Search results for: systemic rejection
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 924

Search results for: systemic rejection

354 L-Carnitine vs Extracorporeal Elimination for Acute Valproic Acid Intoxication: A Systemic Review

Authors: Byung Keun Yang, Jae Eun Ku, Young Seon Joo, Je Sung You, Sung Phil Chung, Hahn Shick Lee

Abstract:

The purpose of this study is to review the evidence comparing the efficacy and safety between L-carnitine and extracorporeal elimination therapy in the management of acute valproic acid L-carnitine vs Extracorporeal Elimination for Acute Valproic acid Intoxication. PubMed, Embase, Cochrane library, Web of Science, KoreaMed, KMbase, and KISS were searched, using the terms carnitine and valproic acid. All studies, regardless of design, reporting efficacy or safety endpoints were included. Reference citations from identified publications were reviewed. Both English and Korean languages were included. Two authors extracted primary data elements including poisoning severity, presenting features, clinical management, and outcomes. Thirty two articles including 33 cases were identified. Poisoning severity was classified as 3 mild, 11 moderate, and 19 severe cases. Nine cases were treated with L-carnitine while 24 cases received extracorporeal therapy without L-carnitine. All patients except one expired patient treated with hemodialysis recovered clinically and no adverse effects were noted. A case report comparing two patients who ingested the same amount of valproic acid showed increased ICU stay (3 vs. 11 days) in case of delayed extracorporeal therapy. Published evidence comparing L-carnitine with extracorporeal therapy is limited. Based on the available evidence, it is reasonable to consider L-carnitine for patients with acute valproic acid overdose. In case of severe poisoning, extracorporeal therapy would also be considered in the early phase of treatment.

Keywords: carnitine, overdose, poisoning, renal dialysis, valproic acid

Procedia PDF Downloads 361
353 Balancing Justice: A Critical Analysis of Plea Bargaining's Impact on Uganda's Criminal Justice System

Authors: Mukisa Daphine Letisha

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Plea bargaining, a practice often associated with more developed legal systems, has emerged as a significant tool within Uganda's criminal justice system despite its absence in formal legal structures inherited from its colonial past. Initiated in 2013 with the aim of reducing case backlogs, expediting trials, and addressing prison congestion, plea bargaining reflects a pragmatic response to systemic challenges. While rooted in international statutes and domestic constitutional provisions, its implementation relies heavily on the Judicature (Plea Bargain) Rules of 2016, which outline procedural requirements and safeguards. Advocates argue that plea bargaining has yielded tangible benefits, including a reduction in case backlog and efficient allocation of resources, with notable support from judicial and prosecutorial authorities. Case examples demonstrate successful outcomes, with accused individuals benefitting from reduced sentences in exchange for guilty pleas. However, challenges persist, including procedural irregularities, inadequate statutory provisions, and concerns about coercion and imbalance of power between prosecutors and accused individuals. To enhance efficacy, recommendations focus on establishing monitoring mechanisms, stakeholder training, and public sensitization campaigns. In conclusion, while plea bargaining offers potential advantages in streamlining Uganda's criminal justice system, addressing its challenges requires careful consideration of procedural safeguards and stakeholder engagement to ensure fairness and integrity in the administration of justice.

Keywords: plea-bargaining, criminal-justice system, uganda, efficacy

Procedia PDF Downloads 48
352 Pharmacogenetics Study of Dapsone-Induced Severe Cutaneous Adverse Reactions and HLA Class I Alleles in Thai Patients

Authors: Patompong Satapornpong, Therdpong Tempark, Pawinee Rerknimitr, Jettanong Klaewsongkram, Chonlaphat Sukasem

Abstract:

Dapsone (4, 4’-diaminodiphenyl sulfone, DDS) is broadly used for the treatment of inflammatory diseases and infections such as; leprosy, Pneumocystis jiroveci pneumonia in patients with HIV infection, neutrophilic dermatoses, dermatitis herpetiformis and autoimmune bullous disease. The severe cutaneous adverse drug reactions (SCARs) including, Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and drug reaction with eosinophilia and systemic symptoms (DRESS) are rare but severe life-threatening adverse drug reactions. Dapsone is one of many culprit drugs induced SJS, TEN and DRESS. Notwithstanding, to our knowledge, there are no studies of the association of HLA class I alleles and dapsone-induced SCARs in non-leprosy Thai patients. This investigation was a prospective cohort study, which performed in a total of 45 non-leprosy patients. Fifteen patients of dapsone-induced SCARs were classified as following the RegiSCAR criteria, and 30 dapsone-tolerant controls were exposed to dapsone more than 6 months without any evidence of cutaneous reactions. The genotyping of HLA-A, -B and –C were performed using sequence-specific oligonucleotides (PCR-SSOs). The Ethics Committee of Ramathibodi hospital, Mahidol University, approved this study. Among all HLA class I alleles, HLA-A*24:07, HLA-B*13:01, HLA-B*15:02, HLA-C*03:04 and HLA-C*03:09 were significantly associated with dapsone-induced SCARs (OR = 10.55, 95% CI = 1.06 – 105.04, p = 0.0360; OR = 56.00, 95% CI = 8.27 – 379.22, p = 0.0001; OR = 7.00, 95% CI = 1.17 – 42.00, p = 0.0322; OR = 6.00, 95% CI = 1.24 – 29.07, p = 0.0425 and OR = 17.08, 95% CI = 0.82 – 355.45, p = 0.0321, respectively). Furthermore, HLA-B*13:01 allele had strong association with dapsone-induced SJS-TEN and DRESS when compared with dapsone-tolerant controls (OR = 42.00, 95% CI = 2.88 – 612.31, p = 0.0064 and OR = 63.00, 95% CI = 7.72 – 513.94 and p = 0.0001, respectively). Consequently, HLA-B*13:01 might serve as a pharmacogenetic marker for screening before initiating the therapy with dapsone for prevention of dapsone-induced SCARs.

Keywords: dapsone-induced SCARs, HLA-B*13:01, HLA class I alleles, severe cutaneous adverse reactions, Thai

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351 STAT6 Mediates Local and Systemic Fibrosis and Type Ii Immune Response via Macrophage Polarization during Acute and Chronic Pancreatitis in Murine Model

Authors: Hager Elsheikh, Matthias Sendler, Juliana Glaubnitz

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In pancreatitis, an inflammatory reaction occurs in the pancreatic secretory cells due to premature activation of proteases, leading to pancreatic self-digestion and necrotic cell death of acinar cells. Acute pancreatitis in patients is characterized by a severe immune reaction that could lead to serious complications, such as organ failure or septic shock, if left untreated. Chronic pancreatitis is a recurrence of episodes of acute pancreatitis resulting in a fibro-inflammatory immune response, in which the type 2 immune response is primarily driven by AAMs in the pancreas. One of the most important signaling pathways for M2 macrophage activation is the IL-4/STAT6 pathway. Pancreatic fibrosis is induced by the hyperactivation of pancreatic stellate cells by dysregulation in the inflammatory response, leading to further damage, autodigestion and possibly necrosis of pancreatic acinar cells. The aim of this research is to investigate the effect of STAT6 knockout in disease severity and development of fibrosis wound healing in the presence of different macrophage populations, regulated by the type 2 immune response, after inducing chronic and/or acute pancreatitis in mice models via cerulean injection. We further investigate the influence of the JAK/STAT6 signaling pathway on the balance of fibrosis and regeneration in STAT6 deficient and wild-type mice. The characterization of resident and recruited macrophages will provide insight into the influence of the JAK/STAT6 signaling pathway on infiltrating cells and, ultimately, tissue fibrosis and disease severity.

