background: Quite disturbing is the huge public health impact of COVID-19: As at today [25th March 2021, the COVID-19 global burden shows over 123 million cases and over 2.7 million deaths worldwide. Rationale: Recent evidence shows calprotectin’s potential as a therapeutic target, stating that tasquinimod, from the Quinoline-3-Carboxamide family is capable of blocking the interaction between calprotectin and TLR4. Hence preventing the cytokine release syndrome, that heralds the functional exhaustion in COVID-19. Early preclinical studies showed that tasquinimod inhibit tumor growth and prevent angiogenesis/cytokine storm. Phase I – III clinical studies in prostate cancer showed it has a good safety profile with good radiologic progression free survival but no effect on overall survival. Rationale/hypothesis: Strategic endeavors have been amplified globally to assess new therapeutic interventions for COVID-19 management – thus the clinical and antiviral efficacy of tasquinimod in COVID-19 remains to be explored. Hence the primary objective of this trial will be to evaluate the efficacy of tasquinimod in the treatment of adult patients with severe COVID-19 infections. Therefore, I hypothesise that among adults with COVID19 infection, tasquinimod will reduce the severe respiratory distress associated with COVID-19 compared to placebo, over a 28-day study period. Method: The setting is in Europe. Design – a randomized, placebo-controlled, phase II double-blinded trial. Trial lasts for 28 days from randomization, Tasquinimod capsule given as 0.5mg daily 1st fortnight, then 1mg daily 2nd fortnight. I0 outcome - assessed using six-point ordinal scale alongside eight 20 outcomes. 125 participants to be enrolled, data collection at baseline and subsequent data points, and safety reporting monitored via serological profile. Significance: This work could potentially establish tasquinimod as an effective and safe therapeutic agent for COVID-19 by reducing the severe respiratory distress, related time to recovery, time on oxygen/admission. It will also drive future research – as in larger multi-centre RCT.

Keywords: Calprotectin, COVID-19, Phase II Trial, Tasquinimod

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Authors: Portia Murphy, Danica Vasic, Anoja W. Gunaratne, Encarnita Sitchon, Teresita Tugonon, Marou Ison, Antoinette Le Busque, Christelle Pagonis, Thomas J. Borody

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Irritable bowel syndrome (IBS) is a chronic gastrointestinal disorder that affects an estimated 11% of the population globally with the most predominant symptoms being abdominal pain, bloating and altered bowel movements. All age groups suffer from IBS although the prevalence of IBS decreases for age groups over 50 years. Women are more likely to suffer from IBS than men. IBS can be categorized into 3 groups based on the type of altered bowel movement: diarrhea-predominant IBS (IBS-D), constipation-predominant IBS (IBS-C) and IBS with mixed bowel habit (IBS-M). The contribution of the gut microbiome to the etiology of IBS is becoming increasingly recognized with rising use of anti-microbial agents. Previous studies on vancomycin and rifaximin used as monotherapy or in combination have been conducted mainly on IBS-C and showed marked improvements in the symptoms. According to our knowledge, no studies reported using these two combinations of antibiotics for IBS-D. Here, we report a consecutive cohort of 18 patients treated with both vancomycin and rifaximin for IBS-D. These patients’ records were reviewed retrospectively. In this cohort, patients ages were between 24-74 years (mean 44 years) and 9 were female. Baseline all patients had diarrhea, 4 with mucus and one with blood. Patients reported other symptoms were abdominal pain (n=11) bloating (n=9), flatulence (n=7), fatigue (n=4) and nausea (n=3). Patients treatments were personalized according to their symptom severity and tolerability and were treated with combination of rifaximin (500 - 3000mg/d) and vancomycin (500mg - 1500mg/d) for an ongoing period. Follow-ups were conducted between 2-32 weeks’ time. Of all patients, 89% patients reported improvement of the symptoms, 1 reported no change and 1 patient’s symptoms got worse. The mechanism of action for both vancomycin and rifaximin involves the inhibition of bacterial cell wall and protein synthesis respectively. The role of these medications in improving the symptoms of this cohort suggests that IBS-D may be microbiome infection driven. In this cohort, similar patient presentations to Clostridium difficile, as well as symptom improvement with the use of rifaximin and particularly vancomycin, suggest that the infectious agent may be an unidentified Clostridium. These preliminary results offer an alternative etiology for IBS-D not previously considered and open the avenue for new research.

Keywords: clostridium deficile, diarrhea predominant Irritable Bowel Syndrome, microbiome, vancomycin/rifaximin combination

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Authors: Yutaro Kyuma, Sung-Jun Yoo, Kazuhide Ito

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A commuter bus remains important as a means to network public transportation between railway stations and terminals within cities. In some cases, the boarding time becomes longer, and the boarding rate tends to be higher corresponding to the development of urban cities. The interior environmental quality, e.g. temperature and air quality, in a commuter bus is relatively heterogeneous and complex compared to that of an indoor environment in buildings due to several factors: solar radiative heat – which comes from large-area windows –, inadequate ventilation rate caused by high density of commuters, and metabolic heat generation from travelers themselves. In addition to this, under conditions where many passengers ride in the enclosed space, contact and airborne infectious risk have attracted considerable attention in terms of public health. From this point of view, it is essential to develop the prediction method for assessment of interior environmental quality and infection risk in commuter bus cabins. In this study, we developed a numerical commuter bus model integrated with computer simulated persons to reproduce realistic indoor environment conditions with high occupancy during commuting. Here, computer simulated persons were newly designed considering different types of geometries, e.g., standing position, seating position, and individual differences. Here we conducted coupled computational fluid dynamics (CFD) analysis with radiative heat transfer analysis under steady state condition. Distributions of heterogeneous air flow patterns, temperature, and moisture surrounding the human body under some different ventilation system were analyzed by using CFD technique, and skin surface temperature distributions were analyzed using thermoregulation model that integrated into computer simulated person. Through these analyses, we discussed the interior environmental quality in specific commuter bus cabins. Further, inhaled air quality of each passenger was also analyzed. This study may have possibility to design the ventilation system in bus for improving thermal comfort of occupants.

