Search results for: beta amyloid 25-35

Authors: Ferreira RC, Simons HZ, Thompson WS, Cutler AJ, Dopico XC, Smyth DJ, Mashar M, Schuilenburg H, Walker NM, Dunger DB, Wallace C, Todd JA, Wicker LS, Pekalski ML

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Type 1 diabetes is caused by autoimmune destruction of insulin-secreting beta cells in the pancreas. T cells are known to play an important role in this immune-mediated destruction; however, there is no general consensus regarding alterations in cytokine production or T cell subsets in peripheral blood of patients with type 1 diabetes. Using polychromatic flow cytometry of peripheral blood mononuclear cells (PBMCs), we assessed production of the proinflammatory cytokines IL-21, IFN-γ and IL-17 by memory CD4 T effector (Teff) cells in 69 patients with type 1 diabetes and 61 healthy donors. We found a 21.9% (95% CI 5.8, 40.2; p = 3.9 × 10(-3)) higher frequency of IL-21(+) CD45RA(-) memory CD4(+) Teffs in patients with type 1 diabetes (geometric mean 5.92% [95% CI 5.44, 6.44]) compared with healthy donors (geometric mean 4.88% [95% CI 4.33, 5.50]). In a separate cohort of 30 patients with type 1 diabetes and 32 healthy donors, we assessed the frequency of circulating T follicular helper (Tfh) cells in whole blood. Consistent with the increased production of IL-21, we also found a 14.9% increase in circulating Tfh cells in the patients with type 1 diabetes (95% CI 2.9, 26.9; p = 0.016). Analysis of IL-21 production by PBMCs from a subset of 46 of the 62 donors immunophenotyped for Tfh showed that frequency of Tfh cells was associated with the frequency of IL-21+ cells (r2 = 0.174, p = 0.004). These results indicate that increased IL-21 production is likely to be an aetiological factor in the pathogenesis of type 1 diabetes that could be considered as a potential therapeutic target.

Keywords: T follicular helper cell, IL-21, IL-17, type 1 diabetes

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Authors: Jerman Madonsela, Wallace Matizamhuka, Akiko Yamamoto, Ronald Machaka, Brendon Shongwe

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In this study, biocompatibility evaluation of nanostructured near beta Ti-24Nb-4Zr-8Sn (Ti2448) alloy with non-toxic elements produced utilizing Spark plasma sintering (SPS) of very fine microsized powders attained through mechanical alloying was performed. The results were compared with pure titanium and Ti-6Al-4V (Ti64) alloy. Cell proliferation test was performed using murine osteoblastic cells, MC3T3-E1 at two cell densities; 400 and 4000 cells/mL for 7 days incubation. Pure titanium took a lead under both conditions suggesting that the presence of other oxide layers influence cell proliferation. No significant difference in cell proliferation was observed between Ti64 and Ti2448. Potentiodynamic measurement in Hanks, 0.9% NaCl and cell culture medium showed no distinct difference on the anodic polarization curves of the three alloys, indicating that the same anodic reaction occurred on their surface but with different rates. However, Ti2448 showed better corrosion resistance in cell culture medium with a slightly lower corrosion rate of 2.96 nA/cm2 compared to 4.86 nA/cm2 and 5.62 nA/cm2 of Ti and Ti64 respectively. Ti2448 adsorbed less protein as compared to Ti and Ti64 though no notable difference in surface wettability was observed.

Keywords: biocompatibility, osteoblast, corrosion, surface wettability, protein adsorption

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Authors: Anjali Verma, Mahesh Pal, Veena Pande, Dalip Kumar Upreti

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The present study is carried out to explore the anti-hyperglycemic activity of Leucas cephalotes plant parts. A fruit, leaves, stems, and roots part of the Leucas cephalotes has been extracted in ethanol and have been evaluated for anti-hyperglycemic activity. The present study indicated that, ethanolic extract of fruit and leaves have shown significant α- amylase inhibitory activity with IC50 value of 92.86 ± 0.89 μg/mL and 98.09 ± 0.69 μg/mL respectively. Two known compounds β-sitosterol and lupeol were isolated from ethanolic extract of L. cephalotes leaves and were subjected to anti-hyperglycemic activity. Lupeol shows the best activity with IC50 55.73 ± 0.47 μg/mL and the results were verified by docking study of these compounds with mammalian α-amylase was carried out on its active site. It was concluded from the study that β-sitosterol and lupeol form one H-bond interactions with the active site residues either Asp212 or Thr21. The estimated free energy binding of β-sitosterol was found to be -9.47 kcal mol-1 with an estimated inhibition constant (Ki) of 558.94 nmol whereas the estimated free energy binding of lupeol was -11.73 kcal mol-1 with an estimated inhibition constant (Ki) of 476.71pmmol. The present study clearly showed that lupeol is more potent in comparison to β-sitosterol. The study indicates that L. cephalotes have significant potential to inhibit α-amylase enzyme.

Keywords: alpha-amylase, beta-sitosterol, hyperglycemia, lupeol

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Authors: Kumaran Narayanan, Pei-Sheng Liew

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This paper adapts the bacteriophage N15 protelomerase enzyme to assemble linear chromosomes as vectors for gene expression in human cells. Phage N15 has the unique ability to replicate as a linear plasmid with telomeres in E. coli during its prophage stage of life-cycle. The virus-encoded protelomerase enzyme cuts its circular genome and caps its ends to form hairpin telomeres, resulting in a linear human-chromosome-like structure in E. coli. In mammalian cells, however, no enzyme with TelN-like activities has been found. In this work, we show for the first-time transfer of the protelomerase from phage into human and mouse cells and demonstrate recapitulation of its activity in these hosts. The function of this enzyme is assayed by demonstrating cleavage of its target DNA, followed by detecting telomere formation based on its resistance to recBCD enzyme digestion. We show protelomerase expression persists for at least 60 days, which indicates limited silencing of its expression. Next, we show that an intact human β-globin gene delivered on this linear chromosome accurately retains its expression in the human cellular environment for at least 60 hours, demonstrating its stability and potential as a vector. These results demonstrate that the N15 protelomerse is able to function in mammalian cells to cut and heal DNA to create telomeres, which provides a new tool for creating novel structures by DNA resolution in these hosts.

