Search results for: anti apoptotic drug
201 A Policy Review on the Transitional Period from MDGs to SDGs: Experience from the Local Economy of Tigrai Regional State of Ethiopia
Authors: Tewele Gerlase Haile
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Sustainable development is development that meets the needs of the present without compromising the ability of future generations to meet their own needs. The global development landscape underwent a transformative shift in 2015 as the international community pivoted from the MDGs to the more ambitious and comprehensive SDGs. The NDGs were a set of eight international development goals established by the United Nations in 2000, with the aim of improving the lives of people around the world by 2015. SDGs are a continuation of the MDGs. Unlike on the other development goals, progress on eradication of extreme hunger and poverty (MDG 1) has been slow at a continental level. The implementation of the MDGs was uneven: some countries have already achieved many of them, while the others have not started any of them yet. With its Poverty Reduction Strategic Papers (PRSPs), Ethiopia has been given special attention to the first MDG since 1993. The Ethiopian government was actively engaged in anti-poverty political campaign leaving other agendas as secondary issues. Poverty in Ethiopia progressively reduced over the years; it was 44.2% in 2000, 38.7% in 2007, 29.6 % in 2011, and it is projected to further reduce to 16.7% by the end of 2020. The long-term impact of war on the sustainability and effectiveness of SDG-related initiatives in post-conflict regions, particularly in how local governance and community resilience are affected. This could involve exploring how war interrupts progress, which specific SDGs are most vulnerable, and what strategies might mitigate these impacts. Reviewing a transitional period enables policy makers to align global or national development goals into local development goals with an uninterrupted policy continuity. The existing literature on development economics often neglects the importance of reviewing the transitional period of consecutive global development goals in a local or regional perspective. Reviewing a transitional period enables policy makers to align global or national development goals into local development goals with an uninterrupted policy continuity. Using a Policy Coherence for Development (PCD) approach as analytical tool, this paper is intended to retrospectively review what happened to the local economy of Tigrai Regional State during the transitional period from MDGs (2000-2015) to SDGs (2015-2030). Taking a retrospective facts and observations into account, policy discontinuity is witnessed in Tigrai following the dissolution of the EPRDF that followed with a terrible war that claimed about a million human lives and worth of over a hundred Billion US dollars economic costs. The unhealthy political reform caused not only a terrible war but also breaks the promising SDGs. Unlike other regional states, Tigrai left unprivileged to translate the ambitious SDGs into its local development policies.Keywords: local development, political reform, war, MDGs, SDGs, Ethiopia, tigrai
Procedia PDF Downloads 21200 Development and Validation of a Turbidimetric Bioassay to Determine the Potency of Ertapenem Sodium
Authors: Tahisa M. Pedroso, Hérida R. N. Salgado
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The microbiological turbidimetric assay allows the determination of potency of the drug, by measuring the turbidity (absorbance), caused by inhibition of microorganisms by ertapenem sodium. Ertapenem sodium (ERTM), a synthetic antimicrobial agent of the class of carbapenems, shows action against Gram-negative, Gram-positive, aerobic and anaerobic microorganisms. Turbidimetric assays are described in the literature for some antibiotics, but this method is not described for ertapenem. The objective of the present study was to develop and validate a simple, sensitive, precise and accurate microbiological assay by turbidimetry to quantify ertapenem sodium injectable as an alternative to the physicochemical methods described in the literature. Several preliminary tests were performed to choose the following parameters: Staphylococcus aureus ATCC 25923, IAL 1851, 8 % of inoculum, BHI culture medium, and aqueous solution of ertapenem sodium. 10.0 mL of sterile BHI culture medium were distributed in 20 tubes. 0.2 mL of solutions (standard and test), were added in tube, respectively S1, S2 and S3, and T1, T2 and T3, 0.8 mL of culture medium inoculated were transferred to each tube, according parallel lines 3 x 3 test. The tubes were incubated in shaker Marconi MA 420 at a temperature of 35.0 °C ± 2.0 °C for 4 hours. After this period, the growth of microorganisms was inhibited by addition of 0.5 mL of 12% formaldehyde solution in each tube. The absorbance was determined in Quimis Q-798DRM spectrophotometer at a wavelength of 530 nm. An analytical curve was constructed to obtain the equation of the line by the least-squares method and the linearity and parallelism was detected by ANOVA. The specificity of the method was proven by comparing the response obtained for the standard and the finished product. The precision was checked by testing the determination of ertapenem sodium in three days. The accuracy was determined by recovery test. The robustness was determined by comparing the results obtained by varying wavelength, brand of culture medium and volume of culture medium in the tubes. Statistical analysis showed that there is no deviation from linearity in the analytical curves of standard and test samples. The correlation coefficients were 0.9996 and 0.9998 for the standard and test samples, respectively. The specificity was confirmed by comparing the absorbance of the reference substance and test samples. The values obtained for intraday, interday and between analyst precision were 1.25%; 0.26%, 0.15% respectively. The amount of ertapenem sodium present in the samples analyzed, 99.87%, is consistent. The accuracy was proven by the recovery test, with value of 98.20%. The parameters varied did not affect the analysis of ertapenem sodium, confirming the robustness of this method. The turbidimetric assay is more versatile, faster and easier to apply than agar diffusion assay. The method is simple, rapid and accurate and can be used in routine analysis of quality control of formulations containing ertapenem sodium.Keywords: ertapenem sodium, turbidimetric assay, quality control, validation
Procedia PDF Downloads 394199 Migration, Labour Market, Capital Formation, and Social Security: A Study of Livelihoods of the Urban Poor in Two Different Cities of West Bengal in India
Authors: Arup Pramanik
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Most of the cities in the developing countries like Siliguri Municipal Corporation Area (SMCA) and Raiganj Municipality (RM) in West Bengal, India are changing typically in terms of demographic, economic and social relationship due to rapid pace of urbanization. The mushrooming growth of slums in SMCA and RM is the direct consequence of urbanization and migration due to regional imbalance, unbalanced growth process which is posing a serious threat to sustainable development of the country. Almost all the slums happen to be a breeding ground for poverty, negligence, and disease. Unpredictable growth of slums and poverty alleviation has now become a serious challenge to the global and national policy makers for the development of the slum dwellers. The ethical dimension of the poor in the cities like SMCA and RM stands on equal opportunities, inclusive and harmonious living without discrimination of any kind. But, the migrant slum dwellers in SMCA and RM do not possess high skill or education to enable them to find well paid employment in the formal sector and the surplus urban labour force is compelled to generate its own means of employment and survival in the informal sector. The survey data of the households has been analysedin terms of percentage, descriptive statistics which includes mean, Standard Deviation (SD), ANOVA (Mean Difference) etc., to analyse the socio economic variables of the households. The study shows that the migrant labour forces living in the slums are derived from the social security measures in both the municipal areas of SMCA and RM. The urban poor in the cities of SMCA and RM rely heavily on social capital amongst all the capital assets to help them ‘get by’ and ‘get ahead’. Despite, the slum dwellers in the study areas are vulnerable with respect to other determinants of capital assets. It is noteworthy that Indian plans of anti-poverty programmes was in a proper place even after the neo-liberal regime, where the basic idea behind the massive shift of various welfare and service oriented strategy to poverty reduction strategy for the benefit of the urban poor with the trickle down effects. But, the overall impact of the trickledown effect was unsatisfactory. The objective of the Paper is to assess the magnitude of migration and absorption in the urban labour market. Issues relating to capital formation, social security measures and the support of the Welfare State in order to meet 'Sustainable Development Goals'. This study also highlights the quality of life of urban poor migrants in terms of capital formation and livelihoods.Keywords: migration, slums, labour market, capital formation, social security
Procedia PDF Downloads 119198 Understanding the Diversity of Antimicrobial Resistance among Wild Animals, Livestock and Associated Environment in a Rural Ecosystem in Sri Lanka
Authors: B. M. Y. I. Basnayake, G. G. T. Nisansala, P. I. J. B. Wijewickrama, U. S. Weerathunga, K. W. M. Y. D. Gunasekara, N. K. Jayasekera, A. W. Kalupahana, R. S. Kalupahana, A. Silva- Fletcher, K. S. A. Kottawatta
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Antimicrobial resistance (AMR) has attracted significant attention worldwide as an emerging threat to public health. Understanding the role of livestock and wildlife with the shared environment in the maintenance and transmission of AMR is of utmost importance due to its interactions with humans for combating the issue in one health approach. This study aims to investigate the extent of AMR distribution among wild animals, livestock, and environment cohabiting in a rural ecosystem in Sri Lanka: Hambegamuwa. One square km area at Hambegamuwa was mapped using GPS as the sampling area. The study was conducted for a period of five months from November 2020. Voided fecal samples were collected from 130 wild animals, 123 livestock: buffalo, cattle, chicken, and turkey, with 36 soil and 30 water samples associated with livestock and wildlife. From the samples, Escherichia coli (E. coli) was isolated, and their AMR profiles were investigated for 12 antimicrobials using the disk diffusion method following the CLSI standard. Seventy percent (91/130) of wild animals, 93% (115/123) of livestock, 89% (32/36) of soil, and 63% (19/30) of water samples were positive for E. coli. Maximum of two E. coli from each sample to a total of 467 were tested for the sensitivity of which 157, 208, 62, and 40 were from wild animals, livestock, soil, and water, respectively. The highest resistance in E. coli from livestock (13.9%) and wild animals (13.3%) was for ampicillin, followed by streptomycin. Apart from that, E. coli from livestock and wild animals revealed resistance mainly against tetracycline, cefotaxime, trimethoprim/ sulfamethoxazole, and nalidixic acid at levels less than 10%. Ten cefotaxime resistant E. coli were reported from wild animals, including four elephants, two land monitors, a pigeon, a spotted dove, and a monkey which was a significant finding. E. coli from soil samples reflected resistance primarily against ampicillin, streptomycin, and tetracycline at levels less than in livestock/wildlife. Two water samples had cefotaxime resistant E. coli as the only resistant isolates out of 30 water samples tested. Of the total E. coli isolates, 6.4% (30/467) was multi-drug resistant (MDR) which included 18, 9, and 3 isolates from livestock, wild animals, and soil, respectively. Among 18 livestock MDRs, the highest (13/ 18) was from poultry. Nine wild animal MDRs were from spotted dove, pigeon, land monitor, and elephant. Based on CLSI standard criteria, 60 E. coli isolates, of which 40, 16, and 4 from livestock, wild animal, and environment, respectively, were screened for Extended Spectrum β-Lactamase (ESBL) producers. Despite being a rural ecosystem, AMR and MDR are prevalent even at low levels. E. coli from livestock, wild animals, and the environment reflected a similar spectrum of AMR where ampicillin, streptomycin, tetracycline, and cefotaxime being the predominant antimicrobials of resistance. Wild animals may have acquired AMR via direct contact with livestock or via the environment, as antimicrobials are rarely used in wild animals. A source attribution study including the effects of the natural environment to study AMR can be proposed as this less contaminated rural ecosystem alarms the presence of AMR.Keywords: AMR, Escherichia coli, livestock, wildlife
