Search results for: soil borne plant disease

Authors: M. Testa, L. Peotta, S. Giusiano, B. Lazzolino, U. Manera, A. Canosa, M. Grassano, F. Palumbo, A. Bombaci, S. Cabras, F. Di Pede, L. Solero, E. Matteoni, C. Moglia, A. Calvo, A. Chio

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Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease of adulthood, which primarily affects the central nervous system and is characterized by progressive bilateral degeneration of motor neurons. The degeneration processes in ALS extend far beyond the neurons of the motor system, and affects cognition, behaviour and language. To outline the prevalence of language deficits in an ALS cohort and explore their profile along with demographic and neuropsychological data. A full neuropsychological battery and language assessment was administered to 56 ALS patients. Neuropsychological assessment included tests of executive functioning, verbal fluency, social cognition and memory. Language was assessed using tests for verbal comprehension, production and pragmatics. Patients were cognitively classified following the Revised Consensus Criteria and divided in three groups showing different levels of language deficits: group 1 - no language deficit; group 2 - one language deficit; group 3 - two or more language deficits. Chi-square for independence and non-parametric measures to compare groups were applied. Nearly half of ALS-CN patients (48%) reported one language test under the clinical cut-off, and only 13% of patents classified as ALS-CI showed no language deficits, while the rest 87% of ALS-CI reported two or more language deficits. ALS-BI and ALS-CBI cases all reported two or more language deficits. Deficits in production and in comprehension appeared more frequent in ALS-CI patients (p=0.011, p=0.003 respectively), with a higher percentage of comprehension deficits (83%). Nearly all ALS-CI reported at least one deficit in pragmatic abilities (96%) and all ALS-BI and ALS-CBI patients showed pragmatic deficits. Males showed higher percentage of pragmatic deficits (97%, p=0.007). No significant differences in language deficits have been found between bulbar and spinal onset. Months from onset and level of impairment at testing (ALS-FRS total score) were not significantly different between levels and type of language impairment. Age and education were significantly higher for cases showing no deficits in comprehension and pragmatics and in the group showing no language deficits. Comparing performances at neuropsychological tests among the three levels of language deficits, no significant differences in neuropsychological performances were found between group 1 and 2; compared to group 1, group 3 appeared to decay specifically on executive testing, verbal/visuospatial learning, and social cognition. Compared to group 2, group 3 showed worse performances specifically in tests of working memory and attention. Language deficits have found to be spread in our sample, encompassing verbal comprehension, production and pragmatics. Our study reveals that also cognitive intact patients (ALS-CN) showed at least one language deficit in 48% of cases. Pragmatic domain is the most compromised (84% of the total sample), present in nearly all ALS-CI (96%), likely due to the influence of executive impairment. Lower age and higher education seem to preserve comprehension, pragmatics and presence of language deficits. Finally, executive functions, verbal/visuospatial learning and social cognition differentiate the group with no language deficits from the group with a clinical language impairment (group 3), while attention and working memory differentiate the group with one language deficit from the clinical impaired group.

Keywords: amyotrophic lateral sclerosis, language assessment, neuropsychological assessment, language deficit

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Authors: Rupali Bhatia, Deepthi Nair, Geetika Khanna, Seema Singhal

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Introduction: Genital tract tuberculosis is a chronic disease (caused by reactivation of organisms from systemic distribution of Mycobacterium tuberculosis) that often presents with low grade symptoms and non-specific complaints. Patients with genital tuberculosis are usually young women seeking workup and treatment for infertility. Infertility is the commonest presentation due to involvement of the fallopian tubes, endometrium and ovarian damage with poor ovarian volume and reserve. The diagnosis of genital tuberculosis is difficult because of the fact that it is a silent invader of genital tract. Since tissue cannot be obtained from fallopian tubes, the diagnosis is made by isolation of bacilli from endometrial tissue obtained by endometrial biopsy curettage and/or aspiration. Problems are associated with sampling technique as well as diagnostic modality due to lack of adequate sample volumes and the segregation of the sample for various diagnostic tests resulting in non-uniform distribution of microorganisms. Moreover, lack of an efficient sampling technique universally applicable for all specific diagnostic tests contributes to the diagnostic challenges. Endometrial sampling plays a key role in accurate diagnosis of female genital tuberculosis. It may be done by 2 methods viz. endometrial curettage and endometrial aspiration. Both endometrial curettage and aspirate have their own limitations as curettage picks up strip of the endometrium from one of the walls of the uterine cavity including tubal osteal areas whereas aspirate obtains total tissue with exfoliated cells present in the secretory fluid of the endometrial cavity. Further, sparse and uneven distribution of the bacilli remains a major factor contributing to the limitations of the techniques. The sample that is obtained by either technique is subjected to histopathological examination, AFB staining, culture and PCR. Aim: Comparison of the sampling techniques viz. endometrial biopsy curettage and endometrial aspiration using different laboratory methods of histopathology, cytology, microbiology and molecular biology. Method: In a hospital based observational study, 75 Indian females suspected of genital tuberculosis were selected on the basis of inclusion criteria. The women underwent endometrial tissue sampling using Novaks biopsy curette and Karmans cannula. One part of the specimen obtained was sent in formalin solution for histopathological testing and another part was sent in normal saline for acid fast bacilli smear, culture and polymerase chain reaction. The results so obtained were correlated using coefficient of correlation and chi square test. Result: Concordance of results showed moderate agreement between both the sampling techniques. Among HPE, AFB and PCR, maximum sensitivity was observed for PCR, though the specificity was not as high as other techniques. Conclusion: Statistically no significant difference was observed between the results obtained by the two sampling techniques. Therefore, one may use either EA or EB to obtain endometrial samples and avoid multiple sampling as both the techniques are equally efficient in diagnosing genital tuberculosis by HPE, AFB, culture or PCR.

Keywords: acid fast bacilli (AFB), histopatholgy examination (HPE), polymerase chain reaction (PCR), endometrial biopsy curettage

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Authors: Mirosław Krzemieniewski, Marcin Zieliński, Marcin Dębowski

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Electrokinetic disintegration is one of the high-voltage electric methods. The design of systems is exceptionally simple. Biomass flows through a system of pipes with alongside mounted electrodes that generate an electric field. Discharges in the electric field deform cell walls and lead to their successive perforation, thereby making their contents easily available to bacteria. The spark-over occurs between electrode surface and pipe jacket which is the second pole and closes the circuit. The value of voltage ranges from 10 to 100kV. Electrodes are supplied by normal “power grid” monophase electric current (230V, 50Hz). Next, the electric current changes into direct current of 24V in modules serving for particular electrodes, and this current directly feeds the electrodes. The installation is completely safe because the value of generated current does not exceed 250mA and because conductors are grounded. Therefore, there is no risk of electric shock posed to the personnel, even in the case of failure or incorrect connection. Low values of the electric current mean small energy consumption by the electrode which is extremely low – only 35W per electrode – compared to other methods of disintegration. Pipes with electrodes with diameter of DN150 are made of acid-proof steel and connected from both sides with 90º elbows ended with flanges. The available S and U types of pipes enable very convenient fitting with system construction in the existing installations and rooms or facilitate space management in new applications. The system of pipes for electrokinetic disintegration may be installed horizontally, vertically, askew, on special stands or also directly on the wall of a room. The number of pipes and electrodes is determined by operating conditions as well as the quantity of substrate, type of biomass, content of dry matter, method of disintegration (single or circulatory), mounting site etc. The most effective method involves pre-treatment of substrate that may be pumped through the disintegration system on the way to the fermentation tank or recirculated in a buffered intermediate tank (substrate mixing tank). Biomass structure destruction in the process of electrokinetic disintegration causes shortening of substrate retention time in the tank and acceleration of biogas production. A significant intensification of the fermentation process was observed in the systems operating in the technical scale, with the greatest increase in biogas production reaching 18%. The secondary, but highly significant for the energetic balance, effect is a tangible decrease of energy input by agitators in tanks. It is due to reduced viscosity of the biomass after disintegration, and may result in energy savings reaching even 20-30% of the earlier noted consumption. Other observed phenomena include reduction in the layer of surface scum, reduced sewage capability for foaming and successive decrease in the quantity of bottom sludge banks. Considering the above, the system for electrokinetic disintegration seems a very interesting and valuable solutions meeting the offer of specialist equipment for the processing of plant biomass, including Virginia fanpetals, before the process of methane fermentation.

Keywords: electrokinetic disintegration, biomass, biogas production, fermentation, Virginia fanpetals

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Authors: Suliman Al-Fayoumi, Sherri Amberg, Huafeng Zhou, Jack W. Singer, James P. Dean

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Pacritinib is an oral kinase inhibitor with specificity for JAK2, FLT3, IRAK1, and CSF1R. In clinical studies, pacritinib was well tolerated with clinical activity in patients with myelofibrosis. The most frequent adverse events (AEs) observed with pacritinib are gastrointestinal (diarrhea, nausea, and vomiting; mostly grade 1-2 in severity) and typically resolve within 2 weeks. A human ADME mass balance study demonstrated that pacritinib is predominantly cleared via hepatic metabolism and biliary excretion (>85% of administered dose). The major hepatic metabolite identified, M1, is not thought to materially contribute to the pharmacological activity of pacritinib. Hepatic diseases are known to impair hepatic blood flow, drug-metabolizing enzymes, and biliary transport systems and may affect drug absorption, disposition, efficacy, and toxicity. This phase 1 study evaluated the pharmacokinetics (PK) and safety of pacritinib and the M1 metabolite in study subjects with mild, moderate, or severe hepatic impairment (HI) and matched healthy subjects with normal liver function to determine if pacritinib dosage adjustments are necessary for patients with varying degrees of hepatic insufficiency. Study participants (aged 18-85 y) were enrolled into 4 groups based on their degree of HI as defined by Child-Pugh Clinical Assessment Score: mild (n=8), moderate (n=8), severe (n=4), and healthy volunteers (n=8) matched for age, BMI, and sex. Individuals with concomitant renal dysfunction or progressive liver disease were excluded. A single 400 mg dose of pacritinib was administered to all participants. Blood samples were obtained for PK evaluation predose and at multiple time points postdose through 168 h. Key PK parameters evaluated included maximum plasma concentration (Cmax), time to Cmax (Tmax), area under the plasma concentration time curve (AUC) from hour zero to last measurable concentration (AUC0-t), AUC extrapolated to infinity (AUC0-∞), and apparent terminal elimination half-life (t1/2). Following treatment, pacritinib was quantifiable for all study participants at 1 h through 168 h postdose. Systemic pacritinib exposure was similar between healthy volunteers and individuals with mild HI. However, there was a significant difference between those with moderate and severe HI and healthy volunteers with respect to peak concentration (Cmax) and plasma exposure (AUC0-t, AUC0-∞). Mean Cmax decreased by 47% and 57% respectively in participants with moderate and severe HI vs matched healthy volunteers. Similarly, mean AUC0-t decreased by 36% and 45% and mean AUC0-∞ decreased by 46% and 48%, respectively in individuals with moderate and severe HI vs healthy volunteers. Mean t1/2 ranged from 51.5 to 74.9 h across all groups. The variability on exposure ranged from 17.8% to 51.8% across all groups. Systemic exposure of M1 was also significantly decreased in study participants with moderate or severe HI vs. healthy participants and individuals with mild HI. These changes were not significantly dissimilar from the inter-patient variability in these parameters observed in healthy volunteers. All AEs were grade 1-2 in severity. Diarrhea and headache were the only AEs reported in >1 participant (n=4 each). Based on these observations, it is unlikely that dosage adjustments would be warranted in patients with mild, moderate, or severe HI treated with pacritinib.

