Search results for: in vitro and in vivo cancer therapy

Authors: Nidhal K. Azawi, John M. Gauch

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Colorectal cancer is one of the leading causes of cancer death in the US and the world, which is why millions of colonoscopy examinations are performed annually. Unfortunately, noise, specular highlights, and motion artifacts corrupt many images in a typical colonoscopy exam. The goal of our research is to produce automated techniques to detect and correct or remove these noninformative images from colonoscopy videos, so physicians can focus their attention on informative images. In this research, we first automatically extract features from images. Then we use machine learning and deep neural network to classify colonoscopy images as either informative or noninformative. Our results show that we achieve image classification accuracy between 92-98%. We also show how the removal of noninformative images together with image alignment can aid in the creation of image panoramas and other visualizations of colonoscopy images.

Keywords: colonoscopy classification, feature extraction, image alignment, machine learning

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Authors: Evelyn Smith, Susan Simpson

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Background: Eating disorder (ED) treatment is complicated by high rates of chronicity, comorbidity, complex personality traits and client dropout. Given these complexities, Schema Therapy (ST) has been identified as a suitable treatment option. The study primarily aims to evaluate the efficacy of group ST for the treatment of EDs. The study further evaluated the effectiveness of ST in reducing schemas and improving quality of life. Method: Participant suitability was ascertained using the Eating Disorder Examination. Following this, participants attended 90-minute weekly group sessions over 25 weeks. Groups consisted of six to eight participants and were facilitated by two psychologists, at least one of who is trained in ST. Measures were completed at pre, mid and post-treatment. Measures assessed ED symptoms, cognitive schemas, schema mode presentations, quality of life, self-compassion and psychological distress. Results: As predicted, measures of ED symptoms were significantly reduced following treatment. No significant changes were observed in early maladaptive schema severity; however, reductions in schema modes were observed. Participants did not report improvements in general quality of life measures following treatment, though improvement in psychological well-being was observed. Discussion: Overall, the findings from the current study support the use of group ST for the treatment of EDs. It is expected that lengthier treatment is needed for the reduction in schema severity. Given participant dropout was considerably low, this has important treatment implications for the suitability of ST for the treatment of EDs.

Keywords: eating disorders, schema therapy, treatment, quality of life

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Authors: Arianna Zhu, Thomas Bakupog

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Taxol (generic name paclitaxel) is an antineoplastic drug used to treat breast, lung, and ovarian cancer. It performs exceptionally well against a wide variety of tumors, including B16 melanoma, L1210 and P388 leukemias, MX-1 mammary tumors, and CX-1 colon tumor xenografts. However, despite taxol’s efficacy in antitumor activity, its aqueous solubility is extremely poor, decreasing its bioavailability and making it difficult for the body to absorb. The objective of this study is to improve the solubility of taxol, thus increasing the bioavailability of the drug in preventing cancer. By modifying the structure of taxol, four novel taxol derivatives were created with improved solubilities. Two of the derivatives were given an additional hydrogen donor and acceptor and thus showed a pronounced positive change in solubility. The results of this work solve the issue of taxol’s inadequate solubility and show potential in increasing the absorption of the drug.

Keywords: Taxol, Solubility, improving bioavailability, logP

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Authors: Sean Hall

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Prior to COVID-19, the world was preoccupied with opioids, effectiveness versus risk, and specifically toxicity versus abuse. Historically underpinning opioid use was a concept of safety. As use over time and real-world data evolved, a pursuit for efficacy associated with non-opioid alternatives became mainstream. On January 8, 2021, the US signed back into the opioid problem, with these two fundamental questions still unresolved. The author will share the current progression of a lead non-opioid cancer bone pain candidate, NanaBis™. NanaBis™ represents two innovative factors: The active ingredients are from cannabinoids; these ingredients are in a proprietary sub-micron delivery platform, NanoCelle®. The author will offer an opinion piece, potentiating the future role of delivery platforms in medicine to increase both patient safety and compliance.

Keywords: NanaBis, nanoCelle, opioids, toxicity

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Authors: Andleeb Zahra, Itrat Rubab, Sumaira Malik, Amina Khan, Muhammad Jawad Khan, M. Qaiser Fatmi

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Oral squamous cell carcinoma (OSCC) is one of the most common cancers worldwide. Recent studies have highlighted the role of miRNA in disease pathology, indicating its potential use in an early diagnostic tool. miRNAs are small, double stranded, non-coding RNAs that regulate gene expression by deregulating mRNAs. miRNAs play important roles in modifying various cellular processes such as cell growth, differentiation, apoptosis, and immune response. Dis-regulated expression of miRNAs is known to affect the cell growth, and this may function as tumor suppressors or oncogenes in various cancers. Objectives: The main objectives of this study were to characterize the extracellular miRNAs involved in oral cancer (OC) to assist early detection of cancer as well as to propose a list of genes that can potentially be used as biomarkers of OC. We used gene expression data by microarrays already available in literature. Materials and Methods: In the first step, a total of 318 miRNAs involved in oral carcinoma were shortlisted followed by the prediction of their target genes. Simultaneously, the differentially expressed genes (DEGs) of oral carcinoma from all experiments were identified. The common genes between lists of DEGs of OC based on experimentally proven data and target genes of each miRNA were identified. These common genes are the targets of specific miRNA, which is involved in OC. Finally, a list of genes was generated which may be used as biomarker of OC. Results and Conclusion: In results, we included some of pathways in cancer to show the change in gene expression under the control of specific miRNA. Ingenuity pathway analysis (IPA) provided a list of major biomarkers like CDH2, CDK7 and functional enrichment analysis identified the role of miRNA in major pathways like cell adhesion molecules pathway affected by cancer. We observed that at least 25 genes are regulated by maximum number of miRNAs, and thereby, they can be used as biomarkers of OC. To better understand the role of miRNA with respect to their target genes further experiments are required, and our study provides a platform to better understand the miRNA-OC relationship at genomics level.