Procedia PDF Downloads 218197 Reclaiming the Lost Jewish Identity of a Second Generation Holocaust Survivor Raised as a Christian: The Role of Art and Art Therapy
Authors: Bambi Ward
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Children of Holocaust survivors have been described as inheriting their parents’ trauma as a result of ‘vicarious memory’. The term refers to a process whereby second generation Holocaust survivors subconsciously remember aspects of Holocaust trauma, despite not having directly experienced it. This can occur even when there has been a conspiracy of silence in which survivors chose not to discuss the Holocaust with their children. There are still people born in various parts of the world such as Poland, Hungary, other parts of Europe, USA, Canada and Australia, who have only learnt of their Jewish roots as adults. This discovery may occur during a parent’s deathbed confession, or when an adult child is sorting through the personal belongings of a deceased family member. Some Holocaust survivors chose to deny their Jewish heritage and raise their children as Christians. Reasons for this decision include the trauma experienced during the Holocaust for simply being Jewish, the existence of anti-Semitism, and the desire to protect one’s self and one’s family. Although there has been considerable literature written about the transgenerational impact of trauma on children of Holocaust survivors, there has been little scholarly investigation into the effects of a hidden Jewish identity on these children. This paper presents a case study of an adult child of Hungarian Holocaust survivors who was raised as a Christian. At the age of eight she was told about her family’s Jewish background, but her parents insisted that she keep this a secret, even if asked directly. She honoured their request until she turned forty. By that time she had started the challenging process of reclaiming her Jewish identity. The paper outlines the tension between family loyalty and individual freedom, and discusses the role that art and art therapy played in assisting the subject of the case study to reclaim her Jewish identity and commence writing a memoir about her spiritual journey. The main methodology used in this case study is creative practice-led research. Particular attention is paid to the utilisation of an autoethnographic approach. The autoethnographic tools used include reflective journals of the subject of the case study. These journals reflect on the subject’s collection of autobiographical data relating to her family history, and include memories, drawings, products of art therapy, diaries, letters, photographs, home movies, objects, and oral history interviews with her mother. The case study illustrates how art and art therapy benefitted a second generation Holocaust survivor who was brought up having to suppress her Jewish identity. The process allowed her to express subconscious thoughts and feelings about her identity and free herself from the burden of the long term secret she had been carrying. The process described may also be of assistance to other traumatised people who have been trying to break the silence and who are seeking to express themselves in a positive and healing way.Keywords: art, hidden identity, holocaust, silence
Procedia PDF Downloads 240196 De-Pigmentary Effect of Ayurvedic Treatment on Hyper-Pigmentation of Skin Due to Chloroquine: A Case Report
Authors: Sunil Kumar, Rajesh Sharma
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Toxic epidermal necrolysis, pruritis, rashes, lichen planus like eruption, hyper pigmentation of skin are rare toxic effects of choloroquine used over a long time. Skin and mucus membrane hyper pigmentation is generally of a bluish black or grayish color and irreversible after discontinuation of the drug. According to Ayurveda, Dushivisha is the name given to any poisonous substance which is not fully endowed with the qualities of poison by nature (i.e. it acts as an impoverished or weak poison) and because of its mild potency, it remains in the body for many years causing various symptoms, one among them being discoloration of skin.The objective of this case report is to investigate the effect of Ayurvedic management of chloroquine induced hyper-pigmentation on the line of treatment of Dushivisha. Case Report: A 26-year-old female was suffering from hyper-pigmentation of the skin over the neck, forehead, temporo-mandibular joints, upper back and posterior aspect of both the arms since 8 years had history of taking Chloroquine came to Out Patient Department of National Institute of Ayurveda, Jaipur, India in Jan. 2015. The routine investigations (CBC, ESR, Eosinophil count) were within normal limits. Punch biopsy skin studied for histopathology under hematoxylin and eosin staining showed epidermis with hyper-pigmentation of the basal layer. In the papillary dermis as well as deep dermis there were scattered melanophages along with infiltration by mononuclear cells. There was no deposition of amyloid-like substances. These histopathological findings were suggestive of Chloroquine induced hyper-pigmentation. The case was treated on the line of treatment of Dushivisha and was given Vamana and Virechana (therapeutic emesis and purgation) every six months followed by Snehana karma (oleation therapy) with Panchatikta Ghrit and Swedana (sudation). Arogyavardhini Vati -1 g, Dushivishari Vati 500 mg, Mahamanjisthadi Quath 20 ml were given twelve hourly and Aragwadhadi Quath 25 ml at bed time orally. The patient started showing lightening of the pigments after six months and almost complete remission after 12 months of the treatment. Conclusion: This patient presented with the Dushivisha effect of Chloroquineandwas administered two relevant procedures from Panchakarma viz. Vamana and Virechana. Both Vamana and Virechanakarma here referred to Shodhana karma (purification procedures) eliminates accumulated toxins from the body. In this process, oleation dislodge the toxins from the tissues and sudation helps to bring them to the alimentary tract. The line of treatment did not target direct hypo pigmentary effects; rather aimed to eliminate the Dushivisha. This gave promising results in this condition.Keywords: Ayurveda, chloroquine, Dushivisha, hyper-pigmentation
Procedia PDF Downloads 235195 Characterization of Main Phenolic Compounds in Eleusine indica L. (Poaceae) by HPLC-DAD and 1H NMR
Authors: E. M. Condori-Peñaloza, S. S. Costa
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Eleusine indica L, known as goose-grass, is considered a troublesome weed that can cause important economic losses in the agriculture worldwide. However, this grass is used as a medicinal plant in some regions of Brazil to treat influenza and pneumonia. In Africa and Asia, it is used to treat malaria and as diuretic, anti-helminthic, among other uses. Despite its therapeutic potential, little is known about the chemical composition and bioactive compounds of E. indica. Hitherto, two major flavonoids, schaftoside and vitexin, were isolated from aerial part of the species and showed inhibitory activity on lung neutrophil influxes in mice, suggesting a beneficial effect on airway inflammation. Therefore, the aim of this study was to analyze the chemical profile of aqueous extracts from aerial parts of Eleusine indica specimens using high performance liquid chromatography (HPLC-DAD) and 1H nuclear magnetic resonance spectroscopy (NMR), with emphasis on phenolic compounds. Specimens of E. indica were collected in Minas Gerais state, Brazil. Aerial parts of fresh plants were extracted by decoction (10% p/v). After spontaneous precipitation of the aqueous extract at 10-12°C for 24 hours, the supernatant obtained was frozen and lyophilized. After that, 1 g of the extract was dissolved into 25 mL of water and fractionated on a reverse phase chromatography column (RP-2), eluted with a gradient of H2O/EtOH. Five fractions were obtained. The extract and fractions had their chemical profile analyzed by using HPLC-DAD (C-18 column: 20 μL, 256 -365 nm; gradient water 0.01% phosphoric acid/ acetonitrile. The extract was also analyzed by NMR (1H, 500 MHz, D2O) in order to access its global chemical composition. HPLC-DAD analyses of crude extract allowed the identification of ten phenolic compounds. Fraction 1, eluted with 100% water, was poor in phenolic compounds and no major peak was detected. In fraction 2, eluted with 100% water, it was possible to observe one major peak at retention time (RT) of 23.75 minutes compatible with flavonoid; fraction 3, also eluted with 100% water, showed four peaks at RT= 21.47, 23.52, 24.33 and 25.84 minutes, all of them compatible with flavonoid. In fraction 4, eluted with 50%/ethanol/50% water, it was possible to observe 3 peaks compatible with flavonoids at RT=24.65, 26.81, 27.49 minutes, and one peak (28.83 min) compatible with a phenolic acid derivative. Finally, in fraction 5, eluted with 100% ethanol, no phenolic substance was detected. The UV spectra of all flavonoids detected were compatible with the flavone subclass (λ= 320-345 nm). The 1H NMR spectra of aerial parts extract showed signals in three regions: δ 0.8-3.0 ppm (aliphatic compounds), δ 3.0-5.5 ppm corresponding to carbohydrates (signals most abundant and overlapped), and δ 6.0-8.5 ppm (aromatic compounds). Signals compatible with flavonoids (rings A and B) could also be detected in the crude extract spectra. These results suggest the presence of several flavonoids in E. indica, which reinforces their therapeutic potential. The pharmacological activities of Eleusine indica extracts and fractions will be further evaluated.Keywords: flavonoids, HPLC, NMR, phenolic compounds
Procedia PDF Downloads 319194 A Comparison of Three Different Modalities in Improving Oral Hygiene in Adult Orthodontic Patients: An Open-Label Randomized Controlled Trial
Authors: Umair Shoukat Ali, Rashna Hoshang Sukhia, Mubassar Fida
