Search results for: peripheral neuropathy
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 439

Search results for: peripheral neuropathy

349 Injection of Bradykinin in Femoral Artery Elicits Cardiorespiratory Reflexes Involving Perivascular Afferents in Rat Models

Authors: Sanjeev K. Singh, Maloy B. Mandal, Revand R.

Abstract:

The physiology of baroreceptors and chemoreceptors present in large blood vessels of the heart is well known in regulation of cardiorespiratory functions. Since large blood vessels and peripheral blood vessels are of same mesodermal origin, therefore, involvement of the latter in regulation of cardiorespiratory system is expected. Role of perivascular nerves in mediating cardiorespiratory alterations produced after intra-arterial injection of a nociceptive agent (bradykinin) was examined in urethane anesthetized male rats. Respiratory frequency, blood pressure, and heart rate were recorded for 30 min after the retrograde injection of bradykinin/saline in the femoral artery. In addition, paw edema was determined and water content was expressed as percentage of wet weight. Injection of bradykinin produced immediate tachypnoeic, hypotensive and bradycardiac responses of shorter latency (5-8 s) favoring the neural mechanisms involved in it. Injection of equi-volume of saline did not produce any responses and served as time matched control. Paw edema was observed in the ipsilateral hind limb. Pretreatment with diclofenac sodium significantly attenuated the bradykinin-induced responses and also blocked the paw edema. Ipsilateral femoral and sciatic nerve sectioning attenuated bradykinin-induced responses significantly indicating the origin of responses from the local vascular bed. Administration of bradykinin in the segment of an artery produced reflex cardiorespiratory changes by stimulating the perivascular nociceptors involving prostaglandins. This is a novel study exhibiting the role of peripheral blood vessels in regulation of cardiorespiratory system.

Keywords: vasosensory reflex, cardiorespiratory changes, nociceptive agent, bradykinin, VR1 receptors

Procedia PDF Downloads 117
348 Use of Selected Cytokines in the Early SIRS/MODS Diagnostic Testing at Patients after Trauma

Authors: Aneta Binkowska, Grzegorz Michalak, Slawomir Pilip, Lukasz Bondaruk, Daniel Celinski, Robert Slotwinski

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Post-traumatic mortality rates are still very high and show an increasing tendency. Early identification of patients at high risk of severe complications has a significant impact on treatment outcomes. The aim of the study was to better understand the early pathological inflammatory response to injury and infection and to determine the usefulness of the assessment of TNF-α and sTNFR1 concentrations in the peripheral blood as early indicators of severe post-traumatic complications. The study was carried out in a group of 51 patients after trauma treated in the ED, including 32 patients that met inclusion criteria for immunological analysis. Patients were divided into two groups using the ISS scale (group A with ISS ≥20, group B with ISS <20). Serum levels of TNF-α and sTNFR1 were determined after admission to the ED and after 3, 6, 12 and 24 hours. The highest TNF-α and sTNFR1 concentrations in both groups were recorded at admission and were significantly higher in group A compared to group B (A vs B TNF-α 2.46 pg/ml vs 1.78 pg/ml; sTNFR1 1667.5 pg/ml vs 875.2 p<0.005). The concentration of sTNFR1 in patients with severe complications was significantly higher compared to patients without complications and preceded clinical symptoms of complications ( C+ vs C- 1561.5 pg/ml vs 930.6 pg/ml). Spearman's correlation showed a statistically significant positive correlation between the baseline concentrations of IL-6 (r=0.38, p<0.043) and sTNFR1 (r=0.59, p=0.001) and the ISS scores. The high diagnostic sensitivity calculated from the ROC (receiver operating characteristic) curves was found for the concentrations of both cytokines: TNF α (AUC=0.91, p=0.004) and sTNFR1 (AUC=0.86, p=0.011). Elevated levels of sTNFR1, determined in the peripheral blood shortly after injury, is significantly associated with the occurrence of later complications, which in some patients lead to death. In contrast, high levels of TNF-α shortly after injury are associated with high mortality.

Keywords: cytokine, SIRS, MODS, trauma

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347 Russian Spatial Impersonal Sentence Models in Translation Perspective

Authors: Marina Fomina

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The paper focuses on the category of semantic subject within the framework of a functional approach to linguistics. The semantic subject is related to similar notions such as the grammatical subject and the bearer of predicative feature. It is the multifaceted nature of the category of subject that 1) triggers a number of issues that, syntax-wise, remain to be dealt with (cf. semantic vs. syntactic functions / sentence parts vs. parts of speech issues, etc.); 2) results in a variety of approaches to the category of subject, such as formal grammatical, semantic/syntactic (functional), communicative approaches, etc. Many linguists consider the prototypical approach to the category of subject to be the most instrumental as it reveals the integrity of denotative and linguistic components of the conceptual category. This approach relates to subject as a source of non-passive predicative feature, an element of subject-predicate-object situation that can take on a variety of semantic roles, cf.: 1) an agent (He carefully surveyed the valley stretching before him), 2) an experiencer (I feel very bitter about this), 3) a recipient (I received this book as a gift), 4) a causee (The plane broke into three pieces), 5) a patient (This stove cleans easily), etc. It is believed that the variety of roles stems from the radial (prototypical) structure of the category with some members more central than others. Translation-wise, the most “treacherous” subject types are the peripheral ones. The paper 1) features a peripheral status of spatial impersonal sentence models such as U menia v ukhe zvenit (lit. I-Gen. in ear buzzes) within the category of semantic subject, 2) makes a structural and semantic analysis of the models, 3) focuses on their Russian-English translation patterns, 4) reveals non-prototypical features of subjects in the English equivalents.

Keywords: bearer of predicative feature, grammatical subject, impersonal sentence model, semantic subject

Procedia PDF Downloads 343
346 Molecular Detection of mRNA bcr-abl and Circulating Leukemic Stem Cells CD34+ in Patients with Acute Lymphoblastic Leukemia and Chronic Myeloid Leukemia and Its Association with Clinical Parameters

Authors: B. Gonzalez-Yebra, H. Barajas, P. Palomares, M. Hernandez, O. Torres, M. Ayala, A. L. González, G. Vazquez-Ortiz, M. L. Guzman

Abstract:

Leukemia arises by molecular alterations of the normal hematopoietic stem cell (HSC) transforming it into a leukemic stem cell (LSC) with high cell proliferation, self-renewal, and cell differentiation. Chronic myeloid leukemia (CML) originates from an LSC-leading to elevated proliferation of myeloid cells and acute lymphoblastic leukemia (ALL) originates from an LSC development leading to elevated proliferation of lymphoid cells. In both cases, LSC can be identified by multicolor flow cytometry using several antibodies. However, to date, LSC levels in peripheral blood (PB) are not established well enough in ALL and CML patients. On the other hand, the detection of the minimal residue disease (MRD) in leukemia is mainly based on the identification of the mRNA bcr-abl gene in CML patients and some other genes in ALL patients. There is no a properly biomarker to detect MDR in both types of leukemia. The objective of this study was to determine mRNA bcr-abl and the percentage of LSC in peripheral blood of patients with CML and ALL and identify a possible association between the amount of LSC in PB and clinical data. We included in this study 19 patients with Leukemia. A PB sample was collected per patient and leukocytes were obtained by Ficoll gradient. The immunophenotype for LSC CD34+ was done by flow cytometry analysis with CD33, CD2, CD14, CD16, CD64, HLA-DR, CD13, CD15, CD19, CD10, CD20, CD34, CD38, CD71, CD90, CD117, CD123 monoclonal antibodies. In addition, to identify the presence of the mRNA bcr-abl by RT-PCR, the RNA was isolated using TRIZOL reagent. Molecular (presence of mRNA bcr-abl and LSC CD34+) and clinical results were analyzed with descriptive statistics and a multiple regression analysis was performed to determine statistically significant association. In total, 19 patients (8 patients with ALL and 11 patients with CML) were analyzed, 9 patients with de novo leukemia (ALL = 6 and CML = 3) and 10 under treatment (ALL = 5 and CML = 5). The overall frequency of mRNA bcr-abl was 31% (6/19), and it was negative in ALL patients and positive in 80% in CML patients. On the other hand, LSC was determined in 16/19 leukemia patients (%LSC= 0.02-17.3). The Novo patients had higher percentage of LSC (0.26 to 17.3%) than patients under treatment (0 to 5.93%). The amount of LSC was significantly associated with the amount of LSC were: absence of treatment, the absence of splenomegaly, and a lower number of leukocytes, negative association for the clinical variables age, sex, blasts, and mRNA bcr-abl. In conclusion, patients with de novo leukemia had a higher percentage of circulating LSC than patients under treatment, and it was associated with clinical parameters as lack of treatment, absence of splenomegaly and a lower number of leukocytes. The mRNA bcr-abl detection was only possible in the series of patients with CML, and molecular detection of LSC could be identified in the peripheral blood of all leukemia patients, we believe the identification of circulating LSC may be used as biomarker for the detection of the MRD in leukemia patients.