Keywords: biomarkers, gene expression, miRNA, oral carcinoma

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Authors: Chiara Cosentino, Carlo Pruneti, Carla Merisio, Domenico Sgromo

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Introduction – Psychoneuroimmunology as approach clearly showed how psychological features can influence health through specific physiological pathways linked to the stress reaction. This can be true also in cancer, in its latter conceptualization seen as a chronic disease. Therefore, it is still not clear how the psychological features can combine with a physiological specific path, for a better adjustment to cancer. The aim of this study is identifying how in Italian survivors, perceived social support, body image, coping and quality of life correlate with or influence Heart Rate Variability (HRV), the physiological parameter that can mirror a condition of chronic stress or a good relaxing capability. Method - The study had an exploratory transversal design. The final sample was made of 38 ovarian cancer survivors aged from 29 to 80 (M= 56,08; SD=12,76) following a program for Ovarian Cancer at the Oncological Clinic, University Hospital of Parma, Italy. Participants were asked to fill: Multidimensional Scale of Perceived Social Support (MSPSS); Derridford Appearance Scale-59 (DAS-59); Mental Adjustment to Cancer (MAC); Quality of Life Questionnaire (EORTC). For each participant was recorded Short-Term HRV (5 minutes) using emWavePro. Results– Data showed many interesting correlations within the psychological features. EORTC scores have a significant correlation with DAS-59 (r =-.327 p <.05), MSPSS (r =.411 p<.05), and MAC scores, in particular with the strategy Fatalism (r =.364 p<.05). A good social support improves HRV (F(1,33)= 4.27 p<.05). Perceiving themselves as effective in their environment, preserving a good role functioning (EORTC), positively affects HRV (F(1,33)=9.810 p<.001). Women admitting concerns towards body image seem prone to emotive disclosure, reducing emotional distress and improving HRV (β=.453); emotional avoidance worsens HRV (β=-.391). Discussion and conclusion - Results showed a strong relationship between body image and Quality of Life. These data suggest that higher concerns on body image, in particular, the negative self-concept linked to appearance, was linked to the worst functioning in everyday life. The relation between the negative self-concept and a reduction in emotional functioning is understandable in terms of possible distress deriving from the perception of body appearance. The relationship between a high perceived social support and a better functioning in everyday life was also confirmed. In this sample fatalism, was associated with a better physical, role and emotional functioning. In these women, the presence of a good support may activate the physiological Social Engagement System improving their HRV. Perceiving themselves effective in their environment, preserving a good role functioning, also positively affects HRV, probably following the same physiological pathway. A higher presence of concerns about appearance contributes to a higher HRV. Probably women admitting more body concerns are prone to a better emotive disclosure. This could reduce emotional distress improving HRV and global health. This study reached preliminary demonstration of an ‘Integrated Model of Defense’ in these cancer survivors. In these model, psychological features interact building a better quality of life and a condition of psychological well-being that is associated and influence HRV, then the physiological condition.

Keywords: cancer survivors, heart rate variability, ovarian cancer, psychophysiological adjustment

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Authors: Elizabeth Laguaite, Alexandria Purdy

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Heart transplant recipients face psycho-physiological stressors, including pain, lengthy hospitalizations, delirium, and existential crises. They pose an increased risk for Post Traumatic Stress Disorder (PTSD) and can be a predictor of poorer mental and physical Health-Related Quality of Life (HRQOL) outcomes and increased mortality. There is limited research on the prevention of Post Traumatic Stress Symptoms (PTSS) in transplant patients. This case report focuses on a collaborative Music and Art Therapy intervention used to improve outcomes for HMH transplant recipient John (Alias). John, a 58-year-old man with congestive heart failure, was admitted to HMH in February of 2021 with cardiogenic shock, cannulated with an Intra-aortic Balloon Pump, Impella 5.5, and Venoarterial Extracorporeal Membrane Oxygenation (VA-ECMO) as a bridge to heart and kidney transplant. He was listed as status 1 for transplant. Music Therapy and Art Therapy (MT and AT) were ordered by the physician for mood regulation, trauma processing and anxiety management. During MT/AT sessions, John reported a history of anxiety and depression exacerbated by medical acuity, shortness of breath, and lengthy hospitalizations. He expressed difficulty sleeping, pain, and existential questions. Initially seen individually by MT/AT, it was determined he could benefit from a collaborative approach due to similar thematic content within sessions. A Life Review intervention was developed by MT/AT. The purpose was for him to creatively express, reflect and process his medical narrative, including the identification of positive and negative events leading up to admission at HMH, the journey to transplant, and his hope for the future. Through this intervention, he created artworks that symbolized each event and paired them with songs, two of which were composed with the MT during treatment. As of September 2023, John has not been readmitted to the hospital and expressed that this treatment is what “got him through transplant”. MT and AT can provide opportunities for a patient to reminisce through creative expression, leading to a shift in the personal meaning of these experiences, promoting resolution, and ameliorating associated trauma. The closer to trauma it is processed, the less likely to develop PTSD. This collaborative MT/AT approach could improve long-term outcomes by reducing mortality and readmission rates for transplant patients.

Keywords: art therapy, music therapy, critical care, PTSD, trauma, transplant

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Authors: E. A. Amao, O. D. Amao, Z. O. Buzari, T. M. Adelegan, W. A. Tiamiyu, M. O. Yunus

