Search results for: targeting antibodies

Authors: Emanuela Zilli, Antonio Madia, Milvia Marchiori, Paola Anello, Chiara Cabbia, Emanuela Velo, Delia Campagnolo, Michele Scomazzon, Emanuela Salvatico, S. Tikvina, Antonio Miotti

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Hepatitis C is an inflammation of the liver caused by the hepatitis C virus (HCV). Antiviral medicines can cure more than 95% of cases of hepatitis C infection, but access to diagnosis and treatment remains low. The ULSS 6 Euganea – Health Trust has implemented a campaign to eradicate hepatitis C in the province of Padua (North-East of Italy), which can be subdivided into three areas: North (300.000 inhabitants), Centre (400.000) and South (300.000). In September 2021, the project was launched in the Northern area; a set of brochures was distributed in outpatient services, general practitioners’ clinics and offices, community pharmacy services, social health districts, and through social networks. The Hepatology Service contacted 460 patients selected by the Clinical Laboratory (positivity for HCV antibodies): 83 patients (18.0%) had been already cured of HCV infection, missing or deceased; 377 patients (82.0%) met the criteria to be eligible for HCV eradication therapy and were therefore included in a Day Service specific agenda and followed by a multidisciplinary team of healthcare professionals, with a dedicated telephone line. Haemato-chemical tests, general medical check-ups and ultrasound tests with fibroscan were performed. Patients were tested for Sars-CoV-2 positivity; those not yet vaccinated against Covid-19 were encouraged to complete the vaccination scheme. All 377 patients (100%) received HCV eradication therapy at the community pharmacy service; a detailed explanation of how to take their medication was provided. At the end of the first phase, Covid-19 vaccination rate was 100% (377/377), including patients already vaccinated and new-vaccinated. Check-up appointments were arranged after 2 or 3 months, according to the treatment plan. The awareness campaign and the organization of HCV eradication therapy service by ULSS 6 Euganea are proving to be effective; the project is now going to be applied to Central and Southern areas of the province (1.132 patients).

Keywords: public health, HCV-eradication, Covid-19 emergency, health communication strategies

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Authors: J. Constanzo, B. Paquette, G. Charest, L. Masson-Côté, M. Guillot

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Targeted and whole-brain irradiation in humans can result in significant side effects causing decreased patient quality of life. To adequately investigate structural and functional alterations after stereotactic radiosurgery, preclinical studies are needed. The first step is to establish a robust standardized method of targeted irradiation on small regions of the rat brain. Eleven euthanized male Fischer rats were imaged in a stereotactic bed, by computed tomographic (CT), to estimate positioning variations regarding to the bregma skull reference point. Using a rat brain atlas and the stereotactic bregma coordinates assessed from CT images, various regions of the brain were delimited and a treatment plan was generated. A dose of 37 Gy at 30% isodose which corresponds to 100 Gy in 100% of the target volume (X = 98.1; Y = 109.1; Z = 100.0) was set by Leksell Gamma Plan using sectors number 4, 5, 7, and 8 of the Gamma Knife unit with the 4-mm diameter collimators. Effects of positioning accuracy of the rat brain on the dose deposition were simulated by Gamma Plan and validated with dosimetric measurements. Our results showed that 90% of the target volume received 110 ± 4.7 Gy and the maximum of deposited dose was 124 ± 0.6 Gy, which corresponds to an excellent relative standard deviation of 0.5%. This dose deposition calculated with the Gamma Plan was validated with the dosimetric films resulting in a dose-profile agreement within 2%, both in X- and Z-axis,. Our results demonstrate the feasibility to standardize the irradiation procedure of a small volume in the rat brain using a Gamma Knife.

Keywords: brain irradiation, dosimetry, gamma knife, small-animal irradiation, stereotactic radiosurgery (SRS)

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Authors: Sadaf Karkoodi, Hassan Karampour

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There is a growing interest in the construction industry towards hybrid systems. The hybrid systems use construction materials such as timber, steel, and concrete smartly, can be prefabricated, and are cost-effective and sustainable solutions to an industry targeting reduced carbon footprint. Moreover, in case of periodical shortage in timber resources, reusable and waste wood such as fibres can be used in the hybrid modules, which facilitates the circular economy. In this research, a hybrid frame is proposed and experimentally validated by introducing dried wood fibre products inside cold-formed steel square hollow sections without using any adhesives. As such, fibre-filled steel tubular (FFST) columns, beams, and 2D frames are manufactured and tested. The results show that the FFST columns have stiffness and strength 44% and 55% higher than cold-formed steel columns, respectively. The bearing strength of the FFST beams shows an increase of 39.5% compared to steel only. The flexural stiffness and strength of the FFST beams are 8.5% and 28% higher than the bare steel beams, respectively. The FFST frame depicted an 18.4% higher ultimate load capacity than the steel-only frame under a mid-point concentrated load. Moreover, the FFST beam-to-column bolted connection showed high ductile performance. The initial results and the proposed simple manufacturing process suggest that the proposed FFST concept can be upscaled and used in real structures.

Keywords: wood fibre, reusing wood, fibre-filled steel, hybrid construction

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Authors: Fajana Sola Isaac

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In the last two decades, we have witnessed an increased interest in exchange rate pass-through (ERPT) in developing economies and emerging markets. This is perhaps due to the acknowledged significance of the pattern of exchange rate pass-through as a key instrument in monetary policy design, principally in retort to a shock in exchange rate in literature. This paper analyzed Exchange Rate Pass-Through by A Model of Oil Prices and Asymmetric Exchange Rate Fluctuations in Selected African Countries. The study adopted A Non-Linear Autoregressive Distributed Lag approach using yearly data on Algeria, Burundi, Nigeria and South Africa from 1986 to 2022. The paper found asymmetry in exchange rate pass-through in net oil-importing and net oil-exporting countries in the short run during the period under review. An ERPT exhibited a complete pass-through in the short run in the case of net oil-importing countries but an incomplete pass-through in the case of the net oil-exporting countries that were examined. An extended result revealed a significant impact of oil price shock on exchange rate pass-through to domestic price in the long run only for net oil importing countries. The Wald restriction test also confirms the evidence of asymmetric with the role of oil price acting as an accelerator to exchange rate pass-through to domestic price in the countries examined. The study found the outcome to be very useful for gaining expansive knowledge on the external shock impact on ERPT and could be of critical value for national monetary policy decisions on inflation targeting, especially for countries examined and other developing net oil importers and exporters.