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Introduction: The objective of the study was to compare outcomes in terms of Bleeding index (BI), Gingival Index (GI), and Orthodontic Plaque Index (OPI) with video graphics and plaque disclosing tablets (PDT) versus verbal instructions in adult orthodontic patients undergoing fixed appliance treatment (FAT). Materials and Methods: Adult orthodontic patients have recruited from outpatient orthodontic clinics who fulfilled the inclusion criteria and were randomly allocated to three groups i.e., video, PDT, and verbal groups. We included patients undergoing FAT for six months of both genders with all teeth bonded mesial to first molars having no co-morbid conditions such as rheumatic fever and diabetes mellitus. Subjects who had gingivitis as assessed by Bleeding Index (BI), Gingival Index (GI), and Orthodontic Plaque Index (OPI) were recruited. We excluded subjects having > 2 mm of clinical attachment loss, pregnant and lactating females, any history of periodontal therapy within the last six months, and any consumption of antibiotics or anti-inflammatory drugs within the last one month. Pre- and post-interventional measurements were taken at two intervals only for BI, GI, and OPI. The primary outcome of this trial was to evaluate the mean change in the BI, GI, and OPI in the three study groups. A computer-generated randomization list was used to allocate subjects to one of the three study groups using a random permuted block sampling of 6 and 9 to randomize the samples. No blinding of the investigator or the participants was performed. Results: A total of 99 subjects were assessed for eligibility, out of which 96 participants were randomized as three of the participants declined to be part of this trial. This resulted in an equal number of participants (32) that were analyzed in all three groups. The mean change in the oral hygiene indices score was assessed, and we found no statistically significant difference among the three interventional groups. Pre- and post-interventional results showed statistically significant improvement in the oral hygiene indices for the video and PDT groups. No statistically significant difference for age, gender, and education level on oral hygiene indices were found. Simple linear regression showed that the video group produced significantly higher mean OPI change as compared to other groups. No harm was observed during the trial. Conclusions: Visual aids performed better as compared to the verbal group. Gender, age, and education level had no statistically significant impact on the oral hygiene indices. Longer follow-ups will be required to see the long-term effects of these interventions. Trial Registration: NCT04386421 Funding: Aga Khan University and Hospital (URC 183022)Keywords: oral hygiene, orthodontic treatment, adults, randomized clinical trial
Procedia PDF Downloads 118193 Multi-Institutional Report on Toxicities of Concurrent Nivolumab and Radiation Therapy
Authors: Neha P. Amin, Maliha Zainib, Sean Parker, Malcolm Mattes
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Purpose/Objectives: Combination immunotherapy (IT) and radiation therapy (RT) is an actively growing field of clinical investigation due to promising findings of synergistic effects from immune-mediated mechanisms observed in preclinical studies and clinical data from case reports of abscopal effects. While there are many ongoing trials of combined IT-RT, there are still limited data on toxicity and outcome optimization regarding RT dose, fractionation, and sequencing of RT with IT. Nivolumab (NIVO), an anti-PD-1 monoclonal antibody, has been rapidly adopted in the clinic over the past 2 years, resulting in more patients being considered for concurrent RT-NIVO. Knowledge about the toxicity profile of combined RT-NIVO is important for both the patient and physician when making educated treatment decisions. The acute toxicity profile of concurrent RT-NIVO was analyzed in this study. Materials/Methods: A retrospective review of all consecutive patients who received NIVO from 1/2015 to 5/2017 at 4 separate centers within two separate institutions was performed. Those patients who completed a course of RT from 1 day prior to initial NIVO infusion through 1 month after last NIVO infusion were considered to have received concurrent therapy and included in the subsequent analysis. Descriptive statistics are reported for patient/tumor/treatment characteristics and observed acute toxicities within 3 months of RT completion. Results: Among 261 patients who received NIVO, 46 (17.6%) received concurrent RT to 67 different sites. The median f/u was 3.3 (.1-19.8) months, and 11/46 (24%) were still alive at last analysis. The most common histology, RT prescription, and treatment site included non-small cell lung cancer (23/46, 50%), 30 Gy in 10 fractions (16/67, 24%), and central thorax/abdomen (26/67, 39%), respectively. 79% (53/67) of irradiated sites were treated with 3D-conformal technique and palliative dose-fractionation. Grade 3, 4, and 5 toxicities were experienced by 11, 1, and 2 patients, respectively. However all grade 4 and 5 toxicities were outside of the irradiated area and attributed to the NIVO alone, and only 4/11 (36%) of the grade 3 toxicities were attributed to the RT-NIVO. The irradiated site in these cases included the brain [2/10 (20%)] and central thorax/abdomen [2/19 (10.5%)], including one unexpected grade 3 pancreatitides following stereotactic body RT to the left adrenal gland. Conclusions: Concurrent RT-NIVO is generally well tolerated, though with potentially increased rates of severe toxicity when irradiating the lung, abdomen, or brain. Pending more definitive data, we recommend counseling patients on the potentially increased rates of side effects from combined immunotherapy and radiotherapy to these locations. Future prospective trials assessing fractionation and sequencing of RT with IT will help inform combined therapy recommendations.Keywords: combined immunotherapy and radiation, immunotherapy, Nivolumab, toxicity of concurrent immunotherapy and radiation
Procedia PDF Downloads 393192 The Influence of Ibuprofen, Diclofenac and Naproxen on Composition and Ultrastructural Characteristics of Atriplex patula and Spinacia oleracea
Authors: Ocsana Opris, Ildiko Lung, Maria L. Soran, Alexandra Ciorita, Lucian Copolovici
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The effects assessment of environmental stress factors on both crop and wild plants of nutritional value are a very important research topic. Continuously worldwide consumption of drugs leads to significant environmental pollution, thus generating environmental stress. Understanding the effects of the important drugs on plant composition and ultrastructural modification is still limited, especially at environmentally relevant concentrations. The aim of the present work was to investigate the influence of three non-steroidal anti-inflammatory drugs (NSAIDs) on chlorophylls content, carotenoids content, total polyphenols content, antioxidant capacity, and ultrastructure of orache (Atriplex patula L.) and spinach (Spinacia oleracea L.). All green leafy vegetables selected for this study were grown in controlled conditions and treated with solutions of different concentrations (0.1‒1 mg L⁻¹) of diclofenac, ibuprofen, and naproxen. After eight weeks of exposure of the plants to NSAIDs, the chlorophylls and carotenoids content were analyzed by high-performance liquid chromatography coupled with photodiode array and mass spectrometer detectors, total polyphenols and antioxidant capacity by ultraviolet-visible spectroscopy. Also, the ultrastructural analyses of the vegetables were performed using transmission electron microscopy in order to assess the influence of the selected NSAIDs on cellular organisms, mainly photosynthetic organisms (chloroplasts), energy supply organisms (mitochondria) and nucleus as a cellular metabolism coordinator. In comparison with the control plants, decreases in the content of chlorophylls were observed in the case of the Atriplex patula L. plants treated with ibuprofen (11-34%) and naproxen (25-52%). Also, the chlorophylls content from Spinacia oleracea L. was affected, the lowest decrease (34%) being obtained in the case of the treatment with naproxen (1 mg L⁻¹). Diclofenac (1 mg L⁻¹) affected the total polyphenols content (a decrease of 45%) of Atriplex patula L. and ibuprofen (1 mg L⁻¹) affected the total polyphenols content (a decrease of 20%) of Spinacia oleracea L. The results obtained also indicate a moderate reduction of carotenoids and antioxidant capacity in the treated plants, in comparison with the controls. The investigations by transmission electron microscopy demonstrated that the green leafy vegetables were affected by the selected NSAIDs. Thus, this research contributes to a better understanding of the adverse effects of these drugs on studied plants. Important to mention is that the dietary intake of these drugs contaminated plants, plants with important nutritional value, may also presume a risk to human health, but currently little is known about the fate of the drugs in plants and their effect on or risk to the ecosystem.Keywords: abiotic stress, green leafy vegetables, pigments content, ultra structure
Procedia PDF Downloads 126191 Production, Characterization and In vitro Evaluation of [223Ra]RaCl2 Nanomicelles for Targeted Alpha Therapy of Osteosarcoma
Authors: Yang Yang, Luciana Magalhães Rebelo Alencar, Martha Sahylí Ortega Pijeira, Beatriz da Silva Batista, Alefe Roger Silva França, Erick Rafael Dias Rates, Ruana Cardoso Lima, Sara Gemini-Piperni, Ralph Santos-Oliveira
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Radium-²²³ dichloride ([²²³Rₐ]RₐCl₂) is an alpha particle-emitting radiopharmaceutical currently approved for the treatment of patients with castration-resistant prostate cancer, symptomatic bone metastases, and no known visceral metastatic disease. [²²³Rₐ]RₐCl₂ is bone-seeking calcium mimetic that bonds into the newly formed bone stroma, especially osteoblastic or sclerotic metastases, killing the tumor cells by inducing DNA breaks in a potent and localized manner. Nonetheless, the successful therapy of osteosarcoma as primary bone tumors is still a challenge. Nanomicelles are colloidal nanosystems widely used in drug development to improve blood circulation time, bioavailability, and specificity of therapeutic agents, among other applications. In addition, the enhanced permeability and retention effect of the nanosystems, and the renal excretion of the nanomicelles reported in most cases so far, are very attractive to achieve selective and increased accumulation in tumor site as well as to increase the safety of [²²³Rₐ]RₐCl₂ in the clinical routine. In the present work, [²²³Rₐ]RₐCl₂ nanomicelles were produced, characterized, in vitro evaluated, and compared with pure [²²³Rₐ]RₐCl2 solution using SAOS2 osteosarcoma cells. The [²²³Rₐ]RₐCl₂ nanomicelles were prepared using the amphiphilic copolymer Pluronic F127. The dynamic light scattering analysis of freshly produced [²²³Rₐ]RₐCl₂ nanomicelles demonstrated a mean size of 129.4 nm with a polydispersity index (PDI) of 0.303. After one week stored in the refrigerator, the mean size of the [²²³Rₐ]RₐCl₂ nanomicelles increased to 169.4 with a PDI of 0.381. Atomic force microscopy analysis of [223Rₐ]RₐCl₂ nanomicelles exhibited spherical structures whose heights reach 1 µm, suggesting the filling of 127-Pluronic nanomicelles with [²²³Rₐ]RₐCl₂. The viability assay with [²²³Rₐ]RₐCl₂ nanomicelles displayed a dose-dependent response as it was observed using pure [²²³Rₐ]RₐCl2. However, at the same dose, [²²³Rₐ]RₐCl₂ nanomicelles were 20% higher efficient in killing SAOS2 cells when compared with pure [²²³Rₐ]RₐCl₂. These findings demonstrated the effectiveness of the nanosystem validating the application of nanotechnology in targeted alpha therapy with [²²³Ra]RₐCl₂. In addition, the [²²³Rₐ]RaCl₂nanomicelles may be decorated and incorporated with a great variety of agents and compounds (e.g., monoclonal antibodies, aptamers, peptides) to overcome the limited use of [²²³Ra]RₐCl₂.Keywords: nanomicelles, osteosarcoma, radium dichloride, targeted alpha therapy
Procedia PDF Downloads 118190 Hypersensitivity Reactions Following Intravenous Administration of Contrast Medium
Authors: Joanna Cydejko, Paulina Mika
