Search results for: drug loading

Authors: komal verma, V. S. Moholkar

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In this current study, the challenge of effectively treating and mineralizing industrial wastewater prior to its discharge into natural water bodies, such as rivers and lakes, is being addressed. Particularly, the focus is on the wastewater produced by chemical process industries, including refineries, petrochemicals, fertilizer, pharmaceuticals, pesticides, and dyestuff industries. These wastewaters often contain stubborn organic pollutants that conventional techniques, such as microbial processes cannot efficiently degrade. To tackle this issue, a ternary hybrid technique comprising of adsorption, heterogeneous Fenton process, and sonication has been employed. The study aims to evaluate the effectiveness of this approach for treating and mineralizing wastewater from a fertilizer industry located in Northeast India. The study comprises several key components, starting with the synthesis of the Fe3O4@AC nanocomposite using the co-precipitation method. The nanocomposite is then subjected to comprehensive characterization through various standard techniques, including FTIR, FE-SEM, EDX, TEM, BET surface area analysis, XRD, and magnetic property determination using VSM. Next, the process parameters of wastewater treatment are statistically optimized, focusing on achieving a high level of COD (Chemical Oxygen Demand) removal as the response variable. The Fe3O4@AC nanocomposite's adsorption characteristics and kinetics are also assessed in detail. The remarkable outcome of this study is the successful application of the ternary hybrid technique, combining adsorption, Fenton process, and sonication. This approach proves highly effective, leading to nearly complete mineralization (or TOC removal) of the fertilizer industry wastewater. The results highlight the potential of the Fe3O4@AC nanocomposite and the ternary hybrid technique as a promising solution for tackling challenging wastewater pollutants from various chemical process industries. This paper reports investigations in the mineralization of industrial wastewater (COD = 3246 mg/L, TOC = 2500 mg/L) using a ternary (ultrasound + Fenton + adsorption) hybrid advanced oxidation process. Fe3O4 decorated activated charcoal (Fe3O4@AC) nanocomposites (surface area = 538.88 m2/g; adsorption capacity = 294.31 mg/g) were synthesized using co-precipitation. The wastewater treatment process was optimized using central composite statistical design. At optimum conditions, viz. pH = 4.2, H2O2 loading = 0.71 M, adsorbent dose = 0.34 g/L, reduction in COD and TOC of wastewater were 94.75% and 89%, respectively. This result results from synergistic interactions among the adsorption of pollutants onto activated charcoal and surface Fenton reactions induced due to the leaching of Fe2+/Fe3+ ions from the Fe3O4 nanoparticles. Micro-convection generated due to sonication assisted faster mass transport (adsorption/desorption) of pollutants between Fe3O4@AC nanocomposite and the solution. The net result of this synergism was high interactions and reactions among and radicals and pollutants that resulted in the effective mineralization of wastewater. The Fe3O4@AC showed excellent recovery (> 90 wt%) and reusability (> 90% COD removal) in 5 successive cycles of treatment. LC-MS analysis revealed effective (> 50%) degradation of more than 25 significant contaminants (in the form of herbicides and pesticides) after the treatment with ternary hybrid AOP. Similarly, the toxicity analysis test using the seed germination technique revealed ~ 60% reduction in the toxicity of the wastewater after treatment.

Keywords: chemical oxygen demand (cod), fe3o4@ac nanocomposite, kinetics, lc-ms, rsm, toxicity

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Authors: Lucia Liu, Matthew Koziol

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Obsessive-compulsive disorder (OCD), a long-lasting anxiety disorder involving recurrent, intrusive thoughts, affects over 2 million adults in the United States. Transcranial magnetic stimulation (TMS) stands out as a noninvasive, cutting-edge therapy that has been shown to reduce symptoms in patients with treatment-resistant OCD. The Food and Drug Administration (FDA) approved protocol pairs TMS sessions with individualized symptom provocation, aiming to improve the susceptibility of brain circuits to stimulation. However, limited standardization or guidance exists on how to conduct symptom provocation and which methods are most effective. This study aims to compare the effect of internal versus external techniques to induce obsessional stress in a clinical setting during TMS therapy. Two symptom provocation methods, (i) Asking patients thought-provoking questions about their obsessions (internal) and (ii) Requesting patients to perform obsession-related tasks (external), were employed in a crossover design with repeated measurement. Thirty-six treatments of NeuroStar TMS were administered to each of two patients over 8 weeks in an outpatient clinic. Patient One received 18 sessions of internal provocation followed by 18 sessions of external provocation, while Patient Two received 18 sessions of external provocation followed by 18 sessions of internal provocation. The primary outcome was the level of self-reported obsessional stress on a visual analog scale from 1 to 10. The secondary outcome was self-reported OCD severity, collected biweekly in a four-level Likert-scale (1 to 4) of bad, fair, good and excellent. Outcomes were compared and tested between provocation arms through repeated measures ANOVA, accounting for intra-patient correlations. Ages were 42 for Patient One (male, White) and 57 for Patient Two (male, White). Both patients had similar moderate symptoms at baseline, as determined through the Yale-Brown Obsessive Compulsive Scale (YBOCS). When comparing obsessional stress induced across the two arms of internal and external provocation methods, the mean (SD) was 6.03 (1.18) for internal and 4.01 (1.28) for external strategies (P=0.0019); ranges were 3 to 8 for internal and 2 to 8 for external strategies. Internal provocation yielded 5 (31.25%) bad, 6 (33.33%) fair, 3 (18.75%) good, and 2 (12.5%) excellent responses for OCD status, while external provocation yielded 5 (31.25%) bad, 9 (56.25%) fair, 1 (6.25%) good, and 1 (6.25%) excellent responses (P=0.58). Internal symptom provocation tactics had a significantly stronger impact on inducing obsessional stress and led to better OCD status (non-significant). This could be attributed to the fact that answering questions may prompt patients to reflect more on their lived experiences and struggles with OCD. In the future, clinical trials with larger sample sizes are warranted to validate this finding. Results support the increased integration of internal methods into structured provocation protocols, potentially reducing the time required for provocation and achieving greater treatment response to TMS.

Keywords: obsessive-compulsive disorder, transcranial magnetic stimulation, mental health, symptom provocation

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Authors: Anuj Tyagi, Balwinder Singh, Naveen Kumar B. T., Niraj K. Singh

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Characterization of diverse microbial communities in specific environment plays a crucial role in the better understanding of their functional relationship with the ecosystem. It is now well established that gut microbiome of fish is not the simple replication of microbiota of surrounding local habitat, and extensive species, dietary, physiological and metabolic variations in fishes may have a significant impact on its composition. Moreover, overuse of antibiotics in human, veterinary and aquaculture medicine has led to rapid emergence and propagation of antibiotic resistance genes (ARGs) in the aquatic environment. Microbial communities harboring specific ARGs not only get a preferential edge during selective antibiotic exposure but also possess the significant risk of ARGs transfer to other non-resistance bacteria within the confined environments. This phenomenon may lead to the emergence of habitat-specific microbial resistomes and subsequent emergence of virulent antibiotic-resistant pathogens with severe fish and consumer health consequences. In this study, gut microbiota of freshwater carp (Labeo rohita) was investigated by shotgun metagenomics to understand its taxonomic composition and functional capabilities. Metagenomic DNA, extracted from the fish gut, was subjected to sequencing on Illumina NextSeq to generate paired-end (PE) 2 x 150 bp sequencing reads. After the QC of raw sequencing data by Trimmomatic, taxonomic analysis by Kraken2 taxonomic sequence classification system revealed the presence of 36 phyla, 326 families and 985 genera in the fish gut microbiome. At phylum level, Proteobacteria accounted for more than three-fourths of total bacterial populations followed by Actinobacteria (14%) and Cyanobacteria (3%). Commonly used probiotic bacteria (Bacillus, Lactobacillus, Streptococcus, and Lactococcus) were found to be very less prevalent in fish gut. After sequencing data assembly by MEGAHIT v1.1.2 assembler and PROKKA automated analysis pipeline, pathway analysis revealed the presence of 1,608 Metacyc pathways in the fish gut microbiome. Biosynthesis pathways were found to be the most dominant (51%) followed by degradation (39%), energy-metabolism (4%) and fermentation (2%). Almost one-third (33%) of biosynthesis pathways were involved in the synthesis of secondary metabolites. Metabolic pathways for the biosynthesis of 35 antibiotic types were also present, and these accounted for 5% of overall metabolic pathways in the fish gut microbiome. Fifty-one different types of antibiotic resistance genes (ARGs) belonging to 15 antimicrobial resistance (AMR) gene families and conferring resistance against 24 antibiotic types were detected in fish gut. More than 90% ARGs in fish gut microbiome were against beta-lactams (penicillins, cephalosporins, penems, and monobactams). Resistance against tetracycline, macrolides, fluoroquinolones, and phenicols ranged from 0.7% to 1.3%. Some of the ARGs for multi-drug resistance were also found to be located on sequences of plasmid origin. The presence of pathogenic bacteria and ARGs on plasmid sequences suggested the potential risk due to horizontal gene transfer in the confined gut environment.

