Search results for: normal operators

Authors: Kamila Dus-Szachniewicz, Artur Bednarkiewicz, Katarzyna Gdesz-Birula, Slawomir Drobczynski

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In modern oncology hyperthermia (HT) is defined as a controlled tumor heating. HT treatment temperatures range between 40–48 °C and can selectively damage heat-sensitive cancer cells or limit their further growth, usually with minimal injury to healthy tissues. Despite many advantages, conventional whole-body and regional hyperthermia have clinically relevant side effects, including cardiac and vascular disorders. Additionally, the lack of accessibility of deep-seated tumor sites and impaired targeting micrometastases renders HT less effective. It is believed that above disadvantages can significantly overcome by the application of biofunctionalized microparticles, which can specifically target tumor sites and become activated by an external stimulus to provide a sufficient cellular response. In our research, the unique optical tweezers system have enabled capturing the silica microparticles, primary cells and tumor spheroids in highly controllable and reproducible environment to study the impact of localized heat stimulation on normal and pathological cell and within multicellular tumor spheroid. High throughput spheroid model was introduced to better mimic the response to HT treatment on tumors in vivo. Additionally, application of local heating of tumor spheroids was performed in strictly controlled conditions resembling tumor microenvironment (temperature, pH, hypoxia, etc.), in response to localized and nonhomogeneous hyperthermia in the extracellular matrix, which promotes tumor progression and metastatic spread. The lack of precise control over these well- defined parameters in basic research leads to discrepancies in the response of tumor cells to the new treatment strategy in preclinical animal testing. The developed approach enables also sorting out subclasses of cells, which exhibit partial or total resistance to therapy, in order to understand fundamental aspects of the resistance shown by given tumor cells in response to given therapy mode and conditions. This work was funded by the National Science Centre (NCN, Poland) under grant no. UMO-2017/27/B/ST7/01255.

Keywords: cancer spheroids, hyperthermia, microparticles, optical tweezers

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Authors: Yelin Zhao, Xinxiu Li, Martin Smelik, Oleg Sysoev, Firoj Mahmud, Dina Mansour Aly, Mikael Benson

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Background: Early diagnosis of pancreatic cancer is clinically challenging due to vague, or no symptoms, and lack of biomarkers. Polygenic risk score (PRS) scores may provide a valuable tool to assess increased or decreased risk of PC. This study aimed to develop such PRS by filtering genetic variants identified by GWAS using transcriptional programs identified by single-cell RNA sequencing (scRNA-seq). Methods: ScRNA-seq data from 24 pancreatic ductal adenocarcinoma (PDAC) tumor samples and 11 normal pancreases were analyzed to identify differentially expressed genes (DEGs) in in tumor and microenvironment cell types compared to healthy tissues. Pathway analysis showed that the DEGs were enriched for hundreds of significant pathways. These were clustered into 40 “programs” based on gene similarity, using the Jaccard index. Published genetic variants associated with PDAC were mapped to each program to generate program PRSs (pPRSs). These pPRSs, along with five previously published PRSs (PGS000083, PGS000725, PGS000663, PGS000159, and PGS002264), were evaluated in a European-origin population from the UK Biobank, consisting of 1,310 PDAC participants and 407,473 non-pancreatic cancer participants. Stepwise Cox regression analysis was performed to determine associations between pPRSs with the development of PC, with adjustments of sex and principal components of genetic ancestry. Results: The PDAC genetic variants were mapped to 23 programs and were used to generate pPRSs for these programs. Four distinct pPRSs (P1, P6, P11, and P16) and two published PRSs (PGS000663 and PGS002264) were significantly associated with an increased risk of developing PC. Among these, P6 exhibited the greatest hazard ratio (adjusted HR[95% CI] = 1.67[1.14-2.45], p = 0.008). In contrast, P10 and P4 were associated with lower risk of developing PC (adjusted HR[95% CI] = 0.58[0.42-0.81], p = 0.001, and adjusted HR[95% CI] = 0.75[0.59-0.96], p = 0.019). By comparison, two of the five published PRS exhibited an association with PDAC onset with HR (PGS000663: adjusted HR[95% CI] = 1.24[1.14-1.35], p < 0.001 and PGS002264: adjusted HR[95% CI] = 1.14[1.07-1.22], p < 0.001). Conclusion: Compared to published PRSs, scRNA-seq-based pPRSs may be used not only to assess increased but also decreased risk of PDAC.

Keywords: cox regression, pancreatic cancer, polygenic risk score, scRNA-seq, UK biobank

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Authors: Chiou-Shiue Ko

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As is explicitly stipulated in Article 7 of the Enforcement Rules of the Special Education Act as amended in 1998, "in principle, children with disabilities should be integrated with normal children for preschool education". Since then, all cities and counties have been committed to promoting preschool inclusive education. The Education Department, New Taipei City Government, has been actively recruiting advisory groups of professors to assist in the implementation of inclusive education in preschools since 2001. Since 2011, the author of this study has been guiding Preschool Rainbow to implement inclusive education. Through field observations, meetings, and teaching demonstration seminars, this study explored the process of how inclusive education has been successfully implemented in collaboration with teachers of special education classes and regular classes in Preschool Rainbow. The implementation phases for inclusive education in a single academic year include the following: 1) Preparatory stage. Prior to implementation, teachers in special education and regular classes discuss ways of conducting inclusive education and organize reading clubs to read books related to curriculum modifications that integrate the eight education strategies, early treatment and education, and early childhood education programs to enhance their capacity to implement and compose teaching plans for inclusive education. In addition to the general objectives of inclusive education, the objective of inclusive education for special children is also embedded into the Individualized Education Program (IEP). 2) Implementation stage. Initially, a promotional program for special education is implemented for the children to allow all the children in the preschool to understand their own special qualities and those of special children. After the implementation of three weeks of reverse inclusion, the children in the special education classes are put into groups and enter the regular classes twice a week to implement adjustments to their inclusion in the learning area and the curriculum. In 2013, further cooperation was carried out with adjacent hospitals to perform development screening activities for the early detection of children with developmental delays. 3) Review and reflection stage. After the implementation of inclusive education, all teachers in the preschool are divided into two groups to record their teaching plans and the lessons learned during implementation. The effectiveness of implementing the objective of inclusive education is also reviewed. With the collaboration of all teachers, in 2015, Preschool Rainbow won New Taipei City’s “Preschool Light” award as an exceptional model for inclusive education. Its model of implementing inclusive education can be used as a reference for other preschools.

Keywords: collaboration, inclusive education, preschool, teachers, special education classes, regular classes

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Authors: Khadijeh Abhari, Seyed Shahram Shekarforoush, Saeid Hosseinzadeh

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Probiotics have been considered as an approach to treat and prevent a wide range of inflammatory diseases. The spore forming probiotic strain Bacillus coagulans has demonstrated anti-inflammatory and immune-modulating effects in both animals and humans. The prebiotic, inulin, also potentially affects the immune system as a result of the change in the composition or fermentation profile of the gastrointestinal microbiota. An in vivo trial was conducted to evaluate the effects of probiotic B. coagulans, and inulin, either separately or in combination, on down regulate immune responses and progression of rheumatoid arthritis using induced arthritis rat model. Forty-eight male Wistar rats were randomly divided into 6 groups and fed as follow: 1) control: Normal healthy rats fed by standard diet, 2) Disease control (RA): Arthritic induced (RA) rats fed by standard diet, 3) Prebiotic (PRE): RA+ 5% w/w long chain inulin, 4) Probiotic (PRO): RA+ 109 spores/day B. coagulans by orogastric gavage, 5) Synbiotic (SYN): RA+ 5% w/w long chain inulin and 109 spores/day B. coagulans and 6) Treatment control: (INDO): RA+ 3 mg/kg/day indomethacin by orogastric gavage. Feeding with mentioned diets started on day 0 and continued to the end of study. On day 14, rats were injected with complete Freund’s adjuvant (CFA) to induce arthritis. Arthritis activity was evaluated by biochemical parameters and paw thickness. Biochemical assay for Fibrinogen (Fn), Serum Amyloid A (SAA), TNF-α and Alpha-1-acid glycoprotein (α1AGp) was performed on day 21, 28 and 35 (1, 2 and 3 weeks post RA induction). Pretreatment with PRE, PRO and SYN diets significantly inhibit SAA and Fn production in arthritic rats (P < 0.001). A significant decrease in production of pro-inflammatory cytokines, TNF-α, was seen in PRE, PRO and SYN groups (P < 0.001) which was similar to the effect of the anti-inflammatory drug Indomethacin. Further, there were no significant anti-inflammatory effects observed following different treatments using α1AGp as a RA indicator. Pretreatment with all supplied diets significantly inhibited the development of paw swelling induced by CFA (P < 0.001). Conclusion: Results of this study support that oral intake of probiotic B. coagulans and inulin are able to improve biochemical and clinical parameters of induced RA in rat.

