Search results for: in vivo/vitro exposure

Authors: A. Mohammad Abdul Motalib Momin, B. Sheikh Mohammad Adil Uddin, C. Md Mamunur Rashid, D. Sheikh Arman Mahbub, E. Mohammad Sazzad Rahman, F. Abdullah Faruque

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The present study was designed to investigate the antioxidant and cytotoxicity potential of methanol and pet ether extracts of the Lagenaria siceraria (LM, LP), Cucumis sativus (CSM, CSP), Cucurbita maxima (CMM, CMP) plants. For the phytochemical screening, crude extract was tested for the presence of different chemical groups. In Lagenaria siceraria the following groups were identified: alkaloids, steroids, glycosides and saponins for methanol extract and alkaloids, steroids, glycosides, tannins and saponins are for pet ether extract. Glycosides, steroids, alkaloids, saponins and tannins are present in the methanol extract of Cucumis sativus; the pet ether extract has the alkaloids, steroids and saponins. Glycosides, steroids, alkaloids, saponins and tannins are present in both the methanolic and pet ether extract of Cucurbita maxima. In vitro antioxidant activity of the extracts were performed using DPPH radical scavenging, nitric oxide (NO) scavenging, total antioxidant capacity, total phenol content, total flavonoid content, and Cupric Reducing Antioxidant Capacity assays. The most prominent antioxidant activity was observed with the CSM in the DPPH free radical scavenging test with an IC50 value of 1667.23±11.00271 μg/ml as opposed to that of standard ascorbic acid (IC50 value of 15.707± 1.181 μg/ml.) In total antioxidant capacity method, CMP showed the highest activity (427.81±11.4 mg ascorbic acid/g). The total phenolic and flavonoids content were determined by Folin-Ciocalteu Reagent and aluminium chloride colorimetric method, respectively. The highest total phenols and total flavonoids content were found in CMM and LP with the value of 79.06±16.06 mg gallic acid/g & 119.0±1.41 mg quercetin/g, respectively. In nitric oxide (NO) scavenging the most prominent antioxidant activity was observed in CMM with an IC50 value of 8.119± 0.0036 μg/ml. The Cupric reducing capacity of the extracts was strong and dose dependent manner and CSM showed lowest reducing capacity. The cytotoxicity was determined by Brine shrimp lethality test and among these extracts most potent cytotoxicity was shown by CMM with LC50 value 16.98 µg/ml. The obtained results indicate that the investigated plants could be potential sources of natural antioxidants and can be used for various types of diseases.

Keywords: antioxidant, cytotoxicity, methanol, petroleum ether

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Authors: Amir Hamed Abd-Elrahman, Mohamed Bessat

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450 fattening cattle and buffaloes aged from 6 to 30 months old were examined clinically to determine patterns of occurrence of hemoparasitic diseases and the efficacy of different anti theilerial drugs. 420 animals examined clinically to determine relation between different outbreak of FMD and LSD in Egypt 2012- 2013 and haemoprotozoal diseases. The clinical pictures of haemoprotozoal diseases are variable, from sever to mild, depending on the endemic situation which governed by frequent previous exposure and tick infestation. B. bigemina is the most common haemoprotozoal diseases in the area of study and the infection rate in a descending manner for B. bigemina, A. marginale and T. annulata were 20%, 9.7% and 6.6% respectively. The species susceptibility of B. bigemina and T. annulata showed a higher incidence in cattle than buffaloes while in A. marginale showed a little difference in cattle and buffaloes susceptibility by 10% and 9.2% respectively. The breed susceptibility of B. bigemina and T. annulata showed a higher incidence in crossbred cattle than native baladi cattle while A. marginale showed a higher incidence in native baladi cattle than crossbred cattle. The maximal infection rates were recorded during summer months. The infection rates of B. bigemina and A. marginale were higher among young animals over 6 months and declined above 2 year old while in T. annulata the infection rates were lower among young animals and increased above 2 year old. The case fatality of T. annulata was higher than A. marginale and B. bigemina. Efficacy of different anti theilerial drugs were studied, cure rate of chlouroquine group and Butalex group were 60% disappearance of schizont in lymph node smear after 9 days and 5 days respectively while cure rate of Oxytetracycline Dihydrate (Alamycine) group 20% with disappearance of schizont in lymph node smear after 14 days. FMD and LSD infection enhancement the occurrence of bovine haemoprotozoal diseases.

Keywords: Babesia bigemina, Anaplasma marginale, Theileria annulata, FMD, LSD, ephemeral fever

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Authors: Bo Hu, Mui-Choo Jong, João Frias, Irina Chubarenko, Gabriel Enrique De-la-Torre, Prabhu Kolandhasamy, Md. Jaker Hossain, Elena Esiukova, Lei Su, Hua Deng, Huahong Shi

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Plastic debris in coastal environments undergoes a series of aging processes due to the diverse environmental conditions they are exposed to. Existing research to date lacks a thorough understanding of how these processes affect exposed and non-exposed sides of plastic fragments, leading to potentially biased conclusions on how degradation occurs. This study addresses this knowledge gap by examining surface aging characteristics on both sides (e.g., cracks, delaminations, pits, wrinkles and color residues) of 1573 plastic fragments collected from 15 coastal sites worldwide and conducting outdoor aging simulations. A clear contrast was observed between the two sides of the plastic fragments, where one of the sides often displayed more pronounced aging features. Three key indicators were introduced to quantify the aging characteristics of plastic fragments, with values ranging from 0.00 to 58.00 mm/mm2 (line density), 0.00 to 92.12% (surface loss) and 0.00 to 1.51 (texture index), respectively. Outdoor simulations revealed that sun-exposed sides of plastic sheets developed more cracks, pores, and bubbles, while the shaded sides remained smoother. The annual average solar radiation intensity of 4.47 kWh in the experimental area exacerbated the degradation of the sun-exposed side, as confirmed by a significant increase in carbonyl index, with PE rising from 0.50 to 1.70, PP from 0.18 to 1.10, and PVC from 0.45 to 1.57, indicating photoaging. These results highlight the uneven weathering patterns of plastic fragments on shorelines due to varying environmental stresses. In particular, the side facing the sun exhibited more pronounced signs of aging. Outdoor experiments confirmed that the fragments’ sun-exposed sides experienced significantly higher degrees of weathering compared to the shaded sides. This study demonstrated that the divergent weathering patterns on the two sides of beach plastic fragments were primarily driven by differences in light exposure, duration, and mechanical stress.

Keywords: plastic fragments, coastal environment, surface aging features, two-sided differences

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Authors: Tatyane Lopes de Freitas, Antonio Diogo S. Vieira, Susana Marta Isay Saad, Maria Ines Genovese

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The fruit processing industries generate a large volume of residues to produce juices, pulps, and jams. These residues, or by-products, consisting of peels, seeds, and pulps, are routinely discarded. Fruits are rich in bioactive compounds, including polyphenols, which have positive effects on health. Dry residues from two fruits, acerola (M. emarginata D. C.) and orange (C. sinensis), were characterized in relation to contents of ascorbic acid, minerals, total dietary fibers, moisture, ash, lipids, proteins, and carbohydrates, and also high performance liquid chromatographic profile of flavonoids, total polyphenols and proanthocyanidins contents, and antioxidant capacity by three different methods (Ferric reducing antioxidant power assay-FRAP, Oxygen Radical Absorbance Capacity-ORAC, 1,1-diphenyl-2-picrylhydrazil (DPPH) radical scavenging activity). Acerola by-products presented the highest acid ascorbic content (605 mg/100 g), and better antioxidant capacity than orange by-products. The dry residues from acerola demonstrated high contents of proanthocyanidins (617 µg CE/g) and total polyphenols (2525 mg gallic acid equivalents - GAE/100 g). Both presented high total dietary fiber (above 60%) and protein contents (acerola: 10.4%; orange: 9.9%), and reduced fat content (acerola: 1.6%; orange: 2.6%). Both residues showed high levels of potassium, calcium, and magnesium, and were considered sources of these minerals. With acerola by-product, four formulations of probiotics fermented milks were produced: F0 (without the addition of acerola residue (AR)), F2 (2% AR), F5 (5% AR) and F10 (10% AR). The physicochemical characteristics of the fermented milks throughout of storage were investigated, as well as the impact of in vitro simulated gastrointestinal conditions on flavonoids and probiotics. The microorganisms analyzed maintained their populations around 8 log CFU/g during storage. After the gastric phase of the simulated digestion, the populations decreased, and after the enteric phase, no colonies were detected. On the other hand, the flavonoids increased after the gastric phase, maintaining or suffering small decrease after enteric phase. Acerola by-products powder is a valuable ingredient to be used in functional foods because is rich in vitamin C, fibers and flavonoids. These flavonoids appear to be highly resistant to the acids and salts of digestion.