Keywords: pacritinib, myelofibrosis, hepatic impairment, pharmacokinetics

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Authors: Etienne Herrick

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As an economically and ecologically feasible method for farmers to introduce greater diversity into their crop rotations, cover cropping presents a valuable opportunity for improving the sustainability of food production. Planted in-between cash crop growing seasons, cover crops serve to enhance agroecosystem functioning, rather than being destined for sale or consumption. In fact, cover crops may hold the capacity to deliver multiple ecosystem functions or services simultaneously (multifunctionality). Building upon this line of research will not only benefit society at present, but also support its continued survival through its potential for restoring depleted soils and reducing the need for energy-intensive and harmful external inputs like fertilizers and pesticides. This study utilizes a trait-based approach to explore the influence of inter- and intra-specific interactions in summer cover crop mixtures and monocultures on functional trait expression and ecosystem services. Functional traits that enhance ecosystem services related to agricultural production include height, specific leaf area (SLA), root, shoot ratio, leaf C and N concentrations, and flowering phenology. Ecosystem services include biomass production, weed suppression, reduced N leaching, N recycling, and support of pollinators. Employing a trait-based approach may allow for the elucidation of mechanistic links between plant structure and resulting ecosystem service delivery. While relationships between some functional traits and the delivery of particular ecosystem services may be readily apparent through existing ecological knowledge (e.g. height positively correlating with weed suppression), this study will begin to quantify those relationships so as to gain further understanding of whether and how measurable variation in functional trait expression across cover crop mixtures and monocultures can serve as a reliable predictor of variation in the types and abundances of ecosystem services delivered. Six cover crop species, including legume, grass, and broadleaf functional types, were selected for growth in six mixtures and their component monocultures based upon the principle of trait complementarity. The tricultures (three-way mixtures) are comprised of a legume, grass, and broadleaf species, and include cowpea/sudex/buckwheat, sunnhemp/sudex/buckwheat, and chickling vetch/oat/buckwheat combinations; the dicultures contain the same legume and grass combinations as above, without the buckwheat broadleaf. By combining species with expectedly complimentary traits (for example, legumes are N suppliers and grasses are N acquirers, creating a nutrient cycling loop) the cover crop mixtures may elicit a broader range of ecosystem services than that provided by a monoculture, though trade-offs could exist. Collecting functional trait data will enable the investigation of the types of interactions driving these ecosystem service outcomes. It also allows for generalizability across a broader range of species than just those selected for this study, which may aid in informing further research efforts exploring species and ecosystem functioning, as well as on-farm management decisions.

Keywords: agroecology, cover crops, functional traits, multifunctionality, trait complementarity

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Authors: Noorh Albadi, Salha Khayyat

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People's moods and well-being are affected by their environment. The built environment impacts one's level of activity and health. In order to enhance users' physical health, sustainable design strategies have been developed for the physical environment to improve users' health. This study aimed to determine whether adult resorts in Saudi Arabia meet standards that ensure physical wellness to identify the needed requirements. It will be significant to the Ministry of Tourism, Sports, developers, and designers. Physical activity affects human health physically and mentally. In Saudi Arabia, the percentage of people who practiced sports in the Kingdom in 2019 was 20.04% - males and females older than 15. On the other hand, there is a lack of physical activity in Saudi Arabia; 90% of the Kingdom's population spends more than two hours sitting down without moving, which puts them at risk of contracting a non-communicable disease. The lack of physical activity and movement led to an increase in the rate of obesity among Saudis by 59% in 2020 and consequently could cause chronic diseases or death. The literature generally endorses that leading an active lifestyle improves physical health and affects mental health. Therefore, the United Nations has set 17 sustainable development goals (SDGs) to ensure healthy lives and promote well-being for all ages. One of SDG3's targets is reducing mortality, which can be achieved by raising physical activity. In order to support sustainable design, many rating systems and strategies have been developed, such as WELL building, Leadership in Energy and Environmental Design, (LEED), Active design strategies, and RIPA plan of work. The survey was used to gather qualitative and quantitative information. It was designed based on the Active Design and WELL building theories targeting beach resorts visitors, professional and beginner athletes, and non-athletics to ask them about the beach resorts they visited in the Kingdom and whether they met the criteria of sports resorts and healthy and active design theories, in addition to gathering information about the preferences of physical activities in the Saudi society in terms of the type of activities that young people prefer, where they prefer to engage in and under any thermal and light conditions. The final section asks about the design of residential units in beach sports resorts, the data collected from 127 participants. Findings revealed that participants prefer outdoor activities in moderate weather and sunlight or the evening with moderate and sufficient lighting and that no beach sports resorts in the country are constructed to support sustainable design criteria for physical activity. Participants agreed that several measures that lessen tension at beach resorts and enhance movement and activity are needed by Saudi society. The study recommends designing resorts that meet the sustainable design criteria regarding physical activity in Saudi Arabia to increase physical activity to achieve psychological and physical benefits and avoid psychological and physical diseases related to physical inactivity.

Keywords: sustainable design, SDGs, active design strategies, well building, beach resort design

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Authors: Duncan Wallace, M-Tahar Kechadi

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In recent years, Machine Learning (ML) approaches have been successfully applied to an analysis of patient symptom data in the context of disease diagnosis, at least where such data is well codified. However, much of the data present in Electronic Health Records (EHR) are unlikely to prove suitable for classic ML approaches. Furthermore, as scores of data are widely spread across both hospitals and individuals, a decentralized, computationally scalable methodology is a priority. The focus of this paper is to develop a method to predict outliers in an out-of-hours healthcare provision center (OOHC). In particular, our research is based upon the early identification of patients who have underlying conditions which will cause them to repeatedly require medical attention. OOHC act as an ad-hoc delivery of triage and treatment, where interactions occur without recourse to a full medical history of the patient in question. Medical histories, relating to patients contacting an OOHC, may reside in several distinct EHR systems in multiple hospitals or surgeries, which are unavailable to the OOHC in question. As such, although a local solution is optimal for this problem, it follows that the data under investigation is incomplete, heterogeneous, and comprised mostly of noisy textual notes compiled during routine OOHC activities. Through the use of Deep Learning methodologies, the aim of this paper is to provide the means to identify patient cases, upon initial contact, which are likely to relate to such outliers. To this end, we compare the performance of Long Short-Term Memory, Gated Recurrent Units, and combinations of both with Convolutional Neural Networks. A further aim of this paper is to elucidate the discovery of such outliers by examining the exact terms which provide a strong indication of positive and negative case entries. While free-text is the principal data extracted from EHRs for classification, EHRs also contain normalized features. Although the specific demographical features treated within our corpus are relatively limited in scope, we examine whether it is beneficial to include such features among the inputs to our neural network, or whether these features are more successfully exploited in conjunction with a different form of a classifier. In this section, we compare the performance of randomly generated regression trees and support vector machines and determine the extent to which our classification program can be improved upon by using either of these machine learning approaches in conjunction with the output of our Recurrent Neural Network application. The output of our neural network is also used to help determine the most significant lexemes present within the corpus for determining high-risk patients. By combining the confidence of our classification program in relation to lexemes within true positive and true negative cases, with an inverse document frequency of the lexemes related to these cases, we can determine what features act as the primary indicators of frequent-attender and non-frequent-attender cases, providing a human interpretable appreciation of how our program classifies cases.

Keywords: artificial neural networks, data-mining, machine learning, medical informatics

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Authors: Sonia A. Stoica, Lexi Frankel, Amalia Ardeljan, Selena Rashid, Ali Yasback, Omar Rashid

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Introduction Enterococcus is a vast genus of lactic acid bacteria, gram-positivecocci species. They are common commensal organisms in the intestines of humans: E. faecalis (90–95%) and E. faecium (5–10%). Rare groups of infections can occur with other species, including E. casseliflavus, E. gallinarum, and E. raffinosus. The most common infections caused by Enterococcus include urinary tract infections, biliary tract infections, subacute endocarditis, diverticulitis, meningitis, septicemia, and spontaneous bacterial peritonitis. The treatment for sensitive strains of these bacteria includes ampicillin, penicillin, cephalosporins, or vancomycin, while the treatment for resistant strains includes daptomycin, linezolid, tygecycline, or streptogramine. Enterococcus faecalis CECT7121 is an encouraging nominee for being considered as a probiotic strain. E. faecalis CECT7121 enhances and skews the profile of cytokines to the Th1 phenotype in situations such as vaccination, anti-tumoral immunity, and allergic reactions. It also enhances the secretion of high levels of IL-12, IL-6, TNF alpha, and IL-10. Cytokines have been previously associated with the development of cancer. The intention of this study was to therefore evaluate the correlation between Enterococcus infections and incidence of bone carcinoma. Methods A retrospective cohort study (2010-2019) was conducted through a Health Insurance Portability and Accountability Act (HIPAA) compliant national database and conducted using International Classification of Disease (ICD) 9th and 10th codes for bone carcinoma diagnosis in a previously Enterococcus infected population. Patients were matched for age range and Charlson Comorbidity Index (CCI). Access to the database was granted by Holy Cross Health for academic research. Chi-squared test was used to assess statistical significance. Results A total number of 17,056 patients was obtained in Enterococcus infected group as well as in the control population (matched by Age range and CCI score). Subsequent bone carcinoma development was seen at a rate of 1.07% (184) in the Enterococcal infectious group and 3.42% (584) in the control group, respectively. The difference was statistically significant by p= 2.2x10-¹⁶, Odds Ratio = 0.355 (95% CI 0.311 - 0.404) Treatment for enterococcus infection was analyzed and controlled for in both enterococcus infected and noninfected populations. 78 out of 6,624 (1.17%) patients with a prior enterococcus infection and treated with antibiotics were compared to 202 out of 6,624 (3.04%) patients with no history of enterococcus infection (control) and received antibiotic treatment. Both populations subsequently developed bone carcinoma. Results remained statistically significant (p<2.2x10-), Odds Ratio=0.456 (95% CI 0.396-0.525). Conclusion This study shows a statistically significant correlation between Enterococcus infection and a decreased incidence of bone carcinoma. The immunologic response of the organism to Enterococcus infection may exert a protecting mechanism from developing bone carcinoma. Further exploration is needed to identify the potential mechanism of Enterococcus in reducing bone carcinoma incidence.

