Search results for: whey protein isolated

Authors: Sultan Z. Mahmud, Emily C. Graff, Adil Bashir

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Phosphoprotein enriched in astrocytes 15 kDa (PEA-15) is a multifunctional adapter protein which is associated with the regulation of apoptotic cell death. Recently it has been discovered that PEA-15 is crucial in normal neurodevelopment of domestic cats, a gyrencephalic animal model, although the exact function of PEA-15 in neurodevelopment is unknown. This study investigates how PEA-15 affects the blood-brain barrier (BBB) permeability in cat brain, which can cause abnormalities in tissue metabolite and energy supplies. Severe polymicrogyria and microcephaly have been observed in cats with a loss of function PEA-15 mutation, affecting the normal neurodevelopment of the cat. This suggests that the vital role of PEA-15 in neurodevelopment is associated with gyrification. Neurodevelopment is a highly energy demanding process. The mammalian brain depends on glucose as its main energy source. PEA-15 plays a very important role in glucose uptake and utilization by interacting with phospholipase D1 (PLD1). Mitochondria also plays a critical role in bioenergetics and essential to supply adequate energy needed for neurodevelopment. Cerebral blood flow regulates adequate metabolite supply and recent findings also showed that blood plasma contains mitochondria as well. So the BBB can play a very important role in regulating metabolite and energy supply in the brain. In this study the blood-brain permeability in cat brain was measured using MRI magnetization transfer (MT) effect on the perfusion signal. Perfusion is the tissue mass normalized supply of blood to the capillary bed. Perfusion also accommodates the supply of oxygen and other metabolites to the tissue. A fraction of the arterial blood can diffuse to the tissue, which depends on the BBB permeability. This fraction is known as water extraction fraction (EF). MT is a process of saturating the macromolecules, which has an effect on the blood that has been diffused into the tissue while having minimal effect on intravascular blood water that has not been exchanged with the tissue. Measurement of perfusion signal with and without MT enables to estimate the microvascular blood flow, EF and permeability surface area product (PS) in the brain. All the experiments were performed with Siemens 7T Magnetom with 32 channel head coil. Three control cats and three PEA-15 mutant cats were used for the study. Average EF in white and gray matter was 0.9±0.1 and 0.86±0.15 respectively, perfusion in white and gray matter was 85±15 mL/100g/min and 97±20 mL/100g/min respectively, PS in white and gray matter was 201±25 mL/100g/min and 225±35 mL/100g/min respectively for control cats. For PEA-15 mutant cats, average EF in white and gray matter was 0.81±0.15 and 0.77±0.2 respectively, perfusion in white and gray matter was 140±25 mL/100g/min and 165±18 mL/100g/min respectively, PS in white and gray matter was 240±30 mL/100g/min and 259±21 mL/100g/min respectively. This results show that BBB is compromised in PEA-15 mutant cat brain, where EF is decreased and perfusion as well as PS are increased in the mutant cats compared to the control cats. This findings might further explain the function of PEA-15 in neurodevelopment.

Keywords: BBB, cat brain, magnetization transfer, PEA-15

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Authors: Benedicta N. Nkeh-Chungag, Constance R. Sewani-Rusike, Isaac M. Malema, Daniel T. Goon, Oladele V. Adeniyi, Idowu A. Ajayi

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Background: Childhood and adolescent obesity is an important predictor of adult cardiometabolic diseases. Current data on age- and gender-specific cardiometabolic risk factors are lacking in the peri-urban Eastern Cape Province, South Africa. However, such information is important in designing innovative strategies to promote healthy living among children and adolescents. The purpose of this pilot study was to compare and determine the extent of cardiometabolic risk factors between samples of lean and overweight/obese adolescent population in a peri-urban township of South Africa. Methods: In this case-control study, age-matched, non-pregnant and non-lactating female adolescents consisting of equal number of cases (50 overweight/obese) and control (50 lean) participated in the study. Fasting venous blood samples were obtained for total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglyceride (Trig), highly sensitive C-reactive protein (hsCRP) and blood sugar. Anthropometric measurements included weight, height, waist and hip circumferences. Body mass index was calculated. Blood pressure was measured; and metabolic syndrome was assessed using appropriate diagnostic criteria for children and adolescents. Results: Of the 76 participants with complete data, 12/38 of the overweight/obese and 1/38 of the lean group met the criteria for adolescent metabolic syndrome. All cardiometabolic risk factors were elevated in the overweight/obese group compared with the lean group: low HDL-C (RR = 2.21), elevated TC (RR = 1.23), elevated LDL-C (RR = 1.42), elevated Trig (RR = 1.73), and elevated hsCRP (RR = 1.9). There were significant atherosclerotic indices among the overweight/obese group compared with the lean group: TC/HDL and LDL/HDL (2.99±0.91 vs 2.63±0.48; p=0.016 and 1.73±0.61 vs 1.41±0.46; p= 0.014, respectively). Conclusion: There are multiple cardiometabolic risk factors among the overweight/obese female adolescent group compared with lean adolescent group in the study. Female adolescent who are overweight and obese have higher relative risks of developing cardiometabolic diseases compared with their lean counterparts in the peri-urban Mthatha, South Africa. School health programme focusing on promoting physical exercise, healthy eating and keeping appropriate weight are needed in the country.

Keywords: adolescents, cardiometabolic risk factors, obesity, peri-urban South Africa

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Authors: Md. M. Hossain, Regan Roat, Jenica Christopherson, Colette Free, Zhiguang Guo

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Long noncoding RNA (lncRNA) mediated post-transcriptional gene regulation, and their epigenetic landscapes have been shown to be involved in many human diseases. However, their regulation in diabetes through governing islet’s β-cell function and survival needs to be elucidated. Due to the technical and ethical constraints, it is difficult to study their role in β-cell function and survival in human under in vivo condition. In this study, humanized mice have been developed through transplanting human pancreatic islet under the kidney capsule of NOD.SCID mice and induced β-cell death leading to diabetes condition to study lncRNA mediated regulation. For this, human islets from 3 donors (3000 IEQ, purity > 80%) were transplanted under the kidney capsule of STZ induced diabetic NOD.scid mice. After at least 2 weeks of normoglycecemia, lymphocytes from diabetic NOD mice were adoptively transferred and islet grafts were collected once blood glucose reached > 200 mg/dl. RNA from human donor islets, islet grafts from humanized mice with either adoptive lymphocyte transfer (ALT) or PBS control (CTL) were ribodepleted; barcoded fragment libraries were constructed and sequenced on the Ion Proton sequencer. lncRNA expression in isolated human islets, islet grafts from humanized mice with and without induced β-cell death and their regulation in human islets function in vitro under glucose challenge, cytokine mediated inflammation and induced apoptotic condition were investigated. Out of 3155 detected lncRNAs, 299 that highly expressed in islets were found to be significantly downregulated and 224 upregulated in ALT compared to CTL. Most of these are found to be collocated within 5 kb upstream and 1 kb downstream of 788 up- and 624 down-regulated mRNAs. Genomic Regions Enrichment of Annotations Analysis revealed deregulated and collocated genes are related to pancreas endocrine development; insulin synthesis, processing, and secretion; pancreatitis and diabetes. Many of them, that found to be located within enhancer domains for islet specific gene activity, are associated to the deregulation of known islet/βcell specific transcription factors and genes that are important for β-cell differentiation, identity, and function. RNA sequencing analysis revealed aberrant lncRNA expression which is associated to the deregulated mRNAs in β-cell function as well as in molecular pathways related to diabetes. A distinct set of candidate lncRNA isoforms were identified as highly enriched and specific to human islets, which are deregulated in human islets from donors with different BMIs and with type 2 diabetes. These RNAs show an interesting regulation in cultured human islets under glucose stimulation and with induced β-cell death by cytokines. Aberrant expression of these lncRNAs was detected in the exosomes from the media of islets cultured with cytokines. Results of this study suggest that the islet specific lncRNAs are deregulated in human islet with β-cell death, hence important in diabetes. These lncRNAs might be important for human β-cell function and survival thus could be used as biomarkers and novel therapeutic targets for diabetes.

Keywords: β-cell, humanized mouse, pancreatic islet, LncRNAs

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Authors: G. J. Fan, T. T. Lee, M. H. Chen, T. F. Shiao, B. Yu, C. F. Lee

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Rice straw with poor feed quality and spent mushroom substrate are both the most abundant agricultural residues in Taiwan. Edible mushrooms from white rot fungi possess lignocellulase activity. It was expected to improve the feeding value of rice straw for ruminant by solid-state fermentation pretreatment using spent mushroom substrate. Six varieties or subspecies of spent edible mushrooms (Pleurotus ostreatus (blue or white color), P. sajor-caju, P. citrinopileatus, P. eryngii and Ganoderma lucidium) substrate were evaluated in solid-state fermentation process with rice straw for 8 wks. Quality improvement of fermented rice straw was determined by its in vitro digestibility, lignocellulose degradability, and cell wall breakdown checked by scanning electron microscope. Results turned out that Pleurotus ostreatus (white color) and P. sajor-caju had the better lignocellulose degradation effect than the others and was chosen for advance in vivo study. Rice straw fermented with spent Pleurotus ostreatus or Pleurotus sajor-caju mushroom substrate 8 wks was prepared for growing and lactating feeding trials of dairy goat, respectively. Pangolagrass hay at 15% diet dry matter was the control diet. Fermented or original rice straw was added to substitute pangolagrass hay in both feeding trials. A total of 30 head of Alpine castrated ram were assigned into three groups for 11 weeks, 5 pens (2 head/pen) each group. A total of 21 head of Saanen and Alpine goats were assigned into three treatments and individually fed in two repeat lactating trials with 28-d each. In castrated ram study, results showed that fermented rice straw by spent Pleurotus ostreatus mushroom substrate attributed the higher daily dry matter intakes (DMI, 1.53 vs. 1.20 kg) and body weight gain (138 vs. 101 g) than goats fed original rice straw. DMI (2.25 vs. 1.81 kg) and milk yield (3.31 vs. 3.02 kg) of lactating goats fed control pangolagrass diet and fermented rice straw by spent Pleurotus sajor-caju mushroom substrate were also higher than those fed original rice straw diet (P < 0.05). Milk compositions, milk fat, protein, total solid and lactose, were similar among treatments. In conclusion, solid-state fermentation by spent Pleurotus ostreatus or Pleurotus sajor-caju mushroom substrate could effectively improve the feeding value of rice straw. Fermented rice straw is a good alternative fiber feed resource for growing and lactating dairy goats and 15% in diet dry matter is recommended.