Keywords: acerola, orange, by-products, fermented milk

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Authors: Marie Sams, Kate Barnett-Richards, Jacqui Speculand, Gemma Tombs

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Business education in the United Kingdom has seen a number of improvements over the years in moving from delivering traditional chalk and talk lectures to using digital technologies and inviting guest lectures from industry to deliver sessions for students. Engaging topical industry talks to enhance course delivery is generally seen as a positive aspect of enhancing curriculum, however it is acknowledged that perhaps there are better ways in which industry can contribute to the quality of business programmes. Additionally, there is a consensus amongst UK industry managers that a bigger involvement in designing and inputting into business curriculum will have a greater impact on the quality of business ready graduates. Funded by the Disruptive Media Learning Lab at Coventry University in the UK, a project (SOPI - Student Online Projects with Industry) was initiated to enable students to work in project teams to respond and engage with real problems and challenges faced by five managers in various industries including retail, events and manufacturing. Over a semester, approximately 200 students were given the opportunity to develop their management, facilitation, problem solving and reflective skills, whilst having some exposure to real challenges in industry with a focus on supply chain and project management. Face to face seminars were re-designed to enable students to work on live issues in a competitive environment, and were guided to consider the theoretical aspects of their module delivery to underpin the solutions that they were generating. Dialogue between student groups and managers took place using Google+ community; an online social media tool which enables private discussions to take place and can be accessed on mobile devices. Results of the project will be shared in how this development has added value to students experience and understanding of the two subject areas. Student reflections will be analysed and evaluated to assess how the project has contributed to their perception of how the theoretical nature of these two business subjects are applied in practical situations.

Keywords: business, education, industry, projects

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Authors: Vinay Kant Shankhdhar

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Purpose: Maxillary defects are three dimensional and require complex bone and soft tissue reconstruction. Maxillary reconstruction using fibula osteocutaneous flaps in situation requiring orbital floor, orbital wall, palatal defects, and external skin, all at the same time require special planning and multiple osteotomies. We tried to improvise our reconstruction using multiple osteotomies and skin paddle designs for fibula and Flexor Hallucis Longus Muscle. This study aims at discussing the planning and outcome in complex maxillary reconstructions using fibula flaps and soft tissue flaps with or without bone grafts. Material and Methods: From 2011 to 2017 a total of 129 Free fibula flaps were done, 67 required two or more struts, 164 Anterolateral Thigh Flaps, 11 Deep Inferior Epigastric Artery perforator flaps and 3 vertical rectus abdominis muscle flaps with iliac crest bone graft. The age range was 2 to 70 years. The reconstruction was evaluated based on the post-operative rehabilitation including orbital support (prevention of diplopia), oral diet, speech and cosmetic appearance. Results: The follow- up is from 5 years to 1 year. In this series, we observed that the common complications were the de-vascularisation of most distal segment of osteotomised fibula and native skin necrosis. Commonest area of breakdown is the medial canthal region. Plate exposure occurs most commonly at the pyriform sinus. There was extrusion of one non-vascularized bone graft. All these complications were noticed post-radiotherapy. Conclusions: The use of free fibula osteocutaneous flap gives very good results when only alveolar reconstruction is required. The reconstruction of orbital floor with extensive skin loss with post operative radiotherapy has maximum complication rate in long term follow up. A soft tissue flap with non vascularized bone graft may be the best option in such cases.

Keywords: maxilla reconstruction, fibula maxilla, post cancer maxillary reconstruction

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Authors: Teresa Smith, Farrah Jacquez

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Health-risk behaviors (e.g., smoking, poor diet) directly increase the risk for chronic disease and morbidity. There is substantial evidence of a negative association between socioeconomic status (SES) and engagement in health-risk behaviors. However, due to the complexity of SES, researchers have suggested looking beyond this factor to fully understand the mechanisms that underlie engagement in health-risk behaviors. Stress is one plausible mechanism through which SES impacts health-risk behaviors. Currently, it remains unclear how stress occurring across the life course might impact health behaviors and explain the association between SES and these behaviors. To address the gaps in the literature, 172 adults between the ages of 18-49 were surveyed about their lifetime stress exposure, sociodemographic variables, and health-risk behaviors via an online recruitment portal, Prolific. Five major findings emerged from the current study. First, SES was negatively associated with engagement in health-risk behaviors and lifetime stress above and beyond current stress and other relevant demographics. Second, lifetime stress was significantly associated with health-risk behaviors above and beyond current stress and relevant demographic variables. Third, lifetime stress fully mediated the association between SES and health-risk behaviors above and beyond current stress and other demographics. Fourth, the severity of stress experienced emerged as the most significant lifetime stress variable that explains the relation between SES and health-risk behaviors. Fifth and finally, lower SES and experiencing financial and legal/crime stressors increased the likelihood of engaging in health-risk behaviors. The current study results align with previous research and suggest that stress occurring over the lifespan impacts the relation between SES and health-risk behaviors, which are in turn known to impact health outcomes. However, our findings move the current literature forward by providing a more nuanced understanding of the specific aspects of stress that influence this association. Specifically, the severity of stress experienced across the entire lifespan was the most important aspect of stress when examining the association between SES and health-risk behaviors. Further, individuals most at risk for engaging in health-risk behaviors are those of the lowest SES and experience financial and legal/crime stressors. These findings have the potential to inform interventions and policies aimed at addressing health-risk behaviors by providing a more sophisticated understanding of the impact of stress.

Keywords: stress, health behaviors, socioeconomic status, health

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Authors: Geminne Manzano, Clairecynth Yu, Lilibeth Salvador-Reyes, Viviene Santiago, Porfirio AliñO

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The distribution and abundance patterns of many marine sessile organisms such as sponges vary among and within reefs. Determining the factors affecting its distribution is essential especially for organisms that produce secondary metabolites with pharmaceutical importance. In this study, the small-scale distribution patterns of the Philippine blue sponge, Xestospongia sp. in relation to some ecological factors were examined. The relationship between the renieramycin-M production and their benthic attributes were also determined. Ecological surveys were conducted on two stations with varying depth and exposure located in Oriental Mindoro, Philippines. Three 30 by 6m belt transect were used to assess the sponge abundance at each station. The substratum of the sponges was also characterized. Fish visual census observations were also taken together with the photo transect methods benthic surveys. Sponge samples were also collected for the extraction of Renieramycin-M and for further chemical analysis. Varying distribution patterns were observed to be attributed to the combination of different ecological and environmental factors. The amount of Renieramycin-production also varied in each station. The common substratum for blue sponges includes hard and soft corals, as well as, dead coral with algal patches. Blue sponges from exposed habitat frequently grow associated with massive and branching corals, Porites sp., while the most frequent substrate found on sheltered habitats is the coral Pavona sp. Exploring the influence of ecological and environmental parameters on the abundance and distribution of sponge assemblages provide ecological insights and their potential applications to pharmaceutical studies. The results of this study provide further impetus in pursuing studies into patterns and processes of the Philippine blue sponge, Xestospongia sp. distribution in relation to the chemical ecology of its secondary metabolites.

