Search results for: sickle disease

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

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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: Robert E. Kenney, Efrain Antunez, Samuel Nodal, Ameer Malik, Richard B. Aguilar

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Physician burnout has gained much attention during the COVID pandemic. After-hours workload, HCC coding, HEDIS metrics, and clinical documentation negatively impact career satisfaction. These and other influences have increased the rate of physicians leaving the workforce. In addition, roughly 1% of the entire physician workforce will be retiring earlier than expected based on pre-pandemic trends. The two Medical Specialties with the highest rates of burnout are Family Medicine and Primary Care. With a predicted shortage of primary care physicians looming, the need to address physician burnout is crucial. Commonly reported issues leading to clinician burnout are clerical documentation requirements, increased time working on Electronic Health Records (EHR) after hours, and a decrease in work-life balance. Clinicians experiencing burnout with physical and emotional exhaustion are at an increased likelihood of providing lower quality and less efficient patient care. This may include a lack of suitable clinical documentation, medication reconciliation, clinical assessment, and treatment plans. While the annual baseline turnover rates of physicians hover around 6-7%, the COVID pandemic profoundly disrupted the delivery of healthcare. A report found that 43% of physicians switched jobs during the initial two years of the COVID pandemic (2020 and 2021), tripling the expected average annual rate to 21.5 %/yr. During this same time, an average of 4% and 1.5% of physicians retired or left the workforce for a non-clinical career, respectively. The report notes that 35.2% made career changes for a better work-life balance and another 35% reported the reason as being unhappy with their administration’s response to the pandemic. A physician-led primary care-focused health organization, Cano Health (CH), based out of Florida, sought to preemptively address this problem by implementing several supportive measures. Working with >120 clinics and >280 PCPs from Miami to Tampa and Orlando, managing nearly 120,000 Medicare Advantage lives, CH implemented a number of changes to assist with the clinician’s workload. Supportive services such as after hour and home visits by APRNs, in-clinic care managers, and patient educators were implemented. In 2021, assistive Artificial Intelligence Software (AIS) was integrated into the EHR platform. This AIS converts free text within PDF files into a usable (copy-paste) format facilitating documentation. The software also systematically and chronologically organizes clinical data, including labs, medical records, consultations, diagnostic images, medications, etc., into an easy-to-use organ system or chronic disease state format. This reduced the excess time and documentation burden required to meet payor and CMS guidelines. A clinician Documentation Support team was employed to improve the billing/coding performance. The effects of these newly designed workflow interventions were measured via analysis of clinician turnover from CH’s hiring and termination reporting software. CH’s annualized average clinician turnover rate in 2020 and 2021 were 17.7% and 12.6%, respectively. This represents a 30% relative reduction in turnover rate compared to the reported national average of 21.5%. Retirement rates during both years were 0.1%, demonstrating a relative reduction of >95% compared to the national average (4%). This model successfully promoted the retention of clinicians in a Value-Based Care setting.

Keywords: clinician burnout, COVID-19, value-based care, burnout, clinician retirement

Procedia PDF Downloads 82

Authors: Kimberly Winnie Achieng Otieno

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The Nairobi Hospital plays a pivotal role in healthcare provision in East and Central Africa, yet it faces challenges in providing accessible dialysis care. This paper explores strategic interventions to enhance dialysis care, improve access and streamline health information management, with an aim of fostering an integrated and patient-centered healthcare system in our region. Challenges at The Nairobi Hospital The Nairobi Hospital currently grapples with insufficient dialysis machines which results in extended turn around times. This issue stems from both staffing bottle necks and infrastructural limitations given our growing demand for renal care services. Our Paper-based record keeping system and fragmented flow of information downstream hinders the hospital’s ability to manage health data effectively. There is also a need for investment in expanding The Nairobi Hospital dialysis facilities to far reaching communities. Setting up satellite clinics that are closer to people who live in areas far from the main hospital will ensure better access to underserved areas. Community Outreach and Education Implementing education programs on kidney health within local communities is vital for early detection and prevention. Collaborating with local leaders and organizations can establish a proactive approach to renal health hence reducing the demand for acute dialysis interventions. We can amplify this effort by expanding The Nairobi Hospital’s corporate social responsibility outreach program with weekend engagement activities such as walks, awareness classes and fund drives. Enhancing Efficiency in Dialysis Care Demand for dialysis services continues to rise due to an aging Kenyan population and the increasing prevalence of chronic kidney disease (CKD). Present at this years International Nursing Conference are a diverse group of caregivers from around the world who can share with us their process optimization strategies, patient engagement techniques and resource utilization efficiencies to catapult The Nairobi Hospital to the 21st century and beyond. Plans are underway to offer ongoing education opportunities to keep staff updated on best practices and emerging technologies in addition to utilizing a patient feedback mechanisms to identify areas for improvement and enhance satisfaction. Staff empowerment and suggestion boxes address The Nairobi Hospital’s organizational challenges. Current financial constraints may limit a leapfrog in technology integration such as the acquisition of new dialysis machines and an investment in predictive analytics to forecast patient needs and optimize resource allocation. Streamlining Health Information Management Fully embracing a shift to 100% Electronic Health Records (EHRs) is a transformative step toward efficient health information management. Shared information promotes a holistic understanding of patients’ medical history, minimizing redundancies and enhancing overall care quality. To manage the transition to community-based care and EHRs effectively, a phased implementation approach is recommended. Conclusion By strategically enhancing dialysis care access and streamlining health information management, The Nairobi Hospital can strengthen its position as a leading healthcare institution in both East and Central Africa. This comprehensive approach aligns with the hospital’s commitment to providing high-quality, accessible, and patient-centered care in an evolving landscape of healthcare delivery.