Keywords: acute and chronic pancreatitis, tissue regeneration, macrophage polarization, Gastroenterology

Procedia PDF Downloads 63
350 Measuring Principal and Teacher Cultural Competency: A Need Assessment of Three Proximate PreK-5 Schools

Authors: Teresa Caswell

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Throughout the United States and within a myriad of demographic contexts, students of color experience the results of systemic inequities as an academic outcome. These disparities continue despite the increased resources provided to students and ongoing instruction-focused professional learning received by teachers. The researcher postulated that lower levels of educator cultural competency are an underlying factor of why resource and instructional interventions are less effective than desired. Before implementing any type of intervention, however, cultural competency needed to be confirmed as a factor in schools demonstrating academic disparities between racial subgroups. A needs assessment was designed to measure levels of individual beliefs, including cultural competency, in both principals and teachers at three neighboring schools verified to have academic disparities. The resulting mixed method study utilized the Optimal Theory Applied to Identity Development (OTAID) model to measure cultural competency quantitatively, through self-identity inventory survey items, with teachers and qualitatively, through one-on-one interviews, with each school’s principal. A joint display was utilized to see combined data within and across school contexts. Each school was confirmed to have misalignments between principal and teacher levels of cultural competency beliefs while also indicating that a number of participants in the self-identity inventory survey may have intentionally skipped items referencing the term oppression. Additional use of the OTAID model and self-identity inventory in future research and across contexts is needed to determine transferability and dependability as cultural competency measures.

Keywords: cultural competency, identity development, mixed-method analysis, needs assessment

Procedia PDF Downloads 146
349 A Comparative Time-Series Analysis and Deep Learning Projection of Innate Radon Gas Risk in Canadian and Swedish Residential Buildings

Authors: Selim M. Khan, Dustin D. Pearson, Tryggve Rönnqvist, Markus E. Nielsen, Joshua M. Taron, Aaron A. Goodarzi

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Accumulation of radioactive radon gas in indoor air poses a serious risk to human health by increasing the lifetime risk of lung cancer and is classified by IARC as a category one carcinogen. Radon exposure risks are a function of geologic, geographic, design, and human behavioural variables and can change over time. Using time series and deep machine learning modelling, we analyzed long-term radon test outcomes as a function of building metrics from 25,489 Canadian and 38,596 Swedish residential properties constructed between 1945 to 2020. While Canadian and Swedish properties built between 1970 and 1980 are comparable (96–103 Bq/m³), innate radon risks subsequently diverge, rising in Canada and falling in Sweden such that 21st Century Canadian houses show 467% greater average radon (131 Bq/m³) relative to Swedish equivalents (28 Bq/m³). These trends are consistent across housing types and regions within each country. The introduction of energy efficiency measures within Canadian and Swedish building codes coincided with opposing radon level trajectories in each nation. Deep machine learning modelling predicts that, without intervention, average Canadian residential radon levels will increase to 176 Bq/m³ by 2050, emphasizing the importance and urgency of future building code intervention to achieve systemic radon reduction in Canada.

Keywords: radon health risk, time-series, deep machine learning, lung cancer, Canada, Sweden

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348 [Keynote Talk]: Some Underlying Factors and Partial Solutions to the Global Water Crisis

Authors: Emery Jr. Coppola

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Water resources are being depleted and degraded at an alarming and non-sustainable rate worldwide. In some areas, it is progressing more slowly. In other areas, irreversible damage has already occurred, rendering regions largely unsuitable for human existence with destruction of the environment and the economy. Today, 2.5 billion people or 36 percent of the world population live in water-stressed areas. The convergence of factors that created this global water crisis includes local, regional, and global failures. In this paper, a survey of some of these factors is presented. They include abuse of political power and regulatory acquiescence, improper planning and design, ignoring good science and models, systemic failures, and division between the powerful and the powerless. Increasing water demand imposed by exploding human populations and growing economies with short-falls exacerbated by climate change and continuing water quality degradation will accelerate this growing water crisis in many areas. Without regional measures to improve water efficiencies and protect dwindling and vulnerable water resources, environmental and economic displacement of populations and conflict over water resources will only grow. Perhaps more challenging, a global commitment is necessary to curtail if not reverse the devastating effects of climate change. Factors will be illustrated by real-world examples, followed by some partial solutions offered by water experts for helping to mitigate the growing water crisis. These solutions include more water efficient technologies, education and incentivization for water conservation, wastewater treatment for reuse, and improved data collection and utilization.

Keywords: climate change, water conservation, water crisis, water technologies

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347 Development of a Novel Nanobiosystem for the Selective Nanophotothermolysis of Meticilin Resistant Staphyloccocous Aureus Using Anti-MRSA Antibody Functionalized Gold Nanoparticles

Authors: Lucian Mocan, Cristian Matea, Flaviu A. Tabaran, Teodora Mocan, Cornel Iancu

Abstract:

Introduction: Due to antibiotic resistance, systemic infections caused by Meticilin resistant Staphyloccocous Aureus (MRSA) are the main cause of millions of deaths each year. Development of new active biomolecules that are highly effective and refractory to antibiotic resistance may open new avenues in the field of antimicrobial therapy. In this research, we have focused on the development of a novel nanobiosystem with high affinity for MRSA microorganism to mediate its selective laser thermal ablation. Materials and Methods: Gold nanoparticles (15nm in diameter) linked to a specific antibody against MRSA surface were selectively delivered (at various concentrations and incubation times) and internalized into MRSA microorganism following the treatment these multidrug-resistant bacteria were irradiated using a 2w, 808 nm LASER. Results and Discussions: The post-irradiation necrotic rate ranged from 51.2% (for 1 mg/L) to 87.3% (for 50 mg/L) at 60 seconds (p<0.001), while at 30 minute the necrotic rate increased from 64.3% (1 mg/L) to 92.1% (50 mg/L), p value<0.001. Significantly lower apoptotic rates were obtained in irradiated MRSA treated with GNPs only (control) treated for 60 seconds and 30 minutes at concentrations ranging from 1 mg/L to 50 mg/L. We show here that the optimal LASER mediated the necrotic effect of MRSA after incubation with anti-MRSA-Ab was obtained at a concentration of 50 mg/L. Conclusion: In the presented research, we obtained a very efficacious pulse laser mode treatment of individual MRSA agents with minimal effects on the surrounding medium, providing highly localized destruction only for MRSA microorganism.