Keywords: stem cells, leukemia, biomarkers, flow cytometry

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345 Acupoint Injection of High Concentration of Glucose Attenuates Mice Chronic Pain and Depression Comorbidity

Authors: Chanya Inprasit, Yi-Wen Lin

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Inflammation causes changes of peripheral and central nervous system properties, affecting both neuronal and non-neuronal cells, resulting in inflammatory pain. Acupoint injection (AI) was developed in the 1950s and has been widely used for relieving pain. It is an acupoint-stimulating technique that utilizes anatomically based meridians derived from Chinese medicine theory. AI has been accepted as an effective treatment and is thought to display superior results when compared to traditional acupuncture methods. However, the mechanism of AI needs to be ratified by more scientific evidence in order to support the theory and its therapeutic development. In this study, we explored the effect of AI on the comorbidity of chronic pain and depression. Mice hindpaw was injected by complete Freund’s adjuvant (CFA) to induce the condition of chronic pain. Measurements of mechanical and thermal hyperalgesia and depression-like behavior were analyzed. The results indicated a positive tendency to AI treatment. The comorbidity of chronic pain and depression was investigated with relation to transient receptor potential V1 (TRPV1) mechanism through the use of TRPV1 gene deletion. The expression of nociceptors such as voltage-gated sodium channels (Navs) or TRPV1, was significantly down-regulated by AI. The expression of inflammation-activated molecules: astrocytic marker glial fibrillary acidic protein (GFAP), the microglial marker Iba-1, S100B, and related kinases, were reversed by AI in both the peripheral and central nervous system. Taken together, these data provided a detailed molecular mechanism of AI-induced analgesia and anti-inflammatory properties. This finding may be utilized for clinical practice to treat chronic pain and depression comorbidity.

Keywords: inflammatory pain, acupoint injection, TRPV1, GFAP, S100B

Procedia PDF Downloads 125
344 Clinical Cases of Rare Types of 'Maturity Onset Diabetes of the Young' Diabetes

Authors: Alla Ovsyannikova, Oksana Rymar, Elena Shakhtshneider, Mikhail Voevoda

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In Siberia endocrinologists increasingly noted young patients with the course of diabetes mellitus differing from 1 and 2 types. Therefore we did a molecular genetic study for this group of patients to verify the monogenic forms of diabetes mellitus in them and researched the characteristics of this pathology. When confirming the monogenic form of diabetes, we performed a correction therapy for many patients (transfer from insulin to tablets), prevented specific complications, examined relatives and diagnosed their diabetes at the preclinical stage, revealed phenotypic characteristics of the pathology which led to the high significance of this work. Materials and Methods: We observed 5 patients (4 families). We diagnosed MODY (Maturity Onset Diabetes of the Young) during the molecular genetic testing (direct automatic sequencing). All patients had a full clinical examination, blood samples for biochemical research, determination of C-peptide and TSH, antibodies to b-cells, microalbuminuria, abdominal ultrasound, heart and thyroid ultrasound, examination of ophthalmologist. Results: We diagnosed 3 rare types of MODY: two women had MODY8, one man – MODY6 and man and his mother - MODY12. Patients with types 8 and 12 had clinical features. Age of onset hyperglycemia ranged from 26 to 34 years. In a patient with MODY6 fasting hyperglycemia was detected during a routine examination. Clinical symptoms, complications were not diagnosed. The patient observes a diet. In the first patient MODY8 was detected during first pregnancy, she had itchy skin and mostly postprandial hyperglycemia. Upon examination we determined glycated hemoglobin 7.5%, retinopathy, non-proliferative stage, peripheral neuropathy. She uses a basic bolus insulin therapy. The second patient with MODY8 also had clinical manifestations of hyperglycemia (pruritus, thirst), postprandial hyperglycemia and diabetic nephropathy, a stage of microalbuminuria. The patient was diagnosed autoimmune thyroiditis. She used inhibitors of DPP-4. The patient with MODY12 had an aggressive course. In the detection of hyperglycemia he had complaints of visual impairment, intense headaches, leg cramps. The patient had a history of childhood convulsive seizures of non-epileptic genesis, without organic pathology, which themselves were stopped at the age of 12 years. When we diagnosed diabetes a patient was 28 years, he had hypertriglyceridemia, atherosclerotic plaque in the carotid artery, proliferative retinopathy (lacerocoagulation). Diabetes and early myocardial infarction were observed in three cases in family. We prescribe therapy with sulfonylureas and SGLT-2 inhibitors with a positive effect. At the patient's mother diabetes began at a later age (30 years) and a less aggressive course was observed. She also has hypertriglyceridemia and uses oral hypoglycemic drugs. Conclusions: 1) When young patients with hyperglycemia have extrapancreatic pathologies and diabetic complications with a short duration of diabetes we can assume they have one of type of MODY diabetes. 2) In patients with monogenic forms of diabetes mellitus, the clinical manifestations of hyperglycemia in each succeeding generation are revealed at an earlier age. Research had increased our knowledge of the monogenic forms of diabetes. The reported study was supported by RSCF, research project No. 14-15-00496-P.

Keywords: diabetes mellitus, MODY diabetes, monogenic forms, young patients

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343 Biocompatibility Tests for Chronic Application of Sieve-Type Neural Electrodes in Rats