Keywords: Africa, urology, diaylsis, healthcare

Procedia PDF Downloads 58

Authors: Sitira Williams, Georgina Cherry, Andrea Wright, Kevin Wells, Taran Rai, Richard Brown, Travis Street, Alasdair Cook

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Social media sources (50) were identified, keywords defined by veterinarians and organised into 6 topics known to be indicative of feline pruritus: body areas, behaviors, symptoms, diagnosis, and treatments. These were augmented using academic literature, a cat owner survey, synonyms, and Google Trends. The content was collected using a social intelligence solution, with keywords tagged and filtered. Data were aggregated and de-duplicated. SL content matching body areas, behaviors and symptoms were reviewed manually, and posts were marked relevant if: posted by a pet owner, identifying an itchy cat and not duplicated. A sub-set of 493 posts published from 2009-2022 was used for reflexive thematic analysis in NVIVO (Burlington, MA) to identify themes. Five themes were identified: allergy, pruritus, additional behaviors, unusual or undesirable behaviors, diagnosis, and treatment. Most (258) posts reported the cat was excessively licking, itching, and scratching. The majority were indoor cats and were less playful and friendly when itchy. Half of these posts did not indicate a known cause of pruritus. Bald spots and scabs (123) were reported, often causing swelling and fur loss, and 56 reported bumps, lumps, and dry patches. Other impacts on the cat’s quality of life were ear mites, cat self-trauma and stress. Seven posts reported their cats’ symptoms caused them ongoing anxiety and depression. Cats with food allergies to poultry (often chicken and beef) causing bald spots featured in 23 posts. Veterinarians advised switching to a raw food diet and/or changing their bowls. Some cats got worse after switching, leaving owners’ needs unmet. Allergic reactions to flea bites causing excessive itching, red spots, scabs, and fur loss were reported in 13 posts. Some (3) posts indicated allergic reactions to medication. Cats with seasonal and skin allergies, causing sneezing, scratching, headshaking, watery eyes, and nasal discharge, were reported 17 times. Eighty-five posts identified additional behaviors. Of these, 13 reported their cat’s burst pimple or insect bite. Common behaviors were headshaking, rubbing, pawing at their ears, and aggressively chewing. In some cases, bites or pimples triggered previously unseen itchiness, making the cat irritable. Twenty-four reported their cat had anxiety: overgrooming, itching, losing fur, hiding, freaking out, breathing quickly, sleeplessness, hissing and vocalising. Most reported these cats as having itchy skin, fleas, and bumps. Cats were commonly diagnosed with an ear infection, ringworm, acne, or kidney disease. Acne was diagnosed in cats with an allergy flare-up or overgrooming. Ear infections were diagnosed in itchy cats with mites or other parasites. Of the treatments mentioned, steroids were most frequently used, then anti-parasitics, including flea treatments and oral medication (steroids, antibiotics). Forty-six posts reported distress following poor outcomes after medication or additional vet consultations. SL provides veterinarians with unique insights. Verbatim comments highlight the detrimental effects of pruritus on pets and owner quality of life. This study demonstrates the need for veterinarians to communicate management and treatment options more effectively to relieve owner frustrations. Data analysis could be scaled up using machine learning for topic modeling.

Keywords: content analysis, feline, itch, pruritus, social media, thematic analysis, veterinary dermatology

Procedia PDF Downloads 191

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

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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

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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 170

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

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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 280

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

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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

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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.

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Authors: Z. S. Haidar

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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

Procedia PDF Downloads 111

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

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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

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