Keywords: computational fluid dynamics, CFD, computer simulated person, CSP, contaminant, indoor environment, public health, ventilation

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Authors: Khosro Barkhordari, Fateme Sadr, Mina Pashang

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Back ground: Blood transfusion is one of the major issues in cardiac surgery patients. Transfusing patients based on fixed cut-off points of hemoglobin is the current protocol in most institutions. The hemoglobin level of 7- 10 has been suggested for blood transfusion in cardiac surgery patients. We aimed to evaluate if blood transfusion based on change in percentage of hematocrit has different outcomes. Methods: In this retrospective cohort study, we investigated the early postoperative outcome of cardiac surgery patients who received blood transfusions at Tehran Heart Center Hospital, IRAN. We reviewed and analyzed the basic characteristics and clinical data of 700 patients who met our exclusion and inclusion criteria. The two groups of blood transfused patients were compared, those who have 30-50 percent decrease in basal hematocrit versus those with 10 -29 percent decrease. Results: This is ongoing study, and the results would be completed in two weeks after analysis of the date. Conclusion: Early analysis has shown no difference in early post-operative outcomes between the two groups, but final analysis will be completed in two weeks. 1-Department of Anesthesiology and Critical Care, Tehran Heart Center, Tehran University of Medical Sciences, Tehran, IRAN 2- Department of Research, Tehran Heart Center, Tehran, IRAN Quantitative variables were compared using the Student t-test or the Mann‐Whitney U test, as appropriate, while categorical variables were compared using the χ2 or the Fisher exact test, as required. Our intention was to compare the early postoperative outcomes between the two groups, which include 30 days mortality, Length of ICU stay, Length of hospital stay, Intubation time, Infection rate, acute kidney injury, and respiratory complications. The main goal was to find if transfusing blood based on changes in hematocrit from a basal level was better than to fixed cut-off point regarding early post-operative outcomes. This has not been studied enough and may need randomized control trials.

Keywords: post-operative, cardiac surgery, outcomes, blood transfusion

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Authors: Mike Yaw Osei-Atweneboana, John Asiedu Larbi, Edward Jenner Tettevi

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Background: The lymphatic filariasis (LF) control programme has been on-going in Ghana since 2000. This community-wide approach involves the use of ivermectin (IVM) and albendazole (ALB). Soil-transmitted helminth (STH) infections control is augmented within this programme; however, in areas where LF is not prevalent, albendazole alone is administered to school children. The purpose of this study was therefore, to determine the efficacy of albendazole against soils transmitted helminths and the impact of mass drug administration of albendazole and ivermectin on the health status of children of school going age and pregnant women. Material/Methods: This was a twelve months longitudinal study. A total of 412 subjects including school children (between the ages of 2-17 years) and pregnant women were randomly selected from four endemic communities in Kpandai district of the Northern region. Coprological assessment for parasites was based on the Kato–Katz technique in both dry and rainy seasons at baseline, 21 days and 3 months post-treatment. Single-dose albendazole treatment was administered to all patients at baseline. Preserved samples are currently under molecular studies to identify possible single nucleotide polymorphism (SNP) within the beta tubulin gene which is associated with benzimidazole resistance. Results: Of all the parasites found (hookworm, Trichuris trichiura, Hymenolepis nana, and Taenia sp.); hookworm was the most prevalent. In the dry season, the overall STHs prevalence at pre-treatment was 29%, while 9% and 13% prevalence was recorded at 21 days, and three months after treatment respectively. However, in the rainy season, the overall STHs prevalence was 8%, while 4% and 12% was recorded at 21 days and three months respectively after ALB treatment. In general, ALB treatment resulted in an overall hookworm egg count reduction rate of 89% in the dry season and 93% in the rainy season, while the T. trichiura egg count reduction rate was 100% in both seasons. Conclusions: STH infections still remains a significant public health burden in Ghana. Hookworm infection seems to respond poorly or sub-optimally to ALB, raising concerns of possible emergence of resistance which may lead to a major setback for the control and elimination of STH infections, especially hookworm infections.

Keywords: hookworm, sub-optimal response, albendazole, trichuriasis, soil-transmitted helminths

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Authors: Zsolt Szucs, Viktor Kelemen, Son Le Thai, Magdolna Csavas, Erzsebet Roth, Gyula Batta, Annelies Stevaert, Evelien Vanderlinden, Aniko Borbas, Lieve Naesens, Pal Herczegh

Abstract:

The approval of modern glycopeptide antibiotics such as dalbavancin and oritavancin which have excellent activity against Gram-positive bacteria, encouraged our research group to prepare semisynthetic compounds from several members of glycopeptides by various chemical methods. Derivatives from the aglycone of ristocetin, eremomycin, vancomycin and a pseudoaglycon of teicoplanin have been synthesized in a systematic manner. Interestingly, some of the aglycoristocetin derivatives displayed noteworthy anti-influenza activity. More recently our group has been focusing on the modifications of one of the pseudoaglycons of teicoplanin. The reaction of N-ethoxycarbonyl maleimide derivatives with the primary amino function, the copper-catalysed azide-alkyne click reaction and the sulfonylation of the N-terminus were utilized to obtain systematic series of compounds. All substituents provide a more lipophilic character to the new molecules compared to the parent antibiotics, which is known to be favourable for activity against resistant bacteria. Lipoglycopeptides are also known to have antiviral properties, which has been predominantly studied on HIV by others. The structure-activity relationship study of our compounds revealed the influence of a few structural elements on biological activity. In many cases, minimal changes in lipophilicity and structure produced great differences in efficacy and cytotoxicity. In vitro experiments showed that these compounds are not only active against glycopeptide resistant Gram-positive bacteria but in several cases they prevent the infection of cell cultures by different strains of influenza viruses. This is probably related to the inhibition of the viral entry into the host cell nucleus, of which the exact mechanism is unknown. In some instances, reasonably low concentrations were sufficient to observe this effect. Several derivatives were highly cytotoxic at the same time, but some of them displayed a good selectivity index. The antiviral properties of the compounds are not restricted to influenza viruses e.g., some of them showed good activity against Human Coronavirus 229E. This work could potentially lead to the development of antiviral drugs which possess the crucial structural motifs that are needed for antiviral activity, while missing those which contribute to the antibacterial effect.

