Search results for: anti-tubercular therapy induced hepatotoxicity

Authors: Tooran Tavangar, Masoud Hosseinpoor, Jeffrey S. Marshall, Ammar Yahia, Kamal Henri Khayat

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In this study, a four-way coupled CFD-DEM methodology was used to simulate the behavior of concrete pipe flow. Fresh concrete, characterized as a biphasic suspension, features aggregates comprising the solid-suspended phase with diverse particle-size distributions (PSD) within a non-Newtonian cement paste/mortar matrix forming the liquid phase. The fluid phase was simulated using CFD, while the aggregates were modeled using DEM. Interaction forces between the fluid and solid particles were considered through CFD-DEM computations. To capture the viscoelastic characteristics of the suspending fluid, a bi-viscous approach was adopted, incorporating a critical shear rate proportional to the yield stress of the mortar. In total, three diphasic suspensions were simulated, each featuring distinct particle size distributions and a concentration of 10% for five subclasses of spherical particles ranging from 1 to 17 mm in a suspending fluid. The adopted bi-viscous approach successfully simulated both un-sheared (plug flow) and sheared zones. Furthermore, shear-induced particle migration (SIPM) was assessed by examining coefficients of variation in particle concentration across the pipe. These SIPM values were then compared with results obtained using CFD-DEM under the Newtonian assumption. The study highlighted the crucial role of yield stress in the mortar phase, revealing that lower yield stress values can lead to increased flow rates and higher SIPM across the pipe.

Keywords: computational fluid dynamics, concrete pumping, coupled CFD-DEM, discrete element method, plug flow, shear-induced particle migration.

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Authors: Thomas Jin-Chee Liu

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In this paper, the thermo-electro-structural coupled-field in a cracked metal plate is studied using the finite element analysis. From the computational results, the compressive stresses reveal near the crack tip. This conclusion agrees with the past reference. Furthermore, the compressive condition can retard and stop the crack growth during the Joule heating process.

Keywords: compressive stress, crack tip, Joule heating, finite element

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Authors: Maham Leeza Adil, Mahrukh Alvi, Muhammad Osman

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Introduction: Sheehan's syndrome (SS) is a rare cause of hypopituitarism resulting from postpartum hemorrhage and pituitary necrosis. It remains an underdiagnosed condition, especially in developing countries, due to poor obstetric care and home deliveries. This case report highlights the significance of recognizing atypical presentations of SS, such as pancytopenia, to aid in early diagnosis and management. Case Presentation: A 40-year-old female presented with acute abdomen symptoms and was initially diagnosed with acalculous cholecystitis. However, a detailed history revealed a history of postpartum hemorrhage 18 years prior, leading to a provisional diagnosis of SS. Further investigations confirmed panhypopituitarism, including hypothyroidism, hypocortisolism, and hypogonadism. Notably, the patient also exhibited pancytopenia, a rarely reported hematological manifestation of SS. Discussion: SS often presents with nonspecific symptoms, leading to delayed or missed diagnoses. In this case, the patient's initial presentation of acute abdomen symptoms was attributed to secondary adrenal insufficiency due to panhypopituitarism. The presence of pancytopenia, along with hyponatremia, further complicated the clinical picture. Hormone replacement therapy led to a remarkable improvement in the patient's condition, emphasizing the importance of early diagnosis and intervention. Conclusion: SS is a common cause of panhypopituitarism in developing countries, but its atypical presentations, such as pancytopenia, are rare and often overlooked. This case highlights the need for increased awareness among clinicians to consider SS in patients with unexplained hematological abnormalities, particularly in regions with high rates of postpartum hemorrhage. Early recognition and appropriate hormone replacement therapy can significantly improve patients' outcomes and prevent long-term complications associated with this underdiagnosed syndrome.

Keywords: Sheehan syndrome, panhypopituitarism, pancytopenia, delayed diagnosis

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Authors: Gabriela Ilie, Robert D. H. Rutledge

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A review of the literature reveals a need for longitudinal studies to properly understand the quality of life of prostate cancer survivors during their prostate cancer journey in order to identify opportunities for patient support and care during prostate cancer survivorship. In this study, mental health and relationship satisfaction were assessed longitudinally and by treatment modality among a population-based sample of Canadian adult men with a history of prostate cancer diagnosis. A total of 98 men, aged 51 or older with a history of prostate cancer completed an on-line 15-minute survey between May 2017 and February 2018, assessing mental health (Kessler Psychological Distress Scale) and relationship satisfaction (Dyadic Adjustment Scale) at baseline and at three months post-treatment with either active or nonactive prostate cancer treatment. Almost 1 in 6 men in this sample screened positive for mental health issues (17.34%, n=17) irrespective of treatment modality and most (n=11) were not currently on medication for depression, anxiety or both. Mental health outcomes were poorer for men with multimorbidity. For every instance of screening positive for mental health issues, 2.021 (95% CI:1.1 to 3.8) times more comorbidities were recorded. Relationship satisfaction and dyadic cohesion were statistically significantly lower from first assessment to 3 months for men who underwent multiple treatment modalities (surgery and radiation with hormonal therapy). Relationship satisfaction was also lower at 3 months for men who underwent radiation therapy. Almost 1 in 2 men in this sample (74%) indicated they did not attend a prostate cancer support group. Results suggest that treatment for mental health is underutilized in men with prostate cancer. Men who undergo multiple forms of active treatment appear more vulnerable to relationship dissatisfaction and feeling disconnected from their partner. Data points to important opportunities for patient education and care support during survivorship.

Keywords: prostate cancer survivorship, mental health, quality of life, relationship satisfaction

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Authors: Ipsita Biswas, Arnab Sarkar, Ashikur Rahaman, Gopeswar Mukherjee, Subhrangsu Chatterjee, Shamee Bhattacharjee, Deba Prasad Mandal

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One of the major reasons for the high mortality rate of lung cancer is the substantial delays in disease detection at late metastatic stages. It is of utmost importance to understand the detailed molecular signaling and detect the molecular markers that can be used for the early diagnosis of cancer. Several studies explored the emerging roles of long noncoding RNAs (lncRNAs) in various cancers as well as lung cancer. A long non-coding RNA LINC00273 was recently discovered to promote cancer cell migration and invasion, and its positive correlation with the pathological stages of metastasis may prove it to be a potential target for inhibiting cancer cell metastasis. Comparing real-time expression of LINC00273 in various human clinical cancer tissue samples with normal tissue samples revealed significantly higher expression in cancer tissues. This long intergenic noncoding RNA was found to be highly expressed in human liver tumor-initiating cells, human gastric adenocarcinoma AGS cell line, as well as human non-small cell lung cancer A549 cell line. SiRNA and shRNA-induced knockdown of LINC00273 in both in vitro and in vivo nude mice significantly subsided AGS and A549 cancer cell migration and invasion. LINC00273 knockdown also reduced TGF-β induced SNAIL, SLUG, VIMENTIN, ZEB1 expression, and metastasis in A549 cells. Plenty of reports have suggested the role of microRNAs of the miR200 family in reversing epithelial to mesenchymal transition (EMT) by inhibiting ZEB transcription factors. In this study, hsa-miR-200a-3p was predicted via IntaRNA-Freiburg RNA tools to be a potential target of LINC00273 with a negative free binding energy of −8.793 kcal/mol, and this interaction was verified as a confirmed target of LINC00273 by RNA pulldown, real-time PCR and luciferase assay. Mechanistically, LINC00273 accelerated TGF-β induced EMT by sponging hsa-miR-200a-3p which in turn liberated ZEB1 and promoted prometastatic functions in A549 cells in vitro as verified by real-time PCR and western blotting. The similar expression patterns of these EMT regulatory pathway molecules, viz. LINC00273, hsa-miR-200a-3p, ZEB1 and TGF-β, were also detected in various clinical samples like breast cancer tissues, oral cancer tissues, lung cancer tissues, etc. Overall, this LINC00273 mediated EMT regulatory signaling can serve as a potential therapeutic target for the prevention of lung cancer metastasis.