Keywords: antibiotic resistance, fish gut, metabolic pathways, microbial diversity

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Authors: Nicole Selvi Hill, Archchana Radhakrishnan

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Introduction: Traumatic brain injury (TBI) is a leading cause of mortality among trauma patients. In the management of TBI, the main principle is avoiding cerebral ischemia, as this is a strong determiner of neurological outcomes. The use of vasoactive drugs, such as vasopressin, has an important role in maintaining cerebral perfusion pressure to prevent secondary brain injury. Current guidelines do not suggest a preferred vasoactive drug to administer in the management of TBI, and there is a paucity of information on the therapeutic potential of vasopressin following TBI. Vasopressin is also an endogenous anti-diuretic hormone (AVP), and pathways mediated by AVP play a large role in the underlying pathological processes of TBI. This creates an overlap of discussion regarding the therapeutic potential of vasopressin following TBI. Currently, its popularity lies in vasodilatory and cardiogenic shock in the intensive care setting, with increasing support for its use in haemorrhagic and septic shock. Methodology: This is a review article based on a literature review. An electronic search was conducted via PubMed, Cochrane, EMBASE, and Google Scholar. The aim was to identify clinical studies looking at the therapeutic administration of vasopressin in severe traumatic brain injury. The primary aim was to look at the neurological outcome of patients. The secondary aim was to look at surrogate markers of cerebral perfusion measurements, such as cerebral perfusion pressure, cerebral oxygenation, and cerebral blood flow. Results: Eight papers were included in the final number. Three were animal studies; five were human studies, comprised of three case reports, one retrospective review of data, and one randomised control trial. All animal studies demonstrated the benefits of vasopressors in TBI management. One animal study showed the superiority of vasopressin in reducing intracranial pressure and increasing cerebral oxygenation over a catecholaminergic vasopressor, phenylephrine. All three human case reports were supportive of vasopressin as a rescue therapy in catecholaminergic-resistant hypotension. The retrospective review found vasopressin did not increase cerebral oedema in TBI patients compared to catecholaminergic vasopressors; and demonstrated a significant reduction in the requirements of hyperosmolar therapy in patients that received vasopressin. The randomised control trial results showed no significant differences in primary and secondary outcomes between TBI patients receiving vasopressin versus those receiving catecholaminergic vasopressors. Apart from the randomised control trial, the studies included are of low-level evidence. Conclusion: Studies favour vasopressin within certain parameters of cerebral function compared to control groups. However, the neurological outcomes of patient groups are not known, and animal study results are difficult to extrapolate to humans. It cannot be said with certainty whether vasopressin’s benefits stand above usage of other vasoactive drugs due to the weaknesses of the evidence. Further randomised control trials, which are larger, standardised, and rigorous, are required to improve knowledge in this field.

Keywords: catecholamines, cerebral perfusion pressure, traumatic brain injury, vasopressin, vasopressors

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Authors: Maryam Nazari

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COVID-19 is a respiratory disease triggered by the novel coronavirus, SARS-CoV-2, that has reached pandemic status today. Acute inflammation and immune cells infiltration into lung injuries result in multi-organ failure. The presence of other non-communicable diseases (NCDs) with systemic inflammation derived from COVID-19 may exacerbate the patient's situation and increase the risk for adverse effects and mortality. This pandemic is a novel situation and the scientific community at this time is looking for vaccines or drugs to treat the pathology. One of the biggest challenges is focused on reducing inflammation without compromising the correct immune response of the patient. In this regard, addressing the nutritional factors should not be overlooked not only as a matter of avoiding the presence of NCDs with severe infections but also as an adjunctive way to modulate the inflammatory status of the patients. Despite the pivotal role of nutrition in modifying immune response, due to the novelty of the COVID-19 disease, information about the effects of specific dietary agents is limited in this area. From the macronutrients point of view, protein deficiency (quantity or quality) has negative effects on the number of functional immunoglobulins and gut-associated lymphoid tissue (GALT). High biological value proteins or some amino acids like arginine and glutamine are well known for their ability to augment the immune system. Among lipids, fish oil has the ability to inactivate enveloped viruses, suppress pro-inflammatory prostaglandin production and block platelet-activating factors and their receptors. In addition, protectin D1, which is an Omega-3 PUFAs derivation, is a novel antiviral drug. So it seems that these fatty acids can reduce the severity and/or improve recovery of patients with COVID-19. Carbohydrates with lower glycemic index and fibers are associated with lower levels of inflammatory cytokines (CRP, TNF-α, and IL-6). Short-Chain Fatty acids not only exert a direct anti-inflammatory effect but also provide appropriate gut microbial, which is important in gastrointestinal issues related to COVID-19. From the micronutrients point of view, Vitamins A, C, D, E, iron, magnesium, zinc, selenium and copper play a vital role in the maintenance of immune function. Inadequate status in these nutrients may result in decreased resistance against COVID-19 infection. There are specific bioactive compounds in the diet that interact with the ACE2 receptor, which is the gateway for SARS and SARS-CoV-2, and thus controls the viral infection. Regarding this, the potential benefits of probiotics, resveratrol (a polyphenol found in grape), oleoylethanolamide (derived from oleic acid), and natural peroxisome proliferator-activated receptor γ agonists in foodstuffs (like curcumin, pomegranate, hot pepper) are suggested. Yet, it should be pointed out that most of these results have been reported in animal models and further human studies are needed to be verified.

Keywords: Covid-19, inflammation, nutrition, dietary agents

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Authors: Priscila Ribeiro dos Santos, Luiz Antonio Daniel

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Inadequate access to clean water and sanitation has become one of the most widespread problems affecting people throughout the developing world, leading to an unceasing need for low-cost and sustainable wastewater treatment systems. The UASB technology has been widely employed as a suitable and economical option for the treatment of sewage in developing countries, which involves low initial investment, low energy requirements, low operation and maintenance costs, high loading capacity, short hydraulic retention times, long solids retention times and low sludge production. Whereas dissolved air flotation process is a good option for the post-treatment of anaerobic effluents, being capable of producing high quality effluents in terms of total suspended solids, chemical oxygen demand, phosphorus, and even pathogens. This work presents an evaluation and monitoring, over a period of 6 months, of one compact full-scale system with this configuration, UASB reactors followed by dissolved air flotation units (DAF), operating in Brazil. It was verified as a successful treatment system, and an issue of relevance since dissolved air flotation process treating UASB reactor effluents is not widely encompassed in the literature. The study covered the removal and behavior of several variables, such as turbidity, total suspend solids (TSS), chemical oxygen demand (COD), Escherichia coli, total coliforms and Clostridium perfringens. The physicochemical variables were analyzed according to the protocols established by the Standard Methods for Examination of Water and Wastewater. For microbiological variables, such as Escherichia coli and total coliforms, it was used the “pour plate” technique with Chromocult Coliform Agar (Merk Cat. No.1.10426) serving as the culture medium, while the microorganism Clostridium perfringens was analyzed through the filtering membrane technique, with the Ágar m-CP (Oxoid Ltda, England) serving as the culture medium. Approximately 74% of total COD was removed in the UASB reactor, and the complementary removal done during the flotation process resulted in 88% of COD removal from the raw sewage, thus the initial concentration of COD of 729 mg.L-1 decreased to 87 mg.L-1. Whereas, in terms of particulate COD, the overall removal efficiency for the whole system was about 94%, decreasing from 375 mg.L-1 in raw sewage to 29 mg.L-1 in final effluent. The UASB reactor removed on average 77% of the TSS from raw sewage. While the dissolved air flotation process did not work as expected, removing only 30% of TSS from the anaerobic effluent. The final effluent presented an average concentration of 38 mg.L-1 of TSS. The turbidity was significantly reduced, leading to an overall efficiency removal of 80% and a final turbidity of 28 NTU.The treated effluent still presented a high concentration of fecal pollution indicators (E. coli, total coliforms, and Clostridium perfringens), showing that the system did not present a good performance in removing pathogens. Clostridium perfringens was the organism which suffered the higher removal by the treatment system. The results can be considered satisfactory for the physicochemical variables, taking into account the simplicity of the system, besides that, it is necessary a post-treatment to improve the microbiological quality of the final effluent.

Keywords: dissolved air flotation, municipal sewage, UASB reactor, treatment

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Authors: Hanan M. Hassan, Laila Abouzeid, Lamya H. Al-Wahaibi, George S. G. Shehatou, Ali A. El-Emam

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Cancer is a major public health problem and the second leading cause of death worldwide. In 2020, cancer diagnosis and treatment have been negatively affected by the coronavirus 2019 (COVID-19) pandemic. During the quarantine, because of the limited access to healthcare and avoiding exposure to COVID-19 as a contagious disease; patients of cancer suffered deferments in follow-up and treatment regimens leading to substantial worsening of disease, death, and increased healthcare costs. Thus, this study is designed to investigate the molecular mechanisms by which adamantne derivatives attenuate hepatocllular carcinoma experimentally and theoretically. There is a close association between increased resistance to anticancer drugs and defective apoptosis that considered a causative factor for oncogenesis. Cancer cells use different molecular pathways to inhibit apoptosis, BAX and Bcl-2 proteins have essential roles in the progression or inhibition of intrinsic apoptotic pathways triggered by mitochondrial dysfunction. Therefore, their balance ratio can promote the cellular apoptotic fate. In this study, the in vitro cytotoxic effects of seven synthetic adamantyl isothiorea derivatives were evaluated against five human tumor cell lines by MTT assay. Compounds 5 and 6 showed the best results, mostly against hepatocellular carcinoma (HCC). Hence, in vivo studies were performed in male Sprague-Dawley (SD) rats in which experimental hepatocellular carcinoma was induced with thioacetamide (TAA) (200 mg/kg, i.p., twice weekly) for 16 weeks. The most promising compounds, 5 and 6, were administered to treat liver cancer rats at a dose of 10 mg/kg/day for an additional two weeks, and the effects were compared with doxorubicin (DR), the anticancer drug. Hepatocellular carcinoma was evidenced by a dramatic increase in liver indices, oxidative stress markers, and immunohistochemical studies that were accompanied by a plethora of inflammatory mediators and alterations in the apoptotic cascade. Our results showed that treatment with adamantane derivatives 5 and 6 significantly suppressed fibrosis, inflammation, and other histopathological insults resulting in the diminished formation of hepatocyte tumorigenesis. Moreover, administration of the tested compounds resulted in amelioration of EGFR protein expression, upregulation of BAX, and lessening down of Bcl-2 levels that prove their role as apoptosis inducers. Also, the docking simulations performed for adamantane showed good fit and binding to the EGFR protein through hydrogen bond formation with conservative amino acids, which gives a shred of strong evidence for its hepatoprotective effect. In most analyses, the effects of compound 6 were more comparable to DR than compound 5. Our findings suggest that adamantane derivatives 5 and 6 are shown to have cytotoxic activity against HCC in vitro and in vivo, by more than one mechanism, possibly by inhibiting the TLR4-MyD88-NF-κB pathway and targeting EGFR signaling.

