Search results for: disease index

Authors: Sara Assi, Berthe Hayar, Claudio Pisano, Nadine Darwiche, Walid Saad

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Nanomedicine, the application of nanotechnology to medicine, is an emerging discipline that has gained significant attention in recent years. Current breakthroughs in nanomedicine have paved the way to develop effective drug delivery systems that can be used to target cancer. The use of nanotechnology provides effective drug delivery, enhanced stability, bioavailability, and permeability, thereby minimizing drug dosage and toxicity. As such, the use of nanoparticle (NP) formulations in drug delivery has been applied in various cancer models and have shown to improve the ability of drugs to reach specific targeted sites in a controlled manner. Cancer is one of the major causes of death worldwide; in particular, colorectal cancer (CRC) is the third most common type of cancer diagnosed amongst men and women and the second leading cause of cancer related deaths, highlighting the need for novel therapies. Retinoids, consisting of natural and synthetic derivatives, are a class of chemical compounds that have shown promise in preclinical and clinical cancer settings. However, retinoids are limited by their toxicity and resistance to treatment. To overcome this resistance, various synthetic retinoids have been developed, including the adamantyl retinoid ST1926, which is a potent anti-cancer agent. However, due to its limited bioavailability, the development of ST1926 has been restricted in phase I clinical trials. We have previously investigated the preclinical efficacy of ST1926 in CRC models. ST1926 displayed potent inhibitory and apoptotic effects in CRC cell lines by inducing early DNA damage and apoptosis. ST1926 significantly reduced the tumor doubling time and tumor burden in a xenograft CRC model. Therefore, we developed ST1926-NPs and assessed their efficacy in CRC models. ST1926-NPs were produced using Flash NanoPrecipitation with the amphiphilic diblock copolymer polystyrene-b-ethylene oxide and cholesterol as a co-stabilizer. ST1926 was formulated into NPs with a drug to polymer mass ratio of 1:2, providing a stable formulation for one week. The contin ST1926-NP diameter was 100 nm, with a polydispersity index of 0.245. Using the MTT cell viability assay, ST1926-NP exhibited potent anti-growth activities as naked ST1926 in HCT116 cells, at pharmacologically achievable concentrations. Future studies will be performed to study the anti-tumor activities and mechanism of action of ST1926-NPs in a xenograft mouse model and to detect the compound and its glucuroconjugated form in the plasma of mice. Ultimately, our studies will support the use of ST1926-NP formulations in enhancing the stability and bioavailability of ST1926 in CRC.

Keywords: nanoparticles, drug delivery, colorectal cancer, retinoids

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Authors: Satendra Pal Singh, Dalip Kr. Kakru, Jyoti Mishra, Rajesh Thakur, Tarana Sarwat

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COVID-19 is still an intrigue as far as morbidity or mortality is concerned. The rate of recovery varies from person to person, & it depends upon the accessibility of the healthcare system and the roles played by the physicians and caregivers. It is envisaged that with the passage of time, people would become immune to this virus, and those who are vulnerable would sustain themselves with the help of vaccines. The proposed study deals with the severeness of COVID-19 is associated with some specific biomarkers linked to correlate age and gender. We will be assessing the overall homeostasis of the persons who were affected by the coronavirus infection and also of those who recovered from it. Some people show more severe effects, while others show very mild symptoms, however, they show low CT values. Thus far, it is unclear why the new strain of Covid has different effects on different people in terms of age, gender, and ABO blood typing. According to data, the fatality rate with heart disease was 10.5 percent, 7.3 percent were diabetic, and 6 percent who are already infected from other comorbidities. However, some COVID-19 cases are worse than others & it is not fully explainable as of date. Overall data show that the ABO blood group is effective or prone to the risk of SARS-COV2 infection, while another study also shows the phenotypic effects of the blood group related to covid. It is an accepted fact that females have more strong immune systems than males, which may be related to the fact that females have two ‘X’ chromosomes, which might contain a more effective immunity booster gene on the X chromosome, and are capable to protect the female. Also specific sex hormones also induce a better immune response in a specific gender. This calls for in-depth analysis to be able to gain insight into this dilemma. COVID-19 is still not fully characterized, and thus we are not very familiar with its biology, mode of infection, susceptibility, and overall viral load in the human body. How many virus particles are needed to infect a person? How, then, comorbidity contribute to coronavirus infection? Since the emergence of this virus in 2020, a large number of papers have been published, and seemingly, vaccines have been prepared. But still, a large number of questions remain unanswered. The proneness of humans for infection by covid-19 needs to be established to be able to develop a better strategy to fight this virus. Our study will be on the Impact of demography on the Severity of covid-19 infection & at the same time, will look into gender-specific sensitivity of Covid-19 and the Operational variation of different biochemical markers in Covid-19 positive patients. Besides, we will be studying the co-relation, if any, of COVID severity & ABO Blood group type and the occurrence of the most common blood group type amongst positive patience.

Keywords: coronavirus, ABO blood group, age, gender

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Authors: P. M. Sreekanth

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Teak (Tectona grandis L. f.) is a tree species indigenous to India and other Southeastern countries. It produces high-value timber and is easily established in plantations. Reforestation requires a constant supply of high quality seeds. Seed Production Areas (SPA) of teak are improved stands used for collection of open-pollinated quality seeds in large quantities. Information on the genetic diversity of major teak SPAs in India is scanty. The genetic structure of four important seed production areas of Kerala State in Southern India was analyzed employing amplified fragment length polymorphism markers using ten selective primer combinations on 80 samples (4 populations X 20 trees). The study revealed that the gene diversity of the SPAs varied from 0.169 (Konni SPA) to 0.203 (Wayanad SPA). The percentage of polymorphic loci ranged from 74.42 (Parambikulam SPA) to 84.06 (Konni SPA). The mean total gene diversity index (HT) of all the four SPAs was 0.2296 ±0.02. A high proportion of genetic diversity was observed within the populations (83%) while diversity between populations was lower (17%) (GST = 0.17). Principal coordinate analysis and STRUCTURE analysis of the genotypes indicated that the pattern of clustering was in accordance with the origin and geographic location of SPAs, indicating specific identity of each population. A UPGMA dendrogram was prepared and showed that all the twenty samples from each of Konni and Parambikulam SPAs clustered into two separate groups, respectively. However, five Nilambur genotypes and one Wayanad genotype intruded into the Konni cluster. The higher gene flow estimated (Nm = 2.4) reflected the inclusion of Konni origin planting stock in the Nilambur and Wayanad plantations. Evidence for population structure investigated using 3D Principal Coordinate Analysis of FAMD software 1.30 indicated that the pattern of clustering was in accordance with the origin of SPAs. The present study showed that assessment of genetic diversity in seed production plantations can be achieved using AFLP markers. The AFLP fingerprinting was also capable of identifying the geographical origin of planting stock and there by revealing the occurrence of the errors in genotype labeling. Molecular marker-based selective culling of genetically similar trees from a stand so as to increase the genetic base of seed production areas could be a new proposition to improve quality of seeds required for raising commercial plantations of teak. The technique can also be used to assess the genetic diversity status of plus trees within provenances during their selection for raising clonal seed orchards for assuring the quality of seeds available for raising future plantations.

Keywords: AFLP, genetic structure, spa, teak

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Authors: Danni Cheng

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Background: Preclinical and epidemiological studies have reported potential protective effects of low-density lipoprotein cholesterol (LDL-C) lowering drugs on head and neck squamous cell cancer (HNSCC) survival, but the causality was not consistent. Genetic variants associated with LDL-C lowering drug targets can predict the effects of their therapeutic inhibition on disease outcomes. Objective: We aimed to evaluate the causal association of genetically proxied cholesterol-lowering drug targets and circulating lipid traits with cancer survival in HNSCC patients stratified by human papillomavirus (HPV) status using two-sample Mendelian randomization (MR) analyses. Method: Single-nucleotide polymorphisms (SNPs) in gene region of LDL-C lowering drug targets (HMGCR, NPC1L1, CETP, PCSK9, and LDLR) associated with LDL-C levels in genome-wide association study (GWAS) from the Global Lipids Genetics Consortium (GLGC) were used to proxy LDL-C lowering drug action. SNPs proxy circulating lipids (LDL-C, HDL-C, total cholesterol, triglycerides, apoprotein A and apoprotein B) were also derived from the GLGC data. Genetic associations of these SNPs and cancer survivals were derived from 1,120 HPV-positive oropharyngeal squamous cell carcinoma (OPSCC) and 2,570 non-HPV-driven HNSCC patients in VOYAGER program. We estimated the causal associations of LDL-C lowering drugs and circulating lipids with HNSCC survival using the inverse-variance weighted method. Results: Genetically proxied HMGCR inhibition was significantly associated with worse overall survival (OS) in non-HPV-drive HNSCC patients (inverse variance-weighted hazard ratio (HR IVW), 2.64[95%CI,1.28-5.43]; P = 0.01) but better OS in HPV-positive OPSCC patients (HR IVW,0.11[95%CI,0.02-0.56]; P = 0.01). Estimates for NPC1L1 were strongly associated with worse OS in both total HNSCC (HR IVW,4.17[95%CI,1.06-16.36]; P = 0.04) and non-HPV-driven HNSCC patients (HR IVW,7.33[95%CI,1.63-32.97]; P = 0.01). A similar result was found that genetically proxied PSCK9 inhibitors were significantly associated with poor OS in non-HPV-driven HNSCC (HR IVW,1.56[95%CI,1.02 to 2.39]). Conclusion: Genetically proxied long-term HMGCR inhibition was significantly associated with decreased OS in non-HPV-driven HNSCC and increased OS in HPV-positive OPSCC. While genetically proxied NPC1L1 and PCSK9 had associations with worse OS in total and non-HPV-driven HNSCC patients. Further research is needed to understand whether these drugs have consistent associations with head and neck tumor outcomes.