Authors: Jeong-Hyun Hong, Wonsuk Choi, Hyungdal Park, Jinseok Kim, Junesun Kim

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Identifying the chronic functions of an implanted neural electrode is an important factor in acquiring neural signals through the electrode or restoring the nerve functions after peripheral nerve injury. The purpose of this study was to investigate the biocompatibility of the chronic implanted neural electrode into the sciatic nerve. To do this, a sieve-type neural electrode was implanted at proximal and distal ends of a transected sciatic nerve as an experimental group (Sieve group, n=6), and the end-to-end epineural repair was operated with the cut sciatic nerve as a control group (reconstruction group, n=6). All surgeries were performed on the sciatic nerve of the right leg in Sprague Dawley rats. Behavioral tests were performed before and 1, 4, 7, 10, 14, and weekly days until 5 months following surgery. Changes in sensory function were assessed by measuring paw withdrawal responses to mechanical and cold stimuli. Motor function was assessed by motion analysis using a Qualisys program, which showed a range of motion (ROM) related to the joints. Neurofilament-heavy chain and fibronectin expression were detected 5 months after surgery. In both groups, the paw withdrawal response to mechanical stimuli was slightly decreased from 3 weeks after surgery and then significantly decreased at 6 weeks after surgery. The paw withdrawal response to cold stimuli was increased from 4 days following surgery in both groups and began to decrease from 6 weeks after surgery. The ROM of the ankle joint was showed a similar pattern in both groups. There was significantly increased from 1 day after surgery and then decreased from 4 days after surgery. Neurofilament-heavy chain expression was observed throughout the entire sciatic nerve tissues in both groups. Especially, the sieve group was showed several neurofilaments that passed through the channels of the sieve-type neural electrode. In the reconstruction group, however, a suture line was seen through neurofilament-heavy chain expression up to 5 months following surgery. In the reconstruction group, fibronectin was detected throughout the sciatic nerve. However, in the sieve group, the fibronectin was observed only in the surrounding nervous tissues of an implanted neural electrode. The present results demonstrated that the implanted sieve-type neural electrode induced a focal inflammatory response. However, the chronic implanted sieve-type neural electrodes did not cause any further inflammatory response following peripheral nerve injury, suggesting the possibility of the chronic application of the sieve-type neural electrodes. This work was supported by the Basic Science Research Program funded by the Ministry of Science (2016R1D1A1B03933986), and by the convergence technology development program for bionic arm (2017M3C1B2085303).

Keywords: biocompatibility, motor functions, neural electrodes, peripheral nerve injury, sensory functions

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342 Dietary Flaxseed Decreases Central Blood Pressure and the Concentrations of Plasma Oxylipins Associated with Hypertension in Patients with Peripheral Arterial Disease

Authors: Stephanie PB Caligiuri, Harold M Aukema, Delfin Rodriguez-Leyva, Amir Ravandi, Randy Guzman, Grant N. Pierce

Abstract:

Background: Hypertension leads to cardiac and cerebral events and therefore is the leading risk factor attributed to death in the world. Oxylipins may be mediators in these events as they can regulate vascular tone and inflammation. Oxylipins are derived from fatty acids. Dietary flaxseed is rich in the n3 fatty acid, alpha-linolenic acid, and, therefore, may have the ability to change the substrate profile of oxylipins. As a result, this could alter blood pressure. Methods: A randomized, double-blinded, controlled clinical trial, the Flax-PAD trial, was used to assess the impact of dietary flaxseed on blood pressure (BP), and to also assess the relationship of plasma oxylipins to BP in 81 patients with peripheral arterial disease (PAD). Patients with PAD were chosen for the clinical trial as they are at an increased risk for hypertension and cardiac and cerebral events. Thirty grams of ground flaxseed were added to food products to consume on a daily basis for 6 months. The control food products contained wheat germ, wheat bran, and mixed dietary oils instead of flaxseed. Central BP, which is more significantly associated to organ damage, cardiac, and cerebral events versus brachial BP, was measured by pulse wave analysis at baseline and 6 months. A plasma profile of 43 oxylipins was generated using solid phase extraction, HPLC-MS/MS, and stable isotope dilution quantitation. Results: At baseline, the central BP (systolic/diastolic) in the placebo and flaxseed group were, 131/73 ± 2.5/1.4 mmHg and 128/71 ± 2.6/1.4 mmHg, respectively. After 6 months of intervention, the flaxseed group exhibited a decrease in blood pressure of 4.0/1.0 mmHg. The 6 month central BP in the placebo and flaxseed groups were, 132/74 ± 2.9/1.8 mmHg and 124/70 ± 2.6/1.6 mmHg (P<0.05). Correlation and logistic regression analyses between central blood pressure and oxylipins were performed. Significant associations were observed between central blood pressure and 17 oxylipins, primarily produced from arachidonic acid. Every 1 nM increase in 16-hydroxyeicosatetraenoic acid (HETE) increased the odds of having high central systolic BP by 15-fold, of having high central diastolic BP by 6-fold and of having high central mean arterial pressure by 15-fold. In addition, every 1 nM increase in 5,6-dihydroxyeicosatrienoic acid (DHET) and 11,12-DHET increased the odds of having high central mean arterial pressure by 45- and 18-fold, respectively. Flaxseed induced a significant decrease in these as well as 4 other vasoconstrictive oxylipins. Conclusion: Dietary flaxseed significantly lowered blood pressure in patients with PAD and hypertension. Plasma oxylipins were strongly associated with central blood pressure and may have mediated the flaxseed-induced decrease in blood pressure.

Keywords: hypertension, flaxseed, oxylipins, peripheral arterial disease

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341 Acute Neurophysiological Responses to Resistance Training; Evidence of a Shortened Super Compensation Cycle and Early Neural Adaptations

Authors: Christopher Latella, Ashlee M. Hendy, Dan Vander Westhuizen, Wei-Peng Teo

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Introduction: Neural adaptations following resistance training interventions have been widely investigated, however the evidence regarding the mechanisms of early adaptation are less clear. Understanding neural responses from an acute resistance training session is pivotal in the prescription of frequency, intensity and volume in applied strength and conditioning practice. Therefore the primary aim of this study was to investigate the time course of neurophysiological mechanisms post training against current super compensation theory, and secondly, to examine whether these responses reflect neural adaptations observed with resistance training interventions. Methods: Participants (N=14) completed a randomised, counterbalanced crossover study comparing; control, strength and hypertrophy conditions. The strength condition involved 3 x 5RM leg extensions with 3min recovery, while the hypertrophy condition involved 3 x 12 RM with 60s recovery. Transcranial magnetic stimulation (TMS) and peripheral nerve stimulation were used to measure excitability of the central and peripheral neural pathways, and maximal voluntary contraction (MVC) to quantify strength changes. Measures were taken pre, immediately post, 10, 20 and 30 mins and 1, 2, 6, 24, 48, 72 and 96 hrs following training. Results: Significant decreases were observed at post, 10, 20, 30 min, 1 and 2 hrs for both training groups compared to control group for force, (p <.05), maximal compound wave; (p < .005), silent period; (p < .05). A significant increase in corticospinal excitability; (p < .005) was observed for both groups. Corticospinal excitability between strength and hypertrophy groups was near significance, with a large effect (η2= .202). All measures returned to baseline within 6 hrs post training. Discussion: Neurophysiological mechanisms appear to be significantly altered in the period 2 hrs post training, returning to homeostasis by 6 hrs. The evidence suggests that the time course of neural recovery post resistance training occurs 18-40 hours shorter than previous super compensation models. Strength and hypertrophy protocols showed similar response profiles with current findings suggesting greater post training corticospinal drive from hypertrophy training, despite previous evidence that strength training requires greater neural input. The increase in corticospinal drive and decrease inl inhibition appear to be a compensatory mechanism for decreases in peripheral nerve excitability and maximal voluntary force output. The changes in corticospinal excitability and inhibition are akin to adaptive processes observed with training interventions of 4 wks or longer. It appears that the 2 hr recovery period post training is the most influential for priming further neural adaptations with resistance training. Secondly, the frequency of prescribed resistance sessions can be scheduled closer than previous super compensation theory for optimal strength gains.