Keywords: rheumatoid arthritis, bacillus coagulans, inulin, animal model

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Authors: Rachnavy Pornthep, Khaothin Thawichai

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The purpose of this paper was to investigate the effects of rowing ergometer exercise on older persons health. The subjects were divided into two groups. Group 1 was control group (10 male and 10 female) Group 2 was experimental group (10 male and 10 female). The time for study was 12 week. Group 1 engage in normal daily activities Group 2 Training with rowing machine for 20 minutes three days a week. The average age of the experimental group was 73.7 years old, mean weight 55.4 kg, height 154.8 cm in the control group, mean age was 74.95 years, mean weight 48.6 kg, mean height 153.85 cm. Physical fitness test composted of body size, flexibility, Strength, muscle endurance and cardiovascular endurance. The comparison between the experimental and control groups before training showed that body weight, body mass index and waist to hip ratio were significantly different. The flexibility, strength, cardiovascular endurance was not significantly different. The comparison between the control group and the experimental group after training showed that body weight, body mass index and cardiovascular endurance were significantly different. The ratio of waist to hips, flexibility and muscular strength were not significantly different. Comparison of physical fitness before training and after training of the control group showed that body weight, flexibility (Sit and reach) and muscular strength (30 – Second chair stand) were significantly different. Body mass index, waist to hip ratio, muscles flexible (Shoulder girdle flexibility), muscle strength (30 – Second arm curl) and the cardiovascular endurance were not significantly difference. Comparison of physical fitness before training and after training the experimental group showed that waist to hip ratio, flexibility (sit and reach) muscle strength (30 – Second chair stand), cardiovascular endurance (Standing leg raises - up to 2 minutes) were significantly different. The Body mass index and the flexibility (Shoulder girdle flexibility) no significantly difference. The study found that exercising with rowing machine can improve the physical fitness of the elderly, especially the cardiovascular endurance, corresponding with the past research on the effects of exercise in the elderly with different exercise such as cycling, treadmill, walking on the elliptical machine. Therefore, we can conclude that exercise by using rowing machine can improve cardiovascular system and flexibility in the elderly.

Keywords: effect, rowing, exercise, elderly

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Authors: Aymen Arfaoui, Abdelkader Soumaya

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The Messalla-Ressas-Bou Kornine (MRB) and Hammamet Korbous (HK) major trending North-South fault zones provide a good opportunity to show the effects of the Eocene compressive phase in northern Tunisia. They acted as paleogeographical boundaries during the Mesozoic and belonged to a significant strike-slip corridor called the «North-South Axis,» extending from the Saharan platform at the South to the Gulf of Tunis at the North. Our study area is situated in a relay zone between two significant strike-slip faults (HK and MRB), separating the Atlas domain from the Pelagian Block. We used a multidisciplinary approach, including fieldwork, stress inversion, and geophysical profiles, to argue the shortening event that affected the study region. The MRB and HK contractional duplex is a privileged area for a local stress field and stress nucleation. The stress inversion of fault slip data reveals an Eocene compression with NW-SE trending SHmax, reactivating most of the ancient Mesozoic normal faults in the region. This shortening phase is represented in the MRB belt by an angular unconformity between the Upper Eocene over various Cretaceous strata. The stress inversion data reveal a compressive tectonic with an average NW-SE trending Shmax. The major N-S faults are reactivated under this shortening as sinistral oblique faults. The orientation of SHmax deviates from NW-SE to E-W near the preexisting deep faults of MRB and HK. This E-W stress direction generated the emerging overlap of Ressas-Messella and blind thrust faults in the Cretaceous deposits. The connection of the sub-meridian reverse faults in depth creates "flower structures" under an E-W local compressive stress. In addition, we detected a reorientation of the SHmax into an N-S direction in the central part of the MRB - HK contractional duplex, creating E-W reverse faults and overlapping zones. Finally, the Eocene compression constituted the first major tectonic phase which inverted the Mesozoic preexisting extensive fault system in Northern Tunisia.

Keywords: Tunisia, eocene compression, tectonic stress field, Bou Kornine-Ressas-Messella

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Authors: M. Gowri, E. K. Girija, V. Ganesh

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Background and Significance: Among the dental infections, inflammation and infection of the root canal are common among all age groups. Currently, the management of root canal infections involves cleaning the canal with powerful irrigants followed by intracanal medicament application. Though these treatments have been in vogue for a long time, root canal failures do occur. Treatment for root canal infections is limited due to the anatomical complexity in terms of small micrometer volumes and poor penetration of drugs. Thus, infections of the root canal seem to be a challenge that demands development of new agents that can eradicate E. faecalis. Methodology: In the present study, we synthesized and screened silver-curcumin nanoparticle against E. faecalis. Morphological cell damage and antibiofilm activity of silver-curcumin nanoparticle on E. faecalis was studied using scanning electron microscopy (SEM). Biochemical evidence for membrane damage was studied using flow cytometry. Further, the antifungal activity of silver-curcumin nanoparticle was evaluated in an ex vivo dentinal tubule infection model. Results: Screening data showed that silver-curcumin nanoparticle was active against E. faecalis. silver-curcumin nanoparticle exerted time kill effect. Further, SEM images of E. faecalis showed that silver-curcumin nanoparticle caused membrane damage and inhibited biofilm formation. Biochemical evidence for membrane damage was confirmed by increased propidium iodide (PI) uptake in flow cytometry. Further, the antifungal activity of silver-curcumin nanoparticle was evaluated in an ex vivo dentinal tubule infection model, which mimics human tooth root canal infection. Confocal laser scanning microscopy studies showed eradication of E. faecalis and reduction in colony forming unit (CFU) after 24 h treatment in the infected tooth samples in this model. Further, silver-curcumin nanoparticle was found to be hemocompatible, not cytotoxic to normal mammalian NIH 3T3 cells and non-mutagenic. Conclusion: The results of this study can pave the way for developing new antibacterial agents with well deciphered mechanisms of action and can be a promising antibacterial agent or medicament against root canal infection.

Keywords: ex vivo dentine model, inhibition of biofilm formation, root canal infection, silver-curcumin nanoparticle

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Authors: Deepthy Ann Joy, N. Sreedevi

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Hearing impairment (HI) at an early age, identified before the onset of language development can reduce the negative effect on speech and language development of children. Early rehabilitation is very important in the improvement of speech production in children with HI. Other than conventional hearing aids, Cochlear Implants are being used in the rehabilitation of children with HI. However, delay in acquisition of speech and language milestones persist in children with Cochlear Implant (CI). Delay in speech milestones are reflected through speech sound errors. These errors reflect the temporal and spectral characteristics of speech. Hence, acoustical analysis of the speech sounds will provide a better representation of speech production skills in children with CI. The present study aimed at investigating the acoustic characteristics of vowels in Malayalam speaking children with a cochlear implant. The participants of the study consisted of 20 Malayalam speaking children in the age range of four and seven years. The experimental group consisted of 10 children with CI, and the control group consisted of 10 typically developing children. Acoustic analysis was carried out for 5 short (/a/, /i/, /u/, /e/, /o/) and 5 long vowels (/a:/, /i:/, /u:/, /e:/, /o:/) in word-initial position. The responses were recorded and analyzed for acoustic parameters such as Vowel duration, Ratio of the duration of a short and long vowel, Formant frequencies (F₁ and F₂) and Formant Centralization Ratio (FCR) computed using the formula (F₂u+F₂a+F₁i+F₁u)/(F₂i+F₁a). Findings of the present study indicated that the values for vowel duration were higher in experimental group compared to the control group for all the vowels except for /u/. Ratio of duration of short and long vowel was also found to be higher in experimental group compared to control group except for /i/. Further F₁ for all vowels was found to be higher in experimental group with variability noticed in F₂ values. FCR was found be higher in experimental group, indicating vowel centralization. Further, the results of independent t-test revealed no significant difference across the parameters in both the groups. It was found that the spectral and temporal measures in children with CI moved towards normal range. The result emphasizes the significance of early rehabilitation in children with hearing impairment. The role of rehabilitation related aspects are also discussed in detail which can be clinically incorporated for the betterment of speech therapeutic services in children with CI.