Keywords: anti-tumoral immunity, bone carcinoma, enterococcus, immunologic response

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Authors: Aura Alejandra Burbano Patino, Mariela Agotegaray, Veronica Lassalle, Fernanda Horst

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Water pollution is of worldwide concern due to its importance as an essential resource for life. Industrial and urbanistic growth are anthropogenic activities that have caused an increase of undesirable compounds in water. In the last decade, emerging pollutants have become of great interest since, at very low concentrations (µg/L and ng/L), they exhibit a hazardous effect on wildlife, aquatic ecosystems, and human organisms. One group of emerging pollutants that are a matter of study are pharmaceuticals. Their high consumption rate and their inappropriate disposal have led to their detection in wastewater treatment plant influent, effluent, surface water, and drinking water. In consequence, numerous technologies have been developed to efficiently treat these pollutants. Adsorption appears like an easy and cost-effective technology. One of the most used adsorbents of emerging pollutants removal is carbon-based materials such as hydrochars. This study aims to use a magnetic hydrochar nanocomposite to be employed as an adsorbent for diclofenac removal. Kinetics models and the adsorption efficiency in real water samples were analyzed. For this purpose, a magnetic hydrochar nanocomposite was synthesized through the hydrothermal carbonization (HTC) technique hybridized to co-precipitation to add the magnetic component into the hydrochar, based on iron oxide nanoparticles. The hydrochar was obtained from sunflower husk residue as the precursor. TEM, TGA, FTIR, Zeta potential as a function of pH, DLS, BET technique, and elemental analysis were employed to characterize the material in terms of composition and chemical structure. Adsorption kinetics were carried out in distilled water and real water at room temperature, pH of 5.5 for distilled water and natural pH for real water samples, 1:1 adsorbent: adsorbate dosage ratio, contact times from 10-120 minutes, and 50% dosage concentration of DCF. Results have demonstrated that magnetic hydrochar presents superparamagnetic properties with a saturation magnetization value of 55.28 emu/g. Besides, it is mesoporous with a surface area of 55.52 m²/g. It is composed of magnetite nanoparticles incorporated into the hydrochar matrix, as can be proven by TEM micrographs, FTIR spectra, and zeta potential. On the other hand, kinetic studies were carried out using DCF models, finding percent removal efficiencies up to 85.34% after 80 minutes of contact time. In addition, after 120 minutes of contact time, desorption of emerging pollutants from active sites took place, which indicated that the material got saturated after that t time. In real water samples, percent removal efficiencies decrease up to 57.39%, ascribable to a possible mechanism of competitive adsorption of organic or inorganic compounds, ions for active sites of the magnetic hydrochar. The main suggested adsorption mechanism between the magnetic hydrochar and diclofenac include hydrophobic and electrostatic interactions as well as hydrogen bonds. It can be concluded that the magnetic hydrochar nanocomposite could be valorized into a by-product which appears as an efficient adsorbent for DCF removal as a model emerging pollutant. These results are being complemented by modifying experimental variables such as pollutant’s initial concentration, adsorbent: adsorbate dosage ratio, and temperature. Currently, adsorption assays of other emerging pollutants are being been carried out.

Keywords: environmental remediation, emerging pollutants, hydrochar, magnetite nanoparticles

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Authors: Ayesha Mushtaq

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Asthma is a pulmonary disease in which blockade of the airway takes place due to inflammation as a response to certain allergens. Breathing troubles, cough, and dyspnea are one of the few symptoms. Several studies have indicated a significant effect on asthma due to changes in dietary routines. Certain food items, such as oily foods and other materials, are known to cause an increase in the symptoms of asthma. Low dietary intake of fruits and vegetables may be important in relation to asthma prevalence. The objective of this study is to assess and compare the nutritional status of asthmatic and non-asthmatic patients. The significance of this study lies in the factor that it will help nutritionists to arrange a feasible dietary routine for asthmatic patients. This research was conducted at the Pulmonology Department of the Pakistan Institute of Medical Science Islamabad. About thirty hundred thirty-four million people are affected by asthma worldwide. Pakistan is on the verge of being an uplifted urban population and asthma cases are increasingly high these days. Several studies suggest an increase in the Asthmatic patient population due to improper diet. Other studies conducted at different institutions have conducted research on similar topics. These studies have suggested that there is a substantial alteration in the nutritional status of asthmatic and non-Asthmatic patients. This is a cross-sectional study aimed at assessing the nutritious standing of Asthmatic and non-asthmatic patients. This research took place at the Pakistan Institute of Medical Sciences (PIMS), Islamabad, Pakistan. The research included asthmatic and non-asthmatic patients coming to the pulmonology department clinic at the Pakistan Institute of Medical Sciences (PIMS). These patients were aged between 20-60 years. A questionnaire was developed for these patients to estimate their dietary plans in these patients. The methodology included four sections. The first section was the Socio-Demographic profile, which included age, gender, monthly income and occupation. The next section was anthropometric measurements which included the weight, height and body mass index (BMI) of the individual. The next section, section three, was about the biochemical attributes, such as for biochemical profiling, pulmonary function testing (PFT) was performed. In the next section, Dietary habits, which were assessed by using a food frequency questionnaire (FFQ) through food habits and consumption pattern, was assessed. The next section life style data, in which the person's level of physical activity, sleep and smoking habits were assessed. The next section was statistical analysis. All the data obtained from the study were statistically analyzed and assessed. Most of the asthma Patients were females, with weight more than normal or even obese. Body Mass Index (BMI) was higher in asthma Patients than those in non-Asthmatic ones. When the nutritional Values were assessed, we came to know that these patients were low on certain nutrients and their diet included more junk and oily food than healthy vegetables and fruits. Beverages intake was also included in the same assessment. It is evident from this study that nutritional status has a contributory effect on asthma. So, patients on the verge of developing asthma or those who have developed asthma should focus on their diet, maintain good eating habits and take healthy diets, including fruits and vegetables rather than oily foods. Proper sleep may also contribute to the control of asthma.

Keywords: NUTRI, BMI, asthma, food

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Authors: Magdalena Chrabąszcz, Teresa Wolniewicz, Cezary Maciejewski, Joanna Czuwara

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BACKGROUND: Dermoscopy is a clinical tool known to improve the early detection of melanoma and other malignancies of the skin. Over the past few years melanoma has grown into a disease of socio-economic importance due to the increasing incidence and persistently high mortality rates. Early diagnosis remains the best method to reduce melanoma and non-melanoma skin cancer– related mortality and morbidity. Dermoscopy is a noninvasive technique that consists of viewing pigmented skin lesions through a hand-held lens. This simple procedure increases melanoma diagnostic accuracy by up to 35%. Dermoscopy is currently the standard for clinical differential diagnosis of cutaneous melanoma and for qualifying lesion for the excision biopsy. Like any clinical tool, training is required for effective use. The introduction of small and handy dermoscopes contributed significantly to the switch of dermatoscopy toward a first-level useful tool. Non-dermatologist physicians are well positioned for opportunistic melanoma detection; however, education in the skin cancer examination is limited during medical school and traditionally lecture-based. AIM: The aim of this randomized study was to determine whether the adjunct of dermoscopy to the standard fourth year medical curriculum improves the ability of medical students to distinguish between benign and malignant lesions and assess acceptability and satisfaction with the intervention. METHODS: We performed a prospective study in 2 cohorts of fourth-year medical students at Medical University of Warsaw. Groups having dermatology course, were randomly assigned to:  cohort A: with limited access to dermatoscopy from their teacher only – 1 dermatoscope for 15 people  Cohort B: with a full access to use dermatoscopy during their clinical classes:1 dermatoscope for 4 people available constantly plus 15-minute dermoscopy tutorial. Students in both study arms got an image-based test of 10 lesions to assess ability to differentiate benign from malignant lesions and postintervention survey collecting minimal background information, attitudes about the skin cancer examination and course satisfaction. RESULTS: The cohort B had higher scores than the cohort A in recognition of nonmelanocytic (P < 0.05) and melanocytic (P <0.05) lesions. Medical students who have a possibility to use dermatoscope by themselves have also a higher satisfaction rates after the dermatology course than the group with limited access to this diagnostic tool. Moreover according to our results they were more motivated to learn dermatoscopy and use it in their future everyday clinical practice. LIMITATIONS: There were limited participants. Further study of the application on clinical practice is still needed. CONCLUSION: Although the use of dermatoscope in dermatology as a specialty is widely accepted, sufficiently validated clinical tools for the examination of potentially malignant skin lesions are lacking in general practice. Introducing medical students to dermoscopy in their fourth year curricula of medical school may improve their ability to differentiate benign from malignant lesions. It can can also encourage students to use dermatoscopy in their future practice which can significantly improve early recognition of malignant lesions and thus decrease melanoma mortality.

