Search results for: severe morbidity
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 2274

Search results for: severe morbidity

84 Lessons Learned from Implementation of Remote Pregnant and Newborn Care Service for Vulnerable Women and Children During COVID-19 and Political Crisis in Myanmar

Authors: Wint Wint Thu, Htet Ko Ko Win, Myat Mon San, Zaw Lin Tun, Nandar Than Aye, Khin Nyein Myat, Hayman Nyo Oo, Nay Aung Lin, Kusum Thapa, Kyaw Htet Aung

Abstract:

Background: In Myanmar, the intense political instability happened to start in Feb-2021, while the COVID-19 pandemic waves are also threatening the public health system, which subsequently led to severe health sector crisis, including difficulties in accessing maternal and newborn health care for vulnerable women and children. The Remote Pregnant and Newborn Care (RPNC) uses a telehealth approach United States Agency for International Development (USAID)-funded Essential Health Project. Implementation: The Remote Pregnant and Newborn Care (RPNC) service has adapted to the MNCH needs of vulnerable pregnant women and was implemented to mitigate the risk of limited access to essential quality MNH care in Yangon, Myanmar, under women, and the project trained 13 service providers on a telehealth care package for pregnancy and newborn developed Jhpiego to ensure understanding of evidence-based MNCH care practices. The phone numbers of the pregnant women were gathered through the preexisting and functioning community volunteers, who reach the most vulnerable pregnant women in the project's targeted area. A total of 212 pregnant women have been reached by service providers for RPNC during the implementation period. The trained service providers offer quality antenatal and postnatal care, including newborn care, via telephone calls. It includes 24/7 incoming calls and time-allotted outgoing calls to the pregnant women during antenatal and postnatal periods, including the newborn care. The required data were collected daily in time with the calls, and the quality of the medical services is made assured with the track of the calls, ensuring data privacy and patient confidentiality. Lessons learned: The key lessons are 1) cost-effectiveness: RPNC service could reduce out of pocket expenditure of pregnant women as it only costs 1.6 United States dollars (USD) per one telehealth call while it costs 8 to 10 USD per one time in-person care service at private service providers, including transportation cost, 2) network of care: telehealth call could not replace the in-person antenatal and postnatal care services, and integration of telehealth calls with in-person care by local healthcare providers with the support of the community is crucial for accessibility to essential MNH services by poor and vulnerable women, and 3) sharing information on health access points: most of the women seem to have financial barriers in accessing private health facilities while public health system collapse and telehealthcare could provide information on low-cost facilities and connect women to relevant health facilities. These key lessons are important for future efforts regarding the implementation of remote pregnancy and newborn care in Myanmar, especially during the political crisis and COVID-19 pandemic situation.

Keywords: telehealth, accessibility, maternal care, newborn care

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83 Modeling Taxane-Induced Peripheral Neuropathy Ex Vivo Using Patient-Derived Neurons

Authors: G. Cunningham, E. Cantor, X. Wu, F. Shen, G. Jiang, S. Philips, C. Bales, Y. Xiao, T. R. Cummins, J. C. Fehrenbacher, B. P. Schneider

Abstract:

Background: Taxane-induced peripheral neuropathy (TIPN) is the most devastating survivorship issue for patients receiving therapy. Dose reductions due to TIPN in the curative setting lead to inferior outcomes for African American patients, as prior research has shown that this group is more susceptible to developing severe neuropathy. The mechanistic underpinnings of TIPN, however, have not been entirely elucidated. While it would be appealing to use primary tissue to study the development of TIPN, procuring nerves from patients is not realistically feasible, as nerve biopsies are painful and may result in permanent damage. Therefore, our laboratory has investigated paclitaxel-induced neuronal morphological and molecular changes using an ex vivo model of human-induced pluripotent stem cell (iPSC)-derived neurons. Methods: iPSCs are undifferentiated and endlessly dividing cells that can be generated from a patient’s somatic cells, such as peripheral blood mononuclear cells (PBMCs). We successfully reprogrammed PBMCs into iPSCs using the Erythroid Progenitor Reprograming Kit (STEMCell Technologiesᵀᴹ); pluripotency was verified by flow cytometry analysis. iPSCs were then induced into neurons using a differentiation protocol that bypasses the neural progenitor stage and uses selected small-molecule modulators of key signaling pathways (SMAD, Notch, FGFR1 inhibition, and Wnt activation). Results: Flow cytometry analysis revealed expression of core pluripotency transcription factors Nanog, Oct3/4 and Sox2 in iPSCs overlaps with commercially purchased pluripotent cell line UCSD064i-20-2. Trilineage differentiation of iPSCs was confirmed with immunofluorescent imaging with germ-layer-specific markers; Sox17 and ExoA2 for ectoderm, Nestin, and Pax6 for mesoderm, and Ncam and Brachyury for endoderm. Sensory neuron markers, β-III tubulin, and Peripherin were applied to stain the cells for the maturity of iPSC-derived neurons. Patch-clamp electrophysiology and calcitonin gene-related peptide (CGRP) release data supported the functionality of the induced neurons and provided insight into the timing for which downstream assays could be performed (week 4 post-induction). We have also performed a cell viability assay and fluorescence-activated cell sorting (FACS) using four cell-surface markers (CD184, CD44, CD15, and CD24) to select a neuronal population. At least 70% of the cells were viable in the isolated neuron population. Conclusion: We have found that these iPSC-derived neurons recapitulate mature neuronal phenotypes and demonstrate functionality. Thus, this represents a patient-derived ex vivo neuronal model to investigate the molecular mechanisms of clinical TIPN.

Keywords: chemotherapy, iPSC-derived neurons, peripheral neuropathy, taxane, paclitaxel

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82 Immobilization of Superoxide Dismutase Enzyme on Layered Double Hydroxide Nanoparticles

Authors: Istvan Szilagyi, Marko Pavlovic, Paul Rouster

Abstract:

Antioxidant enzymes are the most efficient defense systems against reactive oxygen species, which cause severe damage in living organisms and industrial products. However, their supplementation is problematic due to their high sensitivity to the environmental conditions. Immobilization on carrier nanoparticles is a promising research direction towards the improvement of their functional and colloidal stability. In that way, their applications in biomedical treatments and manufacturing processes in the food, textile and cosmetic industry can be extended. The main goal of the present research was to prepare and formulate antioxidant bionanocomposites composed of superoxide dismutase (SOD) enzyme, anionic clay (layered double hydroxide, LDH) nanoparticle and heparin (HEP) polyelectrolyte. To characterize the structure and the colloidal stability of the obtained compounds in suspension and solid state, electrophoresis, dynamic light scattering, transmission electron microscopy, spectrophotometry, thermogravimetry, X-ray diffraction, infrared and fluorescence spectroscopy were used as experimental techniques. LDH-SOD composite was synthesized by enzyme immobilization on the clay particles via electrostatic and hydrophobic interactions, which resulted in a strong adsorption of the SOD on the LDH surface, i.e., no enzyme leakage was observed once the material was suspended in aqueous solutions. However, the LDH-SOD showed only limited resistance against salt-induced aggregation and large irregularly shaped clusters formed during short term interval even at lower ionic strengths. Since sufficiently high colloidal stability is a key requirement in most of the applications mentioned above, the nanocomposite was coated with HEP polyelectrolyte to develop highly stable suspensions of primary LDH-SOD-HEP particles. HEP is a natural anticoagulant with one of the highest negative line charge density among the known macromolecules. The experimental results indicated that it strongly adsorbed on the oppositely charged LDH-SOD surface leading to charge inversion and to the formation of negatively charged LDH-SOD-HEP. The obtained hybrid materials formed stable suspension even under extreme conditions, where classical colloid chemistry theories predict rapid aggregation of the particles and unstable suspensions. Such a stabilization effect originated from electrostatic repulsion between the particles of the same sign of charge as well as from steric repulsion due to the osmotic pressure raised during the overlap of the polyelectrolyte chains adsorbed on the surface. In addition, the SOD enzyme kept its structural and functional integrity during the immobilization and coating processes and hence, the LDH-SOD-HEP bionanocomposite possessed excellent activity in decomposition of superoxide radical anions, as revealed in biochemical test reactions. In conclusion, due to the improved colloidal stability and the good efficiency in scavenging superoxide radical ions, the developed enzymatic system is a promising antioxidant candidate for biomedical or other manufacturing processes, wherever the aim is to decompose reactive oxygen species in suspensions.