Keywords: pass through, exchange rate, ARDL, monetary policy

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Authors: Ireneusz Majsterek, Dariusz Pytel, J. Alan Diehl

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PKR-like ER kinase (PERK) is serine/threonie endoplasmic reticulum (ER) transmembrane kinase activated during ER-stress. PERK can activate signaling pathways known as unfolded protein response (UPR). Attenuation of translation is mediated by PERK via phosphorylation of eukaryotic initiation factor 2α (eIF2α), which is necessary for translation initiation. PERK activation also directly contributes to activation of Nrf2 which regulates expression of anti-oxidant enzymes. An increased phosphorylation of eIF2α has been reported in Alzheimer disease (AD) patient hippocampus, indicating that PERK is activated in this disease. Recent data have revealed activation of PERK signaling in non-Hodgkins lymphomas. Results also revealed that loss of PERK limits mammary tumor cell growth in vitro and in vivo. Consistent with these observations, activation of UPR in vitro increases levels of the amyloid precursor protein (APP), the peptide from which beta-amyloid plaques (AB) fragments are derived. Finally, proteolytic processing of APP, including the cleavages that produce AB, largely occurs in the ER, and localization coincident with PERK activity. Thus, we expect that PERK-dependent signaling is critical for progression of many types of diseases (human cancer, neurodegenerative disease and other). Therefore, modulation of PERK activity may be a useful therapeutic target in the treatment of different diseases that fail to respond to traditional chemotherapeutic strategies, including Alzheimer’s disease. Our goal will be to developed therapeutic modalities targeting PERK activity.

Keywords: PERK kinase, small molecule inhibitor, neurodegenerative disease, Alzheimer’s disease

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Authors: Parul Suraia, Harshit Sosan Lakra

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Indigenous communities represent some of the most marginalized populations globally, with India labeled as tribals, experiencing particularly pronounced marginalization and a concerning decline in their numbers. These communities often inhabit geographically challenging regions characterized by low population densities, posing significant challenges to providing essential infrastructure services. Jharkhand, a Schedule 5 state, is infamous for its low-level health status due to disparities in access to health care. The primary objective of this study is to investigate the spatial inequalities in healthcare accessibility among tribal populations within the state and pinpoint critical areas requiring immediate attention. Health indicators were selected based on the tribal perspective and association of Sustainable Goal 3 (Good Health and Wellbeing) with other SDGs. Focused group discussions in which tribal people and tribal experts were done in order to finalize the indicators. Employing Principal Component Analysis, two essential indices were constructed: the Tribal Health Index (THI) and the Tribal Health Intervention Index (THII). Index values were calculated based on the district-wise secondary data for Jharkhand. The bivariate spatial association technique, Moran’s I was used to assess the spatial pattern of the variables to determine if there is any clustering (positive spatial autocorrelation) or dispersion (negative spatial autocorrelation) of values across Jharkhand. The results helped in facilitating targeting policy interventions in deprived areas of Jharkhand.

Keywords: tribal health, health spatial disparities, health status, Jharkhand

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Authors: Jose A. Aznar-Moreno, Xi Jiang, Stefan Burén, Luis M. Rubio

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Integration of prokaryotic nitrogen fixation (nif) genes into the plastid genome for expression of functional nitrogenase components could render plants capable of assimilating atmospheric N2 making their crops less dependent of nitrogen fertilizers. The nitrogenase Fe protein component (NifH) has been used as proxy for expression and targeting of Nif proteins within plant and yeast cells. Here we use tobacco plants with the Azotobacter vinelandii nifH and nifM genes integrated into the plastid genome. NifH and its maturase NifM were constitutively produced in leaves, but not roots, during light and dark periods. Nif protein expression in transplastomic plants was stable throughout development. Chloroplast NifH was soluble, but it only showed in vitro activity when isolated from leaves collected at the end of the dark period. Exposing the plant extracts to elevated temperatures precipitated NifM and apo-NifH protein devoid of [Fe4S4] clusters, dramatically increasing the specific activity of remaining NifH protein. Our data indicate that the chloroplast endogenous [Fe-S] cluster biosynthesis was insufficient for complete NifH maturation, albeit a negative effect on NifH maturation due to excess NifM in the chloroplast cannot be excluded. NifH and NifM constitutive expression in transplastomic plants did not affect any of the following traits: seed size, germination time, germination ratio, seedling growth, emergence of the cotyledon and first leaves, chlorophyll content and plant height throughout development.

Keywords: NifH, chloroplast, nitrogen fixation, crop improvement, transplastomic plants, fertilizer, biotechnology

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Authors: Desta Brhanu Gebrehiwot

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The purpose of this review was to analyze the overall or combined effect of scholarly studies conducted on the impacts of Food for work (FFW) and Productive Safety Net Program (PSNP) on farm households’ livelihood (agricultural investment on the adoption of fertilizer, food security, livestock holding, nutrition and its’ disincentive effect) in Ethiopia. In addition, to make a critical assessment of the internal and external validity of the existing studies, the review also indicates the possibility to redesign the program. The method of selecting eligible studies for review was PICOS (Participants, Intervention, Comparison, Outcomes, and Settings) framework. The method of analysis was the fixed effects model under Meta-Analysis. The findings of this systematic review confirm the overall or combined positive significant impact of PSNP on fertilizer adoption (combined point estimate=0.015, standard error=0.005, variance=0.000, lower limit 0.004 up to the upper limit=0.026, z-value=2.726, and p-value=0.006). And the program had a significant positive impact on the child nutrition of rural households and had no significant disincentive effect. However, the program had no significant impact on livestock holdings. Thus, PSNP is important for households whose livelihood depends on rain-fed agriculture and are exposed to rainfall shocks. Thus, better to integrate the program into the national agricultural policy. In addition, most of the studies suggested that PSNP needs more attention to the design and targeting issued in order to be effective and efficient in social protection.