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Hypersensitivity reactions are side effects of medications that resemble an allergic reaction. Anaphylaxis is a generalized, severe allergic reaction of the body caused by exposure to a specific agent at a dose tolerated by a healthy body. The most common causes of anaphylaxis are food (about 70%), Hymenoptera venoms (22%), and medications (7%), despite detailed diagnostics in 1% of people, the cause of the anaphylactic reaction was not indicated. Contrast media are anaphylactic agents of unknown mechanism. Hypersensitivity reactions can occur with both immunological and non-immunological mechanisms. Symptoms of anaphylaxis occur within a few seconds to several minutes after exposure to the allergen. Contrast agents are chemical compounds that make it possible to visualize or improve the visibility of anatomical structures. In the diagnosis of computed tomography, the preparations currently used are derivatives of the triiodide benzene ring. Pharmacokinetic and pharmacodynamic properties, i.e., their osmolality, viscosity, low chemotoxicity and high hydrophilicity, have an impact on better tolerance of the substance by the patient's body. In MRI diagnostics, macrocyclic gadolinium contrast agents are administered during examinations. The aim of this study is to present the results of the number and severity of anaphylactic reactions that occurred in patients in all age groups undergoing diagnostic imaging with intravenous administration of contrast agents. In non-ionic iodine CT and in macrocyclic gadolinium MRI. A retrospective assessment of the number of adverse reactions after contrast administration was carried out on the basis of data from the Department of Radiology of the University Clinical Center in Gdańsk, and it was assessed whether their different physicochemical properties had an impact on the incidence of acute complications. Adverse reactions are divided according to the severity of the patient's condition and the diagnostic method used in a given patient. Complications following the administration of a contrast medium in the form of acute anaphylaxis accounted for less than 0.5% of all diagnostic procedures performed with the use of a contrast agent. In the analysis period from January to December 2022, 34,053 CT scans and 15,279 MRI examinations with the use of contrast medium were performed. The total number of acute complications was 21, of which 17 were complications of iodine-based contrast agents and 5 of gadolinium preparations. The introduction of state-of-the-art contrast formulations was an important step toward improving the safety and tolerability of contrast agents used in imaging. Currently, contrast agents administered to patients are considered to be one of the best-tolerated preparations used in medicine. However, like any drug, they can be responsible for the occurrence of adverse reactions resulting from their toxic effects. The increase in the number of imaging tests performed with the use of contrast agents has a direct impact on the number of adverse events associated with their administration. However, despite the low risk of anaphylaxis, this risk should not be marginalized. The growing threat associated with the mass performance of radiological procedures with the use of contrast agents forces the knowledge of the rules of conduct in the event of symptoms of hypersensitivity to these preparations.Keywords: anaphylactic, contrast medium, diagnostic, medical imagine
Procedia PDF Downloads 63189 The Lack of Female Representation in Senior Positions: An Exploratory Study between South Africa and India
Authors: Dina Maria Smit
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Worldwide, it seems as if women are adequately represented in government and parliament but are almost absent from governing boards of private enterprises. The reasons for this seem to be embedded in perceptions of inadequacy, remnants of patriarchy, glass ceilings and even female choice. Direct or indirect discrimination against females have been found to be one of the reasons that female employees are found in traditionally “softer” roles, whilst the old “Boy’s Club” is still operational to keep women out of senior managerial positions, especially in the private sector. The cultural construct of Indian society, focusing on male preference, patriarchy, divorce laws and low educational levels of females as opposed to men, is indicative of a society wherein high gender inequality still exists. The position in South Africa is similar in that substantive gender equality has not been reached despite a progressive constitution and anti-discrimination laws. There is a strong push to propel women to senior positions in South Africa, but these efforts have not yet translated into females taking up senior positions in private companies. In South Africa, females still earn less than their male counterparts whilst performing doing the same jobs, are overrepresented in parliament, but do not captain the ships in the private sector. The lack of female parity in employment leads to a lack of autonomy and authority in both South Africa and India. The divide between formal and informal work, unpaid work, mainly being done by women, need to be investigated to ensure substantive gender parity. The findings will show that females are still not equal to men in employment, especially in senior private positions; mainly due to the remnants of patriarchy and glass ceilings that still need to be shattered. This article aims to set out the reasons why gender disparity still exists in India and South Africa, seen through a legal lense. Both countries are signatories to the CEDAW Convention and have constitutions that advocate for the right of equality. Although equal rights have been implemented in both countries, equality may not be well implemented. This investigation is comparative in nature and aims to contribute to the growing body of evidence on how to ensure gender parity in all occupational levels and categories. The study is in quantitative in nature. If substantive gender equality, as opposed to formative gender equality, is a key motivator to ensure gender equality, an investigation into the reasons for this disparity is warranted before suggestions can be tendered to effect lasting change. The aim of this comparative study is not to plug the legal system of one country into the other, but to take into account of the autonomy of choice, set against cultural differences and similarities in an effort to shatter the glass ceilings for women who aspire to climb the corporate ladders.Keywords: gender inequality, glass ceilings, patriarchy, female disparity
Procedia PDF Downloads 65188 CybeRisk Management in Banks: An Italian Case Study
Authors: E. Cenderelli, E. Bruno, G. Iacoviello, A. Lazzini
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The financial sector is exposed to the risk of cyber-attacks like any other industrial sector. Furthermore, the topic of CybeRisk (cyber risk) has become particularly relevant given that Information Technology (IT) attacks have increased drastically in recent years, and cannot be stopped by single organizations requiring a response at international and national level. IT risk is never a matter purely for the IT manager, although he clearly plays a key role. A bank's risk management function requires a thorough understanding of the evolving risks as well as the tools and practical techniques available to address them. Upon the request of European and national legislation regarding CybeRisk in the financial system, banks are therefore called upon to strengthen the operational model for CybeRisk management. This will require an important change with a more intense collaboration with the structures that deal with information security for the development of an ad hoc system for the evaluation and control of this type of risk. The aim of the work is to propose a framework for the management and control of CybeRisk that will bridge the gap in the literature regarding the understanding and consideration of CybeRisk as an integral part of business management. The IT function has a strong relevance in the management of CybeRisk, which is perceived mainly as operational risk, but with a positive tendency on the part of risk management to the identification of CybeRisk assessment methods that are increasingly complete, quantitative and able to better describe the possible impacts on the business. The paper provides answers to the research questions: Is it possible to define a CybeRisk governance structure able to support the comparison between risk and security? How can the relationships between IT assets be integrated into a cyberisk assessment framework to guarantee a system of protection and risks control? From a methodological point of view, this research uses a case study approach. The choice of “Monte dei Paschi di Siena” was determined by the specific features of one of Italy’s biggest lenders. It is chosen to use an intensive research strategy: an in-depth study of reality. The case study methodology is an empirical approach to explore a complex and current phenomenon that develops over time. The use of cases has also the advantage of allowing the deepening of aspects concerning the "how" and "why" of contemporary events, on which the scholar has little control. The research bases on quantitative data and qualitative information obtained through semi-structured interviews of an open-ended nature and questionnaires to directors, members of the audit committee, risk, IT and compliance managers, and those responsible for internal audit function and anti-money laundering. The added value of the paper can be seen in the development of a framework based on a mapping of IT assets from which it is possible to identify their relationships for purposes of a more effective management and control of cyber risk.Keywords: bank, CybeRisk, information technology, risk management
Procedia PDF Downloads 232187 Poland and the Dawn of the Right to Education and Development: Moving Back in Time
Authors: Magdalena Zabrocka
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The terror of women throughout the governance of the current populist ruling party in Poland, PiS, has been a subject of a heated debate alongside the issues of minorities’ rights, the rule of law, and democracy in the country. The challenges that women and other vulnerable groups are currently facing, however, come down to more than just a lack of comprehensive equality laws, severely limited reproductive rights, hateful slogans, and messages propagated by the central authority and its sympathisers, or a common disregard for women’s fundamental rights. Many sources and media reports are available only in Polish, while international rapporteurs fail to acknowledge the whole picture of the tragedy happening in the country and the variety of factors affecting it. Starting with the authorities’ and Polish catholic church’s propaganda concerning CEDAW and the Istanbul Convention Action against Violence against Women and Domestic Violence by spreading strategic disinformation that it codifies ‘gender ideology’ and ‘anti-Christian values’ in order to convince the electorate that the legal instruments should be ‘abandoned’. Alongside severely restricted abortion rights, bullying medical professionals helping women exercise their reproductive rights, violating women’s privacy by introducing a mandatory registry of pregnancies (so that one’s pregnancy or its ‘loss’ can be tracked and traced), restricting access to the ‘day after pill’ and real sex education at schools (most schools have a subject of ‘knowledge of living in a family’), introducing prison punishment for teachers accused of spreading ‘sex education’, and many other, the current tyrant government, has now decided to target the youngest with its misinformation and indoctrination, via strategically designed textbooks and curriculum. Biology books have seen a big restriction on the size of the chapters devoted to evolution, reproductive system, and sexual health. Approved religion books (which are taught 2-3 times a week as compared to 1 a week sciences) now cover false information about Darwin’s theory and arguments ‘against it’. Most recently, however, the public spoke up against the absurd messages contained in the politically rewritten history books, where the material about some figures not liked by the governing party has already been manipulated. In the recently approved changes to the history textbook, one can find a variety of strongly biased and politically-charged views representative of the conservatives in the states, most notably, equating the ‘gender ideology’ and feminism with Nazism. Thus, this work, by employing a human rights approach, would focus on the right to education and development as well as the considerate obstacles to access to scientific information by the youth.Keywords: Poland, right to education, right to development, authoritarianism, access to information
Procedia PDF Downloads 107186 Benjaminian Translatability and Elias Canetti's Life Component: The Other German Speaking Modernity
Authors: Noury Bakrim
