Search results for: ovarian stimulation

Authors: R. P. Hewawasam, M. H. A. D. de Silva, M. A. G. Iresha

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Obesity is associated with an increased risk of developing insulin resistance. Insulin resistance often progresses to type-2 diabetes mellitus and is linked to a wide variety of other pathophysiological features including hypertension, hyperlipidemia, atherosclerosis (metabolic syndrome) and polycystic ovarian syndrome. Macrosomia is common in infants born to not only women with gestational diabetes mellitus but also non-diabetic obese women. During the past two decades, obesity in children and adolescents has risen significantly in Asian populations including Sri Lanka. There is increasing evidence to believe that infants who are born large for gestational age (LGA) are more likely to be obese in childhood. It is also established from previous studies that Asian populations have higher percentage body fat at a lower body mass index compared to Caucasians. High leptin levels in cord blood have been reported to correlate with fetal adiposity at birth. Previous studies have also shown that cord blood C-peptide and insulin levels are significantly and positively correlated with birth weight. Therefore, the objective of this preliminary study was to determine the relationship between parameters of fetal insulin resistance such as leptin, C-peptide and insulin and the birth weight of the newborn in a study population in Southern Sri Lanka. Umbilical cord blood was collected from 90 newborns and the concentration of insulin, leptin, and C-peptide were measured by ELISA technique. Birth weight, length, occipital frontal, chest, hip and calf circumferences of newborns were measured and characteristics of the mother such as age, height, weight before pregnancy and weight gain were collected. The relationship between insulin, leptin, C-peptide, and anthropometrics were assessed by Pearson’s correlation while the Mann-Whitney U test was used to assess the differences in cord blood leptin, C-peptide, and insulin levels between groups. A significant difference (p < 0.001) was observed between the insulin levels of infants born LGA (18.73 ± 0.64 µlU/ml) and AGA (13.08 ± 0.43 µlU/ml). Consistently, A significant increase in concentration (p < 0.001) was observed in C-peptide levels of infants born LGA (9.32 ± 0.77 ng/ml) compared to AGA (5.44 ± 0.19 ng/ml). Cord blood leptin concentration of LGA infants (12.67 ng/mL ± 1.62) was significantly higher (p < 0.001) compared to the AGA infants (7.10 ng/mL ± 0.97). Significant positive correlations (p < 0.05) were observed among cord leptin levels and the birth weight, pre-pregnancy maternal weight and BMI between the infants of AGA and LGA. Consistently, a significant positive correlation (p < 0.05) was observed between the birth weight and the C peptide concentration. Significantly high concentrations of leptin, C-peptide and insulin levels in the cord blood of LGA infants suggest that they may be involved in regulating fetal growth. Although previous studies suggest comparatively high levels of body fat in the Asian population, values obtained in this study are not significantly different from values previously reported from Caucasian populations. According to this preliminary study, maternal pre-pregnancy BMI and weight may contribute as significant indicators of cord blood parameters of insulin resistance and possibly the birth weight of the newborn.

Keywords: large for gestational age, leptin, C-peptide, insulin

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Authors: Joanna Estkowska

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Sensory integration methods are very useful and improve daily functioning autistic and mentally disabled children. Autism is a neurobiological disorder that impairs one's ability to communicate with and relate to others as well as their sensory system. Children with autism, even highly functioning kids, can find it difficult to process language with surrounding noise or smells. They are hypersensitive to things we can ignore such as sight, sounds and touch. Adolescents with highly functioning autism or Asperger Syndrome can study Science and Math but the social aspect is difficult for them. Nature science is an area of study that attracts many of these kids. It is a systematic field in which the children can focus on a small aspect. If you follow these rules you can come up with an expected result. Sensory integration program and systematic classroom observation are quantitative methods of measuring classroom functioning and behaviors from direct observations. These methods specify both the events and behaviors that are to be observed and how they are to be recorded. Our students with and without autism attended the lessons in the classroom of nature science in the school and in the laboratory of University of Science and Technology in Bydgoszcz. The aim of this study is investigation the effects of sensory integration methods in teaching to students with autism. They were observed during experimental lessons in the classroom and in the laboratory. Their physical characteristics, sensory dysfunction, and behavior in class were taken into consideration by comparing their similarities and differences. In the chemistry classroom, every autistic student is paired with a mentor from their school. In the laboratory, the children are expected to wear goggles, gloves and a lab coat. The chemistry classes in the laboratory were held for four hours with a lunch break, and according to the assistants, the children were engaged the whole time. In classroom of nature science, the students are encouraged to use the interactive exhibition of chemical, physical and mathematical models constructed by the author of this paper. Our students with and without autism attended the lessons in those laboratories. The teacher's goals are: to assist the child in inhibiting and modulating sensory information and support the child in processing a response to sensory stimulation.

Keywords: autism spectrum disorder, science education, sensory integration techniques, student with special educational needs

Procedia PDF Downloads 192

Authors: Ashleigh Beales, Anne Whitworth, Jade Cartwright

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Background: While significant benefits of lexical retrieval intervention are evident within the Primary Progressive Aphasia (PPA) and Alzheimer’s disease (AD) literature, an understanding of the mechanisms that underlie change or improvement is limited. Change mechanisms have been explored in the non-progressive post-stroke literature that may offer insight into how interventions affect change with progressive language disorders. The potential influences of cognitive factors may also play a role here, interacting with the aims of intervention. Exploring how such processes have been applied is likely to grow our understanding of how interventions have, or have not, been effective, and how and why generalisation is likely, or not, to occur. Aims: This review of the literature aimed to (1) investigate the proposed mechanisms of change which underpin lexical interventions, mapping the PPA and AD lexical retrieval literature to theoretical accounts of mechanisms that underlie change within the broader intervention literature, (2) identify whether and which nonlinguistic cognitive functions have been engaged in intervention with these populations and any proposed influence, and (3) explore evidence of linguistic generalisation, with particular reference to change mechanisms employed in interventions. Main contribution: A search of Medline, PsycINFO, and CINAHL identified 36 articles that reported data for individuals with PPA or AD following lexical retrieval intervention. A review of the mechanisms of change identified 10 studies that used stimulation, 21 studies utilised relearning, three studies drew on reorganisation, and two studies used cognitive-relay. Significant treatment gains, predominantly based on linguistic performance measures, were reported for all client groups for each of the proposed mechanisms. Reorganisation and cognitive-relay change mechanisms were only targeted in PPA. Eighteen studies incorporated nonlinguistic cognitive functions in intervention; these were limited to autobiographical memory (16 studies), episodic memory (three studies), or both (one study). Linguistic generalisation outcomes were inconsistently reported in PPA and AD studies. Conclusion: This review highlights that individuals with PPA and AD may benefit from lexical retrieval intervention, irrespective of the mechanism of change. Thorough application of a theory of intervention is required to gain a greater understanding of the change mechanisms, as well as the interplay of nonlinguistic cognitive functions.

Keywords: Alzheimer's disease, lexical retrieval, mechanisms of change, primary progressive aphasia

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Authors: Min Liu, Jirui Gong, Qinpu Luo, Lili Yang, Bo Yang, Zihe Zhang, Yan Pan, Zhanwei Zhai

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Grazing disturbance is one of the important land-use types that affect plant growth and ecosystem processes. In order to study the responses of dominant species to grazing in the semiarid temperate grassland of Inner Mongolia, we set five grazing intensity plots: a control and four levels of grazing (light (LG), moderate (MG), heavy (HG) and extreme heavy grazing (EHG)) to test the morphological and physiological responses of Stipa grandis, Leymus chinensis at the individual levels. With the increase of grazing intensity, Stipa grandis and Leymus chinensis both exhibited reduced plant height, leaf area, stem length and aboveground biomass, showing a significant dwarf phenomenon especially in HG and EHG plots. The photosynthetic capacity decreased along the grazing gradient. Especially in the MG plot, the two dominant species have lowest net photosynthetic rate (Pn) and water use efficiency (WUE). However, in the HG and EHG plots, the two species had high light saturation point (LSP) and low light compensation point (LCP), indicating they have high light-use efficiency. They showed a stimulation of compensatory photosynthesis to the remnant leaves as compared with grasses in MG plot. For Leymus chinensis, the lipid peroxidation level did not increase with the low malondialdehyde (MDA) content even in the EHG plot. It may be due to the high enzymes activity of superoxide dismutase (SOD) and peroxidase (POD) to reduce the damage of reactive oxygen species. Meanwhile, more carbohydrate was stored in the leaf of Leymus chinensis to provide energy to the plant regrowth. On the contrary, Stipa grandis showed the high level of lipid peroxidation especially in the HG and EHG plots with decreased antioxidant enzymes activity. The soluble protein content did not change significantly in the different plots. Therefore, with the increase of grazing intensity, plants changed morphological and physiological traits to defend themselves effectively to herbivores. Leymus chinensis is more resistant to grazing than Stipa grandis in terms of tolerance traits, particularly under heavy grazing pressure.