Keywords: epithelial to mesenchymal transition, long noncoding RNA, microRNA, non-small-cell lung carcinoma

Procedia PDF Downloads 156

Authors: Eun-Seop Kim, Eun-Ha Jang, Rana R. Kim, Sae-Byul Jang

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Objective: Preterm labor is the most common antecedent of preterm birth(PTB), which is characterized by regular uterine contraction before 37 weeks of pregnancy and cervical change. In acute preterm labor, tocolytics are administered as the first-line medication to suppress uterine contractions but rarely delay pregnancy to 37 weeks of gestation. On the other hand, according to the Korean Traditional Medicine, PTB is caused by the deficiency of Qi and unnecessary energy in the body of the mother. The aim of this study was to demonstrate the benefit of Traditional Korean Medicine as an adjuvant therapy in management of early uterine contractions and the prevention of PTB. Methods: It is a case report of a 38-year-old woman (0-0-6-0) hospitalized for irregular uterine contractions and cervical change at 33+3/7 weeks of gestation. Past history includes chemical pregnancies achieved by Artificial Rroductive Technology(ART), one stillbirth (at 7 weeks) and a laparoscopic surgery for endometriosis. After seven trials of IVF and articificial insemination, she had succeeded in conception via in-vitro fertilization (IVF) with help of Traditional Korean Medicine (TKM) treatments. Due to irregular uterine contractions and cervical changes, 2 TKM were prescribed: Gami-Dangguisan, and Antae-eum, known to nourish blood and clear away heat. 120ml of Gami-Dangguisan was given twice a day monring and evening along with same amount of Antae-eum once a day from 31 August 2013 to 28 November 2013. Tocolytics (Ritodrine) was administered as a first aid for maintenance of pregnancy. Information regarding progress until the delivery was collected during the patient’s visit. Results: On admission, the cervix of 15mm in length and cervical os with 0.5cm-dilated were observed via ultrasonography. 50% cervical effacement was also detected in physical examination. Tocolysis had been temporarily maintained. As a supportive therapy, TKM herbal preparations(gami-dangguisan and Antae-eum) were concomitantly given. As of 34+2/7 weeks of gestation, however intermittent uterine contractions appeared (5-12min) on cardiotocography and vaginal bleeding was also smeared at 34+3/7 weeks. However, enhanced tocolytics and continuous administration of herbal medicine sustained the pregnancy to term. At 37+2/7 weeks, no sign of labor with restored cervical length was confirmed. The woman gave a term birth to a healthy infant via vaginal delivery at 39+3/7 gestational weeks. Conclusions: This is the first successful case report about a preter labor patient administered with conventional tocolytic agents as well as TKM herbal decoctions, delaying delivery to term. This case deserves attention considering it is rare to maintain gestation to term only with tocolytic intervention. Our report implies the potential of herbal medicine as an adjuvant therapy for preterm labor treatment. Further studies are needed to assess the safety and efficacy of TKM herbal medicine as a therapeutic alternative for curing preterm birth.

Keywords: preterm labor, traditional Korean medicine, herbal medicine, integrative treatment, complementary and alternative medicine

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Authors: Nabil Omar, Farah Jibril, Oraib Amjad

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Purpose: Trabecatine is a is a potent marine-derived antineoplastic drug which binds to the minor groove of the DNA, bending DNA towards the major groove resulting in a changed conformation that interferes with several DNA transcription factors, repair pathways and cell proliferation. Trabectedin was approved by the European Medicines Agency (EMA; London, UK) for the treatment of adult patients with advanced stage soft tissue sarcomas in whom treatment with anthracyclines and ifosfamide has failed, or for those who are not candidates for these therapies. The recommended dosing regimen is 1.5 mg/m2 IV over 24 hours every 3 weeks. The purpose of this study was to comprehensively review available data on the safety and efficacy of trabectedin used as indicated for patients at a Tertiary Cancer Center at Qatar. Methods: A medication administration report generated in the electronic health record identified all patients who received trabectedin between November 1, 2015 and November 1, 2017. This retrospective chart review evaluated the indication of trabectedin use, compliance to administration protocol and the recommended monitoring parameters, number of patients improved on the drug and continued treatment, number of patients discontinued treatment due to side-effects and the reported side effects. Progress and discharged notes were utilized to report experienced side effects during trabectedin therapy. A total of 3 patients were reviewed. Results: Total of 2 out of 3 patients who received trabectedin were receiving it for non-FDA and non-EMA, approved indications; metastatic rhabdomyosarcoma and ovarian cancer stage IV with poor prognosis. And only one patient received it as indicated for leiomyosarcoma of left ureter with metastases to liver, lungs and bone. None of the patients has continued the therapy due to development of serious side effects. One patient had stopped the medication after one cycle due to disease progression and transient hepatic toxicity, the other one had disease progression and developed 12 % reduction in LVEF after 12 cycles of trabectedin, and the third patient deceased, had disease progression on trabectedin after the 10th cycle that was received through peripheral line which resulted in developing extravasation and left arm cellulitis requiring debridement. Regarding monitoring parameters, at baseline the three patients had ECHO, and Creatine Phosphokinase (CPK) but it was not monitored during treatment as recommended. Conclusion: Utilizing this medication as indicated with performing the appropriate monitoring parameters as recommended can benefit patients who are receiving it. It is important to reinforce the intravenous administration via central intravenous line, the re-assessment of left ventricular ejection fraction (LVEF) by echocardiogram or multigated acquisition (MUGA) scan at 2- to 3-month intervals thereafter until therapy is discontinued, and CPK and LFTs levels prior to each administration of trabectedin.