Keywords: meta-analysis, fixed effect model, PSNP, rural-livelihood, Ethiopia

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Authors: Afnan T. Bagasi, Donia M. Bettaieb, Abeer Alsobahi

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The wayfinding system is related to the course of the museum journey for visitors directly and indirectly. The design aspects of this system play an important role, making it an effective and communication system within the museum space. However, translating the concepts that pertain to its design, such as Intelligibility that is based on integration and connectivity in museum space design, needs more customization in the form of specific design considerations with reference to the most important approaches. Those approaches link the organizational and practical aspects to the semiotic and semantic aspects related to the space syntax by targeting the visual and perceived consistency of visitors. In this context, the study aims to identify how to apply the concept of intelligibility and clarity by employing integration and connectivity to design a wayfinding system in museums as a kind of composite interior space. Using the available plans and images to extrapolate the design considerations used to design the wayfinding system in the Saudi National Museum as a case study, a descriptive-analytical method was used to understand the basic organizational and morphological principles of the museum space through four main aspects in space design: morphological, semantic, semiotic, and pragmatic. The study's findings will assist designers, professionals, and researchers in the field of museum design in understanding the significance of the wayfinding system by delving into it through museum spaces by highlighting the essential aspects using a clear analytical method.

Keywords: wayfinding system, museum journey, intelligibility, integration, connectivity

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Authors: Jiandong Ren, Lijun Zhao, Peng Chen

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Nafamostat (NA), a synthetic broad-spectrum serine protease inhibitor, has been routinely employed for the treatment of acute pancreatitis (AP) and other inflammatory-associated diseases in some East Asia countries. Although the potent inhibitory activity against inflammation-related proteases such as thrombin, trypsin, kallikrein, plasmin, coagulation factors and complement factors is generally considered to be responsible for the anti-inflammatory effects of NA, precise target and molecular mechanism underlying the anti-inflammatory activity in the treatment of AP remain largely unknown yet. As an intracellular inflammatory signaling platform, the NOD-like receptor protein 3 (NLRP3) inflammasome is recently identified to be involved in the development of AP. In present study, we have revealed that NA alleviated pancreatic injury in a caerulein-induced AP model by inhibiting the NLRP3 inflammasome activation in pancreas. Mechanistically, NA interacted with HDAC6, a cytoplasmic deacetylase implicated in the NLRP3 inflammasome pathway, and efficiently abrogated the function of HDAC6. This property enabled NA to influence HDAC6 dependent NF-κB transcriptional activity and thus block NF-κB-driven transcriptional priming of NLRP3 inflammasome. Moreover, NA exerted the potential to interfere HDAC6-mediated intracellular transport of NLRP3, thereby leading to the failure of NLRP3 inflammasome activation. Our current work has provided valuable insight into the molecular mechanism underlying the immunomodulatory effect of NA in treatment of AP, highlighting its promising application in prevention of NLRP3 inflammasome-associated inflammatory pathological damage.

Keywords: acute pancreatitis, HDAC6, nafamostat, NLRP3 inflammasome

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Authors: Charles Bijjah Nkhata, Memory Nekati Mvula, Milton Masautso Kalongonda, Martha Masamba, Isaac Thom Shawa

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Viral Hepatitis is a serious public health concern globally with deaths estimated at 1.4 million annually due to liver fibrosis, cirrhosis, and hepatocellular carcinoma. Hepatitis B and C are the most common viruses that cause liver damage. However, the majority of infected individuals are unaware of their serostatus. Viral Hepatitis has contributed to maternal and neonatal morbidity and mortality. There is no updated data on the Epidemiology of hepatitis B and C among pregnant mothers in Malawi. To assess the epidemiology of Hepatitis B and C viruses among pregnant women at Queen Elizabeth Central Hospital. Specific Objectives • To determine sero-prevalence of HBsAg and Anti-HCV in pregnant women at QECH. • To investigate risk factors associated with HBV and HCV infection in pregnant women. • To determine the distribution of HBsAg and Anti-HCV infection among pregnant women of different age group. A descriptive cross-sectional study was conducted among pregnant women at QECH in last quarter of 2021. Of the 114 pregnant women, 96 participants were consented and enrolled using a convenient sampling technique. 12 participants were dropped due to various reasons; therefore 84 completed the study. A semi-structured questionnaire was used to collect socio-demographic and behavior characteristics to assess the risk of exposure. Serum was processed from venous blood samples and tested for HBsAg and Anti-HCV markers utilizing Rapid screening assays for screening and Enzyme Linked Immunosorbent Assay for confirmatory. A total of 84 pregnant consenting pregnant women participated in the study, with 1.2% (n=1/84) testing positive for HBsAg and nobody had detectable anti-HCV antibodies. There was no significant link between HBV and HCV in any of the socio-demographic data or putative risk variables. The findings indicate a viral hepatitis prevalence lower than the set range by the WHO. This suggests that HBV and HCV are rare in pregnant women at QECH. Nevertheless, accessible screening for all pregnant women should be provided. The prevention of MTCT is key for reduction and prevention of the global burden of chronic viral Hepatitis.