Keywords: clay, enzyme, polyelectrolyte, formulation

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81 Deep Learning in Chest Computed Tomography to Differentiate COVID-19 from Influenza

Authors: Hongmei Wang, Ziyun Xiang, Ying liu, Li Yu, Dongsheng Yue

Abstract:

Intro: The COVID-19 (Corona Virus Disease 2019) has greatly changed the global economic, political and financial ecology. The mutation of the coronavirus in the UK in December 2020 has brought new panic to the world. Deep learning was performed on Chest Computed tomography (CT) of COVID-19 and Influenza and describes their characteristics. The predominant features of COVID-19 pneumonia was ground-glass opacification, followed by consolidation. Lesion density: most lesions appear as ground-glass shadows, and some lesions coexist with solid lesions. Lesion distribution: the focus is mainly on the dorsal side of the periphery of the lung, with the lower lobe of the lungs as the focus, and it is often close to the pleura. Other features it has are grid-like shadows in ground glass lesions, thickening signs of diseased vessels, air bronchi signs and halo signs. The severe disease involves whole bilateral lungs, showing white lung signs, air bronchograms can be seen, and there can be a small amount of pleural effusion in the bilateral chest cavity. At the same time, this year's flu season could be near its peak after surging throughout the United States for months. Chest CT for Influenza infection is characterized by focal ground glass shadows in the lungs, with or without patchy consolidation, and bronchiole air bronchograms are visible in the concentration. There are patchy ground-glass shadows, consolidation, air bronchus signs, mosaic lung perfusion, etc. The lesions are mostly fused, which is prominent near the hilar and two lungs. Grid-like shadows and small patchy ground-glass shadows are visible. Deep neural networks have great potential in image analysis and diagnosis that traditional machine learning algorithms do not. Method: Aiming at the two major infectious diseases COVID-19 and influenza, which are currently circulating in the world, the chest CT of patients with two infectious diseases is classified and diagnosed using deep learning algorithms. The residual network is proposed to solve the problem of network degradation when there are too many hidden layers in a deep neural network (DNN). The proposed deep residual system (ResNet) is a milestone in the history of the Convolutional neural network (CNN) images, which solves the problem of difficult training of deep CNN models. Many visual tasks can get excellent results through fine-tuning ResNet. The pre-trained convolutional neural network ResNet is introduced as a feature extractor, eliminating the need to design complex models and time-consuming training. Fastai is based on Pytorch, packaging best practices for in-depth learning strategies, and finding the best way to handle diagnoses issues. Based on the one-cycle approach of the Fastai algorithm, the classification diagnosis of lung CT for two infectious diseases is realized, and a higher recognition rate is obtained. Results: A deep learning model was developed to efficiently identify the differences between COVID-19 and influenza using chest CT.

Keywords: COVID-19, Fastai, influenza, transfer network

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80 Abortion Care Education in U.S. Accreditation Commission for Midwifery Education Certified Nurse Midwifery Programs: A Call For Expansion

Authors: Maggie Hall, Haley O'Neill

Abstract:

The U.S. faces a severe shortage of abortion providers, exacerbated by the June 2022 Dobbs v. Jackson Women’s Health Organization decision. Midwives, especially certified nurse midwives, are well-positioned to fill this gap in abortion care. However, a lack of clinical education and training prevents midwives from exercising their full scope of practice. National and international organizations that set obstetrics and midwifery education standards, including the International Confederation of Midwives, American College of Obstetricians and Gynecologists, and American Public Health Association, call for expansion of midwifery-managed abortion care through the first trimester. In the U.S., midwifery programs are accredited based on compliance with ACME standards and compliance is a prerequisite for the American Midwifery Certification Board exams. We conducted a literature review of studies in the last five years regarding abortion didactic and clinical education barriers via CINAHL, EBSCO and PubMed database reviews. We gave preference for primary sources within the last five years; however, due to the rapid changes in abortion education and access, we also included literature from 2012-2022. We evaluated ACME-accredited programs in relation to their geography within abortion-protected or restricted states and assessed state-specific barriers to abortion care education and provision as clinical students. There are 43 AMCB-accredited midwifery schools in 28 states across the U.S. Twenty schools (47%) are in the 15 states in which advanced practice clinicians can provide non-surgical abortion care, such as medication abortion and MVA procedures. Twenty-four schools (56%) are in the 16 states in which abortion care provision is restricted to Licensed Physicians and cannot offer in-state clinical training opportunities for midwifery students. Six schools are in the five states in which abortion is completely banned and are geographically concentrated in the southernmost region of the U.S., including Alabama, Kentucky, Louisiana, Tennessee, and Texas. Subsequently, these programs cannot offer in-state clinical training opportunities for midwifery students. Notably, there are seven ACME programs in six states that do not restrict abortion access by gestational age, including Colorado, Connecticut, Washington, D.C., New Jersey, New Mexico, and Oregon. These programs may be uniquely positioned for midwifery involvement in abortion care beyond the first trimester. While the following states don’t house ACME programs, abortion care can be provided by advanced practice clinicians in Rhode Island, Delaware, Hawaii, Maine, Maryland, Montana, New Hampshire, and Vermont, offering clinical placement and/or new ACME program development opportunities. We identify existing barriers to clinical education and training opportunities for midwifery-managed abortion care, which are both geographic and institutional in nature. We recommend expansion and standardization of clinical education and training opportunities for midwifery-managed abortion care in ACME-accredited programs to improve access to abortion care. Midwifery programs and teaching hospitals need to expand education, training, and residency opportunities for midwifery students to strengthen access to midwife-managed abortion care. ACNM and ACME should re-evaluate accreditation criteria and the implications of ACME programs in states where students are not able to learn abortion care in clinical contexts due to state-specific abortion restrictions.

Keywords: midwifery education, abortion, abortion education, abortion access

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79 Isolation and Transplantation of Hepatocytes in an Experimental Model

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

Abstract:

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

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

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78 The Recommended Summary Plan for Emergency Care and Treatment (ReSPECT) Process: An Audit of Its Utilisation on a UK Tertiary Specialist Intensive Care Unit

Authors: Gokulan Vethanayakam, Daniel Aston

Abstract:

Introduction: The ReSPECT process supports healthcare professionals when making patient-centered decisions in the event of an emergency. It has been widely adopted by the NHS in England and allows patients to express thoughts and wishes about treatments and outcomes that they consider acceptable. It includes (but is not limited to) cardiopulmonary resuscitation decisions. ReSPECT conversations should ideally occur prior to ICU admission and should be documented in the eight sections of the nationally-standardised ReSPECT form. This audit evaluated the use of ReSPECT on a busy cardiothoracic ICU in an NHS Trust where established policies advocating its use exist. Methods: This audit was a retrospective review of ReSPECT forms for a sample of high-risk patients admitted to ICU at the Royal Papworth Hospital between January 2021 and March 2022. Patients all received one of the following interventions: Veno-Venous Extra-Corporeal Membrane Oxygenation (VV-ECMO) for severe respiratory failure (retrieved via the national ECMO service); cardiac or pulmonary transplantation-related surgical procedures (including organ transplants and Ventricular Assist Device (VAD) implantation); or elective non-transplant cardiac surgery. The quality of documentation on ReSPECT forms was evaluated using national standards and a graded ranking tool devised by the authors which was used to assess narrative aspects of the forms. Quality was ranked as A (excellent) to D (poor). Results: Of 230 patients (74 VV-ECMO, 104 transplant, 52 elective non-transplant surgery), 43 (18.7%) had a ReSPECT form and only one (0.43%) patient had a ReSPECT form completed prior to ICU admission. Of the 43 forms completed, 38 (88.4%) were completed due to the commencement of End of Life (EoL) care. No non-transplant surgical patients included in the audit had a ReSPECT form. There was documentation of balance of care (section 4a), CPR status (section 4c), capacity assessment (section 5), and patient involvement in completing the form (section 6a) on all 43 forms. Of the 34 patients assessed as lacking capacity to make decisions, only 22 (64.7%) had reasons documented. Other sections were variably completed; 29 (67.4%) forms had relevant background information included to a good standard (section 2a). Clinical guidance for the patient (section 4b) was given in 25 (58.1%), of which 11 stated the rationale that underpinned it. Seven forms (16.3%) contained information in an inappropriate section. In a comparison of ReSPECT forms completed ahead of an EoL trigger with those completed when EoL care began, there was a higher number of entries in section 3 (considering patient’s values/fears) that were assessed at grades A-B in the former group (p = 0.014), suggesting higher quality. Similarly, forms from the transplant group contained higher quality information in section 3 than those from the VV-ECMO group (p = 0.0005). Conclusions: Utilisation of the ReSPECT process in high-risk patients is yet to be well-adopted in this trust. Teams who meet patients before hospital admission for transplant or high-risk surgery should be encouraged to engage with the ReSPECT process at this point in the patient's journey. VV-ECMO retrieval teams should consider ReSPECT conversations with patients’ relatives at the time of retrieval.

Keywords: audit, critical care, end of life, ICU, ReSPECT, resuscitation

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77 COVID-19’s Impact on the Use of Media, Educational Performance, and Learning in Children and Adolescents with ADHD Who Engaged in Virtual Learning

Authors: Christina Largent, Tazley Hobbs

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Objective: A literature review was performed to examine the existing research on COVID-19 lockdown as it relates to ADHD child/adolescent individuals, media use, and impact on educational performance/learning. It was surmised that with the COVID-19 shut-down and transition to remote learning, a less structured learning environment, increased screen time, in addition to potential difficulty accessing school resources would impair ADHD individuals’ performance and learning. A resulting increase in the number of youths diagnosed and treated for ADHD would be expected. As of yet, there has been little to no published data on the incidence of ADHD as it relates to COVID-19 outside of reports from several nonprofit agencies such as CHADD (Children and Adults with Attention-Deficit/Hyperactivity Disorder ), who reported an increased number of calls to their helpline, The New York based Child Mind Institute, who reported an increased number of appointments to discuss medications, and research released from Athenahealth showing an increase in the number of patients receiving new diagnosis of ADHD and new prescriptions for ADHD medications. Methods: A literature search for articles published between 2020 and 2021 from Pubmed, Google Scholar, PsychInfo, was performed. Search phrases and keywords included “covid, adhd, child, impact, remote learning, media, screen”. Results: Studies primarily utilized parental reports, with very few from the perspective of the ADHD individuals themselves. Most findings thus far show that with the COVID-19 quarantine and transition to online learning, ADHD individuals’ experienced decreased ability to keep focused or adhere to the daily routine, as well as increased inattention-related problems, such as careless mistakes or lack of completion in homework, which in turn translated into overall more difficulty with remote learning. To add further injury, one study showed (just on evaluation of two different sites within the US) that school based services for these individuals decreased with the shift to online-learning. Increased screen time, television, social media, and gaming were noted amongst ADHD individuals. One study further differentiated the degree of digital media, identifying individuals with “problematic “ or “non-problematic” use. ADHD children with problematic digital media use suffered from more severe core symptoms of ADHD, negative emotions, executive function deficits, damage to family environment, pressure from life events, and a lower motivation to learn. Conclusions and Future Considerations: Studies found not only was online learning difficult for ADHD individuals but it, in addition to greater use of digital media, was associated with worsening ADHD symptoms impairing schoolwork, in addition to secondary findings of worsening mood and behavior. Currently, data on the number of new ADHD cases, in addition to data on the prescription and usage of stimulants during COVID-19, has not been well documented or studied; this would be well-warranted out of concern for over diagnosing or over-prescribing our youth. It would also be well-worth studying how reversible or long-lasting these negative impacts may be.

Keywords: COVID-19, remote learning, media use, ADHD, child, adolescent

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76 Application of Discrete-Event Simulation in Health Technology Assessment: A Cost-Effectiveness Analysis of Alzheimer’s Disease Treatment Using Real-World Evidence in Thailand

Authors: Khachen Kongpakwattana, Nathorn Chaiyakunapruk

Abstract:

Background: Decision-analytic models for Alzheimer’s disease (AD) have been advanced to discrete-event simulation (DES), in which individual-level modelling of disease progression across continuous severity spectra and incorporation of key parameters such as treatment persistence into the model become feasible. This study aimed to apply the DES to perform a cost-effectiveness analysis of treatment for AD in Thailand. Methods: A dataset of Thai patients with AD, representing unique demographic and clinical characteristics, was bootstrapped to generate a baseline cohort of patients. Each patient was cloned and assigned to donepezil, galantamine, rivastigmine, memantine or no treatment. Throughout the simulation period, the model randomly assigned each patient to discrete events including hospital visits, treatment discontinuation and death. Correlated changes in cognitive and behavioral status over time were developed using patient-level data. Treatment effects were obtained from the most recent network meta-analysis. Treatment persistence, mortality and predictive equations for functional status, costs (Thai baht (THB) in 2017) and quality-adjusted life year (QALY) were derived from country-specific real-world data. The time horizon was 10 years, with a discount rate of 3% per annum. Cost-effectiveness was evaluated based on the willingness-to-pay (WTP) threshold of 160,000 THB/QALY gained (4,994 US$/QALY gained) in Thailand. Results: Under a societal perspective, only was the prescription of donepezil to AD patients with all disease-severity levels found to be cost-effective. Compared to untreated patients, although the patients receiving donepezil incurred a discounted additional costs of 2,161 THB, they experienced a discounted gain in QALY of 0.021, resulting in an incremental cost-effectiveness ratio (ICER) of 138,524 THB/QALY (4,062 US$/QALY). Besides, providing early treatment with donepezil to mild AD patients further reduced the ICER to 61,652 THB/QALY (1,808 US$/QALY). However, the dominance of donepezil appeared to wane when delayed treatment was given to a subgroup of moderate and severe AD patients [ICER: 284,388 THB/QALY (8,340 US$/QALY)]. Introduction of a treatment stopping rule when the Mini-Mental State Exam (MMSE) score goes below 10 to a mild AD cohort did not deteriorate the cost-effectiveness of donepezil at the current treatment persistence level. On the other hand, none of the AD medications was cost-effective when being considered under a healthcare perspective. Conclusions: The DES greatly enhances real-world representativeness of decision-analytic models for AD. Under a societal perspective, treatment with donepezil improves patient’s quality of life and is considered cost-effective when used to treat AD patients with all disease-severity levels in Thailand. The optimal treatment benefits are observed when donepezil is prescribed since the early course of AD. With healthcare budget constraints in Thailand, the implementation of donepezil coverage may be most likely possible when being considered starting with mild AD patients, along with the stopping rule introduced.

