Search results for: stem cell therapy

Authors: Harish Rajak, Kamlesh Raghuwanshi

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Histone deacetylase (HDAC) are promising target for cancer treatment. The panobinostat (Farydak; Novartis; approved by USFDA in 2015) and chidamide (Epidaza; Chipscreen Biosciences; approved by China FDA in 2014) are the novel HDAC inhibitors ratified for the treatment of patients with multiple myeloma and peripheral T cell lymphoma, respectively. On the other hand, two other HDAC inhibitors, Vorinostat (SAHA; approved by USFDA in 2006) and Romidepsin (FK228; approved by USFDA in 2009) are already in market for the treatment of cutaneous T-cell lymphoma. Several hydroxamic acid based HDAC inhibitors i.e., belinostat, givinostat, PCI24781 and JNJ26481585 are in clinical trials. HDAC inhibitors consist of three pharmacophoric features - an aromatic cap group, zinc binding group (ZBG) and a linker chain connecting cap group to ZBG. Herein, we report synthesis, characterization and biological evaluation of HDAC inhibitors possessing substituted isatin moiety as cap group which recognize the surface of active enzyme pocket and thiosemicarbazide moiety incorporated as linker group responsible for connecting cap group to ZBG (hydroxamic acid). Several analogues were found to inhibit HDAC and cellular proliferation of Hela cervical cancer cells with GI50 values in the micro molar range. Some of the compounds exhibited promising results in vitro antiproliferative studies. Attempts were also made to establish the structure activity relationship among synthesized HDAC inhibitors.

Keywords: HDAC inhibitors, hydroxamic acid derivatives, isatin derivatives, antiproliferative activity, docking

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Authors: Esther Mafunda, Simbarashe Muparangi

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The present paper tests the applicability of the Regression Hypothesis on the pathological language dissolution of a Shona male adult with Broca’s aphasia. It particularly assesses the prediction of the Regression Hypothesis, which states that the process according to which language is forgotten will be the reversal of the process according to which it will be acquired. The main aim of the paper is to find out whether mirror symmetries between L1 acquisition and L1 dissolution of tense in Shona and, if so, what might cause these regression patterns. The paper also sought to highlight the practical contributions that Linguistic theory can make to solving language-related problems. Data was collected from a 46-year-old male adult with Broca’s aphasia who was receiving speech therapy at St Giles Rehabilitation Centre in Harare, Zimbabwe. The primary data elicitation method was experimental, using the probe technique. The TART (Test for Assessing Reference Time) Shona version in the form of sequencing pictures was used to access tense by Broca’s aphasic and 3.5-year-old child. Using the SPSS (Statistical Package for Social Studies) and Excel analysis, it was established that the use of the future tense was impaired in Shona Broca’s aphasic whilst the present and past tense was intact. However, though the past tense was intact in the male adult with Broca’s aphasic, a reference to the remote past was made. The use of the future tense was also found to be difficult for the 3,5-year-old speaking child. No difficulties were encountered in using the present and past tenses. This means that mirror symmetries were found between L1 acquisition and L1 dissolution of tense in Shona. On the basis of the results of this research, it can be concluded that the use of tense in a Shona adult with Broca’s aphasia supports the Regression Hypothesis. The findings of this study are important in terms of speech therapy in the context of Zimbabwe. The study also contributes to Bantu linguistics in general and to Shona linguistics in particular. Further studies could also be done focusing on the rest of the Bantu language varieties in terms of aphasia.

Keywords: Broca’s Aphasia, regression hypothesis, Shona, language dissolution

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Authors: Lucia Liu, Matthew Koziol

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Obsessive-compulsive disorder (OCD), a long-lasting anxiety disorder involving recurrent, intrusive thoughts, affects over 2 million adults in the United States. Transcranial magnetic stimulation (TMS) stands out as a noninvasive, cutting-edge therapy that has been shown to reduce symptoms in patients with treatment-resistant OCD. The Food and Drug Administration (FDA) approved protocol pairs TMS sessions with individualized symptom provocation, aiming to improve the susceptibility of brain circuits to stimulation. However, limited standardization or guidance exists on how to conduct symptom provocation and which methods are most effective. This study aims to compare the effect of internal versus external techniques to induce obsessional stress in a clinical setting during TMS therapy. Two symptom provocation methods, (i) Asking patients thought-provoking questions about their obsessions (internal) and (ii) Requesting patients to perform obsession-related tasks (external), were employed in a crossover design with repeated measurement. Thirty-six treatments of NeuroStar TMS were administered to each of two patients over 8 weeks in an outpatient clinic. Patient One received 18 sessions of internal provocation followed by 18 sessions of external provocation, while Patient Two received 18 sessions of external provocation followed by 18 sessions of internal provocation. The primary outcome was the level of self-reported obsessional stress on a visual analog scale from 1 to 10. The secondary outcome was self-reported OCD severity, collected biweekly in a four-level Likert-scale (1 to 4) of bad, fair, good and excellent. Outcomes were compared and tested between provocation arms through repeated measures ANOVA, accounting for intra-patient correlations. Ages were 42 for Patient One (male, White) and 57 for Patient Two (male, White). Both patients had similar moderate symptoms at baseline, as determined through the Yale-Brown Obsessive Compulsive Scale (YBOCS). When comparing obsessional stress induced across the two arms of internal and external provocation methods, the mean (SD) was 6.03 (1.18) for internal and 4.01 (1.28) for external strategies (P=0.0019); ranges were 3 to 8 for internal and 2 to 8 for external strategies. Internal provocation yielded 5 (31.25%) bad, 6 (33.33%) fair, 3 (18.75%) good, and 2 (12.5%) excellent responses for OCD status, while external provocation yielded 5 (31.25%) bad, 9 (56.25%) fair, 1 (6.25%) good, and 1 (6.25%) excellent responses (P=0.58). Internal symptom provocation tactics had a significantly stronger impact on inducing obsessional stress and led to better OCD status (non-significant). This could be attributed to the fact that answering questions may prompt patients to reflect more on their lived experiences and struggles with OCD. In the future, clinical trials with larger sample sizes are warranted to validate this finding. Results support the increased integration of internal methods into structured provocation protocols, potentially reducing the time required for provocation and achieving greater treatment response to TMS.