Keywords: feeding value, fermented rice straw, growing and lactating dairy goat, spent Pleurotus ostreatus and Pleurotus sajor-caju mushroom substrate

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Authors: Oleg Reva, Ilya Korotetskiy, Marina Lankina, Murat Kulmanov, Aleksandr Ilin

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Molecular docking approaches are widely used for design of new antibiotics and modeling of antibacterial activities of numerous ligands which bind specifically to active centers of indispensable enzymes and/or key signaling proteins of pathogens. Widespread drug resistance among pathogenic microorganisms calls for development of new antibiotics specifically targeting important metabolic and information pathways. A generally recognized problem is that almost all molecular targets have been identified already and it is getting more and more difficult to design innovative antibacterial compounds to combat the drug resistance. A promising way to overcome the drug resistance problem is an induction of reversion of drug resistance by supplementary medicines to improve the efficacy of the conventional antibiotics. In contrast to well established computer-based drug design, modeling of drug resistance reversion still is in its infancy. In this work, we proposed an approach to identification of compensatory genetic variants reducing the fitness cost associated with the acquisition of drug resistance by pathogenic bacteria. The approach was based on an analysis of the population genetic of Mycobacterium tuberculosis and on results of experimental modeling of the drug resistance reversion induced by a new anti-tuberculosis drug FS-1. The latter drug is an iodine-containing nanomolecular complex that passed clinical trials and was admitted as a new medicine against MDR-TB in Kazakhstan. Isolates of M. tuberculosis obtained on different stages of the clinical trials and also from laboratory animals infected with MDR-TB strain were characterized by antibiotic resistance, and their genomes were sequenced by the paired-end Illumina HiSeq 2000 technology. A steady increase in sensitivity to conventional anti-tuberculosis antibiotics in series of isolated treated with FS-1 was registered despite the fact that the canonical drug resistance mutations identified in the genomes of these isolates remained intact. It was hypothesized that the drug resistance phenotype in M. tuberculosis requires an adjustment of activities of many genes to compensate the fitness cost of the drug resistance mutations. FS-1 cased an aggravation of the fitness cost and removal of the drug-resistant variants of M. tuberculosis from the population. This process caused a significant increase in genetic heterogeneity of the Mtb population that was not observed in the positive and negative controls (infected laboratory animals left untreated and treated solely with the antibiotics). A large-scale search for linkage disequilibrium associations between the drug resistance mutations and genetic variants in other genomic loci allowed identification of target proteins, which could be influenced by supplementary drugs to increase the fitness cost of the drug resistance and deprive the drug-resistant bacterial variants of their competitiveness in the population. The approach will be used to improve the efficacy of FS-1 and also for computer-based design of new drugs to combat drug-resistant infections.

Keywords: complete genome sequencing, computational modeling, drug resistance reversion, Mycobacterium tuberculosis

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Authors: H. M. Ross-McAlpine

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Much of what is written on diplomacy, globalization and the global economy addresses the changing nature of relationships between major powers. While the most dramatic and influential changes have resulted from these developing relationships the world is not, on deeper inspection, governed neatly by major powers. Due to advances in technology, the shifting balance of power and a changing geopolitical order, small states have the ability to exercise a greater influence than ever before. Increasingly interdependent and ever complex, our world is too delicate to be handled by a mighty few. The pressure of global change requires small states to adapt their diplomatic practices and diversify their strategic alliances and relationships. The nature and practice of diplomacy must be re-evaluated in light of the pressures resulting from globalization. This research examines: how small states can best secure their foreign policy objectives? Small state theory is used as a foundation for exploring the case study of New Zealand. The research draws on secondary sources to evaluate the existing theory in relation to modern practices of diplomacy. As New Zealand lacks the required economic and military power to play an active, influential role in international affairs what strategies are used to exert influence? Furthermore, New Zealand lies in a remote corner of the Pacific and is geographically isolated from its nearest neighbors how does this affect security and trade priorities? The findings note a significant shift since the 1970’s in New Zealand’s diplomatic relations. This shift is arguably a direct result of globalization, regionalism and a growing independence from the traditional bi-lateral relationships. The need to source predictable trade, investment and technology are an essential driving force for New Zealand’s diplomatic relations. A lack of hard power aligns New Zealand’s prosperity with a secure, rules-based international system that increases the likelihood of a stable and secure global order. New Zealand’s diplomacy and prosperity has been intrinsically reliant on its reputation. A vital component of New Zealand’s diplomacy is preserving a reputation for integrity and global responsibility. It is the use of this soft power that facilitates the influence that New Zealand enjoys on the world stage. To weave a comprehensive network of successful diplomatic relationships, New Zealand must maintain a reputation of international credibility. Globalization has substantially influenced the practice of diplomacy for New Zealand. The current world order places economic and military might in the hands of a few, subsequently requiring smaller states to use other means for securing their interests. There are clear strategies evident in New Zealand’s diplomacy practice that draw attention to how other smaller states might best secure their foreign policy objectives. While these findings are limited, as with all case study research, there is value in applying the findings to other small states struggling to secure their interests in the wake of rapid globalization.

Keywords: diplomacy, foreign policy, globalisation, small state

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Authors: Shraddha Rane, Richard Warren, Stephen Eyre

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L-23 is a pro-inflammatory molecule that signals T cells to release cytokines such as IL-17A and IL-22. Psoriasis is driven by a dysregulated immune response, within which IL-23 is now thought to play a key role. Genome-wide association studies (GWAS) have identified a number of genetic risk loci that support the involvement of IL-23 signalling in psoriasis; in particular a robust susceptibility locus at a gene encoding a subunit of the IL-23 receptor (IL23R) (Stuart et al., 2015; Tsoi et al., 2012). The lead psoriasis-associated SNP rs9988642 is located approximately 500 bp downstream of IL23R but is in tight linkage disequilibrium (LD) with a missense SNP rs11209026 (R381Q) within IL23R (r2 = 0.85). The minor (G) allele of rs11209026 is present in approximately 7% of the population and is protective for psoriasis and several other autoimmune diseases including IBD, ankylosing spondylitis, RA and asthma. The psoriasis-associated missense SNP R381Q causes an arginine to glutamine substitution in a region of the IL23R protein between the transmembrane domain and the putative JAK2 binding site in the cytoplasmic portion. This substitution is expected to affect the receptor’s surface localisation or signalling ability, rather than IL23R expression. Recent studies have also identified a psoriatic arthritis (PsA)-specific signal at IL23R; thought to be independent from the psoriasis association (Bowes et al., 2015; Budu-Aggrey et al., 2016). The lead PsA-associated SNP rs12044149 is intronic to IL23R and is in LD with likely causal SNPs intersecting promoter and enhancer marks in memory CD8+ T cells (Budu-Aggrey et al., 2016). It is therefore likely that the PsA-specific SNPs affect IL23R function via a different mechanism compared with the psoriasis-specific SNPs. It could be hypothesised that the risk allele for PsA located within the IL23R promoter causes an increase IL23R expression, relative to the protective allele. An increased expression of IL23R might then lead to an exaggerated immune response. The independent genetic signals identified for psoriasis and PsA in this locus indicate that different mechanisms underlie these two conditions; although likely both affecting the function of IL23R. It is very important to further characterise these mechanisms in order to better understand how the IL-23 receptor and its downstream signalling is affected in both diseases. This will help to determine how psoriasis and PsA patients might differentially respond to therapies, particularly IL-23 biologics. To investigate this further we have developed an in vitro model using CD4 T cells which express either wild type IL23R and IL12Rβ1 or mutant IL23R (R381Q) and IL12Rβ1. Model expressing different isotypes of IL23R is also underway to investigate the effects on IL23R expression. We propose to further investigate the variants for Ps and PsA and characterise key intracellular processes related to the variants.

Keywords: IL23R, psoriasis, psoriatic arthritis, SNP

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Authors: Mohammad Afzal Khan, Fatimah Alanazi, Hala Abdalrahman Ahmed, Talal Shamma, Kilian Kelly, Mohammed A. Hammad, Abdullah O. Alawad, Abdullah Mohammed Assiri, Dieter Clemens Broering

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Lung transplantation is a life-saving surgical replacement of diseased lungs in patients with end-stage respiratory malfunctions. Despite the remarkable short-term recovery, long-term lung survival continues to face several significant challenges, including chronic rejection and severe toxic side-effects due to global immunosuppression. Stem cell-based immunotherapy has been recognized as a crucial immunoregulatory regimen in various preclinical and clinical studies. Despite initial therapeutic outcomes, conventional stem cells face key limitations. The Cymerus™ manufacturing facilitates the production of a virtually limitless supply of consistent human induced pluripotent stem cell (iPSC)-derived mesenchymal stem cells, which could play a key role in selective immunosuppression and graft repair during rejection. Here, we demonstrated the impact of iPSC-derived human MSCs on the development of immune-tolerance and long-term graft survival in mouse orthotopic airway allografts. BALB/c→C57BL/6 allografts were reconstituted with iPSC-derived MSCs (2 million/transplant/ at d0), and allografts were examined for regulatory T cells (Tregs), oxygenation, microvascular blood flow, airway epithelium and collagen deposition during rejection. We demonstrated that iPSC-derived MSC treatment leads to significant increase in tissue expression of hTSG-6 protein, followed by an upregulation of mouse Tregs and IL-5, IL-10, IL-15 cytokines, which augments graft microvascular blood flow and oxygenation, and thereby maintained a healthy airway epithelium and prevented the subepithelial deposition of collagen at d90 post-transplantation. Collectively, these data confirmed that iPSC-derived MSC-mediated immunosuppression has potential to establish immune-tolerance and rescue allograft from sustained hypoxic/ischemic phase and subsequently limits long-term airway epithelial injury and collagen progression, which therapeutically warrant a study of Cymerus iPSC-derived MSCs as a potential management option for immunosuppression in transplant recipients.