Keywords: acoustics, cochlear implant, Malayalam, vowels

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Authors: Ayesha Waqar Khan, Mariam Altaf, Jamil Ahmad, Shaheen Shahzad

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Kidney fibrosis is an anticipated outcome of possibly all types of progressive chronic kidney disease (CKD). Epithelial-mesenchymal transition (EMT) signaling pathway is responsible for production of matrix-producing fibroblasts and myofibroblasts in diseased kidney. In this study, a discrete model of TGF-beta (transforming growth factor) and CTGF (connective tissue growth factor) was constructed using Rene Thomas formalism to investigate renal fibrosis turn over. The kinetic logic proposed by Rene Thomas is a renowned approach for modeling of Biological Regulatory Networks (BRNs). This modeling approach uses a set of constraints which represents the dynamics of the BRN thus analyzing the pathway and predicting critical trajectories that lead to a normal or diseased state. The molecular connection between TGF-beta, Smad 2/3 (transcription factor) phosphorylation and CTGF is modeled using GenoTech. The order of BRN is CTGF, TGF-B, and SMAD3 respectively. The predicted cycle depicts activation of TGF-B (TGF-β) via cleavage of its own pro-domain (0,1,0) and presentation to TGFR-II receptor phosphorylating SMAD3 (Smad2/3) in the state (0,1,1). Later TGF-B is turned off (0,0,1) thereby activating SMAD3 that further stimulates the expression of CTGF in the state (1,0,1) and itself turns off in (1,0,0). Elevated CTGF expression reactivates TGF-B (1,1,0) and the cycle continues. The predicted model has generated one cycle and two steady states. Cyclic behavior in this study represents the diseased state in which all three proteins contribute to renal fibrosis. The proposed model is in accordance with the experimental findings of the existing diseased state. Extended cycle results in enhanced CTGF expression through Smad2/3 and Smad4 translocation in the nucleus. The results suggest that the system converges towards organ fibrogenesis if CTGF remains constructively active along with Smad2/3 and Smad 4 that plays an important role in kidney fibrosis. Therefore, modeling regulatory pathways of kidney fibrosis will escort to the progress of therapeutic tools and real-world useful applications such as predictive and preventive medicine.

Keywords: CTGF, renal fibrosis signaling pathway, system biology, qualitative modeling

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Authors: M. Haruna, O. O. Onafowokan, G. Holt, K. Anderson, R. G. Middleton

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Background: Requirements for satisfactory outcomes following total hip arthroplasty (THA) include restoration of femoral offset, version, and leg length. Various techniques have been described for restoring these biomechanical parameters, with leg length restoration being the most predominantly described. We describe a “quartered head technique” (QHT) which uses a stepwise series of femoral head osteotomies to identify and preserve the centre of rotation of the femoral head during THA in order to ensure reconstruction of leg length, offset and stem version, such that hip biomechanics are restored as near to normal as possible. This study aims to identify whether using the QHT during hip arthroplasty effectively restores leg length and femoral offset to within acceptable parameters. Methods: A retrospective review of 206 hips was carried out, leaving 124 hips in the final analysis. Power analysis indicated a minimum of 37 patients required. All operations were performed using an anterolateral approach by a single surgeon. All femoral implants were cemented, collarless, polished double taper CPT® stems (Zimmer, Swindon, UK). Both cemented, and uncemented acetabular components were used (Zimmer, Swindon, UK). Leg length, version, and offset were assessed intra-operatively and reproduced using the QHT. Post-operative leg length and femoral offset were determined and compared with the contralateral native hip, and the difference was then calculated. For the determination of leg length discrepancy (LLD), we used the method described by Williamson & Reckling, which has been shown to be reproducible with a measurement error of ±1mm. As a reference, the inferior margin of the acetabular teardrop and the most prominent point of the lesser trochanter were used. A discrepancy of less than 6mm LLD was chosen as acceptable. All peri-operative radiographs were assessed by two independent observers. Results: The mean absolute post-operative difference in leg length from the contralateral leg was +3.58mm. 84% of patients (104/124) had LLD within ±6mm of the contralateral limb. The mean absolute post-operative difference in offset from contralateral leg was +3.88mm (range -15 to +9mm, median 3mm). 90% of patients (112/124) were within ±6mm offset of the contralateral limb. There was no statistical difference noted between observer measurements. Conclusion: The QHT provides a simple, inexpensive yet effective method of maintaining femoral leg length and offset during total hip arthroplasty. Combining this technique with pre-operative templating or other techniques described may enable surgeons to reduce even further the discrepancies between pre-operative state and post-operative outcome.

Keywords: leg length discrepancy, technical tip, total hip arthroplasty, operative technique

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Authors: Ingrid Ruzbarska, Martin Zvonar, Piotr Oleśniewicz, Julita Markiewicz-Patkowska, Krzysztof Widawski, Daniel Puciato

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Obese children will probably become obese adults, consequently exposed to an increased risk of comorbidity and premature mortality. Body weight may be indirectly determined by continuous development of coordination and motor skills. The level of motor skills and abilities is an important factor that promotes physical activity since early childhood. The aim of the study is to thoroughly understand the internal relations between motor coordination abilities and the somatic development of prepubertal children and to determine the effect of excess body weight on motor coordination by comparing the motor ability levels of children with different body mass index (BMI) values. The data were collected from 436 children aged 7–10 years, without health limitations, fully participating in school physical education classes. Body height was measured with portable stadiometers (Harpenden, Holtain Ltd.), and body mass—with a digital scale (HN-286, Omron). Motor coordination was evaluated with the Kiphard-Schilling body coordination test, Körperkoordinationstest für Kinder. The normality test by Shapiro-Wilk was used to verify the data distribution. The correlation analysis revealed a statistically significant negative association between the dynamic balance and BMI, as well as between the motor quotient and BMI (p<0.01) for both boys and girls. The results showed no effect of gender on the difference in the observed trends. The analysis of variance proved statistically significant differences between normal weight children and their overweight or obese counterparts. Coordination abilities probably play an important role in preventing or moderating the negative trajectory leading to childhood overweight and obesity. At this age, the development of coordination abilities should become a key strategy, targeted at long-term prevention of obesity and the promotion of an active lifestyle in adulthood. Motor performance is essential for implementing a healthy lifestyle in childhood already. Physical inactivity apparently results in motor deficits and a sedentary lifestyle in children, which may be accompanied by excess energy intake and overweight.