Keywords: obsessive-compulsive disorder, transcranial magnetic stimulation, mental health, symptom provocation

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Authors: Alexandru Grigorescu, Alexandra Protesanu

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Background: Approximately 34-67 percent of cancer patients experience an episode of uncontrolled pain during the course of their disease, depending on the stage. The aim is to provide evidence-based data for pain prevalence, diagnosis and treatment recommendations on an integrative model of medical oncology and palliative care for patients with cancer diagnostic in a day hospital. Patients and method: Consultation registers and electronic records of 166 Patients (Pts) were studied from April 2022 to March 2023. Pts with pain syndrome were selected. The pain was objectified by the visual pain scale. To elucidate the causes of the pain, investigations were carried out: bone scintigraphy, CT scan, and PET-CT. The analgesic treatments were represented by weak and strong morphine, radiotherapy, and bisphosphonates. Result: During the mentioned period, 166 oncological patients (74 women and 92 men) were treated in the oncology day hospitalization service. There were 1,500 consultations, 40 of which were only for pain. The neoplastic locations were: gynecological, malignant melanoma, breast, gastric, bronchopulmonary, colorectal, liver, pancreatic, bladder, and kidney. 70 Pts presented pain syndrome. The causes of the pain were represented by bone metastases, compressive tumors, and post-surgical status. Drug treatment: Tramadol 47 Pts, of which 10 switched to a major opioid (Oxycodonum, Morphine sulfate), 20 Pts were treated with Oxycodonum as the first intention. In 5 patients ry to rotated morphine, 20 Pts received palliative radiotherapy, 10 Pts were treated with bisphosphonates. 2 Pts required neurosurgery consultation for an antalgic intervention. 5 Pts had important adverse reactions to morphine. All patients and their families were advised by a medical oncologist and psychologist for a lifestyle change. Conclusions: The prevalence of pain was similar to that described in the literature. In most cases, the pain could be managed in the day hospital. Weak and strong morphine represented the main pain therapy. Palliative radiotherapy was the second most effective therapy. Treatment with bisphosphonates was useful. Surgical interventions were rarely indicated. Discussions with patients and their families regarding the lifestyle change were important.

Keywords: cancer pain, opioids, medical oncology, palliative care

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Authors: Sangeeta Girdhar, Amanat Grewal, Nahush Bansal

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Introduction: There is an increasing burden of hypertension in India. The morbidity and mortality arising from complications are mainly due to non-adherence to medication, unhealthy dietary habits, and lack of physical activity. Non-adherence is a well-recognised factor contributing to inadequate control of high blood pressure. Adherence to pharmacotherapy for hypertension varies from 43% to 88%. Non-adherence is influenced by various socio-demographic factors. Understanding these factors is useful in managing non-adherence. Therefore, the study was planned to determine adherence among hypertensives and factors associated with non-adherence to treatment. Methodology: A cross-sectional study was conducted at Urban Health Training Centre of Dayanand Medical College and Hospital Ludhiana. Patients attending the OPD over a period of 3 months were included in the study. Prior ethical approval was obtained, and informed consent was taken from subjects. A predesigned semi-structured questionnaire was applied, which included socio-demographic profile, treatment-seeking behaviour, adherence to the antihypertensive medication, lifestyle factors (intake of alcohol, smoking, consumption of junk food, high salt intake) contributing to the development of the disease. Reasons for non-adherence to the therapy were also explored. Data was entered into excel, and SPSS 26 version was used for analysis. Results: A total of 186 individuals were interviewed. Out of these, 113 females (60.8%) and 73 males (39.2%) participated in the study. Mean age of participants was 60.9 ± 10.7 years. Adherence to anti-hypertensive treatment was found in 68.3% of the participants. It was observed that adherence was more in literate individuals as compared to illiterate (p value- 0.78). Adherence was lower among smokers (33.3%) and alcohol consumers (53.8%) as compared to non-users (69.4% and 70.6%, respectively). The predominant reasons for skipping medications were discontinuing medication when feeling well, forgetfulness and unawareness. Conclusion: There is a need to generate awareness regarding the importance of adherence to therapy among patients. Intensive health education and counselling of the patients is the need of the hour.

Keywords: hypertension, anti-hypertensive, adherence, counselling

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Authors: Hassan Samadi, Mustapha El Jarroudi

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In this work, we consider the homogenization of a non-linear problem in periodic medium with two periodic connected media exchanging a heat flux throughout their common interface. The interfacial exchange coefficient λ is assumed to tend to zero or to infinity following a rate λ=λ(ε) when the size ε of the basic cell tends to zero. Three homogenized problems are determined according to some critical value depending of λ and ε. Our method is based on Γ-Convergence techniques.

Keywords: variational methods, epiconvergence, homogenization, convergence technique

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Authors: Ibrahim Iddrisu, Joseph Ayariga, Junhuan Xu, Ayomide Adebanjo, Boakai K. Robertson, Michelle Samuel-Foo, Olufemi Ajayi

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The rise of antimicrobial resistance is a global public health crisis that threatens the effective control and prevention of infections. Due to the emergence of pan drug-resistant bacteria, most antibiotics have lost their efficacy. Bacteriophages or their components are known to target bacterial cell walls, cell membranes, and lipopolysaccharides (LPS) and hydrolyze them. Bacteriophages, being the natural predators of pathogenic bacteria, are inevitably categorized as ‘human friends’, thus fulfilling the adage that ‘the enemy of my enemy is my friend’. Leveraging on their lethal capabilities against pathogenic bacteria, researchers are searching for more ways to overcome the current antibiotic resistance challenge. In this study, we expressed and purified epsilon 34 phage tail spike protein (E34 TSP) from the E34 TSP gene, then assessed the ability of this bacteriophage protein in the killing of two CBD-resistant strains of Salmonella spp. We also assessed the ability of the tail spike protein to cause bacteria membrane disruption and dehydrogenase depletion. We observed that the combined treatment of CBD-resistant strains of Salmonella with CBD and E34 TSP showed poor killing ability, whereas the mono treatment with E34 TSP showed considerably higher killing efficiency. This study demonstrates that the inhibition of the bacteria by E34 TSP was due in part to membrane disruption and dehydrogenase inactivation by the protein. The results of this work provide an interesting background to highlight the crucial role phage proteins such as E34 TSP could play in pathogenic bacterial control.

Keywords: cannabidiol, resistance, Salmonella, antimicrobials, phages

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Authors: Amit Kumar Sinha

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A coal preparation plant typically operates with multiple beneficiation circuits to process individual size fractions of coal obtained from mine so that the targeted overall plant efficiency in terms of yield and ash is achieved. Conventional coal beneficiation plant in India or overseas operates generally in two methods of processing; coarse beneficiation with treatment in dense medium cyclones or in baths and fines beneficiation with treatment in flotation cell. This paper seeks to address the proven application of intermediate circuit along with coarse and fines circuit in Jamadoba New Coal Preparation Plant of capacity 2 Mt/y to treat -0.5 mm+0.25 mm size particles in reflux classifier. Previously this size of particles was treated directly in Flotation cell which had operational and metallurgical limitations which will be discussed in brief in this paper. The paper also details test work results performed on the representative samples of TSL coal washeries to determine the top size of intermediate and fines circuit and discusses about the overlapping process of intermediate circuit and how it is process wise suitable to beneficiate misplaced particles from coarse circuit and fines circuit. This paper also compares the separation efficiency (Ep) of various intermediate circuit process equipment and tries to validate the use of reflux classifier over fine coal DMC or spirals. An overview of Modern coal preparation plant treating Indian coal especially Washery Grade IV coal with reference to Jamadoba New Coal Preparation Plant which was commissioned in 2018 with basis of selection of equipment and plant profile, application of reflux classifier in intermediate circuit and process design criteria is also outlined in this paper.