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Signals from in vivo as well as in vitro studies shows that botanicals play notable roles in the treatment, prevention and management of diseases. Use of natural compounds in botanicals has been suggested as potential alternative to conventional therapeutic options. Therefore this study aimed to evaluate the effect of varying levels of turmeric powder (Curcuma longa) on semen characteristics and haematological indices of cocks. Turmeric (C. longa) was obtained from a local market in Saki in Oyo State, Nigeria, in March 2023. The rhizomes were washed, its skin scraped and air-dried for about 10 h, and further oven-dried at 40◦C for 12 h. afterwards, the dried turmeric was ground into powder using a blender. The product was kept in an air-tight container until the period of usage. The experimental material was drenched in cocks (60 cocks assigned into four treatments with three replicates) at 0.0g (T1), 0.05g (T2), 1.00g (T3) and 1.5g (T4) after 2 weeks of acclimatization. Semen volume, sperm cell progressive motility, sperm cell liveability, acrosome integrity, sperm cell concentration and normal sperm cell were evaluated for semen characteristics. Haematological parameters measured were: PCV, RBC, WBC Hb, MCV, MCH and MCHC. Data obtained were subjected to one-way analysis of variance. Semen volume (0.34 – 0.37ml), sperm cell progressive motility (68.33 – 80%), sperm cell liveability (46.66 – 85.00%), acrosome integrity (50.00 – 85%) and normal sperm cell (66.66 – 90%) shows significant difference (p<0.05) in favour cocks on higher level of turmeric powder. While sperm cell concentration (28.33 -40.00 X109/ml) shows no significant difference (p>0.05). PCV (36.00 – 40.33%), RBC (3.55 – 3.74 X106/ml), WBC (19.01 – 19.71 X109/ml), Hb (11.66 – 13.00 dl), MCV (100.53 – 109.53 ⴄ), MCH (32.57 – 35.31pg) and MCHC (32.00 – 32.37%) shows no significant difference (p>0.05). all serum biochemical indices showed significant difference (p<0.05) with animals on the test ingredient showed higher values in respect of the increase in turmeric powder.

Keywords: semen volume, total protein, packed cell volume, turmeric powder, albumin

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Authors: Lukman Ahmad Jamil, Heather M. Wallace

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Introduction: Numerous epidemiological studies have shown a positive as well as negative association and no association in some cases between chronic use of calcium channel blockers and the increased risk of developing cancer. However, these associations were enmeshed with controversies in the absence of laboratory based studies to back up those claims. Aim: The aim of this study was to determine in mechanistic terms the association between the long-term administration of nifedipine and diltiazem and increased risk of developing cancer using the human embryonic kidney (HEK293) cell line. Methods: Cell counting using the Trypan blue dye exclusion and 3-4, 5-Dimethylthiazol-2-yl-2, 5-diphenyl-tetrazolium bromide (MTT) assays were used to investigate the effect of nifedipine and diltiazem on the growth pattern of HEK293 cells. Protein assay using modified Lowry method and analysis of intracellular polyamines concentration using Liquid Chromatography – Tandem Mass Spectrometry (LC-MS) were performed to ascertain the mechanism through which chronic use of nifedipine increases the risk of developing cancer. Results: Both nifedipine and diltiazem significantly increased the proliferation of HEK293 cells dose and time dependently. This proliferative effect after 24, 48 and 72-hour incubation period was observed at 0.78, 1.56 and 25 µM for nifedipine and 0.39, 1.56 and 25 µM for diltiazem, respectively. The increased proliferation of the cells was found to be statistically significantly (p<0.05). Furthermore, the increased proliferation of the cells induced by nifedipine was associated with the increase in the protein content and elevated intracellular polyamines concentration level. Conclusion: The chronic use of nifedipine is associated with increased proliferation of cells with concomitant elevation of polyamines concentration and elevated polyamine levels have been implicated in many malignant transformations and hence, these provide a possible explanation on the link between long term use of nifedipine and development of some human cancers. Further studies are needed to evaluate the cause of this association.

Keywords: cancer, nifedipine, polyamine, proliferation

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Authors: Jiri Kysucan, Dusan Klos, Katherine Vomackova, Pavel Koranda, Martin Lovecek, Cestmir Neoral, Roman Havlik

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Aim: The prognosis of patients with pancreatic cancer is poor. The median of survival after establishing diagnosis is 3-11 months without surgical treatment, 13-20 months with surgical treatment depending on the disease stage, 5-year survival is less than 5%. Radical surgical resection remains the only hope of curing the disease. Early diagnosis with valid establishment of tumor resectability is, therefore, the most important aim for patients with pancreatic cancer. The aim of the work is to evaluate the contribution and define the role of 18F-FDG PET/CT in preoperative staging. Material and Methods: In 195 patients (103 males, 92 females, median age 66,7 years, 32-88 years) with a suspect pancreatic lesion, as part of the standard preoperative staging, in addition to standard examination methods (ultrasonography, contrast spiral CT, endoscopic ultrasonography, endoscopic ultrasonographic biopsy), a hybrid 18F-FDG PET/CT was performed. All PET/CT findings were subsequently compared with standard staging (CT, EUS, EUS FNA), with peroperative findings and definitive histology in the operated patients as reference standards. Interpretation defined the extent of the tumor according to TNM classification. Limitations of resectability were local advancement (T4) and presence of distant metastases (M1). Results: PET/CT was performed in a total of 195 patients with a suspect pancreatic lesion. In 153 patients, pancreatic carcinoma was confirmed and of these patients, 72 were not indicated for radical surgical procedure due to local inoperability or generalization of the disease. The sensitivity of PET/CT in detecting the primary lesion was 92.2%, specificity was 90.5%. A false negative finding in 12 patients, a false positive finding was seen in 4 cases, positive predictive value (PPV) 97.2%, negative predictive value (NPV) 76,0%. In evaluating regional lymph nodes, sensitivity was 51.9%, specificity 58.3%, PPV 58,3%, NPV 51.9%. In detecting distant metastases, PET/CT reached a sensitivity of 82.8%, specificity was 97.8%, PPV 96.9%, NPV 87.0%. PET/CT found distant metastases in 12 patients, which were not detected by standard methods. In 15 patients (15.6%) with potentially radically resectable findings, the procedure was contraindicated based on PET/CT findings and the treatment strategy was changed. Conclusion: PET/CT is a highly sensitive and specific method useful in preoperative staging of pancreatic cancer. It improves the selection of patients for radical surgical procedures, who can benefit from it and decreases the number of incorrectly indicated operations.