Keywords: adamantane, EGFR, HCC, apoptosis

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Authors: D. Dixon, J. Nicol, J. A. Coulter, E. Harrison

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The ease with which they can be functionalized, combined with their excellent biocompatibility, make gold nanoparticles (AuNPs) ideal candidates for various applications in nanomedicine. Indeed several promising treatments are currently undergoing human clinical trials (CYT-6091 and Auroshell). A successful nanoparticle treatment must first evade the immune system, then accumulate within the target tissue, before enter the diseased cells and delivering the payload. In order to create a clinically relevant drug delivery system, contrast agent or radiosensitizer, it is generally necessary to functionalize the AuNP surface with multiple groups; e.g. Polyethylene Glycol (PEG) for enhanced stability, targeting groups such as antibodies, peptides for enhanced internalization, and therapeutic agents. Creating and characterizing the biological response of such complex systems remains a challenge. The two commonly used methods to attach multiple groups to the surface of AuNPs are the creation of a mixed monolayer, or by binding groups to the AuNP surface using a bi-functional PEG linker. While some excellent in-vitro and animal results have been reported for both approaches further work is necessary to directly compare the two methods. In this study AuNPs capped with both PEG and a Receptor Mediated Endocytosis (RME) peptide were prepared using both mixed monolayer and PEG linker approaches. The PEG linker used was SH-PEG-SGA which has a thiol at one end for AuNP attachment, and an NHS ester at the other to bind to the peptide. The work builds upon previous studies carried out at the University of Ulster which have investigated AuNP synthesis, the influence of PEG on stability in a range of media and investigated intracellular payload release. 18-19nm citrate capped AuNPs were prepared using the Turkevich method via the sodium citrate reduction of boiling 0.01wt% Chloroauric acid. To produce PEG capped AuNPs, the required amount of PEG-SH (5000Mw) or SH-PEG-SGA (3000Mw Jenkem Technologies) was added, and the solution stirred overnight at room temperature. The RME (sequence: CKKKKKKSEDEYPYVPN, Biomatik) co-functionalised samples were prepared by adding the required amount of peptide to the PEG capped samples and stirring overnight. The appropriate amounts of PEG-SH and RME peptide were added to the AuNP to produce a mixed monolayer consisting of approximately 50% PEG and 50% RME. The PEG linker samples were first fully capped with bi-functional PEG before being capped with RME peptide. An increase in diameter from 18-19mm for the ‘as synthesized’ AuNPs to 40-42nm after PEG capping was observed via DLS. The presence of PEG and RME peptide on both the mixed monolayer and PEG linker co-functionalized samples was confirmed by both FTIR and TGA. Bi-functional PEG linkers allow the entire AuNP surface to be capped with PEG, enabling in-vitro stability to be achieved using a lower molecular weight PEG. The approach also allows the entire outer surface to be coated with peptide or other biologically active groups, whilst also offering the promise of enhanced biological availability. The effect of mixed monolayer versus PEG linker attachment on both stability and non-specific protein corona interactions was also studied.

Keywords: nanomedicine, gold nanoparticles, PEG, biocompatibility

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Authors: Chetna Dhand, Venkatesh Mayandi, Silvia Marrero Diaz, Roger W. Beuerman, Seeram Ramakrishna, Rajamani Lakshminarayanan

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Sturdy Insect Cuticle Sclerotization, Incredible Substrate independent Mussel’s bioadhesion, Tanning of Leather are some of catechol(amine)s mediated natural processes. Chemical contemplation spots toward a mechanism instigated with the formation of the quinone moieties from the respective catechol(amine)s, via oxidation, followed by the nucleophilic addition of the amino acids/proteins/peptides to this quinone leads to the development of highly strong, cross-linked and water-resistant proteinacious structures. Inspired with this remarkable catechol(amine)s chemistry towards amino acids/proteins/peptides, we attempted to design highly stable and water-resistant antifungal wound dressing mats with exceptional durability using collagen (protein), dopamine (catecholamine) and antifungal drugs (Amphotericin B and Caspofungin) as the key materials. Electrospinning technique has been used to fabricate desired nanofibrous mat including Collagen (COLL), COLL/Dopamine (COLL/DP) and calcium incorporated COLL/DP (COLL-DP-Ca2+). The prepared protein-based scaffolds have been studied for their microscopic investigations (SEM, TEM, and AFM), structural analysis (FT-IR), mechanical properties, water wettability characteristics and aqueous stability. Biocompatibility of these scaffolds has been analyzed for dermal fibroblast cells using MTS assay, Cell TrackerTM Green CMFDA and confocal imaging. Being the winner sample, COLL-DP-Ca2+ scaffold has been selected for incorporating two antifungal drugs namely Caspofungin (Peptide based) and Amphotericin B (Non-Peptide based). Antifungal efficiency of the designed mats has been evaluated for eight diverse fungal strains employing different microbial assays including disc diffusion, cell-viability assay, time kill kinetics etc. To confirm the durability of these mats, in term of their antifungal activity, drug leaching studies has been performed and monitored using disc diffusion assay each day. Ex-vivo fungal infection model has also been developed and utilized to validate the antifungal efficacy of the designed wound dressings. Results clearly reveal dopamine mediated crosslinking within COLL-antifungal scaffolds that leads to the generation of highly stable, mechanical tough, biocompatible wound dressings having the zone of inhabitation of ≥ 2 cm for almost all the investigated fungal strains. Leaching studies and Ex-vivo model has confirmed the durability of these wound dressing for more than 3 weeks and certified their suitability for commercialization. A model has also been proposed to enlighten the chemical mechanism involved for the development of these antifungal wound dressings with exceptional robustness.

Keywords: catecholamine chemistry, electrospinning technique, antifungals, wound dressings, collagen

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Authors: Anush Patric, M. Jadeyegowda, M. N. Ramesh, M. Ravikumar, C. R. Ajay

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Kodagu district which is situated in Central Western Ghats regions falls in one of the hottest of hot spots of biodiversity which is recognised by UNESCO. The district has one of the highest densities of community managed sacred forests in the world with rich floral and faunal diversity. It is a habitat for more than ten different types of Ethnic Indigenous tribal groups commonly called ‘Girijanas’ (Soligas, Yarvas, Jenukuruba, Bettakuruba etc.), who are having the rich knowledge of medicinal value of the plants that are commonly available in the forest. The tribal men of this region are the treasure house of the traditional plant knowledge and health care practices. An ethnobotanical survey was undertaken in tribal areas of the district to collect information about some of the indigenous medicinal plant knowledge of tribal people by semi-structured interviews, ranking exercises and field observations on their native habitat in order to evaluate the potential medicinal uses of local plants. The study revealed that, the ethnobotanical information of 83 plant species belonging to 45 families, of the total 83 species documented, most plants used in the treatment were trees (11 species), shrubs (41 species), herbs (22 species) and rarely climbers (9 species) which are used in the treatment of Hyperacidity, Respiratory disorders, Snake bite Abortifacient, Anthelmintic, Paralysis, Antiseptic, Fever, Chest pain, Stomachic, Jaundice, Piles, Asthma, Malaria, Renal disorders, Malaria and many other diseases. Maximum of 6 plant species each of Acanthaceae, Apiaceae and were used for drug preparation, followed by Asclepiadaceae, Liliaceae, Fabaceae, Verbenaceae, Caesalpinaceae, Bombaceae, Papilonaceae, Solanaceae, Rubiaceae, Myrtaceae, Amaranthaceae, Asteraceae, Ascelepidaceae, Cucurbitaceae, Apocyanaceae, and Solanaceae etc. In our present study, only medicinal plants and their local medicinal uses are recorded and presented. Information was obtained by local informants having the knowledge about medicinal plants. About 23 local tribes were interviewed. For each plant, necessary information like botanical name, family of plant species, local name and uses are given. Recent trend shows a decline in the number of traditional herbal healers in the tribal areas since the younger generation is not interested to continue this tradition. Hence, there is an urgent need to record and preserve all information on plants used by different ethnic/tribal communities for various purposes before it reaches to verge of extinction. In addition, several wild medicinal plants are declining in numbers due to deforestation and forest fires. There is need for phytochemical analysis and conservation measures to be taken for conserving medicinal plant species which is far better than allopathic medicines and these do not cause any side effects as they are the natural disease healers. So, conservation strategies have to be practiced in all levels and sectors by creating awareness about the value of such medicinal plants, and it is necessary to save the disappearing plants to strengthen the document and to conserve them for future generation.

Keywords: diseases, ethnic groups, folk medicine, Kodagu, medicinal plants

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Authors: Pomozova Kseniia, Gorlachev Gennadiy, Chernyaev Aleksandr, Golanov Andrey

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In clinical practice, and especially in stereotactic radiosurgery planning, the significance of diffusion-weighted imaging (DWI) is growing. This makes the existence of software capable of quickly processing and reliably visualizing diffusion data, as well as equipped with tools for their analysis in terms of different tasks. We are developing the «MRDiffusionImaging» software on the standard C++ language. The subject part has been moved to separate class libraries and can be used on various platforms. The user interface is Windows WPF (Windows Presentation Foundation), which is a technology for managing Windows applications with access to all components of the .NET 5 or .NET Framework platform ecosystem. One of the important features is the use of a declarative markup language, XAML (eXtensible Application Markup Language), with which you can conveniently create, initialize and set properties of objects with hierarchical relationships. Graphics are generated using the DirectX environment. The MRDiffusionImaging software package has been implemented for processing diffusion magnetic resonance imaging (dMRI), which allows loading and viewing images sorted by series. An algorithm for "masking" dMRI series based on T2-weighted images was developed using a deformable surface model to exclude tissues that are not related to the area of interest from the analysis. An algorithm of distortion correction using deformable image registration based on autocorrelation of local structure has been developed. Maximum voxel dimension was 1,03 ± 0,12 mm. In an elementary brain's volume, the diffusion tensor is geometrically interpreted using an ellipsoid, which is an isosurface of the probability density of a molecule's diffusion. For the first time, non-parametric intensity distributions, neighborhood correlations, and inhomogeneities are combined in one segmentation of white matter (WM), grey matter (GM), and cerebrospinal fluid (CSF) algorithm. A tool for calculating the coefficient of average diffusion and fractional anisotropy has been created, on the basis of which it is possible to build quantitative maps for solving various clinical problems. Functionality has been created that allows clustering and segmenting images to individualize the clinical volume of radiation treatment and further assess the response (Median Dice Score = 0.963 ± 0,137). White matter tracts of the brain were visualized using two algorithms: deterministic (fiber assignment by continuous tracking) and probabilistic using the Hough transform. The proposed algorithms test candidate curves in the voxel, assigning to each one a score computed from the diffusion data, and then selects the curves with the highest scores as the potential anatomical connections. White matter fibers were visualized using a Hough transform tractography algorithm. In the context of functional radiosurgery, it is possible to reduce the irradiation volume of the internal capsule receiving 12 Gy from 0,402 cc to 0,254 cc. The «MRDiffusionImaging» will improve the efficiency and accuracy of diagnostics and stereotactic radiotherapy of intracranial pathology. We develop software with integrated, intuitive support for processing, analysis, and inclusion in the process of radiotherapy planning and evaluating its results.

