Search results for: chronic kidney failure disease

Authors: Gabrielle Robertson, Matthew Downs, Joseph Dagher

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Iron deposition in the brain has been linked with a host of neurological disorders such as Alzheimer’s, Parkinson’s, and Multiple Sclerosis. While some treatment options exist, there are no objective measurement tools that allow for the monitoring of iron levels in the brain in vivo. An emerging Magnetic Resonance Imaging (MRI) method has been recently proposed to deduce iron concentration through quantitative measurement of magnetic susceptibility. This is a multi-step process that involves repeated modeling of physical processes via approximate numerical solutions. For example, the last two steps of this Quantitative Susceptibility Mapping (QSM) method involve I) mapping magnetic field into magnetic susceptibility and II) mapping magnetic susceptibility into iron concentration. Process I involves solving an ill-posed inverse problem by using regularization via injection of prior belief. The end result from Process II highly depends on the model used to describe the molecular content of each voxel (type of iron, water fraction, etc.) Due to these factors, the accuracy and repeatability of QSM have been an active area of research in the MRI and medical imaging community. This work aims to estimate iron concentration in the brain via a single step. A synthetic numerical model of the human head was created by automatically and manually segmenting the human head on a high-resolution grid (640x640x640, 0.4mm³) yielding detailed structures such as microvasculature and subcortical regions as well as bone, soft tissue, Cerebral Spinal Fluid, sinuses, arteries, and eyes. Each segmented region was then assigned tissue properties such as relaxation rates, proton density, electromagnetic tissue properties and iron concentration. These tissue property values were randomly selected from a Probability Distribution Function derived from a thorough literature review. In addition to having unique tissue property values, different synthetic head realizations also possess unique structural geometry created by morphing the boundary regions of different areas within normal physical constraints. This model of the human brain is then used to create synthetic MRI measurements. This is repeated thousands of times, for different head shapes, volume, tissue properties and noise realizations. Collectively, this constitutes a training-set that is similar to in vivo data, but larger than datasets available from clinical measurements. This 3D convolutional U-Net neural network architecture was used to train data-driven Deep Learning models to solve for iron concentrations from raw MRI measurements. The performance was then tested on both synthetic data not used in training as well as real in vivo data. Results showed that the model trained on synthetic MRI measurements is able to directly learn iron concentrations in areas of interest more effectively than other existing QSM reconstruction methods. For comparison, models trained on random geometric shapes (as proposed in the Deep QSM method) are less effective than models trained on realistic synthetic head models. Such an accurate method for the quantitative measurement of iron deposits in the brain would be of important value in clinical studies aiming to understand the role of iron in neurological disease.

Keywords: magnetic resonance imaging, MRI, iron deposition, machine learning, quantitative susceptibility mapping

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Authors: Arifur Rahman, Ardeshir Amirkhani, Honghua Hu, Mark Molloy, Karen Vickery

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Introduction and Objectives: Staphylococcus aureus and coagulase-negative staphylococci comprises approximately 65% of infections associated with medical devices and are well known for their biofilm formatting ability. Biofilm-related infections are extremely difficult to eradicate owing to their high tolerance to antibiotics and host immune defences. Currently, there is no efficient method for early biofilm detection. A better understanding to enable detection of biofilm specific proteins in vitro and in vivo can be achieved by studying planktonic and different growth phases of biofilms using a proteome analysis approach. Our goal was to construct a reference map of planktonic and biofilm associated proteins of S. aureus. Methods: S. aureus reference strain (ATCC 25923) was used to grow 24 hours planktonic, 3-day wet biofilm (3DWB), and 12-day wet biofilm (12DWB). Bacteria were grown in tryptic soy broth (TSB) liquid medium. Planktonic growth was used late logarithmic bacteria, and the Centres for Disease Control (CDC) biofilm reactor was used to grow 3 days, and 12-day hydrated biofilms, respectively. Samples were subjected to reduction, alkylation and digestion steps prior to Multiplex labelling using Tandem Mass Tag (TMT) 10-plex reagent (Thermo Fisher Scientific). The labelled samples were pooled and fractionated by high pH RP-HPLC which followed by loading of the fractions on a nanoflow UPLC system (Eksigent UPLC system, AB SCIEX). Mass spectrometry (MS) data were collected on an Orbitrap Elite (Thermo Fisher Scientific) Mass Spectrometer. Protein identification and relative quantitation of protein levels were performed using Proteome Discoverer (version 1.3, Thermo Fisher Scientific). After the extraction of protein ratios with Proteome Discoverer, additional processing, and statistical analysis was done using the TMTPrePro R package. Results and Discussion: The present study showed that a considerable proteomic difference exists among planktonic and biofilms from S. aureus. We identified 1636 total extracellular secreted proteins, of which 350 and 137 proteins of 3DWB and 12DWB showed significant abundance variation from planktonic preparation, respectively. Of these, simultaneous up-regulation in between 3DWB and 12DWB proteins such as extracellular matrix-binding protein ebh, enolase, transketolase, triosephosphate isomerase, chaperonin, peptidase, pyruvate kinase, hydrolase, aminotransferase, ribosomal protein, acetyl-CoA acetyltransferase, DNA gyrase subunit A, glycine glycyltransferase and others we found in this biofilm producer. On the contrary, simultaneous down-regulation in between 3DWB and 12DWB proteins such as alpha and delta-hemolysin, lipoteichoic acid synthase, enterotoxin I, serine protease, lipase, clumping factor B, regulatory protein Spx, phosphoglucomutase, and others also we found in this biofilm producer. In addition, we also identified a big percentage of hypothetical proteins including unique proteins. Therefore, a comprehensive knowledge of planktonic and biofilm associated proteins identified by S. aureus will provide a basis for future studies on the development of vaccines and diagnostic biomarkers. Conclusions: In this study, we constructed an initial reference map of planktonic and various growth phase of biofilm associated proteins which might be helpful to diagnose biofilm associated infections.

Keywords: bacterial biofilms, CDC bioreactor, S. aureus, mass spectrometry, TMT

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Authors: Ikele Chika Bright, Mgbenka Bernard Obialo, Ikele Chioma Faith

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Icthyophthiriasis is a prevalent protozoan (ectoparasite) mostly affecting cultured and aquarium fishes. The majority of the chemotherapeutants lack efficacy for completely eliminating Ich parasite without affecting the environment and they are not safe for human health. The present work is focused on the evaluating different immersion treatments of African catfish (Clarias gariepinus) infected with ichthyophthiriasis and treated with a non-chemical and environmental friendly parasiticides Moringa oleifera. A total number of 800 apparently healthy parasites free (examined) post juvenile catfish were obtained from a reputable farm, disinfected with potassium permanganate in a quarantine tank to remove any possible external parasites. The fish were further challenged with approximately 44,000 infective stages of theronts which were obtained through serial passages by cohabitation. Seven groups (A-G) of post Juvenile were used for the experiment which was carried out into three stages; Dips (60minutes), short term treatment (24-96h) and prolong bath treatment (0-15 days). The concentrations selected were dependent on the outcome of the LC50 of the plant material from which dose-dependent factors were used to select various concentrations of the treatment. In Dips treatment, group D-G were treated with 1,500mg/L, 2500mg/L., 3500mg/L and 4500mg/L, short-term treatment was treated with 150mg/L, 250mg/L, 350mg/L and 450mg/L and prolong bath was treated with 15mg/L, 25mg/L, 35mg/L and 45mg/L of the plant extract whereas group A, B and C were normal control, Ich- infested not treated and Ich- infested treated with standard drug (Acriflavin), respectively. The various types of treatment applied with corresponding concentrations showed almost complete elimination of the adult parasites (trophonts) both in the gills and the body smear, thereby making M. oleifera a potential parasiticides. There were serious pathological alterations in the skin and gills which are usually the main point for Ich parasites invasion but no significant morphological characteristics was noted among the treated groups subjected to different immersion treatment patterns. Epitheliocystis, aneurysm, oedema, hemorrhage, and localization of the adult parasite in the gills were the overall common observations made in the gills whereas degeneration of muscle fibre, dermatitis, hemorrhage, oedema, abscess formation and keratinisation were observed in the skin. However, there are no pathological changes in the control group. Moreover, biochemical parameters such as urea, creatinine, albumin., globulin, total protein, ALT, AST), blood chemistry (sodium, chloride, potassium, bicarbonate), antioxidants (CAT, SOD, GPx, LPO), enzymatic activities (myeloperoxidase, thioreadoxin reductase), Inflammatory response (C-reactive protein), Stress markers (lactate dehydrogenase), heamatological parameters (RBC, PCV, WBC, HB and differential count), lipid profile (total cholesterol, tryglycerides , high density lipoprotein and low density lipoprotein) all showed various significant (P<0.05) and no significant (P>0.05) responses among the Ich-infested fish treated under three immersion treatments. It is suggested that M. oleifera may serve as an alternatives to chemotherapeutants for control of Ichthyophthiriasis in African catfish Clarias gariepinus.

Keywords: Icthyophthirius multifilis, immersion treatment, pathophysiology, African catfish

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Authors: Eric Spruth, Lindsey Herbert, Danielle DiCristofano, Isis Violet Spruth, Drake Von Spruth

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Turning dreams into reality, the lifelong passion of Mr. Spruth and the company is to transform garbage-filled courtyards into flourishing flower and vegetable gardens, bringing light, hope, and wellness to not just the space but to the populations served within these public and private spaces. As an Expressive Art Therapist at Cook County Jail, Eric Spruth has implemented gardening projects, mobile radish carts, plant fostering systems, and large-scale murals. Lindsey Herbert, the Manager of Operations and Events at the International Museum of Surgical Science, supports gardening projects with Mr. Spruth along the front lawn of the museum, which will eventually accumulate into a community wellness garden. Mr. Spruth and Ms. Herbert both have dedicated efforts towards fostering awareness of hope and help and accountability for physical and mental wellbeing. Medicinal plants can rightfully be called one of nature’s wonderful healing tools with therapeutic powers. They can inhibit and kill bacteria, lower blood pressure, blood cholesterol, and blood sugar, prevent blood clotting, boost the immune system, and serve as a digestive aid. Some plants have the ability to stimulate the lymphatic system, which expedites the removal of waste products from the body to fight off evil toxins. Many plants are considered effective antioxidants to protect cells against free radical damage, serving to prevent some forms of cancer, heart disease, strokes, and viral infections. Garlic alone can provide us with over two hundred unusual chemicals that have the capability of protecting the human body from a wide variety of diseases. Besides the medicinal qualities of plants, plant and vegetable gardens also have an echoing effect on non-participants to look at something beautiful rather than a concrete courtyard or an unkempt lawn in front of a beautiful building. Plants also purify spaces and affect mood with color therapy. Collective gardening can foster a sense of community and purpose. Additionally, by recognizing the ever-evolving planet with global warming, horticulture therapy teaches important lessons in responsibility, accountability, and sustainability. Growing local food provides an opportunity to be involved in your own mental and physical health and gives you a chance for your own self-resilience, combating depression and a lack of nutrition. In adolescents, the process of watering and caring for plants can teach important life lessons that transcend beyond the garden by providing knowledge on how to care for yourself and how to be an active member of society. It also gives a sense of purpose and pride in transforming a small seed into a plant that can be consumed or enjoyed by others. Mr. Spruth and Ms. Herbert recognize the importance of bringing more green spaces to urban areas, both to serve a nutritional benefit and provide a beautiful transformation to underutilized areas. Gardens can bring beauty, wellness, and hope to dark spaces and provide immeasurable benefits for all.