Keywords: cancer, PET/CT, staging, surgery

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Authors: Muhammad G. Almatar, Mohammad A. Alnasrallah

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This research focuses on the study of three main issues: 1) The temporal analysis of leukemia for a period of six years (2006-2012), 2) spatial analysis by investigating this phenomenon in the Kuwaiti society spatially in the residential areas within the six governorates, 3) the use of Geographic Information System technology in investigating the hypothesis of the research and its variables using the linear regression, to show the pattern of linear relationship. The study depends on utilizing the map to understand the distribution of blood cancer in Kuwait. Several geodatabases were created for the number of patients and air pollution. Spatial interpolation models were used to generate layers of air pollution in the study area. These geodatabases were tested over the past six years to reach the conclusion: Is there a relationship with significant significance between the two main variables of the study: blood cancer and air pollution? This study is the first to our best knowledge. As far as the researchers know, the distribution of this disease has not been studied geographically at the level of regions in Kuwait within six years and in specific areas as described above. This study investigates the concentration of this type of disease. The study found that there is no relationship of significant value between the two variables studied, and this may be due to the nature of the disease, which are often hereditary. On the other hand, this study has reached a number of suggestions and recommendations that may be useful to decision-makers and interested in the study of leukemia in Kuwait by focusing on the study of genetic diseases, which may be a cause of leukemia rather than air pollution.

Keywords: Kuwait, GIS, cancer, geography

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Authors: Ashish Kumar Jain, Deepak Mishra

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The objective of the present investigation was to prepare and evaluate a vesicular dual drug delivery system for effective management of mucosal ulcer. Inner encapsulating and Double liposomes were prepared by glass bead and reverse phase evaporation method respectively. The formulation consisted of inner liposomes bearing Ranitidine Bismuth Citrate (RBC) and outer liposomes encapsulating Amoxicillin trihydrate (AMOX). The optimized inner liposomes and double liposomes were extensively characterized for vesicle size, morphology, zeta potential, vesicles count, entrapment efficiency and in vitro drug release. In vitro, the double liposomes demonstrated a sustained release of AMOX and RBC viz 91.4±1.8% and 77.2±2.1% respectively at the end of 72 hr. Furthermore binding specificity and targeting propensity toward H. pylori (SKP-56) was confirmed by agglutination and in situ adherence assay. Reduction of the absolute alcohol induced ulcerogenic index from 3.01 ± 0.25 to 0.31 ± 0.09 and 100% H. pylori clearance rate was observed. These results suggested that double liposomes are potential vector for the development of dual drug delivery for effective treatment of H. pylori-associated peptic ulcer.

Keywords: double liposomes, H. pylori targeting, PE liposomes, glass-beads method, peptic ulcers

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Authors: Jiwan P. Lavande, A. V. Chandewar

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In the present study, orodispersible tablets of diphenhydramine hydrochloride were prepared using croscarmellose sodium, crospovidone and camphor, menthol (as subliming agents) in different ratios and ODTs prepared with superdisintegrants were compared with ODTs prepared with camphor and menthol (subliming agents) for the following evaluation of in vitro disintegration time, dispersion time, wetting time, hardness and water absorption ratio. Results revealed that the tablets of all formulations have acceptable physical parameters. The drug and excipients compatibility study was evaluated using FTIR technique and has not detected any incompatibility. The in vitro release of drug from DC6 formulation was quick when compared to other formulations. Stability study was carried out as per ICH guidelines for three months and results revealed that upon storage disintegration time of tablets had not shown any significant difference. Microscopic study of different formulations of sublimed tablets showed formation of pores for the tablets prepared by sublimation method. Thus, conclusion can be made that the stable orodispersible tablets of diphenhydramine hydrochloride can be developed for the rapid release of diphenhydramine hydrochloride.

Keywords: orodispersible tablet, subliming agent, super disintegrants, diphenhydramine hydrochloride

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Authors: Ennus Tajuddin Tamboli, Madhukar Garg, Mohd. Mujeeb, Sayeed Ahmad

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An efficient protocol for simultaneous production of forskolin and rosmarinic acid in in vitro callus derived from the leaves of Coleus forskohlii Briq. has been developed. MS media was used for the establishment of cultures and NAA + 6-BA (1.0 ppm) was found best for callus growth. The callus was further subjected to treatment with various elicitor/precursors viz. chitosan, thidiazuron and methyl jasmonate to observe their effect on production of biomass and accumulation of secondary metabolites. The content of forskolin and rosmarinic acid were estimated by HPTLC, in comparison to natural explant which showed 2 fold and 10 fold rise in forskolin and rosmarinic acid content, respectively. Methy1 jasmonate 50 µM was found best for production of forskolin, whereas thidiazuron showed best results in the yield of rosmarinic acid, separately in static culture. However, combined treatment in suspension culture showed moderated effect for increase in secondary metabolites but the biomass increased significantly as compared to static culture.

Keywords: plant tissue culture, secondary metabolites, coleus, forskolin, rosmarinic acid, HPTLC

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Authors: Ayush Shrivastava, Arpit Chaudhary, Devang Kulshreshtha, Vibhav Prakash Singh, Rajeev Srivastava

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Early diagnosis of breast cancer can improve the survival rate by detecting cancer at an early stage. Breast region segmentation is an essential step in the analysis of digital mammograms. Accurate image segmentation leads to better detection of cancer. It aims at separating out Region of Interest (ROI) from rest of the image. The procedure begins with removal of labels, annotations and tags from the mammographic image using morphological opening method. Pectoral Muscle Sliding Window Algorithm (PMSWA) is used for removal of pectoral muscle from mammograms which is necessary as the intensity values of pectoral muscles are similar to that of ROI which makes it difficult to separate out. After removing the pectoral muscle, Dispersed Region Growing Algorithm (DRGA) is used for segmentation of mammogram which disperses seeds in different regions instead of a single bright region. To demonstrate the validity of our segmentation method, 322 mammographic images from Mammographic Image Analysis Society (MIAS) database are used. The dataset contains medio-lateral oblique (MLO) view of mammograms. Experimental results on MIAS dataset show the effectiveness of our proposed method.