Keywords: childhood, KTK test, physical education, psychomotor competence

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Authors: Nigatu Tadesse, Ying Liu, Juan Li, Hong Ming Liu

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Gastric carcinogenesis is a lengthy process of histopathological transition from normal to atrophic gastritis (AG) to intestinal metaplasia (GIM), dysplasia toward gastric cancer (GC). The stage of GIM identified as precancerous lesions with resistance to H-pylori eradication and recurrence after endoscopic surgical resection therapies. GIM divided in to two morphologically distinct phenotypes such as complete GIM bearing intestinal type morphology whereas the incomplete type has colonic type morphology. The incomplete type GIM considered to be the greatest risk factor for the development of GC. Studies indicated the expression of the caudal type homeobox 2 (CDX2) gene is responsible for the development of complete GIM but its progressive downregulation from incomplete metaplasia toward advanced GC identified as the risk for IM progression and neoplastic transformation. The downregulation of CDX2 gene have promoted cell growth and proliferation in gastric and colon cancers and ascribed in chemo-treatment inefficacies. CDX2 downregulated through promoter region hypermethylation in which the methylation frequency positively correlated with the dietary history of the patients, suggesting the role of diet as methyl carbon donor sources such as methionine. However, the metabolism of exogenous methionine is yet unclear. Targeting exogenous methionine metabolism has become a promising approach to limits tumor cell growth, proliferation and progression and increase treatment outcome. This review article discusses molecular alterations that could shed light on the potential of exogenous methionine metabolisms, such as gut microbiota alteration as sources of methionine to host cells, metabolic pathway signaling via PI3K/AKt/mTORC1-c-MYC to rewire exogenous methionine and signature of increased gene methylation index, cell growth and proliferation in GIM, with insights to new treatment avenue via targeting methionine metabolism, and the need for future integrated studies on molecular alterations and metabolomics to uncover altered methionine metabolism and characterization of CDX2 methylation in gastric intestinal metaplasia for potential therapeutic exploitation.

Keywords: altered methionine metabolism, Intestinal metaplesia, CDX2 gene, gastric cancer

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Authors: Atiwat Khatpibunchai, Taweesak Kritjaroen

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A social enterprise is the innovative hybrid organizations where its ultimate goal is to generate revenue and use it as a fund to solve the social and environmental problem. Although the evidence shows the clear value of economic, social and environmental aspects, the limitations of most of the social enterprises are the expanding impact of social and environmental aspects through the normal market mechanism. This is because the major sources of revenues of social enterprises derive from the business advocates who merely wish to support society and environment by using products and services of social enterprises rather than expect the satisfaction and the distinctive advantage of products and services. Thus, social enterprises cannot reach the achievement as other businesses do. The relevant concepts from the literature review revealed that dynamic capability is the ability to sense, integrate and reconfigure internal resources and utilize external resources to adapt to changing environments, create innovation and achieve competitive advantage. The objective of this research is to study the influence of dynamic capability that affects competitive advantage and sustainable performance, as well as to determine important elements of dynamic capability. The researchers developed a conceptual model from the related concepts and theories of dynamic capability. A conceptual model will support and show the influence of dynamic capability on competitive advantage and sustainable performance of social enterprises. The 230 organizations in South-East Asia served as participants in this study. The results of the study were analyzed by the structural equation model (SEM) and it was indicated that research model is consistent with empirical research. The results also demonstrated that dynamic capability has a direct and indirect influence on competitive advantage and sustainable performance. Moreover, it can be summarized that dynamic capability consists of the five elements: 1) the ability to sense an opportunity; 2) the ability to seize an opportunity; 3) the ability to integrate resources; 4) the ability to absorb resources; 5) the ability to create innovation. The study recommends that related sectors can use this study as a guideline to support and promote social enterprises. The focus should be pointed to the important elements of dynamic capability that are the development of the ability to transform existing resources in the organization and the ability to seize opportunity from changing market.

Keywords: dynamic capability, social enterprise, sustainable competitive advantage, sustainable performance

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Authors: Noriyuki Suyama

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This paper looked into consumer behavioral changes by analyzing the data collected by ASMARKS Co., one of a research companies in Japan. The purpose of the paper is to understand the two differences of before vs. after COVID-19 pandemic and Japanese living in Japan. Subsequently, examining the analysis results helped obtain useful insights into new business models for business parties in Japan as a microlevel perspective. The paper also tried to explore future conditions of globalization by taking into consideration nation’s political and economic changes as a macro-level perspective. The COVID-19 has been continuing its spread across the world with more than 60 million confirmed cases in 190 countries. This pandemic with restricted scopes of behavior mandates have disrupted the consumer habits of their lifestyles. Consumers have tendency to learn new ways when they have trouble in taking routine action. For example, the government forces people to refrain from going out, they try to telecommute at home. If the situation come back to normal, people still change their lifestyles to fit in the best. Some of data show typical effects of COVID-19; forceful exposure to digitalized work-life styles; more flexible time at home; importance of trustful and useful information gathering between what's good and bad;etc. in comparison with before vs. after COVID-19 pandemic. In addition, Japanese have less changed their lifestyles than Expatriates living in Japan. For example, while 94% of the expatriates have decreased their outgo because of self-quarantine, only 55% of the Japanese have done. There are more differences in both comparisons in the analysis results. The economic downtrend resulting from COVID-19 is supposed to be at least as devastating if not more so than that of the financial crisis. With unemployment levels in the US taking two weeks to reach what took 6 months in the 2008 crisis, there is no doubt of a global recession some predict could reach 10% or above of GDP. As a result, globalization in the global supply chain of goods and services will end up with negative impact. A lot of governmental financial and economic policies are supposed to focus on their own profits and interests, exclusing other countries interests as is the case with the Recovery Act just after the global financial crisis from 2007 to 2008. Both micro- and macro-levels analysis successfully reveal important connotations and managerial implications of business in Japan for Japanese consumers as well as after COVID-19 global business.

Keywords: COVID-19, lifestyle in Japan, expatriates, consumer behavior

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Authors: Asowata Osamede

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Optimized gain in respect to output power of stand-alone photovoltaic (PV) systems is one of the major focus of PV in recent times. This is evident to its low carbon emission and efficiency. Power failure or outage from commercial providers in general does not promote development to the public and private sector, these basically limit the development of industries. The need for a well-structured PV system is of importance for an efficient and cost-effective monitoring system. The purpose of this paper is to validate the maximum power point of an off-grid PV system taking into consideration the most effective tilt and orientation angles for PV's in the southern hemisphere. This paper is based on analyzing the system using a solar charger with MPPT from a pulse width modulation (PWM) perspective. The power conditioning device chosen is a solar charger with MPPT. The practical setup consists of a PV panel that is set to an orientation angle of 0o north, with a corresponding tilt angle of 36 o, 26o and 16o. The load employed in this set-up are three Lead Acid Batteries (LAB). The percentage fully charged, charging and not charging conditions are observed for all three batteries. The results obtained in this research is used to draw the conclusion that would provide a benchmark for researchers and scientist worldwide. This is done so as to have an idea of the best tilt and orientation angles for maximum power point in a basic off-grid PV system. A quantitative analysis would be employed in this research. Quantitative research tends to focus on measurement and proof. Inferential statistics are frequently used to generalize what is found about the study sample to the population as a whole. This would involve: selecting and defining the research question, deciding on a study type, deciding on the data collection tools, selecting the sample and its size, analyzing, interpreting and validating findings Preliminary results which include regression analysis (normal probability plot and residual plot using polynomial 6) showed the maximum power point in the system. The best tilt angle for maximum power point tracking proves that the 36o tilt angle provided the best average on time which in turns put the system into a pulse width modulation stage.