Keywords: chromosome, beta-globin, DNA, gene expression, linear vector

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Authors: Kashif Ahmed

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Recent years researchers have been motivated towards extensive exploring of living organism, which could be utilized effectively in intense industrial conditions. The present study shows enhanced production, purification and characterization of industrial enzyme, invertase (Beta-D-fructofuranosidase) from Penicillium lilacinum. Various agricultural based by-products (cotton stalk, sunflower waste, rice husk, molasses and date syrup) were used as energy source. The highest amount of enzyme (13.05 Units/mL) was produced when the strain was cultured on growth medium containing date syrup as energy source. Yeast extract was used as nitrogen source after 96 h of incubation at incubation temperature of 40º C. Initial pH of medium was 8.0, inoculum size 6x10⁶ conidia and 200 rev/min agitation rate. The enzyme was also purified (7 folds than crude) and characterized. Molecular mass of purified enzyme (65 kDa) was determined by 10 % SDS-PAGE. Lineweaver-Burk Plot was used to determine Kinetic constants (Vmax 178.6 U/mL/min and Km 2.76 mM). Temperature and pH optima were 55º C and 5.5 respectively. MnCl₂ (52.9 %), MgSO₄ (48.9 %), BaCl₂ (24.6 %), MgCl₂ (9.6 %), CoCl₂ (5.7 %) and NaCl (4.2 %) enhanced the relative activity of enzyme and HgCl₂ (-92.8 %), CuSO₄ (-80.2 %) and CuCl₂ (-76.6 %) were proved inhibitors. The strain was showing enzyme activity even at extreme conditions of temperature (up to 60º C) and pH (up to 9), so it can be used in industries.

Keywords: invertase, Penicillium lilacinum, submerged fermentation, industrial enzyme

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Authors: Isaac Quiros-Fernandez, Angel Cid-Arregui

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Tumor-reactive T cell receptors (TCRs) are being subject of intense investigation since they offer great potential in adoptive cell therapies against cancer. However, the identification of tumor-specific TCRs has proven challenging, for instance, due to the limited expansion capacity of tumor-infiltrating T cells (TILs) and the extremely low frequencies of tumor-reactive T cells in the repertoire of patients and healthy donors. We have developed an approach for rapid identification and characterization of neoepitope-reactive TCRs from the T cell repertoire of healthy donors. CD8 T cells isolated from multiple donors are subjected to a first sorting step after staining with HLA multimers carrying the peptide of interest. The isolated cells are expanded for two weeks, after which a second sorting is performed using the same peptide-HLA multimers. The cells isolated in this way are then processed for single-cell sequencing of their TCR alpha and beta chains. Newly identified TCRs are cloned in appropriate expression vectors for functional analysis on Jurkat, NK92, and primary CD8 T cells and tumor cells expressing the appropriate antigen. We have identified TCRs specifically binding HLA-A2 presenting epitopes of tumor antigens, which are capable of inducing TCR-mediated cell activation and cytotoxicity in target cancer cell lines. This method allows the identification of tumor-reactive TCRs in about two to three weeks, starting from peripheral blood samples of readily available healthy donors.

Keywords: cancer, TCR, tumor antigens, immunotherapy

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Authors: Hakeem Ade Omokayode Idowu

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The extent of the role played by human capabilities developments as well as knowledge management on employees’ performance in the nuclear energy sector of Nigeria remains unclear. This is in view of the important role which human resource capabilities could play in the desire to generate energy using nuclear resources. This study appraised the extent of human resource capabilities available in the nuclear energy sector of Nigeria. It further examined the relationship between knowledge management and employees’ performance in the nuclear energy sector. The study adopted a descriptive research design with a population that comprised all the 1736 members of staff of the selected centres, institutes, and the headquarters of the Nigeria Atomic Energy Commission (NAEC), Nigerian Nuclear Regulatory Authority (NNRA), and Energy Commission of Nigeria (ECN) and a sample size of 332 employees was selected using purposive and convenience sampling techniques. Data collected were subjected to analysis using frequency counts and simple regression. The results showed that majority of the employees perceived that they have to a high extent of availability of knowledge (118, 35.5%), credibility (134, 40.4%), alignment (130, 39.2%), performance (126, 38%) and innovation (138, 41.6%) The result of the hypothesis tested indicated that knowledge management has a positive and significant effect on employees’ performance (Beta weight = 0.336, R2 =0.113, F-value = 41.959, p-value = 0.000< 0.05). The study concluded that human resource capabilities and knowledge management could enhance employee performance within the nuclear energy sector of Nigeria.

Keywords: human resource capabilities, knowledge management, employees productivity, national development

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Authors: Junjie Liu, David Selby, Mark Obermajer, Andy Mort

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The inaugural application of Re-Os dating, which is based on the beta decay of 187Re to 187Os with a long half-life of 41.577 ± 0.12 Byr and initially used for sulphide minerals and organic rich rocks, to petroleum systems was performed on bitumen of the Polaris Mississippi Valley Type Pb-Zn deposit, Canada. To further our understanding of the Re-Os system and its application to petroleum systems, here we present a study on Duvernay Petroleum System, Western Canadian Sedimentary Basin. The Late Devonian Duvernay Formation organic-rich shales are the only source of the petroleum system. The Duvernay shales reached maturation only during the Laramide Orogeny (80 – 35 Ma) and the generated oil migrated short distances into the interfingering Leduc reefs and overlying Nisku carbonates with no or little secondary alteration post oil-generation. Although very low in Re and Os, the asphaltenes of Duvernay-sourced Leduc and Nisku oils define a Laramide Re-Os age. In addition, the initial Os isotope compositions of the oil samples are similar to that of the Os isotope composition of the Duvernay Formation at the time of oil generation, but are very different to other oil-prone intervals of the basin, showing the ability of the Os isotope composition as an inorganic oil-source correlation tool. In summary, the ability of the Re-Os geochronometer to record the timing of oil generation and trace the source of an oil is confirmed in the Re-Os study of Duvernay Petroleum System.