Keywords: Mendelian randomization analysis, head and neck cancer, cancer survival, cholesterol, statin

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Authors: Christopher R. Triggle, Hong Ding, Khaled Machaca, Gnanapragasam Arunachalam

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The antidiabetic drug, metformin, has been in clinical use for over 50 years and remains the first choice drug for the treatment of type two diabetes. In addition to its effectiveness as an oral anti-hyperglycaemic drug metformin also possesses vasculoprotective effects that are assumed to be secondary to its ability to reduce insulin resistance and control glycated hemoglobin levels; however, recent data from our laboratory indicate that metformin also has direct vasoprotective effects that are mediated, at least in part, via the anti-ageing gene, SIRT1. Diabetes is a major risk factor for the development of cardiovascular disease (CVD) and it is also well established that tobacco use further enhances the risk of CVD; however, it is not known whether treatment with metformin can offset the negative effects of diabetes and tobacco use on cardiac function. The current study was therefore designed to investigate 1: the effects of hyperglycaemia (HG) either alone or in the presence of elevated fatty acids (palmitate) and nicotine on the protein expression levels of the deacetylase sirtuin 1 (the protein product of SIRT1), anti-apoptotic Bcl-2, pro-apoptotic BIM and the pro-apoptotic, tumour suppressor protein, acetylated p53 in cardiomyocytes. 2: the ability of metformin to prevent the detrimental effects of HG, palmitate and nicotine on cardiomyocyte survival. Cell culture protocols were designed using a rat cardiomyocyte cell line, H9c2, either under normal glycaemic (NG) conditions of 5.5mM glucose, or hyperglycaemic conditions (HG) of 25mM glucose with, or without, added palmitate (250μM) or nicotine (1.0mM) for 24h. Immuno-blotting was used to detect the expression of sirtuin 1, Bcl-2, BIM, acetylated (Ac)-p53, p53 with β-actin used as the reference protein. Exposure to HG, palmitate, or nicotine alone significantly reduced expression of sirtuin1, Bcl-2 and raised the expression levels of acetylated p53 and BIM; however, the combination of HG, palmitate and nicotine had a synergistic effect to significantly suppress the expression levels of sirtuin 1 and Bcl-2, but further enhanced the expression of Ac-p53, and BIM. The inclusion of 1000μM, but not 50μM, metformin in the H9c2 cell culture protocol prevented the effects of HG, palmitate and nicotine on the pro-apoptotic pathways. Collectively these data indicate that metformin, in addition to its anti-hyperglycaemic and vasculoprotective properties, also has direct cardioprotective actions that offset the negative effects of hyerglycaemia, elevated free fatty acids and nicotine on cardiac cell survival. These data are of particular significance for the treatment of patients with diabetes who are also smokers as the inclusion of metformin in their therapeutic treatment plan should help reduce cardiac-related morbidity and mortality.

Keywords: apoptosis, cardiac muscle, diabetes, metformin, nicotine

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Authors: Ismatilla Mardanov

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There are three types of countries, the first of which is willing to attract foreign direct investment (FDI) in enormous amounts and do whatever it takes to make this happen. Therefore, FDI pours into such countries. In the second cluster of countries, even if the country is suffering tremendously from the shortage of investments, the governments are hesitant to attract investments because they are at the hands of local oligarchs/cartels. Therefore, FDI inflows are moderate to low in such countries. The third type is countries whose companies prefer investing in the most efficient locations globally and are hesitant to invest in the homeland. Sorting countries into such clusters, the present study examines the essential institutions and economic factors that make these countries different. Past literature has discussed various determinants of FDI in all kinds of countries. However, it did not classify countries based on government motivation, institutional setup, and economic factors. A specific approach to each target country is vital for corporate foreign direct investment risk analysis and decisions. The research questions are 1. What specific institutional and economic factors paint the pictures of the three clusters; 2. What specific institutional and economic factors are determinants of FDI; 3. Which of the determinants are endogenous and exogenous variables? 4. How can institutions and economic and political variables impact corporate investment decisions Hypothesis 1: In the first type, country institutions and economic factors will be favorable for FDI. Hypothesis 2: In the second type, even if country economic factors favor FDI, institutions will not. Hypothesis 3: In the third type, even if country institutions favorFDI, economic factors will not favor domestic investments. Therefore, FDI outflows occur in large amounts. Methods: Data come from open sources of the World Bank, the Fraser Institute, the Heritage Foundation, and other reliable sources. The dependent variable is FDI inflows. The independent variables are institutions (economic and political freedom indices) and economic factors (natural, material, and labor resources, government consumption, infrastructure, minimum wage, education, unemployment, tax rates, consumer price index, inflation, and others), the endogeneity or exogeneity of which are tested in the instrumental variable estimation. Political rights and civil liberties are used as instrumental variables. Results indicate that in the first type, both country institutions and economic factors, specifically labor and logistics/infrastructure/energy intensity, are favorable for potential investors. In the second category of countries, the risk of loss of assets is very high due to governmentshijacked by local oligarchs/cartels/special interest groups. In the third category of countries, the local economic factors are unfavorable for domestic investment even if the institutions are well acceptable. Cluster analysis and instrumental variable estimation were used to reveal cause-effect patterns in each of the clusters.

Keywords: foreign direct investment, economy, institutions, instrumental variable estimation

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Authors: Carmela Nardelli, Laura Iaffaldano, Valentina Capobianco, Antonietta Tafuto, Maddalena Ferrigno, Angela Capone, Giuseppe Maria Maruotti, Maddalena Raia, Rosa Di Noto, Luigi Del Vecchio, Pasquale Martinelli, Lucio Pastore, Lucia Sacchetti

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Maternal obesity and nutrient excess in utero increase the risk of future metabolic diseases in the adult life. The mechanisms underlying this process are probably based on genetic, epigenetic alterations and changes in foetal nutrient supply. In mammals, the placenta is the main interface between foetus and mother, it regulates intrauterine development, modulates adaptive responses to sub optimal in uterus conditions and it is also an important source of human amniotic mesenchymal stem cells (hA-MSCs). We previously highlighted a specific microRNA (miRNA) profiling in amnion from obese (Ob) pregnant women, here we compared the miRNA expression profile of hA-MSCs isolated from (Ob) and control (Co) women, aimed to search for any alterations in metabolic pathways that could predispose the new-born to the obese phenotype. Methods: We isolated, at delivery, hA-MSCs from amnion of 16 Ob- and 7 Co-women with pre-pregnancy body mass index (mean/SEM) 40.3/1.8 and 22.4/1.0 kg/m2, respectively. hA-MSCs were phenotyped by flow cytometry. Globally, 384 miRNAs were evaluated by the TaqMan Array Human MicroRNA Panel v 1.0 (Applied Biosystems). By the TargetScan program we selected the target genes of the miRNAs differently expressed in Ob- vs Co-hA-MSCs; further, by KEGG database, we selected the statistical significant biological pathways. Results: The immunophenotype characterization confirmed the mesenchymal origin of the isolated hA-MSCs. A large percentage of the tested miRNAs, about 61.4% (232/378), was expressed in hA-MSCs, whereas 38.6% (146/378) was not. Most of the expressed miRNAs (89.2%, 207/232) did not differ between Ob- and Co-hA-MSCs and were not further investigated. Conversely, 4.8% of miRNAs (11/232) was higher and 6.0% (14/232) was lower in Ob- vs Co-hA-MSCs. Interestingly, 7/232 miRNAs were obesity-specific, being expressed only in hA-MSCs isolated from obese women. Bioinformatics showed that these miRNAs significantly regulated (P<0.001) genes belonging to several metabolic pathways, i.e. MAPK signalling, actin cytoskeleton, focal adhesion, axon guidance, insulin signaling, etc. Conclusions: Our preliminary data highlight an altered miRNA profile in Ob- vs Co-hA-MSCs and suggest that an epigenetic miRNA-based mechanism of gene regulation could affect pathways involved in placental growth and function, thereby potentially increasing the newborn’s risk of metabolic diseases in the adult life.