Keywords: neural responses, resistance training, super compensation, transcranial magnetic stimulation

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340 Suggested Role for Neutrophil Extracellular Traps Formation in Ewing Sarcoma Immune Microenvironment

Authors: Rachel Shukrun, Szilvia Baron, Victoria Fidel, Anna Shusterman, Osnat Sher, Netanya Kollender, Dror Levin, Yair Peled, Yair Gortzak, Yoav Ben-Shahar, Revital Caspi, Sagi Gordon, Michal Manisterski, Ronit Elhasid

Abstract:

Ewing sarcoma (EWS) is a highly aggressive cancer with a survival rate of 70–80% for patients with localized disease and under 30% for those with metastatic disease. Tumor-infiltrating neutrophils (TIN) can generate extracellular net-like DNA structures known as neutrophil extracellular traps (NETs). However, little is known about the presence and prognostic significance of tumor-infiltrating NETs in EWS. Herein, we investigated 46 patients diagnosed with EWS and treated in the Tel Aviv Medical Center between 2010 and 2021. TINs and NETs were identified in diagnostic biopsies of EWS by immunofluorescent. In addition, NETs were investigated in neutrophils isolated from peripheral blood samples of EWS patients at diagnosis and following neoadjuvant chemotherapy. The relationships between the presence of TINs and NETs, pathological and clinical features, and outcomes were analyzed. Our results demonstrate that TIN and NETs at diagnosis were higher in EWS patients with metastatic disease compared to those with local disease. High NETs formation at diagnosis predicted poor response to neo-adjuvant chemotherapy, relapse, and death from disease (P < .05). NETs formation in peripheral blood samples at diagnosis was significantly elevated among patients with EWS compared to pediatric controls and decreased significantly following neoadjuvant chemotherapy. In conclusion, NETs formation seems to have a role in the EWS immune microenvironment. Their presence can refine risk stratification, predict chemotherapy resistance and survival, and serve as a therapeutic target in patients with EWS.

Keywords: Ewing sarcoma, tumor microenvironment, neutrophil, neutrophil extracellular traps (NETs), prognosis

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339 Signal Processing of the Blood Pressure and Characterization

Authors: Hadj Abd El Kader Benghenia, Fethi Bereksi Reguig

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In clinical medicine, blood pressure, raised blood hemodynamic monitoring is rich pathophysiological information of cardiovascular system, of course described through factors such as: blood volume, arterial compliance and peripheral resistance. In this work, we are interested in analyzing these signals to propose a detection algorithm to delineate the different sequences and especially systolic blood pressure (SBP), diastolic blood pressure (DBP), and the wave and dicrotic to do their analysis in order to extract the cardiovascular parameters.

Keywords: blood pressure, SBP, DBP, detection algorithm

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338 In vitro Modulation of Cytokine Expression by an Aqueous Licorice Extract in Canine

Authors: A. Watson, G. Telford, D. I. Pritchard

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Objective: We investigated the immunomodulatory ability of licorice (Glycyrrhiza glabra). Such activities could have value for the management of common immunological diseases in dogs, such as environmental allergy. This study investigated the potential of a Licorice root extract (LRE) to influence the relative expression of Th-1, Th-2, and Th-17 cytokines in canine peripheral blood mononuclear cells (PBMC). Methods: A LRE was prepared using an alcoholic-aqueous-based solvent method. The extract was tested in three in vitro assays using canine leukocytes to determine its toxicity and immunoregulatory profile. Extract toxicity was assessed using the human T-lymphocyte cell line, Jurkat E6.1. The impact of the extract on the proliferation of concanavalin-activated canine PBMC was also determined. Finally, the extract was assessed for its ability to influence cytokine release in activated PBMC, measuring culture medium concentrations of interleukin-17, interferon gamma, and interleukin-4. One-way ANOVA followed by Dunnett’s post-test was used for statistics using concanavalin positive control as reference (p ≤ 0.05). Results: There was evidence that the LRE had specific immunomodulatory properties, causing significant inhibition of IL4 expression over a non-toxic/non-cytostatic concentration range (p < 0.001). In the same cell incubations, there was no significant impact on IL17 nor IFNg over the same non-toxic/non-cytostatic concentration range. Conclusion: The study provides in vitro evidence that LRE preferentially reduces the expression of a Th-2-type cytokine, IL4. The dog population, as with humans, is prone to conditions associated with a Th-2 bias of the immune system, such as environmental allergy. Based on these results, licorice merits further evaluation as a useful immune modulator for such allergic diseases.

Keywords: cytokine, Glycyrrhiza glabra, peripheral blood mononuclear cells, T-cell activation

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337 Aberrant Genome‐Wide DNA Methylation Profiles of Peripheral Blood Mononuclear Cells from Patients Hospitalized with COVID-19

Authors: Inam Ridha, Christine L. Kuryla, Madhuranga Thilakasiri Madugoda Ralalage Don, Norman J. Kleiman, Yunro Chung, Jin Park, Vel Murugan, Joshua LaBaer

Abstract:

To date, more than 275 million people worldwide have been diagnosed with COVID-19 and the rapid spread of the omicron variant suggests many millions more will soon become infected. Many infections are asymptomatic, while others result in mild to moderate illness. Unfortunately, some infected individuals exhibit more serious symptoms including respiratory distress, thrombosis, cardiovascular disease, multi-organ failure, cognitive difficulties, and, in roughly 2% of cases, death. Studies indicate other coronaviruses can alter the host cell's epigenetic profile and lead to alterations in the immune response. To better understand the mechanism(s) by which SARS-CoV-2 infection causes serious illness, DNA methylation profiles in peripheral blood mononuclear cells (PBMCs) from 90 hospitalized severely ill COVID-19 patients were compared to profiles from uninfected control subjects. Exploratory epigenome-wide DNA methylation analyses were performed using multiplexed methylated DNA immunoprecipitation (MeDIP) followed by pathway enrichment analysis. The findings demonstrated significant DNA methylation changes in infected individuals as compared to uninfected controls. Pathway analysis indicated that apoptosis, cell cycle control, Toll-like receptors (TLR), cytokine interactions, and T cell differentiation were among the most affected metabolic processes. In addition, changes in specific gene methylation were compared to SARS-CoV-2 induced changes in RNA expression using published RNA-seq data from 3 patients with severe COVID-19. These findings demonstrate significant correlations between differentially methylated and differentially expressed genes in a number of critical pathways.

Keywords: COVID19, epigenetics, DNA mathylation, viral infection

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336 Redirection of Cytokine Production Patterns by Dydrogesterone, an Orally-Administered Progestogen

Authors: Raj Raghupathy

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Recurrent Spontaneous Miscarriage (RSM) is a common form of pregnancy loss, 50% of which are due to ‘unexplained’ causes. Evidence exists to suggest that RSM may be caused by immunologic factors such as cytokines which are critical molecules of the immune system, with an impressive array of capabilities. An association appears to exist between Th2-type reactivity (mediated by Th2 or anti-inflammatory cytokines) and normal, successful pregnancy, and between unexplained RSM and Th1 cytokine dominance. If pro-inflammatory cytokines are indeed associated with pregnancy loss, the suppression of these cytokines, and thus the ‘redirection’ of maternal reactivity, may help prevent cytokine-mediated pregnancy loss. The objective of this study was to explore the possibility of modulating cytokine production using Dydrogesterone (Duphaston®), an orally-administered progestogen. Peripheral blood mononuclear cells from 34 women with a history of at least 3 unexplained recurrent miscarriages were stimulated in vitro with a mitogen (to elicit cytokine production) in the presence and absence of dydrogesterone. Levels of selected pro- and anti-inflammatory cytokines produced by peripheral blood mononuclear cells were measured after exposure to these progestogens. Dydrogesterone down-regulates the production of pro-inflammatory cytokines and up-regulates the production of anti-inflammatory cytokines. The ratios of Th2 to Th1 cytokines are markedly elevated in the presence of dydrogesterone, indicating a shift from potentially harmful maternal Th1 reactivity to a more pregnancy-conducive Th2 profile. We used a progesterone receptor antagonist to show that this cytokine-modulating effect of dydrogesterone is mediated via the progesterone receptor. Dydrogesterone also induces the production of the Progesterone-Induced Blocking Factor (PIBF); lymphocytes exposed to PIBF produce higher levels of Th2 cytokines, affecting a Th1 → Th2 cytokine shift which could be favourable to the success of pregnancy. We conclude that modulation of maternal cytokine production profiles is possible with dydrogesterone which has the merits that it can be administered orally and that it is safe.