Keywords: stem cell therapy, immunotolerance, regulatory T cells, hypoxia and ischemia, microvasculature

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Authors: Leslie Raphael de M. Ferraz, Salvana Priscylla M. Costa, Tarcyla de A. Gomes, Giovanna Christinne R. M. Schver, Cristóvão R. da Silva, Magaly Andreza M. de Lyra, Danilo Augusto F. Fontes, Larissa A. Rolim, Amanda Carla Q. M. Vieira, Miracy M. de Albuquerque, Pedro J. Rolim-Neto

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Efavirenz (EFV) is a drug used as first-line treatment of AIDS. However, it has poor aqueous solubility and wettability, presenting problems in the gastrointestinal tract absorption and bioavailability. One of the most promising strategies to improve the solubility is the use of solid dispersions (SD). Therefore, this study aimed to characterize SD EFZ with the polymers: PVP-K30, PVPVA 64 and SOLUPLUS in order to find an optimal formulation to compose a future pharmaceutical product for AIDS therapy. Initially, Physical Mixtures (PM) and SD with the polymers were obtained containing 10, 20, 50 and 80% of drug (w/w) by the solvent method. The best formulation obtained between the SD was selected by in vitro dissolution test. Finally, the drug-carrier system chosen, in all ratios obtained, were analyzed by the following techniques: Differential Scanning Calorimetry (DSC), polarization microscopy, Scanning Electron Microscopy (SEM) and spectrophotometry of absorption in the region of infrared (IR). From the dissolution profiles of EFV, PM and SD, the values of area Under The Curve (AUC) were calculated. The data showed that the AUC of all PM is greater than the isolated EFV, this result is derived from the hydrophilic properties of the polymers thus favoring a decrease in surface tension between the drug and the dissolution medium. In adittion, this ensures an increasing of wettability of the drug. In parallel, it was found that SD whom had higher AUC values, were those who have the greatest amount of polymer (with only 10% drug). As the amount of drug increases, it was noticed that these results either decrease or are statistically similar. The AUC values of the SD using the three different polymers, followed this decreasing order: SD PVPVA 64-EFV 10% > SD PVP-K30-EFV 10% > SD Soluplus®-EFV 10%. The DSC curves of SD’s did not show the characteristic endothermic event of drug melt process, suggesting that the EFV was converted to its amorphous state. The analysis of polarized light microscopy showed significant birefringence of the PM’s, but this was not observed in films of SD’s, thus suggesting the conversion of the drug from the crystalline to the amorphous state. In electron micrographs of all PM, independently of the percentage of the drug, the crystal structure of EFV was clearly detectable. Moreover, electron micrographs of the SD with the two polymers in different ratios investigated, we observed the presence of particles with irregular size and morphology, also occurring an extensive change in the appearance of the polymer, not being possible to differentiate the two components. IR spectra of PM corresponds to the overlapping of polymer and EFV bands indicating thereby that there is no interaction between them, unlike the spectra of all SD that showed complete disappearance of the band related to the axial deformation of the NH group of EFV. Therefore, this study was able to obtain a suitable formulation to overcome the solubility limitations of the EFV, since SD PVPVA 64-EFZ 10% was chosen as the best system in delay crystallization of the prototype, reaching higher levels of super saturation.

Keywords: characterization, dissolution, Efavirenz, solid dispersions

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Authors: M. Kazou, A. Gavriil, O. Kalagkatsi, T. Paschos, E. Tsakalidou

Abstract:

Kopanisti cheese is a Greek soft Protected Designation of Origin (PDO) cheese made of raw cow, sheep or goat milk, or mixtures of them, with similar organoleptic characteristics to that of Roquefort cheese. Traditional manufacturing of Kopanisti cheese is limited in small-scale dairies, without the addition of starter cultures. Instead, an amount of over-mature Kopanisti cheese, called Mana Kopanisti, is used to initiate ripening. Therefore, the selection of proper starter cultures and the understanding of the contribution of various microbial groups to its overall quality is crucial for the production of a high-quality final product with standardized organoleptic and physicochemical characteristics. Taking the above into account, the aim of the present study was the investigation of Kopanisti cheese microbiota and its role in cheese quality. For this purpose, four different types of Kopanisti were produced in triplicates, all with pasteurized cow milk, with the addition of (A) the typical mesophilic species Lactococcus lactis and Lactobacillus paracasei used as starters in the production of soft spread cheeses, (B) strains of Lactobacillus acidipiscis and Lactobacillus rennini previously isolated from Kopanisti and Mana Kopanisti, (C) all the species from (A) and (B) as inoculum, and finally (D) the species from (A) and Mana Kopanisti. Physicochemical and microbiological analysis was performed for milk and cheese samples during ripening. Enumeration was performed for major groups of lactic acid bacteria (LAB), total mesophilic bacteria, yeasts as well as hygiene indicator microorganisms. Bacterial isolates from all the different LAB groups, apart from enterococci, alongside yeasts isolates, were initially grouped using repetitive sequence-based polymerase chain reaction (rep-PCR) and then identified at the species level using 16S rRNA gene and internal transcribed spacer (ITS) DNA region sequencing, respectively. Sensory evaluation was also performed for final cheese samples at the end of the ripening period (35 days). Based on the results of the classical microbiological analysis, the average counts of the total mesophilic bacteria and LAB, apart from enterococci, ranged between 7 and 10 log colony forming unit (CFU) g⁻¹, phychrotrophic bacteria, and yeast extract glucose chloramphenicol (YGC) isolates between 4 and 8 log CFU g⁻¹, while coliforms and enterococci up to 2 log CFU g⁻¹ throughout ripening in cheese samples A, C and D. In contrast, in cheese sample B, the average counts of the total mesophilic bacteria and LAB, apart from enterococci, phychrotrophic bacteria, and YGC isolates ranged between 0 and 10 log CFU g⁻¹ and coliforms and enterococci up to 2 log CFU g⁻¹. Although the microbial counts were not that different among samples, identification of the bacterial and yeasts isolates revealed the complex microbial community structure present in each cheese sample. Differences in the physicochemical characteristics among the cheese samples were also observed, with pH ranging from 4.3 to 5.3 and moisture from 49.6 to 58.0 % in the final cheese products. Interestingly, the sensory evaluation also revealed differences among samples, with cheese sample B ranking first based on the total score. Overall, the combination of these analyses highlighted the impact of different starter cultures on the Kopanisti microbiota as well as on the physicochemical and sensory characteristics of the final product.

Keywords: Kopanisti cheese, microbiota, classical microbiological analysis, physicochemical analysis

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Authors: D. P. Houhoula, J. Papaparaskevas, S. Konteles, A. Dargenta, A. Farka, C. Spyrou, M. Ziaka, S. Koussisis, E. Charvalos

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Objectives: Nanotechnology is providing revolutionary opportunities for the rapid and simple diagnosis of many infectious diseases. Staphylococcus aureus, Listeria monocytogenes and Salmonella enteritis are important human pathogens. Diagnostic assays for bacterial culture and identification are time consuming and laborious. There is an urgent need to develop rapid, sensitive, and inexpensive diagnostic tests. In this study, a gold nanoprobe strategy developed and relies on the colorimetric differentiation of specific DNA sequences based approach on differential aggregation profiles in the presence or absence of specific target hybridization. Method: Gold nanoparticles (AuNPs) were purchased from Nanopartz. They were conjugated with thiolated oligonucleotides specific for the femA gene for the identification of members of Staphylococcus aureus, the mecA gene for the differentiation of Staphylococcus aureus and MRSA Staphylococcus aureus, hly gene encoding the pore-forming cytolysin listeriolysin for the identification of Listeria monocytogenes and the invA sequence for the identification of Salmonella enteritis. DNA isolation from Staphylococcus aureus Listeria monocytogenes and Salmonella enteritis cultures was performed using the commercial kit Nucleospin Tissue (Macherey Nagel). Specifically 20μl of DNA was diluted in 10mMPBS (pH5). After the denaturation of 10min, 20μl of AuNPs was added followed by the annealing step at 58oC. The presence of a complementary target prevents aggregation with the addition of acid and the solution remains pink, whereas in the opposite event it turns to purple. The color could be detected visually and it was confirmed with an absorption spectrum. Results: Specifically, 0.123 μg/μl DNA of St. aureus, L.monocytogenes and Salmonella enteritis was serially diluted from 1:10 to 1:100. Blanks containing PBS buffer instead of DNA were used. The application of the proposed method on isolated bacteria produced positive results with all the species of St. aureus and L. monocytogenes and Salmonella enteritis using the femA, mecA, hly and invA genes respectively. The minimum detection limit of the assay was defined at 0.2 ng/μL of DNA. Below of 0.2 ng/μL of bacterial DNA the solution turned purple after addition of HCl, defining the minimum detection limit of the assay. None of the blank samples was positive. The specificity was 100%. The application of the proposed method produced exactly the same results every time (n = 4) the evaluation was repeated (100% repeatability) using the femA, hly and invA genes. Using the gene mecA for the differentiation of Staphylococcus aureus and MRSA Staphylococcus aureus the method had a repeatability 50%. Conclusion: The proposed method could be used as a highly specific and sensitive screening tool for the detection and differentiation of Staphylococcus aureus Listeria monocytogenes and Salmonella enteritis. The use AuNPs for the colorimetric detection of DNA targets represents an inexpensive and easy-to-perform alternative to common molecular assays. The technology described here, may develop into a platform that could accommodate detection of many bacterial species.