Keywords: hA-MSCs, obesity, miRNA, biosystem

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Authors: Andrey A. Lipovskii, Alexey V. Redkov, Vyacheslav V. Rusan, Dmitry K. Tagantsev, Valentina V. Zhurikhina

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The presented research is related to the development of recently proposed technique of the formation of composite materials, like optical glass-ceramics, with predetermined structure and properties of the crystalline component. The technique is based on the control of the size and concentration of the crystalline grains using the phenomenon of glass-ceramics decrystallization (vitrification) induced by ion-exchange. This phenomenon was discovered and explained in the beginning of the 2000s, while related theoretical description was given in 2016 only. In general, the developed theory enables one to model the process and optimize the conditions of ion-exchange processing of glass-ceramics, which provide given properties of crystalline component, in particular, profile of the average size of the crystalline grains. The optimization is possible if one knows two dimensionless parameters of the theoretical model. One of them (β) is the value which is directly related to the solubility of crystalline component of the glass-ceramics in the glass matrix, and another (γ) is equal to the ratio of characteristic times of ion-exchange diffusion and crystalline grain dissolution. The presented study is dedicated to the development of experimental technique and simulation which allow determining these parameters. It is shown that these parameters can be deduced from the data on the space distributions of diffusant concentrations and average size of crystalline grains in the glass-ceramics samples subjected to ion-exchange treatment. Measurements at least at two temperatures and two processing times at each temperature are necessary. The composite material used was a silica-based glass-ceramics with crystalline grains of Li2OSiO2. Cubical samples of the glass-ceramics (6x6x6 mm3) underwent the ion exchange process in NaNO3 salt melt at 520 oC (for 16 and 48 h), 540 oC (for 8 and 24 h), 560 oC (for 4 and 12 h), and 580 oC (for 2 and 8 h). The ion exchange processing resulted in the glass-ceramics vitrification in the subsurface layers where ion-exchange diffusion took place. Slabs about 1 mm thick were cut from the central part of the samples and their big facets were polished. These slabs were used to find profiles of diffusant concentrations and average size of the crystalline grains. The concentration profiles were determined from refractive index profiles measured with Max-Zender interferometer, and profiles of the average size of the crystalline grains were determined with micro-Raman spectroscopy. Numerical simulation were based on the developed theoretical model of the glass-ceramics decrystallization induced by ion exchange. The simulation of the processes was carried out for different values of β and γ parameters under all above-mentioned ion exchange conditions. As a result, the temperature dependences of the parameters, which provided a reliable coincidence of the simulation and experimental data, were found. This ensured the adequate modeling of the process of the glass-ceramics decrystallization in 520-580 oC temperature interval. Developed approach provides a powerful tool for fine tuning of the glass-ceramics structure, namely, concentration and average size of crystalline grains.

Keywords: diffusion, glass-ceramics, ion exchange, vitrification

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Authors: Pamela R. Jackson, Andrea Hawkins-Daarud, Cassandra R. Rickertsen, Kamala Clark-Swanson, Scott A. Whitmire, Kristin R. Swanson

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Glioblastoma Multiforme (GBM), the most common primary brain tumor, often presents with hyperintensity on T2-weighted or T2-weighted fluid attenuated inversion recovery (T2/FLAIR) magnetic resonance imaging (MRI). This hyperintensity corresponds with vasogenic edema, however there are likely many infiltrating tumor cells within the hyperintensity as well. While MRIs do not directly indicate tumor cells, MRIs do reflect the microenvironmental water abnormalities caused by the presence of tumor cells and edema. The inherent heterogeneity and resulting MRI features of GBMs complicate assessing disease response. To understand how hyperintensity on T2/FLAIR MRI may correlate with edema in the extracellular space (ECS), a multi-compartmental MRI signal equation which takes into account tissue compartments and their associated volumes with input coming from a mathematical model of glioma growth that incorporates edema formation was explored. The reasonableness of two possible extracellular space schema was evaluated by varying the T2 of the edema compartment and calculating the possible resulting T2s in tumor and peripheral edema. In the mathematical model, gliomas were comprised of vasculature and three tumor cellular phenotypes: normoxic, hypoxic, and necrotic. Edema was characterized as fluid leaking from abnormal tumor vessels. Spatial maps of tumor cell density and edema for virtual tumors were simulated with different rates of proliferation and invasion and various ECS expansion schemes. These spatial maps were then passed into a multi-compartmental MRI signal model for generating simulated T2/FLAIR MR images. Individual compartments’ T2 values in the signal equation were either from literature or estimated and the T2 for edema specifically was varied over a wide range (200 ms – 9200 ms). T2 maps were calculated from simulated images. T2 values based on simulated images were evaluated for regions of interest (ROIs) in normal appearing white matter, tumor, and peripheral edema. The ROI T2 values were compared to T2 values reported in literature. The expanding scheme of extracellular space is had T2 values similar to the literature calculated values. The static scheme of extracellular space had a much lower T2 values and no matter what T2 was associated with edema, the intensities did not come close to literature values. Expanding the extracellular space is necessary to achieve simulated edema intensities commiserate with acquired MRIs.

Keywords: extracellular space, glioblastoma multiforme, magnetic resonance imaging, mathematical modeling

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Authors: Maryam Firouzmandi, Moosa Miri

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Common reasons for early tooth loss are trauma, extraction due to caries or periodontal disease and congenital missing. The remaining space after tooth loss may cause functional and esthetic problems. Therefore restorative dentists should attempt to manage these spaces using conservative methods. The goal is to restore the lost esthetic and function, prevent phonetic, self-esteem and personality problems and tongue habits. Preserving alveolar bone is also of great importance during the growth stage. Purpose: When deciding about the management of the missing tooth, space implants are contradicted until the completion of dentoalveolar development. Even in adulthood, due to systemic or periodontal problems or biological and economic issues, the implant might not be indicated. In this article, the alternative conservative restorative methods of space maintenance are going to be discussed. Essix retainers are made chair-side as easy as forming a custom bleaching tray with some modifications. They are esthetically acceptable and not expensive. These temporaries provide support for the lips but could not be used during function. Mini-screw-supported temporaries are another option for maintaining the space, especially after orthodontic treatment when there is a time lag between the termination of orthodontic treatment and definitive restoration. Two techniques will be presented for this kind of restoration: Denture tooth pontic or a composite crown. The benefits are alveolar bone preservation, Physiologic pressure on the alveolar ridge to increase its density and even can be retained until the completion of the definitive treatment. Bonded fixed partial denture includes Maryland bridge, fiber-reinforced composite bridge, resin-bonded bridge, and ceramic bonded bridge. These types of bridges are recommended to be used after a pubertal growth spurt and a recent meta-analysis considered their clinical success similar to conventional FDPs and implant-supported crowns. However, they have several advantages that are going to be discussed by presenting some clinical examples. Practical instruction on how to construct an FRC bridge and a novel chair-side Maryland bridge will be given by means of clinical cases. Clinical relevance: minimally invasive options should always be considered and destruction of healthy enamel and dentin during the preparation phase should be avoided as much as possible.

Keywords: tooth missing, fiber-reinforced composite, Maryland, Essix retainers, screw-retained restoration

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Authors: Arpit Sachan, Nilanshu Kumar

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This paper tries to understand the nuances of feminisation of agriculture in the Indian context and how that is associated with better intrahousehold bargaining power for women. The economic survey of India indicates a constant increase in the share of the female workforce in Indian agriculture in the past few decades. This can be accounted for by many factors like the migration of male workers to urban areas and, therefore, the complete burden of agriculture shifting on the female counterparts. Therefore this study is an attempt to study that how this increase in the female workforce corresponds to a better decision-making ability for women in rural farm households. This paper is an attempt to carefully evaluate this aspect of the feminisation of Indian agriculture. The paper tries to study how various factors that improve the status of women in agriculture change with things like resource ownership. This paper uses both the macro-level and micro-level data to study the dynamics of the proportion of the workforce in agriculture across different states in India and how that has translated into better indicators for women in rural areas. The fall in India’s rank in the global gender wage gap index is alarming in such a context, and this creates a puzzle with increasing female workforce participation. The paper will consider if the condition of women improved over time with the increased share of employment or not? Using field survey data, this paper tries to understand if there exists any digression for some of the indicators both at the macro and micro level. The paper also tries to integrate the economic understanding of gender aspects of the workforce and the sociological stance prevailing in the existing literature. Therefore, this paper takes a mixed-method approach to better understand the role that social structure plays in the improved status of women within and across various households. Therefore, this paper will finally help us understanding if at all there is a feminisation of Indian agriculture or it's just exploitation of a different kind. This study intends to create a distinction between the gendered labour force in Indian agriculture and the complete democratization of Indian agriculture. The study is primarily focused on areas where the exodus of male migrants pushes women to work on agricultural farms. The question posits is whether it is the willingness of women to work in agriculture or is it urbanisation and development-induced conditions that make women work in agriculture as farm labourers? The motive is to understand if factors like resource ownership and the ability to autonomous decision-making are interlinked with an increased proportion of the female workforce or not? Based on this framework, we finally provide a brief comment on policy implications of government intervention in improving Indian agriculture and the gender aspects associated with it.