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Translatability is one of Walter Benjamin’s most influential notions, it is somehow representing the philosophy of language and history of what we might call and what we indeed coined as ‘the other German Speaking Modernity’ which could be shaped as a parallel thought form to the Marxian-Hegelian philosophy of history, the one represented by the school of Frankfurt. On the other hand, we should consider the influence of the plural German speaking identity and the Nietzschian and Goethean heritage, this last being focused on a positive will of power: the humanised human being. Having in perspective the benjaminian notion of translatability (Übersetzbarkeit), to be defined as an internal permanent hermeneutical possibility as well as a phenomenological potential of a translation relation, we are in fact touching this very double limit of both historical and linguistic reason. By life component, we mean the changing conditions of genetic and neurolinguistic post-partum functions, to be grasped as an individuation beyond the historical determinism and teleology of an event. It is, so to speak, the retrospective/introspective canettian auto-fiction, the benjaminian crystallization of the language experience in the now-time of writing/transmission. Furthermore, it raises various questioning points when it comes to translatability, they are basically related to psycholinguistic separate poles, the fatherly ladino Spanish and the motherly Vienna German, but relating more in particular to the permanent ontological quest of a world loss/belonging. Another level of this quest would be the status of Veza Canetti-Taubner Calderón, german speaking Author, Canetti’s ‘literary wife’, writer’s love, his inverted logos, protective and yet controversial ‘official private life partner’, the permanence of the jewish experience in the exiled german language. It sheds light on a traumatic relation of an inadequate/possible language facing the reconstruction of an oral life, the unconscious split of the signifier and above all on the frustrating status of writing in Canetti’s work : Using a suffering/suffered written German to save his remembered acquisition of his tongue/mother tongue by saving the vanishing spoken multilingual experience. While Canetti’s only novel ‘Die Blendung’ designates that fictional referential dynamics focusing on the nazi worldless horizon: the figure of Kien is an onomastic signifier, the anti-Canetti figure, the misunderstood legacy of Kant, the system without thought. Our postulate would be the double translatability of his auto-fiction inventing the bios oral signifier basing on the new praxemes created by Canetti’s german as observed in the English, French translations of his memory corpus. We aim at conceptualizing life component and translatability as two major features of a german speaking modernity.Keywords: translatability, language biography, presentification, bioeme, life Order
Procedia PDF Downloads 427185 Pharmacological Mechanisms of an Indolic Compound in Chemoprevention of Colonic Acf Formation in Azoxymethane-Induced Colon Cancer Rat Model and Cell Lines
Authors: Nima Samie, Sekaran Muniandy, Zahurin Mohamed, M. S. Kanthimathi
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Although number of indole containing compounds have been reported to have anticancer properties in vitro but only a few of them show potential as anticancer compounds in vivo. The current study was to evaluate the mechanism of cytotoxicity of selected indolic compound in vivo and in vitro. In this context, we determined the potency of the compound in the induction of apoptosis, cell cycle arrest, and cytoskeleton rearrangement. HT-29, WiDr, CCD-18Co, human monocyte/macrophage CRL-9855, and B lymphocyte CCL-156 cell lines were used to determine the IC50 of the compound using the MTT assay. Analysis of apoptosis was carried out using immunofluorescence, acridine orange/ propidium iodide double staining, Annexin-V-FITC assay, evaluation of the translocation of NF-kB, oxygen radical antioxidant capacity, quenching of reactive oxygen species content, measurement of LDH release, caspase-3/-7, -8 and -9 assays and western blotting. The cell cycle arrest was examined using flowcytometry and gene expression was assessed using qPCR array. Results displayed a potent suppressive effect on HT-29 and WiDr after 24 h of treatment with IC50 value of 2.52±0.34 µg/ml and 2.13±0.65 µg/ml respectively. This cytotoxic effect on normal, monocyte/macrophage and B-cells was insignificant. Dipping in the mitochondrial membrane potential and increased release of cytochrome c from the mitochondria indicated induction of the intrinsic apoptosis pathway by the compound. Activation of this pathway was further evidenced by significant activation of caspase-9 and 3/7. The compound was also shown to activate the extrinsic pathways of apoptosis via activation of caspase-8 which is linked to the suppression of NF-kB translocation to the nucleus. Cell cycle arrest in the G1 phase and up-regulation of glutathione reductase, based on excessive ROS production were also observed. These findings were further investigated for inhibitory efficiency of the compound on colonic aberrant crypt foci in male rats. Rats were divided in to 5 groups: vehicle, cancer control, positive control groups and the groups treated with 25 and 50 mg/kg of compounds for 10 weeks. Administration of compound suppressed total colonic ACF formation up to 73.4%. The results also showed that treatment with the compound significantly reduced the level of malondialdehyde while increasing superoxide dismutase and catalase activities. Furthermore, the down-regulation of PCNA and Bcl2 and the up-regulation of Bax was confirmed by immunohistochemical staining. The outcome of this study suggest sthat the indolic compound is a potent anti-cancer agent against colon cancer and can be further evaluated by animal trial.Keywords: indolic compound, chemoprevention, crypt, azoxymethane, colon cancer
Procedia PDF Downloads 348184 Rt-Pcr Negative COVID-19 Infection in a Bodybuilding Competitor Using Anabolic Steroids: A Case Report
Authors: Mariana Branco, Nahida Sobrino, Cristina Neves, Márcia Santos, Afonso Granja, João Rosa Oliveira, Joana Costa, Luísa Castro Leite
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This case reports a COVID-19 infection in an unvaccinated adult man with no history of COVID-19 and no relevant clinical history besides anabolic steroid use, undergoing weaning with tamoxifen after a bodybuilding competition. The patient presented a 4cm cervical mass 3 weeks after COVID-19 infection in his cohabitants. He was otherwise asymptomatic and tested negative to multiple RT-PCR tests. Nevertheless, the IgG COVID-19 antibody was positive, suggesting the previous infection. This report raises a potential link between anabolic steroid use and atypical COVID-19 onset. Objectives: The goals of this paper are to raise a potential link between anabolic steroid use and atypical COVID-19 onset but also to report an uncommon case of COVID-19 infection with consecutive negative gold standard tests. Methodology: The authors used CARE guidelines for case report writing. Introduction: This case reports a COVID-19 infection case in an unvaccinated adult man, with multiple serial negative reverse transcription polymerase chain reaction (RT-PCR) test results, presenting with single cervical lymphadenopathy. Although the association between COVID-19 and lymphadenopathy is well established, there are no cases with this presentation, and consistently negative RT-PCR tests have been reported. Methodologies: The authors used CARE guidelines for case report writing. Case presentation: This case reports a 28-year-old Caucasian man with no previous history of COVID-19 infection or vaccination and no relevant clinical history besides anabolic steroid use undergoing weaning with tamoxifendue to participation in a bodybuilding competition. He visits his primary care physician because of a large (4 cm) cervical lump, present for 3 days prior to the consultation. There was a positive family history for COVID-19 infection 3 weeks prior to the visit, during which the patient cohabited with the infected family members. The patient never had any previous clinical manifestation of COVID-19 infection and, despite multiple consecutive RT-PCR testing, never tested positive. The patient was treated with an NSAID and a broad-spectrum antibiotic, with little to no effect. Imagiological testing was performed via a cervical ultrasound, followed by a needle biopsy for histologic analysis. Serologic testing for COVID-19 immunity was conducted, revealing a positive Anti-SARS-CoV-2 IgG (Spike S1) antibody, suggesting the previous infection, given the unvaccinated status of our patient Conclusion: In patients with a positive epidemiologic context and cervical lymphadenopathy, physicians should still consider COVID-19 infection as a differential diagnosis, despite negative PCR testing. This case also raises a potential link between anabolic steroid use and atypical COVID-19 onset, never before reported in scientific literature.Keywords: COVID-19, cervical lymphadenopathy, anabolic steroids, primary care
Procedia PDF Downloads 118183 Determination of 1-Deoxynojirimycin and Phytochemical Profile from Mulberry Leaves Cultivated in Indonesia
Authors: Yasinta Ratna Esti Wulandari, Vivitri Dewi Prasasty, Adrianus Rio, Cindy Geniola
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Mulberry is a plant that widely cultivated around the world, mostly for silk industry. In recent years, the study showed that the mulberry leaves have an anti-diabetic effect which mostly comes from the compound known as 1-deoxynojirimycin (DNJ). DNJ is a very potent α-glucosidase inhibitor. It will decrease the degradation rate of carbohydrates in digestive tract, leading to slower glucose absorption and reducing the post-prandial glucose level significantly. The mulberry leaves also known as the best source of DNJ. Since then, the DNJ in mulberry leaves had received a considerable attention, because of the increased number of diabetic patients and the raise of people awareness to find a more natural cure for diabetic. The DNJ content in mulberry leaves varied depend on the mulberry species, leaf’s age, and the plant’s growth environment. Few of the mulberry varieties that were cultivated in Indonesiaare Morus alba var. kanva-2, M. alba var. multicaulis, M. bombycis var. lembang, and M. cathayana. The lack of data concerning phytochemicals contained in the Indonesian mulberry leaves are restraining their use in the medicinal field. The aim of this study is to fully utilize the use of mulberry leaves cultivated in Indonesia as a medicinal herb in local, national, or global community, by determining the DNJ and other phytochemical contents in them. This study used eight leaf samples which are the young leaves and mature leaves of both Morus alba var. kanva-2, M. alba var. multicaulis, M. bombycis var. lembang, and M. cathayana. The DNJ content was analyzed using reverse phase high performance liquid chromatography (HPLC). The stationary phase was silica C18 column and the mobile phase was acetonitrile:acetic acid 0.1% 1:1 with elution rate 1 mL/min. Prior to HPLC analysis the samples were derivatized with FMOC to ensure the DNJ detectable by VWD detector at 254 nm. Results showed that the DNJ content in samples are ranging from 2.90-0.07 mg DNJ/ g leaves, with the highest content found in M. cathayana mature leaves (2.90 ± 0.57 mg DNJ/g leaves). All of the mature leaf samples also found to contain higher amount of DNJ from their respective young leaf samples. The phytochemicals in leaf samples was tested using qualitative test. Result showed that all of the eight leaf samples contain alkaloids, phenolics, flavonoids, tannins, and terpenes. The presence of this phytochemicals contribute to the therapeutic effect of mulberry leaves. The pyrolysis-gas chromatography-mass spectrometry (Py-GC-MS) analysis was also performed to the eight samples to quantitatively determine their phytochemicals content. The pyrolysis temperature was set at 400 °C, with capillary column Phase Rtx-5MS 60 × 0.25 mm ID stationary phase and helium gas mobile phase. Few of the terpenes found are known to have anticancer and antimicrobial properties. From all the results, all of four samples of mulberry leaves which are cultivated in Indonesia contain DNJ and various phytochemicals like alkaloids, phenolics, flavonoids, tannins, and terpenes which are beneficial to our health.Keywords: Morus, 1-deoxynojirimycin, HPLC, Py-GC-MS