Keywords: power-conversion, meteonorm, PV panels, DC-DC converters

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Authors: Ramin Mehdiabadi

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Background: Breast cancer remains the most prevalent cancer diagnosis and the leading cause of cancer death among women globally, representing 11.7% of new cases and 6.9% of deaths. While the incidence and mortality of major cancers are declining in developed regions like the United States and Western Europe, underdeveloped and developing countries exhibit an increasing trend, attributed to lifestyle factors such as smoking, physical inactivity, and high-calorie diets. Objective: This study explores the intricate relationship between the mammalian transcription factor forkhead box (FoxM1) and the microRNA miR-216b-5p in various subtypes of breast cancer, aiming to deepen the understanding of their roles in tumorigenesis, metastasis, and drug resistance. Methods: Breast cancer subtypes were categorized based on key biomarkers: estrogen receptors, progesterone receptors, and human epidermal growth factor receptor 2. These include luminal A, luminal B, HER2 enriched, triple-negative, and normal-like subtypes. We focused on analyzing the expression levels of FoxM1 and miR-216b-5p, given the known role of FoxM1 in cell proliferation and its implications in cancer pathologies such as lung, gastric, and breast cancers. Concurrently, miR-216b-5p's function as a tumor suppressor was evaluated to ascertain its regulatory effects on FoxM1. Results: Preliminary data indicate a nuanced interplay between FoxM1 and miR-216b-5p, suggesting a potential inverse relationship that varies across breast cancer subtypes. This relationship underscores the dual role of these biomarkers in modulating cancer progression and response to treatments. Conclusion: The findings advocate for the potential of miR-216b-5p to serve as a prognostic biomarker and a therapeutic target, particularly in subtypes where FoxM1 is prominently expressed. Understanding these molecular interactions provides crucial insights into the personalized treatment strategies and could lead to more effective therapeutic interventions in breast cancer management. Implications: The study highlights the importance of molecular profiling in breast cancer treatment and emphasizes the need for targeted therapeutic approaches in managing diverse cancer subtypes, particularly in varying global contexts where lifestyle factors significantly impact cancer dynamics.

Keywords: breast cancer, gene expression, FoxM1, microRNA

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Authors: J. J. Lee, S. R. Sung, E. J. Yum, S. C. Kim, B. H. Hyun, M. Her, H. S. Lee

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Canine brucellosis is a critical problem in dogs leading to reproductive diseases which are mainly caused by Brucella canis. There are, nonetheless, not clear symptoms so that it may go unnoticed in most of the cases. Serodiagnosis for canine brucellosis has not been confirmed. Moreover, it has substantial difficulties due to broad cross-reactivity between the rough cell wall antigens of B. canis and heterospecific antibodies present in normal, uninfected dogs. Thus, this study was conducted to characterize the immunogenic proteins in cytoplasmic antigen (CPAg) of B. canis, which defined the antigenic sensitivity of the humoral antibody responses to B. canis-infected dogs. In analysis of B. canis CPAg, first, we extracted and purified the cytoplasmic proteins from cultured B. canis by hot-saline inactivation, ultrafiltration, sonication, and ultracentrifugation step by step according to the sonicated antigen extract method. For characterization of this antigen, we checked the sort and range of each protein on SDS-PAGE and verified the immunogenic proteins leading to reaction with antisera of B. canis-infected dogs. Selected immunodominant proteins were identified using MALDI-MS/MS. As a result, in an immunoproteomic assay, several polypeptides in CPAg on one or two-dimensional electrophoresis (DE) were specifically reacted to antisera from B. canis-infected dogs but not from non-infected dogs. The polypeptides with approximate 150, 80, 60, 52, 33, 26, 17, 15, 13, 11 kDa on 1-DE were dominantly recognized by antisera from B. canis-infected dogs. In the immunoblot profiles on 2-DE, ten immunodominant proteins in CPAg were detected with antisera of infected dogs between pI 3.5-6.5 at approximate 35 to 10 KDa, without any nonspecific reaction with sera in non-infected dogs. Ten immunodominant proteins identified by MALDI-MS/MS were identified as superoxide dismutase, bacteroferritin, amino acid ABC transporter substrate-binding protein, extracellular solute-binding protein family3, transaldolase, 26kDa periplasmic immunogenic protein, Rhizopine-binding protein, enoyl-CoA hydratase, arginase and type1 glyceraldehyde-3-phosphate dehydrogenase. Most of these proteins were determined by their cytoplasmic or periplasmic localization with metabolism and transporter functions. Consequently, this study discovered and identified the prominent immunogenic proteins in B. canis CPAg, highlighting that those antigenic proteins may accomplish a specific serodiagnosis for canine brucellosis. Furthermore, we will evaluate those immunodominant proteins for applying to the advanced diagnostic methods with high specificity and accuracy.

Keywords: Brucella canis, Canine brucellosis, cytoplasmic antigen, immunogenic proteins

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Authors: Ji Jiazheng, Wang Jingrao, Jin Xin, Zhang Hong

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Diabetes mellitus is a metabolic disease characterized by high blood sugar. A long-standing hyperglycemic state can lead to various tissue damage. Diabetic retinopathy is the most common and widely studied ocular complication and has become the leading cause of blindness in my country. At the same time, diabetes has profound clinically relevant effects on the cornea, leading to keratopathy and vision-threatening. The cornea is an avascular tissue and is sensitive to hyperglycemia, Keratopathy caused by diabetes is usually chronic, they are called diabetic keratopathy or diabetic neurotrophic keratopathy, leading to several diabetic corneal complications including delayed epithelial wound healing, recurrent erosions, neuropathy, loss of sensitivity. Corneal stem cell dysfunction in diabetic patients as an important influencing factor of diabetic keratopathy. The consequences of this condition are often underestimated. The limbus is located between the cornea and the sclera tissue. The limbal stroma consists of a series of radial elevations with fibrovascular centers known as palisades of Vogt (POV). Previous studies have shown that palisades of Vogt (POV), as the main site of limbal stem cells, plays an important role in the homeostasis of the corneal epithelium. Therefore, POV plays a vital role in the healing of corneal epithelial surgery and postoperative evaluation. IVCM can observe the condition of the corneal epithelium at the cellular level. It has profound significance and guidance for the evaluation of limbal and limbal stem cells. We have previously observed structural changes in POV in HSK and HZO patients on IVCM. At present, there have been reports involving limbal stem cell dysfunction in diabetic patients, but the specific pathogenesis is still unclear. However, there are no studies on POV morphological changes in patients with DM. Therefore, we performed statistics and compared the correlation between POV morphological changes and corneal epithelial basal cell density, corneal nerves, and length of disease in DM patients and normal humans using IVCM studies. At the same time, fundoscopy was used to observe the correlation between the thickness of RNFL and the thickness of GCC and POV in diabetic patients. And to observe the correlation between SVD, DVD and POV for research.

Keywords: confocal microscopy, fundus, limbal stem cells, diabetes

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Authors: Brahim Sow

Abstract:

Background: Throughout West Africa, Balanites aegyptiaca (BA), or Zygophyllaceae, is widely used in traditional medicine to treat diabetes, hypertension, inflammation, malaria and liver disorders. In our recent research, we found that BA has nephroprotective potential against diabetes mellitus, hypertension and kidney disorders. However, to our knowledge, no systematic studies have been carried out on its derivative (toxicity) profile. Aim of the study: The study was conducted to assess the potential potency of the hydroalcoholic extract of BA bark in rats by the acute and sub-acute oral route. Materials and methods: Male and female rats in the acute depression study received BA extract orally at single doses of 500 mg/kg, 2000 mg/kg, 3000 mg/kg and 5000 mg/kg (n = 6 per group/sex). To assess acute depression, abnormal behaviour, toxic symptoms, weight and death were observed for 14 consecutive days. For the subacute impairment study, Wistar rats received the extract orally at doses of 125, 250 and 500 mg/kg (n=6 per group/sex) per day for 28 days. Behaviour and body weight were monitored daily. At the end of the treatment period, biochemical, haematological and histopathological examinations were performed, and gross and histopathological examinations of several organs were carried out. To determine the presence or absence of phytochemicals, the BA extract was subjected to gage phage chromatographic examination. Results: The absence of absorption chromatography of BA indicates the absence of cyanide groups. This suggests that the BA extract does not contain toxic substances. No mortality or adverse effects were observed at 5000 mg/kg in the acute depression test. With regard to body weight, general behaviour, relative organ weights, haematological and biochemical parameters, BA extract did not induce any mortality or potentially treatment-related effects in the sub-acute study. The normal architecture of the vital organs was revealed by histopathological examination, indicating the absence of morphological alterations. Conclusion: BA extract administered orally for 28 days at doses up to 500 mg/kg did not cause toxicological damage in rats in the present study. The median lethal dose (LD50) of the extract was estimated to be over 5000 mg/kg in an acute hyperglycaemia study.