Keywords: distribution patterns, Porifera, Renieramycin-M, sponge assemblages, Xestospongia sp.

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Authors: Duane Booysen, Ashraf Kagee

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There is a high prevalence of violent crime and trauma exposure in South African society. Considering the prevalence of continuous violent crimes and traumatization in South Africa, the public mental health sector is required to combat the burgeoning effect of traumatic stress in South Africa. Trauma counselors, especially, provide important mental health services at primary health care to persons affected by traumatic events. Therefore, the evaluation and implementation of evidence-based trauma therapies is essential at a primary health care level in treating traumatic stress. A single-case design was used to evaluate the treatment effect of a Brief Trauma Treatment Programme treating persons who present with symptoms of posttraumatic stress disorder at a primary care trauma centre in Cape Town, South Africa. The sample consisted of six adult participants who presented with symptoms of posttraumatic stress and were assessed at baseline, during treatment, post-intervention and at 3-month follow. All participants received six sessions of trauma therapy. Assessment measures included the posttraumatic stress disorder symptom scale interviews for Diagnostic and Statistical Manual fifth edition (DSM5), the posttraumatic disorder checklist for DSM5, Beck Depression Inventory and Beck Anxiety Inventory. Results demonstrate that participants had noticeable reduced symptoms for traumatic stress, anxiety and depression despite living in contexts of violent crime and trauma. In conclusion, the article critically reflects on the need to evaluate and implement evidence-based treatments for the South African context, and how evidence-based treatments are used in developing socio-economic and cultural diverse contexts with continuous levels of violence and traumatization.

Keywords: psychological interventions, public mental health, traumatic stress, single-case design

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Authors: Eitan Yefenof

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Glucocorticoid (GC) hormones, e.g. Dexamethasone and Prednisone, are widely used in the therapy of leukemia and lymphoma owing to their apoptogenic effect on lymphoid cells. However, the emergence of GC resistant cells during therapy is a major cause for treatment failure, urging the need for novel strategies that maintain leukemia sensitivity to the pro-apoptotic activity of GCs. GCs act by binding to the GC receptor (GR), which, in its inactive state, is sequestered in the cytosol by a multi-subunit complex of heat shock proteins. Upon ligand binding, the complex dissociates, allowing GR activation and translocation to the nucleus, where it regulates transcription of multiple genes. We demonstrated that in addition to gene expression, GR also regulates microRNA (miR) expression. Deep-sequencing analysis revealed 14 miRs that are regulated in GC-sensitive but resistant leukemias upon treatment with GC. GC up-regulates miR-103, miR-15~16 and miR-30e/d, while down-regulates miR-17, mir-18a, miR-19a, miR-19b, miR-20a and miR-92a (members of the miR-17∼92a multi-cistron). Upon transfection, miR-103 confers GC apoptotic sensitivity to otherwise GC-resistant cell. Furthermore, knocking down miR-103 expression reduces the GC apoptotic response of sensitive cells. miR-103 abrogates c-Myc expression, an oncogenic transcription factor which is deregulated in many cancers. In addition, miR-103 up-regulates Bim, a pro-apoptotic protein crucial for GC-induced death. Activated glycogen synthase kinase 3 (GSK3) is also crucial for GC-induced apoptosis. GSK3 is active in GC-sensitive but not in GC-resistant cells. We found that GSK3 associates with the GR multi-subunit complex. Upon GC exposure, it dissociates from the GR and interacts with Bim to enable activation of the mitochondrial apoptosis pathway. miR-103 mediated c-Myc ablation is followed by down-regulation of the multi-cistron miR-17~92a, in particular miR-18a and miR-20a. miR-18a targets GR for degradation whereas miR-20a targets Bim degradation. Hence, miR-103 acts, in concert with Bim and GR, as a "tumor suppressor" that leads to reduced proliferation, cell-cycle arrest and cell death. We suggest that miR-103 can provide a diagnostic tool that predicts the sensitivity of leukemia to GC based therapy. Furthermore, exosomal delivery of miR-103 or up-regulation of the endogenous miR-103 could confer apoptotic sensitivity to resistant cells at the outset, thus becoming a useful therapeutic tool combined with GCs.

Keywords: apoptosis, leukemia, micro-RNA, steroids

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Authors: Elyce Cardonick, Shistri Dhar, Linsdey Seidman

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Background: When breast cancer is diagnosed during pregnancy, the prognosis is comparable to non-pregnant women matched for prognostic indicators when pregnant women receive treatment without delay. Chemotherapy, including taxanes, can be given during pregnancy with normal neonatal development in exposed fetuses. Methods: Cases of primary breast cancer were extracted from the Cancer and Pregnancy Registry and longitudinal study at Cooper Medical School, which collects cases of pregnant women diagnosed and treated for cancer into a single database. Obstetrical, oncology and pediatric records were reviewed, including annual neonatal developmental, behavioral and medical assessments. Results: 270 pregnant women were diagnosed with primary breast cancer at a mean gestational age of 14.7+9weeks. Mean maternal age at diagnosis 34.5+4.5 years. Receptor status is comparable to non-pregnant women of reproductive age. Forty-nine women were advised to terminate. Two hundred two women underwent surgery;244 women received chemotherapy in pregnancy after the first trimester; the majority of Doxorubucin/Cytoxan; 81 of the cases included a taxane. At a mean of 90 months, follow up obtained on 255 newborns.192/255 newborns are meeting developmental milestones. Respiratory illnesses, including asthma, and bronchiolitis, were reported in 64 newborns, the most common medical condition reported. Thirty-one children are undergoing treatment for GERD, 11 for urinary tract infections, and 7 are undergoing treatment for anemia. Twenty-six children with expressive or articulation language delays, 21/26 are mild. Eleven children with gross/ 7 with fine motor delays. Eight children are treated for ADHD, 4 for anxiety and 4 have social skill impairment. The majority of children with developmental, language or motor delays were born preterm. Conclusion: After chemotherapy exposure in utero for breast cancer, the majority of newborns are meeting developmental milestones and are medically healthy. The goal for treating pregnant women with breast cancer is to aim for delivery close to the term.

Keywords: breast cancer, pregnancy, chemotherapy, newborn

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Authors: Giancarlo La Marca, Engy Shokry, Fabio Villanelli

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Epilepsy is one of the most common neurological disorders, with an estimated prevalence of 50 million people worldwide. Twenty five percent of the epilepsy population is represented in children under the age of 15 years. For antiepileptic drugs (AED), there is a poor correlation between plasma concentration and dose especially in children. This was attributed to greater pharmacokinetic variability than adults. Hence, therapeutic drug monitoring (TDM) is recommended in controlling toxicity while drug exposure is maintained. Carbamazepine (CBZ) is a first-line AED and the drug of first choice in trigeminal neuralgia. CBZ is metabolised in the liver into carbamazepine-10,11-epoxide (CBZE), its major metabolite which is equipotent. This develops the need for an assay able to monitor the levels of both CBZ and CBZE. The aim of the present study was to develop and validate a LC-MS/MS method for simultaneous quantification of CBZ and CBZE in dried blood spots (DBS). DBS technique overcomes many logistical problems, ethical issues and technical challenges faced by classical plasma sampling. LC-MS/MS has been regarded as superior technique over immunoassays and HPLC/UV methods owing to its better specificity and sensitivity, lack of interference or matrix effects. Our method combines advantages of DBS technique and LC-MS/MS in clinical practice. The extraction process was done using methanol-water-formic acid (80:20:0.1, v/v/v). The chromatographic elution was achieved by using a linear gradient with a mobile phase consisting of acetonitrile-water-0.1% formic acid at a flow rate of 0.50 mL/min. The method was linear over the range 1-40 mg/L and 0.25-20 mg/L for CBZ and CBZE respectively. The limit of quantification was 1.00 mg/L and 0.25 mg/L for CBZ and CBZE, respectively. Intra-day and inter-day assay precisions were found to be less than 6.5% and 11.8%. An evaluation of DBS technique was performed, including effect of extraction solvent, spot homogeneity and stability in DBS. Results from a comparison with the plasma assay are also presented. The novelty of the present work lies in being the first to quantify CBZ and its metabolite from only one 3.2 mm DBS disc finger-prick sample (3.3-3.4 µl blood) by LC-MS/MS in a 10 min. chromatographic run.