Keywords: Duvernay petroleum system, oil generation, oil-source correlation, Re-Os

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Authors: Nafiseh Mollaei, Reihaneh Kardehi Moghaddam

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In case of Diabetes Mellitus the controlling of insulin is very difficult. This illness is an incurable disease affecting millions of people worldwide. Glucose is a sugar which provides energy to the cells. Insulin is a hormone which supports the absorption of glucose. Fuzzy control strategy is attractive for glucose control because it mimics the first and second phase responses that the pancreas beta cells use to control glucose. We propose two control algorithms a type-1 fuzzy controller and an interval type-2 fuzzy method for the insulin infusion. The closed loop system has been simulated for different patients with different parameters, in present of the food intake disturbance and it has been shown that the blood glucose concentrations at a normoglycemic level of 110 mg/dl in the reasonable amount of time. This paper deals with type 1 diabetes as a nonlinear model, which has been simulated in MATLAB-SIMULINK environment. The novel model, termed the Augmented Minimal Model is used in the simulations. There are some uncertainties in this model due to factors such as blood glucose, daily meals or sudden stress. In addition to eliminate the effects of uncertainty, different control methods may be utilized. In this article, fuzzy controller performance were assessed in terms of its ability to track a normoglycemic set point (110 mg/dl) in response to a [0-10] g meal disturbance. Finally, the development reported in this paper is supposed to simplify the insulin delivery, so increasing the quality of life of the patient.

Keywords: interval type-2, fuzzy controller, minimal augmented model, uncertainty

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Authors: R. M. Noah, N. M. Nasir, M. R. Jais, M. S. S. Wahab, M. H. Abdullah, A. S. S. Raj

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Infectious diseases are getting more difficult to treat due to the resistant strains of bacteria. Current generations of antibiotics are most likely ineffective against multi-drug resistant strains bacteria. Thus, there is an urgent need in search of natural antibiotics in particular from medicinal plants. One of the common medicinal plants, Melaleuca cajuputi, has been reported to possess antibacterial properties. The study was conducted to evaluate and justify the presence of antibacterial activity of Melaleuca cajuputi essential oil (EO) against the multi-drug resistant bacteria. Clinical isolates obtained from the teaching hospital were re-assessed to confirm the exact identity of the bacteria to be tested, namely methicillin-resistant staphylococcus aureus (MRSA), carbapenem-resistant enterobacteriaceae (CRE), and extended-spectrum beta-lactamases producer (ESBLs). A well diffusion method was done to observe the inhibition zones of the essential oil against the bacteria. Minimum inhibitory concentration (MIC) was determined using the microdilution method in 96-well flat microplate. The absorbance was measured using a microplate reader. Minimum bactericidal concentration (MBC) was performed using the agar medium method. The zones of inhibition produced by the EO against MRSA, CRE, and ESBL were comparable to that of generic antibiotics used, gentamicin and augmentin. The MIC and MBC results highlighted the antimicrobial efficacy of the EO. The outcome of this study indicated that the EO of Melaleuca cajuputi had antibacterial activity on the multi-drug resistant bacteria. This finding was eventually substantiated by electron microscopy work.

Keywords: melaleuca cajuputi, antibacterial, resistant bacteria, essential oil

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Authors: Gehan A. Hegazy, Hesham N. Mustafa, Sally A. El Awdan, Marawan AbdelBaset

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Doxorubicin (DOX) is a chemotherapeutic agent used for the treatment of different cancers and its clinical usage is hindered by the oxidative injury-related cardiotoxicity. This work aims to declare if the harmful effects of DOX on the heart can be alleviated with the use of Coenzyme Q10 (CoQ10) or L-carnitine. The study was performed on seventy-two female Wistar albino rats divided into six groups, 12 animals each: Control group; DOX group (10 mg/kg); CoQ10 group (200 mg/kg); L-carnitine group (100 mg/kg); DOX + CoQ10 group; DOX + L-carnitine group. CoQ10 and L-carnitine treatment orally started five days before a single dose of 10 mg/kg DOX that injected intraperitoneally (IP) then the treatment continued for ten days. At the end of the study, serum biochemical parameters of cardiac damage, oxidative stress indices, and histopathological changes were investigated. CoQ10 or L-carnitine showed noticeable effects in improving cardiac functions evidenced reducing serum enzymes as serum interleukin-1 beta (IL-1), tumor necrosis factor alpha (TNF-), leptin, lactate dehydrogenase (LDH), Cardiotrophin-1, Troponin-I and Troponin-T. Also, alleviate oxidative stress, decrease of cardiac Malondialdehyde (MDA), Nitric oxide (NO) and restoring cardiac reduced glutathione levels to normal levels. Both corrected the cardiac alterations histologically and ultrastructurally. With visible improvements in -SMA, vimentin and eNOS immunohistochemical markers. CoQ10 or L-carnitine supplementation improves the functional and structural integrity of the myocardium.

Keywords: CoQ10, doxorubicin, L-Carnitine, cardiotoxicity

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Authors: Narine Ghazaryan, Joana Catarina Macedo, Sara Vaz, Naira Ayvazyan, Elsa Logarinho

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Macrovipera lebetina obtusa (MLO) is a poisonous snake in Armenia. Obtustatin represents the shortest known monomeric disintegrin, isolated from the snake venom of MLO, and is known to specifically inhibit α1β1 integrin. Its oncostatic effect is due to the inhibition of angiogenesis, which likely arises from α1β1 integrin inhibition in the endothelial cells. To explore the therapeutic potential of the MLO snake venom and obtustatin, we studied activity of obtustatin and MLO venom in vitro, by testing their efficacy in human dermal microvascular endothelial cells (HMVEC-D) and in vivo, using chick embryo chorioallantoic membrane assay (CAM assay). Our in vitro results showed that obtustatin in comparison with MLO venom did not exhibit cytotoxic activity in HMVEC-D cells in comparison to MLO venom. But in vivo results have shown that 4µg /embryo (90 µM) of obtustatin inhibited angiogenesis induced by FGF2 by 17% while MLO snake venom induced 22% reduction of the angiogenic index. The concentration of obtustatin in the crude MLO venom was 0.3 nM, which is 300.000 times less than the concentration of the obtustatin itself. Given this enormous difference in concentration, it is likely that some components of the crude venom contribute to the observed anti-angiogenic effect. Hypotheses will be ascertained to justify this action: components in the MLO venom may increase obtustatin efficacy or have independent but synergic anti-angiogenic activities.