Keywords: intermediate circuit, overlapping process, reflux classifier

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Authors: Murat Tosunoglu, Cigdem Gul, Nurcihan Hacioglu, Nurdan Tepeova

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Amphibian and Reptilian species are influenced by pollution and habitat destruction. Blood parameters of Amphibia species were particularly affected by the negative environmental conditions. Studied frog samples 36 clinically normal Pelophylax ridibundus individuals were captured along the Biga Stream between April–June 2014. When comparing our findings with the Turkish legislation (Water pollution control regulation), the 1. Locality of the Biga stream in terms of total coliform classified as "high quality water" (Coliform: 866.66 MPN/100 mL), while the 2. locality was a "contaminated water" (Coliform: 53266.66 MPN/100 mL). Blood samples of the live specimens were obtained in the laboratory within one day of their capture. The blood samples were taken from the etherized frogs by means of ventriculus punctures, via heparinized hematocrit capillaries. Hematological and biochemical analyses based on high quality water and contaminated water, respectively, are as follows: Red blood cell count (444210.52-426846.15 per cubic millimeter of blood), white blood cell count (4215.78-4684.61 per cubic millimeter of blood), hematocrit value (29.25-29.43 %), hemoglobin concentration (7.76-7.22 g/dl), mean corpuscular volume (637.64-719.99 fl), mean corpuscular hemoglobin (184.78-174.75 pg), mean corpuscular hemoglobin concentration (29.44-24.82 %), glucose (103.74-124.13 mg/dl), urea (87.68-81.72 mg/L), cholesterol (148.20-197.39 mg/dl), creatinine (0.29-0.28 mg/dl), uric acid (10.26-7.55 mg/L), albumin (1.13-1.39 g/dl), calcium (11.45-9.70 mg/dl), triglyceride (135.23-155.85 mg/dl), total protein (4.26-3.73 g/dl), phosphorus (6.83-17.86 mg/dl), and magnesium (0.95-1.06 mg/dl). The some hematological parameters in P. ridibundus specimens are given for the first time in this study. No water quality dependent variation was observed in clinic hematology parameters measured.

Keywords: Pelophylax ridibundus, hematological parameters, biochemistry, freshwater quality

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Authors: Yaya Gao, Bing Zhong, Yafeng Liu, Fei Chen

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Aim: The purpose of this study was to explore the difference between acellular dermal matrix (ADM) combined with anterolateral thigh (ALT) flap and ALT flap alone. Methods: HSCC patients were treated and divided into group A (ALT) and group B (ALT+ADM) between January 2014 and December 2018. We compared and analyzed the intraoperative information and postoperative outcomes of the patients. Results: There were 21 and 17 patients in group A and group B, respectively. The operation time, blood loss, defect size and anastomotic vessel selection showed no significant difference between two groups. The postoperative complications, including wound bleeding (n=0 vs. 1, p=0.459), wound dehiscence (n=0 vs. 1, p=0.459), wound infection (n=5vs.3, p=0.709), pharyngeal fistula (n=5vs.4, p=1.000) and hypoproteinemia (n=11 vs. 12, p=0.326) were comparable between the groups. Dysphagia at 6 months (number of liquid diets=0vs. 0; number of partial tube feedings=1vs. 1; number of total tube feedings=1vs. 0, p=0.655) also showed no significant differences. However, significant differences was observed in dysphagia at 12 months (number of liquid diets=0vs. 0; number of partial tube feedings=3 vs. 1; number of total tube feedings=10vs. 1, p=0.006). Conclusion: For HSCC patients, the use of the ALT flap combined ADM, compared to ALT treatment, showed better swallowing function at 12 months. The ALT flap combined ADM may serve as a safe and feasible alternative for selected HSCC patients.

Keywords: hypopharyngeal squamous cell carcinoma, anterolateral thigh free flap, acellular dermal matrix, reconstruction, dysphagia

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Authors: Alazar Nebyou, Sujata Pandit

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Lactic acid bacteria (LAB) are essential ingredients in probiotic foods, intestinal microflora, and dairy products that are capable of coping up with harsh gastrointestinal tract conditions and are available in a variety of environments. The objective of this study is to evaluate the probiotic property of LAB isolated from bovine milk. Milk samples were collected from local dairy farms. Samples were obtained using sterile test tubes and transported to a laboratory in the icebox for further biochemical characterization. Preliminary physiological and biochemical identification of LAB isolates was conducted by growing on MRS agar after ten-fold serial dilution. Seven of the best isolates were selected for the evaluation of the probiotic property. The LAB isolates were checked for resistance to antibiotics and their antimicrobial activity by disc diffusion assay and agar well diffusion assay respectively. Bile salt hydrolase activity of isolates was studied by growing isolates in a BSH medium with bile salt. Cell surface property of isolates was assayed by studying their autoaggregation and coaggregation percentage with S. aerues. All isolates were found BSH positive. In addition, BCM2 and BGM1 were susceptible to all antibiotic disks except BBM1 which was resistant to all antibiotic disks. BCM1 and BGM1 had the highest autoaggregation and coaggregation potential respectively. Since all LAB isolates showed gastrointestinal tolerance and good cell surface property they could be considered as good potential probiotic candidates for treatment and probiotic starter culture preparation.