Keywords: MRSA, photothermolysis, antibiotic resistance, gold nanoparticles

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346 Role of Ologen in Previously Failed Trabeculectomy in Advanced Glaucoma

Authors: Reetika Sharma, Lalit Tejwani, Himanshu Shekhar, Arun Singhvi

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Purpose: Advanced Glaucoma with Failed trab is not an uncommon sight in glaucoma clinic, and such cases usually tend to present with high intraocular pressure (IOP) and advanced cupping, or even glaucomatous atrophy stage. Re-surgery is needed for such cases, and wound modulation poses a major challenge in these cases. We share our experience in this case series with the use of Ologen (collagen matrix implant) along with MMC 0.04% used in surgery. The purpose of the study was to evaluate the efficacy and outcome of collagen matrix implant in re-trabeculectomy in advanced glaucoma cases. Methodology: Eleven eyes of 11 patients (one eye of one patient) underwent re-trabeculectomy surgery with MMC and Ologen. Ologen implant was used in sub scleral and subconjunctival space, as a spacer and wound modulator. In five cases, triple modulation with implant soaked in anti-VEGF was used. Results: All patients had cupping more than 0.9, and one case was GOA. All cases were on maximal medication at presentation and majority were on systemic anti-glaucoma therapy also. Post-surgery, follow-up ranged from 13 – 34 months, and all cases had a follow longer than the gap between previous surgery (which was failed) and re-trab. One case needed AC reformation and one needling was done. Phaco was done at same sitting in four cases. All cases had their IOP lowered post surgery, and vision was maintained in all, however one case was considered as failed re-surgery case. Topical medication was needed in seven cases post-surgery also. Conclusion: Ologen as adjuvant should be considered in all re-trab cases and all high risk and advanced cases, and triple modulation can be next step in these cases. Aggressive IOP control and non- reluctance to continue topical medications post second surgery should be considered in such cases, to give them best possible vision.

Keywords: failed trabeculectomy, ologen, trabeculectomy, advanced glaucoma

Procedia PDF Downloads 332
345 Effects of Advanced Periodontal Disease on Hematological Parameters in Adult Dogs

Authors: Mahzad Yousefi, Azin Tavakoli

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Periodontal disease is an inflammatory reaction; therefore, it is predicted that changes may occur in some inflammatory parameters that can be detected in routine blood tests. The objective of this study was to evaluate the hematological and biochemistry changes that occur in dogs affected with advanced stages of periodontal disease. 87 dogs were diagnosed with periodontal disease (PD group), and 76 healthy dogs entered the study. The PD dogs had been affected with periodontitis stage 3 or 4 and were candidates for any dental extractions. The healthy dogs were either referred for annual checkups or for issuing health travel certificates that their owners asked for complete lab tests. Neither the diseased nor healthy subjects had a history of infectious, or other general health problems or surgery in the past 3 months. Age, as well as all hematologic including PCV, WBC and RBC count, Hb, MCV, MCH, MCHC, PLT, CBC, NLR, and biochemistry data, including total protein, albumin, glucose, BUN, Creatinine, ALT, AST, and ALP, were recorded and analyzed statistically. Results confirmed that aging has a significant direct relationship with the advanced stages of periodontal disease. Mild leukocytosis occurred in the diseased group; however, it was not significant. Also, the mean total protein of the PD group was lower than that of the healthy dogs, and serum levels of albumin were found to be lower significantly in the diseased group (P<0.05). Mean ±SD amount of Platelet, MCH, and ALT were significantly higher in the diseased group in comparison to the healthy dogs (P<0.05). No significant differences were reported in other evaluated parameters. It is concluded that CBC indices of PD dogs are not systemic inflammatory; however, only a decrease in albumin showed inflammatory responses. Some indices in routine laboratory tests can be changed significantly during advanced stages of the periodontal disease dogs.

Keywords: periodontal disease, dogs, hematological factors, advanced stages, blood tests

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344 Biodistribution of Fluorescence-Labelled Epidermal Growth Factor Protein from Slow Release Nanozolid Depots in Mouse

Authors: Stefan Gruden, Charlott Brunmark, Bo Holmqvist, Erwin D. Brenndorfer, Martin Johansson, Jian Liu, Ying Zhao, Niklas Axen, Moustapha Hassan

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Aim: The study was designed to evaluate the ability of the calcium sulfate-based NanoZolid® drug delivery technology to locally release the epidermal growth factor (EGF) protein while maintaining its biological activity. Methods: NanoZolid-formulated EGF protein labelled with a near-infrared dye (EGF-NIR) depots or EGF-NIR dissolved in PBS were injected subcutaneously into mice bearing EGF receptor (EGFR) positive human A549 lung cancer tumors inoculated subcutaneously. The release and biodistribution of the EGF-NIR were investigated in vivo longitudinally up to 96 hours post-administration, utilizing whole-body fluorescence imaging. In order to confirm the in vivo findings, histological analysis of tumor cryosections was performed to investigate EGF-NIR fluorescent signal and EGFR expression level by immunofluorescence labelling. Results: The in vivo fluorescence imaging showed a controlled release profile of the EGF-NIR loaded in the NanoZolid depots compared to free EGF-NIR. Histological analysis of the tumors further demonstrated a prevailing distribution of EGF-NIR in regions with high levels of EGFR expression. Conclusion: Calcium sulfate based depots can be used to formulate EGF while maintaining its biological activity, e.g., receptor binding capability. This may have good clinical potential for local delivery of biomolecules to enhance treatment efficacy and minimize systemic adverse effects.

Keywords: bioresorbable, calcium sulfate, controlled release, NanoZolid

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343 Allergenic Potential of Airborne Algae Isolated from Malaysia

Authors: Chu Wan-Loy, Kok Yih-Yih, Choong Siew-Ling

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The human health risks due to poor air quality caused by a wide array of microorganisms have attracted much interest. Airborne algae have been reported as early as 19th century and they can be found in the air of tropic and warm atmospheres. Airborne algae normally originate from water surfaces, soil, trees, buildings and rock surfaces. It is estimated that at least 2880 algal cells are inhaled per day by human. However, there are relatively little data published on airborne algae and its related adverse health effects except sporadic reports of algae associated clinical allergenicity. A collection of airborne algae cultures has been established following a recent survey on the occurrence of airborne algae in indoor and outdoor environments in Kuala Lumpur. The aim of this study was to investigate the allergenic potential of the isolated airborne green and blue-green algae, namely Scenedesmus sp., Cylindrospermum sp. and Hapalosiphon sp.. The suspensions of freeze-dried airborne algae were adminstered into balb-c mice model through intra-nasal route to determine their allergenic potential. Results showed that Scenedesmus sp. (1 mg/mL) increased the systemic Ig E levels in mice by 3-8 fold compared to pre-treatment. On the other hand, Cylindrospermum sp. and Hapalosiphon sp. at similar concentration caused the Ig E to increase by 2-4 fold. The potential of airborne algae causing Ig E mediated type 1 hypersensitivity was elucidated using other immunological markers such as cytokine interleukin (IL)- 4, 5, 6 and interferon-ɣ. When we compared the amount of interleukins in mouse serum between day 0 and day 53 (day of sacrifice), Hapalosiphon sp. (1mg/mL) increased the expression of IL4 and 6 by 8 fold while the Cylindrospermum sp. (1mg/mL) increased the expression of IL4 and IFɣ by 8 and 2 fold respectively. In conclusion, repeated exposure to the three selected airborne algae may stimulate the immune response and generate Ig E in a mouse model.