Keywords: dermatoscopy, early detection of melanoma, medical education, skin cancer

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Authors: Andreas Latz, Daniela Heinz, Fatima Hashemi, Melek Baygül

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Introduction: Feline leukemia virus (FeLV), feline immunodeficiency virus (FIV), and feline coronavirus (FCoV) are serious infectious diseases affecting cats worldwide. Transmission of these viruses occurs primarily through close contact with infected cats (via saliva, nasal secretions, faeces, etc.). FeLV, FIV, and FCoV infections can occur in combination and are expressed in similar clinical symptoms. Diagnosis can therefore be challenging: Symptoms are variable and often non-specific. Sick cats show very similar clinical symptoms: apathy, anorexia, fever, immunodeficiency syndrome, anemia, etc. Sample volume for small companion animals for diagnostic purposes can be challenging to collect. In addition, multiplex diagnosis of diseases can contribute to an easier, cheaper, and faster workflow in the lab as well as to the better differential diagnosis of diseases. For this reason, we wanted to develop a new diagnostic tool that utilizes less sample volume, reagents, and consumables than multiplesingleplex ELISA assays Methods: The Multiplier from Dynextechonogies (USA) has been used as platform to develop a Multiplex diagnostic tool for the detection of antibodies against FIV and FCoV/FIP and antigens for FeLV. Multiplex diagnostics. The Dynex®Multiplier®is a fully automated chemiluminescence immunoassay analyzer that significantly simplifies laboratory workflow. The Multiplier®ease-of-use reduces pre-analytical steps by combining the power of efficiently multiplexing multiple assays with the simplicity of automated microplate processing. Plastic beads have been coated with antigens for FIV and FCoV/FIP, as well as antibodies for FeLV. Feline blood samples are incubated with the beads. Read out of results is performed via chemiluminescence Results: Bead coating was optimized for each individual antigen or capture antibody and then combined in the multiplex diagnostic tool. HRP: Antibody conjugates for FIV and FCoV antibodies, as well as detection antibodies for FeLV antigen, have been adjusted and mixed. 3 individual prototyple batches of the assay have been produced. We analyzed for each disease 50 well defined positive and negative samples. Results show an excellent diagnostic performance of the simultaneous detection of antibodies or antigens against these feline diseases in a fully automated system. A 100% concordance with singleplex methods like ELISA or IFA can be observed. Intra- and Inter-Assays showed a high precision of the test with CV values below 10% for each individual bead. Accelerated stability testing indicate a shelf life of at least 1 year. Conclusion: The new tool can be used for multiplex diagnostics of the most important feline infectious diseases. Only a very small sample volume is required. Fully automation results in a very convenient and fast method for diagnosing animal diseases.With its large specimen capacity to process over 576 samples per 8-hours shift and provide up to 3,456 results, very high laboratory productivity and reagent savings can be achieved.

Keywords: Multiplex, FIV, FeLV, FCoV, FIP

Procedia PDF Downloads 78

Authors: Su Mon Saw, Joe Rothnagel

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Short open reading frames (sORFs) located in 5’UTR of mRNAs are known as uORFs. Characterization of uORF-encoded peptides (uPEPs) i.e., a subset of short open reading frame encoded peptides (sPEPs) and their translation regulation lead to understanding of causes of genetic disease, proteome complexity and development of treatments. Existence of uORFs within cellular proteome could be detected by LC-MS/MS. The ability of uORF to be translated into uPEP and achievement of uPEP identification will allow uPEP’s characterization, structures, functions, subcellular localization, evolutionary maintenance (conservation in human and other species) and abundance in cells. It is hypothesized that a subset of sORFs are translatable and that their encoded sPEPs are functional and are endogenously expressed contributing to the eukaryotic cellular proteome complexity. This project aimed to investigate whether sORFs encode functional peptides. Liquid chromatography-mass spectrometry (LC-MS) and bioinformatics were thus employed. Due to probable low abundance of sPEPs and small in sizes, the need for efficient peptide enrichment strategies for enriching small proteins and depleting the sub-proteome of large and abundant proteins is crucial for identifying sPEPs. Low molecular weight proteins were extracted using SDS-PAGE from Human Embryonic Kidney (HEK293) cells and Strong Cation Exchange Chromatography (SCX) from secreted HEK293 cells. Extracted proteins were digested by trypsin to peptides, which were detected by LC-MS/MS. The MS/MS data obtained was searched against Swiss-Prot using MASCOT version 2.4 to filter out known proteins, and all unmatched spectra were re-searched against human RefSeq database. ProteinPilot v5.0.1 was used to identify sPEPs by searching against human RefSeq, Vanderperre and Human Alternative Open Reading Frame (HaltORF) databases. Potential sPEPs were analyzed by bioinformatics. Since SDS PAGE electrophoresis could not separate proteins <20kDa, this could not identify sPEPs. All MASCOT-identified peptide fragments were parts of main open reading frame (mORF) by ORF Finder search and blastp search. No sPEP was detected and existence of sPEPs could not be identified in this study. 13 translated sORFs in HEK293 cells by mass spectrometry in previous studies were characterized by bioinformatics. Identified sPEPs from previous studies were <100 amino acids and <15 kDa. Bioinformatics results showed that sORFs are translated to sPEPs and contribute to proteome complexity. uPEP translated from uORF of SLC35A4 was strongly conserved in human and mouse while uPEP translated from uORF of MKKS was strongly conserved in human and Rhesus monkey. Cross-species conserved uORFs in association with protein translation strongly suggest evolutionary maintenance of coding sequence and indicate probable functional expression of peptides encoded within these uORFs. Translation of sORFs was confirmed by mass spectrometry and sPEPs were characterized with bioinformatics.

Keywords: bioinformatics, HEK293 cells, liquid chromatography-mass spectrometry, ProteinPilot, Strong Cation Exchange Chromatography, SDS-PAGE, sPEPs

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Authors: Inas Raafat, Azza El Bassiouny, Waldemar L. Olszewsky, Nagui E. Mikhail, Mona Nossier, Nora E. I. El-Bassiouni, Mona Zoheiry, Houda Abou Taleb, Noha Abd El-Aal, Ali Baioumy, Shimaa Attia

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Background: Orthotopic liver transplantation is an established treatment for patients with severe acute and end-stage chronic liver disease. The shortage of donor organs continues to be the rate-limiting factor for liver transplantation throughout the world. Hepatocyte transplantation is a promising treatment for several liver diseases and can, also, be used as a "bridge" to liver transplantation in cases of liver failure. Aim of the work: This study was designed to develop a highly efficient protocol for isolation and transplantation of hepatocytes in experimental Lewis rat model to provide satisfactory guidelines for future application on humans.Materials and Methods: Hepatocytes were isolated from the liver by double perfusion technique and bone marrow cells were isolated by centrifugation of shafts of tibia and femur of donor Lewis rats. Recipient rats were subjected to sub-lethal dose of irradiation 2 days before transplantation. In a laparotomy operation the spleen was injected by freshly isolated hepatocytes and bone marrow cells were injected intravenously. The animals were sacrificed 45 day latter and splenic sections were prepared and stained with H & E, PAS AFP and Prox1. Results: The data obtained from this study showed that the double perfusion technique is successful in separation of hepatocytes regarding cell number and viability. Also the method used for bone marrow cells separation gave excellent results regarding cell number and viability. Intrasplenic engraftment of hepatocytes and live tissue formation within the splenic tissue were found in 70% of cases. Hematoxylin and eosin stained splenic sections from 7 rats showed sheets and clusters of cells among the splenic tissues. Periodic Acid Schiff stained splenic sections from 7 rats showed clusters of hepatocytes with intensely stained pink cytoplasmic granules denoting the presence of glycogen. Splenic sections from 7 rats stained with anti-α-fetoprotein antibody showed brownish cytoplasmic staining of the hepatocytes denoting positive expression of AFP. Splenic sections from 7 rats stained with anti-Prox1 showed brownish nuclear staining of the hepatocytes denoting positive expression of Prox1 gene on these cells. Also, positive expression of Prox1 gene was detected on lymphocytes aggregations in the spleens. Conclusions: Isolation of liver cells by double perfusion technique using collagenase buffer is a reliable method that has a very satisfactory yield regarding cell number and viability. The intrasplenic route of transplantation of the freshly isolated liver cells in an immunocompromised model was found to give good results regarding cell engraftment and tissue formation. Further studies are needed to assess function of engrafted hepatocytes by measuring prothrombin time, serum albumin and bilirubin levels.

Keywords: Lewis rats, hepatocytes, BMCs, transplantation, AFP, Prox1

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Authors: Kimberly Samaha

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In order to attract new types of investors into the emerging Bio-Economy, a new set of metrics and measurement system is needed to better quantify the environmental, social and economic impacts of circular zero-waste design. The Bio-Hub Ecosystem model was developed to address a critical area of concern within the global energy market regarding the use of biomass as a feedstock for power plants. Lack of an economically-viable business model for bioenergy facilities has resulted in the continuation of idled and decommissioned plants. In particular, the forestry-based plants which have been an invaluable outlet for woody biomass surplus, forest health improvement, timber production enhancement, and especially reduction of wildfire risk. This study looked at repurposing existing biomass-energy plants into Circular Zero-Waste Bio-Hub Ecosystems. A Bio-Hub model that first targets a ‘whole-tree’ approach and then looks at the circular economics of co-hosting diverse industries (wood processing, aquaculture, agriculture) in the vicinity of the Biomass Power Plants facilities. It proposes not only models for integration of forestry, aquaculture, and agriculture in cradle-to-cradle linkages of what have typically been linear systems, but the proposal also allows for the early measurement of the circularity and impact of resource use and investment risk mitigation, for these systems. Typically, life cycle analyses measure environmental impacts of different industrial production stages and are not integrated with indicators of material use circularity. This concept paper proposes the further development of a new set of metrics that would illustrate not only the typical life-cycle analysis (LCA), which shows the reduction in greenhouse gas (GHG) emissions, but also the zero-waste circularity measures of mass balance of the full value chain of the raw material and energy content/caloric value. These new measures quantify key impacts in making hyper-efficient use of natural resources and eliminating waste to landfills. The project utilized traditional LCA using the GREET model where the standalone biomass energy plant case was contrasted with the integration of a jet-fuel biorefinery. The methodology was then expanded to include combinations of co-hosts that optimize the life cycle of woody biomass from tree to energy, CO₂, heat and wood ash both from an energy/caloric value and for mass balance to include reuse of waste streams which are typically landfilled. The major findings of both a formal LCA study resulted in the masterplan for the first Bio-Hub to be built in West Enfield, Maine. Bioenergy facilities are currently at a critical juncture where they have an opportunity to be repurposed into efficient, profitable and socially responsible investments, or be idled and scrapped. If proven as a model, the expedited roll-out of these innovative scenarios can set a new standard for circular zero-waste projects that advance the critical transition from the current ‘take-make-dispose’ paradigm inherent in the energy, forestry and food industries to a more sustainable bio-economy paradigm where waste streams become valuable inputs, supporting local and rural communities in simple, sustainable ways.