Keywords: antioxidant enzymes activity, grazing density, morphological responses, photosynthesis

Procedia PDF Downloads 365

Authors: Rudi Ryacudu, Edi Artono, Gema Wahyudi Purnama

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Oil and gas consumption in Indonesia is currently on the rise due to its nation economic improvement. Unfortunately, Indonesia’s domestic oil production cannot meet it’s own consumption and Indonesia has lost its status as Oil and Gas exporter. Even worse, our conventional oil and gas reserve is declining. Unwilling to give up, the government of Indonesia has taken measures to invite investors to invest in domestic oil and gas exploration to find new potential reserve and ultimately increase production. Yet, it has not bear any fruit. Indonesia has taken steps now to explore new unconventional oil and gas play including Shale Gas, Shale Oil and Tight Sands to increase domestic production. These new plays require definite parameters to differentiate each concept. The purpose of this paper is to provide ways in defining unconventional hydrocarbon reservoir parameters in Shale Gas, Shale Oil and Tight Sands. The parameters would serve as an initial baseline for users to perform analysis of unconventional hydrocarbon plays. Some of the on going concerns or question to be answered in regards to unconventional hydrocarbon plays includes: 1. The TOC number, 2. Has it been well “cooked” and become a hydrocarbon, 3. What are the permeability and the porosity values, 4. Does it need a stimulation, 5. Does it has pores, and 6. Does it have sufficient thickness. In contrast with the common oil and gas conventional play, Shale Play assumes that hydrocarbon is retained and trapped in area with very low permeability. In most places in Indonesia, hydrocarbon migrates from source rock to reservoir. From this case, we could derive a theory that Kitchen and Source Rock are located right below the reservoir. It is the starting point for user or engineer to construct basin definition in relation with the tectonic play and depositional environment. Shale Play concept requires definition of characteristic, description and reservoir identification to discover reservoir that is technically and economically possible to develop. These are the steps users and engineers has to do to perform Shale Play: a. Calculate TOC and perform mineralogy analysis using water saturation and porosity value. b. Reconstruct basin that accumulate hydrocarbon c. Brittlenes Index calculated form petrophysical and distributed based on seismic multi attributes d. Integrated natural fracture analysis e. Best location to place a well.

Keywords: unconventional hydrocarbon, shale gas, shale oil tight sand reservoir parameters, shale play

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Authors: Dipankar Deka

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Exploration and production of Oil & Gas is a very challenging business on which a nation’s energy security depends on. The exploration and Production of hydrocarbon is a very precise and time-bound process. The striking rate of hydrocarbon in a drilled well is so uncertain that the success rate is only 31% in 2021 as per Rigzone. Huge cost is involved in drilling as well as the production of hydrocarbon from a well. Due to this very reason, no one can effort to lose a well because of faulty machines, which increases the non-productive time (NPT). Numerous activities that include manpower and machines synchronized together works in a precise way to complete the full cycle of exploration, rig movement, drilling and production of crude oil. There are several machines, both fixed and mobile, are used in the complete cycle. Most of these machines have a tight schedule of work operating in various drilling sites that are simultaneously being drilled, providing a very narrow window for maintenance. The shutdown of any of these machines for even a small period of time delays the whole project and increases the cost of production of hydrocarbon by manifolds. Moreover, these machines are custom designed exclusively for oil field operations to be only used in Mining Exploration Licensed area (MEL) earmarked by the government and are imported and very costly in nature. The cost of some of these mobile units like Well Logging Units, Coil Tubing units, Nitrogen pumping units etc. that are used for Well stimulation and activation process exceeds more than 1 million USD per unit. So the increase of self-life of these units also generates huge revenues during the extended duration of their services. In this paper we are considering the very critical mobile oil field equipment like Well Logging Unit, Coil Tubing unit, well-killing unit, Nitrogen pumping unit, MOL Oil Field Truck, Hot Oil Circulation Unit etc., and their extensive preventive maintenance in our auto workshop. This paper is the outcome of 10 years of structured automobile maintenance and minute documentation of each associated event that allowed us to perform the comparative study between the new practices of preventive maintenance over the age-old practice of system-based corrective maintenance and its impact on the self-life of the equipment.

Keywords: automobile maintenance, preventive maintenance, symptom based maintenance, workshop technologies

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Authors: Avani Jain, Hasmukh Jain, S. Shelley, M. Indirani, Shilpa Kalal, Jayakanth Amalachandran

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Aim of the Study: To assess the effect of orally administered Itopride on gall bladder ejection fraction by fatty meal cholescintigraphy in patients with diabetes. Materials and Methods: Thirty patients (20 males, 10 females, mean age 46+10 yrs) with history of diabetes mellitus (mean duration 4.8+4.1 yrs, fasting blood glucose level 130+35 mg/dl and 2-hours post-prandial blood glucose level 196+76 mg/dl) and found to have gall bladder dysfunction on fatty-meal stimulated cholescintigraphy were selected for this study. These patients underwent a repeat cholescintigraphy similar to baseline study, with 50 mg of Itopride orally along with fatty meal. Pre- and post-Itopride GBEF were then compared to assess the effect of Itopride on gall bladder contraction. Results: Out of these 30 patients, 2 had dyskinetic, 4 had akinetic, 22 had moderately hypokinetic and the remaining 2 had hypokinetic gall bladder function in the baseline study with > 60% GBEF being taken as the normal value. Mean percentage of GBEF in the baseline study was 32%+13% and the mean percentage of GBEF in the post-Itopride study was 57%+17% with change in mean percentage of GBEF being 24%+21%. GBEF of the “baseline study” was significantly lower as compared to GBEF in the “post-Itopride study” (p < 0.05). Conclusion: Diabetic patients with biliary-type pain often tend to have impaired gallbladder function. Cholescintigraphy with fatty meal-stimulation is a simple, cheap and useful investigation for assessment of gallbladder dysfunction in these patients, before any structural changes occur within the lumen or wall of the gall bladder. Improvement in gallbladder ejection fraction after oral administration of a single dose of Itopride, a newer prokinetic drug with fewer side effects, as assessed by cholescintigraphy, provides enough evidence of future therapeutic response. Administration of Itopride, in therapeutic dosage, therefore may be expected to cause significant improvement in gallbladder ejection fraction and hence prolong stone formation within the gall bladder and also prevent the associated long term complications. Hence, based on scintigraphic evidence, Itopride may be recommended, by clinicians, for management of symptomatic diabetic patients having gallbladder dysfunction.

Keywords: itopride, gall bladder ejection fraction, fatty meal, cholescintigraphy, diabetes

Procedia PDF Downloads 425

Authors: A. Delimitsou, C. Gouedard, E. Konstanta, A. Koletis, S. Patera, E. Manou, K. Spaho, S. Murray

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Background: There remains a lack of International Standard Control Reference materials for Next Generation Sequencing-based approaches or device calibration. We have designed and validated dsDNA biomimetic reference materials for targeted such approaches incorporating proprietary motifs (patent pending) for device/test calibration. They enable internal single-sample calibration, alleviating sample comparisons to pooled historical population-based data assembly or statistical modelling approaches. We have validated such an approach for BRCA Copy Number Variation analytics using iQRS™-CNVSUITE versus Mixed Ligation-dependent Probe Amplification. Methods: Standard BRCA Copy Number Variation analysis was compared between mixed ligation-dependent probe amplification and next generation sequencing using a cohort of 198 breast/ovarian cancer patients. Next generation sequencing based copy number variation analysis of samples spiked with iQRS™ dsDNA biomimetics were analysed using proprietary CNVSUITE software. Mixed ligation-dependent probe amplification analyses were performed on an ABI-3130 Sequencer and analysed with Coffalyser software. Results: Concordance of BRCA – copy number variation events for mixed ligation-dependent probe amplification and CNVSUITE indicated an overall sensitivity of 99.88% and specificity of 100% for iQRS™-CNVSUITE. The negative predictive value of iQRS-CNVSUITE™ for BRCA was 100%, allowing for accurate exclusion of any event. The positive predictive value was 99.88%, with no discrepancy between mixed ligation-dependent probe amplification and iQRS™-CNVSUITE. For device calibration purposes, precision was 100%, spiking of patient DNA demonstrated linearity to 1% (±2.5%) and range from 100 copies. Traditional training was supplemented by predefining the calibrator to sample cut-off (lock-down) for amplicon gain or loss based upon a relative ratio threshold, following training of iQRS™-CNVSUITE using spiked iQRS™ calibrator and control mocks. BRCA copy number variation analysis using iQRS™-CNVSUITE™ was successfully validated and ISO15189 accredited and now enters CE-IVD performance evaluation. Conclusions: The inclusion of a reference control competitor (iQRS™ dsDNA mimetic) to next generation sequencing-based sequencing offers a more robust sample-independent approach for the assessment of copy number variation events compared to mixed ligation-dependent probe amplification. The approach simplifies data analyses, improves independent sample data analyses, and allows for direct comparison to an internal reference control for sample-specific quantification. Our iQRS™ biomimetic reference materials allow for single sample copy number variation analytics and further decentralisation of diagnostics to single patient sample assessment.