Keywords: antiviral, glycopeptide, semisynthetic, teicoplanin

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Authors: Amirreza Razzaghipour Sorkhab

Abstract:

One of the most common disorders among humans is hearing impairment. This paper provides an evidence base that recovers understanding of Meniere’s disease and highlights the physical and mental health correlates of the disorder. Meniere's disease is more common in the elderly. The term idiopathic endolymphatic hydrops has been attributed to this disease by some in the previous. Meniere’s disease demonstrations a genetic tendency, and a family history is found in 10% of cases, with an autosomal dominant inheritance pattern. The COCH gene may be one of the hereditary factors contributing to Meniere’s disease, and the possibility of a COCH mutation should be considered in patients with Meniere’s disease symptoms. Should be considered Missense mutations in the COCH gene cause the autosomal dominant sensorineural hearing loss and vestibular disorder. Meniere’s disease is a complex, heterogeneous disorder of the inner ear and that is characterized by episodes of vertigo lasting from minutes to hours, fluctuating sensorineural hearing loss, tinnitus, and aural fullness. The existing evidence supports the suggestion that age and sleep disorder are risk factors for Meniere's disease. Many factors have been reported to precipitate the progress of Menier, including endolymphatic hydrops, immunology, viral infection, inheritance, vestibular migraine, and altered intra-labyrinthine fluid dynamics. Although there is currently no treatment that has a proven helpful effect on hearing levels or on the long-term evolution of the disease, however, in the primary stages, the hearing may improve among attacks, but a permanent hearing loss occurs in the majority of cases. Current publications have proposed a role for the intratympanic use of medicine, mostly aminoglycosides, for the control of vertigo. more than 85% of patients with Meniere's disease are helped by either changes in lifestyle and medical treatment or minimally aggressive surgical procedures such as intratympanic steroid therapy, intratympanic gentamicin therapy, and endolymphatic sac surgery. However, unilateral vestibular extirpation methods (intratympanic gentamicin, vestibular nerve section, or labyrinthectomy) are more predictable but invasive approaches to control the vertigo attacks. Medical therapy aimed at reducing endolymph volume, such as low-sodium diet, diuretic use, is the typical initial treatment.

Keywords: meniere's disease, endolymphatic hydrops, hearing loss, vertigo, tinnitus, COCH gene

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Authors: Berina Pilipović, Saša Pilipović, Maja Pašić-Kulenović

Abstract:

Inflammation is the body's response to impaired homeostasis caused by infection, injury or trauma resulting in systemic and local effects. Inflammation causes the body's response to injury and is characterized by a series of events including inflammatory response, response to pain receptors and the recovery process. Inflammation can be acute and chronic. The inflammatory response is described in three different phases. Free radical is an atom or molecule that has the unpaired electron and is therefore generally very reactive chemical species. Biologically important example of reaction with free radicals is called Lipid peroxidation (LP). Lipid peroxidation reactions occur in biological membranes, and if at the outset is not stopped with the action of antioxidants, it will bring damage to the membrane, which results in partial or complete loss of their physiological functions. Calcium antagonists and beta-adrenergic receptor antagonists are known drugs, and for many years and widely used in the treatment of cardiovascular diseases. Some of these compounds also show antioxidant activity. The mechanism of antioxidant activities of calcium antagonists and beta-blockers is unknown, since their structure varies widely. This research investigated the possible local anti-inflammatory activity of ointments containing 1% carvedilol in the white petrolatum USP. Ear inflammation was induced by 3% croton oil acetone solution, in quantity of 10 µl on both mouse ears. Albino Swiss mouse (n = 8) are treated with 2.5 mg/ear ointment, and control group was treated on the same way as previous with hydrocortisone 1% ointment (2.5 mg/ear). The other ear of the same animal was used as control one. Ointments were administered once per day, on the left ear. After treatment, ears were observed for three days. After three days, we measured mass (mg) of 6 mm ear punch of treated and controlled ears. The results of testing anti-inflammatory effects of ointments with carvedilol in the mouse ear model show stronger observed effect than ointment with 1% hydrocortisone in the same basis. Identical results were confirmed by the difference between the mass of 6 mm ears punch. The results were also confirmed by histological examination. Ointments with carvedilol showed significant reduction of the inflammation process caused by croton oil on the mouse inflammation model.