Keywords: bio-economy, biomass energy, financing, metrics

Procedia PDF Downloads 139

Authors: Arti Singh, Carolyn Jenkins, Oyedunni S. Arulogun, Mayowa O. Owolabi, Fred S. Sarfo, Bruce Ovbiagele, Enzinne Sylvia

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Background: Stroke, the leading cause of adult-onset disability and the second leading cause of death, is a major public health concern particularly pertinent in Sub-Saharan Africa (SSA), where nearly 80% of all global stroke mortalities occur. The Stroke Investigative Research and Education Network (SIREN) seeks to comprehensively characterize the genomic, sociocultural, economic, and behavioral risk factors for stroke and to build effective teams for research to address and decrease the burden of stroke and other non communicable diseases in SSA. One of the first steps to address this goal was to effectively engage the communities that suffer the high burden of disease in SSA. This study describes how the SIREN project engaged six sites in Ghana and Nigeria over the past three years, describing the community engagement activities that have arisen since inception. Aim: The aim of community engagement (CE) within SIREN is to elucidate information about knowledge, attitudes, beliefs, and practices (KABP) about stroke and its risk factors from individuals of African ancestry in SSA, and to educate the community about stroke and ways to decrease disabilities and deaths from stroke using socioculturally appropriate messaging and messengers. Methods: Community Advisory Board (CABs), Focus Group Discussions (FGDs) and community outreach programs. Results: 27 FGDs with 168 participants including community heads, religious leaders, health professionals and individuals with stroke among others, were conducted, and over 60 CE outreaches have been conducted within the SIREN performance sites. Over 5,900 individuals have received education on cardiovascular risk factors and about 5,000 have been screened for cardiovascular risk factors during the outreaches. FGDs and outreach programs indicate that knowledge of stroke, as well as risk factors and follow-up evidence-based care is limited and often late. Other findings include: 1) Most recognize hypertension as a major risk factor for stroke. 2) About 50% report that stroke is hereditary and about 20% do not know organs affected by stroke. 3) More than 95% willing to participate in genetic testing research and about 85% willing to pay for testing and recommend the test to others. 4) Almost all indicated that genetic testing could help health providers better treat stroke and help scientists better understand the causes of stroke. The CABs provided stakeholder input into SIREN activities and facilitated collaborations among investigators, community members and stakeholders. Conclusion: The CE core within SIREN is a first-of-its kind public outreach engagement initiative to evaluate and address perceptions about stroke and genomics by patients, caregivers, and local leaders in SSA and has implications as a model for assessment in other high-stroke risk populations. SIREN’s CE program uses best practices to build capacity for community-engaged research, accelerate integration of research findings into practice and strengthen dynamic community-academic partnerships within our communities. CE has had several major successes over the past three years including our multi-site collaboration examining the KABP about stroke (symptoms, risk factors, burden) and genetic testing across SSA.

Keywords: community advisory board, community engagement, focus groups, outreach, SSA, stroke

Procedia PDF Downloads 407

Authors: Scott M. Black, Craig Maclean, Pauline Hall Barrientos, Konstantinos Ritos, Asimina Kazakidi

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Aortic aneurysms and dissections are leading causes of death in cardiovascular disease. Both inevitably lead to hemodynamic instability without surgical intervention in the form of vascular stent-graft deployment. An accurate description of the aortic geometry and blood flow in patient-specific cases is vital for treatment planning and long-term success of such grafts, as they must generate physiological branch perfusion and in-stent hemodynamics. The aim of this study was to create patient-specific computational fluid dynamics (CFD) models through a multi-modality, multi-dimensional approach with boundary condition optimization to predict branch flow rates and in-stent hemodynamics in custom stent-graft configurations. Three-dimensional (3D) thoracoabdominal aortae were reconstructed from four-dimensional flow-magnetic resonance imaging (4D Flow-MRI) and computed tomography (CT) medical images. The former employed a novel approach to generate and enhance vessel lumen contrast via through-plane velocity at discrete, user defined cardiac time steps post-hoc. To produce patient-specific boundary conditions (BCs), the aortic geometry was reduced to a one-dimensional (1D) model. Thereafter, a zero-dimensional (0D) 3-Element Windkessel model (3EWM) was coupled to each terminal branch to represent the distal vasculature. In this coupled 0D-1D model, the 3EWM parameters were optimized to yield branch flow waveforms which are representative of the 4D Flow-MRI-derived in-vivo data. Thereafter, a 0D-3D CFD model was created, utilizing the optimized 3EWM BCs and a 4D Flow-MRI-obtained inlet velocity profile. A sensitivity analysis on the effects of stent-graft configuration and BC parameters was then undertaken using multiple stent-graft configurations and a range of distal vasculature conditions. 4D Flow-MRI granted unparalleled visualization of blood flow throughout the cardiac cycle in both the pre- and postsurgical states. Segmentation and reconstruction of healthy and stented regions from retrospective 4D Flow-MRI images also generated 3D models with geometries which were successfully validated against their CT-derived counterparts. 0D-1D coupling efficiently captured branch flow and pressure waveforms, while 0D-3D models also enabled 3D flow visualization and quantification of clinically relevant hemodynamic parameters for in-stent thrombosis and graft limb occlusion. It was apparent that changes in 3EWM BC parameters had a pronounced effect on perfusion distribution and near-wall hemodynamics. Results show that the 3EWM parameters could be iteratively changed to simulate a range of graft limb diameters and distal vasculature conditions for a given stent-graft to determine the optimal configuration prior to surgery. To conclude, this study outlined a methodology to aid in the prediction post-surgical branch perfusion and in-stent hemodynamics in patient specific cases for the implementation of custom stent-grafts.

Keywords: 4D flow-MRI, computational fluid dynamics, vascular stent-grafts, windkessel

Procedia PDF Downloads 156

Authors: Vishal Kumar, Soumitra Satapathi

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Föster Resonance Energy Transfer (FRET) is a powerful technique used to probe close-range molecular interactions. Physically, the FRET phenomenon manifests as a dipole–dipole interaction between closely juxtaposed fluorescent molecules (10–100 Å). Our effort is to employ this FRET technique to make a prototype device for highly sensitive detection of environment pollutant. Among the most common environmental pollutants, nitroaromatic compounds (NACs) are of particular interest because of their durability and toxicity. That’s why, sensitive and selective detection of small amounts of nitroaromatic explosives, in particular, 2,4,6-trinitrophenol (TNP), 2,4-dinitrotoluene (DNT) and 2,4,6-trinitrotoluene (TNT) has been a critical challenge due to the increasing threat of explosive-based terrorism and the need of environmental monitoring of drinking and waste water. In addition, the excessive utilization of TNP in several other areas such as burn ointment, pesticides, glass and the leather industry resulted in environmental accumulation, and is eventually contaminating the soil and aquatic systems. To the date, high number of elegant methods, including fluorimetry, gas chromatography, mass, ion-mobility and Raman spectrometry have been successfully applied for explosive detection. Among these efforts, fluorescence-quenching methods based on the mechanism of FRET show good assembly flexibility, high selectivity and sensitivity. Here, we report a FRET-based sensor system for the highly selective detection of NACs, such as TNP, DNT and TNT. The sensor system is composed of a copolymer Poly [(N,N-dimethylacrylamide)-co-(Boc-Trp-EMA)] (RP) bearing tryptophan derivative in the side chain as donor and dansyl tagged copolymer P(MMA-co-Dansyl-Ala-HEMA) (DCP) as an acceptor. Initially, the inherent fluorescence of RP copolymer is quenched by non-radiative energy transfer to DCP which only happens once the two molecules are within Förster critical distance (R0). The excellent spectral overlap (Jλ= 6.08×10¹⁴ nm⁴M⁻¹cm⁻¹) between donors’ (RP) emission profile and acceptors’ (DCP) absorption profile makes them an exciting and efficient FRET pair i.e. further confirmed by the high rate of energy transfer from RP to DCP i.e. 0.87 ns⁻¹ and lifetime measurement by time correlated single photon counting (TCSPC) to validate the 64% FRET efficiency. This FRET pair exhibited a specific fluorescence response to NACs such as DNT, TNT and TNP with 5.4, 2.3 and 0.4 µM LODs, respectively. The detection of NACs occurs with high sensitivity by photoluminescence quenching of FRET signal induced by photo-induced electron transfer (PET) from electron-rich FRET pair to electron-deficient NAC molecules. The estimated stern-volmer constant (KSV) values for DNT, TNT and TNP are 6.9 × 10³, 7.0 × 10³ and 1.6 × 104 M⁻¹, respectively. The mechanistic details of molecular interactions are established by time-resolved fluorescence, steady-state fluorescence and absorption spectroscopy confirmed that the sensing process is of mixed type, i.e. both dynamic and static quenching as lifetime of FRET system (0.73 ns) is reduced to 0.55, 0.57 and 0.61 ns DNT, TNT and TNP, respectively. In summary, the simplicity and sensitivity of this novel FRET sensor opens up the possibility of designing optical sensor of various NACs in one single platform for developing multimodal sensor for environmental monitoring and future field based study.

Keywords: FRET, nitroaromatic, stern-Volmer constant, tryptophan and dansyl tagged copolymer

Procedia PDF Downloads 111

Authors: Jane Oliver, Angeline Ferdinand, Jessica Kaufman, Peta Edler, Nicole Allard, Margie Danchin, Katherine B. Gibney

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Background: The cohealth Health Concierge program operated in Melbourne, Australia, from July 2020 to 30 June 2022. The program was designed to provide place-based peer-to-peer COVID-19 education and support to culturally and linguistically diverse residents of high-rise public housing estates. During this time, the COVID-19 public health response changed frequently. We conducted a mixed-methods evaluation to determine the program’s impact on residents’ trust, engagement and communication with health services and public health activities. Methods: The RE-AIM model was used to assess program reach, effectiveness, adoption, implementation and maintenance and the evaluation was informed by a Project Reference Group including end-users. Data were collected between March and May 2022 in four estates where the program operated. We surveyed 301 residents, conducted qualitative interviews with 32 stakeholders and analyzed data from 20,901 forms reporting interactions between Health Concierges and residents collected from August 2021 to May 2022. These forms outlined the support provided by Health Concierges during each interaction. Results: Overall, the program was effective in guiding residents to testing and vaccination services and facilitating COVID-19 safe practices. Nearly two-thirds (191; 63.5%) of the 301 surveyed participants reported speaking with a Health Concierge in the previous six months, and some described having meaningful conversations with them. Despite this, many of the interactions residents described having with Health Concierges were superficial. When considering surveyed participants’ responses to the adapted Public Health Disaster Trust Scale, the mean score across all estates was 2.3 (or slightly more than ‘somewhat confident’) in public health authorities’ ability to respond to a localized infectious disease outbreak. While the program was valued during the rapidly changing public health response, many felt it had failed to evolve in the ‘living with COVID’ phase. Some residents expressed frustration with Health Concierges’ having perceived inactive, passive roles - although other residents felt Health Concierges were helpful and appreciated them. A perception that the true impact of Health Concierges’ work was underrecognized was widely voiced by health staff. All 20,901 Interaction Forms identified COVID-19-related supports provided to residents; almost all included provision of facemasks and/or hand sanitiser and 78% identified additional supports that were also provided, most frequently provision of other health information. Conclusions: The program disseminated up-to-date information to a diverse population within a rapidly changing public health setting. Health Concierges were able promote COVID-19-safe behaviours, including vaccine uptake, and link residents with support services. We recommend the program be revised and continued. New programs that draw on the Health Concierge model may be valuable in supporting future pandemic responses and should be considered in preparedness planning.