Keywords: feminisation, intrahousehold bargaining, farm households, migration, agriculture, decision-making

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Authors: Andreea Molnar, Amalia Ardeljan, Lexi Frankel, Marissa Dallara, Brittany Nagel, Omar Rashid

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Background: Escherichia coli is a gram-negative, facultative anaerobic bacteria that belongs to the family Enterobacteriaceae and resides in the intestinal tracts of individuals. E.Coli has numerous strains grouped into serogroups and serotypes based on differences in antigens in their cell walls (somatic, or “O” antigens) and flagella (“H” antigens). More than 700 serotypes of E. coli have been identified. Although most strains of E. coli are harmless, a few strains, such as E. coli O157:H7 which produces Shiga toxin, can cause intestinal infection with symptoms of severe abdominal cramps, bloody diarrhea, and vomiting. Infection with E. Coli can lead to the development of systemic inflammation as the toxin exerts its effects. Chronic inflammation is now known to contribute to cancer development in several organs, including the prostate. The purpose of this study was to evaluate the correlation between E. Coli and the incidence of prostate cancer. Methods: Data collected in this cohort study was provided by a Health Insurance Portability and Accountability Act (HIPAA) compliant national database to evaluate patients infected with E.Coli infection and prostate cancer using the International Classification of Disease (ICD-10 and ICD-9 codes). Permission to use the database was granted by Holy Cross Health, Fort Lauderdale for the purpose of academic research. Data analysis was conducted through the use of standard statistical methods. Results: Between January 2010 and December 2019, the query was analyzed and resulted in 81, 037 patients after matching in both infected and control groups, respectively. The two groups were matched by Age Range and CCI score. The incidence of prostate cancer was 2.07% and 1,680 patients in the E. Coli group compared to 5.19% and 4,206 patients in the control group. The difference was statistically significant by a p-value p<2.2x10-16 with an Odds Ratio of 0.53 and a 95% CI. Based on the specific treatment for E.Coli, the infected group vs control group were matched again with a result of 31,696 patients in each group. 827 out of 31,696 (2.60%) patients with a prior E.coli infection and treated with antibiotics were compared to 1634 out of 31,696 (5.15%) patients with no history of E.coli infection (control) and received antibiotic treatment. Both populations subsequently developed prostate carcinoma. Results remained statistically significant (p<2.2x10-16), Odds Ratio=0.55 (95% CI 0.51-0.59). Conclusion: This retrospective study shows a statistically significant correlation between E.Coli infection and a decreased incidence of prostate cancer. Further evaluation is needed in order to identify the impact of E.Coli infection and prostate cancer development.

Keywords: E. Coli, prostate cancer, protective, microbiology

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Authors: Sudhir Kumar, V. R. Sinha

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Background: The topical and systemic toxicity associated with present nonmelanoma skin cancer (NMSC) treatment therapy using 5-Fluorouracil (5-FU) make it necessary to develop a novel delivery system having lesser toxicity and better control over drug release. Solid lipid nanoparticles offer many advantages like: controlled and localized release of entrapped actives, nontoxicity, and better tolerance. Aim:-To investigate safety and efficacy of 5-FU loaded solid lipid nanoparticles as a topical delivery system for the treatment of nonmelanoma skin cancer. Method: Topical solid lipid nanoparticles of 5-FU were prepared using Compritol 888 ATO (Glyceryl behenate) as lipid component and pluronic F68 (Poloxamer 188), Tween 80 (Polysorbate 80), Tyloxapol (4-(1,1,3,3-Tetramethylbutyl) phenol polymer with formaldehyde and oxirane) as surfactants. The SLNs were prepared with emulsification method. Different formulation parameters viz. type and ratio of surfactant, ratio of lipid and ratio of surfactant:lipid were investigated on particle size and drug entrapment efficiency. Results: Characterization of SLNs like–Transmission Electron Microscopy (TEM), Differential Scannig calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), Particle size determination, Polydispersity index, Entrapment efficiency, Drug loading, ex vivo skin permeation and skin retention studies, skin irritation and histopathology studies were performed. TEM results showed that shape of SLNs was spherical with size range 200-500nm. Higher encapsulation efficiency was obtained for batches having higher concentration of surfactant and lipid. It was found maximum 64.3% for SLN-6 batch with size of 400.1±9.22 nm and PDI 0.221±0.031. Optimized SLN batches and marketed 5-FU cream were compared for flux across rat skin and skin drug retention. The lesser flux and higher skin retention was obtained for SLN formulation in comparison to topical 5-FU cream, which ensures less systemic toxicity and better control of drug release across skin. Chronic skin irritation studies lacks serious erythema or inflammation and histopathology studies showed no significant change in physiology of epidermal layers of rat skin. So, these studies suggest that the optimized SLN formulation is efficient then marketed cream and safer for long term NMSC treatment regimens. Conclusion: Topical and systemic toxicity associated with long-term use of 5-FU, in the treatment of NMSC, can be minimized with its controlled release with significant drug retention with minimal flux across skin. The study may provide a better alternate for effective NMSC treatment.

Keywords: 5-FU, topical formulation, solid lipid nanoparticles, non melanoma skin cancer

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Authors: Hanieh Sakha, Nader Nader, Haleh Farzin

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Introduction: Throughout history, pain theories have been supposed by biomedicine, especially regarding its diagnosis and treatment aspects. Therefore, the feeling of pain is not only a personal experience and is affected by social background; therefore, it involves extensive systems of signals. The challenges in emotional and sentimental dimensions of pain originate from scientific medicine (i.e., the dominant theory is also referred to as the specificity theory); however, this theory has accepted some alterations by emerging physiology. Then, Von Frey suggested the theory of cutaneous senses (i.e., Muller’s concept: the common sensation of combined four major skin receptors leading to a proper sensation) 50 years after the specificity theory. The pain pathway was composed of spinothalamic tracts and thalamus with an inhibitory effect on the cortex. Pain is referred to as a series of unique experiences with various reasons and qualities. Despite the gate control theory, the biological aspect overcomes the social aspect. Vrancken provided a more extensive definition of pain and found five approaches: Somatico-technical, dualistic body-oriented, behaviorist, phenomenological, and consciousness approaches. The Western model combined physical, emotional, and existential aspects of the human body. On the other hand, Kotarba felt confused about the basic origins of chronic pain. Freund demonstrated and argued with Durkhemian about the sociological approach to emotions. Lynch provided a piece of evidence about the correlation between cardiovascular disease and emotionally life-threatening occurrences. Helman supposed a distinction between private and public pain. Conclusion: The consideration of the emotional aspect of pain could lead to effective, emotional, and social responses to pain. On the contrary, the theory of embodiment is based on the sociological view of health and illness. Social epidemiology shows an imbalanced distribution of health, illness, and disability among various social groups. The social support and socio-cultural level can result in several types of pain. It means the status of athletes might define their pain experiences. Gender is one of the important contributing factors affecting the type of pain (i.e., females are more likely to seek health services for pain relief.) Chronic non-cancer pain (CNCP) has become a serious public health issue affecting more than 70 million people globally. CNCP is a serious public health issue which is caused by the lack of awareness about chronic pain management among the general population.

Keywords: pain, sociology, sociological, body

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Authors: Ankita Singh, Chandan Gorain, Amirul I. Mallick

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Successful adherence of the mucosal epithelial cells is the key early step for Campylobacter jejuni pathogenesis (C. jejuni). A set of Surface Exposed Colonization Proteins (SECPs) are among the major factors involved in host cell adherence and invasion of C. jejuni. Among them, constitutively expressed surface-exposed lipoprotein adhesin of C. jejuni, JlpA, interacts with intestinal heat shock protein 90 (hsp90α) and contributes in disease progression by triggering pro-inflammatory response via activation of NF-κB and p38 MAP kinase pathway. Together with its ability to express in the bacterial surface, higher sequence conservation and predicted predominance of several B cells epitopes, JlpA protein reserves its potential to become an effective vaccine candidate against wide range of Campylobacter sps including C. jejuni. Given that chickens are the primary sources for C. jejuni and persistent gut colonization remain as major cause for foodborne pathogenesis to humans, present study explicitly used chickens as model to test the immune-protective efficacy of JlpA protein. Taking into account that gastrointestinal tract is the focal site for C. jejuni colonization, to extrapolate the benefit of mucosal (intragastric) delivery of JlpA protein, a food grade Nisin inducible Lactic acid producing bacteria, Lactococcus lactis (L. lactis) was engineered to express recombinant JlpA protein (rJlpA) in the surface of the bacteria. Following evaluation of optimal surface expression and functionality of recombinant JlpA protein expressed by recombinant L. lactis (rL. lactis), the immune-protective role of intragastric administration of live rL. lactis was assessed in commercial broiler chickens. In addition to the significant elevation of antigen specific mucosal immune responses in the intestine of chickens that received three doses of rL. lactis, marked upregulation of Toll-like receptor 2 (TLR2) gene expression in association with mixed pro-inflammatory responses (both Th1 and Th17 type) was observed. Furthermore, intragastric delivery of rJlpA expressed by rL. lactis, but not the injectable form, resulted in a significant reduction in C. jejuni colonization in chickens suggesting that mucosal delivery of live rL. lactis expressing JlpA serves as a promising vaccine platform to induce strong immune-protective responses against C. jejuni in chickens.