Keywords: viral hepatitis, hepatitis B, hepatitis C, pregnancy, malawi, liver disease, mother to child transmission

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Authors: Parinaz Tavakoli Zaniani, Dimitrios Balomenos

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Mitochondrial reactive oxygen species (mROS) play a crucial role in macrophage pro-inflammatory activation, although a detailed understanding of the mechanism and kinetics by which mROS drive signaling molecules is still lacking. In general, it is thought that NF-κB activation drives mROS and general ROS production. Here, We performed a detailed kinetic analysis of mROS production during macrophage activation. We found early mROS generation after LPS (lipopolysaccharide) stimulation. Remarkably as early as 5 minutes, mROS signaling promoted initial NF-κB, MAPK activation and pro-inflammatory cytokine production, as established through inhibition or quenching of mROS. On the contrary, NF-κB inhibition had no effect on mROS production. Our findings point to a mechanism by which mROS increase TRAF-6 ubiquitination and, thus NF-κB activity. mROS inhibition reduced LPS-induced lethality in an in vivo septic shock model by controlling pro-inflammatory cytokine production. Overall, our research provides novel insights into the role of mROS as a primary messenger in the pathway of macrophage and as a regulator of inflammatory responses. We found that early mROS production promotes initial NF-κB, and MAPK activation by regulating TRAF-6 ubiquitination and that mROS inhibition can reduce LPS-induced inflammatory cytokines and lethality in a septic shock model. These findings might lead to novel immunotherapeutic strategies targeting early mROS production and control of extreme inflammation in the context of sepsis and other inflammatory diseases.

Keywords: mitochondria, reactive oxygen species, nuclear factor κB, lipopolysaccharide, macrophages

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Authors: Ankit Nagar, Dinesh Kumar Nauriyal, Sukhpal Singh

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This paper examines the key determinants of farmers’ access to agricultural extension services, sources of agricultural extension services preferred and accessed by the farmers. An ordered logistic regression model was used to analyse the data of the 360 sample households based on a primary survey conducted in western Uttar Pradesh, India. The study finds that farmers' decision to engage in the agricultural extension programme is significantly influenced by factors such as education level, gender, farming experience, social group, group membership, farm size, credit access, awareness about the extension scheme, farmers' perception, and distance from extension sources. The most intriguing finding of this study is that the progressive farmers, which have long been regarded as a major source of knowledge diffusion, are the most distrusted sources of information as they are suspected of withholding vital information from potential beneficiaries. The positive relationship between farm size and ‘Access’ underlines that the extension services should revisit their strategies for targeting more marginal and small farmers constituting over 85 percent of the agricultural households by incorporating their priorities in their outreach programs. The study suggests that marginal and small farmers' productive potential could still be greatly augmented by the appropriate technology, advisory services, guidance, and improved market access. Also, the perception of poor quality of the public extension services can be corrected by initiatives aimed at building up extension workers' capacity.

Keywords: agriculture, access, extension services, ordered logistic regression

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Authors: Chen Zhang, Nan Chen

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High-dimensional process monitoring becomes increasingly important in many application domains, where usually the process distribution is unknown and much more complicated than the normal distribution, and the between-stream correlation can not be neglected. However, since the process dimension is generally much bigger than the reference sample size, most traditional nonparametric multivariate control charts fail in high-dimensional cases due to the curse of dimensionality. Furthermore, when the process goes out of control, the influenced variables are quite sparse compared with the whole dimension, which increases the detection difficulty. Targeting at these issues, this paper proposes a new nonparametric monitoring scheme for high-dimensional processes. This scheme first projects the high-dimensional process into several subprocesses using random projections for dimension reduction. Then, for every subprocess with the dimension much smaller than the reference sample size, a local nonparametric control chart is constructed based on the spatial rank test to detect changes in this subprocess. Finally, the results of all the local charts are fused together for decision. Furthermore, after an out-of-control (OC) alarm is triggered, a diagnostic framework is proposed. using the square-root LASSO. Numerical studies demonstrate that the chart has satisfactory detection power for sparse OC changes and robust performance for non-normally distributed data, The diagnostic framework is also effective to identify truly changed variables. Finally, a real-data example is presented to demonstrate the application of the proposed method.

Keywords: random projection, high-dimensional process control, spatial rank, sequential change detection

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Authors: Ava Faridi, Pouya Faridi, Aleksandr Kakinen, Ibrahim Javed, Thomas P. Davis, Pu Chun Ke

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Human islet amyloid polypeptide (IAPP) is a hormone associated with glycemic control and type 2 diabetes. Biophysically, the chirality of IAPP fibrils has been little explored with respect to the aggregation and toxicity of the peptide. Biochemically, it remains unclear as for how protein expression in pancreatic beta cells may be altered by cell exposure to the peptide, and how such changes may be mitigated by nanoparticle inhibitors for IAPP aggregation. In this study, we first demonstrated the elimination of the IAPP nucleation phase and shortening of its elongation phase by silica nanoribbons. This accelerated IAPP fibrillization translated to reduced toxicity, especially for the right-handed silica nanoribbons, as revealed by cell viability, helium ion microscopy, as well as zebrafish embryo survival, developmental and behavioral assays. We then examined the proteomes of βTC6 pancreatic beta cells exposed to the three main aggregation states of monomeric, oligomeric and amyloid fibrillar IAPP, and compared that with cellular protein expression modulated by graphene quantum dots (GQDs). A total of 29 proteins were significantly regulated by different forms of IAPP, and the majority of these proteins were nucleotide-binding proteins. A regulatory capacity of GQDs against aberrant protein expression was confirmed. These studies have demonstrated the great potential of employing nanomaterials targeting the mesoscopic enantioselectivity and protein expression dysregulation in pancreatic beta cells.