Keywords: community health, COVID-19 pandemic, infectious diseases, public health, community health workers

Procedia PDF Downloads 73

Authors: Golson Mohamed, Yasmine Gamasy, Khaled EL-Khatib, Anas Al-Natour, Shady Fadel, Haytham Rashwan, Haytham Badawy, Nadia Farghaly

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Introduction: Wilm's tumor is the most common malignant renal tumor in children. Much progress has been made in the management of patients with this malignancy over the last 3 decades. Today treatments are based on several trials and studies conducted by the International Society of Pediatric Oncology (SIOP) in Europe and National Wilm's Tumor Study Group (NWTS) in the USA. It is necessary for us to understand why do we follow either of the protocols, NWTS which follows the upfront surgery principle or the SIOP which follows the upfront chemotherapy principle in all stages of the disease. Objective: The aim of is to assess outcome in patients treated with preoperative chemotherapy and patients treated with upfront surgery to compare their effect on overall survival. Study design: to decide which protocol to follow, study was carried out on records for patients aged 1 day to 18 years old suffering from Wilm's tumor who were admitted to Alexandria University Hospital, pediatric oncology, pediatric urology and pediatric surgery departments, with a retrospective survey records from 2010 to 2015, Design and editing of the transfer sheet with a (PRISMA flow study) Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Data were fed to the computer and analyzed using IBM SPSS software package version 20.0. (11) Qualitative data were described using number and percent. Quantitative data were described using Range (minimum and maximum), mean, standard deviation and median. Comparison between different groups regarding categorical variables was tested using Chi-square test. When more than 20% of the cells have expected count less than 5, correction for chi-square was conducted using Fisher’s Exact test or Monte Carlo correction. The distributions of quantitative variables were tested for normality using Kolmogorov-Smirnov test, Shapiro-Wilk test, and D'Agstino test, if it reveals normal data distribution, parametric tests were applied. If the data were abnormally distributed, non-parametric tests were used. For normally distributed data, a comparison between two independent populations was done using independent t-test. For abnormally distributed data, comparison between two independent populations was done using Mann-Whitney test. Significance of the obtained results was judged at the 5% level. Results: A significantly statistical difference was observed for survival between the two studied groups favoring the upfront chemotherapy(86.4%)as compared to the upfront surgery group (59.3%) where P=0.009. As regard complication, 20 cases (74.1%) out of 27 were complicated in the group of patients treated with upfront surgery. Meanwhile, 30 cases (68.2%) out of 44 had complications in patients treated with upfront chemotherapy. Also, the incidence of intraoperative complication (rupture) was less in upfront chemotherapy group as compared to upfront surgery group. Conclusion: Upfront chemotherapy has superiority over upfront surgery.As the patient who started with upfront chemotherapy shown, higher survival rate, less percent in complication, less percent needed for radiotherapy, and less rate in recurrence.

Keywords: Wilm's tumor, renal tumor, chemotherapy, surgery

Procedia PDF Downloads 302

Authors: Eric Bang

Abstract:

Interactions between receptors and ligands are crucial for many essential biological processes, including neurotransmission and metabolism. Ligand-receptor analyses that examine cell behavior and interactions often utilize cell type-specific RNA expressions from single-cell RNA sequencing (scRNA-seq) data. Using CellPhoneDB, a public repository consisting of ligands, receptors, and ligand-receptor interactions, the cell-cell interactions were explored in a specific scRNA-seq dataset from kidney tissue and portrayed the results with dot plots and heat maps. Depending on the type of cell, each ligand-receptor pair was aligned with the interacting cell type and calculated the positori probabilities of these associations, with corresponding P values reflecting average expression values between the triads and their significance. Using single-cell data (sample kidney cell references), genes in the dataset were cross-referenced with ones in the existing CellPhoneDB dataset. For example, a gene such as Pleiotrophin (PTN) present in the single-cell data also needed to be present in the CellPhoneDB dataset. Using the single-cell transcriptomics data via slide-seq and reference data, the CellPhoneDB program defines cell types and plots them in different formats, with the two main ones being dot plots and heat map plots. The dot plot displays derived measures of the cell to cell interaction scores and p values. For the dot plot, each row shows a ligand-receptor pair, and each column shows the two interacting cell types. CellPhoneDB defines interactions and interaction levels from the gene expression level, so since the p-value is on a -log10 scale, the larger dots represent more significant interactions. By performing an interaction analysis, a significant interaction was discovered for myeloid and T-cell ligand-receptor pairs, including those between Secreted Phosphoprotein 1 (SPP1) and Fibronectin 1 (FN1), which is consistent with previous findings. It was proposed that an effective protocol would involve a filtration step where cell types would be filtered out, depending on which ligand-receptor pair is activated in that part of the tissue, as well as the incorporation of the CellPhoneDB data in a streamlined workflow pipeline. The filtration step would be in the form of a Python script that expedites the manual process necessary for dataset filtration. Being in Python allows it to be integrated with the CellPhoneDB dataset for future workflow analysis. The manual process involves filtering cell types based on what ligand/receptor pair is activated in kidney cells. One limitation of this would be the fact that some pairings are activated in multiple cells at a time, so the manual manipulation of the data is reflected prior to analysis. Using the filtration script, accurate sorting is incorporated into the CellPhoneDB database rather than waiting until the output is produced and then subsequently applying spatial data. It was envisioned that this would reveal wherein the cell various ligands and receptors are interacting with different cell types, allowing for easier identification of which cells are being impacted and why, for the purpose of disease treatment. The hope is this new computational method utilizing spatially explicit ligand-receptor association data can be used to uncover previously unknown specific interactions within kidney tissue.

Keywords: bioinformatics, Ligands, kidney tissue, receptors, spatial transcriptome

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Authors: Emma J. Dale, Christina D. Buesching, Kevin R. Theis, David W. Macdonald

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This study investigates the oral and intestinal microbiomes of wild-living European badgers (Meles meles) and will relate inter-individual differences to social contact networks, somatic and reproductive fitness, varying susceptibility to bovine tuberculous (bTB) and to the olfactory advertisement. Badgers are an interesting model for this research, as they have great variation in body condition, despite living in complex social networks and having access to the same resources. This variation in somatic fitness, in turn, affects breeding success, particularly in females. We postulate that microbiota have a central role to play in determining the successfulness of an individual. Our preliminary results, characterising the microbiota of individual badgers, indicate unique compositions of microbiota communities within social groups of badgers. This basal information will inform further questions related to the extent microbiota influence fitness. Hitherto, the potential role of microbiota has not been considered in determining host condition, but also other key fitness variables, namely; communication and resistance to disease. Badgers deposit their faeces in communal latrines, which play an important role in olfactory communication. Odour profiles of anal and subcaudal gland secretions are highly individual-specific and encode information about group-membership and fitness-relevant parameters, and their chemical composition is strongly dependent on symbiotic microbiota. As badgers sniff/ lick (using their Vomeronasal organ) and over-mark faecal deposits of conspecifics, these microbial communities can be expected to vary with social contact networks. However, this is particularly important in the context of bTB, where badgers are assumed to transmit bTB to cattle as well as conspecifics. Interestingly, we have found that some individuals are more susceptible to bTB than are others. As acquired immunity and thus potential susceptibility to infectious diseases are known to depend also on symbiotic microbiota in other members of the mustelids, a role of particularly oral microbiota can currently not be ruled out as a potential explanation for inter-individual differences in infection susceptibility of bTB in badgers. Tri annually badgers are caught in the context of a long-term population study that began in 1987. As all badgers receive an individual tattoo upon first capture, age, natal as well as previous and current social group-membership and other life history parameters are known for all animals. Swabs (subcaudal ‘scent gland’, anal, genital, nose, mouth and ear) and fecal samples will be taken from all individuals, stored at -80oC until processing. Microbial samples will be processed and identified at Wayne State University’s Theis (Host-Microbe Interactions) Lab, using High Throughput Sequencing (16S rRNA-encoding gene amplification and sequencing). Acknowledgments: Gas-Chromatography/ Mass-spectrometry (in the context of olfactory communication) analyses will be performed through an established collaboration with Dr. Veronica Tinnesand at Telemark University, Norway.

Keywords: communication, energetics, fitness, free-ranging animals, immunology

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Authors: Sujoy Khan

Abstract:

There is a rising concern with increasing allergies affecting both adults and children in rural and urban India. Recent report on adults in a densely populated North Indian city showed sensitization rates for house dust mite, parthenium, and cockroach at 60%, 40% and 18.75% that is now comparable to allergy prevalence in cities in the United States. Data from patients residing in the eastern part of India is scarce. A retrospective study (over 2 years) was done on patients with allergic rhinitis and asthma where allergen-specific IgE levels were measured to see the aero-allergen sensitization pattern in a large metropolitan city of East India. Total IgE and allergen-specific IgE levels were measured using ImmunoCAP (Phadia 100, Thermo Fisher Scientific, Sweden) using region-specific aeroallergens: Dermatophagoides pteronyssinus (d1); Dermatophagoides farinae (d2); cockroach (i206); grass pollen mix (gx2) consisted of Cynodon dactylon, Lolium perenne, Phleum pratense, Poa pratensis, Sorghum halepense, Paspalum notatum; tree pollen mix (tx3) consisted of Juniperus sabinoides, Quercus alba, Ulmus americana, Populus deltoides, Prosopis juliflora; food mix 1 (fx1) consisted of Peanut, Hazel nut, Brazil nut, Almond, Coconut; mould mix (mx1) consisted of Penicillium chrysogenum, Cladosporium herbarum, Aspergillus fumigatus, Alternaria alternate; animal dander mix (ex1) consisted of cat, dog, cow and horse dander; and weed mix (wx1) consists of Ambrosia elatior, Artemisia vulgaris, Plantago lanceolata, Chenopodium album, Salsola kali, following manufacturer’s instructions. As the IgE levels were not uniformly distributed, median values were used to represent the data. 92 patients with allergic rhinitis and asthma (united airways disease) were studied over 2 years including 21 children (age < 12 years) who had total IgE and allergen-specific IgE levels measured. The median IgE level was higher in 2016 than in 2015 with 60% of patients (adults and children) being sensitized to house dust mite (dual positivity for Dermatophagoides pteronyssinus and farinae). Of 11 children in 2015, whose total IgE ranged from 16.5 to >5000 kU/L, 36% of children were polysensitized (≥4 allergens), and 55% were sensitized to dust mites. Of 10 children in 2016, total IgE levels ranged from 37.5 to 2628 kU/L, and 20% were polysensitized with 60% sensitized to dust mites. Mould sensitivity was 10% in both of the years in the children studied. A consistent finding was that ragweed sensitization (molecular homology to Parthenium hysterophorus) appeared to be increasing across all age groups, and throughout the year, as reported previously by us where 25% of patients were sensitized. In the study sample overall, sensitizations to dust mite, cockroach, and parthenium were important risks in our patients with moderate to severe asthma that reinforces the importance of controlling indoor exposure to these allergens. Sensitizations to dust mite, cockroach and parthenium allergens are important predictors of asthma morbidity not only among children but also among adults in Eastern India.