Keywords: probiotic, aggregation, lactic acid bacteria, antimicrobial activity

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Authors: Megan L. Srinivas

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Individuals with underlying rheumatologic diseases such as dermatomyositis may not adequately respond to tuberculin (PPD) skin tests, creating false negative results. These illnesses are frequently treated with immunosuppressive therapy making proper identification of TB infection imperative. A 59-year-old Filipino man was diagnosed with dermatomyositis on the basis of rash, electromyography, and muscle biopsy. He was initially treated with IVIG infusions and transitioned to oral prednisone and mycophenolate. The patient’s symptoms improved on this regimen. Six months after starting mycophenolate, the patient began having fevers, night sweats, and productive cough without hemoptysis. He moved from the Philippines 5 years prior to dermatomyositis diagnosis, denied sick contacts, and was PPD negative both at immigration and immediately prior to starting mycophenolate treatment. A third PPD was negative following the onset of these new symptoms. He was treated for community-acquired pneumonia, but symptoms worsened over 10 days and he developed watery diarrhea and a growing non-tender, non-mobile mass on the left side of his neck. A chest x-ray demonstrated a cavitary lesion in right upper lobe suspicious for TB that had not been present one month earlier. Chest CT corroborated this finding also exhibiting necrotic hilar and paratracheal lymphadenopathy. Neck CT demonstrated the left-sided mass as cervical chain lymphadenopathy. Expectorated sputum and stool samples contained acid-fast bacilli (AFB), cultures showing TB bacteria. Fine-needle biopsy of the neck mass (scrofula) also exhibited AFB. An MRI brain showed nodular enhancement suspected to be a tuberculoma. Mycophenolate was discontinued and dermatomyositis treatment was switched to oral prednisone with a 3-day course of IVIG. The patient’s infection showed sensitivity to standard RIPE (rifampin, isoniazid, pyrazinamide, and ethambutol) treatment. Within a week of starting RIPE, the patient’s diarrhea subsided, scrofula diminished, and symptoms significantly improved. By the end of treatment week 3, the patient’s sputum no longer contained AFB; he was removed from isolation, and was discharged to continue RIPE at home. He was discharged on oral prednisone, which effectively addressed his dermatomyositis. This case illustrates the unreliability of PPD tests in patients with long-term inflammatory diseases such as dermatomyositis. Other immunosuppressive therapies (adalimumab, etanercept, and infliximab) have been affiliated with conversion of latent TB to disseminated TB. Mycophenolate is another immunosuppressive agent with similar mechanistic properties. Thus, it is imperative that patients with long-term inflammatory diseases and high-risk TB factors initiating immunosuppressive therapy receive a TB blood test (such as a quantiferon gold assay) prior to the initiation of therapy to ensure that latent TB is unmasked before it can evolve into a disseminated form of the disease.

Keywords: dermatomyositis, immunosuppressant medications, mycophenolate, disseminated tuberculosis

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Authors: Avik Banerjee, Kavita Saggar

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Infections of the nervous system and adjacent structures are often life-threatening conditions. Despite the recent advances in neuroimaging evaluation, the diagnosis of unclear infectious CNS disease remains a challenge. Our aim is to evaluate the typical and atypical neuro-imaging features of the various routinely encountered CNS infected patients so as to form guidelines for their imaging recognition and differentiation from tumoral, vascular and other entities that warrant a different line of therapy.

Keywords: central nervous system (CNS), Cerebro Spinal Fluid (Csf), Creutzfeldt Jakob Disease (CJD), progressive multifocal leukoencephalopathy (PML)

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Authors: Anjali Roy, Mirza S. Baig

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Atherosclerosis is a chronic inflammatory disease characterized by the formation of lipid rich plaque enriched with necrotic core, modified lipid accumulation, smooth muscle cells, endothelial cells, leucocytes and macrophages. Macrophage foam cells play a critical role in the occurrence and development of inflammatory atherosclerotic plaque. Foam cells are the fat-laden macrophages in the initial stage atherosclerotic lesion formation. Foam cells are an indication of plaque build-up, or atherosclerosis, which is commonly associated with increased risk of heart attack and stroke as a result of arterial narrowing and hardening. The mechanisms that drive atherosclerotic plaque progression remain largely unknown. Dissecting the molecular mechanism involved in process of macrophage foam cell formation will help to develop therapeutic interventions for atherosclerosis. To investigate the mechanism, we studied the role of nitric oxide synthase 1(NOS1)-mediated nitric oxide (NO) on low-density lipoprotein (LDL) uptake by bone marrow derived macrophages (BMDM). Using confocal microscopy, we found that incubation of macrophages with NOS1 inhibitor, TRIM (1-(2-Trifluoromethylphenyl) imidazole) or L-NAME (N omega-nitro-L-arginine methyl ester) prior to LDL treatment significantly reduces the LDL uptake by BMDM. Further, addition of NO donor (DEA NONOate) in NOS1 inhibitor treated macrophages recovers the LDL uptake. Our data strongly suggest that NOS1 derived NO regulates LDL uptake by macrophages and foam cell formation. Moreover, we also checked proinflammatory cytokine mRNA expression through real time PCR in BMDM treated with LDL and copper oxidized LDL (OxLDL) in presences and absences of inhibitor. Normal LDL does not evoke cytokine expression whereas OxLDL induced proinflammatory cytokine expression which significantly reduced in presences of NOS1 inhibitor. Rapid NOS-1-derived NO and its stable derivative formation act as signaling agents for inducible NOS-2 expression in endothelial cells, leading to endothelial vascular wall lining disruption and dysfunctioning. This study highlights the role of NOS1 as critical players of foam cell formation and would reveal much about the key molecular proteins involved in atherosclerosis. Thus, targeting NOS1 would be a useful strategy in reducing LDL uptake by macrophages at early stage of disease and hence dampening the atherosclerosis progression.

Keywords: atherosclerosis, NOS1, inflammation, oxidized LDL

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Authors: Aynur Charkasova

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The scientific and economic contributions of international students cannot be underestimated. International education continues to be a competitive global industry, and many countries are seeking to recruit the best and the brightest to reinforce scientific innovations, boost intercultural learning, and bring more funding to the universities and colleges. Substantial changes in international educational policies and migration regulations have been made in the hopes of recruiting global talent. This paper explores and compares recruitment strategies, employment opportunities, and a legal path to permanent residency policies related to international students in the United States of America and Canada. This study will utilize the legal information available by the government websites of both countries, peer-reviewed scholarly articles and will highlight which approach promises a better path in recruiting and retention of international students. The findings from the study will be discussed and recommendations will be provided.

Keywords: international students, current immigration policies, STEM, visa reforms for international students

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Authors: B. Chandar, M. K. Ramasamy, P. Madasamy

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The discovery and development of newer antibiotics are limited with the increase in resistance of such multi-drug resistant bacteria creating the need for alternative new therapeutic agents. The recently discovered New Delhi Metallo-betalactamase-1 (NDM-1), which confers antibiotic resistance to most of the currently available β-lactams, except colistin and tigecycline, is a global concern. Several antibacterial drugs approved are natural products or their semisynthetic derivatives, but plant extracts remain to be explored to find molecules that are effective against NDM-1 bacteria. Therefore, it is necessary to explore the possibility of finding new and effective antibacterial compounds against NDM-1 bacteria. In the present study, we have screened a diverse set South Indian plant species, and report most plant species as a potential source for antimicrobial compounds against NDM-1 bacteria. Ethanol extracts from the leaves of taxonomically diverse South Indian medicinal plants were screened for antibacterial activity against NDM-1 E. coli using streak plate method. Among the plant screened against NDM-1 E. coli, the ethanol extracts from many plant extracts showed minimum bactericidal concentration between 5 and 15 mg /ml and MIC between 2.54 and 5.12 mg/ml. These extracts also showed a potent synergistic effect when combined with antibiotics colistin and tetracycline. Combretum albidum that was effective was taken for further analysis. At 5mg/L concentration, these extracts inhibited the NDM-1 enzyme in vitro, and residual activity for Combretum albidum was 33.09%. Treatment of NDM-1 E. coli with the extracts disrupted the cell wall integrity and caused 89.7% cell death. The plant extract of Combretum albidum that was effective was subjected to fractionation and the fraction was further subjected to HPLC, LC-MS for identification of antibacterial compound.