Keywords: trabectedin, drug-use evaluation, safety, effectiveness, adverse drug reaction, monitoring

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Authors: Arman Kishan, Mark Haft, Kiyanna Thomas, Duc Nguyen, Dawn Laporte

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Objective: Patients receiving anticoagulation therapy frequently experience increased rates of postoperative complications. Presently, limited data exist regarding the outcomes of patients undergoing carpal tunnel release surgery (CTR) while on anticoagulation. Our objective is to examine and compare the occurrence of complications in patients on anticoagulation who underwent either endoscopic CTR (ECTR) or open CTR (OCTR) for CTS. Methods: The Trinet X database was utilized to retrospectively identify patients who underwent OCTR or ECTR while concurrently on anticoagulation. Demographic data, medical comorbidities, and complication rates were analyzed. We used multivariable analysis to identify differences in postoperative complications, including wound infection within 90 days, wound dehiscence within 90 days, and intraoperative median nerve injury between the two surgical methods in patients on anticoagulation. Results: A total of 10,919 carpal tunnel syndrome patients on anticoagulation were included in the study, with 9082 and 1837 undergoing OCTR and ECTR, respectively. Among patients on anticoagulation, those undergoing ECTR exhibited a significantly lower occurrence of 90-day wound infection (p < 0.001) and nerve injury (p < 0.001) compared to those who underwent OCTR. However, there was no statistically significant difference in the risk of 90-day wound dehiscence between the two groups (p = 0.323). Conclusion:  In prior studies, ECTR demonstrated reduced rates of postoperative complications compared to OCTR in the general population. Our study demonstrates that among patients on anticoagulation, those undergoing ECTR experienced a significantly lower incidence of 90-day wound infection and nerve injury, with risk reductions of 35% and 40%, respectively. These findings support using ECTR as a preferred surgical method for patients with CTS who are on anticoagulation therapy.

Keywords: endoscopic treatment of carpal tunnel syndrome, open treatment of carpal tunnel syndrome, postoperative complications in patients on anticoagulation, carpal tunnel syndrome

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Authors: Muhammad Isa Khan, Jalil Ur Rehman, Muhammad Afzal Khan Rao, James Chow

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Purpose: This study investigates the dose-volume variations in planning target volume (PTV) and organs-at-risk (OARs) using different collimator angles for smart arc prostate volumetric modulated arc therapy (VMAT). Awareness of the collimator angle for PTV and OARs sparing is essential for the planner because optimization contains numerous treatment constraints producing a complex, unstable and computationally challenging problem throughout its examination of an optimal plan in a rational time. Materials and Methods: Single arc VMAT plans at different collimator angles varied systematically (0°-90°) were performed on a Harold phantom and a new treatment plan is optimized for each collimator angle. We analyzed the conformity index (CI), homogeneity index (HI), gradient index (GI), monitor units (MUs), dose-volume histogram, mean and maximum doses to PTV. We also explored OARs (e.g. bladder, rectum and femoral heads), dose-volume criteria in the treatment plan (e.g. D30%, D50%, V30Gy and V38Gy of bladder and rectum; D5%,V14Gy and V22Gy of femoral heads), dose-volume histogram, mean and maximum doses for smart arc VMAT at different collimator angles. Results: There was no significance difference found in VMAT optimization at all studied collimator angles. However, if 0.5% accuracy is concerned then collimator angle = 45° provides higher CI and lower HI. Collimator angle = 15° also provides lower HI values like collimator angle 45°. It is seen that collimator angle = 75° is established as a good for rectum and right femur sparing. Collimator angle = 90° and collimator angle = 30° were found good for rectum and left femur sparing respectively. The PTV dose coverage statistics for each plan are comparatively independent of the collimator angles. Conclusion: It is concluded that this study will help the planner to have freedom to choose any collimator angle from (0°-90°) for PTV coverage and select a suitable collimator angle to spare OARs.

Keywords: VMAT, dose-volume histogram, collimator angle, organs-at-risk

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Authors: Lebogang Jane Msiza, Felix Dapare Dakora

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Photosynthesis is a process by which plants convert light energy to chemical energy for metabolic processes. Plants are known for converting inorganic CO₂ in the atmosphere to organic C by photosynthesis. A decrease in stomatal conductance causes a decrease in the transpiration rate of leaves, thus increasing the water-use efficiency of plants. Water-use efficiency in plants is conditioned by soil moisture availability and is enhanced under conditions of water deficit. This study evaluated leaf photosynthesis and water-use efficiency in 12 legume species inoculated with 26 rhizobial isolates from soybean, 15 from common bean, 10 from cowpea, 15 from Bambara groundnut, 7 from lessertia and 10 from Kersting bean. Gas-exchange studies were used to measure photosynthesis and water-use efficiency. The results revealed a much higher photosynthetic rate (20.95µmol CO₂ m-2s-1) induced by isolated tutpres to a lower rate (7.06 µmol CO₂ m-2s-1) by isolate mgsa 88. Stomatal conductance ranged from to 0.01 mmol m-2.s-1 by mgsa 88 to 0.12 mmol m-2.s-1 by isolate da-pua 128. Transpiration rate also ranged from 0.09 mmol m-2.s-1 induced by da-pua B2 to 3.28 mmol m-2.s-1 by da-pua 3, while water-use efficiency ranged from 91.32 µmol CO₂ m-1 H₂O elicited by mgsa 106 to 4655.50 µmol CO₂ m-1 H₂O by isolate tutswz 13. The results revealed the highest photosynthetic rate in soybean and the lowest in common bean, and also with higher stomatal conductance and transpiration rates in jack bean and Bambara groundnut. Pigeonpea exhibited much higher water-use efficiency than all the tested legumes. The findings showed significant differences between and among the test legume/rhizobia combinations. Leaf photosynthetic rates are reported to be higher in legumes with high stomatal conductance, which suggests that legume productivity can be improved by manipulating leaf stomatal conductance.

Keywords: legumes, photosynthetic rate, stomatal conductance, water-use efficiency

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Authors: Paras Agarwal

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Background: Initially believed to be rare, metastases to the eye are the most common ocular malignancy. The choroid’s high perfusion rate not only makes it the most susceptible ocular site for tumour seeding, but also promotes its growth. The cancers most frequently responsible for choroidal metastases originate from the breast and lung, although a significant proportion have unidentified primaries at the time of presentation. Case Presentation: This case report describes a 34 year old female presenting to the ophthalmology department with a one month history of painless distorted vision. On fundus examination, she was noted to have bilateral choroidal lesionsand subsequently underwent a comprehensive diagnostic work-up. The patient was diagnosed with metastatic pulmonary adenocarcinoma, despite lacking conventional risk factors. As she was found to have a mutation in EGFR, the patient was commenced on tyrosine-kinase inhibition with afatinib. The choroidal lesions regressed with a significant improvement in visual acuity and a dramatic anatomical reduction of the choroidal masses. Conclusions: Our case demonstrates the importance of considering metastases as a differential diagnosis for choroidal lesions. Appropriate and thorough history-taking, examination and investigations may be required in order to deduce the underlying cause. Our case is unusual in view of the choroidal lesion being the primary manifestation of metastatic lung cancer in a young patient with no known risk factors. Early recognition of choroidal metastases is important as it is often the first sign of tumour dissemination and will prompt earlier treatment with systemic medications such as chemotherapy, immunotherapy, targeted therapy or hormonal therapy. Our case report also demonstrates the efficacy of afatinib for the treatment of choroidal metastases, with morphological and functional improvements observed with regard to the choroidal metastatic tumour.