Keywords: validation, diagnostics, oncology, copy number variation, reference material, calibration

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Authors: Holm Zerbe, Laura Macias, Hans-Joachim Schuberth, Wolfram Petzl

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Mastitis is among the most important production diseases in cows. It accounts for large parts of antimicrobial drug use in the dairy industry worldwide. Due to the imminent normative to reduce the use of antimicrobial drugs in livestock, new ways for therapy and prophylaxis of mastitis are needed. Recently epigenetic regulation of inflammation by chromatin modifications has increasingly drawn attention. Currently, some epigenetic modifiers have already been approved for the use in humans, however little is known about their actions in the bovine system. The aim of our study was to investigate whether three selected epigenetic modifiers (Vitamin D3, SAHA and S2101) influence the initial immune response towards mastitis pathogens in bovine udder tissue in vitro. Tissue explants of the teat cistern and udder parenchyma were collected from 21 cows and were incubated for 36 hours in the absence and presence of epigenetic modifiers. Additionally, the tissue was stimulated with heat-inactivated particles of Escherichia coli and Staphylococcus aureus, which are regarded as two of the most important mastitis pathogens. After incubation, the explants were tested by RT-qPCR for transcript abundances of immune-related candidate genes. Gene expression was validated in culture supernatants by an AlphaLISA assay. Furthermore, the culture supernatants were analyzed for their chemotactic capacity through a chemotaxis assay. Statistical analysis of data was performed with the program ‘R’ version 3.2.3. Vitamin D3 had no effect on the immune response of udder tissue in vitro after stimulation with mastitis pathogens. The epigenetic modifiers SAHA and S2101 however significantly blocked the pathogen-induced upregulation of CXCL8, TNFα, S100A9 and LAP (P < 0.05). The regulation of IL10 was not affected by treatment with SAHA and S2101. Transcript abundances for CXCL8 were reflected by IL8 contents and chemotactic activity in culture supernatants. In conclusion, these data show the potential of epigenetic modifiers (SAHA and S2101) to block overshooting inflammation in the udder. Thus epigenetic modifiers may serve in future as immune modulators for the treatment and/or prophylaxis of clinical mastitis. (Funded by Deutsche Forschungsgemeinschaft PE 1495/2-1).

Keywords: mastitis, cattle, epigenetics, immunomodulation

Procedia PDF Downloads 235

Authors: Sonia Butalia, Huong Luu, Alexis Guigue, Karen J. B. Martins, Khanh Vu, Scott W. Klarenbach

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Obesity-related health conditions impose a substantial economic burden on payers due to increased healthcare use. Estimates of healthcare resource use and costs associated with obesity-related comorbidities are needed to inform policies and interventions targeting these conditions. Methods: Adults living with obesity were identified (a procedure-related body mass index code for class 2/3 obesity between 2012 and 2019 in Alberta, Canada; excluding those with bariatric surgery), and outcomes were compared over 1-year (2019/2020) between those who had and did not have specific obesity-related comorbidities. The probability of using a healthcare service (based on the odds ratio of a zero [OR-zero] cost) was compared; 95% confidence intervals (CI) were reported. Logistic regression and a generalized linear model with log link and gamma distribution were used for total healthcare cost comparisons ($CDN); cost ratios and estimated cost differences (95% CI) were reported. Potential socio-demographic and clinical confounders were adjusted for, and incremental cost differences were representative of a referent case. Results: A total of 220,190 adults living with obesity were included; 44% had hypertension, 25% had osteoarthritis, 24% had type-2 diabetes, 17% had cardiovascular disease, 12% had insulin resistance, 9% had chronic back pain, and 4% of females had polycystic ovarian syndrome (PCOS). The probability of hospitalization, ED visit, and ambulatory care was higher in those with a following obesity-related comorbidity versus those without: chronic back pain (hospitalization: 1.8-times [OR-zero: 0.57 [0.55/0.59]] / ED visit: 1.9-times [OR-zero: 0.54 [0.53/0.56]] / ambulatory care visit: 2.4-times [OR-zero: 0.41 [0.40/0.43]]), cardiovascular disease (2.7-times [OR-zero: 0.37 [0.36/0.38]] / 1.9-times [OR-zero: 0.52 [0.51/0.53]] / 2.8-times [OR-zero: 0.36 [0.35/0.36]]), osteoarthritis (2.0-times [OR-zero: 0.51 [0.50/0.53]] / 1.4-times [OR-zero: 0.74 [0.73/0.76]] / 2.5-times [OR-zero: 0.40 [0.40/0.41]]), type-2 diabetes (1.9-times [OR-zero: 0.54 [0.52/0.55]] / 1.4-times [OR-zero: 0.72 [0.70/0.73]] / 2.1-times [OR-zero: 0.47 [0.46/0.47]]), hypertension (1.8-times [OR-zero: 0.56 [0.54/0.57]] / 1.3-times [OR-zero: 0.79 [0.77/0.80]] / 2.2-times [OR-zero: 0.46 [0.45/0.47]]), PCOS (not significant / 1.2-times [OR-zero: 0.83 [0.79/0.88]] / not significant), and insulin resistance (1.1-times [OR-zero: 0.88 [0.84/0.91]] / 1.1-times [OR-zero: 0.92 [0.89/0.94]] / 1.8-times [OR-zero: 0.56 [0.54/0.57]]). After fully adjusting for potential confounders, the total healthcare cost ratio was higher in those with a following obesity-related comorbidity versus those without: chronic back pain (1.54-times [1.51/1.56]), cardiovascular disease (1.45-times [1.43/1.47]), osteoarthritis (1.36-times [1.35/1.38]), type-2 diabetes (1.30-times [1.28/1.31]), hypertension (1.27-times [1.26/1.28]), PCOS (1.08-times [1.05/1.11]), and insulin resistance (1.03-times [1.01/1.04]). Conclusions: Adults with obesity who have specific disease-related health conditions have a higher probability of healthcare use and incur greater costs than those without specific comorbidities; incremental costs are larger when other obesity-related health conditions are not adjusted for. In a specific referent case, hypertension was costliest (44% had this condition with an additional annual cost of $715 [$678/$753]). If these findings hold for the Canadian population, hypertension in persons with obesity represents an estimated additional annual healthcare cost of $2.5 billion among adults living with obesity (based on an adult obesity rate of 26%). Results of this study can inform decision making on investment in interventions that are effective in treating obesity and its complications.

Keywords: administrative data, healthcare cost, obesity-related comorbidities, real world evidence

Procedia PDF Downloads 148

Authors: Seemab Safdar, Shazia Fatima, Ahmad Qureshy, M. Adnan Saeed, M. Faheem

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Background: Thyroid cancer has 586,000 cases per year worldwide, and this translates to 3% of all tumor diagnoses. 90% of the cases fall under differentiated thyroid carcinoma (DTC), which includes follicular thyroid cancer (FTC) and papillary thyroid cancer (PTC). During their illness, 10% of patients develop distant metastases, and two-thirds of them develop resistance to radioactive iodine (RAI) treatment. It has been shown that in some circumstances, like DTC with high TG levels and negative 131I whole-body scintigraphy (TENIS), [18F] FDG-PET-CT is an effective imaging technique. This study determines the role of [18F] FDG-PET-CT in the treatment of TENIS patients. Methods: 16 patients (n = 12 female; 4 males, age 45 ± 15 years) with histologically proven thyroid cancer (Differentiated and poorly differentiated) and high TG with negative iodine scans were included in this prospective study from January 2024 to June 2024. They underwent scanning in state-of-the-art (GE Discovery MI) [18F] FDG-PET-CT for re-staging or diagnostics of recurrent disease using a standardized protocol. All DTC subtypes and PDTC were included. The referring physicians completed standardized questionnaires both before and after PET-CT to prospectively determine the examination's effect on clinical decision-making. Patient outcomes were measured by analysis of medical records. Moreover, after PET-CT, a change in the pre-PET-CT planned therapies was documented in 32% of cases and additional invasive diagnostic procedures could be waived in 37.5 % of cases. TG levels under TSH stimulation were significantly higher in patients showing PET-CT metastases compared to patients without such findings (68.75%). Results: Without PET-CT, physicians referring to the doctors had not established a complete treatment plan for 45% of patients with thyroid carcinoma. 12/16 patients showed FDG avidity in cervical lymph nodes that were not Iodine avid previously, 2 patients had FDG avid disease in the lungs. In the process, PET-CT helped plan patient management and created a clear plan for treatment in 68.75% of patients. Conclusions: This study confirms that [18F] FDG-PET-CT used in a routine clinical setting has a very important impact on the management of patients with thyroid cancer when TG levels are persistently high in the presence of negative Iodine Scans by initiating treatments and replacing additional imaging and invasive tests.