Keywords: graphene quantum dots, IAPP, silica nanoribbons, protein expression, toxicity

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Authors: Mukul R. Gupta, Rajkumar Gandhi, Rajitha Sachan, Naveen K. Khare

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The field of glycoscience has burgeoned in the last several decades, leading to the identification of many glycosides which could serve critical roles in a wide range of biological processes. This has prompted a resurgence in synthetic interest, with a particular focus on new approaches to construct the selective glycosidic bond. Despite the numerous elegant strategies and methods developed for the formation of glycosidic bonds, stereoselective construction of glycosides remains challenging. Here, we have recently developed the novel Hexafluoroisopropanol (HFIP) catalyzed stereoselective glycosylation methods by using KDN imidate glycosyl donor and a variety of alcohols in excellent yield. This method is broadly applicable to a wide range of substrates and with excellent selectivity of glycoside. Also, herein we are reporting the functionalization of the unbiased side of newly formed glycosides by dual-catalytic transition metal systems (Ru- or Fe-). We are using the innovative Reverse & Catalyst strategy, i.e., a reversible activation reaction by one catalyst with a functionalization reaction by another catalyst, together with enabling functionalization of substrates at their inherently unreactive sites. As well, we are targeting the diSia derivative synthesis by Wittig reaction. This synthetic method is applicable in mild conditions, functional group tolerance of the dual-catalytic systems and also highlights the potential of the multicatalytic approach to address challenging transformations to avoid multistep procedures in carbohydrate synthesis.

Keywords: KDN, stereoselective glycosylation, dual-catalytic functionalization, Wittig reaction

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Authors: Nuri Başpınar, Abdullah Başoğlu, Özgür Özdemir, Çağlayan Özel, FundaTerzi, Özgür Yaman

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Current research is targeting new molecular mechanisms that underlie non-alcoholic fatty liver disease (NAFLD) and associated metabolic disorders like nonalcoholic steatohepatitis (NASH). Forty New Zealand White rabbits have been used and fed a high protein (HP) and energy diet based on grains and containing 11.76 MJ/kg. Boron added to 3 experimental groups’ drinking waters (30 mg boron/L) as boron compounds. Biochemical analysis including boron levels, and nuclear magnetic resonance (NMR) based metabolomics evaluation, and mRNA expression of peroxisome proliferator-activated receptor (PPAR) family were performed. LDL-cholesterol concentrations alone were decreased in all the experimental groups. Boron levels in serum and feces were increased. Content of acetate was in about 2x higher for anhydrous borax group, at least 3x higher for boric acid group. PPARα mRNA expression was significantly decreased in boric acid group. Anhydrous borax attenuated mRNA levels of PPARα, which was further suppressed by boric acid. Boron supplementation decreased the degenerative alterations in hepatocytes. Except borax group other boron groups did not have a pronounced change in tubular epithels of kidney. In conclusion, high protein and energy diet leads hepatocytes’ degenerative changes which can be prevented by boron supplementation. Boric acid seems to precede in this effectiveness.

Keywords: high protein and energy diet, boron, metabolomics, transcriptomic

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Authors: L. M. Al-Harbi, A. M. Shokry, J. S. M. Sabir, A. Chaudhary, J. Manikandan, K. S. Saini

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Breast cancer is the second most common cause of cancer death worldwide and is the most common malignancy among Saudi females. During breast carcinogenesis, a wide-array of cytogenetic changes involving deletions, or amplification, or translocations, of part or whole of chromosome regions have been observed. Because of the limitations of various earlier technologies, newer tools are developed to scan for changes at the genomic level. Recently, Array Comparative Genomic Hybridization (aCGH) technique has been applied for detecting segmental genomic alterations at molecular level. In this study, aCGH was performed on twenty breast cancer tumors and their matching non-tumor (normal) counterparts using the Agilent 2x400K. Several regions were identified to be either amplified or deleted in a tumor-specific manner. Most frequent alterations were amplification of chromosome 1q, chromosome 8q, 20q, and deletions at 16q were also detected. The amplification of genetic events at 1q and 8q were further validated using FISH analysis using probes targeting 1q25 and 8q (MYC gene). The copy number changes at these loci can potentially cause a significant change in the tumor behavior, as deletions in the E-Cadherin (CDH1)-tumor suppressor gene as well as amplification of the oncogenes-Aurora Kinase A. (AURKA) and MYC could make these tumors highly metastatic. This study validates the use of aCGH in Saudi breast cancer patients and sets the foundations necessary for performing larger cohort studies searching for ethnicity-specific biomarkers and gene copy number variations.

Keywords: breast cancer, molecular biology, ecology, environment

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Authors: Pavel Damborsky, Martina Zamorova, Jaroslav Katrlik

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Prostate cancer is annually the most common newly diagnosed cancer among men. An extensive number of evidence suggests that traditional serum Prostate-specific antigen (PSA) assay still suffers from a lack of sufficient specificity and sensitivity resulting in vast over-diagnosis and overtreatment. Thus, the early-stage detection of prostate cancer (PCa) plays undisputedly a critical role for successful treatment and improved quality of life. Over the last decade, particular altered glycans have been described that are associated with a range of chronic diseases, including cancer and inflammation. These glycans differences enable a distinction to be made between physiological and pathological state and suggest a valuable biosensing tool for diagnosis and follow-up purposes. Aberrant glycosylation is one of the major characteristics of disease progression. Consequently, the aim of this study was to develop a more reliable tool for early-stage PCa diagnosis employing lectins as glyco-recognition elements. Biosensor and biochip technology putting to use lectin-based glyco-profiling is one of the most promising strategies aimed at providing fast and efficient analysis of glycoproteins. The proof-of-concept experiments based on sandwich assay employing anti-PSA antibody and an aptamer as a capture molecules followed by lectin glycoprofiling were performed. We present a lectin-based biosensing assay for glycoprofiling of serum biomarker PSA using different biosensor and biochip platforms such as label-free surface plasmon resonance (SPR) and microarray with fluorescent label. The results suggest significant differences in interaction of particular lectins with PSA. The antibody-based assay is frequently associated with the sensitivity, reproducibility, and cross-reactivity issues. Aptamers provide remarkable advantages over antibodies due to the nucleic acid origin, stability and no glycosylation. All these data are further step for construction of highly selective, sensitive and reliable sensors for early-stage diagnosis. The experimental set-up also holds promise for the development of comparable assays with other glycosylated disease biomarkers.