Keywords: aAeroallergens, asthma, dust mite, parthenium, rhinitis

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Authors: Oyvind Nordvik, Peder O. L. Heggdal, Jonas Brannstrom, Flemming Vassbotn, Anne Kari Aarstad, Hans Jorgen Aarstad

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Background: Hearing Loss (HL) is a condition that may affect people in all stages of life, but the prevalence increases with age, mostly because of age-related HL, generally referred to as presbyacusis. As human speech is related to relatively high frequencies, even a limited hearing loss at high frequencies may cause impaired speech intelligibility. Being diagnosed with, treated for and living with a chronic condition such as HL, must for many be a disabling and stressful condition that put ones coping resources to test. Stress is a natural part of life and most people will experience stressful events or periods. Chronic diseases, such as HL, are risk factor for distress in individuals, causing anxiety and lowered mood. How an individual cope with HL may be closely connected to the level of distress he or she is experiencing and to personality, which can be defined as those characteristics of a person that account for consistent patterns of feelings, thinking, and behavior. Thus, as to distress in life, such as illness or disease, available coping strategies may be more important than the challenge itself. The same line of arguments applies to level of experienced health-related quality of life (HRQoL). Aim: The aim of this study was to investigate the relationship between distress, HRQoL, reported hearing loss, personality and coping in patients with HL. Method: 158 adult (aged 18-78 years) patients with HL, referred for hearing aid (HA) fitting at Haukeland University Hospital in western Norway, participated in the study. Both first-time users, as well as patients referred for HA renewals were included. First-time users had been pre-examined by an ENT-specialist. The questionnaires were answered before the actual HA fitting procedure. The pure-tone average (PTA; frequencies 0.5, 1, 2, and 4 kHz) was determined for each ear. The Eysenck personality inventory, neuroticism and lie scales, the Theoretically Originated Measure of the Cognitive Activation Theory of Stress (TOMCATS) measuring active coping, hopelessness and helplessness, as well as distress (General Health Questionnaire (GHQ) - 12 items) and the EORTC Quality of Life Questionnaire general part were answered. In addition, we used a revised and shortened version of the Abbreviated Profile of Hearing Aid Benefit (APHAB) as a measure of patient-reported hearing loss. Results: Significant correlations were determined between APHAB (weak), HRQoL scores (strong), distress scores (strong) on the one side and personality and choice of coping scores on the other side. As measured by stepwise regression analyses, the distress and HRQoL scores were scored secondary to the obtained personality and coping scores. The APHAB scores were as determined by regression analyses scored secondary to PTA (best ear), level of neuroticism and lie score. Conclusion: We found that reported employed coping style, distress/HRQoL and personality are closely connected to each other in this patient group. Patient-reported HL was associated to hearing level and personality. There is need for further investigations on these questions, and how these associations may influence the clinical context.

Keywords: coping, distress, hearing loss, personality

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Authors: Sandeep Kumar Agrawal, Aditi Bhattacharya, Janvie Manhas, Krushna Bhatt, Yatin Kholakiya, Nupur Khera, Ajoy Roychoudhury, Sudip Sen

Abstract:

Autologous cultured explants of human oral mucosal epithelial cells (OMEC) are a potential therapeutic modality for limbal stem cell deficiency (LSCD). Injury or inflammation of the ocular surface in the form of burns, chemicals, Stevens Johnson syndrome, ocular cicatricial pemphigoid etc. can lead to destruction and deficiency of limbal stem cells. LSCD manifests in the form of severe ocular surface diseases (OSD) characterized by persistent and recurrent epithelial defects, conjuntivalisation and neovascularisation of the corneal surface, scarring and ultimately opacity and blindness. Most of the cases of OSD are associated with severe dry eye pertaining to diminished mucin and aqueous secretion. Mycophenolate mofetil (MMF) has been shown to upregulate the mucin expression in conjunctival goblet cells in vitro. The aim of this study was to evaluate the effects of MMF on mucin expression in primary cultures of oral mucosal epithelial cells. With institutional ethics committee approval and written informed consent, thirty oral mucosal epithelial tissue samples were obtained from patients undergoing oral surgery for non-malignant conditions. OMEC were grown on human amniotic membrane (HAM, obtained from expecting mothers undergoing elective caesarean section) scaffold for 2 weeks in growth media containing DMEM & Ham’s F12 (1:1) with 10% FBS and growth factors. In vitro dosage of MMF was standardised by MTT assay. Analysis of stem cell markers was done using RT-PCR while mucin mRNA expression was quantified using RT-PCR and q-PCR before and after treating cultured OMEC with graded concentrations of MMF for 24 hours. Protein expression was validated using immunocytochemistry. Morphological studies revealed a confluent sheet of proliferating, stratified oral mucosal epithelial cells growing over the surface of HAM scaffold. The presence of progenitor stem cell markers (p63, p75, β1-Integrin and ABCG2) and cell surface associated mucins (MUC1, MUC15 and MUC16) were elucidated by RT-PCR. The mucin mRNA expression was found to be upregulated in MMF treated primary cultures of OMEC, compared to untreated controls as quantified by q-PCR with β-actin as internal reference gene. Increased MUC1 protein expression was validated by immunocytochemistry on representative samples. Our findings conclude that OMEC have the ability to form a multi-layered confluent sheet on the surface of HAM similar to a cornea, which is important for the reconstruction of the damaged ocular surface. Cultured OMEC has stem cell properties as demonstrated by stem cell markers. MMF can be a novel enhancer of mucin production in OMEC. It has the potential to improve dry eye in patients undergoing OMEC transplantation for bilateral OSD. Further clinical trials are required to establish the role of MMF in patients undergoing OMEC transplantation.

Keywords: limbal stem cell deficiency, mycophenolate mofetil, mucin, ocular surface disease

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Authors: Tatsiana Ihnatovich, Darya Nizheharodava, Mikalai Halabarodzka, Tatsiana Savitskaya, Marina Zafranskaya

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Liver fibrosis is a complex of histological changes resulting from chronic liver disease accompanied by an excessive production and deposition of extracellular matrix components in the hepatic parenchyma. Liver fibrosis is a serious medical and social problem. Hepatic stellate cells (HSCs) make a significant contribution to the extracellular matrix deposition due to liver injury. Mesenchymal stem cells (MSCs) have a pronounced anti-inflammatory, regenerative and immunomodulatory effect; they are able to differentiate into hepatocytes and induce apoptosis of activated HSCs that opens the prospect of their use for preventing the excessive fibro-formation and the development of liver cirrhosis. The aim of the study is to evaluate the effect of MSCs therapy on the expression of fibrogenesis markers genes in liver tissue and HSCs cultures of rats with experimental liver cirrhosis (ELC). Materials and methods: ELC was induced by the common bile duct ligation (CBDL) in female Wistar rats (n = 19) with an average body weight of 250 (220 ÷ 270) g. Animals from the control group (n = 10) were sham-operated. On the 56th day after the CBDL, the rats of the experimental (n = 12) and the control (n = 5) groups received intraportal MSCs in concentration of 1×106 cells/animal (previously obtained from rat’s bone marrow) or saline, respectively. The animals were taken out of the experiment on the 21st day. HSCs were isolated by sequential liver perfusion in situ with following disaggregation, enzymatic treatment and centrifugation of cell suspension on a two-stage density gradient. The expression of collagen type I (Col1a1) and type III (Col3a1), matrix metalloproteinase type 2 (MMP2) and type 9 (MMP9), tissue inhibitor of matrix metalloproteinases type 1 (TIMP1), transforming growth factor β type 1 (TGFβ1) and type 3 (TGFβ3) was determined by real-time polymerase chain reaction. Statistical analysis was performed using Statistica 10.0. Results: In ELC rats compared to sham-operated animals, a significant increase of all studied markers expression was observed. The administration of MSCs led to a significant decrease of all detectable markers in the experimental group compared to rats without cell therapy. In ELC rats, an increased MMP9/TIMP1 ratio after cell therapy was also detected. The infusion of MSCs in the sham-operated animals did not lead to any changes. In the HSCs from ELC animals, the expression of Col1a1 and Col3a1 exceeded the similar parameters of the control group (p <0.05) and statistically decreased after the MSCs administration. The correlation between Col3a1 (Rs = 0.51, p <0.05), TGFβ1 (Rs = 0.6, p <0.01), and TGFβ3 (Rs = 0.75, p <0.001) expression in HSCs cultures and liver tissue has been found. Conclusion: Intraportal administration of MSCs to rats with ELC leads to a decreased Col1a1 and Col3a1, MMP2 and MMP9, TIMP1, TGFβ1 and TGFβ3 expression. The correlation between the expression of Col3a1, TGFβ1 and TGFβ3 in liver tissue and in HSCs cultures indicates the involvement of activated HSCs in the fibrogenesis that allows considering HSCs to be the main cell therapy target in ELC.