Keywords: cytokines, dydrogesterone, progesterone, recurrent spontaneous miscarriage

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335 Physiological Effects of Myrrh and Ginseng Extracts in Diabetic Rats

Authors: Ismail I. Abo-Ghanema, Faheim E. Wehaish, Rasha M. Saleh , Walaa F. Awadin, Mohamed F. Elshal

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The antidiabetic activity of myrrh and ginseng ethanolic extracts were investigated in streptozotocin (STZ)-induced diabetic rats. Thirty male albino rats were divided into five groups, each consisted of six rats. The first group (G1) is the negative control that was fed basal diet, the second group (G2) was injected with STZ and received no treatment, the third group (G3) injected with STZ and received metformin (50 mg/kg, b.wt) as standard anti-diabetic drug, the fourth group (G4) injected with STZ and ginseng (50 mg/kg, b.wt), the fifth group (G5) injected with STZ and received myrrh (500 mg/kg, b.wt). As compared with G1-group, STZ injection increased blood concentrations of glucose (6.2 fold), glycated hemoglobin (HbA1c) (2.51 fold), aspartateaminotransferase (AST), and alanine aminotransferase (ALT) (2.64, 4.60 fold respectively), creatinine (2.91 fold), cholesterol (1.79 fold), triglycerides (2.06 fold), low density lipoprotein-cholesterol (LDL) (2.92 fold), nitric oxide (NO) (20.18 fold), and malondialdehyde (MDA) (2.25 fold), whereas it decreased blood insulin (0.40 fold), albumin (0.60 fold), high density lipoprotein-cholesterol (HDL) (0.33 fold), and reduced glutathione (GSH) (0.49 fold). Vascular permeability index (VPI as measured by Evan's Blue; EB extravasations test) was significantly increased in the skin of diabetic animals (9.6 fold) when compared with the G1-group. In addition, histological alterations in liver, pancreas, kidneys and heart were observed. After 4 weeks of treatment, rats in G4 and G5 showed significant corrections in the all measured parameters and indices. In conclusions, the ethanolic extracts of ginseng and myrrh exhibited promising and safe anti-diabetic activity especially on peripheral circulation as manifested by decreased vascular permeability and improved histopathological alterations of examined organs and insulin secretion. Hence, it may be pursued for their clinical usefulness in the management of diabetes mellitus (DM) and associated vascular complications.

Keywords: diabetic rats, peripheral circulation, natural plants, myrrh, ginseng

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334 Analysis of NMDA Receptor 2B Subunit Gene (GRIN2B) mRNA Expression in the Peripheral Blood Mononuclear Cells of Alzheimer's Disease Patients

Authors: Ali̇ Bayram, Semih Dalkilic, Remzi Yigiter

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N-methyl-D-aspartate (NMDA) receptor is a subtype of glutamate receptor and plays a pivotal role in learning, memory, neuronal plasticity, neurotoxicity and synaptic mechanisms. Animal experiments were suggested that glutamate-induced excitotoxic injuriy and NMDA receptor blockage lead to amnesia and other neurodegenerative diseases including Alzheimer’s disease (AD), Huntington’s disease, amyotrophic lateral sclerosis. Aim of this study is to investigate association between NMDA receptor coding gene GRIN2B expression level and Alzheimer disease. The study was approved by the local ethics committees, and it was conducted according to the principles of the Declaration of Helsinki and guidelines for the Good Clinical Practice. Peripheral blood was collected 50 patients who diagnosed AD and 49 healthy control individuals. Total RNA was isolated with RNeasy midi kit (Qiagen) according to manufacturer’s instructions. After checked RNA quality and quantity with spectrophotometer, GRIN2B expression levels were detected by quantitative real time PCR (QRT-PCR). Statistical analyses were performed, variance between two groups were compared with Mann Whitney U test in GraphpadInstat algorithm with 95 % confidence interval and p < 0.05. After statistical analyses, we have determined that GRIN2B expression levels were down regulated in AD patients group with respect to control group. But expression level of this gene in each group was showed high variability. İn this study, we have determined that NMDA receptor coding gene GRIN2B expression level was down regulated in AD patients when compared with healthy control individuals. According to our results, we have speculated that GRIN2B expression level was associated with AD. But it is necessary to validate these results with bigger sample size.

Keywords: Alzheimer’s disease, N-methyl-d-aspartate receptor, NR2B, GRIN2B, mRNA expression, RT-PCR

Procedia PDF Downloads 367
333 Cytotoxicity and Genotoxicity of Glyphosate and Its Two Impurities in Human Peripheral Blood Mononuclear Cells

Authors: Marta Kwiatkowska, Paweł Jarosiewicz, Bożena Bukowska

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Glyphosate (N-phosphonomethylglycine) is a non-selected broad spectrum ingredient in the herbicide (Roundup) used for over 35 years for the protection of agricultural and horticultural crops. Glyphosate was believed to be environmentally friendly but recently, a large body of evidence has revealed that glyphosate can negatively affect on environment and humans. It has been found that glyphosate is present in the soil and groundwater. It can also enter human body which results in its occurrence in blood in low concentrations of 73.6 ± 28.2 ng/ml. Research conducted for potential genotoxicity and cytotoxicity can be an important element in determining the toxic effect of glyphosate. Due to regulation of European Parliament 1107/2009 it is important to assess genotoxicity and cytotoxicity not only for the parent substance but also its impurities, which are formed at different stages of production of major substance – glyphosate. Moreover verifying, which of these compounds are more toxic is required. Understanding of the molecular pathways of action is extremely important in the context of the environmental risk assessment. In 2002, the European Union has decided that glyphosate is not genotoxic. Unfortunately, recently performed studies around the world achieved results which contest decision taken by the committee of the European Union. World Health Organization (WHO) in March 2015 has decided to change the classification of glyphosate to category 2A, which means that the compound is considered to "probably carcinogenic to humans". This category relates to compounds for which there is limited evidence of carcinogenicity to humans and sufficient evidence of carcinogenicity on experimental animals. That is why we have investigated genotoxicity and cytotoxicity effects of the most commonly used pesticide: glyphosate and its impurities: N-(phosphonomethyl)iminodiacetic acid (PMIDA) and bis-(phosphonomethyl)amine on human peripheral blood mononuclear cells (PBMCs), mostly lymphocytes. DNA damage (analysis of DNA strand-breaks) using the single cell gel electrophoresis (comet assay) and ATP level were assessed. Cells were incubated with glyphosate and its impurities: PMIDA and bis-(phosphonomethyl)amine at concentrations from 0.01 to 10 mM for 24 hours. Evaluating genotoxicity using the comet assay showed a concentration-dependent increase in DNA damage for all compounds studied. ATP level was decreased to zero as a result of using the highest concentration of two investigated impurities, like bis-(phosphonomethyl)amine and PMIDA. Changes were observed using the highest concentration at which a person can be exposed as a result of acute intoxication. Our survey leads to a conclusion that the investigated compounds exhibited genotoxic and cytotoxic potential but only in high concentrations, to which people are not exposed environmentally. Acknowledgments: This work was supported by the Polish National Science Centre (Contract-2013/11/N/NZ7/00371), MSc Marta Kwiatkowska, project manager.