Keywords: antioxidant, carvedilol, inflammation, mouse ear

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Authors: Moses Mncwabe

Abstract:

Both Public Representatives and Legislatures have an imperative role towards strengthening interventions to reduce and cease Sexual Transmitted Infections (STIs) specifically the Human Immunodeficiency Virus (HIV). Scaling-up constituency work in support of interventions earmarked for mitigating the compromising socio-economic impacts of advanced HIV is extremely essential. Though the antiretroviral treatment (ART) has saved million lives that would have perished without it, the Joint United Nations Programme on HIV/AIDS (2012) states that more efforts should be redirected to prevention strategies to close the tap of new infections. It is against this backdrop that Legislatures as law making institutions have undisputed role to play in HIV alleviation because of the position they occupy in the society. Furthermore, Public Representatives are arguably idolised by young people for the role they play hence it is incumbent upon them to use their moral and political responsibility to aid the interventions for HIV prevention (Inter-Parliamentary Union, Joint United Nations Programme on HIV/AIDS & United Nations Development Programme, 2007). Moreover, the continuous HIV infection and its devastating effects specifically in Southern African region has brought closer the disease to public representatives and demanded calculated interventions warranting both public representatives and legislatures to be more visible in various ways such as taking HIV counselling and testing publicly, oversight, reducing stigma and discrimination, partnering with civil society organisations (CSOs) and facilitating debates on HIV across parliamentary and social platforms. The effects of advanced HIV yearn for public representatives to be seen, accessed, felt, engaged, partnered and lobbied for pro-human rights legislations and ideal oversight to coerce the executive to deliver on their core responsibilities like providing basic services to the electorates (AIDS Law Project (2003). The National Democratic Institute for International Affairs and the Southern African Development Community Parliamentary Forum (2004) assert that the omission of Public Representatives and Legislatures in the HIV prevention agenda is a serious deficiency in the fight against HIV and AIDS. In light of this, this paper argues the innovative and legislative ways in which both the Public Representative and the Legislatures should play in HIV prevention.

Keywords: legislature, public representative, oversight, HIV and AIDS, constituency, service delivery

Procedia PDF Downloads 388

Authors: Folajimi Oladimeji Shorunke

Abstract:

Background: As of October 9, 2023, diphtheria has been noted to be re-emerging in four African countries: Algeria, Guinea, Niger, and Nigeria. 14,587 cases with a case fatality rate of 4.1% have been reported across these regions, with Nigeria alone responsible for over 90% of the cases. In Taraba State Nigeria, the index case of Diphtheria was reported on epidemic week 34, August 24, 2023 with 75 confirmed cases found 3 months after the index case and a case fatality of 1.3%. it described the distribution, trend and common symptoms found during the Outbreak. Methods: The Taraba State Diphtheria Outbreak line list on the Surveillance Outbreak Response Management & Analysis System (SORMAS) for all its 16 local government areas (LGAs) was analyzed using descriptive statistics (graphs, chats and maps) for the period between 24th August to 25th November 2023. Primary data was collected through the use of case investigation forms and variables like Age, gender, date of disease onset, LGA of residence, and symptoms exhibited were collected. Naso-pharyngeal and oro-pharyngeal samples were also collected for Laboratory confirmation. The most common diphtheria symptoms during the outbreak were also highlighted. Results: A total of 75 Diphtheria cases were diagnosed in 10 of the 16 LGAs in Taraba State between 24th August to 25th November 2023, 72% of the cases were female, with the age range 0-9 years having the highest proportion of 34 (45.3%), the number of positive diagnosis reduces with age among cases. The Northern part of the State had the highest proportion of cases, 68 (90.7%), with Ardo-Kola LGA having the highest 28 (29%). The remaining 9.2% of cases is shared among the middle belt and southern part of the State. The Epi-curve took the characteristic shape of a propagated infection with peaks at the 37th, 39th and 45th epidemic weeks. The most common symptoms found in cases were fever 71 (94.7%), pharyngitis 65( 86.7%), tonsillitis 60 (80%), and laryngitis 53 (71%). Conclusions: The number of confirmed cases of Diphtheria in Taraba State, Nigeria between 24th August to 25th November 2023 is 75. The condition is higher among females than male and mostly affected children between ages 0-9 with the northern part of the state most affected. The most common symptoms exhibited by cases include fever, pharyngitis, tonsillitis and laryngitis.

Keywords: diphtheria outbreak, taraba nigeria, descriptive epidemiology, trend

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Authors: Mmamapudi Kubjane, Natacha Berkowitz, Rene Goliath, Naomi S. Levitt, Robert J. Wilkinson, Tolu Oni

Abstract:

Background: South Africa remains a high tuberculosis (TB) burden country globally and the burden of diabetes – a TB risk factor is growing rapidly. As an infectious disease, TB also induces transient hyperglycaemia. Therefore, screening for diabetes in newly diagnosed tuberculosis patients may result in misclassification of transient hyperglycaemia as diabetes. Objective: The objective of this study was to determine and compare the prevalence of hyperglycaemia (diabetes and impaired glucose regulation (IGR)) in TB patients and to assess the cross-sectional association between TB and hyperglycaemia at enrolment and after three months of follow-up. Methods: Consecutive adult TB and non-TB participants presenting at a TB clinic in Cape Town were enrolled in this cross-sectional study and follow-up between July 2013 and August 2015. Diabetes was defined as self-reported diabetes, fasting plasma glucose (FPG) ≥ 7.0 mmol·L⁻¹ or glycated haemoglobin (HbA1c) ≥ 6.5%. IGR was defined as FPG 5.5– < 7.0 mmol·L⁻¹ or HbA1c 5.7– < 6.5%. TB patients initiated treatment. After three months, all participants were followed up and screened for diabetes again. The association between TB and hyperglycaemia was assessed using logistic regression adjusting for potential confounders including sex, age, income, hypertension, waist circumference, previous prisoner, marital status, work status, HIV status. Results: Diabetes screening was performed in 852 participants (414 TB and 438 non-TB) at enrolment and in 639 (304 TB and 335 non-TB) at three-month follow-up. The prevalence of HIV-1 infection was 69.6% (95% confidence interval (CI), 64.9–73.8 %) among TB patients, and 58.2% (95% CI, 53.5–62.8 %) among the non-TB participants. Glycaemic levels were much higher in TB patients than in the non-TB participants but decreased over time. Among TB patients, the prevalence of IGR was 65.2% (95% CI 60.1 - 69.9) at enrollment and 21.5% (95% CI 17.2-26.5) at follow-up; and was 50% (45.1 - 54.94) and 32% (95% CI 27.9 - 38.0) respectively, among non-TB participants. The prevalence of diabetes in TB patients was 12.5% (95% CI 9.69 – 16.12%) at enrolment and 9.2% (95% CI, 6.43–13.03%) at follow-up; and was 10.04% (95% CI, 7.55–13.24%) and 8.06% (95% CI, 5.58–11.51) respectively, among non-TB participants. The association between TB and IGT was significant at enrolment (adjusted odds ratio (OR) 2.26 (95% CI, 1.55-3.31) but disappeared at follow-up 0.84 (0.53 - 1.36). However, the TB-diabetes association remained positive and significant both at enrolment (2.41 (95% CI, 1.3-4.34)) and follow-up (OR 3.31 (95% CI, 1.5 - 7.25)). Conclusion: Transient hyperglycaemia exists during tuberculosis. This has implications on diabetes screening in TB patients and suggests a need for diabetes confirmation tests during or after TB treatment. Nonetheless, the association between TB and diabetes noted at enrolment persists at 3 months highlighting the importance of diabetes control and prevention for TB control. Further research is required to investigate the impact of hyperglycaemia (transient or otherwise) on TB outcomes to ascertain the clinical significance of hyperglycemia at enrolment.