Keywords: carbamazepine, carbamazepine-10, 11-epoxide, dried blood spots, LC-MS/MS, therapeutic drug monitoring

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Authors: Molnar Catalina, Lexi Frankel, Amalia Ardeljan, Enoch Kim, Marissa Dallara, Omar Rashid

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Introduction: Clostridium difficile (C. diff) is a toxin-producing bacteria that can cause diarrhea and colitis. U.S. Center for Disease Control and Prevention revealed that C. difficile infection (CDI) has increased from 31 cases per 100,000 persons per year in 1996 to 61 per 100,000 in 2003. Approximately 500,000 cases per year occur in the United States. After exposure, the bacteria colonize the colon, where it adheres to the intestinal epithelium where it produces two toxins: TcdA and TcdB. TcdA affects the intestinal epithelium, causing fluid secretion, inflammation, and tissue necrosis, while TcdB acts as a cytotoxin purpose of this study was to evaluate the association between C diff infection and bronchial lung cancer development. Methods: Using ICD- 9 and ICD-10 codes, the data was provided by a Health Insurance Portability and Accountability Act (HIPAA) compliant national database to assess the patients infected with C diff as opposed to the non-infected patients. The Holy Cross Health, Fort Lauderdale, granted access to the database for the purpose of academic research. Patients were matched for age and Charlson Comorbidity Index (CCI). Standard statistical methods were used. Results: Bronchial lung cancer occurrence in the population not infected with C diff infection was 4741, as opposed to the population infected with C. diff, where 2039 cases of lung cancer were observed. The difference was statistically significant (p-value < 2.2x10^e-16), which reveals that C diff might be protective against bronchial lung cancer. The data was then matched by treatment to create to minimize the effect of treatment bias. Bronchial cancer incidence was 422 and 861 in infected vs. non-infected (p-value of < 2.2x10^e-16), which once more indicates that C diff infection could be beneficial in diminishing bronchial cancer development. Conclusion: This retrospective study conveys a statistical correlation between C diff infection and decreased incidence of lung bronchial cancer. Further studies are needed to comprehend the protective mechanisms of C. Diff infection on lung cancer.

Keywords: C. diff, lung cancer, protective, microbiology

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Authors: Margarita Gáfaro, Karelys Guzmán, Paola Poveda

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This paper establishes the theoretical aspects that explain the barriers to accessing credit for small agricultural producers in developing countries and identifies successful policy experiences to mitigate them. We will test two hypotheses. The first one is that information asymmetries, high transaction costs and high-risk exposure limit the supply of credit to small agricultural producers in developing countries. The second hypothesis is that low levels of financial education and productivity and high uncertainty about the returns of agricultural activity limit the demand for credit. To test these hypotheses, a review of the theoretical and empirical literature on access to rural credit in developing countries will be carried out. The first part of this review focuses on theoretical models that incorporate information asymmetries in the credit market and analyzes the interaction between these asymmetries and the characteristics of the agricultural sector in developing countries. Some of the characteristics we will focus on are the absence of collateral, the underdevelopment of the judicial systems and insurance markets, and the high dependence on climatic factors of production technologies. The second part of this review focuses on the determinants of credit demand by small agricultural producers, including the profitability of productive projects, security conditions, risk aversion or loss, financial education, and cognitive biases, among others. There are policies that focus on resolving these supply and demand constraints and managing to improve credit access. Therefore, another objective of this paper is to present a review of effective policies that have promoted access to credit for smallholders in the world. For this, information available in policy documents will be collected. This information will be complemented by interviews with officials in charge of the design and execution of these policies in a subset of selected countries. The information collected will be analyzed in light of the conceptual framework proposed in the first two parts of this section. The barriers to access to credit that each policy attempts to resolve and the factors that could explain its effectiveness will be identified.

Keywords: agricultural economics, credit access, smallholder, developing countries

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Authors: Mohd Fadzly Yahya, Matthew Teo Yong Chang

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Globally, the increasing life expectancy of human beings has brought more issues with non-communicable diseases, especially work-related musculoskeletal disorders (WMDs). WMSD also is one of the leading causes of health-related absence from work restricted work time in Malaysia. WMDs are cumulative disorders, resulting from repeated exposure to high or low-intensity loads over a long period. Evidence from a previous study showed that office workers in government and private sectors were showing high WRMDs prevalence in Malaysia. The objectives of this study were to determine the prevalence of MSDs among Malaysian office workers in Klang Valley and to identify the association between MSDs pain and working experience among office workers. This is a cross-sectional study focusing on officer workers in the Klang Valley area. The questionnaires consisted of the subject’s demographics, Nordic Musculoskeletal Questionnaire, and The Numeric Pain Rating Scale were distributed online via google forms to all consenting participants. The data were analyzed for descriptive analysis, parametric test, and student T-test using IBM SPSS Statistics Version 27. From a total of 244 participants, 95 (38.9%) were male and 149 (61.1%) were female. 57.8% of the total samples were government staff while private-sector workers were 42.2%. The highest MSDs prevalence was neck pain during the last 12 months which contributed to 69.3% (n=169) of total participants, which is male 38.5% (n=65) and female 61.5% (n=104). Our study revealed that female office workers have a higher prevalence of WMDs and there is a significant difference in elbow pain, wrist, and hands pain, and lower back pain across four different working experience groups. Office workers in this study were highly exposed to MSDs due to poor ergonomics implementation at the workplace. It is crucial to advocate preventative measures to employers such as workplace ergonomics and changes to work practices to reduce the incidence of MSDs cases in office settings.

Keywords: musculoskeletal disorders, pain, prevalence rate, office workers, risks

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Authors: Alan Lai, Wilson Yik

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With rapid urbanization, there has been a dramatic increase in global urban population in Asia and over half of population in Asia will live in urban regions in the near future. Facing with increasing exposure to climate-related stresses and shocks, most of the Asian cities will very likely to experience more frequent heat waves and flooding with rising sea levels, particularly the coastal cities will grapple for intense typhoons and storm surges. These climate changes have severe impacts in urban areas at the costs of infrastructure and population, for example, human health, wellbeing and high risks of dengue fever, malaria and diarrheal disease. With the increasing prominence of adaptation to climate changes, there have been changes in corresponding policies. Smaller cities have greater potentials for integrating the concept of resilience into their infrastructure as well as keeping pace with their rapid growths in population. It is therefore important to explore the potentials of Asian cities adapting to climate change and the opportunities of building climate resilience in urban planning and building design. Furthermore, previous studies have mainly attempted at exploiting the potential of resilience on a macro-level within urban planning rather than that on micro-level within the context of individual building. The resilience of individual building as a research field has not yet been much explored. Nonetheless, recent studies define that the resilience of an individual building is the one which is able to respond to physical damage and recover from such damage in a quickly and cost-effectively manner, while maintain its primary functions. There is also a need to develop an assessment tool to evaluate the resilience on building scale which is still largely uninvestigated as it should be regarded as a basic function of a building. Due to the lack of literature reporting metric for assessing building resilience with sustainability, the research will be designed as a case study to provide insight into the issue. The aim of this research project is to encourage and assist in developing neighborhood climate resilience design strategies for Hong Kong so as to bridge the gap between difference scales and that between theory and practice.