Keywords: growth, hope, mental health, sustainability, transformation, wellness

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Authors: Kartik Gupta, Virendra Kumar, Sanjeev Sinha, N. Jagannathan

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Introduction: A significant number of patients having human immunodeficiency virus (HIV) infection show a neurocognitive decline (NCD) ranging from minor cognitive impairment to severe dementia. The possible causes of NCD in HIV-infected patients include brain injury by HIV before cART, neurotoxic viral proteins and metabolic abnormalities. In the present study, we compared the level of NCD in asymptomatic HIV-infected patients with changes in brain metabolites measured by using magnetic resonance spectroscopy (MRS). Methods: 43 HIV-positive patients (30 males and 13 females) coming to ART center of the hospital and HIV-seronegative healthy subjects were recruited for the study. All the participants completed MRI and MRS examination, detailed clinical assessments and a battery of neuropsychological tests. All the MR investigations were carried out at 3.0T MRI scanner (Ingenia/Achieva, Philips, Netherlands). MRI examination protocol included the acquisition of T2-weighted imaging in axial, coronal and sagittal planes, T1-weighted, FLAIR, and DWI images in the axial plane. Patients who showed any apparent lesion on MRI were excluded from the study. T2-weighted images in three orthogonal planes were used to localize the voxel in left frontal lobe white matter (FWM) and left basal ganglia (BG) for single voxel MRS. Single voxel MRS spectra were acquired with a point resolved spectroscopy (PRESS) localization pulse sequence at an echo time (TE) of 35 ms and a repetition time (TR) of 2000 ms with 64 or 128 scans. Automated preprocessing and determination of absolute concentrations of metabolites were estimated using LCModel by water scaling method and the Cramer-Rao lower bounds for all metabolites analyzed in the study were below 15\%. Levels of total N-acetyl aspartate (tNAA), total choline (tCho), glutamate + glutamine (Glx), total creatine (tCr), were measured. Cognition was tested using a battery of tests validated for Indian population. The cognitive domains tested were the memory, attention-information processing, abstraction-executive, simple and complex perceptual motor skills. Z-scores normalized according to age, sex and education standard were used to calculate dysfunction in these individual domains. The NCD was defined as dysfunction with Z-score ≤ 2 in at least two domains. One-way ANOVA was used to compare the difference in brain metabolites between the patients and healthy subjects. Results: NCD was found in 23 (53%) patients. There was no significant difference in age, CD4 count and viral load between the two groups. Maximum impairment was found in the domains of memory and simple motor skills i.e., 19/43 (44%). The prevalence of deficit in attention-information processing, complex perceptual motor skills and abstraction-executive function was 37%, 35%, 33% respectively. Subjects with NCD had a higher level of Glutamate in the Frontal region (8.03 ± 2.30 v/s. 10.26 ± 5.24, p-value 0.001). Conclusion: Among newly diagnosed, ART-naïve retroviral disease patients from India, cognitive decline was found in 53\% patients using tests validated for this population. Those with neurocognitive decline had a significantly higher level of Glutamate in the left frontal region. There was no significant difference in age, CD4 count and viral load at initiation of ART between the two groups.

Keywords: HIV, neurocognitive decline, neurometabolites, magnetic resonance spectroscopy

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Authors: Paulo Roberto Vasconcellos-Silva

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The "Janeiro Roxo" (Purple January) campaign in Brazil aims to promote awareness of leprosy and its early symptoms. The COVID-19 pandemic has adversely affected institutional campaigns, mostly considering leprosy a neglected disease by the media. Google Trends (GT) is a tool that tracks user searches on Google, providing insights into the popularity of specific search terms. Our prior research has categorized online searches into two types: "Reactive searches," driven by transient campaign-related stimuli, and "Proactive searches," driven by personal interest in early symptoms and self-diagnosis. Using GT we studied: (i) the impact of "Janeiro Roxo" on public interest in leprosy (assessed through reactive searches) and its early symptoms (evaluated through proactive searches) over the past five years; (ii) changes in public interest during and after the COVID-19 pandemic; (iii) patterns in the dynamics of reactive and proactive searches Methods: We used GT's "Relative Search Volume" (RSV) to gauge public interest on a scale from 0 to 100. "HANSENÍASE" (HAN) was a proxy for reactive searches, and "HANSENÍASE SINTOMAS" (leprosy symptoms) (H.SIN) for proactive searches (interest in leprosy or in self-diagnosis). We analyzed 261 weeks of data from 2018 to 2023, using polynomial trend lines to model trends over this period. Analysis of Variance (ANOVA) was used to compare weekly RSV, monthly (MM) and annual means (AM). Results: Over a span of 261 weeks, there was consistently higher Relative Search Volume (RSV) for HAN compared to H.SIN. Both search terms exhibited their highest (MM) in January months during all periods. COVID-19 pandemic: a decline was observed during the pandemic years (2020-2021). There was a 24% decrease in RSV for HAN and a 32.5% decrease for H.SIN. Both HAN and H.SIN regained their pre-pandemic search levels in January 2022-2023. Breakpoints indicated abrupt changes - in the 26th week (February 2019), 55th and 213th weeks (September 2019 and 2022) related to September regional campaigns (interrupted in 2020-2021). Trend lines for HAN exhibited an upward curve between 33rd-45th week (April to June 2019), a pandemic-related downward trend between 120th-136th week (December 2020 to March 2021), and an upward trend between 220th-240th week (November 2022 to March 2023). Conclusion: The "Janeiro Roxo" campaign, along with other media-driven activities, exerts a notable influence on both reactive and proactive searches related to leprosy topics. Reactive searches, driven by campaign stimuli, significantly outnumber proactive searches. Despite the interruption of the campaign due to the pandemic, there was a subsequent resurgence in both types of searches. The recovery observed in reactive and proactive searches post-campaign interruption underscores the effectiveness of such initiatives, particularly at the national level. This suggests that regional campaigns aimed at leprosy awareness can be considered highly successful in stimulating proactive public engagement. The evaluation of internet-based campaign programs proves valuable not only for assessing their impact but also for identifying the needs of vulnerable regions. These programs can play a crucial role in integrating regions and highlighting their needs for assistance services in the context of leprosy awareness.

Keywords: health communication, leprosy, health campaigns, information seeking behavior, Google Trends, reactive searches, proactive searches, leprosy early identification

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Authors: Neusa Fernanda Torres, Buyisile Chibi, Lyn E. Middleton, Vernon P. Solomon, Tivani P. Mashamba-Thompson

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Background: Self-medication with antibiotics (SMA) is a global concern, with a higher incidence in low and middle-income countries (LMICs). Despite intense world-wide efforts to control and promote the rational use of antibiotics, continuing practices of SMA systematically exposes individuals and communities to the risk of antibiotic resistance and other undesirable antibiotic side effects. Moreover, it increases the health systems costs of acquiring more powerful antibiotics to treat the resistant infection. This review thus maps evidence on the factors influencing self-medication with antibiotics in these settings. Methods: The search strategy for this review involved electronic databases including PubMed, Web of Knowledge, Science Direct, EBSCOhost (PubMed, CINAHL with Full Text, Health Source - Consumer Edition, MEDLINE), Google Scholar, BioMed Central and World Health Organization library, using the search terms:’ Self-Medication’, ‘antibiotics’, ‘factors’ and ‘reasons’. Our search included studies published from 2007 to 2017. Thematic analysis was performed to identify the patterns of evidence on SMA in LMICs. The mixed method quality appraisal tool (MMAT) version 2011 was employed to assess the quality of the included primary studies. Results: Fifteen studies met the inclusion criteria. Studies included population from the rural (46,4%), urban (33,6%) and combined (20%) settings, of the following LMICs: Guatemala (2 studies), India (2), Indonesia (2), Kenya (1), Laos (1), Nepal (1), Nigeria (2), Pakistan (2), Sri Lanka (1), and Yemen (1). The total sample size of all 15 included studies was 7676 participants. The findings of the review show a high prevalence of SMA ranging from 8,1% to 93%. Accessibility, affordability, conditions of health facilities (long waiting, quality of services and workers) as long well as poor health-seeking behavior and lack of information are factors that influence SMA in LMICs. Antibiotics such as amoxicillin, metronidazole, amoxicillin/clavulanic, ampicillin, ciprofloxacin, azithromycin, penicillin, and tetracycline, were the most frequently used for SMA. The major sources of antibiotics included pharmacies, drug stores, leftover drugs, family/friends and old prescription. Sore throat, common cold, cough with mucus, headache, toothache, flu-like symptoms, pain relief, fever, running nose, toothache, upper respiratory tract infections, urinary symptoms, urinary tract infection were the common disease symptoms managed with SMA. Conclusion: Although the information on factors influencing SMA in LMICs is unevenly distributed, the available information revealed the existence of research evidence on antibiotic self-medication in some countries of LMICs. SMA practices are influenced by social-cultural determinants of health and frequently associated with poor dispensing and prescribing practices, deficient health-seeking behavior and consequently with inappropriate drug use. Therefore, there is still a need to conduct further studies (qualitative, quantitative and randomized control trial) on factors and reasons for SMA to correctly address the public health problem in LMICs.

Keywords: antibiotics, factors, reasons, self-medication, low and middle-income countries (LMICs)

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Authors: Prem K. Mony, Bharadwaj Amrutur, Prashanth Thankachan, Swarnarekha Bhat, Suman Rao, Maryann Washington, Annamma Thomas, N. Sheela, Hiteshwar Rao, Sumi Antony

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The disease burden among mothers and newborns is caused mostly by a handful of avoidable conditions occurring around the time of childbirth and within the first month following delivery. Real-time monitoring of vital parameters of mothers and neonates offers a potential opportunity to impact access as well as the quality of care in vulnerable populations. We describe the design, development and testing of an innovative wearable device for remote biomonitoring (RBM) of body temperatures in mothers and neonates in a hospital in southern India. The architecture consists of: [1] a low-cost, wearable sensor tag; [2] a gateway device for ‘real-time’ communication link; [3] piggy-backing on a commercial GSM communication network; and [4] an algorithm-based data analytics system. Requirements for the device were: long battery-life upto 28 days (with sampling frequency 5/hr); robustness; IP 68 hermetic sealing; and human-centric design. We undertook pre-clinical laboratory testing followed by clinical trial phases I & IIa for evaluation of safety and efficacy in the following sequence: seven healthy adult volunteers; 18 healthy mothers; and three sets of babies – 3 healthy babies; 10 stable babies in the Neonatal Intensive Care Unit (NICU) and 1 baby with hypoxic ischaemic encephalopathy (HIE). The 3-coin thickness, pebble-design sensor weighing about 8 gms was secured onto the abdomen for the baby and over the upper arm for adults. In the laboratory setting, the response-time of the sensor device to attain thermal equilibrium with the surroundings was 4 minutes vis-a-vis 3 minutes observed with a precision-grade digital thermometer used as a reference standard. The accuracy was ±0.1°C of the reference standard within the temperature range of 25-40°C. The adult volunteers, aged 20 to 45 years, contributed a total of 345 hours of readings over a 7-day period and the postnatal mothers provided a total of 403 paired readings. The mean skin temperatures measured in the adults by the sensor were about 2°C lower than the axillary temperature readings (sensor =34.1 vs digital = 36.1); this difference was statistically significant (t-test=13.8; p<0.001). The healthy neonates provided a total of 39 paired readings; the mean difference in temperature was 0.13°C (sensor =36.9 vs digital = 36.7; p=0.2). The neonates in the NICU provided a total of 130 paired readings. Their mean skin temperature measured by the sensor was 0.6°C lower than that measured by the radiant warmer probe (sensor =35.9 vs warmer probe = 36.5; p < 0.001). The neonate with HIE provided a total of 25 paired readings with the mean sensor reading being not different from the radian warmer probe reading (sensor =33.5 vs warmer probe = 33.5; p=0.8). No major adverse events were noted in both the adults and neonates; four adult volunteers reported mild sweating under the device/arm band and one volunteer developed mild skin allergy. This proof-of-concept study shows that real-time monitoring of temperatures is technically feasible and that this innovation appears to be promising in terms of both safety and accuracy (with appropriate calibration) for improved maternal and neonatal health.