Keywords: choroidal neoplasm, choroidal naevus, pulmonary adenocarcinoma, metastases, lung cancer

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Authors: Kanika Arora, Madhu Bala

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The small intestine epithelium is highly sensitive and major targets of ionizing radiation. Radiation causes gastrointestinal toxicity either by direct deposition of energy or indirectly (inflammation or bystander effects) generating free radicals and reactive oxygen species. Oxidative stress generated as a result of radiation causes active inflammation within the intestinal mucosa leading to structural and functional impairment of gut epithelial barrier. As a result, there is a loss of tolerance to normal dietary antigens and commensal flora together with exaggerated response to pathogens. Dysbiosis may therefore thought to play a role in radiation enteropathy and can contribute towards radiation induced bowel toxicity. Lactobacilli residing in the gut shares a long conjoined evolutionary history with their hosts and by doing so these organisms have developed an intimate and complex symbiotic relationships. The objective behind this study was to look for the strains with varying resistance to ionizing radiation and to see whether the niche of the bacteria is playing any role in radiation resistance property of bacteria. In this study, we have isolated the Lactobacillus spp. from probiotic preparation and murine gastrointestinal tract, both of which were supposed to be the important source for its isolation. Biochemical characterization did not show a significant difference in the properties, while a significant preference was observed in carbohydrate utilization capacity by the isolates. Effect of ionizing radiations induced by Co60 gamma radiation (10 Gy) on lactobacilli cells was investigated. A cellular survival curve versus absorbed doses was determined. Radiation resistance studies showed that the response of isolates towards cobalt-60 gamma radiation differs from each other and significant decrease in survival was observed in a dose-dependent manner. Thus the present study revealed that the property of radioresistance in Lactobacillus depends upon the source from where they have been isolated.

Keywords: dysbiosis, lactobacillus, mitigation, radiation

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Authors: Joanna Gerszon, Aleksandra Rodacka

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In the pathogenesis of neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease, protein and peptide aggregation processes play a vital role in contributing to the formation of intracellular and extracellular protein deposits. One of the major components of these deposits is the oxidatively modified glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Therefore, the purpose of this research was to answer the question whether piceatannol, a stilbene derivative, counteracts and/or slows down oxidative stress-induced GAPDH aggregation. The study also aimed to determine if this natural occurring compound prevents unfavorable nuclear translocation of GAPDH in hippocampal cells. The isothermal titration calorimetry (ITC) analysis indicated that one molecule of GAPDH can bind up to 8 molecules of piceatannol (7.3 ± 0.9). As a consequence of piceatannol binding to the enzyme, the loss of activity was observed. Parallel with GAPDH inactivation the changes in zeta potential, and loss of free thiol groups were noted. Nevertheless, the ligand-protein binding does not influence the secondary structure of the GAPDH. Precise molecular docking analysis of the interactions inside the active center allowed to presume that these effects are due to piceatannol ability to assemble a covalent binding with nucleophilic cysteine residue (Cys149) which is directly involved in the catalytic reaction. Molecular docking also showed that simultaneously 11 molecules of ligand can be bound to dehydrogenase. Taking into consideration obtained data, the influence of piceatannol on level of GAPDH aggregation induced by excessive oxidative stress was examined. The applied methods (thioflavin-T binding-dependent fluorescence as well as microscopy methods - transmission electron microscopy, Congo Red staining) revealed that piceatannol significantly diminishes level of GAPDH aggregation. Finally, studies involving cellular model (Western blot analyses of nuclear and cytosolic fractions and confocal microscopy) indicated that piceatannol-GAPDH binding prevents GAPDH from nuclear translocation induced by excessive oxidative stress in hippocampal cells. In consequence, it counteracts cell apoptosis. These studies demonstrate that by binding with GAPDH, piceatannol blocks cysteine residue and counteracts its oxidative modifications, that induce oligomerization and GAPDH aggregation as well as it prevents hippocampal cells from apoptosis by retaining GAPDH in the cytoplasm. All these findings provide a new insight into the role of piceatannol interaction with GAPDH and present a potential therapeutic strategy for some neurological disorders related to GAPDH aggregation. This work was supported by the by National Science Centre, Poland (grant number 2017/25/N/NZ1/02849).

Keywords: glyceraldehyde-3-phosphate dehydrogenase, neurodegenerative disease, neuroprotection, piceatannol, protein aggregation

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Authors: Nurul Hamirah Kamsani, Mohd Hamim Rajikin, Nor Ashikin Mohamed Noor Khan, Sharaniza Abdul Rahim

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Cytoskeletal structures, in particular actin and tubulin, provide a fundamental framework in all cells, including embryos. Under influence of nicotine, the cytoskeletal organization may be subjected to oxidative stress (OS) insult and cause alteration. Tocotrienol-rich fraction (TRF) is proven to enhance fertility better than the other sub-group of Vitamin E, tocopherols (TCPs). The objective of this study was to evaluate the effects of TRF on 1) actin and tubulin of 2- and 8-cell murine embryos and 2) the regulation of reactive oxygen species (ROS)-scavenging enzymes; induced by nicotine. Twenty four female Balb/C were subjected to either subcutaneous (sc) injection of 0.9% NaCl; sc injection of 3.0 mg/kg bw/day nicotine; sc injection of 3.0 mg/kg bw/day nicotine + oral gavage (OG) of 60 mg/kg bw/day TRF; or OG of 60 mg/kg bw/day TRF for 7 consecutive days. After superovulation and mating, animals were euthanized. 2-cell developing embryos were retrieved. 50% of the retrieved embryos were visualized under confocal laser staining microscopy (CLSM) for alterations of actin and tubulin. The remaining amount of embryos was cultured in vitro until 8-cell stage followed by CLSM visualization. Blood plasma was subjected to OS assays. Plasma malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were determined and analysed accordingly. At both 2- and 8-cell developing stages, actin intensities were significantly reduced in the nicotine group (p<0.001). After the intervention, actin intensity was significantly increased compared to that of the nicotine group (p<0.001). The same trend was seen in tubulin at both cell stages. TRF has minimized the deleterious effects of nicotine in actin and tubulin of both 2- and 8-cell developmental stages during pre-implantation embryonic development in mice in vitro. Levels of endogenous anti-oxidative enzymes were sustained close to control accompanied by decreased levels of OS biomarker.

Keywords: actin, nicotine, pre-implantation embryos, tocotrienol rich fraction, tubulin

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Authors: Caterina Grandi, Lukas Lochner, Marco Padovan, Mirco Rizzi, Paola Sperinde, Fabio Vittadello, Luisa Cavada