Keywords: resilience cities, building resilience, resilient buildings and infrastructure, climate resilience, hot and humid southeast area, high-density cities

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Authors: Bărbuță Alina

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The inter-causal relationship between social inequalities and the digital divide raises the relation issue of gender and information and communication technologies (ICT) - a key element in achieving sustainable development. In preparing generations as future digital citizens and for active socio-economic participation, ICT plays a key role in respecting gender equality. Although several studies over the years have shown that gender plays an important role in digital exclusion, in recent years, many studies with a focus on economically developed or developing countries identify an improvement in these aspects and a gap narrowing. By measuring students' digital competencies level, this paper aims to identify and analyse the existing gender digital inequalities among students. Our analyses are based on a sample of 1526 middle school students residing in rural areas from Republic of Moldova (54.2% girls, mean age 14,00, SD = 1.02). During the online survey they filled in a questionnaire adapted from the (yDSI) ”The Youth Digital Skills Indicator”. The instrument measures the level of five digital competence areas indicated in The European Digital Competence Framework (DigiCom 2.3.). Our results, based on t-test, indicate that depending on gender, there are no statistically significant differences regarding the levels of digital skills in 3 areas: Information navigation and processing; Communication and interaction; Problem solving. However, were identified significant differences in the level of digital skills in the area of ”Digital content creation” [t(1425) = 4.20, p = .000] and ”Safety” [t(1421) = 2.49, p = .000], with higher scores recorded by girls. Our results contradicts the general stereotype regarding the low level of digital competence among girls, in our sample girls scores being on pear with boys and even bigger in knowledge related to digital content creation and online safety skills. Additional investigations related to boys competence on digital safety are necessary as the implication of their low scores on this dimension may suggest boys exposure to digital threats.

Keywords: digital divide, education, gender digital divide, digital literacy, remote learning

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Authors: Radin Siti Aishah Radin A Rahman, Norasmah Othman, Zaidatol Akmaliah Lope Pihie, Hariyaty Ab. Wahid

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The recent instability in economy was found to be influencing the situation in Malaysia whether directly or indirectly. Taking that into consideration, the government needs to find the best approach to balance its citizen’s socio-economic strata level urgently. Through education platform is among the efforts planned and acted upon for the purpose of balancing the effects of the influence, through the exposure of social entrepreneurial activity towards youth especially those in higher institution level. Armed with knowledge and skills that they gained, with the support by entrepreneurial culture and environment while in campus; indirectly, the students will lean more on making social entrepreneurship as a career option when they graduate. Following the issues of marketability and workability of current graduates that are becoming dire, research involving how far the willingness of student to create social innovation that contribute to the society without focusing solely on personal gain is relevant enough to be conducted. With that, this research is conducted with the purpose of identifying the level of entrepreneurial intention and social entrepreneurship among higher institution students in Malaysia. Stratified random sampling involves 355 undergraduate students from five public universities had been made as research respondents and data were collected through surveys. The data was then analyzed descriptively using min score and standard deviation. The study found that the entrepreneurial intention of higher education students are on moderate level, however it is the contrary for social entrepreneurship activities, where it was shown on a high level. This means that while the students only have moderate level of willingness to be a social entrepreneur, they are very committed to created social innovation through the social entrepreneurship activities conducted. The implication from this study can be contributed towards the higher institution authorities in prediction the tendency of student in becoming social entrepreneurs. Thus, the opportunities and facilities for realizing the courses related to social entrepreneurship must be created expansively so that the vision of creating as many social entrepreneurs as possible can be achieved.

Keywords: entrepreneurial intention, higher education institutions (HEIs), social entrepreneurship, social entrepreneurial activity, gender

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Authors: Rana Tabassum, Ravi Kant, Banshi D. Gupta

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Malic acid is an extensively distributed organic acid in numerous horticultural products in minute amounts which significantly contributes towards taste determination by balancing sugar and acid fractions. An enhanced concentration of malic acid is utilized as an indicator of fruit maturity. In addition, malic acid is also a crucial constituent of several cosmetics and pharmaceutical products. An efficient detection and quantification protocol for malic acid is thus highly demanded. In this study, we report a novel detection scheme for malic acid by synergistically collaborating fiber optic surface plasmon resonance (FOSPR) and distinctive features of nanomaterials favorable for sensing applications. The design blueprint involves the deposition of an assembly of malate dehydrogenase enzyme entrapped in ZnO nanowires forming the sensing route over silver coated central unclad core region of an optical fiber. The formation and subsequent decomposition of the enzyme-analyte complex on exposure of the sensing layer to malic acid solutions of diverse concentration results in modification of the dielectric function of the sensing layer which is manifested in terms of shift in resonance wavelength. Optimization of experimental variables such as enzyme concentration entrapped in ZnO nanowires, dip time of probe for deposition of sensing layer and working pH range of the sensing probe have been accomplished through SPR measurements. The optimized sensing probe displays high sensitivity, broad working range and a minimum limit of detection value and has been successfully tested for malic acid determination in real samples of fruit juices. The current work presents a novel perspective towards malic acid determination as the unique and cooperative combination of FOSPR and nanomaterials provides myriad advantages such as enhanced sensitivity, specificity, compactness together with the possibility of online monitoring and remote sensing.

Keywords: surface plasmon resonance, optical fiber, sensor, malic acid

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Authors: Alvarez M., Chapela M. J., Balboa E., Rubianes D., Sinde E., Fernandez de Ana C., Rodríguez-Blanco A.

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The gut microbiota plays an important role as gut inflammation could contribute to colorectal cancer development; however, this role is still not fully understood, and tools able to prevent this progression are yet to be developed. The main objective of this study was to monitor the effects of a mushroom extracts formulation in gut microbial community composition of an Azoxymethane (AOM)/Dextran sodium sulfate (DSS) mice model of inflammation-linked carcinogenesis. For the in vivo study, 41 adult male mice of the C57BL / 6 strain were obtained. 36 of them have been induced in a state of colon carcinogenesis by a single intraperitoneal administration of AOM at a dose of 12.5 mg/kg; the control group animals received instead of the same volume of 0.9% saline. DSS is an extremely toxic polysaccharide sulfate that causes chronic inflammation of the colon mucosa, favoring the appearance of severe colitis and the production of tumors induced by AOM. Induction by AOM/DSS is an interesting platform for chemopreventive intervention studies. This time the model was used to monitor gut microbiota changes as a result of supplementation with a specific mushroom extracts formulation previously shown to have prebiotic activity. The animals have been divided into three groups: (i) Cancer + mushroom extracts formulation experimental group: to which the MicoDigest2.0 mushroom extracts formulation developed by Hifas da Terra S.L has been administered dissolved in drinking water at an estimated concentration of 100 mg / ml. (ii) Control group of animals with Cancer: to which normal water has been administered without any type of treatment. (iii) Control group of healthy animals: these are the animals that have not been induced cancer or have not received any treatment in drinking water. This treatment has been maintained for a period of 3 months, after which the animals were sacrificed to obtain tissues that were subsequently analyzed to verify the effects of the mushroom extract formulation. A microbiological analysis has been carried out to compare the microbial communities present in the intestines of the mice belonging to each of the study groups. For this, the methodology of massive sequencing by molecular analysis of the 16S gene has been used (Ion Torrent technology). Initially, DNA extraction and metagenomics libraries were prepared using the 16S Metagenomics kit, always following the manufacturer's instructions. This kit amplifies 7 of the 9 hypervariable regions of the 16S gene that will then be sequenced. Finally, the data obtained will be compared with a database that makes it possible to determine the degree of similarity of the sequences obtained with a wide range of bacterial genomes. Results obtained showed that, similarly to certain natural compounds preventing colorectal tumorigenesis, a mushroom formulation enriched the Firmicutes and Proteobacteria phyla and depleted Bacteroidetes. Therefore, it was demonstrated that the consumption of the mushroom extracts’ formulation developed could promote the recovery of the microbial balance that is disrupted in the mice model of carcinogenesis. More preclinical and clinical studies are needed to validate this promising approach.