Keywords: diffusion-weighted imaging, medical imaging, stereotactic radiosurgery, tractography

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Authors: U. E. Mochalova, A. V. Demeneva, Shilkin A. G., J. Yu. Artiushina

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Objective. In medical ophthalmology OCT has been actively used in the last decade. It is a modern non-invasive method of high-precision hardware examination, which gives a detailed cross-sectional image of eye tissues structure with a high level of resolution, which provides in vivo morphological information at the microscopic level about corneal tissue, structures of the anterior segment, retina and optic nerve. The purpose of this study was to explore the possibility of using the OCT technology in complex ophthalmological examination in dogs and cats, to characterize the revealed pathological structural changes in corneal tissue in cats and dogs with some of the most common corneal diseases. Procedures. Optical coherence tomography of the cornea was performed in 112 animals: 68 dogs and 44 cats. In total, 224 eyes were examined. Pathologies of the organ of vision included: dystrophy and degeneration of the cornea, endothelial corneal dystrophy, dry eye syndrome, chronic superficial vascular keratitis, pigmented keratitis, corneal erosion, ulcerative stromal keratitis, corneal sequestration, chronic glaucoma and also postoperative period after performed keratoplasty. When performing OCT, we used certified medical devices: "Huvitz HOCT-1/1F», «Optovue iVue 80» and "SOCT Copernicus Revo (60)". Results. The results of a clinical study on the use of optical coherence tomography (OCT)of the cornea in cats and dogs, performed by the authors of the article in the complex diagnosis of keratopathies of variousorigins: endothelial corneal dystrophy, pigmented keratitis, chronic keratoconjunctivitis, chronic herpetic keratitis, ulcerative keratitis, traumatic corneal damage, sequestration of the cornea of cats, chronic keratitis, complicating the course of glaucoma. The characteristics of the OCT scans are givencorneas of cats and dogs that do not have corneal pathologies. OCT scans of various corneal pathologies in dogs and cats with a description of the revealed pathological changes are presented. Of great clinical interest are the data obtained during OCT of the cornea of animals undergoing keratoplasty operations using various forms of grafts. Conclusions. OCT makes it possible to assess the thickness and pathological structural changes of the corneal surface epithelium, corneal stroma and descemet membrane. We can measure them, determine the exact localization, and record pathological changes. Clinical observation of the dynamics of the pathological process in the cornea using OCT makes it possible to evaluate the effectiveness of drug treatment. In case of negative dynamics of corneal disease, it is necessary to determine the indications for surgical treatment (to assess the thickness of the cornea, the localization of its thinning zones, to characterize the depth and area of pathological changes). According to the OCT of the cornea, it is possible to choose the optimal surgical treatment for the patient, the technique and depth of optically constructive surgery (penetrating or anterior lamellar keratoplasty).; determine the depth and diameter of the planned microsurgical trepanation of corneal tissue, which will ensure good adaptation of the edges of the donor material.

Keywords: optical coherence tomography, corneal sequestration, optical coherence tomography of the cornea, corneal transplantation, cat, dog

Procedia PDF Downloads 38

Authors: Shanna Swart, Caryn Fenner, Athanasios Kotsiopoulos, Susan Harrison

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Linear alkanes are produced as by-products from the increasing use of gas-to-liquid fuel technologies for synthetic fuel production and offer great potential for value addition. Their current use as low-value fuels and solvents do not maximize this potential. Therefore, attention has been drawn towards direct activation of these aliphatic alkanes to more useful products such as alcohols, aldehydes, carboxylic acids and derivatives. Cytochrome P450 monooxygenases (P450s) can be used for activation of these aliphatic alkanes using whole-cells or cell-free systems. Some limitations of whole-cell systems include reduced mass transfer, stability and possible side reactions. Since the P450 systems are little studied as cell-free systems, they form the focus of this study. Challenges of a cell-free system include co-factor regeneration, substrate availability and enzyme stability. Enzyme immobilization offers a positive outlook on this dilemma, as it may enhance stability of the enzyme. In the present study, 2 different P450s (CYP153A6 and CYP102A1) as well as the relevant accessory enzymes required for electron transfer (ferredoxin and ferredoxin reductase) and co-factor regeneration (glucose dehydrogenase) have been expressed in E. coli and purified by metal affinity chromatography. Glucose dehydrogenase (GDH), was used as a model enzyme to assess the potential of various enzyme immobilization strategies including; surface attachment on MagReSyn® microspheres with various functionalities and on electrospun nanofibers, using self-assembly based methods forming Cross Linked Enzymes (CLE), Cross Linked Enzyme Aggregates (CLEAs) and spherezymes as well as in a sol gel. The nanofibers were synthesized by electrospinning, which required the building of an electrospinning machine. The nanofiber morphology has been analyzed by SEM and binding will be further verified by FT-IR. Covalent attachment based methods showed limitations where only ferredoxin reductase and GDH retained activity after immobilization which were largely attributed to insufficient electron transfer and inactivation caused by the crosslinkers (60% and 90% relative activity loss for the free enzyme when using 0.5% glutaraldehyde and glutaraldehyde/ethylenediamine (1:1 v/v), respectively). So far, initial experiments with GDH have shown the most potential when immobilized via their His-tag onto the surface of MagReSyn® microspheres functionalized with Ni-NTA. It was found that Crude GDH could be simultaneously purified and immobilized with sufficient activity retention. Immobilized pure and crude GDH could be recycled 9 and 10 times, respectively, with approximately 10% activity remaining. The immobilized GDH was also more stable than the free enzyme after storage for 14 days at 4˚C. This immobilization strategy will also be applied to the P450s and optimized with regards to enzyme loading and immobilization time, as well as characterized and compared with the free enzymes. It is anticipated that the proposed immobilization set-up will offer enhanced enzyme stability (as well as reusability and easy recovery), minimal mass transfer limitation, with continuous co-factor regeneration and minimal enzyme leaching. All of which provide a positive outlook on this robust multi-enzyme system for efficient activation of linear alkanes as well as the potential for immobilization of various multiple enzymes, including multimeric enzymes for different bio-catalytic applications beyond alkane activation.

Keywords: alkane activation, cytochrome P450 monooxygenase, enzyme catalysis, enzyme immobilization

Procedia PDF Downloads 201

Authors: Sharmila Parmanand

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This paper examines dominant media representations of prostitution in the Philippines and interrogates sex workers’ interactions with the media establishment. This analysis of how sex workers are constituted in media, often as both innocent victims and immoral actors, contributes to an understanding of public discourse on sex work in the Philippines, where decriminalisation has recently been proposed and sex workers are currently classified as potential victims under anti-trafficking laws but also as criminals under the penal code. The first part is an analysis of media coverage of two prominent themes on prostitution: first, raid and rescue operations conducted by law enforcement; and second, prostitution on military bases and tourism hotspots. As a result of pressure from activists and international donors, these two themes often define the policy conversations on sex work in the Philippines. The discourses in written and televised news reports and documentaries from established local and international media sources that address these themes are explored through content analysis. Conclusions are drawn based on specific terms commonly used to refer to sex workers, how sex workers are seen as performing their cultural roles as mothers and wives, how sex work is depicted, associations made between sex work and public health, representations of clients and managers and ‘rescuers’ such as the police, anti-trafficking organisations, and faith-based groups, and which actors are presumed to be issue experts. Images of how prostitution is used as a metaphor for relations between the Philippines and foreign nations are also deconstructed, along with common tropes about developing world female subjects. In general, sex workers are simultaneously portrayed as bad mothers who endanger their family’s morality but also as long-suffering victims who endure exploitation for the sake of their children. They are also depicted as unclean, drug-addicted threats to public health. Their managers and clients are portrayed as cold, abusive, and sometimes violent, and their rescuers as moral and altruistic agents who are essential for sex workers’ rehabilitation and restoration as virtuous citizens. The second part explores sex workers’ own perceptions of their interactions with media, through interviews with members of the Philippine Sex Workers Collective, a loose organisation of sex workers around the Philippines. They reveal that they are often excluded by media practitioners and that they do not feel that they have space for meaningful self-revelation about their work when they do engage with journalists, who seem to have an overt agenda of depicting them as either victims or women of loose morals. In their assessment, media narratives do not necessarily reflect their lived experiences, and in some cases, coverage of rescues and raid operations endangers their privacy and instrumentalises their suffering. Media representations of sex workers may produce subject positions such as ‘victims’ or ‘criminals’ and legitimize specific interventions while foreclosing other ways of thinking. Further, in light of media’s power to reflect and shape public consciousness, it is a valuable academic and political project to examine whether sex workers are able to assert agency in determining how they are represented.

Keywords: discourse analysis, news media, sex work, trafficking

Procedia PDF Downloads 357

Authors: Kitti Supchukun, Kris Angkanaporn, Teerapong Yata

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The product innovation using a nutraceutical delivery system on improving the growth performance of broilers is the product planning and development to solve the antibiotics banning policy incurred in the local and global livestock production system. Restricting the use of antibiotics can reduce the quality of chicken meat and increase pathogenic bacterial contamination. Although other alternatives were used to replace antibiotics, the efficacy was inconsistent, reflecting on low chicken growth performance and contaminated products. The product innovation aims to effectively deliver the selected active ingredients into the body. This product is tested on the pharmaceutical lab scale and on the farm-scale for market feasibility in order to create product innovation using the nutraceutical delivery system model. The model establishes the product standardization and traceable quality control process for farmers. The study is performed using mixed methods. Starting with a qualitative method to find the farmers' (consumers) demands and the product standard, then the researcher used the quantitative research method to develop and conclude the findings regarding the acceptance of the technology and product performance. The survey has been sent to different organizations by random sampling among the entrepreneur’s population including integrated broiler farm, broiler farm, and other related organizations. The mixed-method results, both qualitative and quantitative, verify the user and lead users' demands since they provide information about the industry standard, technology preference, developing the right product according to the market, and solutions for the industry problems. The product innovation selected nutraceutical ingredients that can solve the following problems in livestock; bactericidal, anti-inflammation, gut health, antioxidant. The combinations of the selected nutraceutical and nanostructured lipid carriers (NLC) technology aim to improve chemical and pharmaceutical components by changing the structure of active ingredients into nanoparticle, which will be released in the targeted location with accurate concentration. The active ingredients in nanoparticle form are more stable, elicit antibacterial activity against pathogenic Salmonella spp and E.coli, balance gut health, have antioxidant and anti-inflammation activity. The experiment results have proven that the nutraceuticals have an antioxidant and antibacterial activity which also increases the average daily gain (ADG), reduces feed conversion ratio (FCR). The results also show a significant impact on the higher European Performance Index that can increase the farmers' profit when exporting. The product innovation will be tested in technology acceptance management methods from farmers and industry. The production of broiler and commercialization analyses are useful to reduce the importation of animal supplements. Most importantly, product innovation is protected by intellectual property.