Keywords: angiogenesis, alpa1 beta 1 integrin, Macrovipera lebetina obtusa, obtustatin

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Authors: Sergejs Kolesovs, Armands Vigants

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The use of dairy industry by-products and wastewater as a cheap substrate for microalgal growth is gaining recognition. However, the mechanisms of lactose utilization remain understudied, limiting the potential of successful microalgal biomass production using various dairy by-products, such as whey and permeate. The necessity for microalgae to produce a specific enzyme, β-galactosidase, requires the selection of suitable strains. This study focuses on a freshwater microalgal isolate's ability to grow on a semi-synthetic medium supplemented with lactose. After 10 days of agitated cultivation, an axenic microalgal isolate achieved significantly higher biomass production under mixotrophic growth conditions (0.86 ± 0.07 g/L, dry weight) than heterotrophic growth (0.46 ± 0.04 g/L). Moreover, mixotrophic cultivation had significantly higher biomass production compared to photoautotrophic growth (0.67 ± 0.05 g/L). The activity of β-galactosidase was detected in both supernatant and microalgal biomass under mixotrophic and heterotrophic growth conditions, showing the potential of extracellular and intracellular mechanisms of enzyme production. However, the main limiting factor in this study was the increase of pH values during the cultivation, significantly reducing the activity of the β-galactosidase enzyme after 3rd day of cultivation. It highlights the need for stricter control of growth parameters to ensure the enzyme's activity. Further research will assess the isolate's suitability for dairy by-product bioconversion and biomass composition.

Keywords: microalgae, lactose, whey, permeate, beta-galactosidase, mixotrophy, heterotrophy

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Authors: Maha Z. Rizk, Sami A. Fattah, Heba M. Darwish, Sanaa A. Ali, Mai O. Kadry

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The increasing use of nanomaterials in consumer and industrial products has aroused global concern regarding their fate in biological systems resulting in demand for parallel risk assessment. The objective of this study is investigating either the effect of individual or combined doses of idebenone, carnosine and vitamin E on amelioration of some biochemical indices of nano sized titanium dioxide (TiO2 NPS) induced metabolic disorders in mice liver. TiO2-NPS was administered in an oral dose of 150 mg/kg for consecutive 14 days followed by oral daily doses of the aforementioned antioxidants for 1 month. TiO2-NPS induced a significant elevation in serum level of ALT and AST, hepatic inflammatory markers (tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6)) and increased the percent of DNA damage which was assessed by COMET assay in addition to the apoptotic marker Caspase-3. Moreover, mRNA gene expression observed by RT-PCR showed a significant overexpression in nuclear factor relation-2 (Nrf2), nuclear factor kappa beta (NF-Kβ) and the apoptotic factor (bax), and a significant down-regulation in the antiapoptotic factor (bcl2) level. In conclusion, idebenone, carnosine and vitamin E ameliorated the deviated parameters with a variable degree with the most pronounced role in alleviating the hazardous effect of TiO2 NPS toxicity following the combination regimen.

Keywords: idebenone, carnosine, vitamin E, TiO2 NPS, caspase-3, NrF2, NF-KB

Procedia PDF Downloads 357

Authors: Fahmi Hassan, Noorizan Abdul Aziz, Yahaya Hassan, Hazlinda Abu Hassan

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Sepsis incidence in critical care settings is a major problem in health care. Extended antibiotic infusion is thought to be superior to traditional dosing especially when treating critically ill patients with sepsis. We compared clinical outcomes of critically ill patients with sepsis receiving 30-minute meropenem infusion and three-hour meropenem infusion. A retrospective case-control study was conducted among septic patients treated with meropenem infusion in ICUs of three hospitals. Patients included in the study received either extended or standard meropenem infusion as per the practice of individual settings. Outcomes and clinical data were retrospectively collected from the electronic databases and patients’ files. A total of 108 patients received extended meropenem infusion while another 117 patients received standard meropenem infusion. Patients receiving the extended meropenem infusion were found to have a significantly lower shorter length of hospital and ICU stay. It was also found that among those receiving extended meropenem infusion, 54.7% (64/117) had a reduction of SAPS II score, while only 44% (48/108) of patients receiving standard meropenem infusion had reduced scores. This study will strengthen the evidence in using extended meropenem infusion as a standard practice in critical care settings. As this is the first study of its kind done in Malaysia, it proves that prolonged meropenem infusion may be beneficial to critically ill patients with sepsis. However, randomized clinical trials with large sample size should be carried out in local settings in order to minimize other confounders that may influence with the result of the study.

Keywords: antibiotics, beta lactams, critical care, extended infusion, meropenem

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Authors: Akeem Akinboro, Bala Alhaj Kegun

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Haemoglobinopathy is a genetic disorder that has the potentiality to cause death of individuals in whom both the alpha (α) and beta (β) globin chains of the haemoglobin molecule are defective due to mutations in their genes. The haemoglobin genotype variants among some residents of Niger state, Nigeria, were determined using the secondary data available at Bida, Minna and Kotangora general hospitals of the state. A total of 1,639 data, representing 434, 655 and 550, collected from the outside patients who visited the medical laboratory units of the three general hospitals, respectively, over five years period (2015-2020) were analyzed into gene frequency, sex and age to determine their haemoglobin genotypes status. More males (51.6 – 58.7%) than females (41.3 – 48.4%) visited the three hospitals during the period covered and most of the patients were between 11 - 20 years old. The frequency of HbA allele in the human population was 0.72, 0.65, 0.68 for Bida, Minna and Kotangora, respectively, while it was 0.25, 0.29 and 0.28 for HbS allele. The HbC allele was prevalent at 0.03, 0.06 and 0.05 among the human population in Bida, Minna and Kotangora cities of Niger state. In overall, the prevalence of HbA, HbS and HbC alleles in Niger state of Nigeria was 0.68, 0.28 and 0.05. Minna being the capital city of Niger state and the most populous among the three cities in the state seems to have influx of more people who are carriers of abnormal haemoglobin genotypes which has resulted to higher frequency of HbS and HbC than those of the other two cities in this study. These results show that the pattern of haemoglobin genotypes frequency of Kontagora could be a prediction for the whole of Niger state. It is therefore necessary and important to take screening of blood for haemoglobin genotype serious among intending couples to prevent and reduce the possibility of having increase in the number of people with abnormal haemoglobin genotypes in the state.