Keywords: chickens, lipoprotein adhesion of Campylobacter jejuni, immuno-protection, Lactococcus lactis, mucosal delivery

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Authors: Shankaran Sitarama

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New Product Development involves team members coming together and working in teams to come up with innovative solutions to problems, resulting in new products. Thus, a core attribute of a successful NPD team is their creativity and innovation. They need to be creative as a group, generating a breadth of ideas and innovative solutions that solve or address the problem they are targeting and meet the user’s needs. They also need to be very efficient in their teamwork as they work through the various stages of the development of these ideas, resulting in a POC (proof-of-concept) implementation or a prototype of the product. There are two distinctive traits that the teams need to have, one is ideational creativity, and the other is effective and efficient teamworking. There are multiple types of tensions that each of these traits cause in the teams, and these tensions reflect in the team dynamics. Ideational conflicts arising out of debates and deliberations increase the collective knowledge and affect the team creativity positively. However, the same trait of challenging each other’s viewpoints might lead the team members to be disruptive, resulting in interpersonal tensions, which in turn lead to less than efficient teamwork. Teams that foster and effectively manage these creative tensions are successful, and teams that are not able to manage these tensions show poor team performance. In this paper, it explore these tensions as they result in the team communication social network and propose a Creative Tension Balance index along the lines of Degree of Balance in social networks that has the potential to highlight the successful (and unsuccessful) NPD teams. Team communication reflects the team dynamics among team members and is the data set for analysis. The emails between the members of the NPD teams are processed through a semantic analysis algorithm (LSA) to analyze the content of communication and a semantic similarity analysis to arrive at a social network graph that depicts the communication amongst team members based on the content of communication. This social network is subjected to traditional social network analysis methods to arrive at some established metrics and structural balance analysis metrics. Traditional structural balance is extended to include team interaction pattern metrics to arrive at a creative tension balance metric that effectively captures the creative tensions and tension balance in teams. This CTB (Creative Tension Balance) metric truly captures the signatures of successful and unsuccessful (dissonant) NPD teams. The dataset for this research study includes 23 NPD teams spread out over multiple semesters and computes this CTB metric and uses it to identify the most successful and unsuccessful teams by classifying these teams into low, high and medium performing teams. The results are correlated to the team reflections (for team dynamics and interaction patterns), the team self-evaluation feedback surveys (for teamwork metrics) and team performance through a comprehensive team grade (for high and low performing team signatures).

Keywords: team dynamics, social network analysis, new product development teamwork, structural balance, NPD teams

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Authors: Sneha Shankar, Orlando Buendia, Will Evans

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Alpha-1 antitrypsin deficiency (AATD) is a rare, genetic, and multisystemic condition. Underdiagnosis is common, leading to chronic pulmonary and hepatic complications, increased resource utilization, and additional costs to the healthcare system. Currently, there is limited evidence of the direct medical costs of AATD diagnosis in the UK. This study explores the economic impact of AATD patients during the 3 years before diagnosis and to identify the major cost drivers using primary and secondary care electronic health record (EHR) data. The 3 years before diagnosis time period was chosen based on the ability of our tool to identify patients earlier. The AATD algorithm was created using published disease criteria and applied to 148 known AATD patients’ EHR found in a primary care database of 936,148 patients (413,674 Biobank and 501,188 in a single primary care locality). Among 148 patients, 9 patients were flagged earlier by the tool and, on average, could save 3 (1-6) years per patient. We analysed 101 of the 148 AATD patients’ primary care journey and 20 patients’ Hospital Episode Statistics (HES) data, all of whom had at least 3 years of clinical history in their records before diagnosis. The codes related to laboratory tests, clinical visits, referrals, hospitalization days, day case, and inpatient admissions attributable to AATD were examined in this 3-year period before diagnosis. The average cost per patient was calculated, and the direct medical costs were modelled based on the mean prevalence of 100 AATD patients in a 500,000 population. A deterministic sensitivity analysis (DSA) of 20% was performed to determine the major cost drivers. Cost data was obtained from the NHS National tariff 2020/21, National Schedule of NHS Costs 2018/19, PSSRU 2018/19, and private care tariff. The total direct medical cost of one hundred AATD patients three years before diagnosis in primary and secondary care in the UK was £3,556,489, with an average direct cost per patient of £35,565. A vast majority of this total direct cost (95%) was associated with inpatient admissions (£3,378,229). The DSA determined that the costs associated with tier-2 laboratory tests and inpatient admissions were the greatest contributors to direct costs in primary and secondary care, respectively. This retrospective study shows the role of EHRs in calculating direct medical costs and the potential benefit of new technologies for the early identification of patients with AATD to reduce the economic burden in primary and secondary care in the UK.

Keywords: alpha-1 antitrypsin deficiency, costs, digital health, early diagnosis

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Authors: Hyuk Sung Yoon, In-Lee Choi, Mohammad Zahirul Islam, Jun Pill Baek, Ho-Min Kang

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The strawberry ‘Maehyang’ cultivated in South Korea has been increased to export to Southeast Asia. The degradation of quality often occurs in strawberries during short export period. Botrytis cinerea has been known to cause major damage to the export strawberries and the disease was caused during shipping and distribution. This study was conducted to find out the sterilized effect of chlorine dioxide(ClO2) gas and high concentration of CO2 gas injection for ‘Maehyang’ strawberry and it was packaged with oxygen transmission rate (OTR) films. The strawberry was harvested at 80% color changed stage and packaged with OTR film and perforated film (control). The treatments were a MAP used by with 20,000 cc·m-2·day·atm OTR film and gas injection in packages. The gas type of ClO2 and CO2 were injected into OTR film packages, and treatments were 6 mg/L ClO2, 15% CO2, and they were combined. The treated strawberries were stored at 3℃ for 30 days. Fresh weight loss rate was less than 1% in all OTR film packages but it was more than 15% in a perforated film treatment that showed severe deterioration of visual quality during storage. Carbon dioxide concentration within a package showed approximately 15% of the maximum CO2 concentration in all treatments except control until the 21st day, it was the tolerated range of maximum CO2 concentration of strawberry in recommended CA or MA conditions. But, it increased to almost 50% on the 30th day. Oxygen concentration showed a decrease down to approximately 0% in all treatments except control for 25 days. Ethylene concentration was shown to be steady until the 17th day, but it quickly increased on the 17th day and dropped down on the final storage day (30th day). All treatments did not show any significant differences in gas treatments. Firmness increased in CO2 (15%) and ClO2 (6mg/L) + CO2 (15%) treatments during storage. It might be the effect of high concentration CO2 known by reducing decay and cell wall degradation. The soluble solid decreased in all treatments during storage. These results were caused to use up the sugar by the increase of respiration during storage. The titratable acidity showed a similarity in all treatments. Incidence of fungi was 0% in CO2 (15%) and ClO2 (6mg/L)+ CO2 (15%), but was more than 20% in a perforated film treatment. Consequently, The result indicates that Chloride Dioxide(ClO2) and high concentration of CO2 inhibited fungi growth. Due to the fact that fresh weight loss rate and incidence of fungi were lower, the ClO2(6mg/L)+ CO2(15%) prove to be most efficient in sterilization. These results suggest that Chloride Dioxide (ClO2) and high concentration of CO2 gas injection treatments were an effective decontamination technique for improving the safety of strawberries.

Keywords: chloride dioxide, high concentration of CO2, modified atmosphere condition, oxygen transmission rate films

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Authors: Tetyana Kendzerska, David T. Zhu, Michael Pugliese, Douglas Manuel, Mohsen Sadatsafavi, Marcus Povitz, Therese A. Stukel, Teresa To, Shawn D. Aaron, Sunita Mulpuru, Melanie Chin, Claire E. Kendall, Kednapa Thavorn, Rebecca Robillard, Andrea S. Gershon

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The impact of the COVID-19 pandemic on the management of ambulatory care sensitive conditions (ACSCs) remains unknown. To compare observed and expected (projected based on previous years) trends in all-cause mortality and healthcare use for ACSCs in the first year of the pandemic (March 2020 - March 2021). A population-based study using provincial health administrative data.General adult population (Ontario, Canada). Monthly all-cause mortality, and hospitalizations, emergency department (ED) and outpatient visit rates (per 100,000 people at-risk) for seven combined ACSCs (asthma, COPD, angina, congestive heart failure, hypertension, diabetes, and epilepsy) during the first year were compared with similar periods in previous years (2016-2019) by fitting monthly time series auto-regressive integrated moving-average models. Compared to previous years, all-cause mortality rates increased at the beginning of the pandemic (observed rate in March-May 2020 of 79.98 vs. projected of 71.24 [66.35-76.50]) and then returned to expected in June 2020—except among immigrants and people with mental health conditions where they remained elevated. Hospitalization and ED visit rates for ACSCs remained lower than projected throughout the first year: observed hospitalization rate of 37.29 vs. projected of 52.07 (47.84-56.68); observed ED visit rate of 92.55 vs. projected of 134.72 (124.89-145.33). ACSC outpatient visit rates decreased initially (observed rate of 4,299.57 vs. projected of 5,060.23 [4,712.64-5,433.46]) and then returned to expected in June 2020. Reductions in outpatient visits for ACSCs at the beginning of the pandemic combined with reduced hospital admissions may have been associated with temporally increased mortality—disproportionately experienced by immigrants and those with mental health conditions. The Ottawa Hospital Academic Medical Organization

Keywords: COVID-19, chronic disease, all-cause mortality, hospitalizations, emergency department visits, outpatient visits, modelling, population-based study, asthma, COPD, angina, heart failure, hypertension, diabetes, epilepsy

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Authors: Natsuki Kishizawa, Keiko Nakano, Hussam Organji, Amer Shaiban, Mohammad Albeirutty