Keywords: airborne algae, respiratory, allergenic, immune response, Malaysia

Procedia PDF Downloads 235
342 Suicide Conceptualization in Adolescents through Semantic Networks

Authors: K. P. Valdés García, E. I. Rodríguez Fonseca, L. G. Juárez Cantú

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Suicide is a global, multidimensional and dynamic problem of mental health, which requires a constant study for its understanding and prevention. When research of this phenomenon is done, it is necessary to consider the different characteristics it may have because of the individual and sociocultural variables, the importance of this consideration is related to the generation of effective treatments and interventions. Adolescents are a vulnerable population due to the characteristics of the development stage. The investigation was carried out with the objective of identifying and describing the conceptualization of adolescents of suicide, and in this process, we find possible differences between men and women. The study was carried out in Saltillo, Coahuila, Mexico. The sample was composed of 418 volunteer students aged between 11 and 18 years. The ethical aspects of the research were reviewed and considered in all the processes of the investigation with the participants, their parents and the schools to which they belonged, psychological attention was offered to the participants and preventive workshops were carried in the educational institutions. Natural semantic networks were the instrument used, since this hybrid method allows to find and analyze the social concept of a phenomenon; in this case, the word suicide was used as an evocative stimulus and participants were asked to evoke at least five words and a maximum 10 that they thought were related to suicide, and then hierarchize them according to the closeness with the construct. The subsequent analysis was carried with Excel, yielding the semantic weights, affective loads and the distances between each of the semantic fields established according to the words reported by the subjects. The results showed similarities in the conceptualization of suicide in adolescents, men and women. Seven semantic fields were generated; the words were related in the discourse analysis: 1) death, 2) possible triggering factors, 3) associated moods, 4) methods used to carry it out, 5) psychological symptomatology that could affect, 6) words associated with a rejection of suicide, and finally, 7) specific objects to carry it out. One of the necessary aspects to consider in the investigations of complex issues such as suicide is to have a diversity of instruments and techniques that adjust to the characteristics of the population and that allow to understand the phenomena from the social constructs and not only theoretical. The constant study of suicide is a pressing need, the loss of a life from emotional difficulties that can be solved through psychiatry and psychological methods requires governments and professionals to pay attention and work with the risk population.

Keywords: adolescents, psychological construct, semantic networks, suicide

Procedia PDF Downloads 107
341 Replicating Brain’s Resting State Functional Connectivity Network Using a Multi-Factor Hub-Based Model

Authors: B. L. Ho, L. Shi, D. F. Wang, V. C. T. Mok

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The brain’s functional connectivity while temporally non-stationary does express consistency at a macro spatial level. The study of stable resting state connectivity patterns hence provides opportunities for identification of diseases if such stability is severely perturbed. A mathematical model replicating the brain’s spatial connections will be useful for understanding brain’s representative geometry and complements the empirical model where it falls short. Empirical computations tend to involve large matrices and become infeasible with fine parcellation. However, the proposed analytical model has no such computational problems. To improve replicability, 92 subject data are obtained from two open sources. The proposed methodology, inspired by financial theory, uses multivariate regression to find relationships of every cortical region of interest (ROI) with some pre-identified hubs. These hubs acted as representatives for the entire cortical surface. A variance-covariance framework of all ROIs is then built based on these relationships to link up all the ROIs. The result is a high level of match between model and empirical correlations in the range of 0.59 to 0.66 after adjusting for sample size; an increase of almost forty percent. More significantly, the model framework provides an intuitive way to delineate between systemic drivers and idiosyncratic noise while reducing dimensions by more than 30 folds, hence, providing a way to conduct attribution analysis. Due to its analytical nature and simple structure, the model is useful as a standalone toolkit for network dependency analysis or as a module for other mathematical models.

Keywords: functional magnetic resonance imaging, multivariate regression, network hubs, resting state functional connectivity

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340 Protective Effect of the Histamine H3 Receptor Antagonist DL77 in Behavioral Cognitive Deficits Associated with Schizophrenia

Authors: B. Sadek, N. Khan, D. Łażewska, K. Kieć-Kononowicz

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The effects of the non-imidazole histamine H3 receptor (H3R) antagonist DL77 in passive avoidance paradigm (PAP) and novel object recognition (NOR) task in MK801-induced cognitive deficits associated with schizophrenia (CDS) in adult male rats, and applying donepezil (DOZ) as a reference drug were investigated. The results show that acute systemic administration of DL77 (2.5, 5, and 10 mg/kg, i.p.) significantly improved MK801-induced (0.1 mg/kg, i.p.) memory deficits in PAP. The ameliorating activity of DL77 (5 mg/kg, i.p.) in MK801-induced deficits was partly reversed when rats were pretreated with the centrally-acting H2R antagonist zolantidine (ZOL, 10 mg/kg, i.p.) or with the antimuscarinic antagonist scopolamine (SCO, 0.1 mg/kg, i.p.), but not with the CNS penetrant H1R antagonist pyrilamine (PYR, 10 mg/kg, i.p.). Moreover, the memory enhancing effect of DL77 (5 mg/kg, i.p.) in MK801-induced memory deficits in PAP was strongly reversed when rats were pretreated with a combination of ZOL (10 mg/kg, i.p.) and SCO (1.0 mg/kg, i.p.). Furthermore, the significant ameliorative effect of DL77 (5 mg/kg, i.p.) on MK801-induced long-term memory (LTM) impairment in NOR test was comparable to the DOZ-provided memory-enhancing effect, and was abrogated when animals were pretreated with the histamine H3R agonist R-(α)-methylhistamine (RAMH, 10 mg/kg, i.p.). However, DL77(5 mg/kg, i.p.) failed to provide procognitive effect on MK801-induced short-term memory (STM) impairment in NOR test. In addition, DL77 (5 mg/kg) did not alter anxiety levels and locomotor activity of animals naive to elevated-plus maze (EPM), demonstrating that improved performances with DL77 (5 mg/kg) in PAP or NOR are unrelated to changes in emotional responding or spontaneous locomotor activity. These results provide evidence for the potential of H3Rs for the treatment of neurodegenerative disorders related to impaired memory function, e.g. CDS.

Keywords: histamine H3 receptor, antagonist, learning, memory impairment, passive avoidance paradigm, novel object recognition

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339 Farmers Perception in Pesticide Usage in Curry Leaf (Murraya koeinigii (L.))