Procedia PDF Downloads 331182 Tailorability of Poly(Aspartic Acid)/BSA Complex by Self-Assembling in Aqueous Solutions
Authors: Loredana E. Nita, Aurica P. Chiriac, Elena Stoleru, Alina Diaconu, Tudorachi Nita
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Self-assembly processes are an attractive method to form new and complex structures between macromolecular compounds to be used for specific applications. In this context, intramolecular and intermolecular bonds play a key role during self-assembling processes in preparation of carrier systems of bioactive substances. Polyelectrolyte complexes (PECs) are formed through electrostatic interactions, and though they are significantly below of the covalent linkages in their strength, these complexes are sufficiently stable owing to the association processes. The relative ease way of PECs formation makes from them a versatile tool for preparation of various materials, with properties that can be tuned by adjusting several parameters, such as the chemical composition and structure of polyelectrolytes, pH and ionic strength of solutions, temperature and post-treatment procedures. For example, protein-polyelectrolyte complexes (PPCs) are playing an important role in various chemical and biological processes, such as protein separation, enzyme stabilization and polymer drug delivery systems. The present investigation is focused on evaluation of the PPC formation between a synthetic polypeptide (poly(aspartic acid) – PAS) and a natural protein (bovine serum albumin - BSA). The PPC obtained from PAS and BSA in different ratio was investigated by corroboration of various techniques of characterization as: spectroscopy, microscopy, thermo-gravimetric analysis, DLS and zeta potential determination, measurements which were performed in static and/or dynamic conditions. The static contact angle of the sample films was also determined in order to evaluate the changes brought upon surface free energy of the prepared PPCs in interdependence with the complexes composition. The evolution of hydrodynamic diameter and zeta potential of the PPC, recorded in situ, confirm changes of both co-partners conformation, a 1/1 ratio between protein and polyelectrolyte being benefit for the preparation of a stable PPC. Also, the study evidenced the dependence of PPC formation on the temperature of preparation. Thus, at low temperatures the PPC is formed with compact structure, small dimension and hydrodynamic diameter, close to those of BSA. The behavior at thermal treatment of the prepared PPCs is in agreement with the composition of the complexes. From the contact angle determination results the increase of the PPC films cohesion, which is higher than that of BSA films. Also, a higher hydrophobicity corresponds to the new PPC films denoting a good adhesion of the red blood cells onto the surface of PSA/BSA interpenetrated systems. The SEM investigation evidenced as well the specific internal structure of PPC concretized in phases with different size and shape in interdependence with the interpolymer mixture composition.Keywords: polyelectrolyte – protein complex, bovine serum albumin, poly(aspartic acid), self-assembly
Procedia PDF Downloads 246181 Combating Corruption to Enhance Learner Academic Achievement: A Qualitative Study of Zimbabwean Public Secondary Schools
Authors: Onesmus Nyaude
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The aim of the study was to investigate participants’ views on how corruption can be combated to enhance learner academic achievement. The study was undertaken on three select public secondary institutions in Zimbabwe. This study also focuses on exploring the various views of educators; parents and the learners on the role played by corruption in perpetuating the seemingly existing learner academic achievement disparities in various educational institutions. The study further interrogates and examines the nexus between the prevalence of corruption in schools and the subsequent influence on the academic achievement of learners. Corruption is considered a form of social injustice; hence in Zimbabwe, the general consensus is that it is perceived rife to the extent that it is overtaking the traditional factors that contributed to the poor academic achievement of learners. Coupled to this, have been the issue of gross abuse of power and some malpractices emanating from concealment of essential and official transactions in the conduct of business. Through proposing robust anti-corruption mechanisms, teaching and learning resources poured in schools would be put into good use. This would prevent the unlawful diversion and misappropriation of the resources in question which has always been the culture. This study is of paramount significance to curriculum planners, teachers, parents, and learners. The study was informed by the interpretive paradigm; thus qualitative research approaches were used. Both probability and non-probability sampling techniques were adopted in ‘site and participants’ selection. A representative sample of (150) participants was used. The study found that the majority of the participants perceived corruption as a social problem and a human right threat affecting the quality of teaching and learning processes in the education sector. It was established that corruption prevalence within institutions is as a result of the perpetual weakening of ethical values and other variables linked to upholding of ‘Ubuntu’ among general citizenry. It was further established that greediness and weak systems are major causes of rampant corruption within institutions of higher learning and are manifesting through abuse of power, bribery, misappropriation and embezzlement of material and financial resources. Therefore, there is great need to collectively address the problem of corruption in educational institutions and society at large. The study additionally concludes that successful combating of corruption will promote successful moral development of students as well as safeguarding their human rights entitlements. The study recommends the adoption of principles of good corporate governance within educational institutions in order to successfully curb corruption. The study further recommends the intensification of interventionist strategies and strengthening of systems in educational institutions as well as regular audits to overcome the problem associated with rampant corruption cases.Keywords: academic achievement, combating, corruption, good corporate governance, qualitative study
Procedia PDF Downloads 244180 Inhibition of Food Borne Pathogens by Bacteriocinogenic Enterococcus Strains
Authors: Neha Farid
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Due to the abuse of antimicrobial medications in animal feed, the occurrence of multi-drug resistant (MDR) pathogens in foods is currently a growing public health concern on a global scale. MDR infections have the potential to penetrate the food chain by posing a serious risk to both consumers and animals. Food pathogens are those biological agents that have the tendency to cause pathogenicity in the host body upon ingestion. The major reservoirs of foodborne pathogens include food-producing fauna like cows, pigs, goats, sheep, deer, etc. The intestines of these animals are highly condensed with several different types of food pathogens. Bacterial food pathogens are the main cause of foodborne disease in humans; almost 66% of the reported cases of food illness in a year are caused by the infestation of bacterial food pathogens. When ingested, these pathogens reproduce and survive or form different kinds of toxins inside host cells causing severe infections. The genus Listeria consists of gram-positive, rod-shaped, non-spore-forming bacteria. The disease caused by Listeria monocytogenes is listeriosis or gastroenteritis, which induces fever, vomiting, and severe diarrhea in the affected body. Campylobacter jejuni is a gram-negative, curved-rod-shaped bacteria causing foodborne illness. The major source of Campylobacter jejuni is livestock and poultry; particularly, chicken is highly colonized with Campylobacter jejuni. Serious public health concerns include the widespread growth of bacteria that are resistant to antibiotics and the slowing in the discovery of new classes of medicines. The objective of this study is to provide some potential antibacterial activities with certain broad-range antibiotics and our desired bacteriocins, i.e., Enterococcus faecium from specific strains preventing microbial contamination pathways in order to safeguard the food by lowering food deterioration, contamination, and foodborne illnesses. The food pathogens were isolated from various sources of dairy products and meat samples. The isolates were tested for the presence of Listeria and Campylobacter by gram staining and biochemical testing. They were further sub-cultured on selective media enriched with the growth supplements for Listeria and Campylobacter. All six strains of Listeria and Campylobacter were tested against ten antibiotics. Campylobacter strains showed resistance against all the antibiotics, whereas Listeria was found to be resistant only against Nalidixic Acid and Erythromycin. Further, the strains were tested against the two bacteriocins isolated from Enterococcus faecium. It was found that bacteriocins showed better antimicrobial activity against food pathogens. They can be used as a potential antimicrobial for food preservation. Thus, the study concluded that natural antimicrobials could be used as alternatives to synthetic antimicrobials to overcome the problem of food spoilage and severe food diseases.Keywords: food pathogens, listeria, campylobacter, antibiotics, bacteriocins
Procedia PDF Downloads 72179 Female Fans in Global Football Governance: A Call for Change
Authors: Yaron Covo, Tamar Kofman, Shira Palti
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Over the recent decades, debates about the engagement of fans in football governance have focused on the club level and national level, emphasizing the significance of fans’ involvement in increasing the connection of clubs with the community, and in safeguarding the transparency, accountability, and clubs’ financial stability. This paper will offer a different conceptual justification for providing fans with access to decision-making processes in football. First, it will suggest that the participation of fans is necessary for addressing discriminatory practices against women in football stadiums. Second, it will argue that fans’ involvement in football governance is important not only at the club and national level but also at the global level, relying on the principles of Global Administrative Law. In contemporary men’s football, female fans face different forms of discrimination. Iranian women are still prohibited from attending football games at the domestic level; In Saudi Arabia, female fans are only permitted to enter designated family areas; Qatar – the host of the 2022 FIFA world cup – requires women to attend matches wearing modest clothing. Similarly, in Turkey, Lebanon, UAE, and Algeria, women face cultural barriers when attending men’s football games. In other countries, female fans suffer from subtle discrimination, including micro-aggressions, misogyny, sexism, and noninstitutionalized exclusion. Despite the vital role of fans in world football and the importance of football for many women’s lives, little has been done to address this problem. While FIFA recognizes that these discriminatory practices contradict its statutes, this recognition fails to materialize into meaningful change. This paper will argue that FIFA’s omission stems from two interrelated characteristics of world football: (1) the ultra-masculine nature of the game; (2) the insufficient recognition of fans’ significance. While fans have been given a voice in various football bodies on the domestic level, FIFA has yet to allow the representation of fans as stakeholders in world football governance. Since fans are a more heterogeneous group than players, the voices of those fans who do not fit the ultra-masculine model are not heard. Thus, by focusing mainly on male players, FIFA reproduces the hegemonic masculinity that feeds back into fan dynamics and marginalizes female fans. To rectify this problem, we will call on FIFA to provide fans and female fans in particular, with voice mechanisms and access to decision-making processes. In addition to its impact on the formation of fans’ identities, such a move will allow fans to demand better enforcement of existing anti-discrimination norms and new regulations to address their needs. The literature has yet to address the relationship between fans’ gender discrimination and global football governance. Building on Global Administrative Law scholarship and feminist theories, this paper will aim to fill this gap.Keywords: fans, FIFA, football governance, gender discrimination, global administrative law, human rights