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One of the most important tasks in operating desalination plants using a reverse osmosis (RO) method is preventing RO membrane fouling caused by foulants found in seawater. Optimal design of the pre-treatment process of RO process for plants enables the reduction of foulants. Therefore, a quantitative evaluation of the fouling risk in pre-treated water, which is fed to RO, is required for optimal design. Some measurement methods for water quality such as silt density index (SDI) and total organic carbon (TOC) have been conservatively applied for evaluations. However, these methods have not been effective in some situations for evaluating the fouling risk of RO feed water. Furthermore, stable management of plants will be possible by alerts and appropriate control of the pre-treatment process by using the method if it can be applied to the inline monitoring system for the fouling risk of RO feed water. The purpose of this study is to develop a method to evaluate the fouling risk of RO feed water. We applied a quartz crystal microbalance (QCM) to measure the amount of foulants found in seawater using a sensor whose surface is coated with polyamide thin film, which is the main material of a RO membrane. The increase of the weight of the sensor after a certain length of time in which the sample water passes indicates the fouling risk of the sample directly. We classified the values as “FP: Fouling Potential”. The characteristics of the method are to measure the very small amount of substances in seawater in a short time: < 2h, and from a small volume of the sample water: < 50mL. Using some RO cell filtration units, a higher correlation between the pressure increase given by RO fouling and the FP from the method than SDI and TOC was confirmed in the laboratory-scale test. Then, to establish the correlation in the actual bench-scale RO membrane module, and to confirm the feasibility of the monitoring system as a control tool for the pre-treatment process, we have started a long-term test at an experimental desalination site by the Red Sea in Jeddah, Kingdom of Saudi Arabia. Implementing inline equipment for the method made it possible to measure FP intermittently (4 times per day) and automatically. Moreover, for two 3-month long operations, the RO operation pressure among feed water samples of different qualities was compared. The pressure increase through a RO membrane module was observed at a high FP RO unit in which feed water was treated by a cartridge filter only. On the other hand, the pressure increase was not observed at a low FP RO unit in which feed water was treated by an ultra-filter during the operation. Therefore, the correlation in an actual scale RO membrane was established in two runs of two types of feed water. The result suggested that the FP method enables the evaluation of the fouling risk of RO feed water.

Keywords: fouling, monitoring, QCM, water quality

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Authors: Maria Amaia Iza Padilla, Ibai Ostolozaga

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The objective of this paper is to analyze how transportation costs between regions within a country can affect not only domestic trade but also the allocation of resources in a given region, aggregate productivity, and relative domestic prices (tradable versus non-tradable). On the one hand, there is a vast literature that analyzes the transportation costs faced by countries when trading with the rest of the world. However, this paper focuses on the effect of transportation costs on domestic trade. Countries differ in their domestic road infrastructure and transport quality. There is also some literature that focuses on the effect of road infrastructure on the price difference between regions but not on relative prices at the aggregate level. On the other hand, this work is also related to the literature on resource misallocation. Finally, the paper is also related to the literature analyzing the effect of trade on the development of the manufacturing sector. Using the World Bank Enterprise Survey database, it is observed cross-country differences in the proportion of firms that consider transportation as an obstacle. From the International Comparison Program, we obtain a significant negative correlation between GDP per worker and relative prices (manufacturing sector prices relative to the service sector). Furthermore, there is a significant negative correlation between a country’s transportation quality and the relative price of manufactured goods with respect to the price of services in that country. This is consistent with the empirical evidence of a negative correlation between transportation quality and GDP per worker, on the one hand, and the negative correlation between GDP per worker and domestic relative prices, on the other. It is also shown that in a country, the share of manufacturing firms whose main market is at the local (regional) level is negatively related to the quality of the transportation infrastructure within the country. Similarly, this index is positively related to the share of manufacturing firms whose main market is national or international. The data also shows that those countries with a higher proportion of manufacturing firms operating locally have higher relative prices. With this information in hand, the paper attempts to quantify the effects of the allocation of resources between and within sectors. The higher the trade barriers caused by transportation costs, the less efficient allocation, which causes lower aggregate productivity. Second, it is built a two-sector model where regions within a country trade with each other. On the one hand, it is found that with respect to the manufacturing sector, those countries with less trade between their regions will be characterized by a smaller variety of goods, less productive manufacturing firms on average, and higher relative prices for manufactured goods relative to service sector prices. Thus, the decline in the relative price of manufactured goods in more advanced countries could also be explained by the degree of trade between regions. This trade allows for efficient intra-industry allocation (traders are more productive, and resources are allocated more efficiently)).

Keywords: misallocation, relative prices, TFP, transportation cost

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Authors: Lívia Pinheiro Carvalho, Luciana Di Thommazo-Luporini, Rafael Luís Luporini, José Carlos Bonjorno Junior, Renata Pedrolongo Basso Vanelli, Manoel Carneiro de Oliveira Junior, Rodolfo de Paula Vieira, Renata Trimer, Renata G. Mendes, Mylène Aubertin-Leheudre, Audrey Borghi-Silva

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Rationale: Cardiorespiratory fitness (CRF) and functional capacity in young obese and normal-weight people are associated with metabolic and cardiovascular diseases and mortality. However, it remains unclear whether their metabolically healthy (MH) or at risk (AR) phenotype influences cardiorespiratory fitness in this vulnerable population such as obese adults but also in normal-weight people. HOMA insulin resistance index (HI) and leptin-adiponectin ratio (LA) are strong markers for characterizing those phenotypes that we hypothesized to be associated with physical fitness. We also hypothesized that an easy and feasible exercise test could identify a subpopulation at risk to develop metabolic and related disorders. Methods: Thirty-nine sedentary men and women (20-45y; 18.530 kg.m-2) underwent a clinical evaluation, including the six-minute step test (ST), a well-validated and reliable test for young people. Body composition assessment was done by a tetrapolar bioimpedance in a fasting state and in the folicular phase for women. A maximal cardiopulmonary exercise testing, as well as the ST, evaluated the oxygen uptake at the peak of the test (VO2peak) by an ergospirometer Oxycon Mobile. Lipids, glucose, insulin were analysed and the ELISA method quantified the serum leptin and adiponectin from blood samples. Volunteers were divided in two groups: AR or MH according to a HI cutoff of 1.95, which was previously determined in the literature. T-test for comparison between groups, Pearson´s test to correlate main variables and ROC analysis for discriminating AR from up-and-down cycles in ST (SC) were applied (p<0.05). Results: Higher LA, fat mass (FM) and lower HDL, SC, leg lean mass (LM) and VO2peak were found in AR than in MH. Significant correlations were found between VO2peak and SC (r= 0.80) as well as between LA and FM (r=0.87), VO2peak (r=-0.73), and SC (r=-0.65). Area under de curve showed moderate accuracy (0.75) of SC <173 to discriminate AR phenotype. Conclusion: Our study found that at risk obese and normal-weight subjects showed an unhealthy metabolism as well as a poor CRF and functional daily activity capacity. Additionally, a simple and less costly functional test associated with above-mentioned aspects is able to identify ‘at risk’ subjects for primary intervention with important clinical and health implications.

Keywords: aerobic capacity, exercise, fitness, metabolism, obesity, 6MST

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Authors: Justine Garraud, Hervé Capiaux, Cécile Le Guern, Pierre Gaudin, Clémentine Lapie, Samuel Chaffron, Erwan Delage, Thierry Lebeau

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The repeated use of Bordeaux mixture (copper sulphate) and other chemical forms of copper (Cu) has led to its accumulation in wine-growing soils for more than a century, to the point of modifying the ecosystem of these soils. Phytoextraction of copper could progressively reduce the Cu load in these soils, and even to recycle copper (e.g. as a micronutrient in animal nutrition) by cultivating the extracting plants in the inter-row of the vineyards. Soil cleaning up usually requires several years because the chemical speciation of Cu in solution is mainly based on forms complexed with dissolved organic matter (DOM) that are not phytoavailable, unlike the "free" forms (Cu2+). Indeed, more than 98% of Cu in the solution is bound to DOM. The selection and inoculation of invineyardsoils in vineyard soils ofbacteria(bioaugmentation) able to degrade Cu-DOM complexes could increase the phytoavailable pool of Cu2+ in the soil solution (in addition to bacteria which first mobilize Cu in solution from the soil bearing phases) in order to increase phytoextraction performance. In this study, sevenCu-accumulating plants potentially usable in inter-row were tested for their Cu phytoextraction capacity in hydroponics (ray-grass, brown mustard, buckwheat, hemp, sunflower, oats, and chicory). Also, a bacterial consortium was tested: Pseudomonas sp. previously studied for its ability to mobilize Cu through the pyoverdine siderophore (complexing agent) and potentially to degrade Cu-DOM complexes, and a second bacterium (to be selected) able to promote the survival of Pseudomonas sp. following its inoculation in soil. Interaction network method was used based on the notions of co-occurrence and, therefore, of bacterial abundance found in the same soils. Bacteria from the EcoVitiSol project (Alsace, France) were targeted. The final step consisted of incoupling the bacterial consortium with the chosen plant in soil pots. The degradation of Cu-DOMcomplexes is measured on the basis of the absorption index at 254nm, which gives insight on the aromaticity of the DOM. The“free” Cu in solution (from the mobilization of Cu and/or the degradation of Cu-MOD complexes) is assessed by measuring pCu. Eventually, Cu accumulation in plants is measured by ICP-AES. The selection of the plant is currently being finalized. The interaction network method targeted the best positive interactions ofFlavobacterium sp. with Pseudomonassp. These bacteria are both PGPR (plant growth promoting rhizobacteria) with the ability to improve the plant growth and to mobilize Cu from the soil bearing phases (siderophores). Also, these bacteria are known to degrade phenolic groups, which are highly present in DOM. They could therefore contribute to the degradation of DOM-Cu. The results of the upcoming bacteria-plant coupling tests in pots will be also presented.