Keywords: Alzheimer's disease, cost-effectiveness analysis, discrete event simulation, health technology assessment

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75 Pricing Techniques to Mitigate Recurring Congestion on Interstate Facilities Using Dynamic Feedback Assignment

Authors: Hatem Abou-Senna

Abstract:

Interstate 4 (I-4) is a primary east-west transportation corridor between Tampa and Daytona cities, serving commuters, commercial and recreational traffic. I-4 is known to have severe recurring congestion during peak hours. The congestion spans about 11 miles in the evening peak period in the central corridor area as it is considered the only non-tolled limited access facility connecting the Orlando Central Business District (CBD) and the tourist attractions area (Walt Disney World). Florida officials had been skeptical of tolling I-4 prior to the recent legislation, and the public through the media had been complaining about the excessive toll facilities in Central Florida. So, in search for plausible mitigation to the congestion on the I-4 corridor, this research is implemented to evaluate the effectiveness of different toll pricing alternatives that might divert traffic from I-4 to the toll facilities during the peak period. The network is composed of two main diverging limited access highways, freeway (I-4) and toll road (SR 417) in addition to two east-west parallel toll roads SR 408 and SR 528, intersecting the above-mentioned highways from both ends. I-4 and toll road SR 408 are the most frequently used route by commuters. SR-417 is a relatively uncongested toll road with 15 miles longer than I-4 and $5 tolls compared to no monetary cost on 1-4 for the same trip. The results of the calibrated Orlando PARAMICS network showed that percentages of route diversion vary from one route to another and depends primarily on the travel cost between specific origin-destination (O-D) pairs. Most drivers going from Disney (O1) or Lake Buena Vista (O2) to Lake Mary (D1) were found to have a high propensity towards using I-4, even when eliminating tolls and/or providing real-time information. However, a diversion from I-4 to SR 417 for these OD pairs occurred only in the cases of the incident and lane closure on I-4, due to the increase in delay and travel costs, and when information is provided to travelers. Furthermore, drivers that diverted from I-4 to SR 417 and SR 528 did not gain significant travel-time savings. This was attributed to the limited extra capacity of the alternative routes in the peak period and the longer traveling distance. When the remaining origin-destination pairs were analyzed, average travel time savings on I-4 ranged between 10 and 16% amounting to 10 minutes at the most with a 10% increase in the network average speed. High propensity of diversion on the network increased significantly when eliminating tolls on SR 417 and SR 528 while doubling the tolls on SR 408 along with the incident and lane closure scenarios on I-4 and with real-time information provided. The toll roads were found to be a viable alternative to I-4 for these specific OD pairs depending on the user perception of the toll cost which was reflected in their specific travel times. However, on the macroscopic level, it was concluded that route diversion through toll reduction or elimination on surrounding toll roads would only have a minimum impact on reducing I-4 congestion during the peak period.

Keywords: congestion pricing, dynamic feedback assignment, microsimulation, paramics, route diversion

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74 Longitudinal Examination of Depressive Symptoms among U.S. Parents who Gave Birth During the COVID-19 Pandemic

Authors: Amy Claridge, Tishra Beeson

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Background: Maternal depression is a serious health concern impacting between 10-16% of birthing persons. It is associated with difficulty in emotional interaction and the formation of attachment bonds between parent and infant. Longitudinally, maternal depression can have severe, lasting impacts on both parent and child, increasing the risk for mental, social, and physical health issues. Rates of prenatal depression have been higher among individuals who were pregnant during the first year of the COVID-19 pandemic. Pregnant persons are considered a high-risk group for poor clinical outcomes from COVID-19 infection and may also have faced or continue to face additional stressors such as financial burdens, loss of income or employment, and the benefits accompanying employment, especially among those in the United States (U.S.). It is less clear whether individuals who gave birth during the pandemic continue to experience high levels of depressive symptoms or whether symptoms have been reduced as a pandemic response has shifted. The current study examined longitudinal reports of depressive symptoms among individuals in the U.S. who gave birth between March 2020 and September 2021. Methods: This mixed-method study involved surveys and interviews with birthing persons (18-45 years old) in their third trimester of pregnancy and at 8 weeks postpartum. Participants also completed a follow-up survey at 12-18 months postpartum. Participants were recruited using convenience methods via an online survey. Survey participants included 242 U.S. women who self-reported depressive symptoms (10-item Edinburgh Postnatal Depression Scale) at each data collection wave. A subset of 23 women participated in semi-structured prenatal and 8-week postpartum qualitative interviews. Follow-up interviews are currently underway and will be integrated into the presentation. Preliminary Results: Prenatal depressive symptoms were significantly positively correlated to 8-week and 12-18-month postpartum depressive symptoms. Participants who reported clinical levels of depression prenatally were 3.29 times (SE = .32, p < .001) more likely to report clinical levels of depression at 18 months postpartum. Those who reported clinical depression at 8-weeks postpartum were 6.52 times (SE = .41, p < .001) more likely to report clinical levels of depression at 18 months postpartum. Participants who gave birth earlier in the pandemic reported significantly higher prenatal (t(103) = 2.84, p < .01) and 8-week postpartum depressive symptoms (t(126) = 3.31, p < .001). Data from qualitative interviews contextualize the findings. Participants reported negative emotions during pregnancy, including sadness, grief, and anxiety. They attributed this in part to their experiences of pregnancy during the pandemic and uncertainty related to the birth experience and postpartum period. Postpartum interviews revealed some stressors specific to childbirth during the COVID-19 pandemic; however, most women reflected on positive experiences of birth and postpartum. Conclusions: Taken together, findings reveal a pattern of persistent depressive symptoms among U.S. parents who gave birth during the pandemic. Depressive symptoms are of significant concern for the health of parents and children, and the findings of this study suggest a need for continued mental health intervention for parents who gave birth during the pandemic. Policy and practice implications will be discussed.

Keywords: maternal mental health, perinatal depression, postpartum depression, covid-19 pandemic

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73 Immunoliposome-Mediated Drug Delivery to Plasmodium-Infected and Non-Infected Red Blood Cells as a Dual Therapeutic/Prophylactic Antimalarial Strategy

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

Abstract:

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

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

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72 Addressing Water Scarcity in Gomti Nagar, Lucknow, India: Assessing the Effectiveness of Rooftop Rainwater Harvesting Systems

Authors: Rajkumar Ghosh

Abstract:

Water scarcity is a significant challenge in urban areas, even in smart cities (Lucknow, Bangalore, Jaipur, etc.) where efficient resource management is prioritized. The depletion of groundwater resources in Gomti Nagar, Lucknow, Uttar Pradesh, India is particularly severe, posing a significant challenge for sustainable development in the region. This study focuses on addressing the water shortage by investigating the effectiveness of rooftop rainwater harvesting systems (RTRWHs) as a sustainable approach to bridge the gap between groundwater recharge and extraction. The aim of this study is to assess the effectiveness of RTRWHs in reducing aquifer depletion and addressing the water scarcity issue in the Gomti Nagar region. The research methodology involves the utilization of RTRWHs as the primary method for collecting rainwater. RTRWHs will be implemented in residential and commercial buildings to maximize the collection of rainwater. Data for this study were collected through various sources such as government reports, surveys, and existing groundwater abstraction patterns. Statistical analysis and modelling techniques were employed to assess the current water situation, groundwater depletion rate, and the potential impact of implementing RTRWHs. The study reveals that the installation of RTRWHs in the Gomti Nagar region has a positive impact on addressing the water scarcity issue. Currently, RTRWHs cover only a small percentage of the total rainfall collected in the region. However, when RTRWHs are installed in all buildings, their influence on increasing water availability and reducing aquifer depletion will be significantly greater. The study also highlights the significant water imbalance in the region, emphasizing the urgent need for sustainable water management practices. This research contributes to the theoretical understanding of sustainable water management systems in smart cities. By highlighting the effectiveness of RTRWHs in reducing aquifer depletion, it emphasizes the importance of implementing such systems in urban areas. Data for this study were collected through various sources such as government reports, surveys, and existing groundwater abstraction patterns. The collected data were then analysed using statistical analysis and modelling techniques to assess the current water situation, groundwater depletion rate, and the potential impact of implementing RTRWHs. The findings of this study demonstrate that the implementation of RTRWHs can effectively mitigate the water scarcity crisis in Gomti Nagar. By reducing aquifer depletion and bridging the gap between groundwater recharge and extraction, RTRWHs offer a sustainable solution to the region's water scarcity challenges. Widespread adoption of RTRWHs in all buildings and integration into urban planning and development processes are crucial for efficient water management in smart cities like Gomti Nagar. These findings can serve as a basis for policymakers, urban planners, and developers to prioritize and incentivize the installation of RTRWHs as a potential solution to the water shortage crisis.