Keywords: PET-CT, TENIS, role, FDG

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Authors: D. S. Zhuravkova, A. G. Temnikov, O. S. Belova, L. L. Chernensky, T. K. Gerastenok, I. Y. Kalugina, N. Y. Lysov, A.V. Orlov

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Investigation of the discharges from the artificial charged water aerosol clouds in presence of the arrays of the model hydrometeors could help to receive the new data about the peculiarities of the return stroke formation between the thundercloud and the ground when the large volumes of the hail particles participate in the lightning discharge initiation and propagation stimulation. Artificial charged water aerosol clouds of the negative or positive polarity with the potential up to one million volts have been used. Hail has been simulated by the group of the conductive model hydrometeors of the different form. Parameters of the impulse current of the main stage of the discharge between the artificial positively and negatively charged water aerosol clouds and the ground in presence of the model hydrometeors array and of its corresponding electromagnetic radiation have been determined. It was established that the parameters of the array of the model hydrometeors influence on the parameters of the main stage of the discharge between the artificial thundercloud cell and the ground. The maximal values of the main stage current impulse parameters and the electromagnetic radiation registered by the plate antennas have been found for the array of the model hydrometeors of the cylinder revolution form for the negatively charged aerosol cloud and for the array of the hydrometeors of the plate rhombus form for the positively charged aerosol cloud, correspondingly. It was found that parameters of the main stage of the discharge between the artificial charged water aerosol cloud and the ground in presence of the model hydrometeor array of the different considered forms depend on the polarity of the artificial charged aerosol cloud. In average, for all forms of the investigated model hydrometeors arrays, the values of the amplitude and the current rise of the main stage impulse current and the amplitude of the corresponding electromagnetic radiation for the artificial charged aerosol cloud of the positive polarity were in 1.1-1.9 times higher than for the charged aerosol cloud of the negative polarity. Thus, the received results could indicate to the possible more important role of the big volumes of the large hail arrays in the thundercloud on the parameters of the return stroke for the positive lightning.

Keywords: main stage of discharge, hydrometeor form, lightning parameters, negative and positive artificial charged aerosol cloud

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Authors: Yuichi Anada

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Electrical properties of polymer solid is characterized by dielectric relaxation phenomenon. Complex permittivity shows a high dependence on frequency of external stimulation in the broad frequency range from 0.1mHz to 10GHz. The complex-permittivity dispersion gives us a lot of useful information about the molecular motion of polymers and the structure of polymer aggregates. However, the large dispersion of permittivity at low frequencies due to DC conduction of impurity ions often covers the dielectric relaxation in polymer solid. In experimental investigation, many researchers have tried to remove the DC conduction experimentally or analytically for a long time. On the other hand, our laboratory chose another way of research for this problem from the point of view of a reversal in thinking. The way of our research is to use the impurity ions in the DC conduction as a probe to detect the motion of polymer molecules and to investigate the structure of polymer aggregates. In addition to the complex permittivity, the electric modulus and the conductivity relaxation time are strong tools for investigating the ionic motion in DC conduction. In a non-crystalline part of melt-crystallized polymers, free spaces with inhomogeneous size exist between crystallites. As the impurity ions exist in the non-crystalline part and move through these inhomogeneous free spaces, the motion of ions reflects the microstructure of non-crystalline part. The ionic motion of impurity ions in poly(vinylidene fluoride) (PVDF) is investigated in this study. Frequency dependence of the loss permittivity of PVDF shows a characteristic of the direct current (DC) conduction below 1 kHz of frequency at 435 K. The electric modulus-frequency curve shows a characteristic of the dispersion with the single conductivity relaxation time. Namely, it is the Debye-type dispersion. The conductivity relaxation time analyzed from this curve is 0.00003 s at 435 K. From the plot of conductivity relaxation time of PVDF together with the other polymers against permittivity, it was found that there are two group of polymers; one of the group is characterized by small conductivity relaxation time and large permittivity, and another is characterized by large conductivity relaxation time and small permittivity.

Keywords: conductivity relaxation time, electric modulus, ionic motion, permittivity, poly(vinylidene fluoride), DC conduction

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Authors: Don Anushka Sandaruwan Elvitigala, P. D. S. U. Wickramasinghe, Jehee Lee

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Cystatins are a large superfamily of proteins which act as reversible inhibitors of cysteine proteases. Papain proteases and cysteine cathepsins are predominant substrates of cystatins. Cystatin superfamily can be further clustered into three groups as Stefins, Cystatins, and Kininogens. Among them, stefines are also known as family 1 cystatins which harbors cystatin Bs and cystatin As. In this study, a homologue of family one cystatins more close to cystatin Bs was identified from Korean black rockfish (Sebastes schlegeli) using a prior constructed cDNA (complementary deoxyribonucleic acid) database and designated as RfCyt1. The full-length cDNA of RfCyt1 consisted of 573 bp, with a coding region of 294 bp. It comprised a 5´-untranslated region (UTR) of 55 bp, and 3´-UTR of 263 bp. The coding sequence encodes a polypeptide consisting of 97 amino acids with a predicted molecular weight of 11kDa and theoretical isoelectric point of 6.3. The RfCyt1 shared homology with other teleosts and vertebrate species and consisted conserved features of cystatin family signature including single cystatin-like domain, cysteine protease inhibitory signature of pentapeptide (QXVXG) consensus sequence and N-terminal two conserved neighboring glycine (⁸GG⁹) residues. As expected, phylogenetic reconstruction developed using the neighbor-joining method showed that RfCyt1 is clustered with the cystatin family 1 members, in which more closely with its teleostan orthologues. An SYBR Green qPCR (quantitative polymerase chain reaction) assay was performed to quantify the RfCytB transcripts in different tissues in healthy and immune stimulated fish. RfCyt1 was ubiquitously expressed in all tissue types of healthy animals with gill and spleen being the highest. Temporal expression of RfCyt1 displayed significant up-regulation upon infection with Aeromonas salmonicida. Recombinantly expressed RfCyt1 showed concentration-dependent papain inhibitory activity. Collectively these findings evidence for detectable protease inhibitory and immunity relevant roles of RfCyt1 in Sebastes schlegeli.

Keywords: Sebastes schlegeli, family 1 cystatin, immune stimulation, expressional modulation

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Authors: Kamila Dus-Szachniewicz, Artur Bednarkiewicz, Katarzyna Gdesz-Birula, Slawomir Drobczynski

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In modern oncology hyperthermia (HT) is defined as a controlled tumor heating. HT treatment temperatures range between 40–48 °C and can selectively damage heat-sensitive cancer cells or limit their further growth, usually with minimal injury to healthy tissues. Despite many advantages, conventional whole-body and regional hyperthermia have clinically relevant side effects, including cardiac and vascular disorders. Additionally, the lack of accessibility of deep-seated tumor sites and impaired targeting micrometastases renders HT less effective. It is believed that above disadvantages can significantly overcome by the application of biofunctionalized microparticles, which can specifically target tumor sites and become activated by an external stimulus to provide a sufficient cellular response. In our research, the unique optical tweezers system have enabled capturing the silica microparticles, primary cells and tumor spheroids in highly controllable and reproducible environment to study the impact of localized heat stimulation on normal and pathological cell and within multicellular tumor spheroid. High throughput spheroid model was introduced to better mimic the response to HT treatment on tumors in vivo. Additionally, application of local heating of tumor spheroids was performed in strictly controlled conditions resembling tumor microenvironment (temperature, pH, hypoxia, etc.), in response to localized and nonhomogeneous hyperthermia in the extracellular matrix, which promotes tumor progression and metastatic spread. The lack of precise control over these well- defined parameters in basic research leads to discrepancies in the response of tumor cells to the new treatment strategy in preclinical animal testing. The developed approach enables also sorting out subclasses of cells, which exhibit partial or total resistance to therapy, in order to understand fundamental aspects of the resistance shown by given tumor cells in response to given therapy mode and conditions. This work was funded by the National Science Centre (NCN, Poland) under grant no. UMO-2017/27/B/ST7/01255.