Authors: Swarupa Shashi Senivarapu Vemuri

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Curry leaf (Murraya koeinigii (L.)) exported from India had insecticide residues above maximum residue limits, which are hazardous to consumer health and caused rejection of the commodity at the point of entry in Europe and middle east resulting in a check on export of curry leaf. Hence to study current pesticide usage patterns in major curry leaf growing areas, a survey on pesticide use pattern was carried out in curry leaf growing areas in Guntur districts of Andhra Pradesh during 2014-15, by interviewing farmers growing curry leaf utilizing the questionnaire to assess their knowledge and practices on crop cultivation, general awareness on pesticide recommendations and use. Education levels of farmers are less, where 13.96 per cent were only high school educated, and 13.96% were illiterates. 18.60% farmers were found cultivating curry leaf crop in less than 1 acre of land, 32.56% in 2-5 acres, 20.93% in 5-10 acres and 27.91% of the farmers in more than 10 acres of land. Majority of the curry leaf farmers (93.03%) used pesticide mixtures rather than applying single pesticide at a time, basically to save time, labour, money and to combat two or more pests with single spray. About 53.48% of farmers applied pesticides at 2 days interval followed by 34.89% of the farmers at 4 days interval, and about 11.63% of the farmers sprayed at weekly intervals. Only 27.91% of farmers thought that the quantity of pesticides used at their farm is adequate, 90.69% of farmers had perception that pesticides are helpful in getting good returns. 83.72% of farmers felt that crop change is the only way to control sucking pests which damages whole crop. About 4.65% of the curry leaf farmers opined that integrated pest management practices are alternative to pesticides and only 11.63% of farmers felt natural control as an alternative to pesticides. About 65.12% of farmers had perception that high pesticide dose will give higher yields. However, in general, Curry leaf farmers preferred to contact pesticide dealers (100%) and were not interested in contacting either agricultural officer or a scientist. Farmers were aware of endosulfan ban 93.04%), in contrast, only 65.12, per cent of farmers knew about the ban of monocrotophos on vegetables. Very few farmers knew about pesticide residues and decontamination by washing. Extension educational interventions are necessary to produce fresh curry leaf free from pesticide residues.

Keywords: Curry leaf, decontamination, endosulfan, leaf roller, psyllids, tetranychid mite

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338 Teachers' Pedagogical Content Knowledge and Students' Achievement: A Correlational study at the Elementary level

Authors: Abrar Ajmal

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This quantitative study explored elementary school teachers' pedagogical content knowledge and effects on grade 8 students' achievement in Punjab, Pakistan. A teacher sample (N=100) rated competencies across inquiry-focused teaching, conceptual building, interaction practices and peer collaboration promotion. A student sample (N=120) self-reported academic abilities, intrinsic motivation, help-seeking and accountability. Findings reveal teachers highly endorse learner-centric strategies, although peer interaction promotion seems less common currently. Meanwhile, significant gender disparities in self-perceived expertise emerge, favouring female over male educators across all facets measured. Additionally, teachers' knowledge positively—and significantly—correlates with student achievement overall and for both genders, highlighting the importance of professional enrichment. However, female pupils demonstrate greater confidence, drive, utilization of academic support, and ownership over learning than male counterparts. Recommendations include ongoing teacher training, targeted competency building for male students and teachers, leveraging gender peer collaboration similarities, and holistic female support amid widening divides. Sustaining instructional quality through empowering, equitable practices that nurture disadvantaged and gifted learners alike can spur systemic improvements. Ultimately, the fire line confirms the interrelations between teachers' multifaceted knowledge and student success.

Keywords: pedagogical knowledge, academic achievement, teacher gender differences, student gender differences, empowering instruction

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337 Late Presentation of Pseudophakic Macula Edema from Oral Kinase Inhibitors: A Case and Literature Review

Authors: Christolyn Raj, Lewis Levitz

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Introduction: Two cases of late presentation ( > five years ) of bilateral pseudophakic macula edema related to oral tyrosine kinase inhibitors are described. These cases are the first of their type in the published literature. A review of ocular inflammatory complications of tyrosine kinase inhibitors in the current literature is explored. Case Presentations(s): Case 1 is an 83-year-old female who has been stable on Ibrutinib (Imbruvica ®) for chronic lymphocytic leukemia (CLL). She presented with bilateral blurred vision from severe cystoid macula edema seven years following routine cataract surgery. She was treated with intravitreal steroids with complete resolution without relapse. Case 2 is a 76-year-old female who was on therapy for polycythemia vera with Ruxolitinib (Jakafi®). She presented with bilateral blurred vision from mild cystoid macula edema six years following routine cataract surgery. She responded well to topical steroids without relapse. In both cases, oral tyrosine kinase inhibitor agents were presumed to be the underlying cause and were ceased. Over the last five years, there have been increasing reports in the literature of the inflammatory effects of tyrosine kinase inhibitors on the retina, uvea and optic nerve. Conclusion: Late presentation of pseudophakic macula edema following routine cataract surgery is rare. Such presentations should prompt investigation of the chronic use of systemic medications, especially oral kinase inhibitors. Patients who must remain on these agents require ongoing ophthalmologic assessment in view of their long-term inflammatory side effects.

Keywords: macula edema, oral kinase inhibitors, retinal toxicity, pseudo-phakia

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336 Treatment of Drug-Induced Oral Ulceration with Hyaluronic Acid Gel: A Case Report

Authors: Meltem Koray, Arda Ozgon, Duygu Ofluoglu, Mehmet Yaltirik

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Oral ulcerations can be seen as a side effect of different drugs. These ulcers usually appear within a few weeks following drug treatment. In most of cases, these ulcers resist to conventional treatments, such as anesthetics, antiseptics, anti-inflammatory agents, cauterization, topical tetracycline and corticosteroid treatment. The diagnosis is usually difficult, especially in patients receiving multiple drug therapies. Hyaluronan or hyaluronic acid (HA) is a biomaterial that has been introduced as an alternative approach to enhance wound healing and also used for oral ulcer treatment. The aim of this report is to present the treatment of drug-induced oral ulceration on maxillary mucosa with HA gel. 60-year-old male patient was referred to Department of Oral and Maxillofacial Surgery complaining of oral ulcerations during few weeks. He had received chemotherapy and radiotherapy in 2014 with the diagnosis of nasopharyngeal carcinoma, and he has accompanying systemic diseases such as; cardiological, neurological diseases and gout. He is medicated with Escitalopram (Cipralex® 20mg), Quetiapine (Seroquel® 100mg), Mirtazapine (Zestat® 15mg), Acetylsalicylic acid (Coraspin® 100mg), Ramipril-hydrochlorothiazide (Delix® 2.5mg), Theophylline anhydrous (Teokap Sr® 200mg), Colchicine (Colchicum Dispert® 0.5mg), Spironolactone (Aldactone® 100mg), Levothyroxine sodium (Levotiron® 50mg). He had painful oral ulceration on the right side of maxillary mucosa. The diagnosis was 'drug-induced oral ulceration' and HA oral gel (Aftamed® Oral gel) was prescribed 3 times a day for 2 weeks. Complete healing was achieved within 3 weeks without any side effect and discomfort. We suggest that HA oral gel is a potentially useful local drug which can be an alternative for management of drug-induced oral ulcerations.