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Background: In recent years, the use of Complementary Alternative Medicine (CAM) has achieved worldwide popularity. With the increased public interest in CAMs, attention to it within Health Care Schools and Colleges has also improved. Studies generally assess the knowledge and attitudes regarding CAMs in medical and nursing students. The current study focused on the knowledge, attitudes and practice of CAM in healthcare students. Aim: To assess the knowledge and attitudes regarding complementary and alternative medicine (CAM) in healthcare students in South Tyrol, a region in Northern Italy. Methodology: This cross-sectional study was carried out among 361 students. Self-administered questionnaire was adapted and modified by the researchers from several questionnaires. The instrument consisted of three sections: 1) demographical characteristics (gender, place of residence and year of study); 2) general attitudes towards CAM, evaluated through 11 items using a Likert scale (agree, partly agree, partly disagree, disagree); 3) knowledge and use about any particular CAM practices (acupuncture, aromatherapy, creative therapies, diet/nutritional therapies, phytotherapy/herbal therapies, compresses, massage therapy, Ayurvedic therapy, Tibetan medicine, naturopathy, homeopathy, pet therapy, reflexology, therapeutic touch, chiropractic/osteopathy). Results: The sample consisted of 63 males and 297 females, 58% living in villages. 151 students (42%) were in the first year, 99 (27%) in the second and 106 (30%) in the third. Both men and women agreed with statements about the utility and benefits of CAMs. Women were significantly more likely than men to agree that the CAM practices should be included in the curriculum (p < 0.004), that the health professionals should be able to advice their patients about commonly used CAM methods (p < 0.002) and that the clinical care should integrate CAM practices (p < 0.04). Students in the second year showed the highest mean score for the statement 'CAM includes ideas and methods from which conventional medicine could benefit' (p = 0.049), highlighting a positive attitude, while students in the third year achieved the lowest mean score for the negative statement 'The results of CAM are in most cases due to a placebo effect'. Regarding this statement, participants living in villages disagreed significantly than students living in the city (p < 0.001). Females appeared to be significantly more familiar with homeopathy (p < 0.002), aromatherapy (p < 0.033), creative therapies (p < 0.001) and herbal therapies (p<0.002) than males. Moreover, women were likely to use CAM more frequently than men, particularly to solve psychological problems (p < 0.004). In addition, women perceived the benefit significantly more positive than men (p < 0.001). Students in the second year revealed to use the CAM mostly to improve the quality of life (p < 0.023), while students in the third year used CAMs particularly for chronic diseases (p < 0.001). Conclusions: Results from this study suggested that female students show more positive attitudes on CAM than male students. Moreover, the prevalence of CAM use and its perceived benefits differ between males and females, so that women are more willing to use CAM practices.

Keywords: attitude, CAM, complementary and alternative medicine, healthcare students, knowledge

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Authors: Timea Harmath-Tánczos

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Drug-resistant epilepsy (DRE) is defined as the persistence of seizures despite at least two syndrome-adapted antiseizure drugs (ASD) used at efficacious daily doses. About a third of patients with epilepsy suffer from drug resistance. Cognitive assessment has a crucial role in the diagnosis and clinical management of epilepsy. Previous studies have addressed the clinical targets and indications for measuring neuropsychological functions; best to our knowledge, no studies have examined it in a Hungarian therapy-resistant population. To fill this gap, we investigated the Hungarian diagnostic protocol between 18 and 65 years of age. This study aimed to describe and analyze neuropsychological functions in patients with drug-resistant epilepsy and identify factors associated with neuropsychology deficits. We perform a prospective case-control study comparing neuropsychological performances in 50 adult patients and 50 healthy individuals between March 2023 and July 2023. Neuropsychological functions were examined in both patients and controls using a full set of specific tests (general performance level, motor functions, attention, executive facts., verbal and visual memory, language, and visual-spatial functions). Potential risk factors for neuropsychological deficit were assessed in the patient group using a multivariate analysis. The two groups did not differ in age, sex, dominant hand and level of education. Compared with the control group, patients with drug-resistant epilepsy showed worse performance on motor functions and visuospatial memory, sustained attention, inhibition and verbal memory. Neuropsychological deficits could therefore be systematically detected in patients with drug-resistant epilepsy in order to provide neuropsychological therapy and improve quality of life. The analysis of the classical and complex indices of the special neuropsychological tasks presented in the presentation can help in the investigation of normal and disrupted memory and executive functions in the DRE.

Keywords: drug-resistant epilepsy, Hungarian diagnostic protocol, memory, executive functions, cognitive neuropsychology

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Authors: Saranya Ganapathy, Megha N. Parajulee, Michael San Francisco, Hong Zhang

Abstract:

Insect pests are a serious threat to agricultural productivity. Use of chemical pesticides, the predominant control method thus far, has resulted in environmental damage, pest resurgence, and negative effects on non-target species. Genetically modified (GM) crops offer a promising alternative, and Bacillus thuringiensis endotoxin genes have played a major role in this respect. However, to overcome insect tolerance issues and to broaden the target range, it is critical to identify alternative-insecticidal toxins working through novel mechanisms. Our research group has identified a kinase from Chilo iridescent virus (CIV; Family Iridoviridae) that has insecticidal activity and designated it as ISTK (Iridovirus Serine/Threonine Kinase). A 35 kDa truncated form of ISTK, designated iridoptin, was obtained during expression and purification of ISTK in the yeast system. This yeast-expressed CIV toxin induced 50% mortality in cotton aphids and 100% mortality in green peach aphids (GPA). Optimized viral genes (o-ISTK and o-IRI) were stably transformed into the model plant, Arabidopsis. PCR analysis of genomic DNA confirmed the presence of the gene insert (oISTK/oIRI) in selected transgenic lines. The further screening was performed to identify the PCR positive lines that showed expression of respective toxins at the polypeptide level using Western blot analysis. The stable lines expressing either of these two toxins induced moderate to very high mortality in GPAs and significantly affected GPA development and fecundity. The aphicidal potential of these transgenic Arabidopsis lines will be presented.

Keywords: Chilo iridescent virus, insecticidal toxin, iridoviruses, plant-incorporated protectants, serine/threonine kinase

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Authors: Shai Sarussi

Abstract:

Suppose F is a field with valuation v and valuation domain Oᵥ, and R is an Oᵥ-algebra. It is known that there exists a filter quasi-valuation on R; the existence of a quasi-valuation yields several important connections between Oᵥ and R, in particular with respect to their prime spectra. In this paper, the notion of a module valuation is introduced. It is shown that any torsion-free module over Oᵥ has an induced module valuation. Moreover, several results connecting the filter quasi-valuation and module valuations are presented.

Keywords: valuations, quasi-valuations, prime spectrum, algebras over valuation domains

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Authors: Naouel Boussoualim, Hayat Trabsa, Imane Krache, Seddik Khennouf, Noureddine Charef, Lekhmici Arrar, Abderrahmane Baghiani

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Purpose: To evaluate the in-vitro inhibition of xanthine oxidase (purified from bovine milk) by extracts of Lycium arabicum, as well as it is in vivo hypouricemic and renal protective effects. Methods: Four extracts of Lycium arabicum, methanol (CrE), chloroform (ChE), ethyl acetate (EaE) and aqueous (AqE) extracts, were screened for their total phenolics and potential inhibitory effects on purified bovine milk xanthine oxidase (XO) activity by measuring the formation of uric acid or superoxide radical. The mode of inhibition was investigated and compared with the standard drugs, allopurinol, quercitin, and catechin. To evaluate their hypouricemic effect, the extracts were administered to potassium oxonate-induced hyperuricemic mice at a dose of 50 mg/kg body weight. Results: The results showed that EaE had the highest content of phenolic compounds and was the most potent inhibitor of uric acid formation (IC50 = 0.017 ± 0.001 mg/mL) and formation of superoxide (IC50 = 0.035 ± 0.001 mg/ml). Lineweaver-Burk analysis showed that CrE and EaE inhibited XO competitively, whereas the inhibitory activities exerted by ChE and AqE were of a mixed type. Intraperetoneal injection of L. arabicum extracts (50 mg/kg) elicited hypouricemic actions in hyperuricemic mice. Hyperuricemic mice presented a serum uric acid concentration of 4.71 ± 0.29 mg/L but this was reduced to 1.78 ± 0.11 mg/L by EaE, which was the most potent hyporuricemic extract. Conclusion: L. arabicum fractions have a strong inhibitory effect on xanthine oxidase and and also have a significantly lowering effect on serum and liver creatinine and urea levels in hyperuricemic mice.