Keywords: public health, remote biomonitoring, temperature surveillance, wearable sensors, mothers and newborns

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Authors: José Silvestre Mendoza Figueroa, Anders Kvarnheden, Jesús Méndez Lozano, Edgar Antonio Rodríguez Negrete, Manuel Soriano García

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Agroindustrial plants such as cereals and pseudo cereals offer a substantial source of biomacromolecules, as they contain large amounts per tissue-gram of proteins, polysaccharides and lipids in comparison with other plants. In particular, Amaranthus hypochondriacus seeds have high levels of proteins in comparison with other cereal and pseudo cereal species, which makes the plant a good source of bioactive molecules such as peptides. Geminiviruses are one principal class of pathogens that causes important economic losses in crops, affecting directly the development and production of the plant. One such virus is the Tomato yellow leaf curl virus (TYLCV), which affects mainly Solanacea family plants such as tomato species. The symptoms of the disease are curling of leaves, chlorosis, dwarfing and floral abortion. The aim of this work was to get peptides derived from enzymatic hydrolysis of globulins and albumins from amaranth seeds with specific recognition of the replication origin in the TYLCV genome, and to test the antiviral activity on host plants with the idea to generate a direct control of this viral infection. Globulins and albumins from amaranth were extracted, the fraction was enzymatically digested with papain, and the aromatic peptides fraction was selected for further purification. Six peptides were tested against the replication origin (OR) using affinity assays, surface resonance plasmon and fluorescent titration, and two of these peptides showed high affinity values to the replication origin of the virus, dissociation constant values were calculated and showed specific interaction between the peptide Ampep1 and the OR. An in vitro replication test of the total TYLCV DNA was performed, in which the peptide AmPep1 was added in different concentrations to the system reaction, which resulted in a decrease of viral DNA synthesis when the peptide concentration increased. Also, we showed that the peptide can decrease the complementary DNA chain of the virus in Nicotiana benthamiana leaves, confirming that the peptide binds to the OR and that its expected mechanism of action is to decrease the replication rate of the viral genome. In an infection assay, N. benthamiana plants were agroinfected with TYLCV-Israel and TYLCV-Guasave. After confirming systemic infection, the peptide was infiltrated in new infected leaves, and the plants treated with the peptide showed a decrease of virus symptoms and viral titer. In order to confirm the antiviral activity in a commercial crop, tomato plants were infected with TYLCV. After confirming systemic infection, plants were infiltrated with peptide solution as above, and the symptom development was monitored 21 days after treatment, showing that tomato plants treated with peptides had lower symptom rates and viral titer. The peptide was also tested against other begomovirus such as Pepper huasteco yellow vein virus (PHYVV-Guasave), showing a decrease of symptoms in N. benthamiana infected plants. The model of direct biochemical control of TYLCV infection shown in this work can be extrapolated to other begomovirus infections, and the methods reported here can be used for design of antiviral agrochemicals for other plant virus infections.

Keywords: agrochemical screening, antiviral, begomovirus, geminivirus, peptides, plasmon, TYLCV

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Authors: Thembelihle Portia Lubisi, Malusi Ntandoyenkosi Mkhize, Jonas Kalebe Johakimu

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Fertilizers play an important role in maintaining the productivity and quality of plants. Inorganic fertilizers (containing nitrogen, phosphorus, and potassium) are largely used in South Africa as they are considered inexpensive and highly productive. When applied, a portion of the excess fertilizer will be retained in the soil, a portion enters water streams due to surface runoff or the irrigation system adopted. Excess nutrient from the fertilizers entering the water stream eventually results harmful algal blooms (HABs) in freshwater systems, which not only disrupt wildlife but can also produce toxins harmful to humans. Use of agro-chemicals such as pesticides and herbicides has been associated with increased antimicrobial resistance (AMR) in humans as the plants are consumed by humans. This resistance of bacterial poses a threat as it prevents the Health sector from being able to treat infectious disease. Archaeological studies have found that pyrolysis liquids were already used in the time of the Neanderthal as a biocide and plant protection product. Pyrolysis is thermal degradation process of plant biomass or organic material under anaerobic conditions leading to production of char, bio-oils and syn gases. Bio-oil constituents can be categorized as water soluble (wood vinegar) and water insoluble fractions (tar and light oils). Wood vinegar (pyro-ligneous acid) is said to contain contains highly oxygenated compounds including acids, alcohols, aldehydes, ketones, phenols, esters, furans, and other multifunctional compounds with various molecular weights and compositions depending on the biomass material derived from and pyrolysis operating conditions. Various researchers have found the wood vinegar to be efficient in the eradication of termites, effective in plant protection and plant growth, has antibacterial characteristics and was found effective in inhibiting the micro-organisms such as candida yeast, E-coli, etc. This study investigated characterisation of South African forestry product processing waste with intention of evaluating the potential of using the respective biomass waste as feedstock for boil oil production via pyrolysis process. Ability to use biomass waste materials in production of wood-vinegar has advantages that it does not only allows for reduction of environmental pollution and landfill requirement, but it also does not negatively affect food security. The biomass wastes investigated were from the popular tree types in KZN, which are, pine saw dust (PSD), pine bark (PB), eucalyptus saw dust (ESD) and eucalyptus bark (EB). Furthermore, the research investigates the possibility of mixing the different wastes with an aim to lessen the cost of raw material separation prior to feeding into pyrolysis process and mixing also increases the amount of biomass material available for beneficiation. A 50/50 mixture of PSD and ESD (EPSD) and mixture containing pine saw dust; eucalyptus saw dust, pine bark and eucalyptus bark (EPSDB). Characterisation of the biomass waste will look at analysis such as proximate (volatiles, ash, fixed carbon), ultimate (carbon, hydrogen, nitrogen, oxygen, sulphur), high heating value, structural (cellulose, hemicellulose and lignin) and thermogravimetric analysis.

Keywords: characterisation, biomass waste, saw dust, wood waste

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Authors: Charles Shang, Salina Ramirez, Stephen Shang, Maria Estrada, Timothy R. Williams

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Purpose: Over the past decade, proton therapy utilizing pencil beam scanning has emerged as a preferred treatment modality in radiation oncology, particularly for prostate cancer. This retrospective study aims to assess the clinical and radiobiological efficacy of proton scanning beam therapy in the treatment of localized salvage prostate cancer, following initial radiation therapy with a different modality. Despite the previously delivered high radiation doses, this investigation explores the potential of proton reirradiation in controlling recurrent prostate cancer and detrimental quality of life side effects. Methods and Materials: A retrospective analysis was conducted on 45 cases of locally recurrent prostate cancer that underwent salvage proton reirradiation. Patients were followed for 24.6 ± 13.1 months post-treatment. These patients had experienced an average remission of 8.5 ± 7.9 years after definitive radiotherapy for localized prostate cancer (n=41) or post-prostatectomy (n=4), followed by rising PSA levels. Recurrent disease was confirmed by FDG-PET (n=31), PSMA-PET (n=10), or positive local biopsy (n=4). Gross tumor volume (GTV) was delineated based on PET and MR imaging, with the planning target volume (PTV) expanding to an average of 10.9 cm³. Patients received proton reirradiation using two oblique coplanar beams, delivering total doses ranging from 30.06 to 60.00 GyE in 17–30 fractions. All treatments were administered using the ProBeam Compact system with CT image guidance. The International Prostate Symptom Scores (IPSS) and prostate-specific antigen (PSA) levels were evaluated to assess treatment-related toxicity and tumor control. Results and Discussions: In this cohort (mean age: 76.7 ± 7.3 years), 60% (27/45) of patients showed sustained reductions in PSA levels post-treatment, while 36% (16/45) experienced a PSA decline of more than 0.8 ng/mL. Additionally, 73% (33/45) of patients exhibited an initial PSA reduction, though some showed later PSA increases, indicating the potential presence of undetected metastatic lesions. The median post-retreatment IPSS score was 4, significantly lower than scores reported in other treatment studies. Overall, 69% of patients reported mild urinary symptoms, with 96% (43/45) experiencing mild to moderate symptoms. Three patients experienced grade I or II proctitis, while one patient reported grade III proctitis. These findings suggest that regional organs, including the urethra, bladder, and rectum, demonstrate significant radiobiological recovery from prior radiation exposure, enabling tolerance to additional proton scanning beam therapy. Conclusions: This retrospective analysis of 45 patients with recurrent localized prostate cancer treated with salvage proton reirradiation demonstrates favorable outcomes, with a median follow-up of two years. The post-retreatment IPSS scores were comparable to those reported in follow-up studies of initial radiation therapy treatments, indicating stable or improved urinary symptoms compared to the end of initial treatment. These results highlight the efficacy of proton scanning beam therapy in providing effective salvage treatment while minimizing adverse effects on critical organs. The findings also enhance the understanding of radiobiological responses to reirradiation and support proton therapy as a viable option for patients with recurrent localized prostate cancer following previous definitive radiation therapy.

Keywords: prostate salvage radiotherapy, proton therapy, biological radiation tolerance, radiobiology of organs

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Authors: A. J. Al-Graitti, G. A. Khalid, P. Berthelson, A. Mason-Jones, R. Prabhu, M. D. Jones

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Motor vehicle related pedestrian road traffic collisions are a major road safety challenge, since they are a leading cause of death and serious injury worldwide, contributing to a third of the global disease burden. The auto rickshaw, which is a common form of urban transport in many developing countries, plays a major transport role, both as a vehicle for hire and for private use. The most common auto rickshaws are quite unlike ‘typical’ four-wheel motor vehicle, being typically characterised by three wheels, a non-tilting sheet-metal body or open frame construction, a canvas roof and side curtains, a small drivers’ cabin, handlebar controls and a passenger space at the rear. Given the propensity, in developing countries, for auto rickshaws to be used in mixed cityscapes, where pedestrians and vehicles share the roadway, the potential for auto rickshaw impacts with pedestrians is relatively high. Whilst auto rickshaws are used in some Western countries, their limited number and spatial separation from pedestrian walkways, as a result of city planning, has not resulted in significant accident statistics. Thus, auto rickshaws have not been subject to the vehicle impact related pedestrian crash kinematic analyses and/or injury mechanics assessment, typically associated with motor vehicle development in Western Europe, North America and Japan. This study presents a parametric analysis of auto rickshaw related pedestrian impacts by computational simulation, using a Finite Element model of an auto rickshaw and an LS-DYNA 50^th percentile male Hybrid III Anthropometric Test Device (dummy). Parametric variables include auto rickshaw impact velocity, auto rickshaw impact region (front, centre or offset) and relative pedestrian impact position (front, side and rear). The output data of each impact simulation was correlated against reported injury metrics, Head Injury Criterion (front, side and rear), Neck injury Criterion (front, side and rear), Abbreviated Injury Scale and reported risk level and adds greater understanding to the issue of auto rickshaw related pedestrian injury risk. The parametric analyses suggest that pedestrians are subject to a relatively high risk of injury during impacts with an auto rickshaw at velocities of 20 km/h or greater, which during some of the impact simulations may even risk fatalities. The present study provides valuable evidence for informing a series of recommendations and guidelines for making the auto rickshaw safer during collisions with pedestrians. Whilst it is acknowledged that the present research findings are based in the field of safety engineering and may over represent injury risk, compared to “Real World” accidents, many of the simulated interactions produced injury response values significantly greater than current threshold curves and thus, justify their inclusion in the study. To reduce the injury risk level and increase the safety of the auto rickshaw, there should be a reduction in the velocity of the auto rickshaw and, or, consideration of engineering solutions, such as retro fitting injury mitigation technologies to those auto rickshaw contact regions which are the subject of the greatest risk of producing pedestrian injury.