Keywords: water scarcity, urban areas, smart cities, resource management, groundwater depletion, rooftop rainwater harvesting systems, sustainable development, sustainable water management, mitigating water scarcity

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71 Screening for Women with Chorioamnionitis: An Integrative Literature Review

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

Abstract:

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

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

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70 Defective Autophagy Disturbs Neural Migration and Network Activity in hiPSC-Derived Cockayne Syndrome B Disease Models

Authors: Julia Kapr, Andrea Rossi, Haribaskar Ramachandran, Marius Pollet, Ilka Egger, Selina Dangeleit, Katharina Koch, Jean Krutmann, Ellen Fritsche

Abstract:

It is widely acknowledged that animal models do not always represent human disease. Especially human brain development is difficult to model in animals due to a variety of structural and functional species-specificities. This causes significant discrepancies between predicted and apparent drug efficacies in clinical trials and their subsequent failure. Emerging alternatives based on 3D in vitro approaches, such as human brain spheres or organoids, may in the future reduce and ultimately replace animal models. Here, we present a human induced pluripotent stem cell (hiPSC)-based 3D neural in a vitro disease model for the Cockayne Syndrome B (CSB). CSB is a rare hereditary disease and is accompanied by severe neurologic defects, such as microcephaly, ataxia and intellectual disability, with currently no treatment options. Therefore, the aim of this study is to investigate the molecular and cellular defects found in neural hiPSC-derived CSB models. Understanding the underlying pathology of CSB enables the development of treatment options. The two CSB models used in this study comprise a patient-derived hiPSC line and its isogenic control as well as a CSB-deficient cell line based on a healthy hiPSC line (IMR90-4) background thereby excluding genetic background-related effects. Neurally induced and differentiated brain sphere cultures were characterized via RNA Sequencing, western blot (WB), immunocytochemistry (ICC) and multielectrode arrays (MEAs). CSB-deficiency leads to an altered gene expression of markers for autophagy, focal adhesion and neural network formation. Cell migration was significantly reduced and electrical activity was significantly increased in the disease cell lines. These data hint that the cellular pathologies is possibly underlying CSB. By induction of autophagy, the migration phenotype could be partially rescued, suggesting a crucial role of disturbed autophagy in defective neural migration of the disease lines. Altered autophagy may also lead to inefficient mitophagy. Accordingly, disease cell lines were shown to have a lower mitochondrial base activity and a higher susceptibility to mitochondrial stress induced by rotenone. Since mitochondria play an important role in neurotransmitter cycling, we suggest that defective mitochondria may lead to altered electrical activity in the disease cell lines. Failure to clear the defective mitochondria by mitophagy and thus missing initiation cues for new mitochondrial production could potentiate this problem. With our data, we aim at establishing a disease adverse outcome pathway (AOP), thereby adding to the in-depth understanding of this multi-faced disorder and subsequently contributing to alternative drug development.

Keywords: autophagy, disease modeling, in vitro, pluripotent stem cells

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69 Interactions between Sodium Aerosols and Fission Products: A Theoretical Chemistry and Experimental Approach

Authors: Ankita Jadon, Sidi Souvi, Nathalie Girault, Denis Petitprez

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Safety requirements for Generation IV nuclear reactor designs, especially the new generation sodium-cooled fast reactors (SFR) require a risk-informed approach to model severe accidents (SA) and their consequences in case of outside release. In SFRs, aerosols are produced during a core disruptive accident when primary system sodium is ejected into the containment and burn in contact with the air; producing sodium aerosols. One of the key aspects of safety evaluation is the in-containment sodium aerosol behavior and their interaction with fission products. The study of the effects of sodium fires is essential for safety evaluation as the fire can both thermally damage the containment vessel and cause an overpressurization risk. Besides, during the fire, airborne fission product first dissolved in the primary sodium can be aerosolized or, as it can be the case for fission products, released under the gaseous form. The objective of this work is to study the interactions between sodium aerosols and fission products (Iodine, toxic and volatile, being the primary concern). Sodium fires resulting from an SA would produce aerosols consisting of sodium peroxides, hydroxides, carbonates, and bicarbonates. In addition to being toxic (in oxide form), this aerosol will then become radioactive. If such aerosols are leaked into the environment, they can pose a danger to the ecosystem. Depending on the chemical affinity of these chemical forms with fission products, the radiological consequences of an SA leading to containment leak tightness loss will also be affected. This work is split into two phases. Firstly, a method to theoretically understand the kinetics and thermodynamics of the heterogeneous reaction between sodium aerosols and fission products: I2 and HI are proposed. Ab-initio, density functional theory (DFT) calculations using Vienna ab-initio simulation package are carried out to develop an understanding of the surfaces of sodium carbonate (Na2CO3) aerosols and hence provide insight on its affinity towards iodine species. A comprehensive study of I2 and HI adsorption, as well as bicarbonate formation on the calculated lowest energy surface of Na2CO3, was performed which provided adsorption energies and description of the optimized configuration of adsorbate on the stable surface. Secondly, the heterogeneous reaction between (I2)g and Na2CO3 aerosols were investigated experimentally. To study this, (I2)g was generated by heating a permeation tube containing solid I2, and, passing it through a reaction chamber containing Na2CO3 aerosol deposit. The concentration of iodine was then measured at the exit of the reaction chamber. Preliminary observations indicate that there is an effective uptake of (I2)g on Na2CO3 surface, as suggested by our theoretical chemistry calculations. This work is the first step in addressing the gaps in knowledge of in-containment and atmospheric source term which are essential aspects of safety evaluation of SFR SA. In particular, this study is aimed to determine and characterize the radiological and chemical source term. These results will then provide useful insights for the developments of new models to be implemented in integrated computer simulation tool to analyze and evaluate SFR safety designs.

Keywords: iodine adsorption, sodium aerosols, sodium cooled reactor, DFT calculations, sodium carbonate

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68 Clinical Presentation and Immune Response to Intramammary Infection of Holstein-Friesian Heifers with Isolates from Two Staphylococcus aureus Lineages

Authors: Dagmara A. Niedziela, Mark P. Murphy, Orla M. Keane, Finola C. Leonard

Abstract:

Staphylococcus aureus is the most frequent cause of clinical and subclinical bovine mastitis in Ireland. Mastitis caused by S. aureus is often chronic and tends to recur after antibiotic treatment. This may be due to several virulence factors, including attributes that enable the bacterium to internalize into bovine mammary epithelial cells, where it may evade antibiotic treatment, or evade the host immune response. Four bovine-adapted lineages (CC71, CC97, CC151 and ST136) were identified among a collection of Irish S. aureus mastitis isolates. Genotypic variation of mastitis-causing strains may contribute to different presentations of the disease, including differences in milk somatic cell count (SCC), the main method of mastitis detection. The objective of this study was to investigate the influence of bacterial strain and lineage on host immune response, by employing cell culture methods in vitro as well as an in vivo infection model. Twelve bovine adapted S. aureus strains were examined for internalization into bovine mammary epithelial cells (bMEC) and their ability to induce an immune response from bMEC (using qPCR and ELISA). In vitro studies found differences in a variety of virulence traits between the lineages. Strains from lineages CC97 and CC71 internalized more efficiently into bovine mammary epithelial cells (bMEC) than CC151 and ST136. CC97 strains also induced immune genes in bMEC more strongly than strains from the other 3 lineages. One strain each of CC151 and CC97 that differed in their ability to cause an immune response in bMEC were selected on the basis of the above in vitro experiments. Fourteen first-lactation Holstein-Friesian cows were purchased from 2 farms on the basis of low SCC (less than 50 000 cells/ml) and infection free status. Seven cows were infected with 1.73 x 102 c.f.u. of the CC97 strain (Group 1) and another seven with 5.83 x 102 c.f.u. of the CC151 strain (Group 2). The contralateral quarter of each cow was inoculated with PBS (vehicle). Clinical signs of infection (temperature, milk and udder appearance, milk yield) were monitored for 30 days. Blood and milk samples were taken to determine bacterial counts in milk, SCC, white blood cell populations and cytokines. Differences in disease presentation in vivo between groups were observed, with two animals from Group 2 developing clinical mastitis and requiring antibiotic treatment, while one animal from Group 1 did not develop an infection for the duration of the study. Fever (temperature > 39.5⁰C) was observed in 3 animals from Group 2 and in none from Group 1. Significant differences in SCC and bacterial load between groups were observed in the initial stages of infection (week 1). Data is also being collected on cytokines and chemokines secreted during the course of infection. The results of this study suggest that a strain from lineage CC151 may cause more severe clinical mastitis, while a strain from lineage CC97 may cause mild, subclinical mastitis. Diversity between strains of S. aureus may therefore influence the clinical presentation of mastitis, which in turn may influence disease detection and treatment needs.

Keywords: Bovine mastitis, host immune response, host-pathogen interactions, Staphylococcus aureus

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67 Creation of a Test Machine for the Scientific Investigation of Chain Shot

Authors: Mark McGuire, Eric Shannon, John Parmigiani

Abstract:

Timber harvesting increasingly involves mechanized equipment. This has increased the efficiency of harvesting, but has also introduced worker-safety concerns. One such concern arises from the use of harvesters. During operation, harvesters subject saw chain to large dynamic mechanical stresses. These stresses can, under certain conditions, cause the saw chain to fracture. The high speed of harvester saw chain can cause the resulting open chain loop to fracture a second time due to the dynamic loads placed upon it as it travels through space. If a second fracture occurs, it can result in a projectile consisting of one-to-several chain links. This projectile is referred to as a chain shot. It has speeds similar to a bullet but typically has greater mass and is a significant safety concern. Numerous examples exist of chain shots penetrating bullet-proof barriers and causing severe injury and death. Improved harvester-cab barriers can help prevent injury however a comprehensive scientific understanding of chain shot is required to consistently reduce or prevent it. Obtaining this understanding requires a test machine with the capability to cause chain shot to occur under carefully controlled conditions and accurately measure the response. Worldwide few such test machine exist. Those that do focus on validating the ability of barriers to withstand a chain shot impact rather than obtaining a scientific understanding of the chain shot event itself. The purpose of this paper is to describe the design, fabrication, and use of a test machine capable of a comprehensive scientific investigation of chain shot. The capabilities of this machine are to test all commercially-available saw chains and bars at chain tensions and speeds meeting and exceeding those typically encountered in harvester use and accurately measure the corresponding key technical parameters. The test machine was constructed inside of a standard shipping container. This provides space for both an operator station and a test chamber. In order to contain the chain shot under any possible test conditions, the test chamber was lined with a base layer of AR500 steel followed by an overlay of HDPE. To accommodate varying bar orientations and fracture-initiation sites, the entire saw chain drive unit and bar mounting system is modular and capable of being located anywhere in the test chamber. The drive unit consists of a high-speed electric motor with a flywheel. Standard Ponsse harvester head components are used to bar mounting and chain tensioning. Chain lubrication is provided by a separate peristaltic pump. Chain fracture is initiated through ISO standard 11837. Measure parameters include shaft speed, motor vibration, bearing temperatures, motor temperature, motor current draw, hydraulic fluid pressure, chain force at fracture, and high-speed camera images. Results show that the machine is capable of consistently causing chain shot. Measurement output shows fracture location and the force associated with fracture as a function of saw chain speed and tension. Use of this machine will result in a scientific understanding of chain shot and consequently improved products and greater harvester operator safety.

Keywords: chain shot, safety, testing, timber harvesters

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66 Examining Influence of The Ultrasonic Power and Frequency on Microbubbles Dynamics Using Real-Time Visualization of Synchrotron X-Ray Imaging: Application to Membrane Fouling Control

Authors: Masoume Ehsani, Ning Zhu, Huu Doan, Ali Lohi, Amira Abdelrasoul

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Membrane fouling poses severe challenges in membrane-based wastewater treatment applications. Ultrasound (US) has been considered an effective fouling remediation technique in filtration processes. Bubble cavitation in the liquid medium results from the alternating rarefaction and compression cycles during the US irradiation at sufficiently high acoustic pressure. Cavitation microbubbles generated under US irradiation can cause eddy current and turbulent flow within the medium by either oscillating or discharging energy to the system through microbubble explosion. Turbulent flow regime and shear forces created close to the membrane surface cause disturbing the cake layer and dislodging the foulants, which in turn improve the cleaning efficiency and filtration performance. Therefore, the number, size, velocity, and oscillation pattern of the microbubbles created in the liquid medium play a crucial role in foulant detachment and permeate flux recovery. The goal of the current study is to gain in depth understanding of the influence of the US power intensity and frequency on the microbubble dynamics and its characteristics generated under US irradiation. In comparison with other imaging techniques, the synchrotron in-line Phase Contrast Imaging technique at the Canadian Light Source (CLS) allows in-situ observation and real-time visualization of microbubble dynamics. At CLS biomedical imaging and therapy (BMIT) polychromatic beamline, the effective parameters were optimized to enhance the contrast gas/liquid interface for the accuracy of the qualitative and quantitative analysis of bubble cavitation within the system. With the high flux of photons and the high-speed camera, a typical high projection speed was achieved; and each projection of microbubbles in water was captured in 0.5 ms. ImageJ software was used for post-processing the raw images for the detailed quantitative analyses of microbubbles. The imaging has been performed under the US power intensity levels of 50 W, 60 W, and 100 W, in addition to the US frequency levels of 20 kHz, 28 kHz, and 40 kHz. For the duration of 2 seconds of imaging, the effect of the US power and frequency on the average number, size, and fraction of the area occupied by bubbles were analyzed. Microbubbles’ dynamics in terms of their velocity in water was also investigated. For the US power increase of 50 W to 100 W, the average bubble number and the average bubble diameter were increased from 746 to 880 and from 36.7 µm to 48.4 µm, respectively. In terms of the influence of US frequency, a fewer number of bubbles were created at 20 kHz (average of 176 bubbles rather than 808 bubbles at 40 kHz), while the average bubble size was significantly larger than that of 40 kHz (almost seven times). The majority of bubbles were captured close to the membrane surface in the filtration unit. According to the study observations, membrane cleaning efficiency is expected to be improved at higher US power and lower US frequency due to the higher energy release to the system by increasing the number of bubbles or growing their size during oscillation (optimum condition is expected to be at 20 kHz and 100 W).