Keywords: CAD, dispersed region growing algorithm (DRGA), image segmentation, mammography, pectoral muscle sliding window algorithm (PMSWA)

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Authors: Jamal Alasiri, Naif Hakeem, Saoud Almaslmani

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Background: Patients with humeral shaft fractures have two different treatment options. Surgical therapy has lesser risks of non-union, mal-union, and re-intervention than non-surgical therapy. These positive clinical outcomes of the surgical approach make it a preferable treatment option despite the risks of radial nerve palsy and additional surgery-related risk. We aimed to evaluate patients’ outcomes and return to work after surgical vs. non-surgical management of shaft humeral fracture. Methods: We used databases, including PubMed, Medline, and Cochrane Register of Controlled Trials, from 2010 to January 2022 to search for potential randomised controlled trials (RCTs) and cohort studies comparing the patients’ related outcome measures and return to work between surgical and non-surgical management of humerus fracture. Results: After carefully evaluating 1352 articles, we included three RCTs (232 patients) and one cohort study (39 patients). The surgical intervention used plate/nail fixation, while the non-surgical intervention used a splint or brace procedure to manage shaft humeral fracture. The pooled DASH effects of all three RCTs at six (M.D: -7.5 [-13.20, -1.89], P: 0.009) I2:44%) and 12 months (M.D: -1.32 [-3.82, 1.17], p:0.29, I2: 0%) were higher in patients treated surgically than in non-surgical procedures. The pooled constant Murley score at six (M.D: 7.945[2.77,13.10], P: 0.003) I2: 0%) and 12 months (M.D: 1.78 [-1.52, 5.09], P: 0.29, I2: 0%) were higher in patients who received non-surgical than surgical therapy. However, pooled analysis for patients returning to work for both groups remained inconclusive. Conclusion: Altogether, we found no significant evidence supporting the clinical benefits of surgical over non-surgical therapy. Thus, the non-surgical approach remains the preferred therapeutic choice for managing shaft humeral fractures due to its lesser side effects.

Keywords: shaft humeral fracture, surgical treatment, Patient-related outcomes, return to work, DASH

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Authors: Ananda Perera

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Diet therapy has a positive impact on many diseases in General Practice. If a meal plan can be generated as easily as writing a drug prescription for dyspepsia, then the evidence and practice gap in nutrition therapy can be narrowed. Meal plans of 50 diet prescriptions were compared with the criteria for a healthy diet given by Australian authorities. The energy value of each meal plan was compared with the recommended daily energy requirements of the authorities for Diet Prescription Generator (DPG) accuracy. Meal plans generated were within the criteria laid down by the Australian authorities for a healthy diet.

Keywords: dieting, obesity, diabetes, weight loss, computerized decision support systems, dieting software, CDSS, meal plans

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Authors: Alaa Hamed Salama, Rehab Nabil Shamma

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Introduction: Polymeric micelles that can deliver drug to intended sites of the eye have attracted much scientific attention recently. The aim of this study was to review the aqueous-based formulation of drug-loaded polymeric micelles that hold significant promise for ophthalmic drug delivery. This study investigated the synergistic performance of mixed polymeric micelles made of linear and branched poly (ethylene oxide)-poly (propylene oxide) for the more effective encapsulation of Lornoxicam (LX) as a hydrophobic model drug. Methods: The co-micellization process of 10% binary systems combining different weight ratios of the highly hydrophilic poloxamers; Synperonic® PE/P84, and Synperonic® PE/F127 and the hydrophobic poloxamine counterpart (Tetronic® T701) was investigated by means of photon correlation spectroscopy and cloud point. The drug-loaded micelles were tested for their solubilizing capacity towards LX. Results: Results showed a sharp solubility increase from 0.46 mg/ml up to more than 4.34 mg/ml, representing about 136-fold increase. Optimized formulation was selected to achieve maximum drug solubilizing power and clarity with lowest possible particle size. The optimized formulation was characterized by 1HNMR analysis which revealed complete encapsulation of the drug within the micelles. Further investigations by histopathological and confocal laser studies revealed the non-irritant nature and good corneal penetrating power of the proposed nano-formulation. Conclusion: LX-loaded polymeric nanomicellar formulation was fabricated allowing easy application of the drug in the form of clear eye drops that do not cause blurred vision or discomfort, thus achieving high patient compliance.

Keywords: confocal laser scanning microscopy, Histopathological studies, Lornoxicam, micellar solubilization

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Authors: Ashley Hobson, Ashley Efaw

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Professionalism is an essential skill for clinicians, particularly for Occupational Therapy Providers (OTPs). The World Federation of Occupational Therapy (WFOT) Guiding Principles for Ethical Occupational Therapy and American Occupational Therapy Association (AOTA) Code of Ethics establishes expectations for professionalism among OTPs, emphasizing its importance in the field. However, the teaching and assessment of professionalism vary across OTP programs. The flexibility provided by the country standards allows programs to determine their own approaches to meeting these standards, resulting in inconsistency. Educators in both academic and fieldwork settings face challenges in objectively assessing and providing feedback on student professionalism. Although they observe instances of unprofessional behavior, there is no standardized assessment measure to evaluate professionalism in OTP students. While most students are committed to learning and applying professionalism skills, they enter OTP programs with varying levels of proficiency in this area. Consequently, they lack a uniform understanding of professionalism and lack an objective means to self-assess their current skills and identify areas for growth. It is crucial to explicitly teach professionalism, have students to self-assess their professionalism skills, and have OTP educators assess student professionalism. This approach is necessary for fostering students' professionalism journeys. Traditionally, there has been no objective way for students to self-assess their professionalism or for educators to provide objective assessments and feedback. To establish a uniform approach to professionalism, the authors incorporated professionalism content into our curriculum. Utilizing an operational definition of professionalism, the authors integrated professionalism into didactic, fieldwork, and capstone courses. The complexity of the content and the professionalism skills expected of students increase each year to ensure students graduate with the skills to practice in accordance with the WFOT Guiding Principles for Ethical Occupational Therapy Practice and AOTA Code of Ethics. Two professionalism assessments were developed based on the expectations outlined in the both documents. The Professionalism Self-Assessment allows students to evaluate their professionalism, reflect on their performance, and set goals. The Professionalism Assessment for Educators is a modified version of the same tool designed for educators. The purpose of this workshop is to provide educators with a framework and tools for assessing student professionalism. The authors discuss how to integrate professionalism content into OTP curriculum and utilize professionalism assessments to provide constructive feedback and equitable learning opportunities for OTP students in academic, fieldwork, and capstone settings. By adopting these strategies, educators can enhance the development of professionalism among OTP students, ensuring they are well-prepared to meet the demands of the profession.