Keywords: antibacterial activity, combretum albidum, Escherichia coli, NDM-1

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Authors: Silvia Alaimo

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This lecture brings to our attention the theme of spirituality within Gestalt therapy’s theoretical and clinical perspectives and which is closely connected to the fertile emptiness and creative indifference’ experiences. First of all, the premise that must be done is the overcoming traditional western culture’s philosophical and religious misunderstandings, such as the dicotomy between spirituality and pratical/material daily life, as well as the widespread secular perspective of classic psychology. Even fullness and emptiness have traditionally been associated with the concepts of being and not being. "There is only one way through which we can contact the deepest layers of our existence, rejuvenate our thinking and reach intuition (the harmony of thought and being): inner silence" (Perls) *. Therefore, "fertile void" doesn't mean empty in itself, but rather an useful condition of every creative and responsible act, making room for a deeper dimension close to spirituality. Spirituality concerns questions about the meaning of existence, which lays beyond the concrete and literal dimension, looking for the essence of things, and looking at the value of personal experience. Looking at fundamentals of Gestalt epistemology, phenomenology, aesthetics, and the relationship, we can reach the heart of a therapeutic work that takes spiritual contours and which are based on an embodied (incarnate size), through the relational aesthetic knowledge (Spagnuolo Lobb ), the deep contact with each other, the role of compassion and responsibility, as the patient's recognition criteria (Orange, 2013) rooted in the body. The aesthetic dimension, like the spiritual dimension to which it is often associated, is a subtle dimension: it is the dimension of the essence of things, of their "soul." In clinical practice, it implies that the relationship between therapist and patient is "in the absence of judgment," also called "zero point of creative indifference," expressed by ‘therapeutic mentality’. It consists in following with interest and authentic curiosity where the patient wants to go and support him in his intentionality of contact. It’s a condition of pure and simple awareness, of the full acceptance of "what is," a moment of detachment from one's own life in which one does not take oneself too seriously, a starting point for finding a center of balance and integration that brings to the creative act, to growth, and, as Perls would say, to the excitement and adventure of living.

Keywords: spirituality, bodily, embodied aesthetics, phenomenology, relationship

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Authors: Orly Yona Drori, Shirley Ben Shlomo

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Objectives: The participants will be able to recognize the predictors of binge eating addiction among women who suffer from psychological abuse in their relationships and will recognize the role of woman's defense mechanisms in moderating the association between psychological abuse and binge eating addiction. Methods: A convenience sample of 380 Israeli women in relationships were located via the Internet, and after consenting to participate in the study, they completed a series of structured questionnaires (The Yale Food Addiction Scale; The Defense Style Questionnaire; psychological maltreatment of women by their male partners; level of differentiation of self; sociodemographic questionnaire). Results: The higher the level of differentiation and mature defense mechanisms, the less addictive a woman is. However, the level of addiction among women who experience psychological abuse within their intimate relations is higher than women who do not experience psychological abuse in their relationship. Among women who experienced psychological abuse in their relations, the defense mechanisms moderate the association between psychological abuse within intimate relations and the extent of the addiction to binge eating. Conclusions: The study contributes to the therapy of women with binge eating addictions, as it raises awareness of therapeutic-related content that could strengthen women and help them to cope with situations in their lives without the need to binge. One of the significant variables for therapeutic work is the level of differentiation of the self. In addition, identifying the types of defense mechanisms might help to match treatment to the woman's emotional needs. The current study found also that it is important to identify the environmental systems by which the addict is surrounded, such as whether woman is in an abusive relationship. Finally the study leads to the recognition that binge eating, which is usually treated with an emphasis on nutritional behavior change, is an addiction, and as such, it requires a combination of mental, nutritional and behavioral therapy. In view of this approach, it is recommended that treating a woman who is addicted to binge eating should involve a multi-disciplinary team comprised of physicians, clinical dietitians, and clinical psychotherapists.

Keywords: binge eating, defence mechanism, food addiction, psychological abuse

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Authors: Naomi Seidu, Edward Poluyi, Chibuikem Ikwuegbuenyi, Eghosa Morgan

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The current poor prognosis of glioblastoma has called for the need for an improvement in treatment methods in order to improve its survival rate. Despite the different interventions currently available for this tumor, the average survival is still only a few months. (12-15). The aim is to create a more favorable prognosis and have a reduction in the resistance to treatment currently being experienced, even with surgical interventions and chemotherapy. From the available literature, there is a relationship between the presence of HOX genes (Homeobox genes) and glioblastoma, which could be attributable to the increasing treatment resistance. Hence silencing these genes can be a key to improving survival rates of glioblastoma. A series of studies have highlighted the role that HOX genes play in glioblastoma prognosis. Promotion of human glioblastoma initiation, aggressiveness, and resistance to Temozolomide has been associated with HOXA9. The role of HOX gene expression in cancer stem cells should be studied as it could provide a means of designing CSC-targeted therapies, as CSCs play a part in the initiation and progression of solid tumors.

Keywords: GBM- glioblastoma, HOXA gene- homeobox genes cluster, signaling pathways, temozolomide

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Authors: Ying Chern Yeoh, Mark J. Forshaw

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Although hypnosis has been widely endorsed in Europe since 1950s, it was still viewed as a typically new therapy in Asia. There are very little findings regarding hypnosis in Asian countries, especially in culturally diverse countries such as Malaysia. The knowledge of the beneficial effects of hypnosis was not widespread to the public, however knowledge of the negative effects was frequently being highlighted. Therefore, the acceptance of hypnosis as a new effective health treatment can be a challenge in Malaysia. Recognising Malaysian’s perception, belief and attitude towards hypnosis could increase the public awareness of hypnosis, which in turn will alter their misconception and increase acceptance of hypnosis as an effective therapy. Eight individuals (N = 8) from the general public with different background, ethnicity (Malays, Chinese and Indians) and religion (Islamic, Buddhism, Hinduism, Taoism, Christianity, free-thinker) and two local experienced practitioners with minimum of five years experiences (N = 2) were being interviewed to determine their views, beliefs and level of acceptance towards hypnosis. Semi-structured interviews were conducted, transcribed with pseudonyms and analyzed by using Interpretative Phenomenological Analysis. The three emergent themes were illustrated under the captions of ‘traditional vs mainstream’, ‘myths vs truth’, and ‘dissemination and public awareness’. The finding suggested that individual knowledge and personal experience primarily influenced people’s level of acceptance towards hypnosis as a beneficial health treatment, rather than the diversity of cultural and religious background. Subsequent findings regarding hypnosis and the effort of promoting it will provide the society an opportunity to increase public education and health awareness. Several associations had started to advance its development by organizing conferences and setting up therapeutic centers. However, health promotion on hypnosis is yet to be conducted to raise public awareness of its beneficial effects. By requesting for hypnosis to be included as a subject in medical education and psychology curriculum and formatting it under Ministry of Health’s legislation body might enhance the knowledge of hypnosis for Malaysian as one of the health intervention in the future.