Keywords: gold nanoparticles, pathogens, nanotechnology, bacteria

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Authors: Maria Ostroukhova, Zhanneta Zalutskaya, Elena Ermilova

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The alternative oxidase (AOX) mediates cyanide-resistant respiration, which bypasses proton-pumping complexes III and IV of the cytochrome pathway to directly transfer electrons from reduced ubiquinone to molecular oxygen. In Chlamydomonas reinhardtii, AOX is a monomeric protein that is encoded by two genes of discrete subfamilies, AOX1 and AOX2. Although AOX has been proposed to play essential roles in stress tolerance of organisms, the role of subfamily AOX2 is largely unknown. In C. reinhardtii, AOX2 was initially identified as one of constitutively low expressed genes. Like other photosynthetic organisms C. reinhardtii cells frequently experience periods of hypoxia. To examine AOX2 transcriptional regulation and role of AOX2 in hypoxia adaptation, real-time PCR analysis and artificial microRNA method were employed. Two experimental approaches have been used to induce the anoxic conditions: dark-anaerobic and light-anaerobic conditions. C. reinhardtii cells exposed to the oxygen deprivation have shown increased AOX2 mRNA levels. By contrast, AOX1 was not an anoxia-responsive gene. In C. reinhardtii, a subset of genes is regulated by transcription factor CRR1 in anaerobic conditions. Notable, the AOX2 promoter region contains the potential motif for CRR1 binding. Therefore, the role of CRR1 in the control of AOX2 transcription was tested. The CRR1-underexpressing strains, that were generated and characterized in this work, exhibited low levels of AOX2 transcripts under anoxic conditions. However, the transformants still slightly induced AOX2 gene expression in the darkness. These confirmed our suggestions that darkness is a regulatory stimulus for AOX genes in C. reinhardtii. Thus, other factors must contribute to AOX2 promoter activity under dark-anoxic conditions. Moreover, knock-down of CRR1 caused a complete reduction of AOX2 expression under light-anoxic conditions. These results indicate that (1) CRR1 is required for AOX2 expression during hypoxia, and (2) AOX2 gene is regulated by CRR1 together with yet-unknown regulatory factor(s). In addition, the AOX2-underexpressing strains were generated. The analysis of amiRNA-AOX2 strains suggested a role of this alternative oxidase in hypoxia adaptation of the alga. In conclusion, the results reported here show that C. reinhardtii AOX2 gene is stress inducible. CRR1 transcriptional factor is involved in the regulation of the AOX2 gene expression in the absence of oxygen. Moreover, AOX2 but not AOX1 functions under oxygen deprivation. This work was supported by Russian Science Foundation (research grant № 16-14-10004).

Keywords: alternative oxidase 2, artificial microRNA approach, chlamydomonas reinhardtii, hypoxia

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Authors: Wim Hollander, Petrus Louis Nolte

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University sport in South Africa is not isolated from the complexity of globalization and professionalization of sport, as it forms an integral part of the sports development environment in South Africa. In order to align their sports programs with global and professional requirements, several universities opted to develop elite sports programs; recruit specialized personnel such as coaches, administrators, and athletes; provide expert coaching; scientific and medical services; sports testing; fitness, technical and tactical expertise; sport psychological and rehabilitation support; academic guidance and career assistance; and student-athlete accommodation. In addition, universities provide administrative support and high-quality physical resources (training facilities) for the benefit of the overall South African sport system. Although it is not compulsory for universities to develop elite sports programs to prepare their teams for competitions, elite competitions such as the annual Varsity Sport, University Sport South Africa (USSA) and local club competitions and leagues within international university competitions where universities not only compete but also deliver players for representative national netball teams. The aim of this study is, therefore, to describe the perceptions of players of the university elite netball programs they were participating in. This study adopted a descriptive design with a quantitative approach, utilizing a self-structured questionnaire as a research technique. As this research formed part of a national research project for NSA with a population of 172 national and provincial netball players, a sample of 92 university netball players from the population was selected. Content validity of the self-structured questionnaire was secured through a test-retest process, with construct validity through a member of the Statistical Consultation Services (STATCON) of the University of Johannesburg that provided feedback on the structural format of the questionnaire. Reliability was measured utilizing Cronbach Alpha on p < 0.005 level of significance. A reliability score of 0.87 was measured. The research was approved by the Board of Netball South Africa and ethical conduct implemented according to the processes and procedures approved by the Ethics Committees of the Faculty of Health Sciences, the University of Johannesburg with clearance number REC-01-30-2019. From the results, it is evident that university elite netball programs are professional, especially with regards to the employment of knowledgeable and competent coaches and technical officials such as team managers and sport sciences staff. These professionals have access to elite training facilities, support staff, and relatively large groups of elite players, all elements of an elite program that could enhance the national federation’s (Netball South Africa) system. Universities could serve the dual purpose of serving as university netball clubs, as well as providing elite training services and facilities as performance hubs for national players.

Keywords: elite sport programmes, university netball, player experiences, varsity sport netball

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Authors: Mustafa M. Donma, Orkide Donma

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Obesity is a clinical state associated with low-grade inflammation. It is also a major risk factor for insulin resistance (IR). In its advanced stages, metabolic syndrome (MetS), a much more complicated disease which may lead to life-threatening problems, may develop. Obesity-mediated IR seems to correlate with the inflammation. Human studies performed particularly on pediatric population are scarce. The aim of this study is to detect possible associations between inflammation and IR in terms of some related ratios. 549 children were grouped according to their age- and sex-based body mass index (BMI) percentile tables of WHO. MetS components were determined. Informed consent and approval from the Ethics Committee for Clinical Investigations were obtained. The principles of the Declaration of Helsinki were followed. The exclusion criteria were infection, inflammation, chronic diseases and those under drug treatment. Anthropometric measurements were obtained. Complete blood cell, fasting blood glucose, insulin, and C-reactive protein (CRP) analyses were performed. Homeostasis model assessment of insulin resistance (HOMA-IR), systemic immune inflammation (SII) index, tense index, alanine aminotransferase to aspartate aminotransferase ratio (ALT/AST), neutrophils to lymphocyte (NLR), platelet to lymphocyte, and lymphocyte to monocyte ratios were calculated. Data were evaluated by statistical analyses. The degree for statistical significance was 0.05. Statistically significant differences were found among the BMI values of the groups (p < 0.001). Strong correlations were detected between the BMI and waist circumference (WC) values in all groups. Tense index values were also correlated with both BMI and WC values in all groups except overweight (OW) children. SII index values of children with normal BMI were significantly different from the values obtained in OW, obese, morbid obese and MetS groups. Among all the other lymphocyte ratios, NLR exhibited a similar profile. Both HOMA-IR and ALT/AST values displayed an increasing profile from N towards MetS3 group. BMI and WC values were correlated with HOMA-IR and ALT/AST. Both in morbid obese and MetS groups, significant correlations between CRP versus SII index as well as HOMA-IR versus ALT/AST were found. ALT/AST and HOMA-IR values were correlated with NLR in morbid obese group and with SII index in MetS group, (p < 0.05), respectively. In conclusion, these findings showed that some parameters may exhibit informative differences between the early and late stages of obesity. Important associations among HOMA-IR, ALT/AST, NLR and SII index have come to light in the morbid obese and MetS groups. This study introduced the SII index and NLR as important inflammatory markers for the discrimination of normal and obese children. Interesting links were observed between inflammation and IR in morbid obese children and those with MetS, both being late stages of obesity.

Keywords: children, inflammation, insulin resistance, metabolic syndrome, obesity

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Authors: Abdelkhalek Bouchikhi, Elyes Benmokhtar, Sebastien Saletzki

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The aeronautical field is experiencing issues with RF spectrum congestion due to the constant increase in the number of flights, aircrafts and telecom systems on board. In addition, these systems are bulky in size, weight and energy consumption. The cognitive radio helps particularly solving the spectrum congestion issue by its capacity to detect idle frequency channels then, allowing an opportunistic exploitation of the RF spectrum. The present work aims to propose a new use case for aeronautical spectrum sharing and to study the performances of three different detection techniques: energy detector, matched filter and cyclostationary detector within the aeronautical use case. The spectrum in the proposed cognitive radio is allocated dynamically where each cognitive radio follows a cognitive cycle. The spectrum sensing is a crucial step. The goal of the sensing is gathering data about the surrounding environment. Cognitive radio can use different sensors: antennas, cameras, accelerometer, thermometer, etc. In IEEE 802.22 standard, for example, a primary user (PU) has always the priority to communicate. When a frequency channel witch used by the primary user is idle, the secondary user (SU) is allowed to transmit in this channel. The Distance Measuring Equipment (DME) is composed of a UHF transmitter/receiver (interrogator) in the aircraft and a UHF receiver/transmitter on the ground. While the future cognitive radio will be used jointly to alleviate the spectrum congestion issue in the aeronautical field. LDACS, for example, is a good candidate; it provides two isolated data-links: ground-to-air and air-to-ground data-links. The first contribution of the present work is a strategy allowing sharing the L-band. The adopted spectrum sharing strategy is as follow: the DME will play the role of PU which is the licensed user and the LDACS1 systems will be the SUs. The SUs could use the L-band channels opportunely as long as they do not causing harmful interference signals which affect the QoS of the DME system. Although the spectrum sensing is a key step, it helps detecting holes by determining whether the primary signal is present or not in a given frequency channel. A missing detection on primary user presence creates interference between PU and SU and will affect seriously the QoS of the legacy radio. In this study, first brief definitions, concepts and the state of the art of cognitive radio will be presented. Then, a study of three communication channel detection algorithms in a cognitive radio context is carried out. The study is made from the point of view of functions, material requirements and signal detection capability in the aeronautical field. Then, we presented a modeling of the detection problem by three different methods (energy, adapted filter, and cyclostationary) as well as an algorithmic description of these detectors is done. Then, we study and compare the performance of the algorithms. Simulations were carried out using MATLAB software. We analyzed the results based on ROCs curves for SNR between -10dB and 20dB. The three detectors have been tested with a synthetics and real world signals.