Keywords: professionalism, assessments, student learning, student preparedness, ethical practice

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Authors: Loai AbdAllah, Mahmoud Kaiyal

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Missing values in real-world datasets are a common problem. Many algorithms were developed to deal with this problem, most of them replace the missing values with a fixed value that was computed based on the observed values. In our work, we used a distance function based on Bhattacharyya distance to measure the distance between objects with missing values. Bhattacharyya distance, which measures the similarity of two probability distributions. The proposed distance distinguishes between known and unknown values. Where the distance between two known values is the Mahalanobis distance. When, on the other hand, one of them is missing the distance is computed based on the distribution of the known values, for the coordinate that contains the missing value. This method was integrated with Wikaya, a digital health company developing a platform that helps to improve prevention of chronic diseases such as diabetes and cancer. In order for Wikaya’s recommendation system to work distance between users need to be measured. Since there are missing values in the collected data, there is a need to develop a distance function distances between incomplete users profiles. To evaluate the accuracy of the proposed distance function in reflecting the actual similarity between different objects, when some of them contain missing values, we integrated it within the framework of k nearest neighbors (kNN) classifier, since its computation is based only on the similarity between objects. To validate this, we ran the algorithm over diabetes and breast cancer datasets, standard benchmark datasets from the UCI repository. Our experiments show that kNN classifier using our proposed distance function outperforms the kNN using other existing methods.

Keywords: missing values, incomplete data, distance, incomplete diabetes data

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Authors: H. Bouaziz, M. Sefi, J. de Lapuente, M. Borras, N. Zeghal

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Although arsenic trioxide has been the subject of toxicological research, in vitro cytotoxicity and genotoxicity studies using relevant cell models and uniform methodology are not well elucidated. Hence, the aim of the present study was to evaluate the cytotoxicity and genotoxicity induced by arsenic trioxide in human keratinocytes (HaCaT) using the MTT [3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] and alkaline single cell gel electrophoresis (Comet) assays, respectively. Human keratinocytes were treated with different doses of arsenic trioxide for 4 h prior to cytogenetic assessment. Data obtained from the MTT assay indicated that arsenic trioxide significantly reduced the viability of HaCaT cells in a dose-dependent manner, showing a IC50 value of 34.18 ± 0.6 µM. Data generated from the comet assay also indicated a significant dose-dependent increase in DNA damage in HaCaT cells associated with arsenic trioxide exposure. We observed a significant increase in comet tail length and tail moment, showing an evidence of arsenic trioxide -induced genotoxic damage in HaCaT cells. This study confirms that the comet assay is a sensitive and effective method to detect DNA damage caused by arsenic.

Keywords: arsenic trioxide, cytotoxixity, genotoxicity, HaCaT

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Authors: Igna Brajević Gizdić, Gorka Vuletić

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Introduction: Addiction is a chronic brain relapsing disorder. Opioid Substitution Therapy (OST) using buprenorphine as a medical treatment option shows as a promising option for achieving and maintaining abstinence in opioid-addicted patients. This research aimed to determine and evaluate the quality of life (QoL) in opiate-addicted patients after five years of buprenorphine therapy. Method: The total sample included 44 buprenorphine-maintained opiate addicts in outpatient treatment. The participants were administered the QoL questionnaire (WHOQOL-BREF) at two-time points (T1 and T2) with an interval of at least five years. WHOQOL-BREF contains a total of 26 questions. The first two questions, related to overall QoL and general health status, and the remaining questions (3–26), which represented four domains—physical, psychological, social, and environmental health—were evaluated separately. Results: The results indicated no significant differences in overall self-assessed QoL nor in individual domains after five years (T2) of abstinence with OST buprenorphine- maintenance. Conclusion: These findings indicated no improvement in QoL of buprenorphine-maintenance opiate addicts in outpatient treatment. However, this might be due to the smaller sample size and participants' overall high scores in QoL at T1. This study suggests the importance of expectations when considering the QoL and general health of buprenorphine-maintenance opiate addicts in outpatient treatment.

Keywords: abstinence, addicts, buprenorphine, opioid substitution therapy, quality of life

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Authors: Selim M. Khan, Aaron A. Goodarzi, Joshua M. Taron, Tryggve Rönnqvist

Abstract:

Indoor air quality, a prime determinant of health, is strongly influenced by the presence of hazardous radon gas within the built environment. As a health issue, dangerously high indoor radon arose within the 20th century to become the 2nd leading cause of lung cancer. While the 21st century building metrics and human behaviors have captured, contained, and concentrated radon to yet higher and more hazardous levels, the issue is rapidly worsening in Canada. It is established that Canadians in the Prairies are the 2nd highest radon-exposed population in the world, with 1 in 6 residences experiencing 0.2-6.5 millisieverts (mSv) radiation per week, whereas the Canadian Nuclear Safety Commission sets maximum 5-year occupational limits for atomic workplace exposure at only 20 mSv. This situation is also deteriorating over time within newer housing stocks containing higher levels of radon. Deep machine learning (LSTM) algorithms were applied to analyze multiple quantitative and qualitative features, determine the most important contributory factors, and predicted radon levels in the known past (1990-2020) and projected future (2021-2050). The findings showed gradual downwards patterns in Sweden, whereas it would continue to go from high to higher levels in Canada over time. The contributory factors found to be the basement porosity, roof insulation depthness, R-factor, and air dynamics of the indoor environment related to human window opening behaviour. Building codes must consider including these factors to ensure adequate indoor ventilation and healthy living that can prevent lung cancer in non-smokers.