Keywords: carcinogenesis, microbiota, mushroom extracts, inflammation

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Authors: Elizabeth M. Annoni, Elena G. Tolkacheva

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Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia that is a known prognostic marker for stroke, heart failure and death. Reentrant mechanisms of rotor formation, which are stable electrical sources of cardiac excitation, are believed to cause AF. No existing commercial mapping systems have been demonstrated to consistently and accurately predict rotor locations outside of the pulmonary veins in patients with persistent AF. There is a clear need for robust spatio-temporal techniques that can consistently identify rotors using unique characteristics of the electrical recordings at the pivot point that can be applied to clinical intracardiac mapping. Recently, we have developed four new signal analysis approaches – Shannon entropy (SE), Kurtosis (Kt), multi-scale frequency (MSF), and multi-scale entropy (MSE) – to identify the pivot points of rotors. These proposed techniques utilize different cardiac signal characteristics (other than local activation) to uncover the intrinsic complexity of the electrical activity in the rotors, which are not taken into account in current mapping methods. We validated these techniques using high-resolution optical mapping experiments in which direct visualization and identification of rotors in ex-vivo Langendorff-perfused hearts were possible. Episodes of ventricular tachycardia (VT) were induced using burst pacing, and two examples of rotors were used showing 3-sec episodes of a single stationary rotor and figure-8 reentry with one rotor being stationary and one meandering. Movies were captured at a rate of 600 frames per second for 3 sec. with 64x64 pixel resolution. These optical mapping movies were used to evaluate the performance and robustness of SE, Kt, MSF and MSE techniques with respect to the following clinical limitations: different time of recordings, different spatial resolution, and the presence of meandering rotors. To quantitatively compare the results, SE, Kt, MSF and MSE techniques were compared to the “true” rotor(s) identified using the phase map. Accuracy was calculated for each approach as the duration of the time series and spatial resolution were reduced. The time series duration was decreased from its original length of 3 sec, down to 2, 1, and 0.5 sec. The spatial resolution of the original VT episodes was decreased from 64x64 pixels to 32x32, 16x16, and 8x8 pixels by uniformly removing pixels from the optical mapping video.. Our results demonstrate that Kt, MSF and MSE were able to accurately identify the pivot point of the rotor under all three clinical limitations. The MSE approach demonstrated the best overall performance, but Kt was the best in identifying the pivot point of the meandering rotor. Artifacts mildly affect the performance of Kt, MSF and MSE techniques, but had a strong negative impact of the performance of SE. The results of our study motivate further validation of SE, Kt, MSF and MSE techniques using intra-atrial electrograms from paroxysmal and persistent AF patients to see if these approaches can identify pivot points in a clinical setting. More accurate rotor localization could significantly increase the efficacy of catheter ablation to treat AF, resulting in a higher success rate for single procedures.

Keywords: Atrial Fibrillation, Optical Mapping, Signal Processing, Rotors

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Authors: Samaneh Nazeri, Bagher Mojazi Amiri, Hamid Farahmand

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Production of high quality fish eggs with reasonable hatching rate makes a success in aquaculture industries. It is influenced by the environmental stimulators and inhibitors. Diazinon is a widely-used pesticide in Golestan province (Southern Caspian Sea, North of Iran) which is washed to the aquatic environment (3 mg/L in the river). It is little known about the effect of this pesticide on the embryogenesis of sturgeon fish, the valuable species of the Caspian Sea. Hormonal content of the egg is an important factor to guaranty the successful passes of embryonic stages. In this study, the fate of Persian sturgeon embryo to 24, 48, 72, and 96-hours exposure of diazinon (LC₅₀ dose) was tested. Also, the effect of thyroid hormones (T3 and T4) on these embryos was tested concurrently or separately with diazinon LC ₅₀ dose. Fertilized eggs are exposed to T3 (low dose: 1 ng/ml, high dose: 10 ng/ml), T4 (low dose: 1 ng/ml, high dose: 10 ng/ml). Six eggs were randomly selected from each treatment (with three replicates) in five developmental stages (two cell- division, neural, heart present, heart beaten, and hatched larvae). The possibility of changing T3, T4, and cortisol contents of the embryos were determined in all treated groups and in every mentioned embryonic stage. The hatching rate in treated groups was assayed at the end of the embryogenesis to clarify the effect of thyroid hormones and diazinon. The results indicated significant differences in thyroid hormone contents, but no significant differences were recognized in cortisol levels at various early life stages of embryos. There was also significant difference in thyroid hormones in (T3, T4) + diazinon treated embryos (P˂0.05), while no significant difference between control and treatments in cortisol levels was observed. The highest hatching rate was recorded in HT3 treatment, while the lowest hatching rate was recorded for diazinon LC₅₀ treatment. The result confirmed that Persian sturgeon embryo is less sensitive to diazinon compared to teleost embryos, and thyroid hormones may increase hatching rate even in the presence of diazinon.

Keywords: Persian sturgeon, diazinon, thyroid hormones, cortisol, embryo

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Authors: Recep Kesli, Huseyin Bilgin, Yasar Unlu, Gokhan Gungor

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Aim: The aim of this study, was to investigate the presence of Helicobacter pylori (H. pylori) infection by culture, histology, and RUT (Rapid Urease Test) in gastric antrum biopsy samples taken from patients presented with dyspeptic complaints and to determine resistance rates of amoxicillin, clarithromycin, levofloxacin and metronidazole against the H. pylori strains by E-test. Material and Methods: A total of 278 patients who admitted to Konya Education and Research Hospital Department of Gastroenterology with dyspeptic complaints, between January 2011-July 2013, were included in the study. Microbiological and histopathological examinations of biopsy specimens taken from antrum and corpus regions were performed. The presence of H. pylori in biopsy samples was investigated by culture (Portagerm pylori-PORT PYL, Pylori agar-PYL, GENbox microaer, bioMerieux, France), histology (Giemsa, Hematoxylin and Eosin staining), and RUT(CLOtest, Cimberly-Clark, USA). Antimicrobial resistance of isolates against amoxicillin, clarithromycin, levofloxacin, and metronidazole was determined by E-test method (bioMerieux, France). As a gold standard in the diagnosis of H. pylori; it was accepted that the culture method alone was positive or both histology and RUT were positive together. Sensitivity and specificity for histology and RUT were calculated by taking the culture as a gold standard. Sensitivity and specificity for culture were also calculated by taking the co-positivity of both histology and RUT as a gold standard. Results: H. pylori was detected in 140 of 278 of patients with culture and 174 of 278 of patients with histology in the study. H. pylori positivity was also found in 191 patients with RUT. According to the gold standard criteria, a false negative result was found in 39 cases by culture method, 17 cases by histology, and 8 cases by RUT. Sensitivity and specificity of the culture, histology, and RUT methods of the patients were 76.5 % and 88.3 %, 87.8 % and 63 %, 94.2 % and 57.2 %, respectively. Antibiotic resistance was investigated by E-test in 140 H. pylori strains isolated from culture. The resistance rates of H. pylori strains to the amoxicillin, clarithromycin, levofloxacin, and metronidazole was detected as 9 (6.4 %), 22 (15.7 %), 17 (12.1 %), 57 (40.7 %), respectively. Conclusion: In our study, RUT was found to be the most sensitive, culture was the most specific test between culture, histology, and RUT methods. Although we detected the specificity of the culture method as high, its sensitivity was found to be quite low compared to other methods. The low sensitivity of H. pylori culture may be caused by the factors affect the chances of direct isolation such as spoild bacterium, difficult-to-breed microorganism, clinical sample retrieval, and transport conditions.