Procedia PDF Downloads 150178 Human Immuno-Deficiency Virus Co-Infection with Hepatitis B Virus and Baseline Cd4+ T Cell Count among Patients Attending a Tertiary Care Hospital, Nepal
Authors: Soma Kanta Baral
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Background: Since 1981, when the first AIDS case was reported, worldwide, more than 34 million people have been infected with HIV. Almost 95 percent of the people infected with HIV live in developing countries. As HBV & HIV share similar routes of transmission by sexual intercourse or drug use by parenteral injection, co-infection is common. Because of the limited access to healthcare & HIV treatment in developing countries, HIV-infected individuals are present late for care. Enumeration of CD4+ T cell count at the time of diagnosis has been useful to initiate the therapy in HIV infected individuals. The baseline CD4+ T cell count shows high immunological variability among patients. Methods: This prospective study was done in the serology section of the Department of Microbiology over a period of one year from august 2012 to July 2013. A total of 13037 individuals subjected for HIV test were included in the study comprising of 4982 males & 8055 females. Blood sample was collected by vein puncture aseptically with standard operational procedure in clean & dry test-tube. All blood samples were screened for HIV as described by WHO algorithm by Immuno-chromatography rapid kits. Further confirmation was done by biokit ELISA method as per the manufacturer’s guidelines. After informed consent, HIV positive individuals were screened for HBsAg by Immuno-chromatography rapid kits (Hepacard). Further confirmation was done by biokit ELISA method as per the manufacturer’s guidelines. EDTA blood samples were collected from the HIV sero-positive individuals for baseline CD4+ T count. Then, CD4+ T cells count was determined by using FACS Calibur Flow Cytometer (BD). Results: Among 13037 individuals screened for HIV, 104 (0.8%) were found to be infected comprising of 69(66.34%) males & 35 (33.65%) females. The study showed that the high infection was noted in housewives (28.7%), active age group (30.76%), rural area (56.7%) & in heterosexual route (80.9%) of transmission. Out of total HIV infected individuals, distribution of HBV co-infection was found to be 6(5.7%). All co- infected individuals were married, male, above the age of 25 years & heterosexual route of transmission. Baseline CD4+ T cell count of HIV infected patient was found higher (mean CD4+ T cell count; 283cells/cu.mm) than HBV co-infected patients (mean CD4+ T cell count; 91 cells/cu.mm). Majority (77.2%) of HIV infected & all co-infected individuals were presented in our center late (CD4+ T cell count;< 350/cu. mm) for diagnosis and care. Majority of co- infected 4 (80%) were late presented with advanced AIDS stage (CD4+ count; <200/cu.mm). Conclusions: The study showed a high percentage of HIV sero-positive & co- infected individuals. Baseline CD4+ T cell count of majority of HIV infected individuals was found to be low. Hence, more sustained and vigorous awareness campaigns & counseling still need to be done in order to promote early diagnosis and management.Keywords: HIV/AIDS, HBsAg, co-infection, CD4+
Procedia PDF Downloads 217177 Antimicrobial Value of Olax subscorpioidea and Bridelia ferruginea on Micro-Organism Isolates of Dental Infection
Authors: I. C. Orabueze, A. A. Amudalat, S. A. Adesegun, A. A. Usman
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Dental and associated oral diseases are increasingly affecting a considerable portion of the population and are considered some of the major causes of tooth loss, discomfort, mouth odor and loss of confidence. This study focused on the ethnobotanical survey of medicinal plants used in oral therapy and evaluation of the antimicrobial activities of methanolic extracts of two selected plants from the survey for their efficacy against dental microorganisms. The ethnobotanical survey was carried out in six herbal markets in Lagos State, Nigeria by oral interviewing and information obtained from an old family manually complied herbal medication book. Methanolic extracts of Olax subscorpioidea (stem bark) and Bridelia ferruginea (stem bark) were assayed for their antimicrobial activities against clinical oral isolates (Aspergillus fumigatus, Candida albicans, Streptococcus spp, Staphylococcus aureus, Lactobacillus acidophilus and Pseudomonas aeruginosa). In vitro microbial technique (agar well diffusion method and minimum inhibitory concentration (MIC) assay) were employed for the assay. Chlorhexidine gluconate was used as the reference drug for comparison with the extract results. And the preliminary phytochemical screening of the constituents of the plants were done. The ethnobotanical survey produced plants (28) of diverse family. Different parts of plants (seed, fruit, leaf, root, bark) were mentioned but 60% mentioned were either the stem or the bark. O. subscorpioidea showed considerable antifungal activity with zone of inhibition ranging from 2.650 – 2.000 cm against Aspergillus fumigatus but no such encouraging inhibitory activity was observed in the other assayed organisms. B. ferruginea showed antibacterial sensitivity against Streptococcus spp, Staphylococcus aureus, Lactobacillus acidophilus and Pseudomonas aeruginosa with zone of inhibitions ranging from 3.400 - 2.500, 2.250 - 1.600, 2.700 - 1.950, 2.225 – 1.525 cm respectively. The minimum inhibitory concentration of O. subscorpioidea against Aspergillus fumigatus was 51.2 mg ml-1 while that of B. ferruginea against Streptococcus spp was 0.1mg ml-1 and for Staphylococcus aureus, Lactobacillus acidophilus and Pseudomonas aeruginosa were 25.6 mg ml-1. A phytochemical analysis reveals the presence of alkaloids, saponins, cardiac glycoside, tannins, phenols and terpenoids in both plants, with steroids only in B. ferruginea. No toxicity was observed among mice given the two methanolic extracts (1000 mg Kg-1) after 21 days. The barks of both plants exhibited antimicrobial properties against periodontal diseases causing organisms assayed, thus up-holding their folkloric use in oral disorder management. Further research could be done viewing these extracts as combination therapy, checking for possible synergistic value in toothpaste and oral rinse formulations for reducing oral bacterial flora and fungi load.Keywords: antimicrobial activities, Bridelia ferruginea, dental disinfection, methanolic extract, Olax subscorpioidea, ethnobotanical survey
Procedia PDF Downloads 244176 Role of Lipid-Lowering Treatment in the Monocyte Phenotype and Chemokine Receptor Levels after Acute Myocardial Infarction
Authors: Carolina N. França, Jônatas B. do Amaral, Maria C.O. Izar, Ighor L. Teixeira, Francisco A. Fonseca
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Introduction: Atherosclerosis is a progressive disease, characterized by lipid and fibrotic element deposition in large-caliber arteries. Conditions related to the development of atherosclerosis, as dyslipidemia, hypertension, diabetes, and smoking are associated with endothelial dysfunction. There is a frequent recurrence of cardiovascular outcomes after acute myocardial infarction and, at this sense, cycles of mobilization of monocyte subtypes (classical, intermediate and nonclassical) secondary to myocardial infarction may determine the colonization of atherosclerotic plaques in different stages of the development, contributing to early recurrence of ischemic events. The recruitment of different monocyte subsets during inflammatory process requires the expression of chemokine receptors CCR2, CCR5, and CX3CR1, to promote the migration of monocytes to the inflammatory site. The aim of this study was to evaluate the effect of lipid-lowering treatment by six months in the monocyte phenotype and chemokine receptor levels of patients after Acute Myocardial Infarction (AMI). Methods: This is a PROBE (prospective, randomized, open-label trial with blinded endpoints) study (ClinicalTrials.gov Identifier: NCT02428374). Adult patients (n=147) of both genders, ageing 18-75 years, were randomized in a 2x2 factorial design for treatment with rosuvastatin 20 mg/day or simvastatin 40 mg/day plus ezetimibe 10 mg/day as well as ticagrelor 90 mg 2x/day and clopidogrel 75 mg, in addition to conventional AMI therapy. Blood samples were collected at baseline, after one month and six months of treatment. Monocyte subtypes (classical - inflammatory, intermediate - phagocytic and nonclassical – anti-inflammatory) were identified, quantified and characterized by flow cytometry, as well as the expressions of the chemokine receptors (CCR2, CCR5 and CX3CR1) were also evaluated in the mononuclear cells. Results: After six months of treatment, there was an increase in the percentage of classical monocytes and reduction in the nonclassical monocytes (p=0.038 and p < 0.0001 Friedman Test), without differences for intermediate monocytes. Besides, classical monocytes had higher expressions of CCR5 and CX3CR1 after treatment, without differences related to CCR2 (p < 0.0001 for CCR5 and CX3CR1; p=0.175 for CCR2). Intermediate monocytes had higher expressions of CCR5 and CX3CR1 and lower expression of CCR2 (p = 0.003; p < 0.0001 and p = 0.011, respectively). Nonclassical monocytes had lower expressions of CCR2 and CCR5, without differences for CX3CR1 (p < 0.0001; p = 0.009 and p = 0.138, respectively). There were no differences after the comparison between the four treatment arms. Conclusion: The data suggest a time-dependent modulation of classical and nonclassical monocytes and chemokine receptor levels. The higher percentage of classical monocytes (inflammatory cells) suggest a residual inflammatory risk, even under preconized treatments to AMI. Indeed, these changes do not seem to be affected by choice of the lipid-lowering strategy.Keywords: acute myocardial infarction, chemokine receptors, lipid-lowering treatment, monocyte subtypes
Procedia PDF Downloads 121175 Antimicrobial Resistance of Acinetobacter baumannii in Veterinary Settings: A One Health Perspective from Punjab, Pakistan
Authors: Minhas Alam, Muhammad Hidayat Rasool, Mohsin Khurshid, Bilal Aslam