Keywords: radon, building metrics, deep learning, LSTM prediction model, lung cancer, canada, sweden

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Authors: T. O. Ikpesu, I. Tongo, A. Ariyo

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This study was conducted to assess the effects of an organophosphate pesticide glyphosate formulation on neurological enzymes in the brain, liver and serum of juvenile Clarias gariepinus, and also to examine the antidotal prospect of Garcinia kola seeds extract. The fish divided into five groups were exposed to different treatments of glyphosate formulation and Garcinia kola seeds extract. Acetyl cholinesterase activities in the brain, liver and serum of the fish were estimated in the experimental and control fishes on day -7, 14, 21 and of 28 by spectrophotometrical methods. The enzyme was significantly (p < 0.05) inhibited in glyphosate formulation test. The inhibition percentages of AChE ranged for the brain, liver and serum between 40.7–59.4%, 50-57% and 27.5–51.3%, respectively. The aberrated parameters were recovered in G. kola seeds extract treated aquaria, and was dose and time dependent. The present study demonstrated that in vivo glyphosate formulation exposure caused AChE inhibition in the brain, liver and the serum. The brain tissue, however, might be suggested as a good indicator tissue for aquatic pollutants exposure in the fish and G. kola seeds extract has shown to be a good remedy for neurology restoration in a noxious circumstance. The findings has shown that xenobiotics could be eliminated from aquatic organisms, especially fish, and could be put into practice in areas at risk of pollutants. This approach can reduce the risks of biomagnification of poison in sea food. Hence, formulation of this plant extracts into capsule should be encouraged and supported.

Keywords: glyphosate, Clarias gariepinus, brain, Garcinia kola, acetyl cholinesterase, enzymes

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Authors: Bharti Arora, Michael Chen, Steven Lun

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Plasmacytoid urothelial carcinoma (PUC) of the bladder is a rare and aggressive subtype of urothelial carcinoma that usually presents at an advanced clinical stage, has a predilection for early metastatic potential and is associated with poor prognosis. The first reported case of PUC was in 1991 and approximately 100 cases were reported in the literature worldwide. We present a case of a 43 year old female presenting with a 3-month history of urgency and frequency. Failing medical management of her urinary symptoms with anticholinergic medication, she underwent a diagnostic cystoscopy which revealed an erythematous and indurated bladder. Bladder biopsies of these regions revealed plasmacytoid urothelial carcinoma. Pre-operative staging scans were clear of any metastatic disease and the patient subsequently underwent a radical cystectomy and pelvic clearance with the formation of ileal conduit for urinary diversion. Histology confirmed plasmacytoid urothelial carcinoma with involvement of right upper vagina and focally positive margins in soft tissue at right and left sides of bladder. She received adjuvant chemotherapy but passed away within a year from disease progression. PUC can present atypically and our case highlights the role of cystoscopy in patients with persistent urinary symptoms. By reviewing the literature on PUC, we aim to raise awareness and improve understanding of this rare bladder cancer subtype amongst urologists.

Keywords: urology, bladder cancer, plasmacytoid urothelial cancer, literature review

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Authors: Ms Azam Najafkouchak, David Todem, Dorothy Pathak, Pramod Pathak, Joseph Gardiner

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Propensity score (PS) methods have recently become the standard analysis as a tool for the causal inference in the observational studies where exposure is not randomly assigned, thus, confounding can impact the estimation of treatment effect on the outcome. For the binary outcome, the effect of treatment on the outcome can be estimated by odds ratios, relative risks, and risk differences. However, using the different PS methods may give you a different estimation of the treatment effect on the outcome. Several methods of PS analyses have been used mainly, include matching, inverse probability of weighting, stratification, and covariate adjusted on PS. Due to the dangers of discretizing continuous variables (exposure, covariates), the focus of this paper will be on how the variation in cut-points or boundaries will affect the average treatment effect (ATE) utilizing the stratification of PS method. Therefore, we are trying to avoid choosing arbitrary cut-points, instead, we continuously discretize the PS and accumulate information across all cut-points for inferences. We will use Monte Carlo simulation to evaluate ATE, focusing on two PS methods, stratification and covariate adjusted on PS. We will then show how this can be observed based on the analyses of the data from a case-control study of breast cancer, the Polish Women’s Health Study.

Keywords: average treatment effect, propensity score, stratification, covariate adjusted, monte Calro estimation, breast cancer, case_control study

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Authors: Anna Lierova, Jitka Kasparova, Marcela Jelicova, Lucie Korecka, Zuzana Bilkova, Zuzana Sinkorova

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Hyaluronic acid (HA) is a simple linear, unbranched polysaccharide with a lot of exceptional physiological and chemical properties such as high biocompatibility and biodegradability, strong hydration and viscoelasticity that depend on the size of the molecule. It plays the important role in a variety of molecular events as tissue hydration, mechanical protection of tissues and as well as during inflammation, leukocyte migration, and extracellular matrix remodeling. Also, HA-based biomaterials, including HA scaffolds, hydrogels, thin membranes, matrix grafts or nanoparticles are widely use in various biomedical applications. Our goal is to determine the radioprotective effect of hyaluronic acid nanoparticles (HA NPs). We are investigating effect of ionizing radiation on stability of HA NPs, in vitro relative toxicity of nanoscale as well as effect on cell lines and specific surface receptors and their response to ionizing radiation. An exposure to ionizing radiation (IR) can irreversibly damage various cell types and may thus have implications for the level of the whole tissue. Characteristic manifestations are formation of over-granulated tissue, remodeling of extracellular matrix (ECM) and abortive wound healing. Damages are caused by either direct interaction with DNA and IR proteins or indirectly by radicals formed during radiolysis of water Accumulation and turnover of ECM are a hallmark of radiation induces lung injury, characterized by inflammation, repair or remodeling health pulmonary tissue. HA is a major component of ECM in lung and plays an important role in regulating tissue injury, accelerating tissue repair, and controlling disease outcomes. Due to that, HA NPs were applied to in vivo model (C57Bl/6J mice) before total body or partial thorax irradiation. This part of our research is targeting on effect of exogenous HA on the development and/or mitigating acute radiation syndrome and radiation induced lung injuries.