Keywords: haemoglobin, genotype, niger state, gene frequency, general hospitals

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Authors: Levent Taylan Ozgur Yildirim, Qihao Qian, John Yilin Wang

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A critical review of assessments of geological carbon dioxide (CO2) storage resources in Pennsylvania and the surrounding region was completed with a focus on the studies of Midwest Regional Carbon Sequestration Partnership (MRCSP), United States Department of Energy (US-DOE), and United States Geological Survey (USGS). Pennsylvania Geological Survey participated in the MRCSP Phase I research to characterize potential storage formations in Pennsylvania. The MRCSP’s volumetric method estimated ~89 gigatonnes (Gt) of total CO2 storage resources in deep saline formations, depleted oil and gas reservoirs, coals, and shales in Pennsylvania. Meanwhile, the US-DOE calculated storage efficiency factors using log-odds normal distribution and Monte Carlo sampling, revealing contingent storage resources of ~18 Gt to ~20 Gt in deep saline formations, depleted oil and gas reservoirs, and coals in Pennsylvania. Additionally, the USGS employed Beta-PERT distribution and Monte Carlo sampling to determine buoyant and residual storage efficiency factors, resulting in 20 Gt of contingent storage resources across four storage assessment units in Appalachian Basin. However, few studies have explored CO2 storage resources in shales in the region, yielding inconclusive findings. This article provides a critical and most up to date review and analysis of geological CO2 storage resources in Pennsylvania and the region.

Keywords: carbon capture and storage, geological CO2 storage, pennsylvania, appalachian basin

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Authors: Sunil Kumar, Rajesh Sharma

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Toxic epidermal necrolysis, pruritis, rashes, lichen planus like eruption, hyper pigmentation of skin are rare toxic effects of choloroquine used over a long time. Skin and mucus membrane hyper pigmentation is generally of a bluish black or grayish color and irreversible after discontinuation of the drug. According to Ayurveda, Dushivisha is the name given to any poisonous substance which is not fully endowed with the qualities of poison by nature (i.e. it acts as an impoverished or weak poison) and because of its mild potency, it remains in the body for many years causing various symptoms, one among them being discoloration of skin.The objective of this case report is to investigate the effect of Ayurvedic management of chloroquine induced hyper-pigmentation on the line of treatment of Dushivisha. Case Report: A 26-year-old female was suffering from hyper-pigmentation of the skin over the neck, forehead, temporo-mandibular joints, upper back and posterior aspect of both the arms since 8 years had history of taking Chloroquine came to Out Patient Department of National Institute of Ayurveda, Jaipur, India in Jan. 2015. The routine investigations (CBC, ESR, Eosinophil count) were within normal limits. Punch biopsy skin studied for histopathology under hematoxylin and eosin staining showed epidermis with hyper-pigmentation of the basal layer. In the papillary dermis as well as deep dermis there were scattered melanophages along with infiltration by mononuclear cells. There was no deposition of amyloid-like substances. These histopathological findings were suggestive of Chloroquine induced hyper-pigmentation. The case was treated on the line of treatment of Dushivisha and was given Vamana and Virechana (therapeutic emesis and purgation) every six months followed by Snehana karma (oleation therapy) with Panchatikta Ghrit and Swedana (sudation). Arogyavardhini Vati -1 g, Dushivishari Vati 500 mg, Mahamanjisthadi Quath 20 ml were given twelve hourly and Aragwadhadi Quath 25 ml at bed time orally. The patient started showing lightening of the pigments after six months and almost complete remission after 12 months of the treatment. Conclusion: This patient presented with the Dushivisha effect of Chloroquineandwas administered two relevant procedures from Panchakarma viz. Vamana and Virechana. Both Vamana and Virechanakarma here referred to Shodhana karma (purification procedures) eliminates accumulated toxins from the body. In this process, oleation dislodge the toxins from the tissues and sudation helps to bring them to the alimentary tract. The line of treatment did not target direct hypo pigmentary effects; rather aimed to eliminate the Dushivisha. This gave promising results in this condition.

Keywords: Ayurveda, chloroquine, Dushivisha, hyper-pigmentation

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Authors: Polina Prokopovich

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Disease-modifying osteoarthritis drugs (DMOADs) are a new therapeutic class for OA, preventing or inhibiting OA development. Unfortunately, none of the DMOADs have been clinically approved due to their poor therapeutic effects in clinical trials. The joint environment has played a role in the poor clinical performance of these drugs by limiting the amount of drug effectively delivered as well as the time that the drug spends within the joint space. The current study aims to enhance the cartilage uptake and retention time of the DMOADs-model (licofelone), which showed a significant therapeutic effect against OA progression and is currently in phase III. Licofelone will be covalently conjugated to the hydrolysable, cytocompatible, and cationic poly beta-amino ester polymers (PBAE). The cationic polymers (A16 and A87) can be electrostatically attached to the negatively charged cartilage component (glycosaminoglycan), which will increase the drug penetration through the cartilage and extend the drug time within the cartilage. In the cartilage uptake and retention time studies, an increase of 18 to 37 times of the total conjugated licofelone to A87 and A16 was observed when compared to the free licofelone. Furthermore, the conjugated licofelone to A87 was detectable within the cartilage at 120 minutes, while the free licofelone was not detectable after 60 minutes. Additionally, the A87-licofelone conjugate showed no effect on the chondrocyte viability. In conclusion, the cationic A87 and A16 polymers increased the percentage of licofelone within the cartilage, which could potentially enhance the therapeutic effect and pharmacokinetic performance of licofelone or other DMOADs clinically.

Keywords: PBAE, cartilage., osteoarthritis, injectable biomaterials, drug delivery

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Authors: Tien S. H. Pham, Peter J. Mahon, Aimin Yu

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The detection of drug molecules by voltammetry has attracted great interest over the past years. However, many drug molecules exhibit poor electrochemical signals at common electrodes which result in low sensitivity in detection. An efficient way to overcome this problem is to modify electrodes with functional materials. Since discovered in 2004, graphene (or reduced graphene oxide) has emerged as one of the most studied two-dimensional carbon materials in condensed matter physics, electrochemistry, and so on due to its exceptional physicochemical properties. Additionally, the continuous development of technology has opened the new window for the successful fabrications of many novel graphene-based nanomaterials to serve in electrochemical analysis. This research aims to synthesize and characterize gold nanoparticle coated beta-cyclodextrin functionalized reduced graphene oxide (Au NP–β-CD–RGO) nanocomposites with highly conductive and strongly electro-catalytic properties as well as excellent supramolecular recognition abilities for the modification of electrodes. The electrochemical responses of ciprofloxacin at the as-prepared nanocomposite modified electrode was effectively amplified was much higher in comparison with that at the bare electrode. The linear concentration range was from 0.01 to 120 µM, with a detection limit of 2.7 nM using differential pulse voltammetry. Thus, Au NP–β-CD–RGO nanocomposite has great potential as an ideal material to construct sensitive sensors for the electrochemical determination of ciprofloxacin or similar antibacterial drugs in the future based on its excellent stability, selectivity, and reproducibility.