Keywords: nutraceutical, nano structure lipid carrier, anti-microbial drug resistance, broiler, Salmonella

Procedia PDF Downloads 145

Authors: Tanya Anand, Arun Kandasamy, L. N. Suman

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Family based therapy for adolescent substance abuse has been studied to be effective in the West. Whereas, based on literature review, family therapy and interventions for adolescent substance abuse is still in its nascent stages in India. A multidimensional perspective to treatment has been indicated consistently in the Indian literature, but standardized therapy which addresses early substance abuse, from a social-ecological perspective has not been developed and studied for Indian population. While numerous researches have been conducted in India on the need of engaging the family in therapy for the purpose of symptom reduction, long-term maintenance of gains, and reducing family burnout, distress and dysfunction; a family based model in the Indian context has not been developed and tried, to the best of our knowledge. Hence, from the aim of building a model to treat adolescent substance abuse within the family context, experts in the area of mental health and deaddiction were interviewed to inform upon the clinical difficulties, challenges, uniqueness that Indian families present with. The integration of indigenous techniques that would be helpful in engaging families of young individuals with difficulties were also explored. Eight experts' who were interviewed, have 10-30 years of experience in working with families and substance users. An open-ended interview was conducted with the experts individually and audio-recorded. The interviews were then transcribed and subjected to qualitative analysis for building a framework and treatment guideline. Additionally, interviews with patients and their parents were conducted to elicit ‘felt needs’. The results of the analysis revealed culture-specific issues widely experienced within Indian families by adolescents and young adults, centering around the theme of Individuation versus collective identity and living. Substance abuse, in this framework, was found to be perceived as one of the maladaptive ways of the youth to disengage from the family and attempt at individuation and the responsibilities that are considered entitlements in the culture. On the other hand, interviews with family members revealed them to be engaging in inconsistent patterns of care and parenting. This was experienced and observed in terms of fostering interdependence within the family, sometimes within adverse socio-economic and societal conditions, where enacted and perceived stigma kept the individual and family members in a vicious loop of maladaptive coping patterns, dysfunctional family arrangements, and often leading to burnout with poor help seeking. The paper inform upon a framework that lays down the foundation for assessments, planning, case management and therapist competencies, required to address alcohol and drug issues in an Indian family context with such etiological factors at its heart. This paper will cover qualitative results of the interviews and present a model that may guide mental health professionals for treatment of adolescent substance use and family therapy.

Keywords: Indian families, family therapy, de-addiction, adolescent, youth, substance abuse, behavioral issues, felt needs, culture, etiology, model building, framework development, interviews

Procedia PDF Downloads 108

Authors: Hanna Abbo, Siyasanga Noganta, Salam Titinchi

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The global lack of clean water for human sanitation and other purposes has become an emerging dilemma for human beings. The presence of organic pollutants in wastewater produced by textile industries, leather manufacturing and chemical industries is an alarming matter for a safe environment and human health. For the last decades, conventional methods have been applied for the purification of water but due to industrialization these methods fall short. Advanced oxidation processes and their reliable application in degradation of many contaminants have been reported as a potential method to reduce and/or alleviate this problem. Lately it has been assumed that incorporation of some metal nanoparticles such as magnetite nanoparticles as photocatalyst for Fenton reaction which could improve the degradation efficiency of contaminants. Core/shell nanoparticles, are extensively studied because of their wide applications in the biomedical, drug delivery, electronics fields and water treatment. The current study is centred on the synthesis of silver-doped Fe3O4/SiO2/TiO2 photocatalyst. Magnetically separable Fe3O4@SiO2@TiO2 composite with core–shell structure were synthesized by the deposition of uniform anatase TiO2 NPs on Fe3O4@SiO2 by using titanium butoxide (TBOT) as titanium source. Then, the silver is doped on SiO2 layer by hydrothermal method. Integration of magnetic nanoparticles was suggested to avoid the post separation difficulties associated with the powder form of the TiO2 catalyst, increase of the surface area and adsorption properties. The morphology, structure, composition, and magnetism of the resulting composites were characterized and their photocatalytic activities were also evaluated. The results demonstrate that TiO2 NPs were uniformly deposited on the Fe3O4@SiO2 surface. The silver nanoparticles were also uniformly distributed on the surface of TiO2 nanoparticles. The aim of this work is to study the suitability of photocatalysis for the treatment of aqueous streams containing organic pollutants such as methylene blue which is selected as a model compound to represent one of the pollutants existing in wastewaters. Various factors such as initial pollutant concentration, photocatalyst dose and wastewater matrix were studied for their effect on the photocatalytic degradation of the organic model pollutants using the as synthesized catalysts and compared with the commercial titanium dioxide (Aeroxide P25). Photocatalysis was found to be a potential purification method for the studied pollutant also in an industrial wastewater matrix with the removal percentages of over 81 % within 15 minutes. Methylene blue was removed most efficiently and its removal consumed the least of energy in terms of the specific applied energy. The magnetic Ag/SiO2/TiO2 composites show high photocatalytic performance and can be recycled three times by magnetic separation without major loss of activity, which meant that they can be used as efficient and conveniently renewable photocatalyst.

Keywords: Magnetite nanoparticles, Titanium, Photocatalyst, Organic pollutant, Water treatment

Procedia PDF Downloads 239

Authors: Mehdi Soula, Yosra Mani, Estelle Saras, Antoine Drapeau, Raoudha Grami, Mahjoub Aouni, Jean-Yves Madec, Marisa Haenni, Wejdene Mansour

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Multi-resistance to antibiotics in gram-negative bacilli and particularly in enterobacteriaceae, has become frequent in hospitals in Tunisia. However, data on antibiotic resistant bacteria in aquatic products are scarce. The aims of this study are to estimate the proportion of ESBL- and carbapenemase-producing Enterobacterales in seafood (clams and fish) in Tunisia and to molecularly characterize the collected isolates. Two types of seafood were sampled in unrelated markets in four different regions in Tunisia (641 pieces of farmed fish and 1075 mediterranean clams divided into 215 pools, and each pool contained 5 pieces). Once purchased, all samples were incubated in tubes containing peptone salt broth for 24 to 48h at 37°C. After incubation, overnight cultures were isolated on selective MacConkey agar plates supplemented with either imipenem or cefotaxime, identified using API20E test strips (bioMérieux, Marcy-l’Étoile, France) and confirmed by Maldi-TOF MS. Antimicrobial susceptibility was determined by the disk diffusion method on Mueller-Hinton agar plates and results were interpreted according to CA-SFM 2021. ESBL-producing Enterobacterales were detected using the Double Disc Synergy Test (DDST). Carbapenem-resistance was detected using an ertapenem disk and was respectively confirmed using the ROSCO KPC/MBL and OXA-48 Confirm Kit (ROSCO Diagnostica, Taastrup, Denmark). DNA was extracted using a NucleoSpin Microbial DNA extraction kit (Macherey-Nagel, Hoerdt, France), according to the manufacturer’s instructions. Resistance genes were determined using the CGE online tools. The replicon content and plasmid formula were identified from the WGS data using PlasmidFinder 2.0.1 and pMLST 2.0. From farmed fishes, nine ESBL-producing strains (9/641, 1.4%) were isolated, which were identified as E. coli (n=6) and K. pneumoniae (n=3). Among the 215 pools of 5 clams analyzed, 18 ESBL-producing isolates were identified, including 14 E. coli and 4 K. pneumoniae. A low isolation rate of ESBL-producing Enterobacterales was detected 1.6% (18/1075) in clam pools. In fish, the ESBL phenotype was due to the presence of the blaCTX-M-15 gene in all nine isolates, but no carbapenemase gene was identified. In clams, the predominant ESBL phenotype was blaCTX-M-1 (n=6/18). blaCPE (NDM1, OXA48) was detected only in 3 isolates ‘K. pneumoniae isolates’. Replicon typing on the strains carring the ESBL and carbapenemase gene revelead that the major type plasmid carried ESBL were IncF (42.3%) [n=11/26]. In all, our results suggest that seafood can be a reservoir of multi-drug resistant bacteria, most probably of human origin but also by the selection pressure of antibiotic. Our findings raise concerns that seafood bought for consumption may serve as potential reservoirs of AMR genes and pose serious threat to public health.

Keywords: BLSE, carbapenemase, enterobacterales, tunisian seafood

Procedia PDF Downloads 77

Authors: Juan A. Arzate, Funda C. Ertem, M. Nicolas Cruz-Bournazou, Peter Neubauer, Stefan Junne

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— One of the biggest challenges the world faces today is global warming that is caused by greenhouse gases (GHGs) coming from the combustion of fossil fuels for energy generation. In order to mitigate climate change, the European Union has committed to reducing GHG emissions to 80–95% below the level of the 1990s by the year 2050. Renewable technologies are vital to diminish energy-related GHG emissions. Since water and biomass are limited resources, the largest contributions to renewable energy (RE) systems will have to come from wind and solar power. Nevertheless, high proportions of fluctuating RE will present a number of challenges, especially regarding the need to balance the variable energy demand with the weather dependent fluctuation of energy supply. Therefore, biogas plants in this content would play an important role, since they are easily adaptable. Feedstock availability varies locally or seasonally; however there is a lack of knowledge in how biogas plants should be operated in a stable manner by local feedstock. This problem may be prevented through suitable control strategies. Such strategies require the development of convenient mathematical models, which fairly describe the main processes. Modelling allows us to predict the system behavior of biogas plants when different feedstocks are used with different loading rates. Life cycle assessment (LCA) is a technique for analyzing several sides from evolution of a product till its disposal in an environmental point of view. It is highly recommend to use as a decision making tool. In order to achieve suitable strategies, the combination of a flexible energy generation provided by biogas plants, a secure production process and the maximization of the environmental benefits can be obtained by the combination of process modelling and LCA approaches. For this reason, this study focuses on the biogas plant which flexibly generates required energy from the co-digestion of maize, grass and cattle manure, while emitting the lowest amount of GHG´s. To achieve this goal AMOCO model was combined with LCA. The program was structured in Matlab to simulate any biogas process based on the AMOCO model and combined with the equations necessary to obtain climate change, acidification and eutrophication potentials of the whole production system based on ReCiPe midpoint v.1.06 methodology. Developed simulation was optimized based on real data from operating biogas plants and existing literature research. The results prove that AMOCO model can successfully imitate the system behavior of biogas plants and the necessary time required for the process to adapt in order to generate demanded energy from available feedstock. Combination with LCA approach provided opportunity to keep the resulting emissions from operation at the lowest possible level. This would allow for a prediction of the process, when the feedstock utilization supports the establishment of closed material circles within a smart bio-production grid – under the constraint of minimal drawbacks for the environment and maximal sustainability.