Keywords: drug-induced, hyaluronic acid, oral ulceration, maxillary mucosa

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335 Repositioning Sodium Valproate for Amelioration of Bleomycin-induced Scleroderma: The Role of Oxidative Stress, Transforming Growth Factor Beta-1, and the Mammalian Target of Rapamycin

Authors: Ahmed M. Kabel, Maaly A. Abd Elmaaboud

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Scleroderma is one of the connective tissue disorders characterized by skin and systemic fibrosis. Its pathogenesis involves multiple interrelated processes of autoimmunity, vasculopathy, inflammation, and oxidative stress. This study was a trial to explore the possible ameliorative effects of sodium valproate on an experimental model of skin fibrosis induced by bleomycin. Forty male BALB/c mice were divided into four equal groups as follows: control group; bleomycin group; bleomycin + sodium valproate group, and sodium valproate group. Mice were assessed for their body weight every four days throughout the whole study. Skin tissues were used to evaluate the oxidative stress parameters, transforming growth factor beta 1 (TGF-β1), tumor necrosis factor alpha (TNF-α), interleukin 15, and mammalian target of rapamycin (mTOR). Skin fibrosis was evaluated by measuring dermal thickness and staining the skin tissues with Masson trichrome stain. Also, the skin tissues were immunostained with alpha smooth muscle actin (α-SMA). Administration of sodium valproate to bleomycin-treated mice resulted in the restoration of the body weight with a significant decrease in the dermal thickness, amelioration of oxidative stress, suppression of TGF-β1 and mTOR expression, and significant reduction of the percentage of α-SMA immunostaining and the proinflammatory cytokine levels compared to mice treated with bleomycin alone. In conclusion, sodium valproate has an antifibrotic effect on skin fibrosis which may represent a beneficial therapeutic modality for the management of scleroderma.

Keywords: scleroderma, bleomycin, sodium valproate, skin fibrosis

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334 Albendazole Ameliorates Inflammatory Response in a Rat Model of Acute Mesenteric Ischemia Reperfusion Injury

Authors: Kamyar Moradi

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Background: Acute mesenteric ischemia is known as a life-threatening condition. Re-establishment of blood flow in this condition can lead to mesenteric ischemia reperfusion (MIR) injury, which is accompanied by inflammatory response. Still, clear blueprint of inflammatory mechanism underlying MIR injury has not been provided. Interestingly, Albendazole has exhibited notable effects on inflammation and cytokine production. In this study, we aimed to evaluate outcomes of MIR injury following pretreatment with Albendazole with respect to assessment of mesenteric inflammation and ischemia threshold. Methods: Male rats were randomly divided into sham operated, vehicle treated, Albendazole 100 mg/kg, and Albendazole 200 mg/kg groups. MIR injury was induced by occlusion of superior mesenteric artery for 30 minutes followed by 120 minutes of reperfusion. Samples were utilized for assessment of epithelial survival and villous height. Immunohistochemistry study revealed intestinal expression of TNF-α and HIF-1-α. Gene expression of NF-κB/TLR4/TNF-α/IL-6 was measured using RTPCR. Also, protein levels of inflammatory cytokines in serum and intestine were assessed by ELISA method. Results: Histopathological study demonstrated that pretreatment with Albendazole could ameliorate decline in villous height and epithelial survival following MIR injury. Also, systemic inflammation was suppressed after administration of Albendazole. Analysis of possible participating inflammatory pathway could demonstrate that intestinal expression of NF-κB/TLR4/TNF-α/IL-6 is significantly attenuated in treated groups. Eventually, IHC study illustrated concordant decline in mesenteric expression of HIF-1-α/TNF-α. Conclusion: Single dose pretreatment with Albendazole could ameliorate inflammatory response and enhance ischemia threshold following induction of MIR injury. Still, more studies would clarify existing causality in this phenomenon.

Keywords: albendazole, ischemia reperfusion injury, inflammation, mesenteric ischemia

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333 Exploring the Relationship Between Life Experiences and Early Relapse Among Imprisoned Users of Illegal Drugs in Oman: A Focused Ethnography

Authors: Hamida Hamed Said Al Harthi

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Background: Illegal drug use is a rising problem that affects Omani youth. This research aimed to study a group of young Omani men who were imprisoned more than once for illegal drug use, focusing on exploring their lifestyle experiences inside and outside the prison and whether these contributed to their early relapse and re-imprisonment. This is the first study of its kind from Oman conducted in a prison setting. Methods: 19 Omani males aged 18–35 years imprisoned in Oman Central Prison were recruited using purposive sampling. Focused ethnography was conducted over 8 months to explore the drug-related experiences outside the prison and during imprisonment. Face-to-face semi-structured interviews with the participants yielded detailed transcripts and field notes. These were thematically analyzed, and the results were compared with the existing literature. Results: The participants’ voices yielded new insights into the lives of young Omani men imprisoned for illegal drug use, including their sufferings and challenges in prison. These included: entry shock, timing and boredom, drug trafficking in prison, as well as physical and psychological health issues. Overall, imprisonment was reported to have negatively impacted the participants’ health, personality, self-concept, emotions, attitudes, behavior and life expectations. The participants reported how their efforts to reintegrate into the Omani community after release from prison were rebuffed due to stigmatization and rejection from society and family. They also experienced frequent unemployment, police surveillance, accommodation problems and a lack of rehabilitation facilities. The immensity of the accumulated psychophysiological trauma contributed to their early relapse and re-imprisonment. Conclusion: This thesis concludes that imprisonment is largely ineffective in controlling drug use in Oman. Urgent action is required across multiple sectors to improve the lives and prospects of users of illegal drugs within and outside the prison to minimize factors contributing to early relapse. Key Words: illegal drugs, drug users, Oman, addiction, Omani culture, prisoners, relapse, re-imprisonment, qualitative research, ethnography.

Keywords: illigal drugs, Prison, Omani culture lifestyle, post prison life

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332 Analyzing Culture as an Obstacle to Gender Equality in a Non-Western Context: Key Areas of Conflict between International Women’s Rights and Cultural Rights in South Sudan

Authors: C. Leiber

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International human rights treaties ensure basic rights to all people, regardless of nationality. These treaties have developed in a predominantly Western environment, and their implementation into non-western contexts often raises questions of the transfer-ability of value systems and governance structures. International human rights treaties also postulate the right to the full enjoyment and expression of one’s own culture, known as cultural rights. Many cultural practices and traditions in South Sudan serve as an obstacle to the adaptation of human rights and internationally agreed-upon standards, specifically those pertaining to women’s rights and gender equality. This paper analyzes the specific social, political, and economic conflicts between women’s rights and cultural rights within the context of South Sudan’s evolution into a sovereign nation. It comprehensively evaluates the legal status of South Sudanese women and –based on the empirical evidence- assesses gender equality in four key areas: Marriage, Education, Violence against Women, and Inheritance. This work includes an exploration into how South Sudanese culture influences, and indeed is intertwined with, social, political, and economic spheres, and how it limits gender equality and impedes the full implementation of international human rights treaties. Furthermore, any negative effects which systemic gender inequality and cultural practices that are oppressive to women have on South Sudan as a developing nation are explored. Finally, those areas of conflict between South Sudanese cultural rights and international women’s rights are outlined which can be mitigated or resolved in favor of elevating gender equality without imperializing or destroying South Sudanese culture.