Keywords: auto rickshaw, finite element analysis, injury risk level, LS-DYNA, pedestrian impact

Procedia PDF Downloads 193

Authors: Camille Aouinaït, Danilo Christen, Christoph Carlen

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Introduction: Small and Medium-sized Enterprises (SMEs) are facing different challenges such as pressures on environmental resources, the rise of downstream power, and trade liberalization. Remaining competitive by implementing innovations and engaging in collaborations could be a strategic solution. In Switzerland, the Federal Institute for Research in Agriculture (Agroscope), the Federal schools of technology (EPFL and ETHZ), Cantonal universities and Universities of Applied Sciences (UAS) can provide substantial inputs. UAS were developed with specific missions to match the labor markets and society needs. Research projects produce patents, publications and improved networks of scientific expertise. The study’s goal is to measure the contribution of UAS and research organization to innovation and the impact of collaborations with partners in the non-academic environment in Swiss traditional fruit production. Materials and methods: The European projects Traditional Food Network to improve the transfer of knowledge for innovation (TRAFOON) and Social Impact Assessment of Productive Interactions between science and society (SIAMPI) frame the present study. The former aims to fill the gap between the needs of traditional food producing SMEs and innovations implemented following European projects. The latter developed a method to assess the impacts of scientific research. On one side, interviews with market players have been performed to make an inventory of needs of Swiss SMEs producing apricots and berries. The participative method allowed matching the current needs and the existing innovations coming from past European projects. Swiss stakeholders (e.g. producers, retailers, an inter-branch organization of fruits and vegetables) directly rated the needs on a five-Likert scale. To transfer the knowledge to SMEs, training workshops have been organized for apricot and berries actors separately, on specific topics. On the other hand, a mapping of a social network is drawn to characterize the links between actors, with a focus on the Swiss canton of Valais and UAS Valais Wallis. Type and frequency of interactions among actors have identified thanks to interviews. Preliminary results: A list of 369 SMEs needs grouped in 22 categories was produced with 37 fulfilled questionnaires. Swiss stakeholders rated 31 needs very important. Training workshops on apricot are focusing on varietal innovations, storage, disease (bacterial blight), pest (Drosophila suzukii), sorting and rootstocks. Entrepreneurship was targeted through trademark discussions in berry production. The UAS Valais Wallis collaborated on a few projects with Agroscope along with industries, at European and national levels. Political and public bodies interfere with the central area of agricultural vulgarization that induces close relationships between the research and the practical side. Conclusions: The needs identified by Swiss stakeholders are becoming part of training workshops to incentivize innovations. The UAS Valais Wallis takes part in collaboration projects with the research environment and market players that bring innovations helping SMEs in their contextual environment. Then, a Strategic Research and Innovation Agenda will be created in order to pursue research and answer the issues facing by SMEs.

Keywords: agriculture, innovation, knowledge transfer, university and research collaboration

Procedia PDF Downloads 393

Authors: Achraf Al Faraj, Asma Sultana Shaik, Baraa Al Sayed

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Specific and effective targeting of drug delivery systems (DDS) to cancerous sites remains a major challenge for a better diagnostic and therapy. Recently, SWCNTs with their unique physicochemical properties and the ability to cross the cell membrane show promising in the biomedical field. The purpose of this study was first to develop a biocompatible iron oxide tagged SWCNTs as diagnostic nanoprobes to allow their noninvasive detection using MRI and their preferential targeting in a breast cancer murine model by placing an optimized flexible magnet over the tumor site. Magnetic targeting was associated to specific antibody-conjugated SWCNTs active targeting. The therapeutic efficacy of doxorubicin-conjugated SWCNTs was assessed, and the superiority of diffusion-weighted (DW-) MRI as sensitive imaging biomarker was investigated. Short Polyvinylpyrrolidone (PVP) stabilized water soluble SWCNTs were first developed, tagged with iron oxide nanoparticles and conjugated with Endoglin/CD105 monoclonal antibodies. They were then conjugated with doxorubicin drugs. SWCNTs conjugates were extensively characterized using TEM, UV-Vis spectrophotometer, dynamic light scattering (DLS) zeta potential analysis and electron spin resonance (ESR) spectroscopy. Their MR relaxivities (i.e. r1 and r2*) were measured at 4.7T and their iron content and metal impurities quantified using ICP-MS. SWCNTs biocompatibility and drug efficacy were then evaluated both in vitro and in vivo using a set of immunological assays. Luciferase enhanced bioluminescence 4T1 mouse mammary tumor cells (4T1-Luc2) were injected into the right inguinal mammary fat pad of Balb/c mice. Tumor bearing mice received either free doxorubicin (DOX) drug or SWCNTs with or without either DOX or iron oxide nanoparticles. A multi-pole 10x10mm high-energy flexible magnet was maintained over the tumor site during 2 hours post-injections and their properties and polarity were optimized to allow enhanced magnetic targeting of SWCNTs toward the primary tumor site. Tumor volume was quantified during the follow-up investigation study using a fast spin echo MRI sequence. In order to detect the homing of SWCNTs to the main tumor site, susceptibility-weighted multi-gradient echo (MGE) sequence was used to generate T2* maps. Apparent diffusion coefficient (ADC) measurements were also performed as a sensitive imaging biomarker providing early and better assessment of disease treatment. At several times post-SWCNT injection, histological analysis were performed on tumor extracts and iron-loaded SWCNT were quantified using ICP-MS in tumor sites, liver, spleen, kidneys, and lung. The optimized multi-poles magnet revealed an enhanced targeting of magnetic SWCNTs to the primary tumor site, which was found to be much higher than the active targeting achieved using antibody-conjugated SWCNTs. Iron-loading allowed their sensitive noninvasive tracking after intravenous administration using MRI. The active targeting of doxorubicin through magnetic antibody-conjugated SWCNTs nanoprobes was found to considerably decrease the primary tumor site and may have inhibited the development of metastasis in the tumor-bearing mice lung. ADC measurements in DW-MRI were found to significantly increase in a time-dependent manner after the injection of DOX-conjugated SWCNTs complexes.

Keywords: single-walled carbon nanotubes, nanomedicine, magnetic resonance imaging, cancer diagnosis and therapy

Procedia PDF Downloads 328

Authors: Wellemans Isabelle, Remmelink Myriam, Foucart Annick, Rusu Stefan, Compère Christophe

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Primary pulmonary meningioma (PPM) is a very rare tumor, and its occurrence has been reported only sporadically. Multiple PPMs are even more exceptional, and herein, we report, to the best of our knowledge, the fourth case, focusing on the clinicopathological features of the tumor. Moreover, the possible relationship between the use of progesterone–only contraceptives and the development of these neoplasms will be discussed. Case Report: We report a case of a 51-year-old female presenting three solid pulmonary nodules, with the following localizations: right upper lobe, middle lobe, and left lower lobe, described as incidental findings on computed tomography (CT) during a pre-bariatric surgery check-up. The patient revealed no drinking or smoking history. The physical exam was unremarkable except for the obesity. The lesions ranged in size between 6 and 24 mm and presented as solid nodules with lobulated contours. The largest lesion situated in the middle lobe had mild fluorodeoxyglucose (FDG) uptake on F-18 FDG positron emission tomography (PET)/CT, highly suggestive of primary lung neoplasm. For pathological assessment, video-assisted thoracoscopic middle lobectomy and wedge resection of the right upper nodule was performed. Histological examination revealed relatively well-circumscribed solid proliferation of bland meningothelial cells growing in whorls and lobular nests, presenting intranuclear pseudo-inclusions and psammoma bodies. No signs of anaplasia were observed. The meningothelial cells expressed diffusely Vimentin, focally Progesterone receptors and were negative for epithelial (cytokeratin (CK) AE1/AE3, CK7, CK20, Epithelial Membrane Antigen (EMA)), neuroendocrine markers (Synaptophysin, Chromogranin, CD56) and Estrogenic receptors. The proliferation labelling index Ki-67 was low (<5%). Metastatic meningioma was ruled out by brain and spine magnetic resonance imaging (MRI) scans. The third lesion localized in the left lower lobe was followed-up and resected three years later because of its slow but significant growth (14 mm to 16 mm), alongside two new infra centimetric lesions. Those three lesions showed a morphological and immunohistochemical profile similar to previously resected lesions. The patient was disease-free one year post-last surgery. Discussion: Although PPMs are mostly benign and slow-growing tumors with an excellent prognosis, they do not present specific radiological characteristics, and it is difficult to differentiate it from other lung tumors, histopathologic examination being essential. Aggressive behavior is associated with atypical or anaplastic features (WHO grades II–III) The etiology is still uncertain and different mechanisms have been proposed. A causal connection between sexual hormones and meningothelial proliferation has long been suspected and few studies examining progesterone only contraception and meningioma risk have all suggested an association. In line with this, our patient was treated with Levonorgestrel, a progesterone agonist, intra-uterine device (IUD). Conclusions: PPM, defined by the typical histological and immunohistochemical features of meningioma in the lungs and the absence of central nervous system lesions, is an extremely rare neoplasm, mainly solitary and associating, and indolent growth. Because of the unspecific radiologic findings, it should always be considered in the differential diagnosis of lung neoplasms. Regarding multiple PPM, only three cases are reported in the literature, and this is the first described in a woman treated by a progesterone-only IUD to the best of our knowledge.