Keywords: cell viability, DNA damage, glyphosate, impurities, peripheral blood mononuclear cells

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332 Tracking of Intramuscular Stem Cells by Magnetic Resonance Diffusion Weighted Imaging

Authors: Balakrishna Shetty

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Introduction: Stem Cell Imaging is a challenging field since the advent of Stem Cell treatment in humans. Series of research on tagging and tracking the stem cells has not been very effective. The present study is an effort by the authors to track the stem cells injected into calf muscles by Magnetic Resonance Diffusion Weighted Imaging. Materials and methods: Stem Cell injection deep into the calf muscles of patients with peripheral vascular disease is one of the recent treatment modalities followed in our institution. 5 patients who underwent deep intramuscular injection of stem cells as treatment were included for this study. Pre and two hours Post injection MRI of bilateral calf regions was done using 1.5 T Philips Achieva, 16 channel system using 16 channel torso coils. Axial STIR, Axial Diffusion weighted images with b=0 and b=1000 values with back ground suppression (DWIBS sequence of Philips MR Imaging Systems) were obtained at 5 mm interval covering the entire calf. The invert images were obtained for better visualization. 120ml of autologous bone marrow derived stem cells were processed and enriched under c-GMP conditions and reduced to 40ml solution containing mixture of above stem cells. Approximately 40 to 50 injections, each containing 0.75ml of processed stem cells, was injected with marked grids over the calf region. Around 40 injections, each of 1ml normal saline, is injected into contralateral leg as control. Results: Significant Diffusion hyper intensity is noted at the site of injected stem cells. No hyper intensity noted before the injection and also in the control side where saline was injected conclusion: This is one of the earliest studies in literature showing diffusion hyper intensity in intramuscularly injected stem cells. The advantages and deficiencies in this study will be discussed during the presentation.

Keywords: stem cells, imaging, DWI, peripheral vascular disease

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331 Accumulation of Pollutants, Self-Purification and Impact on Peripheral Urban Areas: A Case Study in Shantytowns in Argentina

Authors: N. Porzionato, M. Mantiñan, E. Bussi, S. Grinberg, R. Gutierrez, G. Curutchet

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This work sets out to debate the tensions involved in the processes of contamination and self-purification in the urban space, particularly in the streams that run through the Buenos Aires metropolitan area. For much of their course, those streams are piped; their waters do not come into contact with the outdoors until they have reached deeply impoverished urban areas with high levels of environmental contamination. These are peripheral zones that, until thirty years ago, were marshlands and fields. They are now densely populated areas largely lacking in urban infrastructure. The Cárcova neighborhood, where this project is underway, is in the José León Suárez section of General San Martín country, Buenos Aires province. A stretch of José León Suarez canal crosses the neighborhood. Starting upstream, this canal carries pollutants due to the sewage and industrial waste released into it. Further downstream, in the neighborhood, domestic drainage is poured into the stream. In this paper, we formulate a hypothesis diametrical to the one that holds that these neighborhoods are the primary source of contamination, suggesting instead that in the stretch of the canal that runs through the neighborhood the stream’s waters are actually cleaned and the sediments accumulate pollutants. Indeed, the stretches of water that runs through these neighborhoods act as water processing plants for the metropolis. This project has studied the different organic-load polluting contributions to the water in a certain stretch of the canal, the reduction of that load over the course of the canal, and the incorporation of pollutants into the sediments. We have found that the surface water has considerable ability to self-purify, mostly due to processes of sedimentation and adsorption. The polluting load is accumulated in the sediments where that load stabilizes slowly by means of anaerobic processes. In this study, we also investigated the risks of sediment management and the use of the processes studied here in controlled conditions as tools of environmental restoration.

Keywords: bioremediation, pollutants, sediments, urban streams

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330 Bio-Functionalized Silk Nanofibers for Peripheral Nerve Regeneration

Authors: Kayla Belanger, Pascale Vigneron, Guy Schlatter, Bernard Devauchelle, Christophe Egles

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A severe injury to a peripheral nerve leads to its degeneration and the loss of sensory and motor function. To this day, there still lacks a more effective alternative to the autograft which has long been considered the gold standard for nerve repair. In order to overcome the numerous drawbacks of the autograft, tissue engineered biomaterials may be effective alternatives. Silk fibroin is a favorable biomaterial due to its many advantageous properties such as its biocompatibility, its biodegradability, and its robust mechanical properties. In this study, bio-mimicking multi-channeled nerve guidance conduits made of aligned nanofibers achieved by electrospinning were functionalized with signaling biomolecules and were tested in vitro and in vivo for nerve regeneration support. Silk fibroin (SF) extracted directly from silkworm cocoons was put in solution at a concentration of 10wt%. Poly(ethylene oxide) (PEO) was added to the resulting SF solution to increase solution viscosity and the following three electrospinning solutions were made: (1) SF/PEO solution, (2) SF/PEO solution with nerve growth factor and ciliary neurotrophic factor, and (3) SF/PEO solution with nerve growth factor and neurotrophin-3. Each of these solutions was electrospun into a multi-layer architecture to obtain mechanically optimized aligned nanofibrous mats. For in vitro studies, aligned fibers were treated to induce β-sheet formation and thoroughly rinsed to eliminate presence of PEO. Each material was tested using rat embryo neuron cultures to evaluate neurite extension and the interaction with bio-functionalized or non-functionalized aligned fibers. For in vivo studies, the mats were rolled into 5mm long multi-, micro-channeled conduits then treated and thoroughly rinsed. The conduits were each subsequently implanted between a severed rat sciatic nerve. The effectiveness of nerve repair over a period of 8 months was extensively evaluated by cross-referencing electrophysiological, histological, and movement analysis results to comprehensively evaluate the progression of nerve repair. In vitro results show a more favorable interaction between growing neurons and bio-functionalized silk fibers compared to pure silk fibers. Neurites can also be seen having extended unidirectionally along the alignment of the nanofibers which confirms a guidance factor for the electrospun material. The in vivo study has produced positive results for the regeneration of the sciatic nerve over the length of the study, showing contrasts between the bio-functionalized material and the non-functionalized material along with comparisons to the experimental control. Nerve regeneration has been evaluated not only by histological analysis, but also by electrophysiological assessment and motion analysis of two separate natural movements. By studying these three components in parallel, the most comprehensive evaluation of nerve repair for the conduit designs can be made which can, therefore, more accurately depict their overall effectiveness. This work was supported by La Région Picardie and FEDER.

Keywords: electrospinning, nerve guidance conduit, peripheral nerve regeneration, silk fibroin

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329 Designing Stochastic Non-Invasively Applied DC Pulses to Suppress Tremors in Multiple Sclerosis by Computational Modeling

Authors: Aamna Lawrence, Ashutosh Mishra

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Tremors occur in 60% of the patients who have Multiple Sclerosis (MS), the most common demyelinating disease that affects the central and peripheral nervous system, and are the primary cause of disability in young adults. While pharmacological agents provide minimal benefits, surgical interventions like Deep Brain Stimulation and Thalamotomy are riddled with dangerous complications which make non-invasive electrical stimulation an appealing treatment of choice for dealing with tremors. Hence, we hypothesized that if the non-invasive electrical stimulation parameters (mainly frequency) can be computed by mathematically modeling the nerve fibre to take into consideration the minutest details of the axon morphologies, tremors due to demyelination can be optimally alleviated. In this computational study, we have modeled the random demyelination pattern in a nerve fibre that typically manifests in MS using the High-Density Hodgkin-Huxley model with suitable modifications to account for the myelin. The internode of the nerve fibre in our model could have up to ten demyelinated regions each having random length and myelin thickness. The arrival time of action potentials traveling the demyelinated and the normally myelinated nerve fibre between two fixed points in space was noted, and its relationship with the nerve fibre radius ranging from 5µm to 12µm was analyzed. It was interesting to note that there were no overlaps between the arrival time for action potentials traversing the demyelinated and normally myelinated nerve fibres even when a single internode of the nerve fibre was demyelinated. The study gave us an opportunity to design DC pulses whose frequency of application would be a function of the random demyelination pattern to block only the delayed tremor-causing action potentials. The DC pulses could be delivered to the peripheral nervous system non-invasively by an electrode bracelet that would suppress any shakiness beyond it thus paving the way for wearable neuro-rehabilitative technologies.