Keywords: cultural rights, gender equality, international human rights, South Sudan

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331 A Strategic Perspective on a Qualitative Model of Type II Workplace Aggression in Healthcare Sector

Authors: Francesco Ceresia

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Workplace aggression is broadly recognized as a main work-related risk for healthcare organizations the world over. Scholars underlined that nonfatal workplace aggressions can be also produced by Type II workplace aggression, that occur when the aggressor has a legitimate relationship with the organization and commits an act of hostility while being served or cared for by members of the organization. Several reviews and meta-analysis highlighted the main antecedents and consequences of Type II verbal and physical workplace aggression in the healthcare sector, also focusing on its economic and psychosocial costs. However, some scholars emphasized the need for a systemic and multi-factorial approach to deeply understand and effectively respond to such kind of aggression. The main aim of the study is to propose a qualitative model of Type II workplace aggression in a health care organization in accordance with the system thinking and multi-factorial perspective. A case study research approach, conducted in an Italian non-hospital healthcare organization, is presented. Two main data collection methods have been adopted: individual and group interviews with a sample (N = 24) of physicians, nurses and clericals. A causal loop diagram (CLD) that describes the main causal relationships among the key-variables of the proposed model has been outlined. The main feedback loops and the causal link polarities have been also defined to fully describe the structure underlining the Type II workplace aggression phenomenon. The proposed qualitative model shows how the Type II workplace aggression is related with burnout, work performance, job satisfaction, turnover intentions, work motivation and emotional dissonance. Finally, strategies and policies to reduce the strength of workplace aggression’s drivers are suggested.

Keywords: healthcare, system thinking, work motivation, workplace aggression

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330 Attitude to the Types of Organizational Change

Authors: O. Y. Yurieva, O. V. Yurieva, O. V. Kiselkina, A. V. Kamaseva

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Since the early 2000s, there are some innovative changes in the civil service in Russia due to administrative reform. Perspectives of the reform of the civil service include a fundamental change in the personnel component, increasing the level of professionalism of officials, increasing their capacity for self-organization and self-regulation. In order to achieve this, the civil service must be able to continuously change. Organizational changes have long become the subject of scientific understanding; problems of research in the field of organizational change is presented by topics focused on the study of the methodological aspects of the implementation of the changes, the specifics of changes in different types of organizations (business, government, and so on), design changes in the organization, including based on the change in organizational culture. In this case, the organizational changes in the civil service are the least studied areas; research of problems of its transformation is carried out in fragments. According to the theory of resistance of Herbert Simon, the root of the opposition and rejection of change is in the person who will resist any change, if it threatens to undermine the degree of satisfaction as a member of the organization (regardless of the reasons for this change). Thus, the condition for successful adaptation to changes in the organization is the ability of its staff to perceive innovation. As part of the problem, the study sought to identify the innovation civil servants, to determine readiness for the development of proposals for the implementation of organizational change in the public service. To identify the relationship to organizational changes case study carried out by the method of "Attitudes to organizational change" of I. Motovilina, which allowed predicting the type of resistance to changes, to reveal the contradictions and hidden results. The advantage of the method of I. Motovilina is its brevity, simplicity, the analysis of the responses to each question, the use of "overlapping" issues potentially conflicting factors. Based on the study made by the authors, it was found that respondents have a positive attitude to change more local than those that take place in reality, such as "increase opportunities for professional growth", "increase the requirements for the level of professionalism of", "the emergence of possible manifestations initiatives from below". Implemented by the authors diagnostics related to organizational changes in the public service showed the presence of specific problem areas, with roots in the lack of understanding of the importance of innovation personnel in the process of bureaucratization of innovation in public service organizations.

Keywords: innovative changes, self-organization, self-regulation, civil service

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329 Bilateral Simultaneous Acute Primary Angle Closure Glaucoma: A Remarkable Case

Authors: Nita Nurlaila Kadarwaty

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Purpose: This study presents a rare case of bilateral Acute Primary Angle Closure Glaucoma (PACG). Method: A case report of a 64-year-old woman with a good outcome Acute PACG in both eyes who underwent phacotrabeculectomy surgery. Result: A 64-year-old woman complained of acute pain in both eyes, accompanied by decreased vision, photophobia, and seeing halos for three weeks. There was no history of trauma, steroid or other systemic drugs used, or intraocular surgery before. Ophthalmologic examination revealed a right eye (RE) visual acuity of 0.1, left eye (LE) 0.2. RE intraocular pressure (IOP) was 12 mmhg and LE: 36.4 mmHg in medication of timolol maleat ED and acetazolamide oral. Both eyes' anterior segments revealed mixed injection, corneal edema, shallow anterior chamber, posterior synechiae, mid-dilatation pupil with negative pupillary reflection, and cloudy lens without intumescent. There was a glaucomatous optic and closed iridocorneal angle on the gonioscopy. Initial treatments included oral acetazolamide and potassium aspartate 250 mg three times a day, timolol maleate ED 0.5% twice a day, and prednisolone acetate ED 1% four times a day. This patient underwent trabeculectomy, phacoemulsification, and implantation of IOL in both eyes. One week after the surgeries, both eyes showed decreased IOP and good visual improvement. Conclusion: Bilateral simultaneous Acute PACG is generally severe and results in a poor outcome. It causes rapidly progressive visual loss and is often irreversible. Phacotrabeculectomy has more benefits compared to only phacoemulsification for the intervention regarding the reduced IOP post-surgical.

Keywords: acute primary angle closure glaucoma, intraocular pressure, phacotrabeculectomy, glaucoma

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328 Product Separation of Green Processes and Catalyst Recycling of a Homogeneous Polyoxometalate Catalyst Using Nanofiltration Membranes

Authors: Dorothea Voß, Tobias Esser, Michael Huber, Jakob Albert

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The growing world population and the associated increase in demand for energy and consumer goods, as well as increasing waste production, requires the development of sustainable processes. In addition, the increasing environmental awareness of our society is a driving force for the requirement that processes must be as resource and energy efficient as possible. In this context, the use of polyoxometalate catalysts (POMs) has emerged as a promising approach for the development of green processes. POMs are bifunctional polynuclear metal-oxo-anion cluster characterized by a strong Brønsted acidity, a high proton mobility combined with fast multi-electron transfer and tunable redox potential. In addition, POMs are soluble in many commonly known solvents and exhibit resistance to hydrolytic and oxidative degradation. Due to their structure and excellent physicochemical properties, POMs are efficient acid and oxidation catalysts that have attracted much attention in recent years. Oxidation processes with molecular oxygen are worth mentioning here. However, the fact that the POM catalysts are homogeneous poses a challenge for downstream processing of product solutions and recycling of the catalysts. In this regard, nanofiltration membranes have gained increasing interest in recent years, particularly due to their relative sustainability advantage over other technologies and their unique properties such as increased selectivity towards multivalent ions. In order to establish an efficient downstream process for the highly selective separation of homogeneous POM catalysts from aqueous solutions using nanofiltration membranes, a laboratory-scale membrane system was designed and constructed. By varying various process parameters, a sensitivity analysis was performed on a model system to develop an optimized method for the recovery of POM catalysts. From this, process-relevant key figures such as the rejection of various system components were derived. These results form the basis for further experiments on other systems to test the transferability to serval separation tasks with different POMs and products, as well as for recycling experiments of the catalysts in processes on laboratory scale.