Keywords: aeronautic, communication, navigation, surveillance systems, cognitive radio, spectrum sensing, software defined radio

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Authors: Sulalit Bandyopadhyay, Muhammad Awais Ashfaq Alvi, Anuvansh Sharma, Wilhelm R. Glomm

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Release of drugs from nanogels and nanogel-based systems can occur under the influence of external stimuli like temperature, pH, magnetic fields and so on. pNIPAm-AAc nanogels respond to the combined action of both temperature and pH, the former being mostly determined by hydrophilic-to-hydrophobic transitions above the volume phase transition temperature (VPTT), while the latter is controlled by the degree of protonation of the carboxylic acid groups. These nanogels based systems are promising candidates in the field of drug delivery. Combining nanogels with magneto-plasmonic nanoparticles (NPs) introduce imaging and targeting modalities along with stimuli-response in one hybrid system, thereby incorporating multifunctionality. Fe@Au core-shell NPs possess optical signature in the visible spectrum owing to localized surface plasmon resonance (LSPR) of the Au shell, and superparamagnetic properties stemming from the Fe core. Although there exist several synthesis methods to control the size and physico-chemical properties of pNIPAm-AAc nanogels, yet, there is no comprehensive study that highlights the dependence of incorporation of one or more layers of NPs to these nanogels. In addition, effective determination of volume phase transition temperature (VPTT) of the nanogels is a challenge which complicates their uses in biological applications. Here, we have modified the swelling-collapse properties of pNIPAm-AAc nanogels, by combining with Fe@Au NPs using different solution based methods. The hydrophilic-hydrophobic transition of the nanogels above the VPTT has been confirmed to be reversible. Further, an analytical method has been developed to deduce the average VPTT which is found to be 37.3°C for the nanogels and 39.3°C for nanogel coated Fe@Au NPs. An opposite swelling –collapse behaviour is observed for the latter where the Fe@Au NPs act as bridge molecules pulling together the gelling units. Thereafter, Cyt C, a model protein drug and L-Dopa, a drug used in the clinical treatment of Parkinson’s disease were loaded separately into the nanogels and nanogel coated Fe@Au NPs, using a modified breathing-in mechanism. This gave high loading and encapsulation efficiencies (L Dopa: ~9% and 70µg/mg of nanogels, Cyt C: ~30% and 10µg/mg of nanogels respectively for both the drugs. The release kinetics of L-Dopa, monitored using UV-vis spectrophotometry was observed to be rather slow (over several hours) with highest release happening under a combination of high temperature (above VPTT) and acidic conditions. However, the release of L-Dopa from nanogel coated Fe@Au NPs was the fastest, accounting for release of almost 87% of the initially loaded drug in ~30 hours. The chemical structure of the drug, drug incorporation method, location of the drug and presence of Fe@Au NPs largely alter the drug release mechanism and the kinetics of these nanogels and Fe@Au NPs coated with nanogels.

Keywords: controlled release, nanogels, volume phase transition temperature, l-dopa

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Authors: Neelam Taneja, Abhishek Mewara, Ajay Kumar

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Multidrug resistant shigellae have emerged as a therapeutic challenge in India. At our 2000 bed tertiary care referral centre in Chandigarh, North India, which caters to a large population of 7 neighboring states, antibiotic resistance in Shigella is being constantly monitored. Shigellae are isolated from 3 to 5% of all stool samples. In 1990 nalidixic acid was the drug of choice as 82%, and 63% of shigellae were resistant to ampicillin and cotrimoxazole respectively. Nalidixic acid resistance emerged in 1992 and rapidly increased from 6% during 1994-98 to 86% by the turn of 21st century. In the 1990s, the WHO recommended ciprofloxacin as the drug of choice for empiric treatment of shigellosis in view of the existing high level resistance to agents like chloramphenicol, ampicillin, cotrimoxazole and nalidixic acid. First resistance to ciprofloxacin in S. flexneri at our centre appeared in 2000 and rapidly rose to 46% in 2007 (MIC>4mg/L). In between we had an outbreak of ciprofloxacin resistant S.dysenteriae serotype 1 in 2003. Therapeutic failures with ciprofloxacin occurred with both ciprofloxacin-resistant S. dysenteriae and ciprofloxacin-resistant S. flexneri. The severity of illness was more with ciprofloxacin-resistant strains. Till 2000, elsewhere in the world ciprofloxacin resistance in S. flexneri was sporadic and uncommon, though resistance to co-trimoxazole and ampicillin was common and in some areas resistance to nalidixic acid had also emerged. Fluoroquinolones due to extensive use and misuse for many other illnesses in our region are thus no longer the preferred group of drugs for managing shigellosis in India. WHO presently recommends ceftriaxone and azithromycin as alternative drugs to fluoroquinolone-resistant shigellae, however, overreliance on this group of drugs also seems to soon become questionable considering the emerging cephalosporin-resistant shigellae. We found 15.1% of S. flexneri isolates collected over a period of 9 years (2000-2009) resistant to at least one of the third-generation cephalosporins (ceftriaxone/cefotaxime). The first isolate showing ceftriaxone resistance was obtained in 2001, and we have observed an increase in number of isolates resistant to third generation cephalosporins in S. flexneri 2005 onwards. This situation has now become a therapeutic challenge in our region. The MIC values for Shigella isolates revealed a worrisome rise for ceftriaxone (MIC90:12 mg/L) and cefepime (MIC90:8 mg/L). MIC values for S. dysenteriae remained below 1 mg/L for ceftriaxone, however for cefepime, the MIC90 has raised to 4 mg/L. These infections caused by ceftriaxone-resistant S. flexneri isolates were successfully treated by azithromycin at our center. Most worrisome development in the present has been the emergence of DSA(Decreased susceptibility to azithromycin) which surfaced in 2001 and has increased from 4.3% till 2011 to 34% thereafter. We suspect plasmid-mediated resistance as we detected qnrS1-positive Shigella for the first time from the Indian subcontinent in 2 strains from 2010, indicating a relatively new appearance of this PMQR determinant among Shigella in India. This calls for a continuous and strong surveillance of antibiotic resistance across the country. The prevention of shigellosis by developing cost-effective vaccines is desirable as it will substantially reduce the morbidity associated with diarrhoea in the country

Keywords: Shigella, antimicrobial, resistance, India

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Authors: Paola Modesto, Floriana Fruscione, Isabella Martini, Simona Perga, Federica Riccardo, Mariateresa Camerino, Davide Giacobino, Cecilia Gola, Luca Licenziato, Elisabetta Razzuoli, Katia Varello, Lorella Maniscalco, Elena Bozzetta, Angelo Ferrari

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Canine and human melanoma, osteosarcoma (OSA), and mammary carcinomas are aggressive tumors with common characteristics making dogs a good model for comparative oncology. Novel therapeutic strategies against these tumors could be useful to both species. In humans, chondroitin sulphate proteoglycan 4 (CSPG4) is a marker involved in tumor progression and could be a candidate target for immunotherapy. The anti-CSPG4 DNA electrovaccination has shown to be an effective approach for canine malignant melanoma (CMM) [1]. An immunohistochemistry evaluation of CSPG4 expression in tumour tissue is generally performed prior to electrovaccination. To assess the possibility to perform a rapid molecular evaluation and in order to validate these spontaneous canine tumors as the model for human studies, we investigate the CSPG4 gene expression by RT qPCR in CMM, OSA, and canine mammary tumors (CMT). The total RNA was extracted from RNAlater stored tissue samples (CMM n=16; OSA n=13; CMT n=6; five paired normal tissues for CMM, five paired normal tissues for OSA and one paired normal tissue for CMT), retro-transcribed and then analyzed by duplex RT-qPCR using two different TaqMan assays for the target gene CSPG4 and the internal reference gene (RG) Ribosomal Protein S19 (RPS19). RPS19 was selected from a panel of 9 candidate RGs, according to NormFinder analysis following the protocol already described [2]. Relative expression was analyzed by CFX Maestro™ Software. Student t-test and ANOVA were performed (significance set at P<0.05). Results showed that gene expression of CSPG4 in OSA tissues is significantly increased by 3-4 folds when compared to controls. In CMT, gene expression of the target was increased from 1.5 to 19.9 folds. In melanoma, although an increasing trend was observed, no significant differences between the two groups were highlighted. Immunohistochemistry analysis of the two cancer types showed that the expression of CSPG4 within CMM is concentrated in isles of cells compared to OSA, where the distribution of positive cells is homogeneous. This evidence could explain the differences in gene expression results.CSPG4 immunohistochemistry evaluation in mammary carcinoma is in progress. The evidence of CSPG4 expression in a different type of canine tumors opens the way to the possibility of extending the CSPG4 immunotherapy marker in CMM, OSA, and CMT and may have an impact to translate this strategy modality to human oncology.

Keywords: canine melanoma, canine mammary carcinomas, canine osteosarcoma, CSPG4, gene expression, immunotherapy

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Authors: Pola Goldberg Oppenheimer, Stephan Hofmann, Sumeet Mahajan

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Owing to its fingerprint molecular specificity and high sensitivity, surface-enhanced Raman scattering (SERS) is an established analytical tool for chemical and biological sensing capable of single-molecule detection. A strong Raman signal can be generated from SERS-active platforms given the analyte is within the enhanced plasmon field generated near a noble-metal nanostructured substrate. The key requirement for generating strong plasmon resonances to provide this electromagnetic enhancement is an appropriate metal surface roughness. Controlling nanoscale features for generating these regions of high electromagnetic enhancement, the so-called SERS ‘hot-spots’, is still a challenge. Significant advances have been made in SERS research, with wide-ranging techniques to generate substrates with tunable size and shape of the nanoscale roughness features. Nevertheless, the development and application of SERS has been inhibited by the irreproducibility and complexity of fabrication routes. The ability to generate straightforward, cost-effective, multiplex-able and addressable SERS substrates with high enhancements is of profound interest for miniaturised sensing devices. Carbon nanotubes (CNTs) have been concurrently, a topic of extensive research however, their applications for plasmonics has been only recently beginning to gain interest. CNTs can provide low-cost, large-active-area patternable substrates which, coupled with appropriate functionalization capable to provide advanced SERS-platforms. Herein, advanced methods to generate CNT-based SERS active detection platforms will be discussed. First, a novel electrohydrodynamic (EHD) lithographic technique will be introduced for patterning CNT-polymer composites, providing a straightforward, single-step approach for generating high-fidelity sub-micron-sized nanocomposite structures within which anisotropic CNTs are vertically aligned. The created structures are readily fine-tuned, which is an important requirement for optimizing SERS to obtain the highest enhancements with each of the EHD-CNTs individual structural units functioning as an isolated sensor. Further, gold-functionalized VACNTFs are fabricated as SERS micro-platforms. The dependence on the VACNTs’ diameters and density play an important role in the Raman signal strength, thus highlighting the importance of structural parameters, previously overlooked in designing and fabricating optimized CNTs-based SERS nanoprobes. VACNTs forests patterned into predesigned pillar structures are further utilized for multiplex detection of bio-analytes. Since CNTs exhibit electrical conductivity and unique adsorption properties, these are further harnessed in the development of novel chemical and bio-sensing platforms.