Keywords: awareness, hypnosis, intervention, Malaysian, promotion

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Authors: J. Iqbal, Z. Zara

Abstract:

Five new Acceptor-Donor-Acceptor (A-D-A) type small donor molecules (M1-M5) namely; dimethyl cyanoacetate terthiophene di(methylthiophene) dibenzosilole (DMCAO3TBS) (M1), dimelononitrile terthiophene di(methylthiophene) dibenzosilole (DMCNTBS) (M2), dimethyl rhodanine terthiophene di(methylthiophene) dibenzosilole (DMRTBS) (M3), dimelanonitrile terthiophene di(methylthiophene) methyl fluorene (DMCNTF) (M4) and dimethyl rhodanine terthiophene di(methylthiophene) methyl fluorine (DMRTF) (M5) were designed and theoretically explored their electronic, photophysical and geometrical properties via DFT best functional MPW1PW91/6-311G (d,p) level of theory with respect to reference molecules dioctyl cyanoacetate terthiophene di(octylthiophene) dioctylfluorene (DCAO3TF) (Ra) and dioctyl cyanoacetate terthiophene di(octylthiophene) octylcarbazole (DCAO3TCz) (Rb). Among the designed donor molecules (M1-M5), M2 and M4 represented lowest band gap value (2.480 eV and 2.47 eV) with distinctive broad absorption peak at 598 and 601 nm in chloroform due to the presence of stronger electron withdrawing acceptor molecule which pulls the λmax value towards red shift. Theoretically estimated reorganization energies of these molecules recommended excellent property of charge mobility. The designed donor molecules M1-M5, demonstrated lower λe value with reference to their λh, showing that these molecules could be ideal candidates for the transfer of electron with and M2, M4 are best among these as champion molecules with having lowest λe (0.006 D and 0.005 D respectively). Additionally, the Voc of M2 and M4 are 2.01 eV and 1.85 eV respectively with reference respect to PCBM. Thus, our present investigation suggested that our designed donor molecules (M1-M5) are suitable candidates for the solar cell and proposed for high and better performance for the small molecule based solar cell devices.

Keywords: dibenzisilol, donor materials, hole mobility, organic solar cells

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Authors: Amir Saber Gharamaleki, Beitollah Alipour, Zeinab Faghfoori, Ahmad YariKhosroushahi

Abstract:

Colorectal cancer (CRC) is one of the most prevalent cancers and intestinal microbial community plays an important role in colorectal tumorigenesis. Probiotics have recently been assessed as effective anti-proliferative agents and thus this study was performed to examine whether CRC undergo apoptosis by treating with isolated Iranian native dairy yeast, Kluyveromyces marxianus YAS, secretion metabolites. The cytotoxicity assessments on cells (HT-29, Caco-2) were accomplished through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay as well as qualitative DAPI (4',6-diamidino-2-phenylindole staining) and quantitative (flow cytometry assessments) evaluations of apoptosis. To evaluate the main mechanism of apoptosis, Real time PCR method was applied. Kluyveromyces marxianus YAS secretions (IC50) showed significant cytotoxicity against HT-29 and Caco-2 cancer cell lines (66.57 % and 66.34 % apoptosis) similar to 5-Fluorouracil (5-FU) while apoptosis only was developed in 27.57 % of KDR normal cells. The prophylactic effects of Kluyveromyces marxianus (PTCC 5195), as a reference yeast, was not similar to Kluyveromyces marxianus YAS indicating strain dependency of bioactivities on CRC disease prevention. Based on real time PCR results, the main cytotoxicity is related to apoptosis phenomenon and the core related mechanism is depended on the overexpression of BAX, CASP 9, CASP 8 and CASP 3 inducing apoptosis genes. However, several investigations should be conducted to precisely determine the effective compounds to be used as anticancer therapeutics in the future.

Keywords: anticancer, anti-proliferative, apoptosis, cytotoxicity, yeast

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Authors: Abigail Tan, Heng Liang Tan, Vanessa Ding, James Hui, Eng Hin Lee, Andre Choo

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Introduction: Comparative oncology investigates the similarities in spontaneous carcinogenesis between humans and animals, in order to identify treatments that can benefit these patients. Companion animals (CA), like canines and felines, are of special interest when it comes to studying human cancers due to their exposure to the same environmental factors and develop tumours with similar features. The purpose of this study is to explore the cross-reactivity of monoclonal antibodies (mAbs) across cancers in humans and CA. Material and Methods: A panel of CA mAbs generated in the lab was screened on multiple human cancer cell lines through flow cytometry to identify for positive binders. Shortlisted candidates were then characterised by biochemical and functional assays e.g., antibody-drug conjugate (ADC) and western blot assays, including glycan studies. Results: Candidate mAb KP52 was generated from whole-cell immunisation using feline mammary carcinoma. KP52 showed strong positive binding to human cancer cells, such as breast cancer and ovarian cancer. Furthermore, KP52 demonstrated strong killing ( > 50%) as an ADC with Saporin as the payload. Western blot results revealed the molecular weight of the antigen targets to be approximately 45kD and 50kD under reduced conditions. Glycan studies suggest that the epitope is glycan in nature, specifically an O-linked glycan. Conclusion: Candidate mAb KP52 has a therapeutic potential as an ADC against feline mammary cancer, human ovarian cancer, human mammary cancer, human pancreatic cancer, and human gastric cancer.

Keywords: ADC, comparative oncology, mAb, therapeutic

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Authors: Deybith Venegas-Rojas, Sercan Keskin, Svenja Riekeberg, Sana Azim, Stephanie Manz, R. J. Dwayne Miller, Hoc Khiem Trieu

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Liquid Transmission Electron Microscopy (TEM) is a growing area with a broad range of applications from physics and chemistry to material engineering and biology, in which it is possible to image in-situ unseen phenomena. For this, a nanofluidic device is used to insert the nanoflow with the sample inside the microscope in order to keep the liquid encapsulated because of the high vacuum. In the last years, Si3N4 windows have been widely used because of its mechanical stability and low imaging contrast. Nevertheless, the pressure difference between the inside fluid and the outside vacuum in the TEM generates bulging in the windows. This increases the imaged fluid volume, which decreases the signal to noise ratio (SNR), limiting the achievable spatial resolution. With the proposed device, the membrane is fortified with a microstructure capable of stand higher pressure differences, and almost removing completely the bulging. A theoretical study is presented with Finite Element Method (FEM) simulations which provide a deep understanding of the membrane mechanical conditions and proves the effectiveness of this novel concept. Bulging and von Mises Stress were studied for different membrane dimensions, geometries, materials, and thicknesses. The microfabrication of the device was made with a thin wafer coated with thin layers of SiO2 and Si3N4. After the lithography process, these layers were etched (reactive ion etching and buffered oxide etch (BOE) respectively). After that, the microstructure was etched (deep reactive ion etching). Then the back side SiO2 was etched (BOE) and the array of free-standing micro-windows was obtained. Additionally, a Pyrex wafer was patterned with windows, and inlets/outlets, and bonded (anodic bonding) to the Si side to facilitate the thin wafer handling. Later, a thin spacer is sputtered and patterned with microchannels and trenches to guide the nanoflow with the samples. This approach reduces considerably the common bulging problem of the window, improving the SNR, contrast and spatial resolution, increasing substantially the mechanical stability of the windows, allowing a larger viewing area. These developments lead to a wider range of applications of liquid TEM, expanding the spectrum of possible experiments in the field.