Keywords: antimicrobial resistance, culture, histology, H. pylori, RUT

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Authors: Frans J. Smit, Wisdom A. Munzeiwa, Hermanus C. M. Vosloo, Lyn-Marie Birkholtz, Richard K. Haynes

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Malaria and antimicrobial infections remain significant global health concerns, necessitating the continuous search for novel therapeutic approaches. This abstract presents an overview of the potential use of triazenes as effective agents against malaria and various antimicrobial pathogens. Triazenes are a class of compounds characterized by a linear arrangement of three nitrogen atoms, rendering them structurally distinct from their cyclic counterparts. This study investigates the efficacy of triazenes against malaria and explores their antimicrobial activity. Preliminary results revealed significant antimalarial activity of the triazenes, as evidenced by in vitro screening against P. falciparum, the causative agent of malaria. Furthermore, the compounds exhibited broad-spectrum antimicrobial activity, indicating their potential as effective antimicrobial agents. These compounds have shown inhibitory effects on various essential enzymes and processes involved in parasite survival, replication, and transmission. The mechanism of action of triazenes against malaria involves interactions with critical molecular targets, such as enzymes involved in the parasite's metabolic pathways and proteins responsible for host cell invasion. The antimicrobial activity of the triazenes against bacteria and fungi was investigated through disc diffusion screening. The antimicrobial efficacy of triazenes has been observed against both Gram-positive and Gram-negative bacteria, as well as multidrug-resistant strains, making them potential candidates for combating drug-resistant infections. Furthermore, triazenes possess favourable physicochemical properties, such as good stability, solubility, and low toxicity, which are essential for drug development. The structural versatility of triazenes allows for the modification of their chemical composition to enhance their potency, selectivity, and pharmacokinetic properties. These modifications can be tailored to target specific pathogens, increasing the potential for personalized treatment strategies. In conclusion, this study highlights the potential of triazenes as promising candidates for the development of novel antimalarial and antimicrobial therapeutics. Further investigations are necessary to determine the structure-activity relationships and optimize the pharmacological properties of these compounds. The results warrant additional research, including MIC studies, to further explore the antimicrobial activity of the triazenes. Ultimately, these findings contribute to the development of more effective strategies for combating malaria and microbial infections.

Keywords: malaria, anti-microbials, triazene, resistance

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Authors: Ilham Aji Dermawan, M. Sapari Dwi Hadian, R. Irvan Sophian, Iyan Haryanto

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The study of the geological structure in the surrounding area of Cidaun, Cianjur Regency, West Java Province, Indonesia was conducted around the southern coast of Java Island. This study aims to determine the potentially structural trap deposits of freshwater resources in the study area, according to that the study area is an area directly adjacent to the beach, where the water around it did not seem fresh and brackish due to the exposure of sea water intrusion. This study uses the method of geomorphological analysis and geological mapping by taking the data directly in the field within 10x10 km of the research area. Geomorphological analysis was done by calculating the watershed drainage density value and roundness of watershed value ratio. The goal is to determine the permeability of the sub-soil conditions, rock constituent, and the flow of surface water. While the field geological mapping aims to take the geological structure data and then will do the reconstruction to determine the geological conditions of research area. The result, from geomorphology aspects, that the considered area of potential groundwater consisted of permeable surface material, permeable sub-soil, and low of water run-off flow. It is very good for groundwater recharge area. While the results of geological reconstruction after conducted of geological mapping is joints that present were initiated for the Cipandak Fault that cuts Cipandak River. That fault across until the Cibako Syncline fold through the Cibako River. This syncline is expected to place of influent groundwater aquifer. The tip of Cibako River then united with Cipandak River, where the Cipandak River extends through Cipandak Syncline fold axis in the southern regions close to its estuary. This syncline is expected to place of influent groundwater aquifer too.

Keywords: geological structure, groundwater, hydrogeology, influent aquifer, structural trap

Procedia PDF Downloads 204

Authors: Yifat Koren Carmi, Abed Agbarya, Hazem Khamaisi, Raymond Farah, Yelena Shechtman, Roman Korobochka, Jacob Gopas, Jamal Mahajna

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Ovarian cancer (OC), the second most common form of gynecological malignancy, has a poor prognosis and is frequently identified in its late stages. The recommended treatment for OC typically includes a platinum-based chemotherapy, like carboplatin. Nonetheless, OC treatment has proven challenging due to toxicity and development of acquired resistance to therapy. Chemoresistance is a significant obstacle to a long-lasting response in OC patients, believed to arise from alterations within the cancer cells as well as within the tumor microenvironments (TME). Malignant ascites is a presenting feature in more than one-third of OC patients. It serves as a reservoir for a complex mixture of soluble factors, metabolites, and cellular components, providing a pro-inflammatory and tumor-promoting microenvironment for the OC cells. Malignant ascites is also associated with metastasis and chemoresistance. In an attempt to elucidate the role of TME in chemoresistance of OC, we monitored the ability of soluble factors derived from ascites fluids to affect platinum sensitivity of OC cells. This research, compared ascites fluids from non-malignant cirrhotic patients to those from OC patients in terms of their ability to alter the platinum sensitivity of OC cells. Our findings indicated that exposure to OC ascites induces platinum chemoresistance on OC cells in 11 out of 13 cases (85%). In contrast, 75% of cirrhosis ascites (3 out of 4) failed to confer platinum chemoresistance to OC cells. Cytokine array analysis revealed that IL-6, and to a lesser extent HGF were enriched in OC ascites, whereas IL-22 was enriched in cirrhosis ascites. Pharmaceutical inhibitors that target the IL-6/JAK signaling pathway were mildly effective in overcoming the platinum chemoresistance induced by malignant ascites. In contrast, Crizotinib an HGF/c-MET inhibitor, and 2-hydroxyestradiol (2HE2) were effective in restoring platinum chemoresistance to OC. Our findings demonstrate the importance of OC ascites in supporting platinum chemoresistance as well as the potential of a combination therapy with Crizotinib and the estradiol metabolite 2HE2 to regain OC cells chemosensitivity.

Keywords: ovarian cancer, platinum chemoresistance, malignant ascites, tumor microenvironment, IL-6, 2-hydroxyestradiol, HGF, crizotinib

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Authors: Garreth Kestell, Lukah Dykes, Danielle Zerk, Kyla Trewartha, Rhianon Marshall, Elena Rudnik

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Adolescent mental health is an international priority and the impact of innovative service models must be evaluated. Secondary school-based mental health services (SBMHS) involving private general practitioners and psychologists are a model of care being trialed in South Australia. Measures of depression, anxiety, and stress are routinely collected throughout psychotherapy sessions. This research set out to quantify the impact of psychotherapy for rural adolescents in a school setting and explore the importance of session frequency. Methods: Demographics, session date and DASS21 scores from students (n=65) seen in 2016 by three psychologists working at the SBMHS were recorded. Students were aged 13-18 years (M=15.43, SD= 1.24), mostly female (F=51, M=14), attended between 1 and 23 sessions with a median of 6 sessions (MAD 5.93) in one-year. The treating psychologist collected self-administered DASS21 scores. A mixed model analysis was used with age, sex, treating psychologist, months from first session, and session number as fixed effects, with response variables of DASS depression, anxiety, and stress scores. Results: 71.5% were classified as having extreme or severe anxiety and half had extreme or severe depression and/or stress scores. On average males had a greater increase in DASS scores over time but males attending more sessions benefited most from therapy. Discussion: Psychologists are treating rural adolescents in schools for severe anxiety, depression, and stress. This pilot study indicates that a predictive model combining demographics, session frequency, and DASS scores may help identify who is most likely to benefit from individual psychotherapy. Variations in DAS scores of individuals over time indicate the need for the collection of information such as living situation and exposure to alcohol. A larger sample size and additional data are currently being collected to allow for a more robust analysis.