Keywords: lycium arabicum, uric acid, creatinine, superoxide, phenolic compounds, flavonoids, hyperuricemia

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Authors: Nejla Fourati, Zied Fessi, Fatma Dhouib, Wicem Siala, Leila Farhat, Afef Khanfir, Wafa Mnejja, Jamel Daoud

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Purpose: Radiation induced hypothyroidism in nasopharyngeal cancer (NPC) ranged from 15% to 55%. In reported data, it is considered as a common late complication of definitive radiation and is mainly observed 2 years after the end of treatment. The aim of this study was to evaluate the incidence of early hypothyroidism within 6 months after radiotherapy. Patients and methods: From June 2017 to February 2020, 35 patients treated with concurrent chemo-radiotherapy (CCR) for NPC were included in this prospective study. Median age was 49 years [23-68] with a sex ratio of 2.88. All patients received intensity modulated radiotherapy (IMRT) at a dose of 69.96 Gy in 33 daily fractions with weekly cisplatin (40mg/m²) chemotherapy. Thyroid stimulating hormone (TSH) and Free Thyroxine 4 (FT4) dosage was performed before the start of radiotherapy and 6 months after. Different dosimetric parameters for the thyroid gland were reported: the volume (cc); the mean dose (Dmean) and the %age of volume receiving more than 45 Gy (V45Gy). Wilcoxon Test was used to compare these different parameters between patients with or without hypothyroidism. Results: At baseline, 5 patients (14.3%) had hypothyroidism and were excluded from the analysis. For the remaining 30 patients, 9 patients (30%) developed a hypothyroidism 6 months after the end of radiotherapy. The median thyroid volume was 10.3 cc [4.6-23]. The median Dmean and V45Gy were 48.3 Gy [43.15-55.4] and 74.8 [38.2-97.9] respectively. No significant difference was noted for all studied parameters. Conclusion: Early hypothyroidism occurring within 6 months after CCR for NPC seems to be a common complication (30%) that should be screened. Good patient monitoring with regular dosage of TSH and FT4 makes it possible to treat hypothyroidism in asymptomatic phase. This would be correlated with an improvement in the quality of life of these patients. The results of our study do not show a correlation between the thyroid doses and the occurrence of hypothyroidism. This is probably related to the high doses received by the thyroid in our series. These findings encourage more optimization to limit thyroid doses and then the risk of radiation-induced hypothyroidism

Keywords: nasopharyngeal carcinoma, hypothyroidism, early complication, thyroid dose

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Authors: Nayira A. Abd Elbaky, Amal J. Fatani, Hazar Yaqub, Nouf M. Al-Rasheed, Naglaa El-Orabi, Mai Osman

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The present work is aimed to evaluate the protective effect of N-acetyl cystiene (NAC), coenzyme Q10 (CoQ10), and their combination against carbon tetrachloride (CCl4)-induced cardiotoxicity in rats. CCl4 treatment significantly elevated the levels of cardiac oxidative stress bio markers including nitric oxide (NO) and malondialdehyde (MDA). A concomitant decrease in the level of reduced glutathione and the activity of membrane bound enzyme, calcium-adenosine triphosphatase were observed in the hearts of rats exposed to CCl4 compared to respective values in normal group. Quantitative analysis of myocardial energy metabolism revealed a significant decrease in the glucose content coupled with depletion in the activities of myocardial glycolytic enzymes as hexokinase (HK), phosphofructokinase (PFK) and lactate dehydrogenase (LDH) after CCl4 treatment. In addition, a significant elevation in myocardial hydroxyproline level was observed in CCl4 intoxicated rats indicating interstitial collagen accumulation. Pretreatment with either NAC, CoQ10 or their combination successively alleviated the alterations in myocardial oxidative stress and antioxidant markers, as well as effectively up-regulated the decrease in cardiac energetic biomarkers in CCl4 intoxicated rats. Moreover, these antioxidants markedly reduced myocardial hydroxyproline level versus that of CCl4-treated animals. In conclusion, the present results illustrated that the prophylactic use of the current antioxidant resulted in a remarkable cardioprotective effect against CCl4 induced myocardial damage, which suggest that they may candidates as prophylactic agents against different cardio-toxins.

Keywords: carbon tetrachloride, lipid peroxidation, antioxidant, energy metabolism, hydroxyproline

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Authors: Srinivasan Chandrasekaran, Shihas A. Khader

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Motion response of floating structures is of great concern in marine engineering. Nonlinearity is an inherent property of any floating bodies subjected to irregular waves. These floating structures are continuously subjected to environmental loadings from wave, current, wind etc. This can result in undesirable motions of the vessel which may challenge the operability. For a floating body to remain in its position, it should be able to induce a restoring force when displaced. Mooring is provided to enable this restoring force. This paper discuss the hydrodynamic performance and motion characteristics of an 8 point spread mooring system applied to a pipe laying barge operating in the West African sea. The modelling of the barge is done using a computer aided-design (CAD) software RHINOCEROS. Irregular waves are generated using a suitable wave spectrum. Both frequency domain and time domain analysis is done. Numerical simulations based on potential theory are carried out to find the responses and hydrodynamic performance of the barge in both free floating as well as moored conditions. Initially, potential flow frequency domain analysis is done to obtain the Response Amplitude Operator (RAO) which gives an idea about the structural motion in free floating state. RAOs for different wave headings are analyzed. In the following step, a time domain analysis is carried out to obtain the responses of the structure in the moored condition. In this study, wave induced motions are only taken into consideration. Wind and current loads are ruled out and shall be included in future studies. For the current study, 5000 seconds simulation is taken. The results represent wave-induced motion responses, mooring line tensions and identifies critical mooring lines.

Keywords: irregular wave, moored barge, time domain analysis, numerical simulation

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Authors: Lina Paola Orozco Marin, Yuliet Montoya Osorio, John Bustamante Osorno