Keywords: liquid cell, liquid transmission electron microscopy, nanofluidics, nanofluidic cell, thin films

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Authors: Akan C. Offong, E. J. Anthony, Vasilije Manovic

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A modified steady-state numerical model is developed for the electrochemical reduction of CO₂ to formic acid. The numerical model achieves a CD (current density) (~60 mA/cm²), FE-faradaic efficiency (~98%) and conversion (~80%) for CO₂ electro-reduction to formic acid in a microfluidic cell. The model integrates charge and species transport, mass conservation, and momentum with electrochemistry. Specifically, the influences of Bi-Sn based nanoparticle catalyst (on the cathode surface) at different mole fractions and 1-ethyl-3-methyl imidazolium tetra-fluoroborate ([EMIM][BF₄]) electrolyte, on CD, FE and CO₂ conversion to formic acid is studied. The reaction is carried out at a constant concentration of electrolyte (85% v/v., [EMIM][BF₄]). Based on the mass transfer characteristics analysis (concentration contours), mole ratio 0.5:0.5 Bi-Sn catalyst displays the highest CO₂ mole consumption in the cathode gas channel. After validating with experimental data (polarisation curves) from literature, extensive simulations reveal performance measure: CD, FE and CO₂ conversion. Increasing the negative cathode potential increases the current densities for both formic acid and H₂ formations. However, H₂ formations are minimal as a result of insufficient hydrogen ions in the ionic liquid electrolyte. Moreover, the limited hydrogen ions have a negative effect on formic acid CD. As CO₂ flow rate increases, CD, FE and CO₂ conversion increases.

Keywords: carbon dioxide, electro-chemical reduction, ionic liquids, microfluidics, modelling

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Authors: Elene Zhuravliova, Tamar Barbakadze, Irina Kalandadze, Elnari Zaalishvili, Lali Shanshiashvili, David Mikeladze

Abstract:

Background: Multiple sclerosis (MS) is an inflammatory, neurodegenerative disease, which is accompanied by demyelination and autoimmune response to myelin proteins. Among post-translational modifications, which mediate the modulation of inflammatory pathways during MS, methylation is the main one. The methylation of DNA, also amino acids lysine and arginine, occurs in the cell. It was found that decreased trans-methylation is associated with neuroinflammatory diseases. Therefore, abnormal regulation of the methyl cycle could induce demyelination through the action on PAD (peptidyl-arginine-deiminase) gene promoter. PAD takes part in protein citrullination and targets myelin basic protein (MBP), which is affected during demyelination. To determine whether MBP charge isomers are changing the methyl cycle, we have estimated the concentrations of methyl cycle metabolites in MBP-activated primary astrocytes and oligodendrocytes. For this purpose, the action of the citrullinated MBP- C8 and the most cationic MBP-C1 isomers on the primary cells were investigated. Methods: Primary oligodendrocyte and astrocyte cell cultures were prepared from whole brains of 2-day-old Wistar rats. The methyl cycle metabolites, including homocysteine, S-adenosylmethionine (SAM), and S-adenosylhomocysteine (SAH), were estimated by HPLC analysis using fluorescence detection and prior derivatization. Results: We found that the action of MBP-C8 and MBP-C1 induces a decrease in the concentration of both methyl cycle metabolites, S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH), in astrocytes compared to the control cells. As for oligodendrocytes, the concentration of SAM was increased by the addition of MBP-C1, while MBP-C8 has no significant effect. As for SAH, its concentration was increased compared to the control cells by the action of both MBP-C1 and MBP-C8. A significant increase in homocysteine concentration was observed by the action of the MBP-C8 isomer in both oligodendrocytes and astrocytes. Conclusion: These data suggest that MBP charge isomers change the concentration of methyl cycle metabolites. MBP-C8 citrullinated isomer causes elevation of homocysteine in astrocytes and oligodendrocytes, which may be the reason for decreased astrocyte proliferation and increased oligodendrocyte cell death which takes place in neurodegenerative processes. Elevated homocysteine levels and subsequent abnormal regulation of methyl cycles in oligodendrocytes possibly change the methylation of DNA that activates PAD gene promoter and induces the synthesis of PAD, which in turn provokes the process of citrullination, which is the accompanying process of demyelination. Acknowledgment: This research was supported by the SRNSF Georgia RF17_534 grant.

Keywords: myelin basic protein, astrocytes, methyl cycle metabolites, homocysteine, oligodendrocytes

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Authors: Daniel Manaye Kabtamu, Anteneh Wodaje Bayeh

Abstract:

With the development and utilization of new energy technology, people’s demand for large-scale energy storage system has become increasingly urgent. Vanadium redox flow battery (VRFB) is one of the most promising technologies for grid-scale energy storage applications because of numerous attractive features, such as long cycle life, high safety, and flexible design. However, the relatively low energy efficiency and high production cost of the VRFB still limit its practical implementations. It is of great attention to enhance its energy efficiency and reduce its cost. One of the main components of VRFB that can impressively impact the efficiency and final cost is the electrode materials, which provide the reactions sites for redox couples (V₂₊/V³⁺ and VO²⁺/VO₂⁺). Graphite felt (GF) is a typical carbon-based material commonly employed as electrode for VRFB due to low-cost, good chemical and mechanical stability. However, pristine GF exhibits insufficient wettability, low specific surface area, and poor kinetics reversibility, leading to low energy efficiency of the battery. Therefore, it is crucial to further modify the GF electrode to improve its electrochemical performance towards VRFB by employing active electrocatalysts, such as less expensive metal oxides. This study successfully fabricates low-cost plate-like bismuth vanadate (BiVO₄) material through a simple one-step hydrothermal route, employed as an electrocatalyst to adorn the GF for use as the negative electrode in VRFB. The experimental results show that BiVO₄-3h exhibits the optimal electrocatalytic activity and reversibility for the vanadium redox couples among all samples. The energy efficiency of the VRFB cell assembled with BiVO₄-decorated GF as the negative electrode is found to be 75.42% at 100 mA cm−2, which is about 10.24% more efficient than that of the cell assembled with heat-treated graphite felt (HT-GF) electrode. The possible reasons for the activity enhancement can be ascribed to the existence of oxygen vacancies in the BiVO₄ lattice structure and the relatively high surface area of BiVO₄, which provide more active sites for facilitating the vanadium redox reactions. Furthermore, the BiVO₄-GF electrode obstructs the competitive irreversible hydrogen evolution reaction on the negative side of the cell, and it also has better wettability. Impressively, BiVO₄-GF as the negative electrode shows good stability over 100 cycles. Thus, BiVO₄-GF is a promising negative electrode candidate for practical VRFB applications.