Keywords: biomarker, glycosylation, lectin, prostate cancer

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Authors: M. Bolacali

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The aim of the study is to determine the effect of immunocastration vaccine administration at different doses on fattening performance of feedlot Holstein bulls. Bopriva® is a vaccine that stimulates the animals' own immune system to produce specific antibodies against gonadotropin releasing factor (GnRF). Ninety four Holstein male calves (309.5 ± 2.58 kg body live weight and 267 d-old) assigned to the 4 treatments. Control group; 1 mL of 0.9% saline solution was subcutaneously injected to intact bulls on 1st and 60th days of the feedlot as placebo. On the same days of the feedlot, Bopriva® at two doses of 1 mL and 1 mL for Trial-1 group, 1.5 mL, and 1.5 mL for Trial-2 group, 1.5 mL, and 1 mL for Trial-3 group were subcutaneously injected to bulls. The study was conducted in a private establishment in the Sirvan district of Siirt province and lasted 180 days. The animals were weighed at the beginning of fattening and at 30-day intervals to determine their live weights at various periods. The statistical analysis for normal distribution data of the treatment groups was carried out with the general linear model procedure of SPSS software. The fattening initial live weight in Control, Trial-1, Trial-2 and Trial-3 groups was respectively 309.21, 306.62, 312.11, and 315.39 kg. The fattening final live weight was respectively 560.88, 536.67, 548.56, and 548.25 kg. The daily live weight gain during the trial was respectively 1.40, 1.28, 1.31, and 1.29 kg/day. The cold carcass yield was respectively 51.59%, 50.32%, 50.85%, and 50.77%. Immunocastration vaccine administration at different doses did not affect the live weights and cold carcass yields of Holstein male calves reared under intensive conditions (P > 0.05). However, it was determined to reduce fattening performance between 61-120 days (P < 0.05) and 1-180 days (P < 0.01). In addition, it was determined that the best performance among the vaccine-treated groups occurred in the group administered a 1.5 mL of vaccine on the 1st and 60th study days. In animals, castration is used to control fertility, aggressive and sexual behaviors. As a result, the fact that stress is induced by physical castration in animals and active immunization against GnRF maintains performance by maximizing welfare in bulls improves carcass and meat quality and controls unwanted sexual and aggressive behavior. Considering such features, it may be suggested that immunocastration vaccine with Bopriva® can be administered as a 1.5 mL dose on the 1st and 60th days of the fattening period in Holstein bulls.

Keywords: anti-GnRF, fattening, growth, immunocastration

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Authors: Jennifer McNeill

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Over the years UK Governments have extended the use of welfare conditionality to more marginalised groups. Whereas in the past, disabled people’s rights to unconditional welfare were defended, significant numbers of disabled people have in recent years been re-classified as ‘fit for work’ as a result of this policy shift towards increased conditionality targeting more welfare service user groups. This paper discusses findings from a five-year project exploring the ethics and efficacy of welfare conditionality. Drawing on repeat interviews over three years with 58 disabled welfare service users across England and Scotland, the paper explores the experience of, and impact of conditionality upon, disabled participants. In particular, participants described the process of claiming disability-related benefits as stigmatising, with some describing the medical assessments as demeaning, traumatic and even painful. The medical assessments are conducted by private contractors and participants felt they were treated unfairly, under suspicion and under surveillance. This finding is important in line with a recent UN report concerned with the practice of such assessments. The findings reveal that notions of ‘deservedness’ are embedded in this system as disabled recipients argue for their entitlement to welfare claims relative to what are deemed to be less deserving groups of benefit claimants. This indicates an increasing competition ethic within different sections of the most marginalised social groups that facilitate further forms of social fragmentation, particularly in relation to opposition to benefit cuts and other changes requiring concerted and organised forms of resistance. The impact of media and political scapegoating of the most marginal has generated divisions within even those who position themselves as legitimate recipients.

Keywords: disability, medical assessments, stigma, welfare conditionality

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Authors: Betül Garda

Abstract:

Technological developments have diversified marketing activities of the tourism sector and it has increased tourism opportunities to compete on a global scale for tourism businesses. Tourism businesses have been forced to use its core skills and knowledge effectively with the increase in effectiveness of the technology in the global competitive environment. Tourism businesses have been reached beyond the traditional boundaries because of their commercial activities, so, the boundaries of the national market either eliminated or blurred. Therefore, the internet is the alternative promotion tool and distribution channel to providing unlimited facilities for tourism suppliers. For example, the internet provides an opportunity to reach customers on a global scale with direct email marketing, advertising, customer service, promotion, sales, and marketing. Tourism businesses have improved themselves with the continuous information flows and also they have provided the permanence of the changes. Especially in terms of tourism businesses, social media is emerging as an extremely important tool in the use of knowledge effectively. This research paper investigates the impact of social media on the tourism businesses. A social networking site is a type of social media that provides a platform for business and people to connect with each other. Social media is so flexible that it can be used for both leisure and business purposes. In the tourism industry, social networking sites are one of the essential tools that play an important and beneficial role. The topic that will be discussed in this research paper are consumer behavior, connection with consumers, effectiveness in terms of time and cost, creating brand awareness and building the image of the company, promoting company, targeting consumers in a conceptual frame.

Keywords: branding, promoting, social media in tourism, tourism marketing tools

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Authors: Ugoh Kelechi Melford, Anene O.

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Introduction: Evidence has shown that there are increasing rates of new HIV and other STI infections occurring among Men who have Sex with Men (MSM) in Nigeria, with the prevalence 3 times higher than the general population as reported by the 2011 National Integrated Bio Behavioral Surveillance Survey. The poor state of health care and support services hinders our effort to control the high rates of these new infections among MSM. Methods: The Initiative for Improved Male Health (IMH-Initiative) works to provide a safe space for young MSM living with HIV to access comprehensive palliative care and support, as well as referrals for other services through drama and dance competitions. An STI assessment was conducted in IMH-Initiative’s Community Center in Calabar, for gay men and other MSM. An STI history was conducted for all clients who visited the community clinic specifically for HCT and STI counseling and referrals within a 5 month period, and their data were collated. Results: 61 MSM were diagnosed, and reported the following in the last 6 months. 49 where living with HIV. 46 had previous histories of untreated anal warts. 20 had previous histories of treated Gonorrhea by self-medication and herbs. 21 had untreated boils and rashes around the genitals. 10 clients where living with HIV, and reported untreated penile and rectal gonorrhea. All clients indicated that there were not comfortable discussing STI infections with staff of public hospitals. Conclusion: It is evident that a reasonable number of STI infections among MSM are not completely treated or ignored. This thereby increases the individual’s risk of HIV infection, and cripples HIV prevention programming in Nigeria. HIV programs targeting MSM must incorporate STI syndromic management, so as to increase access to non-stigmatized diagnosis and treatment of STIs. Also, access to STI drugs for clients cannot be overemphasized.