Keywords: carbon nanotubes (CNTs), EHD patterning, SERS, vertically aligned carbon nanotube forests (VACNTF)

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Authors: Ching-Yi Yiu, Hui-Chen Hsu

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Objectives: Head and neck cancer (HNC) is a big global health problem in the world. Despite the development of diagnosis and treatment, the overall survival of HNC is still low. The well recognition of the interaction of the host immune system and cancer cells has led to realizing the processes of tumor initiation, progression and metastasis. Many systemic inflammatory responses have been shown to play a crucial role in cancer progression. The pre and post-treatment nutritional and immunological status of HNC patients is a reliable prognostic indicator of tumor outcomes and survivors. Methods: Between July 2020 to June 2022, We have enrolled 60 HNC patients, including 59 males and 1 female, in Chi Mei Medical Center, Liouying, Taiwan. The age distribution was from 37 to 81 years old (y/o), with a mean age of 57.6 y/o. We evaluated the pre-and post-treatment nutritional and immunological status of these HNC patients with body weight, body weight loss, body mass index (BMI), whole blood count including hemoglobin (Hb), lymphocyte, neutrophil and platelet counts, biochemistry including prealbumin, albumin, c-reactive protein (CRP), with the time period of before treatment, post-treatment 3 and 6 months. We calculated the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) to assess how these biomarkers influence the outcomes of HNC patients. Results: We have carcinoma of the hypopharynx in 21 cases with 35％, carcinoma of the larynx in 9 cases, carcinoma of the tonsil and tongue every 6 cases, carcinoma soft palate and tongue base every 5 cases, carcinoma of buccal mucosa, retromolar trigone and mouth floor every 2 cases, carcinoma of the hard palate and low lip each 1 case. There were stage I 15 cases, stage II 13 cases, stage III 6 cases, stage IVA 10 cases, and stage IVB 16 cases. All patients have received surgery, chemoradiation therapy or combined therapy. We have wound infection in 6 cases, 2 cases of pharyngocutaneous fistula, flap necrosis in 2 cases, and mortality in 6 cases. In the wound infection group, the average BMI is 20.4 kg/m2; the average Hb is 12.9 g/dL, the average albumin is 3.5 g/dL, the average NLR is 6.78, and the average PLR is 243.5. In the PC fistula and flap necrosis group, the average BMI is 21.65 kg/m2; the average Hb is 11.7 g/dL, the average albumin is 3.15 g/dL, average NLR is 13.28, average PLR is 418.84. In the mortality group, the average BMI is 22.3 kg/m2; the average Hb is 13.58 g/dL, the average albumin is 3.77 g/dL, the average NLR is 6.06, and the average PLR is 275.5. Conclusion: HNC is a big challenging public health problem worldwide, especially in the high prevalence of betel nut consumption area Taiwan. Besides the definite risk factors of smoking, drinking and betel nut related, the other biomarkers may play significant prognosticators in the HNC outcomes. We concluded that the average BMI is less than 22 kg/m2, the average Hb is low than 12.0 g/dL, the average albumin is low than 3.3 g/dL, the average NLR is low than 3, and the average PLR is more than 170, the surgical complications and mortality will be increased, and the prognosis is poor in HNC patients.

Keywords: nutritional, immunological, neutrophil-to-lymphocyte ratio, paltelet-to-lymphocyte ratio.

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Authors: Martha E. Aguiar-Barrera, Humberto Gutierrez-Pulido, Veronica Vargas-Alejo

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Identifying and modeling random phenomena is a fundamental cognitive process to understand and transform reality. Recognizing situations governed by chance and giving them a scientific interpretation, without being carried away by beliefs or intuitions, is a basic training for citizens. Hence the importance of generating teaching-learning processes, supported using technology, paying attention to model creation rather than only executing mathematical calculations. In order to develop the student's knowledge about basic probability distributions and decision making; in this work a model eliciting activity (MEA) is reported. The intention was applying the Model and Modeling Perspective to design an activity related to civil engineering that would be understandable for students, while involving them in its solution. Furthermore, the activity should imply a decision-making challenge based on sample data, and the use of the computer should be considered. The activity was designed considering the six design principles for MEA proposed by Lesh and collaborators. These are model construction, reality, self-evaluation, model documentation, shareable and reusable, and prototype. The application and refinement of the activity was carried out during three school cycles in the Probability and Statistics class for Civil Engineering students at the University of Guadalajara. The analysis of the way in which the students sought to solve the activity was made using audio and video recordings, as well as with the individual and team reports of the students. The information obtained was categorized according to the activity phase (individual or team) and the category of analysis (sample, linearity, probability, distributions, mechanization, and decision-making). With the results obtained through the MEA, four obstacles have been identified to understand and apply the binomial distribution: the first one was the resistance of the student to move from the linear to the probabilistic model; the second one, the difficulty of visualizing (infering) the behavior of the population through the sample data; the third one, viewing the sample as an isolated event and not as part of a random process that must be viewed in the context of a probability distribution; and the fourth one, the difficulty of decision-making with the support of probabilistic calculations. These obstacles have also been identified in literature on the teaching of probability and statistics. Recognizing these concepts as obstacles to understanding probability distributions, and that these do not change after an intervention, allows for the modification of these interventions and the MEA. In such a way, the students may identify themselves the erroneous solutions when they carrying out the MEA. The MEA also showed to be democratic since several students who had little participation and low grades in the first units, improved their participation. Regarding the use of the computer, the RStudio software was useful in several tasks, for example in such as plotting the probability distributions and to exploring different sample sizes. In conclusion, with the models created to solve the MEA, the Civil Engineering students improved their probabilistic knowledge and understanding of fundamental concepts such as sample, population, and probability distribution.

Keywords: linear model, models and modeling, probability, randomness, sample

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Authors: Alec Chabwinja, Cannan Tawonezvi, Jerneja Vidmar, Constance Chingwaru, Walter Chingwaru

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Objective: To evaluate the potential of commercial fermented / probiotic products available in Zimbabwe or internationally, and strains of Lactobacillus plantarum (L. plantarum) as prophylaxis and therapy against diarrhoeal and sexually transmitted infections. Methods: The antimicrobial potential of cultures of lactobacilli enriched from 4 Zimbabwean commercial food/beverage products, namely Dairibord Lacto sour milk (DLSM), Probrand sour milk (PSM), Kefalos Vuka cheese (KVC) and Chibuku opaque beer (COB); three probiotic products obtainable in Europe and internationally; and four strains of L. plantarum obtained from Balkan traditional cheeses and Zimbabwean foods against clinical strains of Escherichia coli (E. coli) and non-clinical strains of Candida albicans and Rhodotorula spp. was assayed using the well diffusion method. Three commercial Agar diffusion assay and a competitive exclusion assay were carried out on Mueller-Hinton agar. Results: Crude cultures of putative lactobacillus strains obtained from Zimbabwean dairy products (Probrand sour milk, Kefalos Vuka vuka cheese and Chibuku opaque beer) exhibited significantly greater antimicrobial activities against clinical strains of E. coli than strains of L. plantarum isolated from Balkan cheeses (CLP1, CLP2 or CLP3) or crude microbial cultures from commercial paediatric probiotic products (BG, PJ and PL) of a culture of Lactobacillus rhamnosus LGG (p < 0.05). Furthermore, the following has high antifungal activities against the two yeasts: supernatant-free microbial pellet (SFMP) from an extract of M. azedarach leaves (27mm ± 2.5) > cell-free culture supernatants (CFCS) from Maaz Dairy sour milk and Mnandi sour milk (approximately 26mm ± 1.8) > CFCS and SFMP from Amansi hodzeko (25mm ± 1.5) > CFCS from Parinari curatellifolia fruit (24mm ± 1.5), SFMP from P. curatellifolia fruit (24mm ± 1.4) and SFMP from mahewu (20mm ± 1.5). These cultures also showed high tolerance to acidic conditions (~pH4). Conclusions: The putative lactobacilli from four commercial Zimbabwean dairy products (Probrand sour milk, Kefalos Vuka vuka cheese and Chibuku opaque beer), and three strains of L. plantarum from Balkan cheeses (CLP1, CLP2 or CLP3) exhibited high antibacterial activities, while Maaz Dairy sour-, Mnandi sour- and Amansi hodzeko milk products had high antifungal activities. Our selection of Zimbabwean probiotic products has potential for further development into probiotic products for use in the control diarrhea caused by pathogenic strains of E. coli or yeast infections. Studies to characterise the probiotic potential of the live cultures in the products are underway.