Keywords: AMOCO model, GHG emissions, life cycle assessment, modelling

Procedia PDF Downloads 166

Authors: Leo Nnamdi Ozurumba-Dwight

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Messenger ribooxynucleic acid (mRNA) molecules are compositional, protein-based. These proteins, encoding mRNA molecules (which collectively connote the transcriptome), when analyzed by RNA sequencing (RNAseq), unveils the nature of gene expression in the RNA. The obtained gene expression provides clues of cellular traits and their dynamics in presentations. These can be studied in relation to function and responses. RNAseq is a practical concept in Genomics as it enables detection and quantitative analysis of mRNA molecules. Single cell and spatial transcriptomics both present varying avenues for expositions in genomic characteristics of single cells and pooled cells in disease conditions such as cancer, auto-immune diseases, hematopoietic based diseases, among others, from investigated biological tissue samples. Single cell transcriptomics helps conduct a direct assessment of each building unit of tissues (the cell) during diagnosis and molecular gene expressional studies. A typical technique to achieve this is through the use of a single-cell RNA sequencer (scRNAseq), which helps in conducting high throughput genomic expressional studies. However, this technique generates expressional gene data for several cells which lack presentations on the cells’ positional coordinates within the tissue. As science is developmental, the use of complimentary pre-established tissue reference maps using molecular and bioinformatics techniques has innovatively sprung-forth and is now used to resolve this set back to produce both levels of data in one shot of scRNAseq analysis. This is an emerging conceptual approach in methodology for integrative and progressively dependable transcriptomics analysis. This can support in-situ fashioned analysis for better understanding of tissue functional organization, unveil new biomarkers for early-stage detection of diseases, biomarkers for therapeutic targets in drug development, and exposit nature of cell-to-cell interactions. Also, these are vital genomic signatures and characterizations of clinical applications. Over the past decades, RNAseq has generated a wide array of information that is igniting bespoke breakthroughs and innovations in Biomedicine. On the other side, spatial transcriptomics is tissue level based and utilized to study biological specimens having heterogeneous features. It exposits the gross identity of investigated mammalian tissues, which can then be used to study cell differentiation, track cell line trajectory patterns and behavior, and regulatory homeostasis in disease states. Also, it requires referenced positional analysis to make up of genomic signatures that will be sassed from the single cells in the tissue sample. Given these two presented approaches to RNA transcriptomics study in varying quantities of cell lines, with avenues for appropriate resolutions, both approaches have made the study of gene expression from mRNA molecules interesting, progressive, developmental, and helping to tackle health challenges head-on.

Keywords: transcriptomics, RNA sequencing, single cell, spatial, gene expression.

Procedia PDF Downloads 99

Authors: Lijuan Li

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Nitric oxide (NO) has become a fascinating entity in biological chemistry over the past few years. It is a gaseous lipophilic radical molecule that plays important roles in several physiological and pathophysiological processes in mammals, including activating the immune response, serving as a neurotransmitter, regulating the cardiovascular system, and acting as an endothelium-derived relaxing factor. NO functions in eukaryotes both as a signal molecule at nanomolar concentrations and as a cytotoxic agent at micromolar concentrations. The latter arises from the ability of NO to react readily with a variety of cellular targets leading to thiol S-nitrosation, amino acid N-nitrosation, and nitrosative DNA damage. Nitric oxide can readily bind to metals to give metal-nitrosyl (M-NO) complexes. Some of these species are known to play roles in biological NO storage and transport. These complexes have different biological, photochemical, or spectroscopic properties due to distinctive structural features. These recent discoveries have spawned a great interest in the development of transition metal complexes containing NO, particularly its iron complexes that are central to the role of nitric oxide in the body. Spectroscopic evidence would appear to implicate species of “Fe(NO)2+” type in a variety of processes ranging from polymerization, carcinogenesis, to nitric oxide stores. Our research focuses on isolation and structural studies of non-heme iron nitrosyls that mimic biologically active compounds and can potentially be used for anticancer drug therapy. We have shown that reactions between Fe(NO)2(CO)2 and a series of imidazoles generated new non-heme iron nitrosyls of the form Fe(NO)2(L)2 [L = imidazole, 1-methylimidazole, 4-methylimidazole, benzimidazole, 5,6-dimethylbenzimidazole, and L-histidine] and a tetrameric cluster of [Fe(NO)2(L)]4 (L=Im, 4-MeIm, BzIm, and Me2BzIm), resulted from the interactions of Fe(NO)2 with a series of substituted imidazoles was prepared. Recently, a series of sulfur bridged iron di nitrosyl complexes with the general formula of [Fe(µ-RS)(NO)2]2 (R = n-Pr, t-Bu, 6-methyl-2-pyridyl, and 4,6-dimethyl-2-pyrimidyl), were synthesized by the reaction of Fe(NO)2(CO)2 with thiols or thiolates. Their structures and properties were studied by IR, UV-vis, 1H-NMR, EPR, electrochemistry, X-ray diffraction analysis and DFT calculations. IR spectra of these complexes display one weak and two strong NO stretching frequencies (νNO) in solution, but only two strong νNO in solid. DFT calculations suggest that two spatial isomers of these complexes bear 3 Kcal energy difference in solution. The paramagnetic complexes [Fe2(µ-RS)2(NO)4]-, have also been investigated by EPR spectroscopy. Interestingly, the EPR spectra of complexes exhibit an isotropic signal of g = 1.998 - 2.004 without hyperfine splitting. The observations are consistent with the results of calculations, which reveal that the unpaired electron dominantly delocalize over the two sulfur and two iron atoms. The difference of the g values between the reduced form of iron-sulfur clusters and the typical monomeric di nitrosyl iron complexes is explained, for the first time, by of the difference in unpaired electron distributions between the two types of complexes, which provides the theoretical basis for the use of g value as a spectroscopic tool to differentiate these biologically active complexes.

Keywords: di nitrosyl iron complex, metal nitrosyl, non-heme iron, nitric oxide

Procedia PDF Downloads 279

Authors: Dila Ram Bhandari

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Throughout the 20th century, new governments were created where identities such as ethnic, religious, linguistic, caste, communal, tribal, and others played a part in the development of constitutions and the legal system of victim and criminal justice. Acute issues with extremism, poverty, environmental degradation, cybercrimes, human rights violations, crime against, and victimization of both individuals and groups have recently plagued South Asian nations. Everyday massive number of crimes are steadfast, these frequent crimes have made the lives of common citizens restless. Crimes are one of the major threats to society and also for civilization. Crime is a bone of contention that can create a societal disturbance. The old-style crime solving practices are unable to live up to the requirement of existing crime situations. Crime analysis is one of the most important activities of the majority of intelligent and law enforcement organizations all over the world. The South Asia region lacks such a regional coordination mechanism, unlike central Asia of Asia Pacific regions, to facilitate criminal intelligence sharing and operational coordination related to organized crime, including illicit drug trafficking and money laundering. There have been numerous conversations in recent years about using data mining technology to combat crime and terrorism. The Data Detective program from Sentient as a software company, uses data mining techniques to support the police (Sentient, 2017). The goals of this internship are to test out several predictive model solutions and choose the most effective and promising one. First, extensive literature reviews on data mining, crime analysis, and crime data mining were conducted. Sentient offered a 7-year archive of crime statistics that were daily aggregated to produce a univariate dataset. Moreover, a daily incidence type aggregation was performed to produce a multivariate dataset. Each solution's forecast period lasted seven days. Statistical models and neural network models were the two main groups into which the experiments were split. For the crime data, neural networks fared better than statistical models. This study gives a general review of the applied statistics and neural network models. A detailed image of each model's performance on the available data and generalizability is provided by a comparative analysis of all the models on a comparable dataset. Obviously, the studies demonstrated that, in comparison to other models, Gated Recurrent Units (GRU) produced greater prediction. The crime records of 2005-2019 which was collected from Nepal Police headquarter and analysed by R programming. In conclusion, gated recurrent unit implementation could give benefit to police in predicting crime. Hence, time series analysis using GRU could be a prospective additional feature in Data Detective.