Keywords: Balanites aegyptiaca L Delile, haematology, biochemistry, rat

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Authors: Nicolas Bae, Theodore L. Karavasilis

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Increasingly, a large number of new and existing tall buildings are required to improve their resilient performance against strong winds and earthquakes to minimize direct, as well as indirect damages to society. Those advent stationary functions of tall building structures in metropolitan regions can be severely hazardous, in socio-economic terms, which also increase the requirement of advanced seismic performance. To achieve these progressive requirements, the seismic reinforcement for some old, conventional buildings have become enormously costly. The methods of increasing the buildings’ resilience against wind or earthquake loads have also become more advanced. Up to now, vibration control devices, such as the passive damper system, is still regarded as an effective and an easy-to-install option, in improving the seismic resilience of buildings at affordable prices. The main purpose of this paper is to examine 1) the optimization of the shape of visco plastic brace damper (VPBD) system which is one of hybrid damper system so that it can maximize its energy dissipation capacity in tall buildings against wind and earthquake. 2) the verification of the seismic performance of the visco plastic brace damper system in tall buildings; up to forty-storey high steel frame buildings, by comparing the results of Non-Linear Response History Analysis (NLRHA), with and without a damper system. The most significant contribution of this research is to introduce the optimized hybrid damper system that is adequate for high rise buildings. The efficiency of this visco plastic brace damper system and the advantages of its use in tall buildings can be verified since tall buildings tend to be affected by wind load at its normal state and also by earthquake load after yielding of steel plates. The modeling of the prototype tall building will be conducted using the Opensees software. Three types of modeling were used to verify the performance of the damper (MRF, MRF with visco-elastic, MRF with visco-plastic model) 22-set seismic records used and the scaling procedure was followed according to the FEMA code. It is shown that MRF with viscous, visco-elastic damper, it is superior effective to reduce inelastic deformation such as roof displacement, maximum story drift, roof velocity compared to the MRF only.

Keywords: tall steel building, seismic retrofit, viscous, viscoelastic damper, performance based design, resilience based design

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Authors: Gayatri Swarnakar

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Paramphistomiasis and fascioliasis diseases have been prevalent due to presence of trematode parasites in the rumen and liver of domestic buffalo (Bubalus bubalis) in Udaipur, India. The trematode parasites such as Paramphistomum cervi, Gastrothylax crumenifer, Cotylophoron cotylophorum, Orthocoelium scoliocoelium, Fasciola hepatica and Fasciola gigantica were collected from infected rumen and liver of the freshly slaughtered buffaloes (Bubalus bubalis) at local zoo abattoir in Udaipur. Live trematodes were washed in normal saline, fixed in 0.2M cacodylate fixative, post fixed in osmium tetraoxide, dehydrated, dried, coated with gold sputter and observed under scanning electronic microscope (SEM). The surface tegument of Paramphistomum cervi was spineless with transverse folds, discontinuous with ridges and grooves. Two types of sensory papillae such as knob like and button shaped were also observed. The oral opening of Cotylophoron cotylophorum was surrounded by wrinkled and ridged tegument which formed concentric elevated rings. Tegument of Cotylophoron cotylophorum in acetabulum region was observed to be rough and bee-comb like structure. Genital sucker of this worm was surrounded by a tyre- shaped elevation of the tegument. Orthocoelium scoliocoelium showed circular and concentric rings of tegumental folds around the oral sucker. Genital pore had knob like papillae with radial tegumental folds. Surface topography of Fasciola gigantica and Fasciola hepatica were found to be rough due to occurrence of different types of spines, three types of sensory papillae, transverse folds and grooves. Oral and ventral suckers were spineless and covered with thick rims of transverse folds. Genital pore showed small scattered spines. Present research work would provide knowledge for ultrastructural characteristics of trematode parasites for chemotherapeutic measures and help us to evolve suitable strategy for the eradication of trematode parasites from the domestic buffalo (Bubalus bubalis).

Keywords: Domestic buffalo, tegument, trematode parasites, ultrastructure

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Authors: Reham Hajomer, Ikram Elsiddig, Amna Hamad

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Lepidium sativum (Garden Cress) belonging to Brassicaceae family is an annual herb locally known as El-rshad. In Ayurveda it is an important medicinal plant, traditionally used for the treatment of jaundice, liver problems, spleen diseases, gastrointestinal disorders, menstrual problems, fracture, arthritis, inflammatory conditions and for treatment of hypothyroidism. Hypothyroidism is a condition in which the thyroid gland does not produce enough thyroid hormones (Triiodithyronine T3 and Thyroxine T4) which are commonly caused by iodine deficiency. It’s divided into primary and secondary hypothyroidism, the primary caused by failure of thyroid function and secondary due to the failure of adequate thyroid-stimulating hormone (TSH) secretion from the pituitary gland or thyroid -releasing hormone (TRH) from the hypothalamus. The disease is most common in women over age 60. The objective regarding this study is to know whether Lepidium sativum would affect the level of thyroid hormones. The extract was prepared with 96% ethanol using Soxhlet apparatus. The anti-hypothyroidism activity was tested by using thirty male Wistar rats weighing (100-140 g) were used in the experiment. They were grouping into five groups, Group 1: Normal group= Administered only distilled water. Then 10 mg/kg Propylthiouracil was added to the drinking water of all other groups to induce hypothyroidism. Group 2: Negative control without any treatment; Group 3: Test group= treated with oral administration of 500mg/kg extract; Group 4: treated with oral administration of 250mg/kg of the extract; Group 5: Standard group (positive control) = treated with intraperitoneal Levothyroxine. All rats were incubated for 20 days at animal house with room temperature of proper ventilation provided with standard diet. The result show that the Lepidium sativum extract was found to increases the T3 and T4 in the propylthiouracil induced rats with values (0.29 ng/dl T3 and 0.57 U T4) for the 500mg/kg and (0.27 ng/dl T3 and 0.517 U T4) for the 250mg/kg in comparison with standard with values (0.241 ng/dl T3 and 0.516 U T4) so that Lepidium sativum can be stimulatory to thyroid function and possess significant anti-hypothyroidism effect with p-values ranges from (0.000006*-0.893472). In conclusion, from results obtained, Lepidium sativum plant extract was found to posses anti-hypothyroidism effects so its act as an agent that stimulates thyroid hormone secretion.

Keywords: anti-hypothyroidism, extract, lepidium, sativum

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Authors: Emma R. Arakelova, Stepan G. Grigoryan, Flora G. Arsenyan, Nelli S. Babayan, Ruzanna M. Grigoryan, Natalia K. Sarkisyan

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Novel nanosize zinc oxide composites of doxorubicin obtained by deposition of 180 nm thick zinc oxide film on the drug surface using DC-magnetron sputtering of a zinc target in the form of gels (PEO+Dox+ZnO and Starch+NaCMC+Dox+ZnO) were studied for drug delivery applications. The cancer specificity was revealed both in in vitro and in vivo models. The cytotoxicity of the test compounds was analyzed against human cancer (HeLa) and normal (MRC5) cell lines using MTT colorimetric cell viability assay. IC50 values were determined and compared to reveal the cancer specificity of the test samples. The mechanistic study of the most active compound was investigated using Flow cytometry analyzing of the DNA content after PI (propidium iodide) staining. Data were analyzed with Tree Star FlowJo software using cell cycle analysis Dean-Jett-Fox module. The in vivo anticancer activity estimation experiments were carried out on mice with inoculated ascitic Ehrlich’s carcinoma at intraperitoneal introduction of doxorubicin and its zinc oxide compositions. It was shown that the nanosize zinc oxide film deposition on the drug surface leads to the selective anticancer activity of composites at the cellular level with the range of selectivity index (SI) from 4 (Starch+NaCMC+Dox+ZnO) to 200 (PEO(gel)+Dox+ZnO) which is higher than that of free Dox (SI = 56). The significant increase in vivo antitumor activity (by a factor of 2-2.5) and decrease of general toxicity of zinc oxide compositions of doxorubicin in the form of the above mentioned gels compared to free doxorubicin were shown on the model of inoculated Ehrlich's ascitic carcinoma. Mechanistic studies of anticancer activity revealed the cytostatic effect based on the high level of DNA biosynthesis inhibition at considerable low concentrations of zinc oxide compositions of doxorubicin. The results of studies in vitro and in vivo behavior of PEO+Dox+ZnO and Starch+NaCMC+Dox+ZnO composites confirm the high potential of the nanosize zinc oxide composites as a vector delivery system for future application in cancer chemotherapy.