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Ischemic events can culminate in acute myocardial infarction by irreversible cardiac lesions that cannot be restored due to the limited regenerative capacity of the heart. Cell therapy seeks to replace these injured or necrotic cells by transplanting healthy and functional cells. The therapeutic alternatives proposed by tissue engineering and cardiovascular regenerative medicine are the use of biomaterials to mimic the native extracellular medium, which is full of proteins, proteoglycans, and glycoproteins. The selected biomaterials must provide structural support to the encapsulated cells to avoid their migration and death in the host tissue. In this context, the present research work focused on developing a natural thermosensitive hydrogel, its physical and chemical characterization, and the determination of its biocompatibility in vitro. The hydrogel was developed by mixing hydrolyzed bovine and porcine collagen at 2% w/v, chitosan at 2.5% w/v, and beta-glycerolphosphate at 8.5% w/w and 10.5% w/w in magnetic stirring at 4°C. Once obtained, the thermosensitivity and gelation time were determined, incubating the samples at 37°C and evaluating them through the inverted tube method. The morphological characterization of the hydrogels was carried out through scanning electron microscopy. Chemical characterization was carried out employing infrared spectroscopy. The biocompatibility was determined using the MTT cytotoxicity test according to the ISO 10993-5 standard for the hydrogel’s precursors using the fetal human ventricular cardiomyocytes cell line RL-14. The RL-14 cells were also seeded on the top of the hydrogels, and the supernatants were subculture at different periods to their observation under a bright field microscope. Four types of thermosensitive hydrogels were obtained, which differ in their composition and concentration, called A1 (chitosan/bovine collagen/beta-glycerolphosphate 8.5%w/w), A2 (chitosan/porcine collagen/beta-glycerolphosphate 8.5%), B1 (chitosan/bovine collagen/beta-glycerolphosphate 10.5%) and B2 (chitosan/porcine collagen/beta-glycerolphosphate 10.5%). A1 and A2 had a gelation time of 40 minutes, and B1 and B2 had a gelation time of 30 minutes at 37°C. Electron micrographs revealed a three-dimensional internal structure with interconnected pores for the four types of hydrogels. This facilitates the exchange of nutrients, oxygen, and the exit of metabolites, allowing to preserve a microenvironment suitable for cell proliferation. In the infrared spectra, it was possible to observe the interaction that occurs between the amides of polymeric compounds with the phosphate groups of beta-glycerolphosphate. Finally, the biocompatibility tests indicated that cells in contact with the hydrogel or with each of its precursors are not affected in their proliferation capacity for a period of 16 days. These results show the potential of the hydrogel to increase the cell survival rate in the cardiac cell therapies under investigation. Moreover, the results lay the foundations for its characterization and biological evaluation in both in vitro and in vivo models.

Keywords: cardiac cell therapy, cardiac ischemia, natural polymers, thermosensitive hydrogel

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Authors: Maha Salah Abdullah Ismail, Manal S. Ismail, Amir M. Saleh

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Reflexology treatment is a method for enhancing body relaxation. It is a widely recognized as an alternative therapy, effective for many health conditions. This study aimed to evaluate the effect of reflexology treatment on arterial blood gases among mechanically ventilated patients. A quasi-experimental (pre and post-test) research design was used. Research hypothesis was mechanically ventilated patients who will receive the reflexology treatment will have improvement in their arterial blood gases than those who will not. The current study was carried out in different Intensive Care Units at the Cairo University Hospitals. A purposeful sample of 100 adults’ mechanically ventilated patients was recruited over a period of three months of data collection. The participants were divided into two equally matched groups; (1) The study group who has received the routine care, in addition, two reflexology sessions on the feet, (2) The control group who has received only the routine care. One tool was utilized to collect data pertinent to the study; mechanically ventilated patients' data sheet that consists of demographic and medical data. Result: Majority (58% of the study group and 82% of the control group) were males, with mean age of 50.9 years in both groups. Patients who received the reflexology treatment significantly increase in the oxygen saturation pre second session (t=5.15, p=.000), immediate post sessions (t=4.4, p=.000) and post two hours (t= 4.7, p= .000). The study group was more likely to have lower PaO2 (F=5.025, p=.015), PaCo2 (F=4.952, p=.025) and higher HCo3 (F=15.211, p=.000) than the control group. Conclusion: This study results support the positive effect of reflexology treatment in improving some arterial blood gases among mechanically ventilated patients’ with the conventional therapy as in the study group there was increase in the oxygen saturation. In differences between groups there decrease PaO2, PaCo2 and increase HCo3 in the study group. Recommendation: Nurses should be trained how to demonstrate the foot reflexology among mechanically ventilated patients.

Keywords: arterial blood gases, foot, mechanical ventilated patient, reflexology

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Authors: Isabelle Snyder

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Microgrid protection presents challenges to conventional protection techniques due to the low induced fault current. Protection relays present in microgrid applications require a combination of settings groups to adjust based on the architecture of the microgrid in islanded and grid-connected mode. In a radial system where the microgrid is at the other end of the feeder, directional elements can be used to identify the direction of the fault current and switch settings groups accordingly (grid connected or microgrid connected). However, with multiple microgrid connections, this concept becomes more challenging, and the direction of the current alone is not sufficient to identify the source of the fault current contribution. ORNL has previously developed adaptive relaying schemes through other DOE-funded research projects that will be evaluated and used as a baseline for this research. The four protection techniques in this study are the following: (1) Adaptive Current only Protection System (ACPS), Intentional (2) Unbalanced Control for Protection Control (IUCPC), (3) Adaptive Protection System with Communication Controller (APSCC) (4) Adaptive Model-Driven Protective Relay (AMDPR). The first two methods focus on identifying the islanded mode without communication by monitoring the current sequence component generated by the system (ACPS) or induced with inverter control during islanded mode (IUCPC) to identify the islanding condition without communication at the relay to adjust the settings. These two methods are used as a backup to the APSCC, which relies on a communication network to communicate the islanded configuration to the system components. The fourth method relies on a short circuit model inside the relay that is used in conjunction with communication to adjust the system configuration and computes the fault current and adjusts the settings accordingly.

Keywords: adaptive relaying, microgrid protection, sequence components, islanding detection, communication controlled protection, integrated short circuit model

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Authors: Petcharat Kerdonfag, Surasak Taneepanichskul, Winai Wadwongtham

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Background: Although there have not been effective treatments for Noise Induced Hearing Loss (NIHL), it can be definitely preventable with promoting the use of Hearing Protection devices (HPDs) among workers who have been exposed to excessive noise for a long period. Objectives: The objectives of this study were to explore the use of HPDs among steel industrial workers in the high noise level zone in Samut Prakan province, Thailand and to examine the relationships of the HPDs use and hearing loss. Materials and Methods: In this cross-sectional study, eligible ninety-three participants were recruited in the designated zone of higher noise (> 85dBA) of two factories, using simple random sampling. The use of HPDs was gathered by the self-record form, examined and confirmed by the researcher team. Hearing loss was assessed by the audiometric screening at the regional Samut Prakan hospital. If an average threshold level exceeds 25 dBA at high frequency (4 and 6 Hz) in each ear, participants would be lost of hearing. Data were collected from October to December, 2016. All participants were examined by the same examiners for the validity. An Audiometric testing was performed with the participants who have been exposed to high noise levels at least 14 hours from workplace. Results: Sixty participants (64.5%) had secondary level of education. The average mean score of percent time of using HPDs was 60.5% (SD = 25.34). Sixty-seven participants (72.0%) had abnormal hearing which they have still needed to increase lower percent time of using HPDs (Mean = 37.01, SD = 23.81) than those having normal hearing (Mean = 45.77, SD = 28.44). However, there was no difference in the mean average of percent time of using HPDs between these two groups.Conclusion: The findings of this study have confirmed that the steel industrial workers still need to be motivated to use HPDs regularly. Future research should pay more attentions for creating a meaningful innovation to steel industrial workers.