Keywords: time series analysis, forecasting, ARIMA, machine learning

Procedia PDF Downloads 136

Authors: Miguel A. Figueroa, José A. Lara-Ramos, Miguel A. Mueses

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Pharmaceutical residues are a section of emerging contaminants of anthropogenic origin that are present in a myriad of waters with which human beings interact daily and are starting to affect the ecosystem directly. Conventional waste-water treatment systems are not capable of degrading these pharmaceutical effluents because their designs cannot handle the intermediate products and biological effects occurring during its treatment. That is why it is necessary to hybridize conventional waste-water systems with non-conventional processes. In the specific case of an ozonation process, its efficiency highly depends on a perfect dispersion of ozone, long times of interaction of the gas-liquid phases and the size of the ozone bubbles formed through-out the reaction system. In order to increase the efficiency of these parameters, the use of a modified flotation cell has been proposed recently as a reactive system, which is used at an industrial level to facilitate the suspension of particles and spreading gas bubbles through the reactor volume at a high rate. The objective of the present work is the development of a mathematical model that can closely predict the kinetic rates of reactions taking place in the flotation cell at an experimental scale by means of identifying proper reaction mechanisms that take into account the modified chemical and hydrodynamic factors in the FeO-catalyzed Ozonation of Diclofenac aqueous solutions in a flotation cell. The methodology is comprised of three steps: an experimental phase where a modified flotation cell reactor is used to analyze the effects of ozone concentration and loading catalyst over the degradation of Diclofenac aqueous solutions. The performance is evaluated through an index of utilized ozone, which relates the amount of ozone supplied to the system per milligram of degraded pollutant. Next, a theoretical phase where the reaction mechanisms taking place during the experiments must be identified and proposed that details the multiple direct and indirect reactions the system goes through. Finally, a kinetic model is obtained that can mathematically represent the reaction mechanisms with adjustable parameters that can be fitted to the experimental results and give the model a proper physical meaning. The expected results are a robust reaction rate law that can simulate the improved results of Diclofenac mineralization on water using the modified flotation cell reactor. By means of this methodology, the following results were obtained: A robust reaction pathways mechanism showcasing the intermediates, free-radicals and products of the reaction, Optimal values of reaction rate constants that simulated Hatta numbers lower than 3 for the system modeled, degradation percentages of 100%, TOC (Total organic carbon) removal percentage of 69.9 only requiring an optimal value of FeO catalyst of 0.3 g/L. These results showed that a flotation cell could be used as a reactor in ozonation, catalytic ozonation and photocatalytic ozonation processes, since it produces high reaction rate constants and reduces mass transfer limitations (Ha > 3) by producing microbubbles and maintaining a good catalyst distribution.

Keywords: advanced oxidation technologies, iron oxide, emergent contaminants, AOTS intensification

Procedia PDF Downloads 84

Authors: Rachana Tank, Donald. M. Lyall, Kristin Flegal, Joey Ward, Jonathan Cavanagh

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Alzheimer’s research UK estimates by 2050, 2 million individuals will be living with Late Onset Alzheimer’s disease (LOAD). However, individuals experience considerable cognitive deficits and brain pathology over decades before reaching clinically diagnosable LOAD and studies have utilised gene candidate studies such as genome wide association studies (GWAS) and polygenic risk (PGR) scores to identify high risk individuals and potential pathways. This investigation aims to determine whether high genetic risk of LOAD is associated with worse brain MRI and cognitive performance in healthy older adults within the UK Biobank cohort. Previous studies investigating associations of PGR for LOAD and measures of MRI or cognitive functioning have focused on specific aspects of hippocampal structure, in relatively small sample sizes and with poor ‘controlling’ for confounders such as smoking. Both the sample size of this study and the discovery GWAS sample are bigger than previous studies to our knowledge. Genetic interaction between loci showing largest effects in GWAS have not been extensively studied and it is known that APOE e4 poses the largest genetic risk of LOAD with potential gene-gene and gene-environment interactions of e4, for this reason we  also analyse genetic interactions of PGR with the APOE e4 genotype. High genetic loading based on a polygenic risk score of 21 SNPs for LOAD is associated with worse brain MRI and cognitive outcomes in healthy individuals within the UK Biobank cohort. Summary statistics from Kunkle et al., GWAS meta-analyses (case: n=30,344, control: n=52,427) will be used to create polygenic risk scores based on 21 SNPs and analyses will be carried out in N=37,000 participants in the UK Biobank. This will be the largest study to date investigating PGR of LOAD in relation to MRI. MRI outcome measures include WM tracts, structural volumes. Cognitive function measures include reaction time, pairs matching, trail making, digit symbol substitution and prospective memory. Interaction of the APOE e4 alleles and PGR will be analysed by including APOE status as an interaction term coded as either 0, 1 or 2 e4 alleles. Models will be adjusted partially for adjusted for age, BMI, sex, genotyping chip, smoking, depression and social deprivation. Preliminary results suggest PGR score for LOAD is associated with decreased hippocampal volumes including hippocampal body (standardised beta = -0.04, P = 0.022) and tail (standardised beta = -0.037, P = 0.030), but not with hippocampal head. There were also associations of genetic risk with decreased cognitive performance including fluid intelligence (standardised beta = -0.08, P<0.01) and reaction time (standardised beta = 2.04, P<0.01). No genetic interactions were found between APOE e4 dose and PGR score for MRI or cognitive measures. The generalisability of these results is limited by selection bias within the UK Biobank as participants are less likely to be obese, smoke, be socioeconomically deprived and have fewer self-reported health conditions when compared to the general population. Lack of a unified approach or standardised method for calculating genetic risk scores may also be a limitation of these analyses. Further discussion and results are pending.

Keywords: Alzheimer's dementia, cognition, polygenic risk, MRI

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Authors: Ekemini M. Okon, Reuben C. Okocha, Babatunde T. Adesina, Judith O. Ehigie, Babatunde M. Falana, Boluwape T. Okikiola

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Antimicrobial resistance (AMR) has evolved to become a significant threat to global public health and food safety. The development of AMR in animals has been associated with antimicrobial overuse. In recent years, the number of antimicrobials used in food animals such as fish and poultry has escalated. It, therefore, becomes imperative to understand the patterns of AMR in fish and poultry and map out future directions for better surveillance efforts. This study used the Preferred Reporting Items for Systematic reviews and Meta-Analyses(PRISMA) to assess the trend, patterns, and spatial distribution for AMR research in Egypt, Nigeria, and South Africa. A literature search was conducted through the Scopus and Web of Science databases in which published studies on AMR between 1989 and 2021 were assessed. A total of 172 articles were relevant for this study. The result showed progressive attention on AMR studies in fish and poultry from 2018 to 2021 across the selected countries. The period between 2018 (23 studies) and 2021 (25 studies) showed a significant increase in AMR publications with a peak in 2019 (28 studies). Egypt was the leading exponent of AMR research (43%, n=74) followed by Nigeria (40%, n=69), then South Africa (17%, n=29). AMR studies in fish received relatively little attention across countries. The majority of the AMR studies were on poultry in Egypt (82%, n=61), Nigeria (87%, n=60), and South Africa (83%, n=24). Further, most of the studies were on Escherichia and Salmonella species. Antimicrobials frequently researched were ampicillin, erythromycin, tetracycline, trimethoprim, chloramphenicol, and sulfamethoxazole groups. Multiple drug resistance was prevalent, as demonstrated by antimicrobial resistance patterns. In poultry, Escherichia coli isolates were resistant to cefotaxime, streptomycin, chloramphenicol, enrofloxacin, gentamycin, ciprofloxacin, oxytetracycline, kanamycin, nalidixic acid, tetracycline, trimethoprim/sulphamethoxazole, erythromycin, and ampicillin. Salmonella enterica serovars were resistant to tetracycline, trimethoprim/sulphamethoxazole, cefotaxime, and ampicillin. Staphylococcusaureus showed high-level resistance to streptomycin, kanamycin, erythromycin, cefoxitin, trimethoprim, vancomycin, ampicillin, and tetracycline. Campylobacter isolates were resistant to ceftriaxone, erythromycin, ciprofloxacin, tetracycline, and nalidixic acid at varying degrees. In fish, Enterococcus isolates showed resistance to penicillin, ampicillin, chloramphenicol, vancomycin, and tetracycline but sensitive to ciprofloxacin, erythromycin, and rifampicin. Isolated strains of Vibrio species showed sensitivity to florfenicol and ciprofloxacin, butresistance to trimethoprim/sulphamethoxazole and erythromycin. Isolates of Aeromonas and Pseudomonas species exhibited resistance to ampicillin and amoxicillin. Specifically, Aeromonashydrophila isolates showed sensitivity to cephradine, doxycycline, erythromycin, and florfenicol. However, resistance was also exhibited against augmentinandtetracycline. The findings constitute public and environmental health threats and suggest the need to promote and advance AMR research in other countries, particularly those on the global hotspot for antimicrobial use.

Keywords: antibiotics, antimicrobial resistance, bacteria, environment, public health

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Authors: Alaa Abdellatif, Gabrièle Breda

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Background. Advanced therapy medicinal products (ATMPs) are innovative therapies that mainly target orphan diseases and high unmet medical needs. ATMP includes gene therapy medicinal products (GTMP), somatic cell therapy medicinal products (CTMP), and tissue-engineered therapies (TEP). Since legislation opened the way in 2007, 25 ATMPs have been approved in the EU, which is about the same amount as the U.S. Food and Drug Administration. However, not all of the ATMPs that have been approved have successfully reached the market and retained their approval. Objectives. We aim to understand all the factors limiting the market access to very promising therapies in a systemic approach, to be able to overcome these problems, in the future, with scientific, regulatory and commercial innovations. Further to recent reviews that focus either on specific countries, products, or dimensions, we will address all the challenges faced by ATMP development today. Methodology. We used mixed methods and a multi-level approach for data collection. First, we performed an updated academic literature review on ATMP development and their scientific and market access challenges (papers published between 2018 and April 2023). Second, we analyzed industry feedback from cell and gene therapy webinars and white papers published by providers and pharmaceutical industries. Finally, we established a comparative analysis of the regulatory guidelines published by EMA and the FDA for ATMP approval. Results: The main challenges in bringing these therapies to market are the high development costs. Developing ATMPs is expensive due to the need for specialized manufacturing processes. Furthermore, the regulatory pathways for ATMPs are often complex and can vary between countries, making it challenging to obtain approval and ensure compliance with different regulations. As a result of the high costs associated with ATMPs, challenges in obtaining reimbursement from healthcare payers lead to limited patient access to these treatments. ATMPs are often developed for orphan diseases, which means that the patient population is limited for clinical trials which can make it challenging to demonstrate their safety and efficacy. In addition, the complex manufacturing processes required for ATMPs can make it challenging to scale up production to meet demand, which can limit their availability and increase costs. Finally, ATMPs face safety and efficacy challenges: dangerous adverse events of these therapies like toxicity related to the use of viral vectors or cell therapy, starting material and donor-related aspects. Conclusion. As a result of our mixed method analysis, we found that ATMPs face a number of challenges in their development, regulatory approval, and commercialization and that addressing these challenges requires collaboration between industry, regulators, healthcare providers, and patient groups. This first analysis will help us to address, for each challenge, proper and innovative solution(s) in order to increase the number of ATMPs approved and reach the patients

Keywords: advanced therapy medicinal products (ATMPs), product development, market access, innovation