Keywords: Au nanoparticles, β-CD, ciprofloxacin, electrochemical determination, graphene based nanomaterials

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Authors: Shenaz Ahmed, Hussain Jafri, Muhammed Faran, Wajeeha Naseer Ahmed, Yasmin Rashid, Yasmin Ehsan, Shabnam Bashir, Mushtaq Ahmed

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Low uptake of cascade screening for βeta-Thalassaemia Major (β-TM) in the ‘Punjab Thalassaemia Prevention Project’ (PTPP) in Pakistan led to the development of a ‘decision support intervention for relatives’ (DeSIRe). This paper presents the experiences of relatives of children with β-TM of the DeSIRe following its use by PTPP field officers in routine clinical practice. Fifty-four semi-structured qualitative interviews were conducted (April to June 2021) with relatives in seven cities in the Punjab province (Lahore, Sheikhupura, Nankana Sahab, Kasur, Gujranwala, Multan, and Faisalabad). Thematic analysis shows that participants were satisfied with the content of the DeSIRe and its delivery by the field officers in a family meeting. They understood the main purpose of the DeSIRe was to improve their knowledge of β-TM and its inheritance, to enable them to make decisions about thalassemia carrier testing, particularly before marriage. While participants raised concerns about the stigma of testing positive, they believed the DeSIRe was an appropriate intervention, which supported relatives to make informed decisions. Our findings show the DeSIRe is appropriate for use by healthcare professionals in routine practice in a low-middle income country and has the potential to facilitate shared decision-making about cascade screening for thalassemia. Further research is needed to prove the efficacy of the DeSIRe.

Keywords: thalassemia, Pakistan, cascade screening, decision support

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Authors: M. Mathuthu, N. N. Gaxela, R. Y. Olobatoke

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A study was carried out to assess the heavy metal and radionuclide concentrations of water from the waste water treatment plant in Mafikeng Local Municipality to evaluate treatment efficiency. Ten water samples were collected from various stages of water treatment which included sewage delivered to the plant, the two treatment stages and the effluent and also the community. The samples were analyzed for heavy metal content using Inductive Coupled Plasma Mass Spectrometer. Gross α/β activity concentration in water samples was evaluated by Liquid Scintillation Counting whereas the concentration of individual radionuclides was measured by gamma spectroscopy. The results showed marked reduction in the levels of heavy metal concentration from 3 µg/L (As)–670 µg/L (Na) in sewage into the plant to 2 µg/L (As)–170 µg/L (Fe) in the effluent. Beta activity was not detected in water samples except in the in-coming sewage, the concentration of which was within reference limits. However, the gross α activity in all the water samples (7.7-8.02 Bq/L) exceeded the 0.1 Bq/L limit set by World Health Organization (WHO). Gamma spectroscopy analysis revealed very high concentrations of 235U and 226Ra in water samples, with the lowest concentrations (9.35 and 5.44 Bq/L respectively) in the in-coming sewage and highest concentrations (73.8 and 47 Bq/L respectively) in the community water suggesting contamination along water processing line. All the values were considerably higher than the limits of South Africa Target Water Quality Range and WHO. However, the estimated total doses of the two radionuclides for the analyzed water samples (10.62 - 45.40 µSv yr-1) were all well below the reference level of the committed effective dose of 100 µSv yr-1 recommended by WHO.

Keywords: gross α/β activity, heavy metals, radionuclides, 235U, 226Ra, water sample

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Authors: Soomal Hamza, Uzma Imran

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Organochlorine pesticides bio-accumulate into the fat of fish, birds, and animals through which it enters the human food cycle. Due to their persistence and stability in the environment, many health impacts are associated with them, most of which are carcinogenic in nature. In this study, the level of organochlorine pesticides has been detected in Keenjhar Lake and remediated using Rhizoremediation technique. 14 OC pesticides namely, Aldrin, Deldrin, Heptachlor, Heptachlor epoxide, Endrin, Endosulfun I and II, DDT, DDE, DDD, Alpha, Beta, Gamma BHC and two plants namely, Water Hyacinth and Slvinia Molesta were used in the system using pot experiment which processed for 11 days. A consortium was inoculated in both plants to increase its efficiency. Water samples were processed using liquide-liquid extraction. Sediments and roots samples were processed using Soxhlet method followed by clean-up and Gas Chromatography. Delta-BHC was the predominantly found in all samples with mean concentration (ppb) and standard deviation of 0.02 ± 0.14, 0.52 ± 0.68, 0.61 ± 0.06, in Water, Sediments and Roots samples respectively. The highest levels were of Endosulfan II in the samples of water, sediments and roots. Water Hyacinth proved to be better bioaccumulaor as compared to Silvinia Molesta. The pattern of compounds reduction rate by the end of experiment was Delta-BHC>DDD > Alpha-BHC > DDT> Heptachlor> H.Epoxide> Deldrin> Aldrin> Endrin> DDE> Endosulfun I > Endosulfun II. Not much significant difference was observed between the pots with the consortium and pots without the consortium addition. Phytoremediation is a promising technique, but more studies are required to assess the bioremediation potential of different aquatic plants and plant-endophyte relationship.

Keywords: aquatic plant, bio remediation, gas chromatography, liquid liquid extraction

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Authors: Lebogang L. R. Mphahlele, Bruce B. Sithole

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Chicken meat is the highest consumed meat in south Africa, with a per capita consumption of >33 kg yearly. Hence, South Africa produces over 250 million kg of waste chicken feathers each year, the majority of which is landfilled or incinerated. The discarded feathers have caused environmental pollution and natural protein resource waste. Therefore, the valorisation of waste chicken feathers is measured as a more environmentally friendly and cost-effective treatment. Feather contains 91% protein, the main component being beta-keratin, a fibrous and insoluble structural protein extensively cross linked by disulfide bonds. Keratin is usually converted it into nanofibers via electrospinning for a variety of applications. keratin nanofiber composites have many potential biomedical applications for their attractive features, such as high surface-to-volume ratio and very high porosity. The application of nanofibers in the biomedical wound dressing requires antimicrobial properties for materials. One approach is incorporating inorganic nanoparticles, among which silver nanoparticles played an important alternative antibacterial agent and have been studied against many types of microbes. The objective of this study is to combine synthetic polymer, chicken feather keratin, and antibacterial nanoparticles to develop novel electrospun antibacterial nanofibrous composites for possible wound dressing application. Furthermore, this study will converting a two-dimensional electrospun nanofiber membrane to three-dimensional fiber networks that resemble the structure of the extracellular matrix (ECM)