Keywords: complexes Cu-DOM, bioaugmentation, phytoavailability, phytoextraction

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Authors: A. Mulry, C. Kealey, D. B. Brady

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Planktonic bacteria can form biofilms which are microbial aggregates embedded within a matrix of extracellular polymeric substances (EPS). They can be found attached to abiotic or biotic surfaces. Biofilms are responsible for oral diseases such as dental caries, gingivitis and the progression of periodontal disease. Biofilms can resist 500 to 1000 times the concentration of biocides and antibiotics used to kill planktonic bacteria. Biofilm development on oral surfaces involves four stages, initial attachment, early development, maturation and dispersal of planktonic cells. The Minimum Inhibitory Concentration (MIC) was determined using a range of saturated and unsaturated fatty acids using the resazurin assay, followed by serial dilution and spot plating on BHI agar plates to establish the Minimum Bactericidal Concentration (MBC). Log reduction of bacteria was also evaluated for each fatty acid. The Minimum Biofilm Inhibition Concentration (MBIC) was determined using crystal violet assay in 96 well plates on forming and pre-formed S. mutans biofilms using BHI supplemented with 1% sucrose. Saturated medium-chain fatty acids Octanoic (C8.0), Decanoic (C10.0) and Undecanoic acid (C11.0) do not display strong antibiofilm properties; however, Lauric (C12.0) and Myristic (C14.0) display moderate antibiofilm properties with 97.83% and 97.5% biofilm inhibition with 1000 µM respectively. Monounsaturated, Oleic acid (C18.1) and polyunsaturated large chain fatty acids, Linoleic acid (C18.2) display potent antibiofilm properties with biofilm inhibition of 99.73% at 125 µM and 100% at 65.5 µM, respectively. Long-chain polyunsaturated Omega-3 fatty acids α-Linoleic (C18.3), Eicosapentaenoic Acid (EPA) (C20.5), Docosahexaenoic Acid (DHA) (C22.6) have displayed strong antibiofilm efficacy from concentrations ranging from 31.25-250µg/ml. DHA is the most promising antibiofilm agent with an MBIC of 99.73% with 15.625µg/ml. This may be due to the presence of six double bonds and the structural orientation of the fatty acid. To conclude, fatty acids displaying the most antimicrobial activity appear to be medium or long-chain unsaturated fatty acids containing one or more double bonds. Most promising agents include Omega-3-fatty acids Linoleic, α-Linoleic, EPA and DHA, as well as Omega-9 fatty acid Oleic acid. These results indicate that fatty acids have the potential to be used as antimicrobials and antibiofilm agents against S. mutans. Future work involves further screening of the most potent fatty acids against a range of bacteria, including Gram-positive and Gram-negative oral pathogens. Future work will involve incorporating the most effective fatty acids onto dental implant devices to prevent biofilm formation.

Keywords: antibiofilm, biofilm, fatty acids, S. mutans

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Authors: Rakesh Mishra, Rajni Singh, Mukunda Upadhyay

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Since the last few decades, the prima facie of development has shifted towards the working population in India. There has been a paradigm shift in the development approach with the realization that the present demographic dividend has to be harnessed for sustainable development. Rapid urbanization and improved socioeconomic characteristics experienced within its territory has catalyzed various forms of migration into it, resulting in massive transference of workforce between its states. Workforce in any country plays a very crucial role in deciding development of both the places, from where they have out-migrated and the place they are residing currently. In India, people are found to be migrating from relatively less developed states to a well urbanized and developed state for satisfying their neediness. Linking migration to HDI at place of destination, the regression coefficient (β ̂) shows affirmative association between them, because higher the HDI of the place would be, higher would be chance of earning and hence likeliness of the migrants would be more to choose that place as a new destination and vice versa. So the push factor is compromised by the cost of rearing and provides negative impulse on the in migrants letting down their numbers to metro cities or megacities of the states but increasing their mobility to the suburban areas and vice versa. The main objective of the study is to check the role of migration in deciding the dividend of the place of destination as well as people at the place of their usual residence with special focus to highly urban states in India. Idealized scenario of Indian migrants refers to some new theories in making. On analyzing the demographic dividend of the places we got to know that Uttar Pradesh provides maximum dividend to Maharashtra, West Bengal and Delhi, and the demographic divided of migrants are quite comparable to the native’s shares in the demographic dividend in these places. On analyzing the data from National Sample Survey 64th round and Census of India-2001, we have observed that for males in rural areas, the share of unemployed person declined by 9 percentage points (from 45% before migration to 36 % after migration) and for females in rural areas the decline was nearly 12 percentage points (from 79% before migration to 67% after migration. It has been observed that the shares of unemployed males in both rural and urban areas, which were significant before migration, got reduced after migration while the share of unemployed females in the rural as well as in the urban areas remained almost negligible both for before and after migration. So increase in the number of employed after migration provides an indication of changes in the associated cofactors like health and education of the place of destination and arithmetically to the place from where they have migrated out. This paper presents the evidence on the patterns of prevailing migration dynamics and corresponding demographic benefits in India and its states, examines trends and effects, and discusses plausible explanations.

Keywords: migration, demographic shift, human development index, multilevel analysis

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Authors: Arunas Emeljanovas, Brigita Mieziene, Vida Cesnaitiene, Ingunn Fjortoft, Lise Kjonniksen

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Background: Gender differences in physical fitness were tracked in many studies with lower effect in preschool children and increasing difference among genders across age. In Lithuania, on a population level, secular trends in physical fitness were regularly observed each ten years for the last two decades for 11-18 years old students. However, there is apparently a lack of such epidemiological studies among primary school students. Assessing and monitoring physical fitness from an early age is of particular importance seeking to develop and strengthen physical abilities of youths for future health benefits. The goal of the current study was to indicate age and gender differences in anthropometric measures, musculoskeletal, motor and cardiorespiratory fitness in Lithuanian primary school children. Methods: The study included 3456 1-4th grade students from 6 to 10 years. The data reliably represents the population of primary school children in Lithuania. Among them, 1721 (49.8 percent) were boys. Physical fitness was measured by the 9-item test battery, developed by Fjørtoft and colleagues (2011). Height and weight were measured and body mass index was calculated. Student t test evaluated differences in physical fitness between boys and girls, ANOVA was performed to indicate differences across age. Results: All anthropometric and fitness means that were identified as significantly different were better in boys than in girls and in older than younger students (p < .05). Among anthropometric measures, height was higher in boys aged 7 through 9 years. Weight and BMI differed among boys and girls only at 8 years old. Means of height and weight increased significantly across all ages. Among musculoskeletal fitness tests, means of standing broad jump, throwing a tennis ball and pushing a medicine ball were different between genders within each age group and across all ages. Differences between genders were less likely in motor fitness than in musculoskeletal or cardiorespiratory fitness. Differences in means of shuttle run 10 x 5 test between genders occurred at age 6, 9 and 10 years; running 20 m at age 6 and 9 years, and climbing wall bars at age 9 and 10. Means of Reduced Cooper test representing cardiorespiratory fitness were different between genders within each age group but did not differ among age 6 and 8 as well as 7 and 8 years in boys, and among age 7 and 8 years in girls. Conclusion: In general, the current study confirms gender differences in musculoskeletal, motor and cardiorespiratory fitness found in other studies across the world in primary school and older children. Observed gender differences might be explained by higher physical activity in boys rather than girls. As it is explained by previous literature, older boys and girls had better performances than younger ones, because of the components of fitness change as a function of growth, maturation, development, and interactions among the three processes.