Keywords: diabetes, impaired glucose regulation, transient hyperglycaemia, tuberculosis

Procedia PDF Downloads 159

Authors: Danilo A. F. Fontes, Magaly A. M.Lyra, Maria L. C. Moura, Leslie R. M. Ferraz, Salvana P. M. Costa, Amanda C. Q. M. Vieira, Larissa A. Rolim, Giovanna C. R. M. Schver, Ping I. Lee, Severino Alves-Júnior, José L. Soares-Sobrinho, Pedro J. Rolim-Neto

Abstract:

Efavirenz (EFV) is a first-choice drug in antiretroviral therapy with high efficacy in the treatment of infection by Human Immunodeficiency Virus, which causes Acquired Immune Deficiency Syndrome (AIDS). EFV has low solubility in water resulting in a decrease in the dissolution rate and, consequently, in its bioavailability. Among the technological alternatives to increase solubility, the Lamellar Double Hydroxides (LDH) have been applied in the development of systems with poorly water-soluble drugs. The use of analytical techniques such as X-Ray Diffraction (XRD), Infrared Spectroscopy (IR) and Differential Scanning Calorimetry (DSC) allowed the elucidation of drug interaction with the lamellar compounds. The objective of this work was to characterize and develop the binary systems with EFV and LDH in order to increase the solubility of the drug. The LDH-CaAl was synthesized by the method of co-precipitation from salt solutions of calcium nitrate and aluminum nitrate in basic medium. The systems EFV-LDH and their physical mixtures (PM) were obtained at different concentrations (5-60% of EFV) using the solvent technique described by Takahashi & Yamaguchi (1991). The characterization of the systems and the PM’s was performed by XRD techniques, IR, DSC and dissolution test under non-sink conditions. The results showed improvements in the solubility of EFV when associated with LDH, due to a possible change in its crystal structure and formation of an amorphous material. From the DSC results, one could see that the endothermic peak at 173°C, temperature that correspond to the melting process of EFZ in the crystal form, was present in the PM results. For the EFZ-LDH systems (with 5, 10 and 30% of drug loading), this peak was not observed. XRD profiles of the PM showed well-defined peaks for EFV. Analyzing the XRD patterns of the systems, it was found that the XRD profiles of all the systems showed complete attenuation of the characteristic peaks of the crystalline form of EFZ. The IR technique showed that, in the results of the PM, there was the appearance of one band and overlap of other bands, while the IR results of the systems with 5, 10 and 30% drug loading showed the disappearance of bands and a few others with reduced intensity. The dissolution test under non-sink conditions showed that systems with 5, 10 and 30% drug loading promoted a great increase in the solubility of EFV, but the system with 10% of drug loading was the only one that could keep substantial amount of drug in solution at different pHs.

Keywords: Efavirenz, Lamellar Double Hydroxides, Pharmaceutical Techonology, Solubility

Procedia PDF Downloads 581

Authors: Ibrahim Siddig Hamid, Ikram Mohamed Eltayeb

Abstract:

Trachyspermum ammi belongs to the family Apiaceae, is used traditionally for the treatment of gastrointestinal ailments, lack of appetite and bronchial problems as well used as antiseptic, antimicrobial, antipyretic, febrifugal and in the treatment of typhoid fever. Peganum harmala belongs to the family Zygophyllaceae it has been reported to have an antibacterial activity and used to treat depression and recurring fevers. It also used to kill algae, bacteria, intestinal parasites and molds. In Sudan, the combination of two plants are traditionally used for the treatment of bacillary dysentery. Bacillary dysentery is caused by one or more types of Shigella species bacteria mainly Shigella dysenteri and shigella flexneri. Bacillary dysentery is mainly found in hot countries like Sudan with poor hygiene and sanitation. Bacillary dysentery causes sudden onset of high fever and chills, abdominal pain, cramps and bloating, urgency to pass stool, weight loss, and dehydration and if left untreated it can lead to serious complications including delirium, convulsions and coma. A serious infection like this can be fatal within 24 hours. The objective of this study is to investigate the in vitro susceptibility of Sh. flexneri and Sh. dysenteriae to the T. ammi and P. harmala. T. ammi and P. harmala were extracted by 96% ethanol using Soxhlet apparatus. The antimicrobial activity of the extracts was investigated according to the disc diffusion method. The discs were prepared by soaking sterilized filter paper discs in 20 microliter of serially diluted solutions of each plant extract with the concentrations (100, 50, 25, 12.5, 6.25mg/dl) then placing them on Muller Hinton Agar plates that were inoculated with bacterial suspension separately, the plates were incubated for 24 hours at 37c and the minimum inhibitory concentration of the extract which was the least concentration of the extract to inhibit fungal growth was determined. The results showed the high antimicrobial activity of T. ammi extract with an average diameter zone ranging from 18-20 mm and its minimum inhibitory concentration was found to be 25 mg/ml against the two shigella species. P. harmala extract was found to have slight antibacterial effect against the two bacteria. This result justified the Sudanese traditional use of Trachyspermum ammi plant for the treatment of bacillary dysentery.