Keywords: chicken feather keratin, nanofibers, nanoparticles, nanocomposites, wound dressing

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Authors: Lydia Foucan, Christine Rambhojan, Rachel Billy, Christophe Armand, Carl-Thony Michel, Jean-Marc Lacorte, Laurent Larifla

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Leptin, an adipocyte-derived hormone, modulates insulin secretion and action via the leptin receptor (LEPR) that is expressed in pancreatic beta cells, adipose tissue, and muscle. Several polymorphisms have been described in the human LEPR gene including p.K109R (rs1137100), p.Q223R (rs1137101) and p.K656N (rs1805094) polymorphisms. The role of these polymorphisms is not yet studied in Guadeloupian population. Our aim was to explore the association of LEPR polymorphisms (K109R, Q223R and K656N) with leptin levels and obesity in non-diabetic Afro-Caribbean subjects. Genotypic analysis of the three polymorphisms was performed in 425 subjects using TaqMan and KASPar Assays. Serum leptin was measured with ELISA kits Biovendor® (RD191001100). Logistic regressions were used for assessment of statistical associations. Mean age was 47.6 ± 12.7 years. Among the participants, 238 (56 %) were women, 124 (30%) were obese and 155 (36.5%) had abdominal obesity. Carriers of LEPR K656N rs1805094 rare allele had significant higher frequencies of obesity (P = 0.007), abdominal obesity (P = 0.004) and metabolic syndrome (P = 0.021) but mean leptin level was not significantly different between both groups (P = 0.075). Odds ratios, adjusted for age and sex associated with presence of rs1805094 rare allele were 1.8 (1.1-2.9), P = 0.012 for obesity, 2.0 (1.2-3.3), P = 0.008 for abdominal obesity and 1.8 (1.1-3.0), P = 0.031 for MetS. No significant association was found with K109R, Q223R. These findings suggest that the K656N polymorphism (but not the K109R or Q223R polymorphism) of LEPR is associated with obesity, abdominal obesity and metabolic syndrome in this Afro-Caribbean non-diabetic population.

Keywords: Afro-Caribbean, leptin levels, leptin receptor gene polymorphisms, obesity

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Authors: Arunporn Itharat, Kamonmas Srikwan, Srisopa Ruangnoo, Pakakrong Thongdeeying

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Background: The rhizomes of Smilax glabra (SG) has long been used in Traditional Chinese and Thai herbal medicine to treat a variety of infectious diseases and immunological disorders. Objective: To investigate the in vitro anti-allergic activities of crude extracts and pure isolated flavonoid compounds from SG by determination of inhibitory effects on antigen-induced release of β-hexosaminidase from RBL-2H3 cells. Methods: The in vitro inhibitory effects of crude aqueous and organic extracts on beta-hexosaminidase release in RBL-2H3 cells were evaluated as an in vitro indication of possible anti-allergic activity in vivo. Bioassay-guided fractionation of extracts was used to isolate flavonoid compounds from the ethanolic extracts. Results: The 95% and 50% ethanolic extracts of SG showed remarkably high anti-allergic activity, with IC50 values of 5.74 ± 2.44 and 23.54 ± 4.75 μg/ml, much higher activity than that for Ketotifen (IC50 58.90 μM). The water extract had negligible activity (IC50 > 100 μg/ml). The two isolated flavonols, Engeletin and Astilbin, showed weak anti-allergic activity, IC50 values 97.46 ± 2.04 and > 100 μg/ml, respectively. Conclusions: The 95% and 50% ethanolic extracts of SG showed strong anti-allergic activity but two flavonol constituents did not show any significant anti-allergic activity. These findings suggest that a combination of effects of various phytochemicals in crude extracts used in traditional medicine are responsible for the purported anti-allergic activity of SG herbal preparations. The plethora of constituents in crude extracts, as yet unidentified, are likely to be acting synergistically to account for the strong observed anti-allergic in vitro activity.

Keywords: Smilax glabra, anti-allergic activity, RBL-2H3 cells, flavonoid compounds

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Authors: Alexander N. Savostyanov, Tatiana A. Dolgorukova, Elena A. Esipenko, Mikhail S. Zaleshin, Margherita Malanchini, Anna V. Budakova, Alexander E. Saprygin, Tatiana A. Golovko, Yulia V. Kovas

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EEG correlates of mathematical and trait anxiety level were studied in 52 healthy Russian-speakers during execution of error-recognition tasks with lexical, arithmetic and algebraic conditions. Event-related spectral perturbations were used as a measure of brain activity. The ERSP plots revealed alpha/beta desynchronizations within a 500-3000 ms interval after task onset and slow-wave synchronization within an interval of 150-350 ms. Amplitudes of these intervals reflected the accuracy of error recognition, and were differently associated with the three conditions. The correlates of anxiety were found in theta (4-8 Hz) and beta2 (16-20 Hz) frequency bands. In theta band the effects of mathematical anxiety were stronger expressed in lexical, than in arithmetic and algebraic condition. The mathematical anxiety effects in theta band were associated with differences between anterior and posterior cortical areas, whereas the effects of trait anxiety were associated with inter-hemispherical differences. In beta1 and beta2 bands effects of trait and mathematical anxiety were directed oppositely. The trait anxiety was associated with increase of amplitude of desynchronization, whereas the mathematical anxiety was associated with decrease of this amplitude. The effect of mathematical anxiety in beta2 band was insignificant for lexical condition but was the strongest in algebraic condition. EEG correlates of anxiety in theta band could be interpreted as indexes of task emotionality, whereas the reaction in beta2 band is related to tension of intellectual resources.