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The genus Acinetobacter has emerged as a significant concern in hospital-acquired infections, particularly due to the versatility of Acinetobacter baumannii in causing nosocomial infections. The organism's remarkable metabolic adaptability allows it to thrive in various environments, including the environment, animals, and humans. However, the extent of antimicrobial resistance in Acinetobacter species from veterinary settings, especially in developing countries like Pakistan, remains unclear. This study aimed to isolate and characterize Acinetobacter spp. from veterinary settings in Punjab, Pakistan. A total of 2,230 specimens were collected, including 1,960 samples from veterinary settings (nasal and rectal swabs from dairy and beef cattle), 200 from the environment, and 70 from human clinical settings. Isolates were identified using routine microbiological procedures and confirmed by polymerase chain reaction (PCR). Antimicrobial susceptibility was determined by the disc diffusion method, and minimum inhibitory concentration (MIC) was measured by the micro broth dilution method. Molecular techniques, such as PCR and DNA sequencing, were used to screen for antimicrobial-resistant determinants. Genetic diversity was assessed using standard techniques. The results showed that the overall prevalence of A. baumannii in cattle was 6.63% (65/980). However, among cattle, a higher prevalence of A. baumannii was observed in dairy cattle, 7.38% (54/731), followed by beef cattle, 4.41% (11/249). Out of 65 A. baumannii isolates, the carbapenem resistance was found in 18 strains, i.e. 27.7%. The prevalence of A. baumannii in nasopharyngeal swabs was higher, i.e., 87.7% (57/65), as compared to rectal swabs, 12.3% (8/65). Class D β-lactamases genes blaOXA-23 and blaOXA-51 were present in all the CRAB from cattle. Among carbapenem-resistant isolates, 94.4% (17/18) were positive for class B β-lactamases gene blaIMP, whereas the blaNDM-1 gene was detected in only one isolate of A. baumannii. Among 70 clinical isolates of A. baumannii, 58/70 (82.9%) were positive for the blaOXA-23-like gene, and 87.1% (61/70) were CRAB isolates. Among all clinical isolates of A. baumannii, blaOXA-51-like gene was present. Hence, the co-existence of blaOXA-23 and blaOXA-51 was found in 82.85% of clinical isolates. From the environmental settings, a total of 18 A. baumannii isolates were recovered; among these, 38.88% (7/18) strains showed carbapenem resistance. All environmental isolates of A. baumannii harbored class D β-lactamases genes, i.e., blaOXA-51 and blaOXA-23 were detected in 38.9% (7/18) isolates. Hence, the co-existence of blaOXA-23 and blaOXA-51 was found in 38.88% of isolates. From environmental settings, 18 A. baumannii isolates were recovered, with 38.88% showing carbapenem resistance. All environmental isolates harbored blaOXA-51 and blaOXA-23 genes, with co-existence in 38.88% of isolates. MLST results showed ten different sequence types (ST) in clinical isolates, with ST 589 being the most common in carbapenem-resistant isolates. In veterinary isolates, ST2 was most common in CRAB isolates from cattle. Immediate control measures are needed to prevent the transmission of CRAB isolates among animals, the environment, and humans. Further studies are warranted to understand the mechanisms of antibiotic resistance spread and implement effective disease control programs.Keywords: Acinetobacter baumannii, carbapenemases, drug resistance, MSLT
Procedia PDF Downloads 71174 Switchable Lipids: From a Molecular Switch to a pH-Sensitive System for the Drug and Gene Delivery
Authors: Jeanne Leblond, Warren Viricel, Amira Mbarek
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Although several products have reached the market, gene therapeutics are still in their first stages and require optimization. It is possible to improve their lacking efficiency by the use of carefully engineered vectors, able to carry the genetic material through each of the biological barriers they need to cross. In particular, getting inside the cell is a major challenge, because these hydrophilic nucleic acids have to cross the lipid-rich plasmatic and/or endosomal membrane, before being degraded into lysosomes. It takes less than one hour for newly endocytosed liposomes to reach highly acidic lysosomes, meaning that the degradation of the carried gene occurs rapidly, thus limiting the transfection efficiency. We propose to use a new pH-sensitive lipid able to change its conformation upon protonation at endosomal pH values, leading to the disruption of the lipidic bilayer and thus to the fast release of the nucleic acids into the cytosol. It is expected that this new pH-sensitive mechanism promote endosomal escape of the gene, thereby its transfection efficiency. The main challenge of this work was to design a preparation presenting fast-responding lipidic bilayer destabilization properties at endosomal pH 5 while remaining stable at blood pH value and during storage. A series of pH-sensitive lipids able to perform a conformational switch upon acidification were designed and synthesized. Liposomes containing these switchable lipids, as well as co-lipids were prepared and characterized. The liposomes were stable at 4°C and pH 7.4 for several months. Incubation with siRNA led to the full entrapment of nucleic acids as soon as the positive/negative charge ratio was superior to 2. The best liposomal formulation demonstrated a silencing efficiency up to 10% on HeLa cells, very similar to a commercial agent, with a lowest toxicity than the commercial agent. Using flow cytometry and microscopy assays, we demonstrated that drop of pH was required for the transfection efficiency, since bafilomycin blocked the transfection efficiency. Additional evidence was brought by the synthesis of a negative control lipid, which was unable to switch its conformation, and consequently exhibited no transfection ability. Mechanistic studies revealed that the uptake was mediated through endocytosis, by clathrin and caveolae pathways, as reported for previous lipid nanoparticle systems. This potent system was used for the treatment of hypercholesterolemia. The switchable lipids were able to knockdown PCSK9 expression on human hepatocytes (Huh-7). Its efficiency is currently evaluated on in vivo mice model of PCSK9 KO mice. In summary, we designed and optimized a new cationic pH-sensitive lipid for gene delivery. Its transfection efficiency is similar to the best available commercial agent, without the usually associated toxicity. The promising results lead to its use for the treatment of hypercholesterolemia on a mice model. Anticancer applications and pulmonary chronic disease are also currently investigated.Keywords: liposomes, siRNA, pH-sensitive, molecular switch
Procedia PDF Downloads 204173 Implementation of a PDMS Microdevice for the Improved Purification of Circulating MicroRNAs
Authors: G. C. Santini, C. Potrich, L. Lunelli, L. Vanzetti, S. Marasso, M. Cocuzza, C. Pederzolli
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The relevance of circulating miRNAs as non-invasive biomarkers for several pathologies is nowadays undoubtedly clear, as they have been found to have both diagnostic and prognostic value able to add fundamental information to patients’ clinical picture. The availability of these data, however, relies on a time-consuming process spanning from the sample collection and processing to the data analysis. In light of this, strategies which are able to ease this procedure are in high demand and considerable effort have been made in developing Lab-on-a-chip (LOC) devices able to speed up and standardise the bench work. In this context, a very promising polydimethylsiloxane (PDMS)-based microdevice which integrates the processing of the biological sample, i.e. purification of extracellular miRNAs, and reverse transcription was previously developed in our lab. In this study, we aimed at the improvement of the miRNA extraction performances of this micro device by increasing the ability of its surface to absorb extracellular miRNAs from biological samples. For this purpose, we focused on the modulation of two properties of the material: roughness and charge. PDMS surface roughness was modulated by casting with several templates (terminated with silicon oxide coated by a thin anti-adhesion aluminum layer), followed by a panel of curing conditions. Atomic force microscopy (AFM) was employed to estimate changes at the nanometric scale. To introduce modifications in surface charge we functionalized PDMS with different mixes of positively charged 3-aminopropyltrimethoxysilanes (APTMS) and neutral poly(ethylene glycol) silane (PEG). The surface chemical composition was characterized by X-ray photoelectron spectroscopy (XPS) and the number of exposed primary amines was quantified with the reagent sulfosuccinimidyl-4-o-(4,4-dimethoxytrityl) butyrate (s-SDTB). As our final end point, the adsorption rate of all these different conditions was assessed by fluorescence microscopy by incubating a synthetic fluorescently-labeled miRNA. Our preliminary analysis identified casting on thermally grown silicon oxide, followed by a curing step at 85°C for 1 hour, as the most efficient technique to obtain a PDMS surface roughness in the nanometric scaleable to trap miRNA. In addition, functionalisation with 0.1% APTMS and 0.9% PEG was found to be a necessary step to significantly increase the amount of microRNA adsorbed on the surface, therefore, available for further steps as on-chip reverse transcription. These findings show a substantial improvement in the extraction efficiency of our PDMS microdevice, ultimately leading to an important step forward in the development of an innovative, easy-to-use and integrated system for the direct purification of less abundant circulating microRNAs.Keywords: circulating miRNAs, diagnostics, Lab-on-a-chip, polydimethylsiloxane (PDMS)
Procedia PDF Downloads 318172 Ventilator Associated Pneumonia in a Medical Intensive Care Unit, Incidence and Risk Factors: A Case Control Study
Authors: Ammar Asma, Bouafia Nabiha, Ben Cheikh Asma, Ezzi Olfa, Mahjoub Mohamed, Sma Nesrine, Chouchène Imed, Boussarsar Hamadi, Njah Mansour
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Background: Ventilator-associated pneumonia (VAP) is currently recognized as one of the most relevant causes of morbidity and mortality among intensive care unit (ICU) patients worldwide. Identifying modifiable risk factors for VAP could be helpful for future controlled interventional studies aiming at improving prevention of VAP. The purposes of this study were to determine the incidence and risk factors for VAP in in a Tunisian medical ICU. Materials / Methods: A retrospective case-control study design based on the prospective database collected over a 14-month period from September 15th, 2015 through November 15th, 2016 in an 8-bed medical ICU. Patients under ventilation for over 48 h were included. The number of cases was estimated by Epi-info Software with the power of statistical test equal to 90 %. Each case patient was successfully matched to two controls according to the length of mechanical ventilation (MV) before VAP for cases and the total length of MV in controls. VAP in the ICU was defined according to American Thoracic Society; Infectious Diseases Society of America guidelines. Early onset or late-onset VAP were defined whether the infectious process occurred within or after 96 h of ICU admission. Patients’ risk factors, causes of admission, comorbidities and respiratory specimens collected were reviewed. Univariate and multivariate analyses were performed to determine variables associated with VAP with a p-value < 0.05. Results: During the period study, a total of 169 patients under mechanical ventilation were considered, 34 patients (20.11%) developed at least one episode of VAP in the ICU. The incidence rate for VAP was 14.88/1000 ventilation days. Among these cases, 9 (26.5 %) were early-onset VAP and 25 (73.5 %) were late-onset VAP. It was a certain diagnosis in 66.7% of cases. Tracheal aspiration was positive in 80% of cases. Multi-drug resistant Acinerobacter baumanii was the most common species detected in cases; 67.64% (n=23). The rate of mortality out of cases was 88.23% (n= 30). In univariate analysis, the patients with VAP were statistically more likely to suffer from cardiovascular diseases (p=0.035) and prolonged duration of sedation (p=0.009) and tracheostomy (p=0.001), they also had a higher number of re-intubation (p=0.017) and a longer total time of intubation (p=0.012). Multivariate analysis showed that cardiovascular diseases (OR= 4.44; 95% IC= [1.3 - 14]; p=0.016), tracheostomy (OR= 4.2; 95% IC= [1.16 -15.12]; p= 0.028) and prolonged duration of sedation (OR=1.21; 95% IC= [1.07, 1.36]; p=0.002) were independent risk factors for the development of VAP. Conclusion: VAP constitutes a therapeutic challenge in an ICU setting, therefore; strategies that effectively prevent VAP are needed. An infection control-training program intended to all professional heath care in this unit insisting on bundles and elaboration of procedures are planned to reduce effectively incidence rate of VAP.Keywords: case control study, intensive care unit, risk factors, ventilator associated pneumonia
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