Keywords: BiVO₄ electrocatalyst, electrochemical energy storage, graphite felt, vanadium redox flow battery

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Authors: Yuxi Zhu, Zhenqian Chen

Abstract:

It is of great interest to investigate the thermal properties of non-precious metal catalysts for Proton exchange membrane fuel cell (PEMFC) based on the thermal management requirements. Due to the low symmetry of materials, to accurately obtain the thermal conductivity of materials, it is necessary to obtain the second and third order force constants by combining density functional theory and machine learning interatomic potential. To be specific, the interatomic force constants are obtained by moment tensor potential (MTP), which is trained by the computational trajectory of Ab initio molecular dynamics (AIMD) at 50, 300, 600, and 900 K for 1 ps each, with a time step of 1 fs in the AIMD computation. And then the thermal conductivity can be obtained by solving the Boltzmann transport equation. In this paper, the thermal transport properties of single metal atom catalysts are studied for the first time to our best knowledge by machine-learning interatomic potential (MLIP). Results show that the single metal atom catalysts exhibit anisotropic thermal conductivities and partially exhibit good thermal conductivity. The average lattice thermal conductivities of G-FeN₄, G-CoN₄ and G-NiN₄ at 300 K are 88.61 W/mK, 205.32 W/mK and 210.57 W/mK, respectively. While other single metal atom catalysts show low thermal conductivity due to their low phonon lifetime. The results also show that low-frequency phonons (0-10 THz) dominate thermal transport properties. The results provide theoretical insights into the application of single metal atom catalysts in thermal management.

Keywords: proton exchange membrane fuel cell, single metal atom catalysts, density functional theory, thermal conductivity, machine-learning interatomic potential

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Authors: Makda Aamir, Sood Aayushi, Syed Omar, Nihan Khuld, Iskander Peter, Ijaz Naeem, Sharma Nishant

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Introduction:Glycogen Storage Disease Type-1 (GSD-1) is a rare phenomenon primarily affecting the liver and kidney. Excessive accumulation of glycogen and fat in liver, kidney, and intestinal mucosa is noted in patients with deficiency of Glucose-6-phosphatase deficiency. Patients with GSD-1 have a wide spectrum of symptoms, including hepatomegaly, hypoglycemia, lactic acidemia, hyperlipidemia, hyperuricemia, and growth retardation. Age of onset, rate of disease progression and its severity is variable in this disease.Case:An 18-year-old male with GSD-1a, Von Gierke’s disease, hyperuricemia, and hypertension presented to the hospital with nausea and vomiting. The patient followed an hourly cornstarch regimen during the day and overnight through infusion via a PEG tube. The complaints started at work, where he was unable to tolerate oral cornstarch. He washemodynamically stable on arrival. ABG showed pH 7.372, PaCO2 30.3, and PaO2 92.2. WBC 16.80, K+ 5.8, HCO3 13, BUN 28, Cr 2.2, Glucose 60, AST 115, ALT 128, Cholesterol 352, Triglycerides >1000, Uric Acid 10.6, Lactic Acid 11.8 which trended down to 8.0. CT abdomen showed hepatomegaly and fatty infiltration with the PEG tube in place.He was admitted to the ICU and started on D5NS for hypoglycemia and lactic acidosis. Per request by the patient’s pediatrician, he was transitioned to IV D10/0.45NS at 110mL/Hr to maintain blood glucose above 75 mg/L. Frequent accuchecks were done till he could tolerate his dietary regimen with cornstarch. Lactic acid downtrend to 2.9, and accuchecks ranged between 100-110. Cr improved to 1.3, and his home medications (Allopurinol and Lisinopril) were resumed. He was discharged in stable condition with plans for further genetic therapy work up.Discussion:Mainstay therapy for Von Gierke’s Disease is the prevention of metabolic derangements for which dietary and lifestyle changes are recommended. A low fructose and sucrose diet is recommended by limiting the intake of galactose and lactose to one serving per day. Hypoglycemia treatment in such patients is two-fold, utilizing both quick and stable release sources. Cornstarch has been one such therapy since the 1980s; its slow digestion provides a steady release of glucose over a longer period of time as compared with other sources of carbohydrates. Dosing guidelines vary from age to age and person to person, but it is highly recommended to check BG levels frequently to maintain a BG > 70 mg/dL. Associated high levels of triglycerides and cholesterol can be treated with statins, fibrates, etc. Conclusion:The management of hypoglycemia in GSD 1 disease presents various obstacles which could prove to be fatal. Due to the deficiency of G6P, treatment with a specialized hypoglycemic regimen is warranted. A D10 ½ NS infusion can be used to maintain blood sugar levels as well as correct metabolic or lactate imbalances. Infusion should be gradually weaned off after the patient can tolerate oral feeds as this can help prevent the risk of hypoglycemia and other derangements. Further research is needed in regards to these patients for more sustainable regimens.

Keywords: von gierke, glycogen storage disease, hypoglycemia, genetic disease

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Authors: O. H. Gebril, N. A. Meguid

Abstract:

Background: Iron had been a focus of interest recently as a main exaggerating factor for oxidative stresses in the central nervous system and a link to various neurological disorders is suspected. Many studies with various techniques showed evidence of disturbed iron-related proteins in the cell in human and animal models of neurodegenerative disorders. Also, linkage to significant pathological changes had been evidenced e.g. apoptosis and cell signaling. On the other hand, the role of iron in neurodevelopmental disorders is still unclear. With increasing prevalence of autism worldwide, some changes in iron parameters and its stores were documented in many studies. This study includes Haemochromatosis HFE gene polymorphisms (p.H63D and p.C282Y) and ferroportin gene (SLC40A1) Q248H polymorphism in autism and control children. Materials and Methods: Whole genome DNA was extracted; p.H63D and p.C282Y genotyping was studied using specific sequence amplification followed by restriction enzyme digestion on a sample of autism patients (25 cases) and twenty controls. Results: The p.H63D is seen more than the C282Y among both autism and control samples, with no significant association of p.H63D or p.C282Y polymorphism and autism was revealed. Also, no association with Q248H polymorphism was evidenced. Conclusion: The study results do not prove the role of cellular iron genes polymorphisms as risk factors for neurodevelopmental disorders, and in turn highlights the specificity of cellular iron related pathways in neurodegeneration. These results demand further gene expression studies to elucidate the main pathophysiological pathways that are disturbed in autism and other neurodevelopmental disorders.

Keywords: iron, neurodevelopmental, oxidative stress, haemohromatosis, ferroportin, genes

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