Keywords: cancer spheroids, hyperthermia, microparticles, optical tweezers

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Authors: I. V. Palamarchuk, N. V. Zaichko

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Background and Aims: Galectin-3 is a marker of subclinical cardiac injury and is elevated in individuals with type 2 diabetes mellitus; while hydrogen sulfide (H₂S), metabolite of sulfur-containing amino acids, is considered having antifibrogenic effects. This study was designed to investigate whether metformin and its combination with NaHS can influence plasma galectin-3 and cystathionine-γ-lyase/hydrogen sulfide (CSE/H₂S) system in diabetic rat’s heart. Methods: 32 healthy male rats (180-250 g) were divided into 4 groups. To induct diabetes, rats (group 2-4) were injected with streptozotocin (STZ, 40 mg/kg/i.p., 0.1 M citrate buffer (pH 4.5). Rats from 3d (STZ+Metf) and 4th (STZ+Metf+NaHS) groups were given metformin (500 mg/kg/day) orally, and rats from 4th (STZ+Metf+NaHS) group were injected sodium hydrosulfide (NaHS, 3 mg/kg/i.p.) once per day starting from 3 to 28 day after streptozotocin injection. Rats of first group (control) were administered the equivalent volumes of 0.9% NaCl. Plasma galectin-3 was measured by ELISA. Rats’ hearts were sampled for determination of H2S by reaction with N,N-Dimethyl-p-phenylenediamine. Determination of CSE gene expression was performed in real time using PCR in the presence of SYBR Green I, using DT-Light detecting amplifier ('DNA-technology', Russia). Results: Induction of streptozotocin diabetes (STZ-diabetes, group 2) was followed by low myocardial H2S concentration and CSE expression (by 35%, p < 0.05 and 60.5%, p < 0.001 respectively, than that in controls), while plasma galectin-3 in this group was significantly higher than in controls (by 3.8 times, p < 0.05). Administration of metformin (group 3) resulted in significantly higher H₂S concentration (by 28.5%, p < 0.05), whereas CSE expression was only by 6% more than that in STZ-diabetes, as well as plasma galectin-3 was only by 14.8% lower in comparison with untreated diabetic rats. The inhibition of H₂S generation and CSE activity by diabetes was greatly attenuated in STZ+Metf+NaHS group. The combination of metformin with NaHS significantly stimulated H₂S production (by 48%, p < 0.05 and 15%, p < 0.05 more than STZ-diabetes and STZ+Metf respectively) and CSE gene expression (by 64.8%, p < 0.05 compared to STZ-diabetes and by 55.4%,p < 0.05 compared to STZ+Metf). Besides, plasma galectin-3 in rats receiving metformin and NaHS was significantly lower by 42%, p < 0.05 and 32.5%, p < 0.05 compared to STZ-diabetes and STZ+Metf groups respectively. Conclusions: To summarize, dysfunction of CSE/H2S system and galectin-3 stimulation was found in streptozotocin-induced diabetic rats. Metformin and its combination with exogenous H2S effectively prevented the development of metabolic changes induced by diabetes. These findings suggest that CSE/H₂S system can be integrated into pathogenesis of diabetic complications through modulation of pro-inflammatory and pro-fibrogenic mediator galectin-3.

Keywords: cystathionine-γ-lyase, diabetic heart, galectin-3, hydrogen sulfide, metformin, sodium hydrosulfide

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Authors: Taku Numao, Kazu Amimoto, Tomoko Shimada, Kyohei Ichikawa

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Background: Unilateral spatial neglect (USN) is a common syndrome following damage to one hemisphere of the brain (usually the right side), in which a patient fails to report or respond to stimulation from the contralesional side. These symptoms are not due to primary sensory or motor deficits, but instead, reflect an inability to process input from that side of their environment. Prism adaptation (PA) is a therapeutic treatment for USN, wherein a patient’s visual field is artificially shifted laterally, resulting in a sensory-motor adaptation. However, patients with USN also tend to perceive a left-leaning subjective vertical in the frontal plane. The traditional PA cannot be used to correct a tilt in the subjective vertical, because a prism can only polarize, not twist, the surroundings. However, this can be accomplished using a head mounted display (HMD) and a web-camera. Therefore, this study investigated whether an HMD system could be used to correct the spatial perception of USN patients in the frontal as well as the horizontal plane. We recruited healthy subjects in order to collect data for the refinement of USN patient therapy. Methods: Eight healthy subjects sat on a chair wearing a HMD (Oculus rift DK2), with a web-camera (Ovrvision) displaying a 10 degree leftward rotation and a 10 degree counter-clockwise rotation along the frontal plane. Subjects attempted to point a finger at one of four targets, assigned randomly, a total of 48 times. Before and after the intervention, each subject’s body-centre judgment (BCJ) was tested by asking them to point a finger at a touch panel straight in front of their xiphisternum, 10 times sight unseen. Results: Intervention caused the location pointed to during the BCJ to shift 35 ± 17 mm (Ave ± SD) leftward in the horizontal plane, and 46 ± 29 mm downward in the frontal plane. The results in both planes were significant by paired-t-test (p<.01). Conclusions: The results in the horizontal plane are consistent with those observed following PA. Furthermore, the HMD and web-camera were able to elicit 3D effects, including in both the horizontal and frontal planes. Future work will focus on applying this method to patients with and without USN, and investigating whether subject posture is also affected by the HMD system.

Keywords: head mounted display, posture, prism adaptation, unilateral spatial neglect

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Authors: Gobinathan Devathasan, Kezia Devathasan

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Objective: To improve the current modified Broca-Wernicke-Lichtheim-Kussmaul speech schema and provide insight into autism. Methods: We reviewed the pertinent literature. Current findings, involving Brodmann areas 22, 46, 9,44,45,6,4 are based on neuropathology and functional MRI studies. However, in primary autism, there is no lucid explanation and changes described, whether neuropathology or functional MRI, appear consequential. Findings: We forward an enhanced model which may explain the enigma related to autism. Vowel output is subcortical and does need cortical representation whereas consonant speech is cortical in origin. Left lateralization is needed to commence the circuitry spin as our life have evolved with L-amino acids and left spin of electrons. A fundamental species difference is we are capable of three syllable-consonants and bi-syllable expression whereas cetaceans and songbirds are confined to single or dual consonants. The 4 key sites for speech are superior auditory cortex, Broca’s two areas, and the supplementary motor cortex. Using the Argand’s diagram and Reimann’s projection, we theorize that the Euclidean three dimensional synaptic neuronal circuits of speech are quantized to coherent waves, and then decoherence takes place at area 6 (spherical representation). In this quantum state complex, 3-consonant languages are instantaneously integrated and multiple languages can be learned, verbalized and differentiated. Conclusion: We postulate that evolutionary human speech is elevated to quantum interaction unlike cetaceans and birds to achieve the three consonants/bi-syllable speech. In classical primary autism, the sudden speech switches off and on noted in several cases could now be explained not by any anatomical lesion but failure of coherence. Area 6 projects directly into prefrontal saccadic area (8); and this further explains the second primary feature in autism: lack of eye contact. The third feature which is repetitive finger gestures, located adjacent to the speech/motor areas, are actual attempts to communicate with the autistic child akin to sign language for the deaf.