Keywords: harmala, peganum, shigella, trachyspermum

Procedia PDF Downloads 242

Authors: H. Akhloufi, M. Hulscher, J. M. Prins, I. H. Van Der Sijs, D. Melles, A. Verbon

Abstract:

Background: A timely switch from intravenous to oral antibiotic therapy has many advantages, such as reduced incidence of IV-line related infections, a decreased hospital length of stay and less workload for healthcare professionals with equivalent patient safety. Additionally, numerous studies have demonstrated significant decreases in costs of a timely intravenous to oral antibiotic therapy switch, while maintaining efficacy and safety. However, a considerable variation in iv to oral antibiotic switch therapy criteria has been described in literature. Here, we report the development of a set of iv to oral switch criteria that are generally applicable in all hospitals. Material/methods: A RAND-modified Delphi procedure, which was composed of 3 rounds, was used. This Delphi procedure is a widely used structured process to develop consensus using multiple rounds of questionnaires within a qualified panel of selected experts. The international expert panel was multidisciplinary and composed out of clinical microbiologists, infectious disease consultants and clinical pharmacists. This panel of 19 experts appraised 6 major intravenous to oral antibiotic switch therapy criteria and operationalized these criteria using 41 measurable conditions extracted from the literature. The procedure to select a concise set of iv to oral switch criteria included 2 questionnaire rounds and a face-to-face meeting. Results: The procedure resulted in the selection of 16 measurable conditions, which operationalize 6 major intravenous to oral antibiotic switch therapy criteria. The following 6 major switch therapy criteria were selected: (1) Vital signs should be good or improving when bad. (2) Signs and symptoms related to the infection have to be resolved or improved. (3) The gastrointestinal tract has to be intact and functioning. (4) The oral route should not be compromised. (5) Absence of contra-indicated infections. (6) An oral variant of the antibiotic with good bioavailability has to exist. Conclusions: This systematic stepwise method which combined evidence and expert opinion resulted in a feasible set of 6 major intravenous to oral antibiotic switch therapy criteria operationalized by 16 measurable conditions. This set of early antibiotic iv to oral switch criteria can be used in daily practice in all adult hospital patients. Future use in audits and as rules in computer assisted decision support systems will lead to improvement of antimicrobial steward ship programs.

Keywords: antibiotic resistance, antibiotic stewardship, intravenous to oral, switch therapy

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Authors: Mohammadjavad Sotoudeheian

Abstract:

COVID-19, which began in December 2019, uses the angiotensin-converting enzyme 2 (ACE2) receptor to enter and spread through the cells. ACE2 mRNA is present in almost every organ, including nasopharynx, lung, as well as the brain. Ports of entry of SARS-CoV-2 into the central nervous system (CNS) may include arterial circulation, while viremia is remarkable. However, it is imperious to develop neurological symptoms evaluation CSF analysis in patients with COVID-19, but theoretically, ACE2 receptors are expressed in cerebellar cells and may be a target for SARS-CoV-2 infection in the brain. Recent evidence agrees that SARS-CoV-2 can impact the brain through direct and indirect injury. Two biomarkers for CNS injury, glial fibrillary acidic protein (GFAP) and neurofilament light chain (NFL) detected in the plasma of patients with COVID-19. NFL, an axonal protein expressed in neurons, is related to axonal neurodegeneration, and GFAP is over-expressed in CNS inflammation. GFAP cytoplasmic accumulation causes Schwan cells to misfunction, so affects myelin generation, reduces neuroskeletal support over NfLs during CNS inflammation, and leads to axonal degeneration. Interleukin-6 (IL-6), which extensively over-express due to interleukin storm during COVID-19 inflammation, regulates gene expression, as well as GFAP through STAT molecular pathway. IL-6 also impresses the phosphoinositide 3-kinase (PI3K)/STAT/smads pathway. The PI3K/ protein kinase B (Akt) pathway is the main modulator upstream of the mammalian target of rapamycin (mTOR), and alterations in this pathway are common in neurodegenerative diseases. Most neurodegenerative diseases show a disruption of autophagic function and display an abnormal increase in protein aggregation that promotes cellular death. Therefore, induction of autophagy has been recommended as a rational approach to help neurons clear abnormal protein aggregates and survive. The mTOR is a major regulator of the autophagic process and is regulated by cellular stressors. The mTORC1 pathway and mTORC2, as complementary and important elements in mTORC1 signaling, have become relevant in the regulation of the autophagic process and cellular survival through the extracellular signal-regulated kinase (ERK) pathway.