Keywords: primary school children, motor fitness, musculoskeletal fitness, cardiovascular fitness

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Authors: Danna Jia, Bin Li

Abstract:

Background: Atopic dermatitis (AD) is a chronic and refractory inflammatory skin disease characterized by relapsing eczematous and pruritic skin lesions. The global prevalence of AD ranges from 1~ 20%, and its incidence rates are increasing. It affects individuals from infancy to adulthood, significantly impacting their daily lives and social activities. Despite its major health burden, the precise mechanisms underlying AD remain unknown. Understanding the genetic differences associated with AD is crucial for advancing diagnosis and targeted treatment development. This study aims to identify candidate genes of AD by using bioinformatics analysis. Methods: We conducted a comprehensive analysis of four pooled transcriptomic datasets (GSE16161, GSE32924, GSE130588, and GSE120721) obtained from the Gene Expression Omnibus (GEO) database. Differential gene expression analysis was performed using the R statistical language. The differentially expressed genes (DEGs) between AD patients and normal individuals were functionally analyzed using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. Furthermore, a protein-protein interaction (PPI) network was constructed to identify candidate genes. Results: Among the patient-level gene expression datasets, we identified 114 shared DEGs, consisting of 53 upregulated genes and 61 downregulated genes. Functional analysis using GO and KEGG revealed that the DEGs were mainly associated with the negative regulation of transcription from RNA polymerase II promoter, membrane-related functions, protein binding, and the Human papillomavirus infection pathway. Through the PPI network analysis, we identified eight core genes: CD44, STAT1, HMMR, AURKA, MKI67, and SMARCA4. Conclusion: This study elucidates key genes associated with AD, providing potential targets for diagnosis and treatment. The identified genes have the potential to contribute to the understanding and management of AD. The bioinformatics analysis conducted in this study offers new insights and directions for further research on AD. Future studies can focus on validating the functional roles of these genes and exploring their therapeutic potential in AD. While these findings will require further verification as achieved with experiments involving in vivo and in vitro models, these results provided some initial insights into dysfunctional inflammatory and immune responses associated with AD. Such information offers the potential to develop novel therapeutic targets for use in preventing and treating AD.

Keywords: atopic dermatitis, bioinformatics, biomarkers, genes

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Authors: Shams Khaled Abdelrahman Abdallah Elbaz, Alaa Aldeen Abd Al Hakeem Balbaa

Abstract:

Purpose: The purpose of this study was to compare the effects of Positional Release Technique versus Kinesio Tape on pain level, pressure pain threshold level and functional disability in patients with back myofascial pain syndrome at iliocostalis lumborum. Backgrounds/significance: Myofascial Pain Syndrome is a common muscular pain syndrome that arises from trigger points which are hyperirritable, painful and tender points within a taut band of skeletal muscle. In more recent literature, about 75% of patients with musculoskeletal pain presenting to a community medical centres suffer from myofascial pain syndrome.Iliocostalis lumborum are most likely to develop active trigger points. Subjects: Thirty patients diagnosed as back myofascial pain syndrome with active trigger points in iliocostalis lumborum muscle bilaterally had participated in this study. Methods and materials: Patients were randomly distributed into two groups. The first group consisted of 15 patients (8 males and 7 females) with mean age 30.6 (±3.08) years, they received positional release technique which was applied 3 times per session, 3/week every other day for 2 weeks. The second group consisted of 15 patients(5 males, 10 females) with a mean age 30.4 (±3.35) years, they received kinesio tape which was applied and changed every 3 days with one day off for a total 3 times in 2 weeks. Both techniques were applied over trigger points of the iliocostalis lumborum bilaterally. Patients were evaluated pretreatment and posttreatment program for Pain intensity (Visual analogue scale), pressure pain threshold (digital pressure algometry), and functional disability (The Oswestry Disability Index). Analyses: Repeated measures MANOVA was used to detect differences within and between groups pre and post treatment. Then the univariate ANOVA test was conducted for the analysis of each dependant variable within and between groups. All statistical analyses were done using SPSS. with significance level set at p<0.05 throughout all analyses. Results: The results revealed that there was no significant difference between positional release technique and kinesio tape technique on pain level, pressure pain threshold and functional activities (p > 0.05). Both groups of patients showed significant improvement in all the measured variables (p < 0.05) evident by significant reduction of both pain intensity and functional disability as well as significant increase of pressure pain threshold Conclusions : Both positional release technique and kinesio taping technique are effective in reducing pain level, improving pressure pain threshold and improving function in treating patients who suffering from back myofascial pain syndrome at iliocostalis lumborum. As there was no statistically significant difference was proven between both of them.

Keywords: positional release technique, kinesio tape, myofascial pain syndrome, Iliocostalis lumborum

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Authors: Haoming Ma, Guo Yu, Peiru Zhou

Abstract:

Background: Previous studies show that dysglycemia, mostly hyperglycemia, hypoglycemia and glycemic variability(GV), are associated with excess mortality in critically ill patients, especially those without diabetes. Glycemic variability is an increasingly important measure of glucose control in the intensive care unit (ICU) due to this association. However, there is limited data pertaining to the relationship between different clinical factors and glycemic variability and clinical outcomes categorized by their DM status. This retrospective study of 958 intensive care unit(ICU) patients was conducted to investigate the relationship between GV and outcome in critically ill patients and further to determine the significant factors that contribute to the glycemic variability. Aim: We hypothesize that the factors contributing to mortality and the glycemic variability are different from critically ill patients with or without diabetes. And the primary aim of this study was to determine which dysglycemia (hyperglycemia\hypoglycemia\glycemic variability) is independently associated with an increase in mortality among critically ill patients in different groups (DM/Non-DM). Secondary objectives were to further investigate any factors affecting the glycemic variability in two groups. Method: A total of 958 diabetic and non-diabetic patients with severe diseases in the ICU were selected for this retrospective analysis. The glycemic variability was defined as the coefficient of variation (CV) of blood glucose. The main outcome was death during hospitalization. The secondary outcome was GV. The logistic regression model was used to identify factors associated with mortality. The relationships between GV and other variables were investigated using linear regression analysis. Results: Information on age, APACHE II score, GV, gender, in-ICU treatment and nutrition was available for 958 subjects. Predictors remaining in the final logistic regression model for mortality were significantly different in DM/Non-DM groups. Glycemic variability was associated with an increase in mortality in both DM(odds ratio 1.05; 95%CI:1.03-1.08,p＜0.001) or Non-DM group(odds ratio 1.07; 95%CI:1.03-1.11,p=0.002). For critically ill patients without diabetes, factors associated with glycemic variability included APACHE II score(regression coefficient, 95%CI:0.29,0.22-0.36,p＜0.001), Mean BG(0.73,0.46-1.01,p＜0.001), total parenteral nutrition(2.87,1.57-4.17,p＜0.001), serum albumin(-0.18,-0.271 to -0.082,p＜0.001), insulin treatment(2.18,0.81-3.55,p=0.002) and duration of ventilation(0.006,0.002-1.010,p=0.003).However, for diabetes patients, APACHE II score(0.203,0.096-0.310,p＜0.001), mean BG(0.503,0.138-0.869,p=0.007) and duration of diabetes(0.167,0.033-0.301,p=0.015) remained as independent risk factors of GV. Conclusion: We found that the relation between dysglycemia and mortality is different in the diabetes and non-diabetes groups. And we confirm that GV was associated with excess mortality in DM or Non-DM patients. Furthermore, APACHE II score, Mean BG, total parenteral nutrition, serum albumin, insulin treatment and duration of ventilation were significantly associated with an increase in GV in Non-DM patients. While APACHE II score, mean BG and duration of diabetes (years) remained as independent risk factors of increased GV in DM patients. These findings provide important context for further prospective trials investigating the effect of different clinical factors in critically ill patients with or without diabetes.

Keywords: diabetes, glycemic variability, predictors, severe disease

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Authors: Celeste E. van Rinsum, Sanne M. P. L. Gerards, Geert M. Rutten, Ien A. M. van de Goor, Stef P. J. Kremers

Abstract:

Combined lifestyle interventions have shown to be effective in changing and maintaining behavioral lifestyle changes and reducing overweight and obesity. A lifestyle coach is expected to promote lifestyle changes in adults related to physical activity and diet. The present Coaching on Lifestyle (CooL) study examined participants’ physical activity level, dietary behavioral, and motivational changes immediately after the intervention and at 1.5 years after baseline. In CooL intervention a lifestyle coach coaches individuals from eighteen years and older with (a high risk of) obesity in group and individual sessions. In addition a process evaluation was conducted in order to examine the implementation process and to be able to interpret the changes within the participants. This action-oriented research has a pre-post design. Participants of the CooL intervention (N = 200) completed three questionnaires: at baseline, immediately after the intervention (on average after 44 weeks), and at 1.5 years after baseline. T-tests and linear regressions were conducted to test self-reported changes in physical activity (IPAQ), dietary behaviors, their quality of motivation for physical activity (BREQ-3) and for diet (REBS), body mass index (BMI), and quality of life (EQ-5D-3L). For the process evaluation, we used individual and group interviews, observations and document analyses to gain insight in the implementation process (e.g. the recruitment) and how the intervention was valued by the participants, lifestyle coaches, and referrers. The study is currently ongoing and therefore the results presented here are preliminary. On average, the participants that finished the intervention and those that have completed the long-term measurement improved their level of vigorous-intense physical activity, sedentary behavior, sugar-sweetened beverage consumption and BMI. Mixed results were observed in motivational regulation for physical activity and nutrition. Moreover, an improvement on the quality of life dimension anxiety/depression was found, also in the long-term. All the other constructs did not show significant change over time. The results of the process evaluation have shown that recruitment of clients was difficult. Participants evaluated the intervention positively and the lifestyle coaches have continuously adapted the structure and contents of the intervention throughout the study period, based on their experiences and feedback from research. Preliminary results indicate that the CooL-intervention may have beneficial effects on overweight and obese participants in terms of energy balance-related behaviors, weight reduction, and quality of life. Recruitment of participants and embedding the position of the lifestyle coach in traditional care structures is challenging.

Keywords: combined lifestyle intervention, effect evaluation, lifestyle coaching, process evaluation, overweight, the Netherlands

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