Keywords: pulmonary meningioma, multiple meningioma, meningioma, pulmonary nodules

Procedia PDF Downloads 112

Authors: Katarzyna Lubecka, Kirsty Flower, Megan Beetch, Lucinda Kurzava, Hannah Buvala, Samer Gawrieh, Suthat Liangpunsakul, Tracy Gonzalez, George McCabe, Naga Chalasani, James M. Flanagan, Barbara Stefanska

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Hepatocellular carcinoma (HCC), the most prevalent type of primary liver cancer, is the second leading cause of cancer death worldwide. Late onset of clinical symptoms in HCC results in late diagnosis and poor disease outcome. Approximately 85% of individuals with HCC have underlying liver cirrhosis. However, not all cirrhotic patients develop cancer. Reliable early detection biomarkers that can distinguish cirrhotic patients who will develop cancer from those who will not are urgently needed and could increase the cure rate from 5% to 80%. We used Illumina-450K microarray to test whether blood DNA, an easily accessible source of DNA, bear site-specific changes in DNA methylation in response to HCC before diagnosis with conventional tools (pre-diagnostic). Top 11 differentially methylated sites were selected for validation by pyrosequencing. The diagnostic potential of the 11 pyrosequenced probes was tested in blood samples from a prospective cohort of cirrhotic patients. We identified 971 differentially methylated CpG sites in pre-diagnostic HCC cases as compared with healthy controls (P < 0.05, paired Wilcoxon test, ICC ≥ 0.5). Nearly 76% of differentially methylated CpG sites showed lower levels of methylation in cases vs. controls (P = 2.973E-11, Wilcoxon test). Classification of the CpG sites according to their location relative to CpG islands and transcription start site revealed that those hypomethylated loci are located in regulatory regions important for gene transcription such as CpG island shores, promoters, and 5’UTR at higher frequency than hypermethylated sites. Among 735 CpG sites hypomethylated in cases vs. controls, 482 sites were assigned to gene coding regions whereas 236 hypermethylated sites corresponded to 160 genes. Bioinformatics analysis using GO, KEGG and DAVID knowledgebase indicate that differentially methylated CpG sites are located in genes associated with functions that are essential for gene transcription, cell adhesion, cell migration, and regulation of signal transduction pathways. Taking into account the magnitude of the difference, statistical significance, location, and consistency across the majority of matched pairs case-control, we selected 11 CpG loci corresponding to 10 genes for further validation by pyrosequencing. We established that methylation of CpG sites within 5 out of those 10 genes distinguish cirrhotic patients who subsequently developed HCC from those who stayed cancer free (cirrhotic controls), demonstrating potential as biomarkers of early detection in populations at risk. The best predictive value was detected for CpGs located within BARD1 (AUC=0.70, asymptotic significance ˂0.01). Using an additive logistic regression model, we further showed that 9 CpG loci within those 5 genes, that were covered in pyrosequenced probes, constitute a panel with high diagnostic accuracy (AUC=0.887; 95% CI:0.80-0.98). The panel was able to distinguish pre-diagnostic cases from cirrhotic controls free of cancer with 88% sensitivity at 70% specificity. Using blood as a minimally invasive material and pyrosequencing as a straightforward quantitative method, the established biomarker panel has high potential to be developed into a routine clinical test after validation in larger cohorts. This study was supported by Showalter Trust, American Cancer Society (IRG#14-190-56), and Purdue Center for Cancer Research (P30 CA023168) granted to BS.

Keywords: biomarker, DNA methylation, early detection, hepatocellular carcinoma

Procedia PDF Downloads 303

Authors: Delsy Salinas, Andreia Garcês, Augusto Silva, Paula Brilhante Simões

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Urinary tract infection (UTI) is a common disease affecting dogs and cats in both community and hospital environment. Bacteria is the most frequent agent isolated, fewer than 1% of infections are due to parasitic, fungal, or viral agents. Common symptoms and laboratory abnormalities includeabdominal pain, pyrexia, renomegaly, and neutrophilia with left shift. A rapid and precise identification of the bacterial agent is still a challenge in veterinarian laboratories. Therefore, this cross-sectional study aims to describe bacterial colony patterns of urine samples by using chromID™ CPS® EliteAgar (BioMérieux, France) from canine and feline specimens submitted to a veterinary laboratory in Portugal (INNO Veterinary Laboratory, Braga)from January to March2022. All urine samples were cultivated in CPS Elite Agar with calibrated 1 µL inoculating loop and incubated at 37ºC for 18-24h. Color,size, and shape (regular or irregular outline)were recorded for all samples. All colonies were classified as Gram-negative or Gram-positive bacteriausing Gram stain (PREVI® Color BioMérieux, France) and determined if they were pure colonies. Identification of bacteria species was performed using GP and GN cards inVitek 2® Compact(BioMérieux, France). A total of 256/1003 submitted urine samples presented bacterial growth, from which 172 isolates were included in this study. The sample’s population included 111 dogs (n=45 males and n=66 females) and 61 cats (n=35 males and n=26 females). The most frequent isolated bacteria wasEscherichia coli (44,7%), followed by Proteus mirabilis (13,4%). All Escherichia coli isolates presented red to burgundy colonies, a colony diameter between 2 to 6 mm, and regular or irregular outlines. Similarly, 100% of Proteus mirabilis isolates were dark yellow colonies with a diffuse pigment and the same size and shape as Escherichia coli. White and pink pale colonies where Staphylococcus species exclusively and S. pseudintermedius was the most frequent (8,2 %). Cian to blue colonies were mostly Enterococcusspp. (8,2%) and Streptococcus spp. (4,6%). Beige to brown colonies were Pseudomonas aeruginosa (2,9%) and Citrobacter spp. (1,2%).Klebsiella spp.,Serratia spp. and Enterobacter spp were green colonies. All Gram-positive isolates were 1 to 2 mm diameter long and had a regular outline, meanwhile, Gram-negative rods presented variable patterns. This results showed that theprevalence of E coli and P. mirabilis as uropathogenic agents follows the same trends in Europe as previously described in other studies. Both agents presented a particular color pattern in CPS Elite Agar to identify them without needing complementary tests. No other bacteria genus could be correlated strongly to a specific color pattern, and similar results have been observed instudies using human’s samples. Chromogenic media shows a great advantage for common urine bacteria isolation than traditional COS, McConkey, and CLEDAgar mediums in a routine context, especially when mixed fermentative Gram-negative agents grow simultaneously. In addition, CPS Elite Agar is versatile for Artificial Intelligent Reading Plates Systems. Routine veterinarian laboratories could use CPS Elite Agar for a rapid screening for bacteria identification,mainlyE coli and P.mirabilis, saving 6h to 10h of automatized identification.

Keywords: cats, CPS elite agar, dogs, urine pathogens

Procedia PDF Downloads 102

Authors: Ankur Chaudhuri, Sibani Sen Chakraborty

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In human, glutaminyl cyclase activity is highly abundant in neuronal and secretory tissues and is preferentially restricted to hypothalamus and pituitary. The N-terminal modification of β-amyloids (Aβs) peptides by the generation of a pyro-glutamyl (pGlu) modified Aβs (pE-Aβs) is an important process in the initiation of the formation of neurotoxic plaques in Alzheimer’s disease (AD). This process is catalyzed by glutaminyl cyclase (QC). The expression of QC is characteristically up-regulated in the early stage of AD, and the hallmark of the inhibition of QC is the prevention of the formation of pE-Aβs and plaques. A computer-aided drug design (CADD) process was employed to give an idea for the designing of potentially active compounds to understand the inhibitory potency against human glutaminyl cyclase (QC). This work elaborates the ligand-based and structure-based pharmacophore exploration of glutaminyl cyclase (QC) by using the known inhibitors. Three dimensional (3D) quantitative structure-activity relationship (QSAR) methods were applied to 154 compounds with known IC50 values. All the inhibitors were divided into two sets, training-set, and test-sets. Generally, training-set was used to build the quantitative pharmacophore model based on the principle of structural diversity, whereas the test-set was employed to evaluate the predictive ability of the pharmacophore hypotheses. A chemical feature-based pharmacophore model was generated from the known 92 training-set compounds by HypoGen module implemented in Discovery Studio 2017 R2 software package. The best hypothesis was selected (Hypo1) based upon the highest correlation coefficient (0.8906), lowest total cost (463.72), and the lowest root mean square deviation (2.24Å) values. The highest correlation coefficient value indicates greater predictive activity of the hypothesis, whereas the lower root mean square deviation signifies a small deviation of experimental activity from the predicted one. The best pharmacophore model (Hypo1) of the candidate inhibitors predicted comprised four features: two hydrogen bond acceptor, one hydrogen bond donor, and one hydrophobic feature. The Hypo1 was validated by several parameters such as test set activity prediction, cost analysis, Fischer's randomization test, leave-one-out method, and heat map of ligand profiler. The predicted features were then used for virtual screening of potential compounds from NCI, ASINEX, Maybridge and Chembridge databases. More than seven million compounds were used for this purpose. The hit compounds were filtered by drug-likeness and pharmacokinetics properties. The selective hits were docked to the high-resolution three-dimensional structure of the target protein glutaminyl cyclase (PDB ID: 2AFU/2AFW) to filter these hits further. To validate the molecular docking results, the most active compound from the dataset was selected as a reference molecule. From the density functional theory (DFT) study, ten molecules were selected based on their highest HOMO (highest occupied molecular orbitals) energy and the lowest bandgap values. Molecular dynamics simulations with explicit solvation systems of the final ten hit compounds revealed that a large number of non-covalent interactions were formed with the binding site of the human glutaminyl cyclase. It was suggested that the hit compounds reported in this study could help in future designing of potent inhibitors as leads against human glutaminyl cyclase.

Keywords: glutaminyl cyclase, hit lead, pharmacophore model, simulation

Procedia PDF Downloads 130

Authors: Andreea Campu, Ilinica Muresan, Simona Cainap, Simion Astilean, Monica Focsan

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Acute myocardial infarction (AMI) is the most severe cardiovascular disease, which has threatened human lives for decades, thus a continuous interest is directed towards the detection of cardiac biomarkers such as cardiac troponin I (cTnI) in order to predict risk and, implicitly, fulfill the early diagnosis requirements in AMI settings. Microfluidics is a major technology involved in the development of efficient sensing devices with real-time fast responses and on-site applicability. Microfluidic devices have gathered a lot of attention recently due to their advantageous features such as high sensitivity and specificity, miniaturization and portability, ease-of-use, low-cost, facile fabrication, and reduced sample manipulation. The integration of gold nanoparticles into the structure of microfluidic sensors has led to the development of highly effective detection systems, considering the unique properties of the metallic nanostructures, specifically the Localized Surface Plasmon Resonance (LSPR), which makes them highly sensitive to their microenvironment. In this scientific context, herein, we propose the implementation of a novel detection device, which successfully combines the efficiency of gold bipyramids (AuBPs) as signal transducers and thermal generators with the sample-driven advantages of the microfluidic channels into a miniaturized, portable, low-cost, specific, and sensitive test for the dual LSPR-thermographic cTnI detection. Specifically, AuBPs with longitudinal LSPR response at 830 nm were chemically synthesized using the seed-mediated growth approach and characterized in terms of optical and morphological properties. Further, the colloidal AuBPs were deposited onto pre-treated silanized glass substrates thus, a uniform nanoparticle coverage of the substrate was obtained and confirmed by extinction measurements showing a 43 nm blue-shift of the LSPR response as a consequence of the refractive index change. The as-obtained plasmonic substrate was then integrated into a microfluidic “Y”-shaped polydimethylsiloxane (PDMS) channel, fabricated using a Laser Cutter system. Both plasmonic and microfluidic elements were plasma treated in order to achieve a permanent bond. The as-developed microfluidic plasmonic chip was further coupled to an automated syringe pump system. The proposed biosensing protocol implicates the successive injection inside the microfluidic channel as follows: p-aminothiophenol and glutaraldehyde, to achieve a covalent bond between the metallic surface and cTnI antibody, anti-cTnI, as a recognition element, and target cTnI biomarker. The successful functionalization and capture of cTnI was monitored by LSPR detection thus, after each step, a red-shift of the optical response was recorded. Furthermore, as an innovative detection technique, thermal determinations were made after each injection by exposing the microfluidic plasmonic chip to 785 nm laser excitation, considering that the AuBPs exhibit high light-to-heat conversion performances. By the analysis of the thermographic images, thermal curves were obtained, showing a decrease in the thermal efficiency after the anti-cTnI-cTnI reaction was realized. Thus, we developed a microfluidic plasmonic chip able to operate as both LSPR and thermal sensor for the detection of the cardiac troponin I biomarker, leading thus to the progress of diagnostic devices.