Keywords: downstream processing, nanofiltration, polyoxometalates, homogeneous catalysis, green chemistry

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327 Therapeutic Role of T Subpopulations Cells (CD4, CD8 and Treg (CD25 and FOXP3+ Cells) of UC MSC Isolated from Three Different Methods in Various Disease

Authors: Kumari Rekha, Mathur K Dhananjay, Maheshwari Deepanshu, Nautiyal Nidhi, Shubham Smriti, Laal Deepika, Sinha Swati, Kumar Anupam, Biswas Subhrajit, Shiv Kumar Sarin

Abstract:

Background: Mesenchymal stem cells are multipotent stem cells derived from mesoderm and are used for therapeutic purposes because of their self-renewal, homing capacity, Immunomodulatory capability, low immunogenicity and mitochondrial transfer signaling. MSCs have the ability to regulate the mechanism of both innate as well as adaptive immune responses through the modulation of cellular response and the secretion of inflammatory mediators. Different sources of MSC are UC MSC, BM MSC, Dental Pulp, and Adipose MSC. The most frequent source used is umbilical cord tissue due to its being easily available and free of limitations of collection procedures from respective hospitals. The immunosuppressive role of MSCs is particularly interesting for clinical use since it confers resistance to rejection by the host immune response. Methodology: In this study, T helper cells (TH4), Cytotoxic T cells (CD-8), immunoregulatory cells (CD25 +FOXP3+) are compared from isolated MSC from three different methods, UC Dissociation Kit (Miltenyi), Explant Culture and Collagenase Type-IV. To check the immunomodulatory property, these MSCs were seeded with PBMC(Coculture) in CD3 coated 24 well plates. Cd28 antibody was added in coculture for six days. The coculture was analyzed in FACS Verse flow cytometry. Results: From flow cytometry analysis of coculture, it found that All over T helper cells (CD4+) number p<0.0264 increases in (All Enzymes) MSC rather than explant MSC(p>0.0895) as compared to Collagenase(p>0.7889) in a coculture of Activated T cell and Mesenchymal Stem Cell. Similar T reg cells (CD25+, FOXP3+) expression p<0.0234increases in All Enzymes), decreases in Explant and Collagenase. Experiments have shown that MSCs can also directly prevent the cytotoxic activity of CD8 lymphocytes mainly by blocking their proliferation rather than by inhibiting the cytotoxic effect. And promoting the t-reg cells, which helps in the mediation of immune response in various diseases. Conclusion: MSC suppress Cytotoxic CD8 T cell and Enhance immunoregulatory T reg (CD4+, CD25+, FOXP3+) Cell expression. Thus, MSC maintains a proper balance(ratio) between CD4 T cells and Cytotoxic CD8 T cells.

Keywords: MSC, disease, T cell, T regulatory

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326 Bionaut™: A Microrobotic Drug-Device Platform for the Local Treatment of Brainstem Gliomas

Authors: Alex Kiselyov, Suehyun Cho, Darrell Harrington; Florent Cros, Olin Palmer, John Caputo, Michael Kardosh, Eran Oren, William Loudon, Michael Shpigelmacher

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Despite the most aggressive surgical and adjuvant therapeutic strategies, treatment of both pediatric and adult brainstem tumors remains problematic. Novel strategies, including targeted biologics, immunotherapy, and specialized delivery systems such as convection-enhanced delivery (CED), have been proposed. While some of these novel treatments are entering phase I trials, the field is still in need of treatment(s) that exhibits dramatically enhanced potency with optimal therapeutic ratio. Bionaut Labs has developed a modular microrobotic platform for performing localized delivery of diverse therapeutics in vivo. Our biocompatible particles (Bionauts™) are externally propelled and visualized in real-time. Bionauts™ are specifically designed to enhance the effect of radiation therapy via anatomically precise delivery of a radiosensitizing agent, as exemplified by temozolomide (TMZ) and Avastin™ to the brainstem gliomas of diverse origin. The treatment protocol is designed to furnish a better therapeutic outcome due to the localized (vs systemic) delivery of the drug to the neoplastic lesion(s) for use as a synergistic combination of radiation and radiosensitizing agent. In addition, the procedure is minimally invasive and is expected to be appropriate for both adult and pediatric patients. Current progress, including platform optimization, selection of the lead radiosensitizer as well as in vivo safety studies of the Bionauts™ in large animals, specifically the spine and the brain of porcine and ovine models, will be discussed.

Keywords: Bionaut, brainstem, glioma, local delivery, micro-robot, radiosensitizer

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325 Transdermal Medicated- Layered Extended-Release Patches for Co-delivery of Carbamazepine and Pyridoxine

Authors: Sarah K. Amer, Walaa Alaa

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Epilepsy is an important cause of mortality and morbidity, according to WHO statistics. It is characterized by the presence of frequent seizures occurring more than 24 hours apart. Carbamazepine (CBZ) is considered first-line treatment for epilepsy. However, reports have shown that CBZ oral formulations failed to achieve optimum systemic delivery, minimize side effects, and enhance patient compliance. Besides, the literature has signified the lack of therapeutically efficient CBZ transdermal formulation and the urge for its existence owing to its ease and convenient method of application and highlighted capability to attain higher bioavailability and more extended-release profiles compared to conventional oral CBZ tablets. This work aims to prepare CBZ microspheres (MS) that are embedded in a transdermal gel containing Vitamin B to be co-delivered. MS were prepared by emulsion-solvent diffusion method using Eudragit S as core forming polymer and hydroxypropyl methylcellulose (HPMC) polymer. The MS appeared to be spherical and porous in nature, offering a large surface area and high entrapment efficiency of CBZ. The transdermal gel was prepared by solvent-evaporation technique using HPMC that, offered high entrapment efficiency and Eudragit S that provided an extended-release profile. Polyethylene glycol, Span 80 and Pyridoxine were also added. Data indicated that combinations of CBZ with pyridoxine can reduce epileptic seizures without affecting motor coordination. Extended-release profiles were evident for this system. The patches were furthermore tested for thickness, moisture content, folding endurance, spreadability and viscosity measurements. This novel pharmaceutical formulation would be of great influence on seizure control, offering better therapeutic effects.

Keywords: epilepsy, carbamazepine, pyridoxine, transdermal

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