Keywords: cell therapy, experimental liver cirrhosis, hepatic stellate cells, mesenchymal stem cells

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Authors: Sahar Nasr, Lin Li, Edwin Wang

Abstract:

Bladder cancer (BLCA) is known as the 13th cause of death among cancer patients worldwide, and ~575,000 new BLCA cases are diagnosed each year. Urothelial carcinoma (UC) is the most prevalent subtype among BLCA patients, which can be categorized into muscle-invasive bladder cancer (MIBC) and non-muscle-invasive bladder cancer (NMIBC). Currently, various therapeutic options are available for UC patients, including (1) transurethral resection followed by intravesical instillation of chemotherapeutics or Bacillus Calmette-Guérin for NMIBC patients, (2) neoadjuvant platinum-based chemotherapy (NAC) plus radical cystectomy is the standard of care for localized MIBC patients, and (3) systematic chemotherapy for metastatic UC. However, conventional treatments may lead to several challenges for treating patients. As an illustration, some patients may suffer from recurrence of the disease after the first line of treatment. Recently, immune checkpoint therapy (ICT) has been introduced as an alternative treatment strategy for the first or second line of treatment in advanced or metastatic BLCA patients. Although ICT showed lucrative results for a fraction of BLCA patients, ~80% of patients were not responsive to it. Therefore, novel treatment methods are required to augment the ICI response rate within BLCA patients. It has been shown that the infiltration of T-cells into the tumor microenvironment (TME) is positively correlated with the response to ICT within cancerous patients. Therefore, the goal of this study is to enhance the infiltration of cytotoxic T-cells into TME through the identification of target genes within the tumor that are responsible for the non-T-cell inflamed TME and their inhibition. BLCA bulk RNA-sequencing data from The Cancer Genome Atlas (TCGA) and immune score for TCGA samples were used to determine the Pearson correlation score between the expression of different genes and immune score for each sample. The genes with strong negative correlations were selected (r < -0.2). Thereafter, the correlation between the expression of each gene and survival in BLCA patients was calculated using the TCGA data and Cox regression method. The genes that are common in both selected gene lists were chosen for further analysis. Afterward, BLCA bulk and single-cell RNA-sequencing data were ranked based on the expression of each selected gene and the top and bottom 25% samples were used for pathway enrichment analysis. If the pathways related to the T-cell infiltration (e.g., antigen presentation, interferon, or chemokine pathways) were enriched within the low-expression group, the gene was included for downstream analysis. Finally, the selected genes will be used to calculate the correlation between their expression and the infiltration rate of the activated CD+8 T-cells, natural killer cells and the activated dendric cells. A list of potential target genes has been identified and ranked based on the above-mentioned analysis and criteria. SUN-1 got the highest score within the gene list and other identified genes in the literature as benchmarks. In conclusion, inhibition of SUN1 may increase the tumor-infiltrating lymphocytes and the efficacy of ICI in BLCA patients. BLCA tumor cells with and without SUN-1 CRISPR/Cas9 knockout will be injected into the syngeneic mouse model to validate the predicted SUN-1 effect on increasing tumor-infiltrating lymphocytes.

Keywords: data analysis, gene expression analysis, gene identification, immunoinformatic, functional genomics, transcriptomics

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Authors: Ernest Moles, Patricia Urbán, María Belén Jiménez-Díaz, Sara Viera-Morilla, Iñigo Angulo-Barturen, Maria Antònia Busquets, Xavier Fernàndez-Busquets

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Bearing in mind the absence of an effective vaccine against malaria and its severe clinical manifestations causing nearly half a million deaths every year, this disease represents nowadays a major threat to life. Besides, the basic rationale followed by currently marketed antimalarial approaches is based on the administration of drugs on their own, promoting the emergence of drug-resistant parasites owing to the limitation in delivering drug payloads into the parasitized erythrocyte high enough to kill the intracellular pathogen while minimizing the risk of causing toxic side effects to the patient. Such dichotomy has been successfully addressed through the specific delivery of immunoliposome (iLP)-encapsulated antimalarials to Plasmodium falciparum-infected red blood cells (pRBCs). Unfortunately, this strategy has not progressed towards clinical applications, whereas in vitro assays rarely reach drug efficacy improvements above 10-fold. Here, we show that encapsulation efficiencies reaching >96% can be achieved for the weakly basic drugs chloroquine (CQ) and primaquine using the pH gradient active loading method in liposomes composed of neutrally charged, saturated phospholipids. Targeting antibodies are best conjugated through their primary amino groups, adjusting chemical crosslinker concentration to retain significant antigen recognition. Antigens from non-parasitized RBCs have also been considered as targets for the intracellular delivery of drugs not affecting the erythrocytic metabolism. Using this strategy, we have obtained unprecedented nanocarrier targeting to early intraerythrocytic stages of the malaria parasite for which there is a lack of specific extracellular molecular tags. Polyethylene glycol-coated liposomes conjugated with monoclonal antibodies specific for the erythrocyte surface protein glycophorin A (anti-GPA iLP) were capable of targeting 100% RBCs and pRBCs at the low concentration of 0.5 μM total lipid in the culture, with >95% of added iLPs retained into the cells. When exposed for only 15 min to P. falciparum in vitro cultures synchronized at early stages, free CQ had no significant effect over parasite viability up to 200 nM drug, whereas iLP-encapsulated 50 nM CQ completely arrested its growth. Furthermore, when assayed in vivo in P. falciparum-infected humanized mice, anti-GPA iLPs cleared the pathogen below detectable levels at a CQ dose of 0.5 mg/kg. In comparison, free CQ administered at 1.75 mg/kg was, at most, 40-fold less efficient. Our data suggest that this significant improvement in drug antimalarial efficacy is in part due to a prophylactic effect of CQ found by the pathogen in its host cell right at the very moment of invasion.

Keywords: immunoliposomal nanoparticles, malaria, prophylactic-therapeutic polyvalent activity, targeted drug delivery

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Authors: Nadia Obaed, Lexi Frankel, Amalia Ardeljan, Denis Nigel, Anniki Witter, Omar Rashid

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Breast cancer is the most common cancer among women, with a lifetime risk of one in eight of all women in the United States. Although breast cancer is prevalent throughout the world, the uneven distribution in incidence and mortality rates is shaped by the variation in population structure, environment, genetics and known lifestyle risk factors. Furthermore, the bacterial profile in healthy and cancerous breast tissue differs with a higher relative abundance of bacteria capable of causing DNA damage in breast cancer patients. Previous bacterial infections may change the composition of the microbiome and partially account for the environmental factors promoting breast cancer. One study found that higher amounts of Staphylococcus, Bacillus, and Enterobacteriaceae, of which Escherichia coli (E. coli) is a part, were present in breast tumor tissue. Based on E. coli’s ability to damage DNA, it is hypothesized that there is an increased risk of breast cancer associated with previous E. coli infection. Therefore, the purpose of this study was to evaluate the correlation between E. coli infection and the incidence of breast cancer. Holy Cross Health, Fort Lauderdale, provided access to the Health Insurance Portability and Accountability (HIPAA) compliant national database for the purpose of academic research. International Classification of Disease 9th and 10th Codes (ICD-9, ICD-10) was then used to conduct a retrospective analysis using data from January 2010 to December 2019. All breast cancer diagnoses and all patients infected versus not infected with E. coli that underwent typical E. coli treatment were investigated. The obtained data were matched for age, Charlson Comorbidity Score (CCI score), and antibiotic treatment. Standard statistical methods were applied to determine statistical significance and an odds ratio was used to estimate the relative risk. A total of 81286 patients were identified and analyzed from the initial query and then reduced to 31894 antibiotic-specific treated patients in both the infected and control group, respectively. The incidence of breast cancer was 2.51% and present in 2043 patients in the E. coli group compared to 5.996% and present in 4874 patients in the control group. The incidence of breast cancer was 3.84% and present in 1223 patients in the treated E. coli group compared to 6.38% and present in 2034 patients in the treated control group. The decreased incidence of breast cancer in the E. coli and treated E. coli groups was statistically significant with a p-value of 2.2x10-16 and 2.264x10-16, respectively. The odds ratio in the E. coli and treated E. coli groups was 0.784 and 0.787 with a 95% confidence interval, respectively (0.756-0.813; 0.743-0.833). The current study shows a statistically significant decrease in breast cancer incidence in association with previous Escherichia coli infection. Researching the relationship between single bacterial species is important as only up to 10% of breast cancer risk is attributable to genetics, while the contribution of environmental factors including previous infections potentially accounts for a majority of the preventable risk. Further evaluation is recommended to assess the potential and mechanism of E. coli in decreasing the risk of breast cancer.

Keywords: breast cancer, escherichia coli, incidence, infection, microbiome, risk

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Authors: Allison Herlene Du Plessis, Dalena (R.M.) Van Rooyen, Wilma Ten Ham-Baloyi, Sihaam Jardien-Baboo

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Introduction: Women die in pregnancy and childbirth for five main reasons—severe bleeding, infections, unsafe abortions, hypertensive disorders (pre-eclampsia and eclampsia), and medical complications including cardiac disease, diabetes, or HIV/AIDS complicated by pregnancy. In 2015, WHO classified sepsis as the third highest cause for maternal mortalities in the world. Chorioamnionitis is a clinical syndrome of intrauterine infection during any stage of the pregnancy and it refers to ascending bacteria from the vaginal canal up into the uterus, causing infection. While the incidence rates for chorioamnionitis are not well documented, complications related to chorioamnionitis are well documented and midwives still struggle to identify this condition in time due to its complex nature. Few diagnostic methods are available in public health services, due to escalated laboratory costs. Often the affordable biomarkers, such as C-reactive protein CRP, full blood count (FBC) and WBC, have low significance in diagnosing chorioamnionitis. A lack of screening impacts on effective and timeous management of chorioamnionitis, and early identification and management of risks could help to prevent neonatal complications and reduce the subsequent series of morbidities and healthcare costs of infants who are health foci of perinatal infections. Objective: This integrative literature review provides an overview of current best research evidence on the screening of women at risk for chorioamnionitis. Design: An integrative literature review was conducted using a systematic electronic literature search through EBSCOhost, Cochrane Online, Wiley Online, PubMed, Scopus and Google. Guidelines, research studies, and reports in English related to chorioamnionitis from 2008 up until 2020 were included in the study. Findings: After critical appraisal, 31 articles were included. More than one third (67%) of the literature included ranked on the three highest levels of evidence (Level I, II and III). Data extracted regarding screening for chorioamnionitis was synthesized into four themes, namely: screening by clinical signs and symptoms, screening by causative factors of chorioamnionitis, screening of obstetric history, and essential biomarkers to diagnose chorioamnionitis. Key conclusions: There are factors that can be used by midwives to identify women at risk for chorioamnionitis. However, there are a paucity of established sociological, epidemiological and behavioral factors to screen this population. Several biomarkers are available to diagnose chorioamnionitis. Increased Interleukin-6 in amniotic fluid is the better indicator and strongest predictor of histological chorioamnionitis, whereas the available rapid matrix-metalloproteinase-8 test requires further testing. Maternal white blood cells count (WBC) has shown poor selectivity and sensitivity, and C-reactive protein (CRP) thresholds varied among studies and are not ideal for conclusive diagnosis of subclinical chorioamnionitis. Implications for practice: Screening of women at risk for chorioamnionitis by health care providers providing care for pregnant women, including midwives, is important for diagnosis and management before complications arise, particularly in resource-constraint settings.

Keywords: chorioamnionitis, guidelines, best evidence, screening, diagnosis, pregnant women

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