Keywords: demyelination, Hodgkin-Huxley model, non-invasive electrical stimulation, tremor

Procedia PDF Downloads 104
328 Gender Justice and Feminist Self-Management Practices in the Solidarity Economy: A Quantitative Analysis of the Factors that Impact Enterprises Formed by Women in Brazil

Authors: Maria de Nazaré Moraes Soares, Silvia Maria Dias Pedro Rebouças, José Carlos Lázaro

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The Solidarity Economy (SE) acts in the re-articulation of the economic field to the other spheres of social action. The significant participation of women in SE resulted in the formation of a national network of self-managed enterprises in Brazil: The Solidarity and Feminist Economy Network (SFEN). The objective of the research is to identify factors of gender justice and feminist self-management practices that adhere to the reality of women in SE enterprises. The conceptual apparatus related to feminist studies in this research covers Nancy Fraser approaches on gender justice, and Patricia Yancey Martin approaches on feminist management practices, and authors of postcolonial feminism such as Mohanty and Maria Lugones, who lead the discussion to peripheral contexts, a necessary perspective when observing the women’s movement in SE. The research has a quantitative nature in the phases of data collection and analysis. The data collection was performed through two data sources: the database mapped in Brazil in 2010-2013 by the National Information System in Solidary Economy and 150 questionnaires with women from 16 enterprises in SFEN, in a state of Brazilian northeast. The data were analyzed using the multivariate statistical technique of Factor Analysis. The results show that the factors that define gender justice and feminist self-management practices in SE are interrelated in several levels, proving statistically the intersectional condition of the issue of women. The evidence from the quantitative analysis allowed us to understand the dimensions of gender justice and feminist management practices intersectionality; in this sense, the non-distribution of domestic work interferes in non-representation of women in public spaces, especially in peripheral contexts. The study contributes with important reflections to the studies of this area and can be complemented in the future with a qualitative research that approaches the perspective of women in the context of the SE self-management paradigm.

Keywords: feminist management practices, gender justice, self-management, solidarity economy

Procedia PDF Downloads 103
327 Rapid Detection of the Etiology of Infection as Bacterial or Viral Using Infrared Spectroscopy of White Blood Cells

Authors: Uraib Sharaha, Guy Beck, Joseph Kapelushnik, Adam H. Agbaria, Itshak Lapidot, Shaul Mordechai, Ahmad Salman, Mahmoud Huleihel

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Infectious diseases cause a significant burden on the public health and the economic stability of societies all over the world for several centuries. A reliable detection of the causative agent of infection is not possible based on clinical features, since some of these infections have similar symptoms, including fever, sneezing, inflammation, vomiting, diarrhea, and fatigue. Moreover, physicians usually encounter difficulties in distinguishing between viral and bacterial infections based on symptoms. Therefore, there is an ongoing need for sensitive, specific, and rapid methods for identification of the etiology of the infection. This intricate issue perplex doctors and researchers since it has serious repercussions. In this study, we evaluated the potential of the mid-infrared spectroscopic method for rapid and reliable identification of bacterial and viral infections based on simple peripheral blood samples. Fourier transform infrared (FTIR) spectroscopy is considered a successful diagnostic method in the biological and medical fields. Many studies confirmed the great potential of the combination of FTIR spectroscopy and machine learning as a powerful diagnostic tool in medicine since it is a very sensitive method, which can detect and monitor the molecular and biochemical changes in biological samples. We believed that this method would play a major role in improving the health situation, raising the level of health in the community, and reducing the economic burdens in the health sector resulting from the indiscriminate use of antibiotics. We collected peripheral blood samples from young 364 patients, of which 93 were controls, 126 had bacterial infections, and 145 had viral infections, with ages lower than18 years old, limited to those who were diagnosed with fever-producing illness. Our preliminary results showed that it is possible to determine the infectious agent with high success rates of 82% for sensitivity and 80% for specificity, based on the WBC data.

Keywords: infectious diseases, (FTIR) spectroscopy, viral infections, bacterial infections.

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326 Promoter Methylation of RASSF1A and MGMT Genes in Head and Neck Squamous Cell Carcinoma

Authors: Vitor Rafael Regiani, Carlos Henrique Viesi Do Nascimento Filho, Patricia Matos Biselli-Chicote, Claudia Aparecida Rainho, Luiz Sergio Raposo, José Victor Maniglia, Eny Maria Goloni-Bertollo, Erika Cristina Pavarino

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Promoter hypermethylation of tumor-related genes has been associated with prognosis in early-stage head-and-neck cancers, providing strong evidence that these hypermethylated genes are valuable biomarkers for prognostic evaluation. Hence, we selected the MGMT and RASSF1A genes to examine the methylation status in head and neck squamous cell carcinomas (HNSCC) samples matched with non-tumor tissues (tumor-surrounding tissues or peripheral blood samples). DNA methylation analysis was based on Methylation-Sensitive High Resolution Melting, and the methylation status was correlated with clinic-pathological characteristics of the patients. RASSF1A and MGMT promoter methylation was detected in 43.24% (16/37) and in 44.44% (16/36) of the tumors, respectively. RASSF1A and MGMT methylation was significantly more frequent in tumor tissue than non-tumor tissues, as well as, simultaneous methylation of RASSF1A and MGMT also was higher in tumor tissue than non-tumor tissues. In relation to anatomic site, larynx cancer presented significant methylation of MGMT gene compared to tumor-surrounding tissue. The frequency of RASSF1A and MGMT promoter methylated was higher in tumor tissues in relation to peripheral blood from the same patient. No association was found between methylation and the variables analyzed, including gender, age, smoking or alcohol drinking habits. Clinic-pathological characteristics also showed no association in the presence of methylation. The Kaplan–Meier's method showed no association of methylation and both disease-free and overall survival. In conclusion, the presence of epigenetic abnormalities in normal-appearing tissue corroborates the hypothesis of the ‘field cancerization', or it can reflect preneoplastic and/or preinvasive. Moreover, MGMT methylation may serve as an important laryngeal cancer biomarker because it showed significant difference between laryngeal cancer and surrounding tumor tissues.

Keywords: head and neck cancer, DNA methylation, MGMT promoter methylation, RASSF1A promoter methylation

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325 A Study on The Relationship between Building Façade and Solar Energy Utilization Potential in Urban Residential Area in West China

Authors: T. Wen, Y. Liu, J. Wang, W. Zheng, T. Shao

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Along with the increasing density of urban population, solar energy potential of building facade in high-density residential areas become a question that needs to be addressed. This paper studies how the solar energy utilization potential of building facades in different locations of a residential areas changes with different building layouts and orientations in Xining, a typical city in west China which possesses large solar radiation resource. Solar energy potential of three typical building layouts of residential areas, which are parallel determinant, gable misalignment, transverse misalignment, are discussed in detail. First of all, through the data collection and statistics of Xining new residential area, the most representative building parameters are extracted, including building layout, building height, building layers, and building shape. Secondly, according to the results of building parameters extraction, a general model is established and analyzed with rhinoceros 6.0 and its own plug-in grasshopper. Finally, results of the various simulations and data analyses are presented in a visualized way. The results show that there are great differences in the solar energy potential of building facades in different locations of residential areas under three typical building layouts. Generally speaking, the solar energy potential of the west peripheral location is the largest, followed by the East peripheral location, and the middle location is the smallest. When the deflection angle is the same, the solar energy potential shows the result that the West deflection is greater than the East deflection. In addition, the optimal building azimuth range under these three typical building layouts is obtained. Within this range, the solar energy potential of the residential area can always maintain a high level. Beyond this range, the solar energy potential drops sharply. Finally, it is found that when the solar energy potential is maximum, the deflection angle is not positive south, but 5 °or 15°south by west. The results of this study can provide decision analysis basis for residential design of Xining city to improve solar energy utilization potential and provide a reference for solar energy utilization design of urban residential buildings in other similar areas.