Keywords: bubble dynamics, cavitational bubbles, membrane fouling, ultrasonic cleaning

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65 Absolute Quantification of the Bexsero Vaccine Component Factor H Binding Protein (fHbp) by Selected Reaction Monitoring: The Contribution of Mass Spectrometry in Vaccinology

Authors: Massimiliano Biagini, Marco Spinsanti, Gabriella De Angelis, Sara Tomei, Ilaria Ferlenghi, Maria Scarselli, Alessia Biolchi, Alessandro Muzzi, Brunella Brunelli, Silvana Savino, Marzia M. Giuliani, Isabel Delany, Paolo Costantino, Rino Rappuoli, Vega Masignani, Nathalie Norais

Abstract:

The gram-negative bacterium Neisseria meningitidis serogroup B (MenB) is an exclusively human pathogen representing the major cause of meningitides and severe sepsis in infants and children but also in young adults. This pathogen is usually present in the 30% of healthy population that act as a reservoir, spreading it through saliva and respiratory fluids during coughing, sneezing, kissing. Among surface-exposed protein components of this diplococcus, factor H binding protein is a lipoprotein proved to be a protective antigen used as a component of the recently licensed Bexsero vaccine. fHbp is a highly variable meningococcal protein: to reflect its remarkable sequence variability, it has been classified in three variants (or two subfamilies), and with poor cross-protection among the different variants. Furthermore, the level of fHbp expression varies significantly among strains, and this has also been considered an important factor for predicting MenB strain susceptibility to anti-fHbp antisera. Different methods have been used to assess fHbp expression on meningococcal strains, however, all these methods use anti-fHbp antibodies, and for this reason, the results are affected by the different affinity that antibodies can have to different antigenic variants. To overcome the limitations of an antibody-based quantification, we developed a quantitative Mass Spectrometry (MS) approach. Selected Reaction Monitoring (SRM) recently emerged as a powerful MS tool for detecting and quantifying proteins in complex mixtures. SRM is based on the targeted detection of ProteoTypicPeptides (PTPs), which are unique signatures of a protein that can be easily detected and quantified by MS. This approach, proven to be highly sensitive, quantitatively accurate and highly reproducible, was used to quantify the absolute amount of fHbp antigen in total extracts derived from 105 clinical isolates, evenly distributed among the three main variant groups and selected to be representative of the fHbp circulating subvariants around the world. We extended the study at the genetic level investigating the correlation between the differential level of expression and polymorphisms present within the genes and their promoter sequences. The implications of fHbp expression on the susceptibility of the strain to killing by anti-fHbp antisera are also presented. To date this is the first comprehensive fHbp expression profiling in a large panel of Neisseria meningitidis clinical isolates driven by an antibody-independent MS-based methodology, opening the door to new applications in vaccine coverage prediction and reinforcing the molecular understanding of released vaccines.

Keywords: quantitative mass spectrometry, Neisseria meningitidis, vaccines, bexsero, molecular epidemiology

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64 Wheat Cluster Farming Approach: Challenges and Prospects for Smallholder Farmers in Ethiopia

Authors: Hanna Mamo Ergando

Abstract:

Climate change is already having a severe influence on agriculture, affecting crop yields, the nutritional content of main grains, and livestock productivity. Significant adaptation investments will be necessary to sustain existing yields and enhance production and food quality to fulfill demand. Climate-smart agriculture (CSA) provides numerous potentials in this regard, combining a focus on enhancing agricultural output and incomes while also strengthening resilience and responding to climate change. To improve agriculture production and productivity, the Ethiopian government has adopted and implemented a series of strategies, including the recent agricultural cluster farming that is practiced as an effort to change, improve, and transform subsistence farming to modern, productive, market-oriented, and climate-smart approach through farmers production cluster. Besides, greater attention and focus have been given to wheat production and productivity by the government, and wheat is the major crop grown in cluster farming. Therefore, the objective of this assessment was to examine various opportunities and challenges farmers face in a cluster farming system. A qualitative research approach was used to generate primary and secondary data. Respondents were chosen using the purposeful sampling technique. Accordingly, experts from the Federal Ministry of Agriculture, the Ethiopian Agricultural Transformation Institute, the Ethiopian Agricultural Research Institute, and the Ethiopian Environment Protection Authority were interviewed. The assessment result revealed that farming in clusters is an economically viable technique for sustaining small, resource-limited, and socially disadvantaged farmers' agricultural businesses. The method assists farmers in consolidating their products and delivering them in bulk to save on transportation costs while increasing income. Smallholders' negotiating power has improved as a result of cluster membership, as has knowledge and information spillover. The key challenges, on the other hand, were identified as a lack of timely provision of modern inputs, insufficient access to credit services, conflict of interest in crop selection, and a lack of output market for agro-processing firms. Furthermore, farmers in the cluster farming approach grow wheat year after year without crop rotation or diversification techniques. Mono-cropping has disadvantages because it raises the likelihood of disease and insect outbreaks. This practice may result in long-term consequences, including soil degradation, reduced biodiversity, and economic risk for farmers. Therefore, the government must devote more resources to addressing the issue of environmental sustainability. Farmers' access to complementary services that promote production and marketing efficiencies through infrastructure and institutional services has to be improved. In general, the assessment begins with some hint that leads to a deeper study into the efficiency of the strategy implementation, upholding existing policy, and scaling up good practices in a sustainable and environmentally viable manner.

Keywords: cluster farming, smallholder farmers, wheat, challenges, opportunities

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63 Prospects of Low Immune Response Transplants Based on Acellular Organ Scaffolds

Authors: Inna Kornienko, Svetlana Guryeva, Anatoly Shekhter, Elena Petersen

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Transplantation is an effective treatment option for patients suffering from different end-stage diseases. However, it is plagued by a constant shortage of donor organs and the subsequent need of a lifelong immunosuppressive therapy for the patient. Currently some researchers look towards using of pig organs to replace human organs for transplantation since the matrix derived from porcine organs is a convenient substitute for the human matrix. As an initial step to create a new ex vivo tissue engineered model, optimized protocols have been created to obtain organ-specific acellular matrices and evaluated their potential as tissue engineered scaffolds for culture of normal cells and tumor cell lines. These protocols include decellularization by perfusion in a bioreactor system and immersion-agitation on an orbital shaker with use of various detergents (SDS, Triton X-100) and freezing. Complete decellularization – in terms of residual DNA amount – is an important predictor of probability of immune rejection of materials of natural origin. However, the signs of cellular material may still remain within the matrix even after harsh decellularization protocols. In this regard, the matrices obtained from tissues of low-immunogenic pigs with α3Galactosyl-tranferase gene knock out (GalT-KO) may be a promising alternative to native animal sources. The research included a study of induced effect of frozen and fresh fragments of GalT-KO skin on healing of full-thickness plane wounds in 80 rats. Commercially available wound dressings (Ksenoderm, Hyamatrix and Alloderm) as well as allogenic skin were used as a positive control and untreated wounds were analyzed as a negative control. The results were evaluated on the 4th day after grafting, which corresponds to the time of start of normal wound epithelization. It has been shown that a non-specific immune response in models treated with GalT-Ko pig skin was milder than in all the control groups. Research has been performed to measure technical skin characteristics: stiffness and elasticity properties, corneometry, tevametry, and cutometry. These metrics enabled the evaluation of hydratation level, corneous layer husking level, as well as skin elasticity and micro- and macro-landscape. These preliminary data may contribute to development of personalized transplantable organs from GalT-Ko pigs with significantly limited potential of immune rejection. By applying growth factors to a decellularized skin sample it is possible to achieve various regenerative effects based on the particular situation. In this particular research BMP2 and Heparin-binding EGF-like growth factor have been used. Ideally, a bioengineered organ must be biocompatible, non-immunogenic and support cell growth. Porcine organs are attractive for xenotransplantation if severe immunologic concerns can be bypassed. The results indicate that genetically modified pig tissues with knock-outed α3Galactosyl-tranferase gene may be used for production of low-immunogenic matrix suitable for transplantation.