Keywords: MSM, IBBSS, STI, IMH

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Authors: Efua Ehiaguina, Haruna Moda

Abstract:

Interest in the development of appropriate safety culture in the oil and gas industry has taken centre stage among stakeholders in the industry. Human behaviour has been identified as a major contributor to occupational accidents, where abnormal activities associated with safety management are taken as normal behaviour. Poor safety culture is one of the major factors that influence employee’s safety behaviour at work, which may consequently result in injuries and accidents and strengthening such a culture can improve workers safety performance. Nigeria oil and gas industry has contributed to the growth and development of the country in diverse ways. However, in terms of safety and health of workers, this industry is a dangerous place to work as workers are often exposed to occupational safety and health hazard. To ascertain the impact of employees’ safety and how it impacts health and safety compliance within the local industry, online safety culture survey targeting frontline workers within the industry was administered covering major subjects that include; perception of management commitment and style of leadership; safety communication method and its resultant impact on employees’ behaviour; employee safety commitment and training needs. The preliminary result revealed that 54% of the participants feel that there is a lack of motivation from the management to work safely. In addition, 55% of participants revealed that employers place more emphasis on work delivery over employee’s safety on the installation. It is expected that the study outcome will provide measures aimed at strengthening and sustaining safety culture in the Nigerian oil and gas industry.

Keywords: oil and gas safety, safety behaviour, safety culture, safety compliance

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Authors: Engin Berber, Nurettin Canakoglu, Ibrahim Sozdutmaz, Merve Caliskan, Shaikh Terkis Islam Pavel, Hazel Yetiskin, Aykut Ozdarendeli

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Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne virus in the family Bunyaviridae, genus Nairovirus. The CCHFV genome consists of three molecules of negative-sense single-stranded RNA, each encapsulated separately. The virion particle contains viral RNA polymerase (L segment), surface glycoproteins Gn and Gc (Msegment), and a nucleocapsid protein NP (S segment). CCHF is characterized by high case mortality, occurring in Asia, Africa, the Middle East and Eastern Europe. Clinical CCHF was first recognized in Turkey in 2002. The numbers of CCHF cases have gradually increased in Turkey making the virus a public health concern. Between 2002 and 2014, more than 8000 the CCHF cases have been reported in Turkey and mortality rate is around 5%. So, Turkey is one of the countries where the epidemy has become spread to the wider geography and the biggest outbreaks of CCHF have occurred in the world. We have recently developed an inactivated cell-culture based vaccine against CCHF. We have showed that the Balb/c mice immunized with the CCHF vaccine induced the high level of neutralizing antibodies. In this study, we aimed to determine the immunodominant regions of nucleoprotein (NP) CCHFV Kelkit06 strain which stimulate T cells. For this purpose, pools of overlapping NP were used for an IFN- γ ELISPOT assay. Balb/c mice were divided into two groups for the experiment. Two groups (n = 10 each) were immunized via the intraperitoneal route with 5, or 10μg of the cell culture-based vaccine. The control group (n = 6) was mock immunized with PBS. Booster injections with the same formulation were given on days 21 and 42 after the first immunization. The higher reactivity against the CCHFV NP pools 31-40 and 80-90 was determined in the two dose groups. In order to analyze the vaccine-induced T cell responses in Balb/c mice immunized with varying doses of the vaccine, we have been also currently working on CD4+, CD8+ and CD3 + T cells by flow cytometry.

Keywords: Crimean-Congo hemorrhagic fever virus, immunodominant regions of NP, T cell response, vaccine

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Authors: Yasser A. Ahmed, Juleen M Dickson, Evan S. Krystofiak, Julie A. Oliver

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Cancer cells urgently need folate to support their rapid division. Folate receptors (FR) are over-expressed on a wide range of tumor cells, including breast cancer cells. FR are distributed over the entire surface of cancer cells, but are polarized to the apical surface of normal cells. Targeting of cancer cells using specific surface molecules such as folate receptors may be one of the strategies used to kill cancer cells without hurting the neighing normal cells. The aim of the current study was to try a method of SEM detecting FR in a murine breast cancer cell model (4T1 cells) using secondary antibody conjugated to gold or gold-coated magnetite nanoparticles. 4T1 cells were suspended in RPMI medium witth FR antibody and incubated with secondary antibody for fluorescence microscopy. The cells were cultured on 30mm Thermanox coverslips for 18 hours, labeled with FR antibody then incubated with secondary antibody conjugated to gold or gold-coated magnetite nanoparticles and processed to scanning electron microscopy (SEM) analysis. The fluorescence microscopy study showed strong punctate FR expression on 4T1 cell membrane. With SEM, the labeling with gold or gold-coated magnetite conjugates showed a similar pattern. Specific labeling occurred in nanoparticle clusters, which are clearly visualized in backscattered electron images. The 4T1 tumor cell model may be useful for the development of FR-targeted tumor therapy using gold-coated magnetite nano-particles.