Keywords: anticancer activity, cancer specificity, doxorubicin, zinc oxide

Procedia PDF Downloads 411

Authors: Patti Kastanias, Wei Wang, Karyn Mackenzie, Sandra Robinson, Susan Wnuk

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Obesity is a worldwide epidemic and is recognized as a chronic disease. Pain in the obese individual is a multidimensional issue. An increase in BMI is positively correlated with pain incidence and severity, especially in central obesity where individuals are twice as likely to have chronic pain. Both obesity and chronic pain are also associated with mood disorders. Pain is worse among obese individuals with depression and anxiety. Bariatric surgery provides patients with an effective solution for long-term weight loss and associated health problems. However, not much is known about acute and chronic pain after bariatric surgery and its contributing factors, including mood disorders. Nurse practitioners (NPs) at one large multidisciplinary bariatric surgery centre led two studies to examine acute and chronic pain and pain management over time after bariatric surgery. The purpose of the initial study was to examine the incidence and severity of acute and chronic pain after bariatric surgery. The aim of the secondary study was to further examine chronic pain, specifically looking at psychological factors that influence severity or incidence of both neuropathic and somatic pain as well as changes in opioid use. The initial study was a prospective, longitudinal study where patients having bariatric surgery at one surgical center were followed up to 6 months postop. Data was collected at 7 time points using validated instruments for pain severity, pain interference, and patient satisfaction. In the second study, subjects were followed longitudinally starting preoperatively and then at 6 months and 1 year postoperatively to capture changes in chronic pain and influencing variables over time. Valid and reliable instruments were utilized for all major study outcomes. In the first study, there was a trend towards decreased acute post-operative pain over time. The incidence and severity of chronic pain was found to be significantly reduced at 6 months post bariatric surgery. Interestingly, interference of chronic pain in daily life such as normal work, mood, and walking ability was significantly improved at 6 months postop however; this was not the case with sleep. Preliminary results of the secondary study indicate that pain severity, pain interference, anxiety and depression are significantly improved at 6 months postoperatively. In addition, preoperative anxiety, depression and emotional regulation were predictive of pain interference, but not pain severity. The results of our regression analyses provide evidence for the impact of pre-existing psychological factors on pain, particularly anxiety in obese populations.

Keywords: bariatric surgery, mood disorders, obesity, pain

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Authors: Kitti Szoke, Laszlo Szoke, Attila Czompa, Arpad Tosaki, Istvan Lekli

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Autophagy plays an important role in cardiac hypertrophy, which is one of the most common causes of heart failure in the world. This self-degradative catabolic process, responsible for protein quality control, balancing sources of energy at critical times, and elimination of damaged organelles. The autophagic activity can be triggered by starvation, oxidative stress, or pharmacological agents, like rapamycin. This induced autophagy can promote cell survival during starvation or pathological stress. In this study, it is investigated the effect of the induced autophagic process on angiotensin induced hypertrophic H9c2 cells. In our study, it is used H9c2 cells as an in vitro model. To induce hypertrophy, cells were treated with 10000 nM angiotensin-II, and to activate autophagy, 100 nM rapamycin treatment was used. The following groups were formed: 1: control, 2: 10000 nM AT-II, 3: 100 nM rapamycin, 4: 100 nM rapamycin pretreatment then 10000 nM AT-II. The cell viability was examined via MTT (cell proliferation assay) assay. The cells were stained with rhodamine-conjugated phalloidin and DAPI to visualize F-actin filaments and cell nuclei then the cell size alteration was examined in a fluorescence microscope. Furthermore, the expression levels of autophagic and apoptotic proteins such as Beclin-1, p62, LC3B-II, Cleaved Caspase-3 were evaluated by Western blot. MTT assay result suggests that the used pharmaceutical agents in the tested concentrations did not have a toxic effect; however, at group 3, a slight decrement was detected in cell viability. In response to AT-II treatment, a significant increase was detected in the cell size; cells became hypertrophic. However, rapamycin pretreatment slightly reduced the cell size compared to group 2. Western blot results showed that AT-II treatment-induced autophagy, because the increased expression of Beclin-1, p62, LC3B-II were observed. However, due to the incomplete autophagy, the apoptotic Cleaved Caspase-3 expression also increased. Rapamycin pretreatment up-regulated Beclin-1 and LC3B-II, down-regulated p62 and Cleaved Caspase-3, indicating that rapamycin-induced autophagy can restore the normal autophagic flux. Taken together, our results suggest that rapamycin activated autophagy reduces angiotensin-II induced hypertrophy.

Keywords: angiotensin-II, autophagy, H9c2 cell line, hypertrophy, rapamycin

Procedia PDF Downloads 147

Authors: Dipanshu Sur, Ratnabali Chakravorty, Rimi Pal, Siddhartha Chatterjee, Joyshree Chaterjee, Amal Mallik

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Background: Polycystic ovary syndrome (PCOS) is a common endocrine disease in reproductive women with a complex hormonal disturbance that affects the menstrual cycle and leads to metabolic consequences in later life. Hyperandrogenaemia is noticeable features of PCOS and influence the process of folliculogenesis in women. The levels of Antimüllerian Hormone (AMH) reflect the number of pre-antral follicles and thus are a marker of oocyte pool – germinal reserve of the ovary for reproduction. Besides its utilization in IVF (In-vitro fertilization), determination of AMH may serve as an additional marker in the diagnostics of PCOS, where increased AMH levels reflect the severity of the disease. The positive correlation of serum AMH with the number of antral follicles was found also in patients with PCOS. Objective: The objective of this study was to investigate the relationship between AMH androgens and whether AMH contributes to altered folliculogenesis in non-obese women with PCOS. Methods: We designed a prospective study which included a total of 65 IVF individuals. It enrolled 26 cases of PCOS based on 2003 Rotterdam criteria and 39 ovulatory normal- non PCOS, healthy, age-matched controls. AMH levels and ovarian morphology were assessed. The relationships between AMH and androgenaemia in patients with and without PCOS were studied. Results: Mean age of PCOS patients were slightly higher than controls (32±4 and 28±3 years, respectively). AMH generally increased with antral follicle count (AFC) [P=0.001], testosterone, and luteinising hormone, and decreased with age, and serum sex hormone binding globulin (SHBG). No significant relationships were found between circulating AMH levels and BMI between PCOS and non-PCOS patients. The calculation of AMH production per antral follicle (AMH/AF) showed that there was a significant difference in median AMH/AF between PCOS and non-PCOS (P =0.001). Both PCOS and non-PCOS groups showed a very similar increase in AMH with increases in AFC, but the PCOS patients had consistently higher AMH across all AFC levels. Conclusions: These observations indicate that there is a connection between AMH and androgens levels between PCOS and non-PCOS East Indian women. Excessive granulosa cell activity may be implicated in the abnormal follicular dynamic of the syndrome. They are higher in women with PCOS and, on the other hand, very low in women with an ovarian failure.