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Authors: Osman Adiguzel

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Shape memory alloys take place in a class of smart materials by exhibiting a peculiar property called the shape memory effect. This property is characterized by the recoverability of two certain shapes of material at different temperatures. These materials are often called smart materials due to their functionality and their capacity of responding to changes in the environment. Shape memory materials are used as shape memory devices in many interdisciplinary fields such as medicine, bioengineering, metallurgy, building industry and many engineering fields. The shape memory effect is performed thermally by heating and cooling after first cooling and stressing treatments, and this behavior is called thermoelasticity. This effect is based on martensitic transformations characterized by changes in the crystal structure of the material. The shape memory effect is the result of successive thermally and stress-induced martensitic transformations. Shape memory alloys exhibit thermoelasticity and superelasticity by means of deformation in the low-temperature product phase and high-temperature parent phase region, respectively. Superelasticity is performed by stressing and releasing the material in the parent phase region. Loading and unloading paths are different in the stress-strain diagram, and the cycling loop reveals energy dissipation. The strain energy is stored after releasing, and these alloys are mainly used as deformation absorbent materials in control of civil structures subjected to seismic events, due to the absorbance of strain energy during any disaster or earthquake. Thermal-induced martensitic transformation occurs thermally on cooling, along with lattice twinning with cooperative movements of atoms by means of lattice invariant shears, and ordered parent phase structures turn into twinned martensite structures, and twinned structures turn into the detwinned structures by means of stress-induced martensitic transformation by stressing the material in the martensitic condition. Thermal induced transformation occurs with the cooperative movements of atoms in two opposite directions, <110 > -type directions on the {110} - type planes of austenite matrix which is the basal plane of martensite. Copper-based alloys exhibit this property in the metastable β-phase region, which has bcc-based structures at high-temperature parent phase field. Lattice invariant shear and twinning is not uniform in copper-based ternary alloys and gives rise to the formation of complex layered structures, depending on the stacking sequences on the close-packed planes of the ordered parent phase lattice. In the present contribution, x-ray diffraction and transmission electron microscopy (TEM) studies were carried out on two copper-based CuAlMn and CuZnAl alloys. X-ray diffraction profiles and electron diffraction patterns reveal that both alloys exhibit superlattice reflections inherited from the parent phase due to the displacive character of martensitic transformation. X-ray diffractograms taken in a long time interval show that diffraction angles and intensities of diffraction peaks change with the aging duration at room temperature. In particular, some of the successive peak pairs providing a special relation between Miller indices come close to each other. This result refers to the rearrangement of atoms in a diffusive manner.

Keywords: shape memory effect, martensitic transformation, reversibility, superelasticity, twinning, detwinning

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Authors: Berengere Vire, Nicolas Salvetat, Yoann Lannay, Guillaume Marcellin, Siem Van Der Laan, Franck Molina, Dinah Weissmann

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Predicting suicidal behaviors is one of the most complex challenges of daily psychiatric practices. Today, suicide risk prediction using biological tools is not validated and is only based on subjective clinical reports of the at-risk individual. Therefore, there is a great need to identify biomarkers that would allow early identification of individuals at risk of suicide. Alterations of adenosine-to-inosine (A-to-I) RNA editing of neurotransmitter receptors and other proteins have been shown to be involved in etiology of different psychiatric disorders and linked to suicidal behavior. RNA editing is a co- or post-transcriptional process leading to a site-specific alteration in RNA sequences. It plays an important role in the epi transcriptomic regulation of RNA metabolism. On postmortem human brain tissue (prefrontal cortex) of depressed suicide victims, Alcediag found specific alterations of RNA editing activity on the mRNA coding for the serotonin 2C receptor (5-HT2cR). Additionally, an increase in expression levels of ADARs, the RNA editing enzymes, and modifications of RNA editing profiles of prime targets, such as phosphodiesterase 8A (PDE8A) mRNA, have also been observed. Interestingly, the PDE8A gene is located on chromosome 15q25.3, a genomic region that has recurrently been associated with the early-onset major depressive disorder (MDD). In the current study, we examined whether modifications in RNA editing profile of prime targets allow identifying disease-relevant blood biomarkers and evaluating suicide risk in patients. To address this question, we performed a clinical study to identify an RNA editing signature in blood of depressed patients with and without the history of suicide attempts. Patient’s samples were drawn in PAXgene tubes and analyzed on Alcediag’s proprietary RNA editing platform using next generation sequencing technology. In addition, gene expression analysis by quantitative PCR was performed. We generated a multivariate algorithm comprising various selected biomarkers to detect patients with a high risk to attempt suicide. We evaluated the diagnostic performance using the relative proportion of PDE8A mRNA editing at different sites and/or isoforms as well as the expression of PDE8A and the ADARs. The significance of these biomarkers for suicidality was evaluated using the area under the receiver-operating characteristic curve (AUC). The generated algorithm comprising the biomarkers was found to have strong diagnostic performances with high specificity and sensitivity. In conclusion, we developed tools to measure disease-specific biomarkers in blood samples of patients for identifying individuals at the greatest risk for future suicide attempts. This technology not only fosters patient management but is also suitable to predict the risk of drug-induced psychiatric side effects such as iatrogenic increase of suicidal ideas/behaviors.

Keywords: blood biomarker, next-generation-sequencing, RNA editing, suicide

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Authors: Brian Bacia, Esther Githaiga, Teresia Kabucho, Paul Moses Ndegwa, Lucy Gichohi

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Purpose: The aim of the study is to ensure an appropriate mix of evidence-based prevention strategies geared towards the reduction of new HIV infections and the incidence of Sexually transmitted Illnesses Background: In Nakuru County, more than 90% of all HIV-infected patients are adults and on a single-dose medication-one pill that contains a combination of several different HIV drugs. Nakuru town has been identified as the hardest hit by HIV/Aids in the County according to the latest statistics from the County Aids and STI group, with a prevalence rate of 5.7 percent attributed to the high population and an active urban center. Method: 2 key studies were carried out to provide evidence for the effectiveness of antiretroviral therapy (ART) when used optimally on preventing sexual transmission of HIV. Discussions based on an examination, assessments of successes in planning, program implementation, and ultimate impact of prevention and treatment were undertaken involving health managers, health workers, community health workers, and people living with HIV/AIDS between February -August 2021. Questionnaires were carried out by a trained duo on ethical procedures at 15 HIV treatment clinics targeting patients on ARVs and caregivers on ARV prevention and treatment of pediatric HIV infection. Findings: Levels of AIDS awareness are extremely high. Advances in HIV treatment have led to an enhanced understanding of the virus, improved care of patients, and control of the spread of drug-resistant HIV. There has been a tremendous increase in the number of people living with HIV having access to life-long antiretroviral drugs (ARV), mostly on generic medicines. Healthcare facilities providing treatment are stressed challenging the administration of the drugs, which require a clinical setting. Women find it difficult to take a daily pill which reduces the effectiveness of the medicine. ART adherence can be strengthened largely through the use of innovative digital technology. The case management approach is useful in resource-limited settings. The county has made tremendous progress in mother-to-child transmission reduction through enhanced early antenatal care (ANC) attendance and mapping of pregnant women Recommendations: Treatment reduces the risk of transmission to the child during pregnancy, labor, and delivery. Promote research of medicines through patients and community engagement. Reduce the risk of transmission through breastfeeding. Enhance testing strategies and strengthen health systems for sustainable HIV service delivery. Need exists for improved antenatal care and delivery by skilled birth attendants. Develop a comprehensive maternal reproductive health policy covering equitability, efficient and effective delivery of services. Put in place referral systems.

Keywords: evidence-based prevention strategies, service delivery, human management, integrated approach

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Authors: S. Candamano, A. Iorfida, L. Pagnotta, F. Crea

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Basalt fabric reinforced cementitious composites (FRCM) have attracted great attention because they result in being effective in structural strengthening and eco-efficient. In this study, authors investigate their mechanical behavior when an alkali-activated binder, with tuned properties and containing high amounts of industrial by-products, such as ground granulated blast furnace slag, is used. Reinforcement is made up of a balanced, coated bidirectional fabric made out of basalt fibres and stainless steel micro-wire, with a mesh size of 8x8 mm and an equivalent design thickness equal to 0.064 mm. Mortars mixes have been prepared by maintaining constant the water/(reactive powders) and sand/(reactive powders) ratios at 0.53 and 2.7 respectively. Tensile tests were carried out on composite specimens of nominal dimensions equal to 500 mm x 50 mm x 10 mm, with 6 embedded rovings in the loading direction. Direct shear tests (DST), aimed to the stress-transfer mechanism and failure modes of basalt-FRCM composites, were carried out on brickwork substrate using an externally bonded basalt-FRCM composite strip 10 mm thick, 50 mm wide and a bonded length of 300 mm. Mortars exhibit, after 28 days of curing, a compressive strength of 32 MPa and a flexural strength of 5.5 MPa. Main hydration product is a poorly crystalline CASH gel. The constitutive behavior of the composite has been identified by means of direct tensile tests, with response curves showing a tri-linear behavior. The first linear phase represents the uncracked (I) stage, the second (II) is identified by crack development and the third (III) corresponds to cracked stage, completely developed up to failure. All specimens exhibit a crack pattern throughout the gauge length and failure occurred as a result of sequential tensile failure of the fibre bundles, after reaching the ultimate tensile strength. The behavior is mainly governed by cracks development (II) and widening (III) up to failure. The main average values related to the stages are σI= 173 MPa and εI= 0.026% that are the stress and strain of the transition point between stages I and II, corresponding to the first mortar cracking; σu = 456 MPa and εu= 2.20% that are the ultimate tensile strength and strain, respectively. The tensile modulus of elasticity in stage III is EIII= 41 GPa. All single-lap shear test specimens failed due to composite debonding. It occurred at the internal fabric-to-matrix interface, and it was the result of fracture of the matrix between the fibre bundles. For all specimens, transversal cracks were visible on the external surface of the composite and involved only the external matrix layer. This cracking appears when the interfacial shear stresses increase and slippage of the fabric at the internal matrix layer interface occurs. Since the external matrix layer is bonded to the reinforcement fabric, it translates with the slipped fabric. Average peak load around 945 N, peak stress around 308 MPa, and global slip around 6 mm were measured. The preliminary test results allow affirming that Alkali Activated Binders can be considered a potentially valid alternative to traditional mortars in designing FRCM composites.

Keywords: alkali activated binders, basalt-FRCM composites, direct shear tests, structural strengthening

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