Keywords: quantum neuronal paradigm, cetaceans and human speech, autism and rapid magnetic stimulation, coherence and decoherence of speech

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Authors: Jingyi Li, Laurence Stamford, Alejandro Gallego-Schmid

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Renewable electricity has become an indispensable contributor to achieving net-zero by the mid-century to tackle climate change. Unlike solar, wind, or hydro, geothermal was stagnant in its electricity production development for decades. However, with the significant breakthrough made in recent years, especially the implementation of enhanced geothermal systems (EGS) in various regions globally, geothermal electricity could play a pivotal role in alleviating greenhouse gas emissions. Life cycle assessment has been applied to analyze specific geothermal power generation technologies, which proposed suggestions to optimize its environmental performance. For instance, selecting a high heat gradient region enables a higher flow rate from the production well and extends the technical lifespan. Although such process-level improvements have been made, the significance of geothermal power generation technologies so far has not explicitly displayed its competitiveness on a broader horizon. Therefore, this review-based study integrates a circular economy framework into life cycle assessment, clarifying the underlying added values for geothermal power plants to complete the sustainability profile. The derived results have provided an enlarged platform to discuss geothermal power generation technologies: (i) recover the heat and electricity from the process to reduce the fossil fuel requirements; (ii) recycle the construction materials, such as copper, steel, and aluminum for future projects; (iii) extract the lithium ions from geothermal brine and make geothermal reservoir become a potential supplier of the lithium battery industry; (iv) repurpose the abandoned oil and gas wells to build geothermal power plants; (v) integrate geothermal energy with other available renewable energies (e.g., solar and wind) to provide heat and electricity as a hybrid system at different weather; (vi) rethink the fluids used in stimulation process (EGS only), replace water with CO2 to achieve negative emissions from the system. These results provided a new perspective to the researchers, investors, and policymakers to rethink the role of geothermal in the energy supply network.

Keywords: climate, renewable energy, R strategies, sustainability

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Authors: A. Díaz-Roa, P. I. Silva Junior, F. J. Bello

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Sarconesiopsis magellanica (Diptera: Calliphoridae) is a medically important necrophagous fly which is used for establishing the post-mortem interval. Dipterous maggots release diverse proteins and peptides contained in larval excretion and secretion (ES) products playing a key role in digestion. The most important mechanism for combating infection using larval therapy depends on larval ES. These larvae are protected against infection by a diverse spectrum of antimicrobial peptides (AMPs), one already known like lucifensin. Special interest in these peptides has also been aroused regarding understanding their role in wound healing since they degrade necrotic tissue and kill different bacteria during larval therapy. The action of larvae on wounds occurs through 3 mechanisms of action: removal of necrotic tissue, stimulation of granulation tissue, and antibacterial action of larval ES. Some components of the ES include calcium, urea, allantoin ammonium bicarbonate and reducing the viability of Gram positive and Gram negative bacteria. The Lucilia sericata fly larvae have been the most used, however, we need to evaluate new species that could potentially be similar or more effective than fly above. This study was thus aimed at identifying and characterizing S. magellanica AMPs contained in ES products for the first time and compared them with the common fly used L. sericata. These products were obtained from third-instar larvae taken from a previously established colony. For the first analysis, ES fractions were separate by Sep-Pak C18 disposable columns (first step). The material obtained was fractionated by RP-HPLC by using Júpiter C18 semi-preparative column. The products were then lyophilized and their antimicrobial activity was characterized by incubation with different bacterial strains. The first chromatographic analysis of ES from L. sericata gives 6 fractions with antimicrobial activity against Gram-positive bacteria Micrococus luteus, and 3 fractions with activity against Gram-negative bacteria Pseudomonae aeruginosa while the one from S. magellanica gaves 1 fraction against M. luteus and 4 against P. aeruginosa. Maybe one of these fractions could correspond to the peptide already known from L. sericata. These results show the first work for supporting further experiments aimed at validating S. magellanica use in larval therapy. We still need to search if we find some new molecules, by making mass spectrometry and ‘de novo sequencing’. Further studies are necessary to identify and characterize them to better understand their functioning.

Keywords: antimicrobial peptides, larval therapy, Lucilia sericata, Sarconesiopsis magellanica

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Authors: Pamela Chia, Tay Yoong Chuan

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Introduction: Severe pulmonary hypertension (PH) patients requiring non-cardiac surgery risk have increased mortality rates ranging. These patients are plagued with cardiorespiratory failure, dysrhythmias and anticoagulation potentially with concurrent sepsis and renal insufficiency, perioperative morbidity. We present a deaf-mute patient with severe idiopathic PH emergently prepared for ruptured ectopic laparotomy. Case Report: A 20 year-old female, 62kg (BMI 25 kg/m2) with severe idiopathic PH (2DE Ejection Fraction was 41%, Pulmonary Artery Systolic Pressure (PASP) 105 mmHg, Right ventricle strain and hypertrophy) and selective mutism was rushed in for emergency laparotomy after presenting to the emergency department for abdominal pain. The patient had an NYHA Class II with room air SpO2 93-95%. While awaiting lung transplant, the patient takes warfarin, Sildanefil, Macitentan and even Selexipag for rising PASP. At presentation, vital signs: BP 95/63, HR 119 SpO2 88% (room air). Despite decreasing haemoglobin 14 to 10g/dL, INR 2.59 was reversed with prothrombin concentrate, and Vitamin K. ECG revealed Right Bundle Branch Block with right ventricular strain and x-ray showed cardiomegaly, dilated Right Ventricle, Pulmonary Arteries, basal atelectasis. Arterial blood gas showed compensated metabolic acidosis pH 7.4 pCO2 32 pO2 53 HCO3 20 BE -4 SaO2 88%. The cardiothoracic surgeon concluded no role for Extracorporeal Membrane Oxygenation (ECMO). We inserted invasive arterial and central venous lines with blood transfusion via an 18G cannula before the patient underwent a midline laparotomy, haemostasis of ruptured ovarian cyst with 2.4L of clots under general anesthesia and FloTrac cardiac output monitoring. Rapid sequence induction was done with Midazolam/Propofol, remifentanil infusion, and rocuronium. The patient was maintained on Desflurane. Blood products and colloids were transfused for further 1.5L blood loss. Postoperatively, the patient was transferred to the intensive care unit and was extubated uneventfully 7hours later. The patient went home a week later. Discussion: Emergency hemostasis laparotomy in anticoagulated WHO Class I PH patient awaiting lung transplant with no ECMO backup poses tremendous stress on the deaf-mute patient and the anesthesiologist. Balancing hemodynamics avoiding hypotension while awaiting hemostasis in the presence of pulmonary arterial dilators and anticoagulation requires close titration of volatiles, which decreases RV contractility. We review the contraindicated anesthetic agents (ketamine, N2O), choice of vasopressors in hypotension to maintain Aortic-right ventricular pressure gradients and nitric oxide use perioperatively. Conclusion: Interdisciplinary communication with a deaf-mute moribund patient and anesthesia considerations pose many rare challenges worth sharing.

Keywords: pulmonary hypertension, case report, warfarin reversal, emergency surgery

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Authors: Qiaoyue Kuang, Yang Li, Mizuki Endo, Takeaki Ozawa

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G protein-coupled receptors (GPCR) are the largest family of receptor proteins that detect molecules outside the cell and activate cellular responses. Of the GPCRs, dopamine receptors, which recognize extracellular dopamine, are essential to mammals due to their roles in numerous physiological events, including autonomic movement, hormonal regulation, emotions, and the reward system in the brain. To precisely understand the physiological roles of dopamine receptors, it is important to spatiotemporally control the signaling mediated by dopamine receptors, which is strongly dependent on their surface expression. Conventionally, chemical-induced interactions were applied to trigger the endocytosis of cell surface receptors. However, these methods were subjected to diffusion and therefore lacked temporal and special precision. To further understand the receptor-mediated signaling and to control the plasma membrane expression of receptors, an optogenetic tool called E-fragment was developed. The C-terminus of a light-sensitive photosensory protein cyptochrome2 (CRY2) was attached to β-Arrestin, and the E-fragment was generated by fusing the C-terminal peptide of vasopressin receptor (V2R) to CRY2’s binding partner protein CIB. The CRY2-CIB heterodimerization triggered by blue light stimulation brings β-Arrestin to the vicinity of membrane receptors and results in receptor endocytosis. In this study, the E-fragment system was applied to dopamine receptors 1 and 2 (DRD1 and DRD2) to control dopamine signaling. First, confocal fluorescence microscope observation qualitatively confirmed the light-induced endocytosis of E-fragment fused receptors. Second, NanoBiT bioluminescence assay verified quantitatively that the surface amount of E-fragment labeled receptors decreased after light treatment. Finally, GloSensor bioluminescence assay results suggested that the E-fragment-dependent receptor light-induced endocytosis decreased cAMP production in DRD1 signaling and attenuated the inhibition effect of DRD2 on cAMP production. The developed optogenetic tool was able to induce receptor endocytosis by external light, providing opportunities to further understand numerous physiological activities by controlling receptor-mediated signaling spatiotemporally.