Keywords: mTORC1, COVID-19, PI3K, autophagy, neurodegeneration

Procedia PDF Downloads 85

Authors: Mohamad Ammar Ayass, Natalya Griko, Victor Pashkov, Wanying Cao, Kevin Zhu, Jin Zhang, Lina Abi Mosleh

Abstract:

Respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent for coronavirus disease 2019 (COVID-19). Early evidence pointed at the angiotensin-converting enzyme 2 (ACE-2) expressed on the epithelial cells of the lung as the main entry point of SARS-CoV-2 into the cells. The viral entry is mediated by the binding of the Receptor Binding Domain (RBD) of the spike protein that is expressed on the surface of the virus to the ACE-2 receptor. As the number of SARS-CoV-2 variants continues to increase, mutations arising in the RBD of SARS-CoV-2 may lead to the ineffectiveness of RBD targeted neutralizing antibodies. To address this limitation, the objective of this study is to develop a combination of aptamers that target different regions of the RBD, preventing the binding of the spike protein to ACE-2 receptor and subsequent viral entry and replication. A safe and innovative biomedical tool was developed to inhibit viral infection and reduce the harms of COVID-19. In the present study, DNA aptamers were developed against a recombinant trimer S protein using the Systematic Evolution of Ligands by Exponential enrichment (SELEX). Negative selection was introduced at round number 7 to select for aptamers that bind specifically to the RBD domain. A series of 9 aptamers (ADI2010, ADI2011, ADI201L, ADI203L, ADI205L, ADIR68, ADIR74, ADIR80, ADIR83) were selected and characterized with high binding affinity and specificity to the RBD of the spike protein. Aptamers (ADI25, ADI2009, ADI203L) were able to bind and pull down endogenous spike protein expressed on the surface of SARS-CoV-2 virus in COVID-19 positive patient samples and determined by liquid chromatography- tandem mass spectrometry analysis (LC-MS/MS). LC-MS/MS data confirmed that aptamers can bind to the RBD of the spike protein. Furthermore, results indicated that the combination of the 9 best aptamers inhibited the binding of the purified trimer spike protein to the ACE-2 receptor found on the surface of Vero E6 cells. In the same experiment, the combined aptamers displayed a better neutralizing effect than antibodies. The data suggests that the selected aptamers could be used in therapy to neutralize the effect of the SARS-CoV-2 virus by inhibiting the interaction between the RBD and ACE-2 receptor, preventing viral entry into target cells and therefore blocking viral replication.

Keywords: aptamer, ACE-2 receptor, binding inhibitor, COVID-19, spike protein, SARS-CoV-2, treatment

Procedia PDF Downloads 183

Authors: Aasaithambi Kalaiselvi, Michael Gabriel Paulraj, Ekambaram Nakkeeran

Abstract:

Emergences of mosquito vector-borne diseases are considered as a perpetual problem globally in tropical countries. The outbreak of several diseases such as chikungunya, zika virus infection and dengue fever has created a massive threat towards the living population. Frequent usage of synthetic insecticides like Dichloro Diphenyl Trichloroethane (DDT) eventually had its adverse harmful effects on humans as well as the environment. Since there are no perennial vaccines, prevention, treatment or drugs available for these pathogenic vectors, WHO is more concerned in eradicating their breeding sites effectively without any side effects on humans and environment by approaching plant-derived natural eco-friendly bio-insecticides. The aim of this study is to investigate the larvicidal potency of Cinnamomum verum essential oil (CEO) loaded niosomes. Cholesterol and surfactant variants of Span 20, 60 and 80 were used in synthesizing CEO loaded niosomes using Transmembrane pH gradient method. The synthesized CEO loaded niosomes were characterized by Zeta potential, particle size, Fourier Transform Infrared Spectroscopy (FT-IR), GC-MS and SEM analysis to evaluate charge, size, functional properties, the composition of secondary metabolites and morphology. The Z-average size of the formed niosomes was 1870.84 nm and had good stability with zeta potential -85.3 meV. The entrapment efficiency of the CEO loaded niosomes was determined by UV-Visible Spectrophotometry. The bio-potency of CEO loaded niosomes was treated and assessed against gram-positive (Bacillus subtilis) and gram-negative (Escherichia coli) bacteria and fungi (Aspergillus fumigatus and Candida albicans) at various concentrations. The larvicidal activity was evaluated against II to IV instar larvae of Aedes aegypti, Anopheles stephensi and Culex quinquefasciatus at various concentrations for 24 h. The mortality rate of LC₅₀ and LC₉₀ values were calculated. The results exhibited that CEO loaded niosomes have greater efficiency against mosquito larvicidal activity. The results suggest that niosomes could be used in various applications of biotechnology and drug delivery systems with greater stability by altering the drug of interest.

Keywords: Cinnamomum verum, niosomes, entrapment efficiency, bactericidal and fungicidal, mosquito larvicidal activity

Procedia PDF Downloads 163

Authors: Kemal Kehan, Emine Aktas Bajalan

Abstract:

This study was carried out to determine the burnout levels and related factors of teachers working in primary schools affiliated to the Turkish Republic of Northern Cyprus (TRNC) Ministry of National Education during the COVID-19 pandemic period. The research was conducted in descriptive cross-sectional design. The population of the research consists of 1071 teachers working in 93 primary schools in 6 central districts affiliated to the TRNC Ministry of National Education in the 2021-2022 academic year. When the sample size of the study was calculated by power analysis, it was determined that 202 teachers should be reached with 95% confidence (1-α), 95% test power (1-β) and d=0.5 effect size. Within the scope of the inclusion criteria of the research, the main sample of the study consisted of 300 teachers and the baist random sampling method was used. The data were collected using the Sociodemographic Data Form consisting of 34 questions, including the sociodemographic characteristics of the teachers and the 22-item Maslach Burnout Scale (MBS). The analysis of the data was carried out using descriptive and correlational analyzes in the SPSS 22 package program. In the study, it was determined that 65% of the teachers were women, 68% were married, 84% had a bachelor's degree, 70.33% had children, and 67.67% were dependents. Regarding how teachers evaluate the COVID-19 pandemic period; 90% of them said, “I am worried about my family's health and the risk of infection”, 80% of them, “I feel that my profession does not get the value it deserves”, 75.67% of them mentioned “My hopes for the future have started to wane”, 75.33% of them say “I am worried about my own health”. It was determined that they gave the answer of, “I am worried about the issue”. It was found that the teachers' MBS total score average was 48.63±8.01, the burnout level was moderate, and the average score they got from the sub-dimensions of the scale was also moderate. It has been found that there are negative correlations between the professional satisfaction scores of the teachers during and before the COVID-19 pandemic and the scores they received from the general and sub-dimensions of MBS. It was determined that there was a statistically significant difference (p<0.05) between the scores of teachers diagnosed with COVID-19 from the scale and its sub-dimensions. As a result, it is suggested that social activities should be increased and professional development and promotion opportunities should be offered in order to ensure that teachers are satisfied with their work areas, to reduce their burnout levels or to prevent them completely.

Keywords: teachers, burnout, maslach burnout scale, pandemic, online education

Procedia PDF Downloads 63

Authors: Ibrahim Mohamed Ibrahim Hassanin, Hany Hassan Mostafa, Mona Mohamed Shaban, Ahlam El Said Kamel

Abstract:

Background: New so-called minimally invasive devices have been developed to limit groin pain after sling placement for treatment of stress urinary incontinence (SUI) to minimize the risk of postoperative pain and organ perforation. A new generation of suburethral slings was described that avoided skin incision to pull out and tension the sling. Evaluation of this device through prospective short-term series has shown controversial results compared with other tension-free techniques. The aim of this study is to compare success rates and complications for tension-free vaginal tape secur (TVT secur) and trans-obturator sub urethral tape inside-out technique (TVT-O) for treatment of stress urinary incontinence (SUI). Materials and Methods: Fifty patients with genuine SUI were divided into two groups: group S (n=25) were operated upon using (TVT secur) and group O (n=25) were operated upon using trans-obturator suburethral tape inside-out technique (TVT-O). Success rate, quality of life and postoperative complications such as groin pain, urgency, urine retention and vaginal tape erosion were reported in both groups at one, three, and six months after surgery. Results: As regards objective cure rate at one, three, six months intervals; there was a significant difference between group S (56%, 64%, and 60%), and group O (80%, 88%, and 88%) respectively (P <0.05). As regards subjective cure rate at one, three, six months intervals; there was a significant difference between group S (44%, 44%, and 48%), and group O (76%, 80%, and 80%) respectively (P <0.05). Quality of life (QoL) parameters improved significantly in cured patients with no difference between both groups. As regards complications, group O had a higher frequency of complications than group S; groin pain (12% vs 12% p= 0.05), urgency (4% (1 case) vs 0%), urine retention (8% (2 cases) vs 0%), vaginal tape erosion (4% (1 case) vs 0%). No cases were complicated with wound infection. Conclusion: Compared to TVT secur, TVT-O showed higher subjective and objective cure rates after six months but higher rate of complications. Both techniques were comparable as regards improvement of quality of life after surgery.

Keywords: stress urinary incontinence, trans-vaginal tape-obturator, TVT Secur, TVT-O

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Authors: Ugo Rovigatti

Abstract:

Neuroblastoma (NBL) has epitomized for at least 40 years our understanding of cancer cellular and molecular biology and its potential applications to novel therapeutic strategies. This includes the discovery of the very first oncogene aberrations and tumorigenesis suppression by differentiation in the 80s; the potential role of suppressor genes in the 90s; the relevance of immunotherapy in the millennium first, and the discovery of additional mutations by NGS technology in the millennium second decade. Similar discoveries were achieved in the majority of human cancers, and similar therapeutic interventions were obtained subsequently to NBL discoveries. Unfortunately, targeted therapies suggested by specific mutations (such as MYCN amplification –MNA- present in ¼ or 1/5 of cases) have not elicited therapeutic successes in aggressive NBL, where the prognosis is still dismal. The reasons appear to be linked to Tumor Heterogeneity, which is particularly evident in NBL but also a clear hallmark of aggressive human cancers generally. The new avenue of cancer immunotherapy (CIT) provided new hopes for cancer patients, but we still ignore the cellular or molecular targets. CIT is emblematic of high-risk disease (HR-NBL) since the mentioned GD2 passive immunotherapy is still providing better survival. We recently critically reviewed and evaluated the literature depicting the genomic landscapes of HR-NBL, coming to the qualified conclusion that among hundreds of affected genes, potential targets, or chromosomal sites, none correlated with anti-GD2 sensitivity. A better explanation is provided by the Micro-Foci inducing Virus (MFV) model, which predicts that neuroblasts infection with the MFV, an RNA virus isolated from a cancer-cluster (space-time association) of HR-NBL cases, elicits the appearance of MNA and additional genomic aberrations with mechanisms resembling chromothripsis. Neuroblasts infected with low titers of MFV amplified MYCN up to 100 folds and became highly transformed and malignant, thus causing neuroblastoma in young rat pups of strains SD and Fisher-344 and larger tumor masses in nu/nu mice. An association was discovered with GD2 since this glycosphingolipid is also the receptor for the family of MFV virus (dsRNA viruses). It is concluded that a dsRNA virus, MFV, appears to provide better explicatory mechanisms for the genesis of i) specific genomic aberrations such as MNA; ii) extensive tumor heterogeneity and chromothripsis; iii) the effects of passive immunotherapy with anti-GD2 monoclonals and that this and similar models should be further investigated in both pediatric and adult cancers.

Keywords: neuroblastoma, MYCN, amplification, viruses, GD2

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