Keywords: gold nanobipyramids, microfluidic device, localized surface plasmon resonance detection, thermographic detection

Procedia PDF Downloads 128

Authors: Sajeli A. Begum, Ameer Basha, Kirti Hira, Rukaiyya Khan

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Cyclic dipeptides are simple diketopiperazine derivatives being investigated by several scientists for their biological effects which include anticancer, antimicrobial, haematological, anticonvulsant, immunomodulatory effect, etc. They are potentially active microbial metabolites having been synthesized too, for developing into drug candidates. Cultures of Pseudomonas species have earlier been reported to produce cyclic dipeptides, helping in quorum sensing signals and bacterial–host colonization phenomena during infections, causing cell anti-proliferation and immunosuppression. Fluorescing Pseudomonas species have been identified to secrete lipid derivatives, peptides, pyrroles, phenazines, indoles, aminoacids, pterines, pseudomonic acids and some antibiotics. In the present work, results of investigation on the cyclic dipeptide metabolites secreted by the culture broth of Pseudomonas species as potent pro-inflammatory cytokine inhibitors are discussed. The bacterial strain was isolated from the rhizospheric soil of groundnut crop and identified as Pseudomonas aeruginosa by 16S rDNA sequence (GenBank Accession No. KT625586). Culture broth of this strain was prepared by inoculating into King’s B broth and incubating at 30 ºC for 7 days. The ethyl acetate extract of culture broth was prepared and lyophilized to get a dry residue (EEPA). Lipopolysaccharide (LPS)-induced ELISA assay proved the inhibition of tumor necrosis factor-alpha (TNF-α) secretion in culture supernatant of RAW 264.7 cells by EEPA (IC50 38.8 μg/mL). The effect of oral administration of EEPA on plasma TNF-α level in rats was tested by ELISA kit. The LPS mediated plasma TNF-α level was reduced to 45% with 125 mg/kg dose of EEPA. Isolation of the chemical constituents of EEPA through column chromatography yielded ten cyclic dipeptides, which were characterized using nuclear magnetic resonance and mass spectroscopic techniques. These cyclic dipeptides are biosynthesized in microorganisms by multifunctional assembly of non-ribosomal peptide synthases and cyclic dipeptide synthase. Cyclo (Gly-L-Pro) was found to be more potentially (IC50 value 4.5 μg/mL) inhibiting TNF-α production followed by cyclo (trans-4-hydroxy-L-Pro-L-Phe) (IC50 value 14.2 μg/mL) and the effect was equal to that of standard immunosuppressant drug, prednisolone. Further, the effect was analyzed by determining mRNA expression of TNF-α in LPS-stimulated RAW 264.7 macrophages using quantitative real-time reverse transcription polymerase chain reaction. EEPA and isolated cyclic dipeptides demonstrated diminution of TNF-α mRNA expression levels in a dose-dependent manner under the tested conditions. Also, they were found to control the expression of other pro-inflammatory cytokines like IL-1β and IL-6, when tested through their mRNA expression levels in LPS-stimulated RAW 264.7 macrophages under LPS-stimulated conditions. In addition, significant inhibition effect was found on Nitric oxide production. Further all the compounds exhibited weak toxicity to LPS-induced RAW 264.7 cells. Thus the outcome of the study disclosed the effectiveness of EEPA and the isolated cyclic dipeptides in down-regulating key cytokines involved in pathophysiology of autoimmune diseases.In another study led by the investigators, microbial cyclic dipeptides were found to exhibit excellent antimicrobial effect against Fusarium moniliforme which is an important causative agent of Sorghum grain mold disease. Thus, cyclic dipeptides are emerging small molecular drug candidates for various autoimmune diseases.

Keywords: cyclic dipeptides, cytokines, Fusarium moniliforme, Pseudomonas, TNF-alpha

Procedia PDF Downloads 210

Authors: Magdy I. A. Alshourbagi

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Background: The National Institute for Deafness and Communication Disorders defines idiopathic sudden sensorineural hearing loss as the idiopathic loss of hearing of at least 30 dB across 3 contiguous frequencies occurring within 3 days.The most common clinical presentation involves an individual experiencing a sudden unilateral hearing loss, tinnitus, a sensation of aural fullness and vertigo. The etiologies and pathologies of ISSNHL remain unclear. Several pathophysiological mechanisms have been described including: vascular occlusion, viral infections, labyrinthine membrane breaks, immune associated disease, abnormal cochlear stress response, trauma, abnormal tissue growth, toxins, ototoxic drugs and cochlear membrane damage. The rationale for the use of hyperbaric oxygen to treat ISSHL is supported by an understanding of the high metabolism and paucity of vascularity to the cochlea. The cochlea and the structures within it require a high oxygen supply. The direct vascular supply, particularly to the organ of Corti, is minimal. Tissue oxygenation to the structures within the cochlea occurs via oxygen diffusion from cochlear capillary networks into the perilymph and the cortilymph. . The perilymph is the primary oxygen source for these intracochlear structures. Unfortunately, perilymph oxygen tension is decreased significantly in patients with ISSHL. To achieve a consistent rise of perilymph oxygen content, the arterial-perilymphatic oxygen concentration difference must be extremely high. This can be restored with hyperbaric oxygen therapy. Subject and Methods: A 37 year old man was presented at the clinic with a five days history of muffled hearing and tinnitus of the right ear. Symptoms were sudden onset, with no associated pain, dizziness or otorrhea and no past history of hearing problems or medical illness. Family history was negative. Physical examination was normal. Otologic examination revealed normal tympanic membranes bilaterally, with no evidence of cerumen or middle ear effusion. Tuning fork examination showed positive Rinne test bilaterally but with lateralization of Weber test to the left side, indicating right ear sensorineural hearing loss. Audiometric analysis confirmed sensorineural hearing loss across all frequencies of about 70- dB in the right ear. Routine lab work were all within normal limits. Clinical diagnosis of idiopathic sudden sensorineural hearing loss of the right ear was made and the patient began a medical treatment (corticosteroid, vasodilator and HBO therapy). The recommended treatment profile consists of 100% O2 at 2.5 atmospheres absolute for 60 minutes daily (six days per week) for 40 treatments .The optimal number of HBOT treatments will vary, depending on the severity and duration of symptomatology and the response to treatment. Results: As HBOT is not yet a standard for idiopathic sudden sensorineural hearing loss, it was introduced to this patient as an adjuvant therapy. The HBOT program was scheduled for 40 sessions, we used a 12-seat multi place chamber for the HBOT, which was started at day seven after the hearing loss onset. After the tenth session of HBOT, improvement of both hearing (by audiogram) and tinnitus was obtained in the affected ear (right). Conclusions: In conclusion, HBOT may be used for idiopathic sudden sensorineural hearing loss as an adjuvant therapy. It may promote oxygenation to the inner ear apparatus and revive hearing ability. Patients who fail to respond to oral and intratympanic steroids may benefit from this treatment. Further investigation is warranted, including animal studies to understand the molecular and histopathological aspects of HBOT and randomized control clinical studies.

Keywords: idiopathic sudden sensorineural hearing loss (issnhl), hyperbaric oxygen therapy (hbot), the decibel (db), oxygen (o2)

Procedia PDF Downloads 431

Authors: Federica Verna, Alessandra Pautasso, Maria Caramelli, Cristiana Maurella, Walter Mignone, Cristina Casalone

Abstract:

Mosquito-Borne Diseases (MBDs) are dangerously increasing in prevalence, geographical distribution and severity, representing an emerging threat for both humans and animals. Interaction between multiple disciplines is needed for an effective early warning, surveillance and control of MBDs, according to the One Health concept. This work reports the integrated surveillance system enforced by IZSPLV in Piedmont, Liguria and Valle d’Aosta regions (Northwestern Italy) in order to control MDBs spread. Veterinary services and local human health authority are involved in an information network, to connect the surveillance of human clinical cases with entomological surveillance and veterinary monitoring in order to implement control measures in case of outbreak. A systematic entomological surveillance is carried out during the vector season using mosquitoes traps located in sites selected according to risk factors. Collected mosquitoes are counted, identified to species level by morphological standard classification keys and pooled by collection site, date and species with a maximum of 100 individuals. Pools are analyzed, after RNA extraction, by Real Time RT-PCR distinctive for West Nile Virus (WNV) Lineage 1 and Lineage 2, Real Time RT-PCR USUTU virus (USUV) and a traditional flavivirus End-point RT-PCR. Positive pools are sequenced and the related sequences employed to perform a basic local alignment search tool (BLAST) in the GenBank library. Positive samples are sent to the National Reference Centre for Animal Exotic Diseases (CESME, Teramo) for confirmation. With particular reference to WNV, after the confirmation, as provided by national legislation, control measures involving both local veterinary and human health services are activated: equine sera are randomly sampled within a 4 km radius from the positive collection sites and tested with ELISA kit and WNV NAT screening of blood donors is introduced. This surveillance network allowed to detect since 2011 USUV circulation in this area of Italy. WNV was detected in Piedmont and Liguria for the first time in 2014 in mosquitoes. During the 2015 vector season, we observed the expansion of its activity in Piedmont. The virus was detected in almost all Provinces both in mosquitoes (6 pools) and animals (19 equine sera, 4 birds). No blood bag tested resulted infected. The first neuroinvasive human case occurred too. Competent authorities should be aware of a potentially increased risk of MBDs activity during the 2016 vector season. This work shows that this surveillance network allowed to early detect the presence of MBDs in humans and animals, and provided useful information to public authorities, in order to apply control measures. Finally, an additional value of our diagnostic protocol is the ability to detect all viruses belonging to the Flaviviridae family, considering the emergence caused by other Flaviviruses in humans such as the recent Zika virus infection in South America. Italy has climatic and environmental features conducive to Zika virus transmission, the competent vector and many travellers from Brazil reported every year.

Keywords: integrated surveillance, mosquito borne disease, West Nile virus, Zika virus

Procedia PDF Downloads 361

Authors: A. Chandra, M. Arthur, L. Mize, A. Pomeroy-Stevens

Abstract:

Background: Lower and middle-income countries (LMICs) in Asia face rapid urbanization resulting in both economic opportunities (the urban advantage) and emerging health challenges. Urban health risks are magnified in informal settlements and include infectious disease outbreaks, inadequate access to health services, and poor air quality. Over the coming years, urban spaces in Asia will face accelerating public health risks related to migration, climate change, and environmental health. These challenges are complex and require multi-sectoral and multi-stakeholder solutions. The Building Health Cities (BHC) program is funded by the United States Agency for International Development (USAID) to work with smart city initiatives in the Asia region. BHC approaches urban health challenges by addressing policies, planning, and services through a health equity lens, with a particular focus on informal settlements and migrant communities. The program works to develop data-driven decision-making, build inclusivity through stakeholder engagement, and facilitate the uptake of appropriate technology. Methodology: The BHC program has partnered with the smart city initiatives of Indore in India, Makassar in Indonesia, and Da Nang in Vietnam. Implementing partners support municipalities to improve health delivery and equity using two key approaches: political economy analysis and participatory systems mapping. Political economy analyses evaluate barriers to collective action, including corruption, security, accountability, and incentives. Systems mapping evaluates community health challenges using a cross-sectoral approach, analyzing the impact of economic, environmental, transport, security, health system, and built environment factors. The mapping exercise draws on the experience and expertise of a diverse cohort of stakeholders, including government officials, municipal service providers, and civil society organizations. Results: Systems mapping and political economy analyses identified significant barriers for health care in migrant populations. In Makassar, migrants are unable to obtain the necessary card that entitles them to subsidized health services. This finding is being used to engage with municipal governments to mitigate the barriers that limit migrant enrollment in the public social health insurance scheme. In Indore, the project identified poor drainage of storm and wastewater in migrant settlements as a cause of poor health. Unsafe and inadequate infrastructure placed residents of these settlements at risk for both waterborne diseases and injuries. The program also evaluated the capacity of urban primary health centers serving migrant communities, identifying challenges related to their hours of service and shortages of health workers. In Da Nang, the systems mapping process has only recently begun, with the formal partnership launched in December 2019. Conclusion: This paper explores lessons learned from BHC’s systems mapping, political economy analyses, and stakeholder engagement approaches. The paper shares progress related to the health of migrants in informal settlements. Case studies feature barriers identified and mitigating steps, including governance actions, taken by local stakeholders in partner cities. The paper includes an update on ongoing progress from Indore and Makassar and experience from the first six months of program implementation from Da Nang.