Keywords: hearing protection devices, noise induced hearing loss, audiometric testing, steel industry

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Authors: Valeriu Mihai But, Sorana Daniela Bolboacă, Adriana Elena Bulboacă

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The nutraceutical compound Curcumin (Curcuma longa L.) is known for its anti-inflammatory, anti-cancer, and antioxidant effects. This study aimed to evaluate the antioxidative and analgesic effects of Curcumin (CC) compared to Tramadol (T) in chemical-induced nociceptive pain in rats. Thirty-five rats were randomly divided into five groups of seven rats each and were treated as follows: C group (control group): treated with saline solution 0.9%, (1 ml, i.p. administration), ethanoic acid (EA) group: pretreated with saline solution 0.9% - 30 min before EA nociceptive pain induction, (1 ml, i.p. administration), T group: pretreated with Tramadol, 10 mg/kg body weight (bw), i.p. administration - 30 min before EA nociceptive pain induction, CC1-group: pretreated with 1 mg/100g bw Curcumin i.p. administration - 2 days before EA pain induction and CC2-group: pretreated with Curcumin 2 mg/100g bw i.p. administration - 2 days before EA nociceptive pain induction. The following oxidative stress parameters were assessed: malondialdehyde (MDA), nitric oxide (NOx), total oxidative status (TOS), total antioxidative capacity (TAC), and thiol (Th). The antalgic activity was measured by the ethanoic acid writhing test. Treatment with Curcumin, both 1 mg/100g bw, and 2 mg/100g bw, showed significant differences as compared with the control group (p<0.001) regarding malondialdehyde (MDA), nitric oxide (NOx), and total oxidative status (TOS) oxidative biomarkers. Pretreatment with 2 mg/100g bw of Curcumin presented a significant decrease in MDA values compared with Tramadol (p<0.001). The TAC significantly increased in pretreatment with Curcumin compared with group control. (p<0.001) The nociceptive response to EA was significantly reduced in Curcumin and Tramadol groups. Treatment with Curcumin at a higher concentration was more effective. In an experimental pain model, this study demonstrates an important antioxidant and antinociceptive activity of Curcumin comparable with Tramadol treatment.

Keywords: curcumin, nociception, oxidative stress, pain

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Authors: Sophia Cyril Vincent

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Background: As per the Indian Census 2011, there is nearly 104 million elderly population aged above 60 years (53 million females and 51 males), and the count is expected to be 173 million by the end of 2026. Nearly 5.5% of women and 1.5% of men are living alone.1 In India, even though it is the moral duty of the children to take care of aged parents, many elders are landing in old age homes due to the social transformation factors like mushrooming of nuclear families, migration of children, cultural echoes, differences in mindset and values. Nearly 728 old age homes are seen across the country, out of which 78 old age homes with approximately 3000 inmates are seen only in Bangalore2. The existing literature shows that elderly women residing in old age homes experience the challenges like- loneliness, health issues, rejection from children, grief, death anxiety, etc, which leads to mental and physical wellbeing in numerous and tangible ways3. Hence the best and cost-effective way to improve the meaning and quality of life among elderly females is logotherapy, a type of psychotherapeutic analysis and treatment, motivating and driving force4 within the human experience to lead a decent life. Aim: The current research is aimed at studying the effectiveness of a logotherapy intervention on meaning and quality of life among elderly women of old age homes. Samples:200 women aged < 60 years and staying in the old age home for more than 1 year were randomly allocated to the control group and experimental group. Methodology: Using the Meaning in life questionnaire (MLQ)and the World health organization quality of life (WHOQOL) questionnaire, meaning and quality of life were assessed among both groups' women. Intensive Logotherapy and meaning in life program for five days were provided for the experimental group and the control group, with no treatment. Result: Under analysis. Conclusion: It is the right of the elderly woman to lead a happy and peaceful life till her death irrespective of the residing place. Hence, continuous monitoring and effective management are necessary for elderly women.

Keywords: quality of life, meaning of life, logo therapy, old age home

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Authors: Clotilde Guyon, Nada Jmari, Yen-Chin Li, Jean Denoyel, Noriyuki Fujikado, Christophe Blanchet, David Root, Matthieu Giraud

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Aire induces ectopic expression of a large repertoire of tissue-specific antigen (TSA) genes in thymic medullary epithelial cells (MECs), driving immunological self-tolerance in maturing T cells. Although important mechanisms of Aire-induced transcription have recently been disclosed through the identification and the study of Aire’s partners, the fine transcriptional functions underlied by a number of them and conferred to Aire are still unknown. Alternative cleavage and polyadenylation (APA) is an essential mRNA processing step regulated by the termination complex consisting of 85 proteins, 10 of them have been related to Aire. We evaluated APA in MECs in vivo by microarray analysis with mRNA-spanning probes and RNA deep sequencing. We uncovered the preference of Aire-dependent transcripts for short-3’UTR isoforms and for proximal poly(A) site selection marked by the increased binding of the cleavage factor Cstf-64. RNA interference of the 10 Aire-related proteins revealed that Clp1, a member of the core termination complex, exerts a profound effect on short 3’UTR isoform preference. Clp1 is also significantly upregulated in the MECs compared to 25 mouse tissues in which we found that TSA expression is associated with longer 3’UTR isoforms. Aire-dependent transcripts escape a global 3’UTR lengthening associated with MEC differentiation, thereby potentiating the repressive effect of microRNAs that are globally upregulated in mature MECs. Consistent with these findings, RNA deep sequencing of actinomycinD-treated MECs revealed the increased stability of short 3’UTR Aire-induced transcripts, resulting in TSA transcripts accumulation and contributing for their enrichment in the MECs.

Keywords: Aire, central tolerance, miRNAs, transcription termination

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Authors: Fares A. Mayia, Mahmoud A. Yamany, Mushabbab A. Asiri

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In recent years, non-invasive Focused Ultrasound (FU) has been utilized for generating bubbles (cavities) to ablate target tissue by mechanical fractionation. Intensities >10 kW/cm² are required to generate the inertial cavities. The generation, rapid growth, and collapse of these inertial cavities cause tissue fractionation and the process is called Histotripsy. The ability to fractionate tissue from outside the body has many clinical applications including the destruction of the tumor mass. The process of tissue fractionation leaves a void at the treated site, where all the affected tissue is liquefied to particles at sub-micron size. The liquefied tissue will eventually be absorbed by the body. Histotripsy is a promising non-invasive treatment modality. This paper presents a technique for generating inertial cavities at lower intensities (< 1 kW/cm²). The technique (patent pending) is based on amplitude modulation (AM), whereby a low frequency signal modulates the amplitude of a higher frequency FU wave. Cavitation threshold is lower at low frequencies; the intensity required to generate cavitation in water at 10 kHz is two orders of magnitude lower than the intensity at 1 MHz. The Amplitude Modulation technique can operate in both continuous wave (CW) and pulse wave (PW) modes, and the percentage modulation (modulation index) can be varied from 0 % (thermal effect) to 100 % (cavitation effect), thus allowing a range of ablating effects from Hyperthermia to Histotripsy. Furthermore, changing the frequency of the modulating signal allows controlling the size of the generated cavities. Results from in vitro work demonstrate the efficacy of the new technique in fractionating soft tissue and solid calcium carbonate (Chalk) material. The technique, when combined with MR or Ultrasound imaging, will present a precise treatment modality for ablating diseased tissue without affecting the surrounding healthy tissue.

Keywords: focused ultrasound therapy, histotripsy, inertial cavitation, mechanical tissue ablation

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