Keywords: dopamine receptors, endocytosis, G protein-coupled receptors, optogenetics

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Authors: Jillian M. Hagel, Joseph E. Tucker, Peter J. Facchini

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With the aim of establishing a holistic approach for the treatment of central nervous system (CNS) disorders, we are pursuing a drug development program rapidly progressing through discovery and characterization phases. The drug candidates identified in this program are referred to as neuroplastogens owing to their ability to mediate neuroplasticity, which can be beneficial to patients suffering from anxiety, depression, or posttraumatic stress disorder. These and other related neuropsychiatric conditions are associated with the onset of neuronal atrophy, which is defined as a reduction in the number and/or productivity of neurons. The stimulation of neuroplasticity results in an increase in the connectivity between neurons and promotes the restoration of healthy brain function. We have synthesized a substantial catalogue of proprietary indolethylamine derivatives based on the general structures of serotonin (5-hydroxytryptamine) and psychedelic molecules such as N,N-dimethyltryptamine (DMT) and psilocin (4-hydroxy-DMT) that function as neuroplastogens. A primary objective in our screening protocol is the identification of derivatives associated with a significant reduction in hallucination, which will allow administration of the drug at a dose that induces neuroplasticity and triggers other efficacious outcomes in the treatment of targeted CNS disorders but which does not cause a psychedelic response in the patient. Both neuroplasticity and hallucination are associated with engagement of the 5HT2A receptor, requiring drug candidates differentially coupled to these two outcomes at a molecular level. We use novel and proprietary artificial intelligence algorithms to predict the mode of binding to the 5HT2A receptor, which has been shown to correlate with the hallucinogenic response. Hallucination is tested using the mouse head-twitch response model, whereas mouse marble-burying and sucrose preference assays are used to evaluate anxiolytic and anti-depressive potential. Neuroplasticity is assays using dendritic outgrowth assays and cell-based ELISA analysis. Pharmacokinetics and additional receptor-binding analyses also contribute the selection of lead candidates. A summary of the program is presented.

Keywords: neuroplastogen, non-hallucinogenic, drug development, anxiety, depression, PTSD, indolethylamine derivatives, psychedelic-inspired, 5-HT2A receptor, computational chemistry, head-twitch response behavioural model, neurite outgrowth assay

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Authors: Mohsine Jebbour

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Motivation and classroom interaction are of prime significance for second/foreign language learning to take place effectively. Thus, a considerable amount of motivation and classroom interaction helps ensure students’ success in and continuation of learning the TL. One way to enhance students’ motivation and classroom interaction in the Moroccan EFL classroom then is through the use of self-disclosure. For the purposes of this study, self-disclosure has been defined as the verbal communication of positive personal information including opinions, feelings, experiences, family and friendship stories to classmates and teachers. This paper is meant to demonstrate that positive self-disclosure can serve as an effective tool for helping students develop favorable attitudes toward the EFL classroom (i.e., English courses, teacher of English, and classroom activities) and promoting their intrinsic motivation (IM to know and IM toward stimulation). A further objective is that since self-disclosure is reciprocal, when teachers of English reveal their personal information, students will uncover their personal matters in return. This will help ensure effective classroom participation, foster teacher-student communication, and encourage students to practice and hence improve their oral proficiency (i.e., the speaking skill). A questionnaire was used to collect data in this study. 164 undergraduate students (99 females and 65 males) from the department of English at the faculty of letters and humanities, Dher el Mehraz, Sidi Mohammed Ben Abd Allah University completed a questionnaire that assessed self-disclosure in relation to motivation (i.e., attitudes toward the learning situation and intrinsic motivation) and classroom interaction (i.e., teacher-student interaction, participation, and out-of-class communication) on a 1 to 5 scale with (1) Strongly Disagree and (5) Strongly Agree. The level of agreement on the positive dimension of self-disclosure was ranked first by the respondents. The hypothesis set at the very beginning of the study, which posited that positive self-disclosure is essential to enhancing motivation and classroom interaction in the EFL context, was confirmed. In this regard, the findings suggest that implementing self-disclosure in the Moroccan EFL classroom may serve as an effective tool to have positive affect of teacher, class and classroom activities. This in turn will encourage the learners to attend classes, enjoy the language learning activity, complete classroom assignments, participate in class discussions, and interact with their teachers and classmates. It is hoped that teachers benefit from the results of this study and hence encourage the use of positive self-disclosure to develop English language learning in the Moroccan context where opportunities of using English outside the classroom are limited.

Keywords: EFL classroom, classroom interaction, motivation, self-disclosure

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Authors: Björn de Kruijf, Arjen Edzes, Sietske Waslander

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In an ever-quickly changing society, lifelong development is seen as a solution to labor market problems by politicians and policymakers. In this paper, we investigate how policy instruments are used to increase participation in lifelong development and on which behavioral principles policy is based. Digitization, automation, and an aging population change society and the labor market accordingly. Skills that were once most sought after in the workforce can become abundantly present. For people to remain relevant in the working population, they need to continue adapting new skills useful in the current labor market. Many reports have been written that focus on the role of lifelong development in this changing society and how lifelong development can help keep people adapt and stay relevant. Inspired by these reports, governments have implemented a broad range of policies to support participation in lifelong development. The question we ask ourselves is how government policies promote participation in lifelong development. This stems from a complex interplay of policy instruments and learning. Regulation, economic and soft instruments can be combined to promote lifelong development, and different types of education further complex policies on lifelong development. Literature suggests that different stages in people’s lives might warrant different methods of learning. Governments could anticipate this in their policies. In order to influence people’s behavior, the government can tap into a broad range of sociological, psychological, and (behavioral) economic principles. The traditional economic assumption that behavior is rational is known to be only partially true, and the government can use many biases in human behavior to stimulate participation in lifelong development. In this paper, we also try to find which biases the government taps into to promote participation if they tap into any of these biases. The goal of this paper is to analyze government policies intended to promote participation in lifelong development. To do this, we develop a framework to analyze the policies on lifelong development. We specifically incorporate the role of learning and the behavioral principles underlying policy instruments in the framework. We apply this framework to the case of the Netherlands, where we examine a set of policy documents. We single out the policies the government has put in place and how they are vertically and horizontally related. Afterward, we apply the framework and classify the individual policies by policy instrument and by type of learning. We find that the Dutch government focuses on formal and non-formal learning in their policy instruments. However, the literature suggests that learning at a later age is mainly done in an informal manner through experiences.

Keywords: learning, lifelong development, policy analysis, policy instruments

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Authors: David Martinez-Pernia, Alvaro Rivera-Rei, Alejandro Troncoso, Gonzalo Forno, Andrea Slachevsky, David Huepe, Victoria Silva-Mack, Jorge Calderon, Mayte Vergara, Valentina Carrera

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Background: Recent theories in the field of emotions have taken the relevance of motor control beyond a system related to personal autonomy (walking, running, grooming), and integrate it into the emotional dimension. However, to our best knowledge, there are no studies that specifically investigate how emotional stimuli related to motor control modify emotional states in terms of postural control and phenomenological experience. Objective: The main aim of this work is to investigate the emotions produced by stimuli of bodily imbalance (neutral, pleasant and unpleasant) in the postural control and the phenomenological experience of young, healthy adults. Methodology: 46 healthy young people are shown emotional videos (neutral, pleasant, motor unpleasant, and non-motor unpleasant) related to the body imbalance. During the period of stimulation of each of the videos (60 seconds) the participant is standing on a force platform to collect temporal and spatial data of postural control. In addition, the electrophysiological activity of the heart and electrodermal activity is recorded. In relation to the two unpleasant conditions (motor versus non-motor), a phenomenological interview is carried out to collect the subjective experience of emotion and body perception. Results: Pleasant and unpleasant emotional videos have significant changes with respect to the neutral condition in terms of greater area, higher mean velocity, and greater mean frequency power on the anterior-posterior axis. The results obtained with respect to the electrodermal response was that the pleasurable and unpleasant conditions produced a significant increase in the phasic component with respect to the neutral condition. Regarding the electrophysiology of the heart, no significant change was found in any condition. Phenomenological experiences in the two unpleasant conditions differ in body perception and the emotional meaning of the experience. Conclusion: Emotional stimuli related to bodily imbalance produce changes in postural control, electrodermal activity, and phenomenological experience. This experimental setting could be relevant to be implemented in people with motor disorders (Parkinson, Stroke, TBI) to know how emotions affect motor control.