Keywords: informal settlements, migration, stakeholder engagement mapping, urban health

Procedia PDF Downloads 119

Authors: Pejman Salimi, Sebastiano Tieuli, Somayeh Taghavi, Michela Signoretto, Remo Proietti Zaccaria

Abstract:

Increasing the growth of industrial waste due to the large quantities of production leads to numerous environmental and economic challenges, such as climate change, soil and water contamination, human disease, etc. Energy recovery of waste can be applied to produce heat or electricity. This strategy allows for the reduction of energy produced using coal or other fuels and directly reduces greenhouse gas emissions. Among different factories, leather manufacturing plays a very important role in the whole world from the socio-economic point of view. The leather industry plays a very important role in our society from a socio-economic point of view. Even though the leather industry uses a by-product from the meat industry as raw material, it is considered as an activity demanding integrated prevention and control of pollution. Along the entire process from raw skins/hides to finished leather, a huge amount of solid and water waste is generated. Solid wastes include fleshings, raw trimmings, shavings, buffing dust, etc. One of the most abundant solid wastes generated throughout leather tanning is shaving waste. Leather shaving is a mechanical process that aims at reducing the tanned skin to a specific thickness before tanning and finishing. This product consists mainly of collagen and tanning agent. At present, most of the world's leather processing is chrome-tanned based. Consequently, large amounts of chromium-containing shaving wastes need to be treated. The major concern about the management of this kind of solid waste is ascribed to chrome content, which makes the conventional disposal methods, such as landfilling and incineration, not practicable. Therefore, many efforts have been developed in recent decades to promote eco-friendly/alternative leather production and more effective waste management. Herein, shaving waste resulting from metal-free tanning technology is proposed as low-cost precursors for the preparation of carbon material as anodes for lithium-ion batteries (LIBs). In line with the philosophy of a reduced environmental impact, for preparing fully sustainable and environmentally friendly LIBs anodes, deionized water and carboxymethyl cellulose (CMC) have been used as alternatives to toxic/teratogen N-methyl-2- pyrrolidone (NMP) and to biologically hazardous Polyvinylidene fluoride (PVdF), respectively. Furthermore, going towards the reduced cost, we employed water solvent and fluoride-free bio-derived CMC binder (as an alternative to NMP and PVdF, respectively) together with LiFePO₄ (LFP) when a full cell was considered. These actions make closer to the 2030 goal of having green LIBs at 100 $ kW h⁻¹. Besides, the preparation of the water-based electrodes does not need a controlled environment and due to the higher vapour pressure of water in comparison with NMP, the water-based electrode drying is much faster. This aspect determines an important consequence, namely a reduced energy consumption for the electrode preparation. The electrode derived from leather waste demonstrated a discharge capacity of 735 mAh g⁻¹ after 1000 charge and discharge cycles at 0.5 A g⁻¹. This promising performance is ascribed to the synergistic effect of defects, interlayer spacing, heteroatoms-doped (N, O, and S), high specific surface area, and hierarchical micro/mesopore structure of the biochar. Interestingly, these features of activated biochars derived from the leather industry open the way for possible applications in other EESDs as well.

Keywords: biowaste, lithium-ion batteries, physical activation, waste management, leather industry

Procedia PDF Downloads 168

Authors: L. Malic, X. Zhang, D. Brassard, L. Clime, J. Daoud, C. Luebbert, V. Barrere, A. Boutin, S. Bidawid, N. Corneau, J. Farber, T. Veres

Abstract:

The incidence of infections caused by foodborne pathogens such as Listeria monocytogenes (L. monocytogenes) poses a great potential threat to public health and safety. These issues are further exacerbated by legal repercussions due to “zero tolerance” food safety standards adopted in developed countries. Unfortunately, a large number of related disease outbreaks are caused by pathogens present in extremely low counts currently undetectable by available techniques. The development of highly sensitive and rapid detection of foodborne pathogens is therefore crucial, and requires robust and efficient pre-analytical sample preparation. Immunomagnetic separation is a popular approach to sample preparation. Microfluidic chips combined with external magnets have emerged as viable high throughput methods. However, external magnets alone are not suitable for the capture of nanoparticles, as very strong magnetic fields are required. Devices that incorporate externally applied magnetic field and microstructures of a soft magnetic material have thus been used for local field amplification. Unfortunately, very complex and costly fabrication processes used for integration of soft magnetic materials in the reported proof-of-concept devices would prohibit their use as disposable tools for food and water safety or diagnostic applications. We present a sample preparation magnetic microfluidic device implemented in low-cost thermoplastic polymers using fabrication techniques suitable for mass-production. The developed magnetic capture chip (M-chip) was employed for rapid capture and release of L. monocytogenes conjugated to immunomagnetic nanoparticles (IMNs) in buffer and beef filtrate. The M-chip relies on a dense array of Nickel-coated high-aspect ratio pillars for capture with controlled magnetic field distribution and a microfluidic channel network for sample delivery, waste, wash and recovery. The developed Nickel-coating process and passivation allows generation of switchable local perturbations within the uniform magnetic field generated with a pair of permanent magnets placed at the opposite edges of the chip. This leads to strong and reversible trapping force, wherein high local magnetic field gradients allow efficient capture of IMNs conjugated to L. monocytogenes flowing through the microfluidic chamber. The experimental optimization of the M-chip was performed using commercially available magnetic microparticles and fabricated silica-coated iron-oxide nanoparticles. The fabricated nanoparticles were optimized to achieve the desired magnetic moment and surface functionalization was tailored to allow efficient capture antibody immobilization. The integration, validation and further optimization of the capture and release protocol is demonstrated using both, dead and live L. monocytogenes through fluorescence microscopy and plate- culture method. The capture efficiency of the chip was found to vary as function of listeria to nanoparticle concentration ratio. The maximum capture efficiency of 30% was obtained and the 24-hour plate-culture method allowed the detection of initial sample concentration of only 16 cfu/ml. The device was also very efficient in concentrating the sample from a 10 ml initial volume. Specifically, 280% concentration efficiency was achieved in 17 minutes only, demonstrating the suitability of the system for food safety applications. In addition, flexible design and low-cost fabrication process will allow rapid sample preparation for applications beyond food and water safety, including point-of-care diagnosis.

Keywords: array of pillars, bacteria isolation, immunomagnetic sample preparation, polymer microfluidic device

Procedia PDF Downloads 279

Authors: Tim Crocker-Buque, Sandra Mounier-Jack, Natasha Howard

Abstract:

Background: Due to both the increasing scale and speed of urbanisation, urban areas in low and middle-income countries (LMICs) host increasingly large populations of under-immunized children, with the additional associated risks of rapid disease transmission in high-density living environments. Multiple interdependent factors are associated with these coverage disparities in urban areas and most evidence comes from relatively few countries, e.g., predominantly India, Kenya, Nigeria, and some from Pakistan, Iran, and Brazil. This study aimed to identify, describe, and assess the main tools used to measure or improve coverage of immunisation services in poor urban areas. Methods: Authors used a qualitative review design, including academic and non-academic literature, to identify tools used to improve coverage of public health interventions in urban areas. Authors selected and extracted sources that provided good examples of specific tools, or categories of tools, used in a context relevant to urban immunization. Diagnostic (e.g., for data collection, analysis, and insight generation) and programme tools (e.g., for investigating or improving ongoing programmes) and interventions (e.g., multi-component or stand-alone with evidence) were selected for inclusion to provide a range of type and availability of relevant tools. These were then prioritised using a decision-analysis framework and a tool selection guide for programme managers developed. Results: Authors reviewed tools used in urban immunisation contexts and tools designed for (i) non-immunization and/or non-health interventions in urban areas, and (ii) immunisation in rural contexts that had relevance for urban areas (e.g., Reaching every District/Child/ Zone). Many approaches combined several tools and methods, which authors categorised as diagnostic, programme, and intervention. The most common diagnostic tools were cross-sectional surveys, key informant interviews, focus group discussions, secondary analysis of routine data, and geographical mapping of outcomes, resources, and services. Programme tools involved multiple stages of data collection, analysis, insight generation, and intervention planning and included guidance documents from WHO (World Health Organisation), UNICEF (United Nations Children's Fund), USAID (United States Agency for International Development), and governments, and articles reporting on diagnostics, interventions, and/or evaluations to improve urban immunisation. Interventions involved service improvement, education, reminder/recall, incentives, outreach, mass-media, or were multi-component. The main gaps in existing tools were an assessment of macro/policy-level factors, exploration of effective immunization communication channels, and measuring in/out-migration. The proposed framework uses a problem tree approach to suggest tools to address five common challenges (i.e. identifying populations, understanding communities, issues with service access and use, improving services, improving coverage) based on context and available data. Conclusion: This study identified many tools relevant to evaluating urban LMIC immunisation programmes, including significant crossover between tools. This was encouraging in terms of supporting the identification of common areas, but problematic as data volumes, instructions, and activities could overwhelm managers and tools are not always suitably applied to suitable contexts. Further research is needed on how best to combine tools and methods to suit local contexts. Authors’ initial framework can be tested and developed further.

Keywords: health equity, immunisation, low and middle-income countries, poverty, urban health

Procedia PDF Downloads 139

Authors: Jolene M. Helena, Annie M. Joubert, Peace Mabeta, Magdalena Coetzee, Roy Lakier, Anne E. Mercier

Abstract:

Targeting the distant tumour and its microenvironment whilst preserving bone density is important in improving the outcomes of patients with bone metastases. 2-Ethyl-3-O-sulphamoyl-estra1,3,5(10)16-tetraene (ESE-16) is an in-silico-designed 2- methoxyestradiol analogue which aimed at enhancing the parent compound’s cytotoxicity and providing a more favourable pharmacokinetic profile. In this study, the potential radiosensitization effects of ESE-16 were investigated in an in vitro bone metastasis model consisting of murine pre-osteoblastic (MC3T3-E1) and pre-osteoclastic (RAW 264.7) bone cells, metastatic prostate (DU 145) and breast (MDA-MB-231) cancer cells, as well as human umbilical vein endothelial cells (HUVECs). Cytotoxicity studies were conducted on all cell lines via spectrophotometric quantification of 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide. The experimental set-up consisted of flow cytometric analysis of cell cycle progression and apoptosis detection (Annexin V-fluorescein isothiocyanate) to determine the lowest ESE-16 and radiation doses to induce apoptosis and significantly reduce cell viability. Subsequent experiments entailed a 24-hour low-dose ESE-16-exposure followed by a single dose of radiation. Termination proceeded 2, 24 or 48 hours thereafter. The effect of the combination treatment was investigated on osteoclasts via tartrate-resistant acid phosphatase (TRAP) activity- and actin ring formation assays. Tumour cell experiments included investigation of mitotic indices via haematoxylin and eosin staining; pro-apoptotic signalling via spectrophotometric quantification of caspase 3; deoxyribonucleic acid (DNA) damage via micronuclei analysis and histone H2A.X phosphorylation (γ-H2A.X); and Western blot analyses of bone morphogenetic protein-7 and matrix metalloproteinase-9. HUVEC experiments included flow cytometric quantification of cell cycle progression and free radical production; fluorescent examination of cytoskeletal morphology; invasion and migration studies on an xCELLigence platform; and Western blot analyses of hypoxia-inducible factor 1-alpha and vascular endothelial growth factor receptor 1 and 2. Tumour cells yielded half-maximal growth inhibitory concentration (GI50) values in the nanomolar range. ESE-16 concentrations of 235 nM (DU 145) and 176 nM (MDA-MB-231) and a radiation dose of 4 Gy were found to be significant in cell cycle and apoptosis experiments. Bone and endothelial cells were exposed to the same doses as DU 145 cells. Cytotoxicity studies on bone cells reported that RAW 264.7 cells were more sensitive to the combination treatment than MC3T3-E1 cells. Mature osteoclasts were more sensitive than pre-osteoclasts with respect to TRAP activity. However, actin ring morphology was retained. The mitotic arrest was evident in tumour and endothelial cells in the mitotic index and cell cycle experiments. Increased caspase 3 activity and superoxide production indicated pro-apoptotic signalling in tumour and endothelial cells. Increased micronuclei numbers and γ-H2A.X foci indicated increased DNA damage in tumour cells. Compromised actin and tubulin morphologies and decreased invasion and migration were observed in endothelial cells. Western blot analyses revealed reduced metastatic and angiogenic signalling. ESE-16-induced radiosensitization inhibits metastatic signalling and tumour cell survival whilst preferentially preserving bone cells. This low-dose combination treatment strategy may promote the quality of life of patients with metastatic bone disease. Future studies will include 3-dimensional in-vitro and murine in-vivo models.

Keywords: angiogenesis, apoptosis, bone metastasis, cancer, cell migration, cytoskeleton, DNA damage, ESE-16, radiosensitization.

Procedia PDF Downloads 160

Authors: Z. S. Haidar

Abstract:

Millions of teeth are removed annually, and dental extraction is one of the most commonly performed surgical procedures globally. Whether due to caries, periodontal disease, or trauma, exodontia and the ensuing wound healing and bone remodeling processes of the resultant socket (hole in the jaw bone) usually result in serious deformities of the residual alveolar osseous ridge and surrounding soft tissues (reduced height/width). Such voluminous changes render the placement of a proper conventional bridge, denture, or even an implant-supported prosthesis extremely challenging. Further, most extractions continue to be performed with no regard for preventing the onset of alveolar osteitis (also known as dry socket, a painful and difficult-to-treat/-manage condition post-exodontia). Hence, such serious resorptive morphological changes often result in significant facial deformities and a negative impact on the overall Quality of Life (QoL) of patients (and oral health-related QoL); alarming, particularly for the geriatric with compromised healing and in light of the thriving longevity statistics. Despite advances in tissue/wound grafting, serious limitations continue to exist, including efficacy and clinical outcome predictability, cost, treatment time, expertise, and risk of immune reactions. For cases of dry socket, specifically, the commercially available and often-prescribed home remedies are highly-lacking. Indeed, most are not recommended for use anymore. Alveogyl is a fine example. Hence, there is a great market demand and need for alternative solutions. Herein, SockGEL/PLUG (patent pending), an innovative, all-natural, drug-free, and injectable thermo-responsive hydrogel, was designed, formulated, characterized, and evaluated as an osteogenic, angiogenic, anti-microbial, and pain-soothing suture-free intra-alveolar dressing, safe and efficacious for use in fresh extraction sockets, immediately post-exodontia. It is composed of FDA-approved, biocompatible and biodegradable polymers, self-assembled electro-statically to formulate a scaffolding matrix to (1) prevent the on-set of alveolar osteitis via securing the fibrin-clot in situ and protecting/sealing the socket from contamination/infection; and (2) endogenously promote/accelerate wound healing and bone remodeling to preserve the volume of the alveolus. The intrinsic properties of the SockGEL/PLUG hydrogel were evaluated physical-chemical-mechanically for safety (cell viability), viscosity, rheology, bio-distribution, and essentially, capacity to induce wound healing and osteogenesis (small defect, in vivo) without any signaling cues from exogenous cells, growth factors or drugs. The proposed animal model of cranial critical-sized and non-vascularized bone defects shall provide new and critical insights into the role and mechanism of the employed natural bio-polymer blend and gel product in endogenous reparative regeneration of soft tissues and bone morphogenesis. Alongside, the fine-tuning of our modified formulation method will further tackle appropriateness, reproducibility, scalability, ease, and speed in producing stable, biodegradable, and sterilizable thermo-sensitive matrices (3-dimensional interpenetrating yet porous polymeric network) suitable for the intra-socket application. Findings are anticipated to provide sufficient evidence to translate into pilot clinical trials and validate the innovation before engaging the market for feasibility, acceptance, and cost-effectiveness studies.

Keywords: hydrogel, nanotechnology, bioengineering, bone regeneration, nanogel, drug delivery

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Authors: David J. Foran, Nhan Do, Samuel Ajjarapu, Wenjin Chen, Tahsin Kurc, Joel H. Saltz

Abstract:

The large-scale data and computational requirements of investigators throughout the clinical and research communities demand an informatics infrastructure that supports both existing and new investigative and translational projects in a robust, secure environment. In some subspecialties of medicine and research, the capacity to generate data has outpaced the methods and technology used to aggregate, organize, access, and reliably retrieve this information. Leading health care centers now recognize the utility of establishing an enterprise-wide, clinical data warehouse. The primary benefits that can be realized through such efforts include cost savings, efficient tracking of outcomes, advanced clinical decision support, improved prognostic accuracy, and more reliable clinical trials matching. The overarching objective of the work presented here is the development and implementation of a flexible Intelligent Retrieval and Interrogation System (IRIS) that exploits the combined use of computational imaging, genomics, and data-mining capabilities to facilitate clinical assessments and translational research in oncology. The proposed System includes a multi-modal, Clinical & Research Data Warehouse (CRDW) that is tightly integrated with a suite of computational and machine-learning tools to provide insight into the underlying tumor characteristics that are not be apparent by human inspection alone. A key distinguishing feature of the System is a configurable Extract, Transform and Load (ETL) interface that enables it to adapt to different clinical and research data environments. This project is motivated by the growing emphasis on establishing Learning Health Systems in which cyclical hypothesis generation and evidence evaluation become integral to improving the quality of patient care. To facilitate iterative prototyping and optimization of the algorithms and workflows for the System, the team has already implemented a fully functional Warehouse that can reliably aggregate information originating from multiple data sources including EHR’s, Clinical Trial Management Systems, Tumor Registries, Biospecimen Repositories, Radiology PAC systems, Digital Pathology archives, Unstructured Clinical Documents, and Next Generation Sequencing services. The System enables physicians to systematically mine and review the molecular, genomic, image-based, and correlated clinical information about patient tumors individually or as part of large cohorts to identify patterns that may influence treatment decisions and outcomes. The CRDW core system has facilitated peer-reviewed publications and funded projects, including an NIH-sponsored collaboration to enhance the cancer registries in Georgia, Kentucky, New Jersey, and New York, with machine-learning based classifications and quantitative pathomics, feature sets. The CRDW has also resulted in a collaboration with the Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC) at the U.S. Department of Veterans Affairs to develop algorithms and workflows to automate the analysis of lung adenocarcinoma. Those studies showed that combining computational nuclear signatures with traditional WHO criteria through the use of deep convolutional neural networks (CNNs) led to improved discrimination among tumor growth patterns. The team has also leveraged the Warehouse to support studies to investigate the potential of utilizing a combination of genomic and computational imaging signatures to characterize prostate cancer. The results of those studies show that integrating image biomarkers with genomic pathway scores is more strongly correlated with disease recurrence than using standard clinical markers.

Keywords: clinical data warehouse, decision support, data-mining, intelligent databases, machine-learning.

Procedia PDF Downloads 126

Authors: Ziyad S. Haidar

Abstract:

Millions of teeth are removed annually, and dental extraction is one of the most commonly performed surgical procedures globally. Whether due to caries, periodontal disease or trauma, exodontia and the ensuing wound healing and bone remodeling processes of the resultant socket (hole in the jaw bone) usually result in serious deformities of the residual alveolar osseous ridge and surrounding soft tissues (reduced height/width). Such voluminous changes render the placement of a proper conventional bridge, denture or even an implant-supported prosthesis extremely challenging. Further, most extractions continue to be performed with no regard for preventing the onset of alveolar osteitis (also known as dry socket, a painful and difficult-to-treat/-manage condition post-exodontia). Hence, such serious resorptive morphological changes often result in significant facial deformities and a negative impact on the overall Quality of Life (QoL) of patients (and oral health-related QoL), alarming, particularly for the geriatric with compromised healing and in light of the thriving longevity statistics. Opportunity: Despite advances in tissue/wound grafting, serious limitations continue to exist, including efficacy and clinical outcome predictability, cost, treatment time, expertise and risk of immune reactions. For cases of dry sockets, specifically, the commercially-available and often-prescribed home remedies are highly lacking. Indeed, most are not recommended for use anymore. Alveogyl is a fine example. Hence, there is a great market demand and need for alternative solutions. Solution: Herein, SockGEL/PLUG (patent pending), an all-natural, drug-free and injectable stimuli-responsive hydrogel, was designed, formulated, characterized and evaluated as an osteogenic, angiogenic, anti-microbial and pain-soothing suture-free intra-alveolar dressing, safe and efficacious for use in several oro-dental and cranio-maxillo-facial interventional applications; for example: in fresh dental extraction sockets, immediately post-exodontia. It is composed of FDA-approved, biocompatible and biodegradable polymers, self-assembled electro-statically to formulate a scaffolding matrix to (a) prevent the onset of alveolar osteitis via securing the fibrin-clot in situ and protecting/sealing the socket from contamination/infection; and (b) endogenously promote/accelerate wound healing and bone remodeling to preserve the volume of the alveolus. Findings: The intrinsic properties of the SockGEL/PLUG hydrogel were evaluated physico-chemico-mechanically for safety (cell viability), viscosity, rheology, bio-distribution and essentially, capacity to induce wound healing and osteogenesis (small defect, in vivo) without any signaling cues from exogenous cells, growth factors or drugs. The performed animal model of cranial critical-sized and non-vascularized bone defects shall provide vitally critical insights into the role and mechanism of the employed natural bio-polymer blend and gel product in endogenous reparative regeneration of soft tissues and bone morphogenesis. Alongside, the fine-tuning of our modified formulation method will further tackle appropriateness, reproducibility, scalability, ease and speed in producing stable, biodegradable and sterilizable stimuli (thermo-sensitive and photo-responsive) matrices (3-dimensional interpenetrating yet porous polymeric network) suitable for an intra-socket application, and beyond. Conclusions and Perspective: Findings are anticipated to provide sufficient evidence to translate into pilot clinical trials and validate the bionanomaterial before engaging the market for feasibility, acceptance and cost-effectiveness studies. The SockGEL/PLUG platform is patent pending: SockGEL is a bio-inspired drug-free hydrogel; SockPLUG is a drug-loaded hydrogel designed for complex indications.

Keywords: hydrogel, injectable, dentistry, craniomaxillofacial complex, bioinspired, nanobiotechnology, biopolymer, sol-gel, stimuli-responsive, matrix, tissue engineering, regenerative medicine

Procedia PDF Downloads 69