Keywords: lactic acid bacteria, Staphylococcus aureus, Streptococcus spp, yeast, inhibition, acid tolerance

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Authors: K. S. Al-Mugren, A. Yahya, S. Alodah, R. Alharbi, S. H. Almsaid , A. Alqahtani, H. Jaber, A. Basaqer, N. Alajra, N. Almoghati, A. Alsalman, Khalid Alharbi

Abstract:

Context: The production of biofertilizers from naturally occurring microorganisms is an area of research that aims to enhance agricultural practices by utilizing local resources. This research project focuses on isolating and screening indigenous microorganisms with PK-fixing and phosphate solubilizing characteristics from local sources. Research Aim: The aim of this project is to develop a biofertilizer product using indigenous microorganisms and composted agro waste as a carrier. The objective is to enhance crop productivity and soil fertility through the application of biofertilizers. Methodology: The research methodology includes several key steps. Firstly, indigenous microorganisms will be isolated from local resources using the ten-fold serial dilutions technique. Screening assays will be conducted to identify microorganisms with phosphate solubilizing and PK-fixing activities. Agro-waste materials will be collected from local agricultural sources, and composting experiments will be conducted to convert them into organic matter-rich compost. Physicochemical analysis will be performed to assess the composition of the composted agro-waste. Gamma and X-ray irradiation will be used to sterilize the carrier material. The sterilized carrier will be tested for sterility using the ten-fold serial dilutions technique. Finally, selected indigenous microorganisms will be developed into biofertilizer products. Findings: The research aims to find suitable indigenous microorganisms with phosphate solubilizing and PK-fixing characteristics for biofertilizer production. Additionally, the research aims to assess the suitability of composted agro waste as a carrier for biofertilizers. The impact of gamma irradiation sterilization on pathogen elimination will also be investigated. Theoretical Importance: This research contributes to the understanding of utilizing indigenous microorganisms and composted agro waste for biofertilizer production. It expands knowledge on the potential benefits of biofertilizers in enhancing crop productivity and soil fertility. Data Collection and Analysis Procedures: The data collection process involves isolating indigenous microorganisms, conducting screening assays, collecting and composting agro waste, analyzing the physicochemical composition of composted agro waste, and testing carrier sterilization. The analysis procedures include assessing the abilities of indigenous microorganisms, evaluating the composition of composted agro waste, and determining the sterility of the carrier material. Conclusion: The research project aims to develop biofertilizer products using indigenous microorganisms and composted agro waste as a carrier. Through the isolation and screening of indigenous microorganisms, the project aims to enhance crop productivity and soil fertility by utilizing local resources. The research findings will contribute to the understanding of the suitability of composted agro waste as a carrier and the efficacy of gamma irradiation sterilization. The research outcomes will have theoretical importance in the field of biofertilizer production and agricultural practices.

Keywords: biofertilizer, microorganisms, agro waste, nuclear technologies

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Authors: Nirali Sanghavi, Julia Ash, Amy Wasserman

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Introduction: To the best of our knowledge, there is only one case report that found an association between leuprolide and scleroderma renal crisis (SRC). Leuprolide has been noted to cause acute renal failure in some patients. Given the close timing of the leuprolide injection and the worsening renal function in our patient, leuprolide likely caused exacerbation of lupus nephritis and SRC. Interestingly, our patient on long-term hydroxychloroquine (HCQ) with normal baseline cardiac function was found to have HCQ cardiomyopathy highlighting the need for close monitoring of HCQ toxicity. We know that some of the risk factors that are involved in HCQ induced cardiomyopathy are older age, females, increased dose and >10 years of HCQ use, and pre-existing cardiac and renal insufficiency. Case presentation: A 34-year-old African American woman with a history of overlap of systemic lupus erythematosus (SLE) and scleroderma features and class III lupus nephritis presented with severe headaches, elevated blood pressure (180/120 mmHg) and worsening creatinine levels (2.07 mg/dL). The headaches started 1 month ago after she started leuprolide injections for fibroids. She was being treated with mycophenolate mofetil 1 gm twice a day, belimumab weekly, HCQ 200mg, and prednisone 5 mg daily. She has been on HCQ since her teenage years. The examination was unremarkable except for proximal interphalangeal joint contractures in the right hand and sclerodactyly of bilateral hands, unchanged from baseline. Laboratory findings include urinalysis, which showed 3+ protein, 1+ blood, 6 red blood cells, and 14 white blood cells ruling out thrombotic microangiopathy. C3 was 32 mg/dL, C4 <5 mg/dL, and +dsDNA increased >1000. She was started on captopril and discharged once creatinine and blood pressure was controlled. She was readmitted with hypertension, hyperkalemia, worsening creatinine, nephrotic range proteinuria, complaints of chest pressure, and shortness of breath with pleuritic chest pain. Physical examination and lab findings were unchanged. She was treated with pulse dose methyl prednisone followed by taper and multiple anti-hypertensive agents, including captopril, for presumed lupus nephritis flare versus SRC. Renal biopsy was consistent with SRC and class IV lupus nephritis and was started on cyclophosphamide. While cardiac biopsy showed borderline myocarditis without necrosis and cytoplasmic vacuolization consistent with HCQ cardiomyopathy, hence HCQ was discontinued. Summary: It highlights a rare association of leuprolide causing exacerbation of lupus nephritis or SRC. Although rare, the current case reinforces the importance of close monitoring for HCQ toxicity in patients with renal insufficiency.

Keywords: leuprolide, lupus nephritis, scleroderma, SLE

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Authors: Rajish Shil, Amal Alduhoori, Vipin Thomachan, Jamal Teir, Radhakrishnan Renganathan

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Background: Antiphospholipid antibody syndrome (APS) has a broad spectrum of thrombotic and non-thrombotic clinical manifestations. We present a case of APS presenting with seizure, stroke, and atrial mass. Case Description: A 38-year-old male presented with headache of 10 days duration and tonic-clonic seizure. The neurological examination was normal. Magnetic resonance imaging of brain showed small acute right cerebellar infarct. Magnetic resonance angiography of brain and neck showed a focal narrowing in the origin of the internal carotid artery bilaterally. Electroencephalogram was normal. He was started on aspirin, atorvastatin, and carbamazepine. Transthoracic and trans-esophageal echocardiography showed a pedunculated and lobular atrial mass, measuring 1 X 1.5 cm, which was freely mobile across mitral valve opening across the left ventricular inflow. Autoimmune screening showed positive Antiphospholipid antibodies in high titer (Cardiolipin IgG > 120 units/ml, B2 glycoprotein IgG 90 units/mL). Anti-nuclear antibody was negative. Erythrocyte sedimentation rate and C-reactive protein levels were normal. Platelet count was low (111 x 109/L). The patient underwent successful surgical removal of the mass, which looked like a thrombotic clot, and Histopathological analysis confirmed it as a fibrinous clot, with no evidence of tumor cells. The patient was started on full anticoagulation treatment and was followed up regularly in the clinic, where our patient did not have any further complications from the disease. Discussion: Our patient was diagnosed to have APS based on the features of high positive anticardiolipin antibody IgG and B2 glycoprotein IgG levels, Stroke, thrombocytopenia, and abnormal echo findings. Thrombotic vegetation can mimic an atrial myxoma on echo. Conclusion: APS can present with neurological and cardiac manifestations, and therefore a high index of suspicion is necessary for a diagnosis of the disease as it can affect both short and long term treatment plans and prognosis. Therefore, in patients presenting with neurological symptoms like seizures, weakness and radiological diagnosis of stroke in a young patient, where atrial masses could be thought to be the cause of stroke, they should be screened for any concomitant findings of thrombocytopenia and/or activated partial thromboplastin time prolongation, which should raise the suspicion of vasculitis, specifically APS to be the primary cause of the clinical presentation.

Keywords: antiphospholipid syndrome, seizures, atrial mass, stroke

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Authors: Farhana Nosheen, Maleeha Fatima

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This study on Afghan refugee women living in Punjab, Pakistan, shows a strong relationship between poor socio-economic status and lower nutritional health status. Pakistan is one of the significant countries accepting refugees from the Afghan war. Universally, refugees are vulnerable to food security and basic life necessities. The in-hand study aimed to investigate food insecurity among afghan refugees who recently migrated to Pakistan. Purposive sampling technique was employed to collect the data from afghan women refugees settled in refugee camp settled in Capital city Islamabad, Pakistan. Data was collected through an interview tool. It revealed from data that the majority of women were underweight, about 74.7% in their reproductive years, which is an alarming situation for the forthcoming children and families. It is also shown that There’s a strong impact of their income level, education, dietary habits and food insecurity on their overall health status. It can also be observed in their Body Mass Index and in their physical appearance; they also show extremely poor levels of hemoglobin which is directly indicated anemic condition, especially iron deficiency anemia among the young Afghan refugee women. The illiteracy rate is about 93.33% among the selected participants as well as a majority of this population has 10-12 family size in comparison with their income level of about 10,000-15,000 Pakistani rupees per month, which can hardly meet their daily food expenditure. Adequate food is rarely accessible to young girls and women due to fewer national and international food aids program available in Pakistan. The majority have pale yellowish skin color (due to low iron content) along with clear white eyes (low hemoglobin level), thin hairs (protein deficiency) and spoon-shaped nails (a direct indicator of low iron level). Data showed a significant relation between appetite and BMI as their appetite is very low, which is directly indicated in their underweight body condition. About 56.67% of the participants had Urinary Tract Infections. The main causes included personal unhygienic conditions and lack of washrooms as well as drinking water facilities in their refugee camps. It is suggested that National and international food aid programs should cater to the nutritional demands of women refugees in the world to protect them from food insecurities as well as future researchers should find out better ways of analysis and treatment plans for such kind of communities who are highly prone to nutritional deficiencies and lack of basic supplies.