Keywords: anti-Mullerian hormone, polycystic ovary syndrome, antral follicle count, androgens

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Authors: Trenton Hubbard, Kenneth Soyemi, Emily Siffermann

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Introduction: According to the American Academy of Pediatrics (AAP) there are different weight-based recommendations for the treatment of Chlamydia trachomatis (CT) in patients who are being evaluated for sexual assault. Current AAP Red Book guidelines recommend that uncomplicated C. trachomatis anogenital infection in prepubertal patients weighing less than =<45 kg be treated with oral erythromycin 50 mg/kg/day QID for 14 days with no alternative therapies, and for patients whose weight => 45 kg are Azithromycin 1 gm PO once. Our study objective was to determine the efficacy of single-dose Azithromycin therapy for the treatment of Chlamydia trachomatis in patients weighing less than 50 kg who were evaluated for child sexual abuse in an urban setting. Methods: We conducted a retrospective chart review of historical medical records (paper and electronic) patients weighing less than 50 kg who were evaluated for child sexual abuse and subsequently treated for C. trachomatis infection with Azithromycin (20 mg/kg PO once up to a maximum 1 gm) and received a Test of Cure (TOC) from 2006-2016. Qualitative variables were expressed as percentages. Quantitative variables were expressed as mean values (+/- standard deviation [SD]) if they followed a normal distribution or as median values (interquartile range[IQR]) if they did not. Wilcoxson two-sample test was used to compare means of Azithromycin Dose, mg/kg, and TOC timing between treatment responders and non-responders. Results: We reviewed records of 34 patients, average age (SD) was 5.4 (2.0) years, 33 (97%) were treated for CT and 1(3%) for both GC and CT. 25 (74%) were females. Urine PCR was the most commonly used test at evaluation and as TOC with 13 (38%) patients completing both tests. The average (SD) dose of Azithromycin at treatment was 470 (136) mg and average (SD) mg/kg dose of 20 (1.9) mg/kg for all patients. Median (IQR) timing for TOC testing was 19 (14-26) days. Of the 33 with complete data 25 (74%) had a negative TOC. When compared with treatment non-responders (TOC failures), treatment responders received higher doses (average dose (SD) received 495 (139) vs 401(110), P 0.06)); similar average (SD) weight base dosing received (20.8(2.0) vs 19.7 (1.5), P 0.15)), and earlier average (SD)TOC test timing (18.8 (5.6) vs 32 (28.6) P 0.02)). Conclusion: Azithromycin dosing appears to be efficacious in the treatment of CT post sexual assault as majority of patients responded. Although treatment responders and non-responders received similar weight based doses, there is need for additional studies to understand variances and predictors of response.

Keywords: child sexual abuse, chlmaydia trachmotis infection, single-dose azithromycin, weight less than or equal to 45 kilograms

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Authors: Omar Youssef, Aija Knuuttila, Paivi Piirilä, Virinder Sarhadi, Sakari Knuutila

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Exhaled breath condensate (EBC) is a unique sample that allows studying different genetic changes in lung carcinoma through a non-invasive way. With the aid of next generation sequencing (NGS) technology, analysis of genetic mutations has been more efficient with increased sensitivity for detection of genetic variants. In order to investigate the possibility of applying this method for cancer diagnostics, mutations in EBC DNA from lung cancer patients and healthy individuals were studied by using NGS. The key aim is to assess the feasibility of using this approach to detect clinically important mutations in EBC. EBC was collected from 20 healthy individuals and 9 lung cancer patients (four lung adenocarcinomas, four 8 squamous cell carcinoma, and one case of mesothelioma). Mutations in hotpot regions of 22 genes were studied by using Ampliseq Colon and Lung cancer panel and sequenced on Ion PGM. Results demonstrated that all nine patients showed a total of 19 cosmic mutations in APC, BRAF, EGFR, ERBB4, FBXW7, FGFR1, KRAS, MAP2K1, NRAS, PIK3CA, PTEN, RET, SMAD4, and TP53. In controls, 15 individuals showed 35 cosmic mutations in BRAF, CTNNB1, DDR2, EGFR, ERBB2, FBXW7, FGFR3, KRAS, MET, NOTCH1, NRAS, PIK3CA, PTEN, SMAD4, and TP53. Additionally, 45 novel mutations not reported previously were also seen in patients’ samples, and 106 novel mutations were seen in controls’ specimens. KRAS exon 2 mutations G12D was identified in one control specimen with mutant allele fraction of 6.8%, while KRAS G13D mutation seen in one patient sample showed mutant allele fraction of 17%. These findings illustrate that hotspot mutations are present in DNA from EBC of both cancer patients and healthy controls. As some of the cosmic mutations were seen in controls too, no firm conclusion can be drawn on the clinical importance of cosmic mutations in patients. Mutations reported in controls could represent early neoplastic changes or normal homeostatic process of apoptosis occurring in lung tissue to get rid of mutant cells. At the same time, mutations detected in patients might represent a non-invasive easily accessible way for early cancer detection. Follow up of individuals with important cancer mutations is necessary to clarify the significance of these mutations in both healthy individuals and cancer patients.

Keywords: exhaled breath condensate, lung cancer, mutations, next generation sequencing

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Authors: Chen Wang, Jared Evans, Yan Asmann

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With the quick evolvement of next-generation sequencing techniques, whole-exome or exome-panel data have become a cost-effective way for detection of small exonic mutations, but there has been a growing desire to accurately detect copy number variations (CNVs) as well. In order to address this research and clinical needs, we developed a sequencing coverage pattern-based method not only for copy number detections, data integrity checks, CNV calling, and visualization reports. The developed methodologies include complete automation to increase usability, genome content-coverage bias correction, CNV segmentation, data quality reports, and publication quality images. Automatic identification and removal of poor quality outlier samples were made automatically. Multiple experimental batches were routinely detected and further reduced for a clean subset of samples before analysis. Algorithm improvements were also made to improve somatic CNV detection as well as germline CNV detection in trio family. Additionally, a set of utilities was included to facilitate users for producing CNV plots in focused genes of interest. We demonstrate the somatic CNV enhancements by accurately detecting CNVs in whole exome-wide data from the cancer genome atlas cancer samples and a lymphoma case study with paired tumor and normal samples. We also showed our efficient reuses of existing exome sequencing data, for improved germline CNV calling in a family of the trio from the phase-III study of 1000 Genome to detect CNVs with various modes of inheritance. The performance of the developed method is evaluated by comparing CNV calling results with results from other orthogonal copy number platforms. Through our case studies, reuses of exome sequencing data for calling CNVs have several noticeable functionalities, including a better quality control for exome sequencing data, improved joint analysis with single nucleotide variant calls, and novel genomic discovery of under-utilized existing whole exome and custom exome panel data.

Keywords: bioinformatics, computational genetics, copy number variations, data reuse, exome sequencing, next generation sequencing

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Authors: Mayowa Adeyeye, Kehinde Adeyemo

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The direct free kick is considered a great opportunity to score a goal but this is not always the case amidst Nigerian and other elite footballers. This study, therefore, examined the extent to which an 8 weeks mental skill training programme is effective for improving accuracy in direct free kick in football. Sixty (n-60) students of Pepsi Football Academy participated in the study. They were randomly distributed into two groups of positive self-talk group (intervention n-30) and control group (n-30). The instrument used in the collection of data include a standard football goal post while the research materials include a dummy soccer wall, a cord, an improvised vanishing spray, a clipboard, writing materials, a recording sheet, a self-talk log book, six standard 5 football, cones, an audiotape and a compact disc. The Weinberge and Gould (2011) mental skills training manual was used. The reliability coefficient of the apparatus following a pilot study stood at 0.72. Before the commencement of the mental skills training programme, the participants were asked to take six simulated direct free kick. At the end of each physical skills training session after the pre-test, the researcher spent at least 15 minutes with the groups exposing them to the intervention. The mental skills training programme alongside physical skills training took place in two different locations for the different groups under study, these included Agege Stadium Main bowl Football Pitch (Imagery Group), and Ogba Ijaye (Control Group). The mental skills training programme lasted for eight weeks. After the completion of the mental skills training programme, all the participants were asked to take another six simulated direct free kick attempts using the same field used for the pre-test to determine the efficacy of the treatments. The pre-test and post-test data were analysed using inferential statistics of t-test, while the alpha level was set at 0.05. The result revealed significant differences in t-test for positive self-talk and control group. Based on the findings, it is recommended that athletes should be exposed to positive self-talk alongside their normal physical skills training for quality delivery of accurate direct free kick during training and competition.

Keywords: accuracy, direct free kick, pepsi football academy, positive self-talk

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