Keywords: EEG, brain activity, lexical and numerical error-recognition tasks, mathematical and trait anxiety

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Authors: Samad Lotfollahzadeh

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To evaluate the effect of intramuscular administration of vitamin A during dry period in pregnant dairy cows, which already received it in their daily ration, on vitamin A status of neonatal calves, a total of 30 cows were randomly selected and divided to two main groups; treatment and control group. Animals in the treatment group were subdivided into two groups. Single intramuscular injection of 2000000 IU vitamin A; was carried in 10 dairy cows at 7 months of pregnancy (group 1). In the second group of treated animals (10 cows) the injection was performed in 8 months of pregnancy (group 2). Ten pregnant dairy cows were received saline injection as placebo and selected as the control group. Blood samples were collected from experimental dairy cows at 7 and 8 months of pregnancy as well as their newborn calves’ pre and after colostrum intake. There was no significant difference between vitamin A and β- carotene concentration of dairy cows of three groups in two last months of pregnancy (P > 0.05). Vitamin A concentration of calves of two treatment groups before and after receiving of colostrum were significantly higher than that in the control group (P < 0.05). There was no significant difference between serum concentrations of vitamin A in calves of two treated groups (P > 0.05). β- Carotene concentration of serum samples of dairy cows and neonatal calves of three groups were not significantly different as compared with together. From results of the present study it can be concluded that daily supplementation of vitamin A in late pregnancy in dairy cows may not compensate the calves need for vitamin A and single injection of this vitamin A during dry either in 7 or 8 months of pregnancy can significantly increase level of vitamin A in their colostrum and neonatal calves.

Keywords: dry cow, beta carotene, newborn calves, vitamin A, dry cows

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Authors: Frederick Huie, Lauren Fusfeld, William Burchenal, Scott Howell, Alyssa McVey, Thomas F. Goss

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Alzheimer’s Disease (AD) is a degenerative brain disease characterized by memory loss and cognitive decline that presents a substantial economic burden for patients and health insurers in the US. This study evaluates the payer budget impact of the DISCERN™ test in the diagnosis and management of patients with symptoms of dementia evaluated for AD. DISCERN™ comprises three assays that assess critical factors related to AD that regulate memory, formation of synaptic connections among neurons, and levels of amyloid plaques and neurofibrillary tangles in the brain and can provide a quicker, more accurate diagnosis than tests in the current diagnostic pathway (CDP). An Excel-based model with a three-year horizon was developed to assess the budget impact of DISCERN™ compared with CDP in a Medicare Advantage plan with 1M beneficiaries. Model parameters were identified through a literature review and were verified through consultation with clinicians experienced in diagnosis and management of AD. The model assesses direct medical costs/savings for patients based on the following categories: •Diagnosis: costs of diagnosis using DISCERN™ and CDP. •False Negative (FN) diagnosis: incremental cost of care avoidable with a correct AD diagnosis and appropriately directed medication. •True Positive (TP) diagnosis: AD medication costs; cost from a later TP diagnosis with the CDP versus DISCERN™ in the year of diagnosis, and savings from the delay in AD progression due to appropriate AD medication in patients who are correctly diagnosed after a FN diagnosis.•False Positive (FP) diagnosis: cost of AD medication for patients who do not have AD. A one-way sensitivity analysis was conducted to assess the effect of varying key clinical and cost parameters ±10%. An additional scenario analysis was developed to evaluate the impact of individual inputs. In the base scenario, DISCERN™ is estimated to decrease costs by $4.75M over three years, equating to approximately $63.11 saved per test per year for a cohort followed over three years. While the diagnosis cost is higher with DISCERN™ than with CDP modalities, this cost is offset by the higher overall costs associated with CDP due to the longer time needed to receive a TP diagnosis and the larger number of patients who receive a FN diagnosis and progress more rapidly than if they had received appropriate AD medication. The sensitivity analysis shows that the three parameters with the greatest impact on savings are: reduced sensitivity of DISCERN™, improved sensitivity of the CDP, and a reduction in the percentage of disease progression that is avoided with appropriate AD medication. A scenario analysis in which DISCERN™ reduces the utilization for patients of computed tomography from 21% in the base case to 16%, magnetic resonance imaging from 37% to 27% and cerebrospinal fluid biomarker testing, positive emission tomography, electroencephalograms, and polysomnography testing from 4%, 5%, 10%, and 8%, respectively, in the base case to 0%, results in an overall three-year net savings of $14.5M. DISCERN™ improves the rate of accurate, definitive diagnosis of AD earlier in the disease and may generate savings for Medicare Advantage plans.

Keywords: Alzheimer’s disease, budget, dementia, diagnosis.

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Authors: Ghadeer Jalloul, Nour Hijazi, Cassia Boyadjian, Hussein Awala, Mohammad N. Ahmad, ‎Ahmad Albadarin

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In this study, we applied Fe-sensitized TiO₂ supported over embryonic Beta zeolite (BEA) zeolite ‎for the photocatalytic degradation of Tetracycline (TC) antibiotic under visible light. Four different ‎samples having 20, 40, 60, and 100% w/w as a ratio of TiO₂/BEA were prepared. The ‎immobilization of solgel TiO₂ (33 m²/g) over BEA (390 m²/g) increased its surface area to (227 ‎m²/g) and enhanced its adsorption capacity from 8% to 19%. To expand the activity of TiO₂ ‎photocatalyst towards the visible light region (λ>380 nm), we explored two different metal ‎sensitization techniques with Iron ions (Fe³⁺). In the ion-exchange method, the substitutional cations ‎in the zeolite in TiO₂/BEA were exchanged with (Fe³⁺) in an aqueous solution of FeCl₃. In the ‎doping technique, solgel TiO₂ was doped with (Fe³⁺) from FeCl₃ precursor during its synthesis and ‎before its immobilization over BEA. (Fe-TiO₂/BEA) catalysts were characterized using SEM, XRD, ‎BET, UV-VIS DRS, and FTIR. After testing the performance of the various ion-exchanged catalysts ‎under blue and white lights, only (Fe-TiO₂/BEA 60%) showed better activity as compared to pure ‎TiO₂ under white light with 100 ppm initial catalyst concentration and 20 ppm TC concentration. As ‎compared to ion-exchanged (Fe-TiO₂/BEA), doped (Fe-TiO₂/BEA) resulted in higher photocatalytic ‎efficiencies under blue and white lights. The 3%-Fe-doped TiO₂/BEA removed 92% of TC ‎compared to 54% by TiO₂ under white light. The catalysts were also tested under real solar ‎irradiations. This improvement in the photocatalytic performance of TiO₂ was due to its higher ‎adsorption capacity due to BEA support combined with the presence of Iron ions that enhance the ‎visible light absorption and minimize the recombination effect by the charge carriers. ‎

Keywords: Tetracycline, photocatalytic degradation, immobilized TiO₂, zeolite, iron-doped TiO₂, ion-exchange

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