Keywords: cancer cell, nanoparticles, cell culture, SEM

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Authors: Claudia Cedeno Nadal, Mei-Ling Villafana, Griela Rodriguez, Jessica Martin, Jennifer Martin, Megan Patel

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This study systematically examines the impact of Transcendental Mindfulness Meditation on anxiety symptoms in young females aged 18-25. Through a comprehensive literature review, we found consistent evidence supporting the positive influence of Transcendental Mindfulness Meditation on reducing anxiety, enhancing overall well-being, and decreasing perceived stress levels within this demographic. The mechanisms underlying these effects include heightened self-awareness, improved emotional regulation, and the development of effective stress-coping strategies. These findings have significant implications for mental health interventions targeting young females. However, the reviewed studies had some limitations, such as small sample sizes and reliance on self-report measures. To advance this field, future research should focus on larger sample sizes and utilize a broader range of measurement methods, including neuroscience assessments. Additionally, investigating the temporal relationships between Transcendental Mindfulness Meditation, proposed mediators, and anxiety symptoms will help establish causal specificity and a deeper understanding of the precise mechanisms of action. The development of integrative models based on these mechanisms can further enhance the effectiveness of Transcendental Mindfulness Meditation as an intervention for anxiety in this demographic. This study contributes to the current knowledge on the potential benefits of Transcendental Mindfulness Meditation for reducing anxiety in young females, paving the way for more targeted and effective mental health interventions in this population.

Keywords: mindfulness, meditation, anxiety, transcendental mindfulness

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Authors: Anurag Gaur Nidhi

Abstract:

Targeted drug delivery is a method of delivering medication to a patient in a manner that increases the concentration of the medication in some parts of the body relative to others. Targeted drug delivery seeks to concentrate the medication in the tissues of interest while reducing the relative concentration of the medication in the remaining tissues. This improves efficacy of the while reducing side effects. In the present work, we investigate the effect of magnetic field, flow rate and particle concentration on the capturing of magnetic particles transported in a stent implanted fluidic channel. Iron oxide magnetic nanoparticles (Fe3O4) nanoparticles were synthesized via co-precipitation method. The synthesized Fe3O4 nanoparticles were added in the de-ionized (DI) water to prepare the Fe3O4 magnetic particle suspended fluid. This fluid is transported in a cylindrical tube of diameter 8 mm with help of a peristaltic pump at different flow rate (25-40 ml/min). A ferromagnetic coil of SS 430 has been implanted inside the cylindrical tube to enhance the capturing of magnetic nanoparticles under magnetic field. The capturing of magnetic nanoparticles was observed at different magnetic magnetic field, flow rate and particle concentration. It is observed that capture efficiency increases from 47-67 % at magnetic field 2-5kG, respectively at particle concentration 0.6 mg/ml and at flow rate 30 ml/min. However, the capture efficiency decreases from 65 to 44 % by increasing the flow rate from 25 to 40 ml/min, respectively. Furthermore, it is observed that capture efficiency increases from 51 to 67 % by increasing the particle concentration from 0.3 to 0.6 mg/ml, respectively.

Keywords: capture efficiency, implant assisted-Magnetic drug targeting (IA-MDT), magnetic nanoparticles, In-vitro study

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Authors: Isaiah Chacha, Samuel Arimi, Andrew Thaiya

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Background: This study was conducted to assess knowledge, attitudes and practices regarding anthrax in Maragua, Kenya to provide baseline information to design interventions. Methods: A cross sectional survey was conducted among head of households, health and veterinary workers in Maragua Sub-county in August and September 2014. Administered questionnaires were used to collect data from household members and a key informant interview held with health and veterinary workers. Multi stage sampling was used to obtain participants’ knowledge, attitudes and practices. Questions were scored and descriptively analyzed using Excel spreadsheet then exported to GenStat Discovery Edition 4. Results: A total of 293 community members were recruited in this study. The overall level of knowledge was 77.9% of all community members regarding cause, transmission, symptoms and prevention of the disease in both humans and animals. Majority of the participants (96.3%) had heard about anthrax. A total of 99 (33.8%) correspondents had seen a person with anthrax and 75.1% think that anthrax is a very serious disease in the area. Of the interviewed correspondents, 14.3% of them have had their animals (mostly cattle) suffer from anthrax while 15.7% had either suffered from anthrax or have had their family member who suffered from anthrax. Conclusion: The study findings indicate above average knowledge on cause, symptoms, transmission and prevention of anthrax among community members in humans and animals. Practices in this study were still risk among community members. Veterinary and Medical health planners should design anthrax awareness interventions as a team targeting to reach these communities and the public through barazas, radio, CHW and other communication channel on a regular basis.

Keywords: anthrax, attitudes, Kenya, knowledge, Maragua, practices

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Authors: Bello Gonzalez, Setten Van M., Brouwer M.

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The chicken small intestine represents a dynamic and complex organ in which the enzymatic digestion and absorption of nutrients take place. The development of an in vitro fermentation chicken small intestinal model could be used as an alternative to explore the interaction between the microbiota and nutrient metabolism and to enhance the efficacy of targeting interventions to improve animal health. In the present study we have developed an in vitro fermentation chicken ileum microbiota model for unrevealing the complex interaction of ileum microbial community under physiological conditions. A two-vessel continuous fermentation process simulating in real-time the physiological conditions of the ileum content (pH, temperature, microaerophilic/anoxic conditions, and peristaltic movements) has been standardized as a proof of concept. As inoculum, we use a pool of ileum microbial community obtained from chicken broilers at the age of day 14. The development and validation of the model provide insight into the initial characterization of the ileum microbial community and its dynamics over time-related to nutrient assimilation and fermentation. Samples can be collected at different time points and can be used to determine the microbial compositional structure, dynamics, and diversity over time. The results of studies using this in vitro model will serve as the foundation for the development of a whole small intestine in vitro fermentation chicken gastrointestinal model to complement our already established in vitro fermentation chicken caeca model. The insight gained from this model could provide us with some information about the nutritional strategies to restore and maintain chicken gut homeostasis. Moreover, the in vitro fermentation model will also allow us to study relationships between gut microbiota composition and its dynamics over time associated with nutrients, antimicrobial compounds, and disease modelling.

Keywords: broilers, in vitro model, ileum microbiota, fermentation

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