Keywords: adolescent health, psychotherapy, school based mental health services, DAS21

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Authors: Dativa Maria Aliddeki, Fred Monje, Godfrey Nsereko, Benon Kwesiga, Daniel Kadobera, Alex Riolexus Ario

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Background: Cholera is a severe gastrointestinal disease caused by Vibrio cholera. It has caused several pandemics. On 26 February 2018, a suspected cholera outbreak, with one death, occurred in School X in Hoima Municipality, western Uganda. We investigated to identify the scope and mode of transmission of the outbreak, and recommend evidence-based control measures. Methods: We defined a suspected case as onset of diarrhea, vomiting, or abdominal pain in a student or staff of School X or their family members during 14 February–10 March. A confirmed case was a suspected case with V. cholerae cultured from stool. We reviewed medical records at Hoima Hospital and searched for cases at School X. We conducted descriptive epidemiologic analysis and hypothesis-generating interviews of 15 case-patients. In a retrospective cohort study, we compared attack rates between exposed and unexposed persons. Results: We identified 15 cases among 75 students and staff of School X and their family members (attack rate=20%), with onset from 25-28 February. One patient died (case-fatality rate=6.6%). The epidemic curve indicated a point-source exposure. On 24 February, a student brought fried fish from her home in a fishing village, where a cholera outbreak was ongoing. Of the 21 persons who ate the fish, 57% developed cholera, compared with 5.6% of 54 persons who did not eat (RR=10; 95% CI=3.2-33). None of 4 persons who recooked the fish before eating, compared with 71% of 17 who did not recook it, developed cholera (RR=0.0, 95%CIFisher exact=0.0-0.95). Of 12 stool specimens cultured, 6 yielded V. cholerae. Conclusion: This cholera outbreak was caused by eating fried fish, which might have been contaminated with V. cholerae in a village with an ongoing outbreak. Lack of thorough cooking of the fish might have facilitated the outbreak. We recommended thoroughly cooking fish before consumption.

Keywords: cholera, disease outbreak, foodborne, global health security, Uganda

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Authors: Line Massé, Claire Baudry, Claudia Verret, Marie-France Nadeau, Anne Brault-Labbé

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Little research has been conducted on educational services adapted for twice exceptional students. Within an action research, a cluster grouping was set up in an elementary school in Quebec, bringing together gifted or doubly exceptional (2E) students (n = 11) and students not identified as gifted (n = 8) within a multilevel class (3ᵣ𝒹 and 4ₜₕ years). 2E students had either attention deficit hyperactivity disorder (n = 8, including 3 with specific learning disability) or autism spectrum disorder (n = 2). Differentiated instructions strategies were implemented, including the possibility of progressing at their own pace of learning, independent study or research projects, flexible accommodation, tutoring with older students and the development of socio-emotional learning. A specialized educator also supported the teacher in the class for behavioural and socio-affective aspects. Objectives: The study aimed to assess the impacts of the grouping on all students, their academic motivation, and their socio-emotional adaptation. Method: A mixed method was used, combining a qualitative approach with a quantitative approach. Semi-directed interviews were conducted with students (N = 18, 4 girls and 14 boys aged 8 to 9) and one of their parents (N = 18) at the end of the school year. Parents and students completed two questionnaires at the beginning and end of the school year: the Behavior Assessment System for Children-3, children or parents versions (BASC-3, Reynolds and Kampus, 2015) and the Academic Motivation in Education (Vallerand et al., 1993). Parents also completed the Multidimensional Student Life Satisfaction Scale (Huebner, 1994, adapted by Fenouillet et al., 2014) comprising three domains (school, friendships, and motivation). Mixed thematic analyzes were carried out on the data from the interviews using the N'Vivo software. Related-samples Wilcoxon rank-sums tests were conducted for the data from the questionnaires. Results: Different themes emerge from the students' comments, including a positive impact on school motivation or attitude toward school, improved school results, reduction of their behavioural difficulties and improvement of their social relations. These remarks were more frequent among 2E students. Most 2E students also noted an improvement in their academic performance. Most parents reported improvements in attitudes toward school and reductions in disruptive behaviours in the classroom. Some parents also observed changes in behaviours at home or in the socio-emotional well-being of their children, here again, particularly parents of 2E children. Analysis of questionnaires revealed significant differences at the end of the school year, more specifically pertaining to extrinsic motivation identified, problems of conduct, attention, emotional self-control, executive functioning, negative emotions, functional deficiencies, and satisfaction regarding friendships. These results indicate that this approach could benefit not only gifted and doubly exceptional students but also students not identified as gifted.

Keywords: Cluster grouping, elementary school, giftedness, mixed methods, twice exceptional students

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Authors: Alexander A. Osmolovskiy, Anastasia V. Orekhova, Daria M. Bednenko, Yelyzaveta Boiko

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Micromycetes from Aspergillus genus can produce proteases capable of promoting proteolysis of hemostasis proteins or, along with hydrolytic activity, to show the ability to convert proenzymes of this system activating them into an active form. At the same time, practical medicine needs specific activators for quantitation of the level of some plasma enzymes, especially protein C and factor X, the lack of which leads to the development of thromboembolic diseases. Thus, some micromycetes of the genus Aspergillus were screened for the ability to synthesize extracellular proteases with promising activity for designing anti-thrombotic and diagnostic preparations. Such standard methods like salting out, electrophoresis, isoelectrofocusing were used for isolation, purification and study of physicochemical properties of proteases. Enzyme activity was measured spectrophotometrically fibrin as a substrate of the reaction and chromogenic peptide substrates of different proteases of the human hemostasis system. As a result of the screening, four active producers were selected: Aspergillus janus 301, A. flavus 1, A. terreus 2, and A. ochraceus L-1. The enzyme of A. janus 301 showed the greatest fibrinolytic activity (around 329.2 μmol Tyr/(ml × min)). The protease produced by A. terreus 2 had the highest plasmin-like activity (54.1 nmol pNA/(ml × min)), but fibrinolytic activity was lower than A. janus 301 demonstrated (25.2 μmol Tyr/(ml × min)). For extracellular protease of micromycete A. flavus a high plasmin-like activity was also shown (39.8 nmol pNA / (ml × min)). Moreover, according to our results proteases one of the fungi - A. terreus 2 were able to activate protein C of human plasma - the key factor of the human anticoagulant hemostasis system. This type of activity was 39.8 nmol pNA/(ml × min)). It was also shown that A. ochraceus L-1 could produce extracellular proteases with protein C and factor X activator activities (65.9 nmol pNA/(ml × min) and 34.6 nmol pNA/(ml × min) respectively). The maximum accumulation of the proteases falls on the 4th day of cultivation. Using isoelectrofocusing was demonstrated that the activation of both proenzymes might proceed via limited proteolysis induced by proteases of A. ochraceus L-1. The activatory activity of A. ochraceus L-1 proteases toward essential hemostatic proenzymes, protein C and X factor may be useful for practical needs. It is well known that similar enzymes, activators of protein C and X factor isolated from snake venom, South American copperhead Agkistrodon contortrix contortrix and Russell’s viper Daboia russelli russeli, respectively, are used for the in vitro diagnostics of the functional state of these proteins in blood plasma. Thus, the proteases of Aspergillus genus can be used as cheap components for enzyme thrombolytic preparations.

Keywords: anti-trombotic drugs, fibrinolysis, diagnostics, proteases, micromycetes

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