Keywords: building facade, solar energy potential, solar radiation, urban residential area, visualization, Xining city

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324 Assessing the Quality of Maternity Care in Sub-Saharan Africa Using the Donabedian Quality of Care Framework: A Systematic Scoping Review

Authors: Bernice Boafoaa Gyapong, Anne Jones, Sam Bassett, Janet Anderson

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Background: Maternal mortality and morbidity are global concerns, especially in sub-Saharan Africa (SSA). Most maternal mortalities occur at the time of birth. Quality intrapartum care is essential for improving maternal and newborn health outcomes. This scoping review aimed to assess and describe the quality of care during childbirth in SSA to provide an overview of the regional trend of the quality of intrapartum care, the challenges to quality care provision, and identify research gaps. Methods: A scoping review based on Arksey and O’Malley’s scoping review framework was conducted. Medline, CINAHL, PsycINFO, and maternal-infant databases were searched to identify the relevant studies for this review. A narrative summary was presented using themes based on the Donabedian structure, process, and outcome quality of care model. Results: A total of five hundred and forty-seven (547) publications were identified. Fifty-six (56) studies conducted in twenty (20) countries were included in the review. Thirty-four (34) were quantitative, sixteen (16) were qualitative, and six (6) were mixed methods. Most of the studies were related to the process component of quality of care. The provision of emergency obstetric care services, infrastructure, and availability of essential staff and equipment for perinatal care was inadequate in many facilities, particularly rural and peripheral health facilities. Many women experienced disrespectful care during childbirth. Routine care during labour and delivery was observed to be sub-optimal, yet some women reported high satisfaction with care. The use of health facilities for delivery was lower in health centres compared to hospitals. Conclusion: There are variations in the quality of maternity care provided in SSA. Intrapartum care quality is generally deficient in SSA, particularly in peripheral health facilities, health centres, and community clinics. Many of the quality-of-care issues identified are related to the structure component. Stakeholders must develop interventions that comprehensively address these interrelated issues to improve maternal healthcare quality, especially in primary healthcare facilities.

Keywords: quality of care, maternity health, Sub-Saharan Africa, intrapartum

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323 Investigation of Mutagenicity and DNA Binding Properties of Metal-Free and Metallophthalocyanines Containing α-Napththolbenzein Groups on the Peripheral Positions

Authors: Meltem Betül Sağlam, Halil İbrahim Güler, Aykut Sağlam

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In this work, phthalocyanine compounds containing α-naphtholbenzeinunits have been synthesized. Mutagenicity and DNA binding properties of the compounds were investigated by Salmonella/Microsome Assay and spectrophotometer. According to the results of the preliminary range finding tests, the compounds gave no toxic effect to all tester strain S. typhimurium TA98 and TA100 at doses of 500, 1100, 350, 500 and 750 µg/plate in the presence and absence of S9, respectively. This study showed that all compounds exhibited efficient DNA-binding activity. In conclusion, these non-toxic compounds may be used as effective DNA dyes for molecular biology studies.

Keywords: dye, mutagenicity, phthalocyanine, toxicity

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322 A 30 Year Audit of the Vascular Complications of Ports: Permanent Intravascular Access Devices

Authors: S. Kershaw, P. J. Barry, K. Webb

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Background: Cystic Fibrosis (CF) is a chronic lung disease where patients have chronic lung infection punctuated by acute exacerbations that require intermittent intravenous (IV) antibiotics during their lives. With time, peripheral venous access can become difficult and limited. Accessing these veins can become arduous, traumatic, painful and unworkable. A permanent intravascular access device or Port is a small device that is inserted into the central venous system that allows the delivery of medicine eliminating the need for peripheral venous access. Ports represent a convenient and efficient method when venous access is required on a permanent basis however they are also associated with significant vascular complications. Superior Vena Cava Obstruction (SVCO) is a rare but significant vascular complication of ports in this setting. Objective: We aimed to look at a single CF centre’s experience of port-related SVCO over a thirty year period. Methods: Retrospective data was extracted using patient’s notes, electronic radiological reports and local databases over a period in excess of 30 years from 1982 to 2014. Results: 13 patients were identified with SVCO as a result of their port. 11 patients had CF (9 female, 2 male), one male patient had Primary Ciliary Dyskinesia and one female patient had severe Asthma. The mean port function was 1532 days (range 110 – 4049) and the mean age at SVCO was 24 years (range 11.1 to 36.5 years). The most common symptoms were facial oedema (n=8, 61.5%) and dilated veins (n=6, 46.2%). 7 patients had their Ports removed after SVCO. 6 patients underwent attempted stenting (46.2%) and 6 did not. 4 out of the 6 who underwent stenting required/had re-intervention. 3 of the 6 patients who underwent stenting had symptom resolution, however, 4 of the 6 patients who were not stented had symptom resolution also. Symptom resolution was not guaranteed with stenting and required re-intervention in two-thirds. Conclusion: This case series represents the experience of one of the longest established CF units in the UK and represents the largest cohort ever reported in the literature.

Keywords: ports, Superior Vena Cava Obstruction, cystic fibrosis, access devices

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321 A Dynamic Model for Assessing the Advanced Glycation End Product Formation in Diabetes

Authors: Victor Arokia Doss, Kuberapandian Dharaniyambigai, K. Julia Rose Mary

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Advanced Glycation End (AGE) products are the end products due to the reaction between excess reducing sugar present in diabetes and free amino group in protein lipids and nucleic acids. Thus, non-enzymic glycation of molecules such as hemoglobin, collagen, and other structurally and functionally important proteins add to the pathogenic complications such as diabetic retinopathy, neuropathy, nephropathy, vascular changes, atherosclerosis, Alzheimer's disease, rheumatoid arthritis, and chronic heart failure. The most common non-cross linking AGE, carboxymethyl lysine (CML) is formed by the oxidative breakdown of fructosyllysine, which is a product of glucose and lysine. CML is formed in a wide variety of tissues and is an index to assess the extent of glycoxidative damage. Thus we have constructed a mathematical and computational model that predicts the effect of temperature differences in vivo, on the formation of CML, which is now being considered as an important intracellular milieu. This hybrid model that had been tested for its parameter fitting and its sensitivity with available experimental data paves the way for designing novel laboratory experiments that would throw more light on the pathological formation of AGE adducts and in the pathophysiology of diabetic complications.

Keywords: advanced glycation end-products, CML, mathematical model, computational model

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320 A Framework for Consumer Selection on Travel Destinations

Authors: J. Rhodes, V. Cheng, P. Lok

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The aim of this study is to develop a parsimonious model that explains the effect of different stimulus on a tourist’s intention to visit a new destination. The model consists of destination trust and interest as the mediating variables. The model was tested using two different types of stimulus; both studies empirically supported the proposed model. Furthermore, the first study revealed that advertising has a stronger effect than positive online reviews. The second study found that the peripheral route of the elaboration likelihood model has a stronger influence power than the central route in this context.

Keywords: advertising, electronic word-of-mouth, elaboration likelihood model, intention to visit, trust

Procedia PDF Downloads 435