Keywords: body imbalance stimuli, emotion, phenomenological experience, postural control

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Authors: Shau-Ping Shiu, Shu-Ling Lin

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Pregnancy lead a process of changing in the endocrine system. Either pregnancy itself or the surrounding affect such as the attitude of family to the pregnant lady can bring lots of stress. Sever stress may lead pregnant women display serious mental problem such as mood swings, impulsivity, and abnormal behavior. A method of self management of stress(SMS) has been proved that help patient of cancer in release their stress. This study were going to use SMS to help pregnant women. Methods: In this study, 42 ladies in the first to third months of pregnancy process applied to join SMS of program have divided into 21 participants in both control and experimental group by draw. 24 sessions of Yoga program were conducted once a week for 6 months for experimental group. Verbatim used to gather more feedbacks from the interview followed by each Yoga sessions. Brief symptom Rating scale also conducted pre and post experiment for 42 participations. Results: Overall score of Brief Symptom Rating Scale reduced 17.82 points and suicide drop 9 points in experimental group, compared to the control group increasing 10.24 point of overall score and suicide add 7 points. Feedback from interviews showed participations improved in emotion, physical health and stress management. They indicated having more positive emotion daily, having better gastrointestinal peristalsis movement, releasing back tention, well weight control, reducing stress and changing the quality of interpersonal relationships. Conclusion: SMS of Yoga program in this study included four key training directions which were stimulation, relaxation, awareness and pranayama lead a great improvment of stress management for pregnant lady. Throughout this Yoga program, women learned to ignite eustress, remove distress, create calmness and breath slows down. As the result, Yoga program has helped women in experiment group lower their tension, and bring the extra benifits in emotion and relationships. It support women to overcome their pregnancy. Suggestion: An unexpected result of this study showed all participants had no morning sickness since they engaged in SMS program, and no one absent from course due to the benefits of it. We strongly suggest that SMS of Yoga program can be a add of medication for women in pregnancy, however, the position of Forward in the SMS sequence has been point out pressing participant’s stomach, which can be replace to Bridge position to comfort participants.

Keywords: self-management of stress(SMS), yoga program, pregnant women, early pregnancy

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Authors: Wei-Ju Huang, Hung-Pin Hsu

Abstract:

[Background] In congestive heart failure (CHF), it has always been the principle of clinical treatment to control the water retention mechanism in the body to prevent excessive fluid retention. Early control of sympathetic nerves, Renin-Angiotensin-Aldosterone system (RAA system, RAAS), or strengthening of Atrial Natriuretic Peptide (ANP) was the point. In RAA system, related hormones, such as angiotensin, or enzymes in the pathway, such as ACE-I, can be used with corresponding inhibitors to reduce water content.[Aim] In recent years, clinical studies have pointed out that if different mechanisms are combined, the control effect seems to be better. For example, recent studies showed that ENTRESTO, a combination of Sacubitril and Valsartan, is a good new drug for CHF. Sacubitril is a prodrug. After activation, it can inhibit neprilysin and act as a neprilysin inhibitor (ARNI) to reduce the breakdown of natriuretic peptides(ANP). Valsartan is a kind of angiotensin receptor blocker (ARB), both of which are used to treat heart failure at the same time, have excellent curative effects.[Materials and Methods] Considering the side effects of this drug, coughing and a few cases of diarrhea were observed. However, the effect of this drug on the patient's intestinal tract has not been confirmed. On the other hand, studies have pointed out that ANP supplement can improve the CHF and increase the inhibitory effect on cancer cells. Therefore, the purpose of this study is to use a special microbial detection method to prove that whether oral drugs have an effect on microorganisms.The experimental method uses Nissui Compact Dry to observe the situation in different types of microorganisms. After the drug is dissolved in water, it is implanted in a petri dish, and the presence of different microorganisms is detected through different antibody reactions to confirm whether the drug has some toxicology in the gut.[Results and Discussion]From the above experimental results, it can be known that among the effects of Sacubitril and Valsartan on the basic microbial flora of the human body, low doses had no significant effect on Escherichia coli or intestinal bacteria. If Sacubitril or Valsartan with a high concentration of 3mg/ml is used alone or under the stimulation of a high concentration of the two drugs, it has a significant inhibitory effect on Escherichia coli. However, in terms of the effect on intestinal bacteria, high concentration of Sacubitril has a more significant inhibitory effect on intestinal bacteria, while high concentration of Valsartan has a less significant inhibitory effect on intestinal bacteria. The inhibitory effect of the combination of the two drugs on intestinal bacteria is also less significant.[Conclusion]The results of this study can be used as a further reference for the possible side effects of the clinical use of Sacubitril and Valsartan on the intestinal tract of patients,

Keywords: sacubitril, valsartan, entresto, congestive heart failure (CHF)

Procedia PDF Downloads 67

Authors: Mikhail V. Khachaturyan, Inga A. Koryagina, Maria Nikishova

Abstract:

The study investigates the impact of the ongoing financial crisis, started in the 2^nd half of 2014, on marketing budgets spent by Fast-moving consumer goods companies. In these conditions, special importance is given to efficient possessory risk management systems. The main objective for establishing and developing possessory risk management systems for FMCG companies in a crisis is to analyze the data relating to the external environment and consumer behavior in a crisis. Another important objective for possessory risk management systems of FMCG companies is to develop measures and mechanisms to maintain and stimulate sales. In this regard, analysis of risks and threats which consumers define as the main reasons affecting their level of consumption become important. It is obvious that in crisis conditions the effective risk management systems responsible for development and implementation of strategies for consumer demand stimulation, as well as the identification, analysis, assessment and management of other types of risks of economic security will be the key to sustainability of a company. In terms of financial and economic crisis, the problem of forming and developing possessory risk management systems becomes critical not only in the context of management models of FMCG companies, but for all the companies operating in other sectors of the Russian economy. This study attempts to analyze the specifics of formation and development of company possessory risk management systems. In the modern economy, special importance among all the types of owner’s risks has the risk of reduction in consumer activity. This type of risk is common not only for the consumer goods trade. Study of consumer activity decline is especially important for Russia due to domestic market of consumer goods being still in the development stage, despite its significant growth. In this regard, it is especially important to form and develop possessory risk management systems for FMCG companies. The authors offer their own interpretation of the process of forming and developing possessory risk management systems within owner’s management models of FMCG companies as well as in Russian economy in general. Proposed methods and mechanisms of problem analysis of formation and development of possessory risk management systems in FMCG companies and the results received can be helpful for researchers interested in problems of consumer goods market development in Russia and overseas.

Keywords: FMCG companies, marketing budget, risk management, owner, Russian economy, organization, formation, development, system

Procedia PDF Downloads 376

Authors: S. Mamoucha, J. Rahul, N. Christodoulakis

Abstract:

Introduction: Nature has been the source of medicinal agents since the dawn of the human existence on Earth. Currently, millions of people, in the developing world, rely on medicinal plants for primary health care, income generation and lifespan improvement. In Greece, more than 5500 plant taxa are reported while about 250 of them are considered to be of great pharmaceutical importance. Among the plants used for medical purposes, Vitex agnus-castus L. (Verbenaceae) is known since ancient times. It is a small tree or shrub, widely distributed in the Mediterranean basin up to the Central Asia. It is also known as chaste tree or monks pepper. Theophrastus mentioned the shrub several times, as ‘agnos’ in his ‘Enquiry into Plants’. Dioscorides mentioned the use of V. agnus-castus for the stimulation of lactation in nursing mothers and the treatment of several female disorders. The plant has important medicinal properties and a long tradition in folk medicine as an antimicrobial, diuretic, digestive and insecticidal agent. Materials and methods: Leaves were cleaned, detached, fixed, sectioned and investigated with light and Scanning Electron Microscopy (SEM). Histochemical tests were executed as well. Specific histochemical reagents (osmium tetroxide, H2SO4, vanillin/HCl, antimony trichloride, Wagner’ s reagent, Dittmar’ s reagent, potassium bichromate, nitroso reaction, ferric chloride and di methoxy benzaldehyde) were used for the sub cellular localization of secondary metabolites. Results: Light microscopical investigations of the elongated leaves of V. agnus-castus revealed three layers of palisade parenchyma, just below the single layered adaxial epidermis. The spongy parenchyma is rather loose. Adaxial epidermal cells are larger in magnitude, compared to those of the abaxial epidermis. Four different types of capitate, secreting trichomes, were localized among the abaxial epidermal cells. Stomata were observed at the abaxial epidermis as well. SEM revealed the interesting arrangement of trichomes. Histochemical treatment on fresh and plastic embedded tissue sections revealed the nature and the sites of secondary metabolites accumulation (flavonoids, steroids, terpenes). Acknowledgment: This work was supported by IKY - State Scholarship Foundation, Athens, Greece.

Keywords: Vitex agnus-castus, leaf anatomy, histochemical reagents, secondary metabolites

Procedia PDF Downloads 386