Keywords: hyaluronic acid, ionizing radiation, nanoparticles, radiation induces lung damages

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Authors: Brigitta Bodnár, Lajos Kovács, Zoltán Kupihár

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The cancer cells require higher amount of nucleoside building blocks for their proliferation, therefore they have significantly higher uptake of nucleosides by the different nucleoside transporters. Therefore, the conjugation with nucleosides may significantly increase the efficiency and selectivity of potential active pharmaceutical ingredients. On the other hand, the advantage of using a nucleoside could be either the higher activity on targeted enzymes overrepresented in cancer cells or an enhanced cellular uptake of the bioconjugates in these cells compared to the healthy ones. This fact can be used to make the nucleosides, as targeting moieties covalently bound to anti-cancer drug molecules which can selectively accumulate in cancer cells. However, in order to form the nucleoside-drug conjugates, such nucleoside building blocks are needed, which can selectively be coupled to the drug molecules containing even a high number of diverse functional groups. One of the most selective conjugation techniques is the copper-catalyzed azide-alkyne click reaction that requires the presence of an alkyl group on one of the conjugated molecules and an azide group on the other. In case of nucleosides, the development of azide group is simpler for which the replacement of the 5'-hydroxy group is the most suitable. This transformation generally involves many side reactions and result in very low yields. In addition, during our experiments, the transformation of the 2'-deoxyguanosine to the corresponding 5'-deoxy-5’-azido-2’-deoxyguanosine could not be performed with any of the methods described in the literature. Therefore, we have tried to overcome these difficulties with not only using the traditional process based on the 2 step exchange of tosyl to azide, but also using the Mitsunobu reaction which requires only one step. However, this path proved to be unsuccessful in spite of the optimizing the reaction conditions. Finally, a method has been developed whereby the azide groups were incorporated into the 5’-position resulting in significantly better yields compared to all other previous methods, and we were able to produce all the four nucleoside derivatives.

Keywords: 5'-azidonucleosides, bioconjugate, click reaction, proliferation

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Authors: Chao Hsing Yeh, Wei Chun Lin

Abstract:

Background: Current management of aromatase inhibitor-induced arthralgia (AIA) in postmenopausal breast cancer survivors (PBCS) has limited effect. Method: In this prospective randomized clinical trial (RCT), a 4-week APA treatment was used to manage AIA. Twenty PBCS participated. After baseline data was collected, participants were waited for a month before they receive APA at a convenient time once a week for 4 weeks. Blood samples from participants in both groups were collected at baseline and after 4 weeks of treatment. The primary outcomes included: pain intensity, pain interference, stiffness, and physical function. Results: After the 4-week APA treatment, the pro-inflammatory cytokines and chemokines display a trend of mean percentage reduction (i.e., -22% in IL-1α, -4% in IL-1β, -1% in IL-2, -3% in IL-6, -19% in IL-12, -9% in Eotaxin, and -2% in MCP-1). The anti-inflammatory cytokine IL-10 and IL-13 (i.e., 5% in IL-10 and 29% in IL-13) increased from pre- to post-APA treatment. Significant positive correlation of percentage mean change was observed between symptom severity and eotaxin (ρ = 0.56; p < 0.01) & MCP-1 (ρ = 0.65; p < 0.01). Interference and chemokines (eotaxin & MIP-1) also shows positive correlation (ρ = 0.48; p < 0.01 & ρ = 0.39; p < 0.05). Another positive correlation was found between worst pain and chemokines (eotaxin, ρ = 0.48; p < 0.01 & MIP-1, ρ = 0.39; p < 0.05). Additionally, interference also shows positive correlation among IL-1α (ρ = 0.36; p < 0.05) and IL-β (ρ = 0.33; p < 0.05). Conclusion: These findings suggest that APA intervention may inhibit inflammation of AIA patients and chemokine could be one of the key factors of AIA symptom improvement.

Keywords: acupressure, cytokine, pain management, breast cancer survivors

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Authors: Akimitsu Kugimiya, Kouhei Iwato, Toru Saito, Jiro Kohda, Yasuhisa Nakano, Yu Takano

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The measurement of amino acid content is reported to be useful for the diagnosis of several types of diseases, including lung cancer, gastric cancer, colorectal cancer, breast cancer, prostate cancer, and diabetes. The conventional detection methods for amino acid are high-performance liquid chromatography (HPLC) and liquid chromatography-mass spectrometry (LC-MS), but they have several drawbacks as the equipment is cumbersome and the techniques are costly in terms of time and costs. In contrast, biosensors and biosensing methods provide more rapid and facile detection strategies that use simple equipment. The authors have reported a novel approach for the detection of each amino acid that involved the use of aminoacyl-tRNA synthetase (aaRS) as a molecular recognition element because aaRS is expected to a selective binding ability for corresponding amino acid. The consecutive enzymatic reactions used in this study are as follows: aaRS binds to its cognate amino acid and releases inorganic pyrophosphate. Hydrogen peroxide (H₂O₂) was produced by the enzyme reactions of inorganic pyrophosphatase and pyruvate oxidase. The Trinder’s reagent was added into the reaction mixture, and the absorbance change at 556 nm was measured using a microplate reader. In this study, an amino acid-sensing method using histidyl-tRNA synthetase (HisRS; histidine-specific aaRS) as molecular recognition element in combination with the Trinder’s reagent spectrophotometric method was developed. The quantitative performance and selectivity of the method were evaluated, and the optimal enzyme reaction and detection conditions were determined. The authors developed a simple and rapid method for detecting histidine with a combination of enzymatic reaction and spectrophotometric detection. In this study, HisRS was used to detect histidine, and the reaction and detection conditions were optimized for quantitation of these amino acids in the ranges of 1–100 µM histidine. The detection limits are sufficient to analyze these amino acids in biological fluids. This work was partly supported by Hiroshima City University Grant for Special Academic Research (General Studies).

Keywords: amino acid, aminoacyl-tRNA synthetase, biosensing, enzyme reaction

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