Keywords: food insecurity, refugees, women, vulnerable

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Authors: Hye-Hyun Lee, Hyo-Kon Chun, Kyung-Hee Kim Kim, Mi-Hee Kim, Saet-Byul Chu, Sang-Jong Lee, Seung-Hyeop Lee, Seung-Won Yi

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Some chemicals such as malachite green, methylene blue, and copper sulfate had been used frequently as disinfectants controlling fungal infection in aquaculture. However, their carcinogenicity, mutagenicity and teratogenicity were reported in mammals. After their accumulation in food fish and its consumers was confirmed, concerns about public health has resulted in enhanced monitoring and increased demand for eco-friendly treatments. Therefore, this study aimed to evaluate safety to fish and efficacy of sulfur solution processed by effective microorganisms (EM-PSS) against Saprolegnia parasitica, for use of a potential aquatic fungicidal disinfectant. The natural sulfur purchased from Kawah Ijen volcano, East Java, Indonesia was processed by the liquid mixture consisting of following twelve effective microorganisms (Rapha-el®; Lbiotech, Jeonnam, Korea), Lactobacillus parafarraginis, L. paracasei, L. harbinensis, L. buchneri, L. perolens, L. rhamnosus, L. vaccinostercus, Acetobacter lovaniensis, A. peroxydans, Pichia fermentans, Candida ethanolica, Saccharomycopsis schoenii isolated from fermentation process of oriental medicinal herbs including green tea, privet, and puer tea. The material was applied to in vitro antifungal activity test for Saprolegnia parasitica using agar dilution method. In addition, an acute toxicity test was performed on carp (Cyprinus carpio), eel (Anguilla japonica), and mud fish (Misgurnus mizolepis) for 96 hours. After three species of fish (n=15) were accustomed to experimental water environment for three days, the EM-PSS was added to each tank as final concentrations to be 0 to 500 ppm. The fish were taken into necropsy, and the histological sections of the gill, liver, and spleen were counter-stained with hematoxylin and eosin (H-E). And hence, no observed effect concentration (NOEC) of the solution was used for taking a medicinal bath for mudfish infected by Saprolegnia parasitica in practice. The result of in vitro antifungal activity test showed the growth inhibition of the fungus at 100 ppm, which and the lower concentrations occurred no fatal case in any fish species tested until the end of the examination. The 125 ppm of the solution, however, resulted in 13.3 %, 13.3 %, and 6.3 % of mortality in carp, eel, and mudfish, respectively. But both 250 and 500 ppm of the solution leaded lethality to all population of each fish species within 24 hours. Besides, H-E staining also showed no specific evidence for toxicity in fish at lesser than 100 ppm of EM-PSS. On the other hand, as a result of field application of the solution, no growth of fungal mycelium was found in fish bodies from gross observation 5 days post treatment. In conclusion, 100ppm of EM-PSS resulted in inhibition and treatment of Saprolegnia parasitica infection. In addition, the use of EM-PSS lower than 100 ppm is safe for fish. Therefore, EM-PSS could be used as aquatic fungicide, and also may be possible to be a potential eco-friendly disinfectant in aquaculture.

Keywords: antifungal activity, effective microorganism, toxicity, saprolegnia, processed sulfur solution

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Authors: Sumeet Rai, Anuj Tyagi, B. T. Naveen Kumar, Shubhkaramjeet Kaur, Niraj K. Singh

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Since their discovery, indiscriminate use of antibiotics in human, veterinary and aquaculture systems has resulted in global emergence/spread of multidrug-resistant bacterial pathogens. Thus, the need for alternative approaches to control bacterial infections has become utmost important. High selectivity/specificity of bacteriophages (phages) permits the targeting of specific bacteria without affecting the desirable flora. In this study, a lytic phage (Ahp1) specific to Aeromonas hydrophila subsp. hydrophila was isolated from finfish aquaculture pond. The host range of Ahp1 range was tested against 10 isolates of A. hydrophila, 7 isolates of A. veronii, 25 Vibrio cholerae isolates, 4 V. parahaemolyticus isolates and one isolate each of V. harveyi and Salmonella enterica collected previously. Except the host A. hydrophila subsp. hydrophila strain, no lytic activity against any other bacterial was detected. During the adsorption rate and one-step growth curve analysis, 69.7% of phage particles were able to get adsorbed on host cell followed by the release of 93 ± 6 phage progenies per host cell after a latent period of ~30 min. Phage nucleic acid was extracted by column purification methods. After determining the nature of phage nucleic acid as dsDNA, phage genome was subjected to next-generation sequencing by generating paired-end (PE, 2 x 300bp) reads on Illumina MiSeq system. De novo assembly of sequencing reads generated circular phage genome of 42,439 bp with G+C content of 58.95%. During open read frame (ORF) prediction and annotation, 22 ORFs (out of 49 total predicted ORFs) were functionally annotated and rest encoded for hypothetical proteins. Proteins involved in major functions such as phage structure formation and packaging, DNA replication and repair, DNA transcription and host cell lysis were encoded by the phage genome. The complete genome sequence of Ahp1 along with gene annotation was submitted to NCBI GenBank (accession number MF683623). Stability of Ahp1 preparations at storage temperatures of 4 °C, 30 °C, and 40 °C was studied over a period of 9 months. At 40 °C storage, phage counts declined by 4 log units within one month; with a total loss of viability after 2 months. At 30 °C temperature, phage preparation was stable for < 5 months. On the other hand, phage counts decreased by only 2 log units over a period of 9 during storage at 4 °C. As some of the phages have also been reported as glycerol sensitive, the stability of Ahp1 preparations in (0%, 15%, 30% and 45%) glycerol stocks were also studied during storage at -80 °C over a period of 9 months. The phage counts decreased only by 2 log units during storage, and no significant difference in phage counts was observed at different concentrations of glycerol. The Ahp1 phage discovered in our study had a very narrow host range and it may be useful for phage typing applications. Moreover, the endolysin and holin genes in Ahp1 genome could be ideal candidates for recombinant cloning and expression of antimicrobial proteins.

Keywords: Aeromonas hydrophila, endolysin, phage, narrow host range

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Authors: Md Iqbal Hossain, Tahmeed Ahmed, Kenneth H. Brown

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Objective: To assess the effect of community-based follow up, with or without food-supplementation and/or psychosocial stimulation, as an alternative to current hospital-based follow-up of children with moderate-acute-malnutrition (WHZ < -2 to -3) (MAM). Design/methods: The study was conducted at the ICDDR,B Dhaka Hospital and in four urban primary health care centers of Dhaka, Bangladesh during 2005-2007. The efficacy of five different randomly assigned interventions was compared with respect to the rate of completion of follow-up, growth and morbidity in 227 MAM children aged 6-24 months who were initially treated at ICDDR,B for diarrhea and/or other morbidities. The interventions were: 1) Fortnightly follow-up care (FFC) at the ICDDR,B’s outpatient-unit, including growth monitoring, health education, and micro-nutrient supplementation (H-C, n=49). 2) FFC at community follow-up unit (CNFU) [established in the existing urban primary health-care centers close to the residence of the child] but received the same regimen as H-C (C-C, n=53). 3) As per C-C plus cereal-based supplementary food (SF) (C-SF, n=49). The SF packets were distributed on recruitment and at every visit in CNFU [@1 packet/day for 6–11 and 2 packets/day for 12-24 month old children. Each packet contained 20g toasted rice-powder, 10g toasted lentil-powder, 5g molasses, and 3g soy bean oil, to provide a total of ~ 150kcal with 11% energy from protein]. 4) As per C-C plus psychosocial stimulation (PS) (C-PS, n=43). PS consisted of child-stimulation and parental-counseling conducted by trained health workers. 5) As per C-C plus both SF+PS (C-SF+PS, n=33). Results: A total of 227children (48.5% female), with a mean ± SD age of 12.6 ±3.8 months, and WHZ of - 2.53±0.28 enrolled. Baseline characteristics did not differ by treatment group. The rate of spontaneous attendance at scheduled follow-up visits gradually decreased in all groups. Follow-up attendance and gain in weight and length were greater in groups C-SF, C-SF+PS, and C-PS than C-C, and these indicators were observed least in H-C. Children in the H-C group more often suffered from diarrhea (25 % vs. 4-9%) and fever (28% vs. 8-11%) than other groups (p < 0.05). Children who attended at least five of the total six scheduled follow-up visits gained more in weight (median: 0.86 vs. 0.62 kg, p=0.002), length (median: 2.4 vs. 2.0 cm, p=0.009) than those who attended fewer. Conclusions: Community-based service delivery, especially including supplementary food with or without psychosocial stimulation, permits better rehabilitation of children with MAM compared to current hospital outpatients-based care. By scaling the community-based follow-up including food supplementation with or without psychosocial stimulation, it will be possible to rehabilitate a greater number of MAM children in a better way.

Keywords: community-based management, moderate acute malnutrition, psychosocial stimulation, supplementary food

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Authors: Shiva Shakori Poshteh

Abstract:

Lung cancer is a highly prevalent and devastating disease, representing a significant global health concern with profound implications for healthcare systems and society. Its high incidence, mortality rates, and late-stage diagnosis contribute to its formidable nature. To address these challenges, nanoparticle-based drug delivery has emerged as a promising therapeutic strategy. Curcumin (CUR), a natural compound derived from turmeric, has garnered attention as a potential nanomedicine for lung cancer treatment. Nanoparticle formulations of CUR offer several advantages, including improved drug delivery efficiency, enhanced stability, controlled release kinetics, and targeted delivery to lung cancer cells. CUR exhibits a diverse array of effects on cancer cells. It induces apoptosis by upregulating pro-apoptotic proteins, such as Bax and Bak, and downregulating anti-apoptotic proteins, such as Bcl-2. Additionally, CUR inhibits cell proliferation by modulating key signaling pathways involved in cancer progression. It suppresses the PI3K/Akt pathway, crucial for cell survival and growth, and attenuates the mTOR pathway, which regulates protein synthesis and cell proliferation. CUR also interferes with the MAPK pathway, which controls cell proliferation and survival, and modulates the Wnt/β-catenin pathway, which plays a role in cell proliferation and tumor development. Moreover, CUR exhibits potent antioxidant activity, reducing oxidative stress and protecting cells from DNA damage. Utilizing CUR as a standalone treatment is limited by poor bioavailability, lack of targeting, and degradation susceptibility. Nanoparticle-based delivery systems can overcome these challenges. They enhance CUR’s bioavailability, protect it from degradation, and improve absorption. Further, Nanoparticles enable targeted delivery to lung cancer cells through surface modifications or ligand-based targeting, ensuring sustained release of CUR to prolong therapeutic effects, reduce administration frequency, and facilitate penetration through the tumor microenvironment, thereby enhancing CUR’s access to cancer cells. Thus, nanoparticle-based CUR delivery systems promise to improve lung cancer treatment outcomes. This article provides an overview of lung cancer, explores CUR nanoparticles as a treatment approach, discusses the benefits and challenges of nanoparticle-based drug delivery, and highlights prospects for CUR nanoparticles in lung cancer treatment. Future research aims to optimize these delivery systems for improved efficacy and patient prognosis in lung cancer.

Keywords: lung cancer, curcumin, nanomedicine, nanoparticle-based drug delivery

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