Keywords: decellularization, low-immunogenic, matrix, scaffolds, transplants

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62 Moderating and Mediating Effects of Business Model Innovation Barriers during Crises: A Structural Equation Model Tested on German Chemical Start-Ups

Authors: Sarah Mueller-Saegebrecht, André Brendler

Abstract:

Business model innovation (BMI) as an intentional change of an existing business model (BM) or the design of a new BM is essential to a firm's development in dynamic markets. The relevance of BMI is also evident in the ongoing COVID-19 pandemic, in which start-ups, in particular, are affected by limited access to resources. However, first studies also show that they react faster to the pandemic than established firms. A strategy to successfully handle such threatening dynamic changes represents BMI. Entrepreneurship literature shows how and when firms should utilize BMI in times of crisis and which barriers one can expect during the BMI process. Nevertheless, research merging BMI barriers and crises is still underexplored. Specifically, further knowledge about antecedents and the effect of moderators on the BMI process is necessary for advancing BMI research. The addressed research gap of this study is two-folded: First, foundations to the subject on how different crises impact BM change intention exist, yet their analysis lacks the inclusion of barriers. Especially, entrepreneurship literature lacks knowledge about the individual perception of BMI barriers, which is essential to predict managerial reactions. Moreover, internal BMI barriers have been the focal point of current research, while external BMI barriers remain virtually understudied. Second, to date, BMI research is based on qualitative methodologies. Thus, a lack of quantitative work can specify and confirm these qualitative findings. By focusing on the crisis context, this study contributes to BMI literature by offering a first quantitative attempt to embed BMI barriers into a structural equation model. It measures managers' perception of BMI development and implementation barriers in the BMI process, asking the following research question: How does a manager's perception of BMI barriers influence BMI development and implementation in times of crisis? Two distinct research streams in economic literature explain how individuals react when perceiving a threat. "Prospect Theory" claims that managers demonstrate risk-seeking tendencies when facing a potential loss, and opposing "Threat-Rigidity Theory" suggests that managers demonstrate risk-averse behavior when facing a potential loss. This study quantitively tests which theory can best predict managers' BM reaction to a perceived crisis. Out of three in-depth interviews in the German chemical industry, 60 past BMIs were identified. The participating start-up managers gave insights into their start-up's strategic and operational functioning. After, each interviewee described crises that had already affected their BM. The participants explained how they conducted BMI to overcome these crises, which development and implementation barriers they faced, and how severe they perceived them, assessed on a 5-point Likert scale. In contrast to current research, results reveal that a higher perceived threat level of a crisis harms BM experimentation. Managers seem to conduct less BMI in times of crisis, whereby BMI development barriers dampen this relation. The structural equation model unveils a mediating role of BMI implementation barriers on the link between the intention to change a BM and the concrete BMI implementation. In conclusion, this study confirms the threat-rigidity theory.

Keywords: barrier perception, business model innovation, business model innovation barriers, crises, prospect theory, start-ups, structural equation model, threat-rigidity theory

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61 Assessment of Rooftop Rainwater Harvesting in Gomti Nagar, Lucknow

Authors: Rajkumar Ghosh

Abstract:

Water scarcity is a pressing issue in urban areas, even in smart cities where efficient resource management is a priority. This scarcity is mainly caused by factors such as lifestyle changes, excessive groundwater extraction, over-usage of water, rapid urbanization, and uncontrolled population growth. In the specific case of Gomti Nagar, Lucknow, Uttar Pradesh, India, the depletion of groundwater resources is particularly severe, leading to a water imbalance and posing a significant challenge for the region's sustainable development. The aim of this study is to address the water shortage in the Gomti Nagar region by focusing on the implementation of artificial groundwater recharge methods. Specifically, the research aims to investigate the effectiveness of rainwater collection through rooftop rainwater harvesting systems (RTRWHs) as a sustainable approach to reduce aquifer depletion and bridge the gap between groundwater recharge and extraction. The research methodology for this study involves the utilization of RTRWHs as the main method for collecting rainwater. This approach is considered effective in managing and conserving water resources in a sustainable manner. The focus is on implementing RTRWHs in residential and commercial buildings to maximize the collection of rainwater and its subsequent utilization for various purposes in the Gomti Nagar region. The study reveals that the installation of RTRWHs in the Gomti Nagar region has a positive impact on addressing the water scarcity issue. Currently, RTRWHs cover only a small percentage (0.04%) of the total rainfall collected in the region. However, when RTRWHs are installed in all buildings, their influence on increasing water availability and reducing aquifer depletion will be significantly greater. The study also highlights the significant water imbalance of 24519 ML/yr in the region, emphasizing the urgent need for sustainable water management practices. This research contributes to the theoretical understanding of sustainable water management systems in smart cities. By highlighting the effectiveness of RTRWHs in reducing aquifer depletion, it emphasizes the importance of implementing such systems in urban areas. The findings of this study can serve as a basis for policymakers, urban planners, and developers to prioritize and incentivize the installation of RTRWHs as a potential solution to the water shortage crisis. The data for this study were collected through various sources such as government reports, surveys, and existing groundwater abstraction patterns. The collected data were then analysed to assess the current water situation, groundwater depletion rate, and the potential impact of implementing RTRWHs. Statistical analysis and modelling techniques were employed to quantify the water imbalance and evaluate the effectiveness of RTRWHs. The findings of this study demonstrate that the implementation of RTRWHs can effectively mitigate the water scarcity crisis in Gomti Nagar. By reducing aquifer depletion and bridging the gap between groundwater recharge and extraction, RTRWHs offer a sustainable solution to the region's water scarcity challenges. The study highlights the need for widespread adoption of RTRWHs in all buildings and emphasizes the importance of integrating such systems into the urban planning and development process. By doing so, smart cities like Gomti Nagar can achieve efficient water management, ensuring a better future with improved water availability for its residents.

Keywords: rooftop rainwater harvesting, rainwater, water management, aquifer

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60 Transcriptional Differences in B cell Subpopulations over the Course of Preclinical Autoimmunity Development

Authors: Aleksandra Bylinska, Samantha Slight-Webb, Kevin Thomas, Miles Smith, Susan Macwana, Nicolas Dominguez, Eliza Chakravarty, Joan T. Merrill, Judith A. James, Joel M. Guthridge

Abstract:

Background: Systemic Lupus Erythematosus (SLE) is an interferon-related autoimmune disease characterized by B cell dysfunction. One of the main hallmarks is a loss of tolerance to self-antigens leading to increased levels of autoantibodies against nuclear components (ANAs). However, up to 20% of healthy ANA+ individuals will not develop clinical illness. SLE is more prevalent among women and minority populations (African, Asian American and Hispanics). Moreover, African Americans have a stronger interferon (IFN) signature and develop more severe symptoms. The exact mechanisms involved in ethnicity-dependent B cell dysregulation and the progression of autoimmune disease from ANA+ healthy individuals to clinical disease remains unclear. Methods: Peripheral blood mononuclear cells (PBMCs) from African (AA) and European American (EA) ANA- (n=12), ANA+ (n=12) and SLE (n=12) individuals were assessed by multimodal scRNA-Seq/CITE-Seq methods to examine differential gene signatures in specific B cell subsets. Library preparation was done with a 10X Genomics Chromium according to established protocols and sequenced on Illumina NextSeq. The data were further analyzed for distinct cluster identification and differential gene signatures in the Seurat package in R and pathways analysis was performed using Ingenuity Pathways Analysis (IPA). Results: Comparing all subjects, 14 distinct B cell clusters were identified using a community detection algorithm and visualized with Uniform Manifold Approximation Projection (UMAP). The proportion of each of those clusters varied by disease status and ethnicity. Transitional B cells trended higher in ANA+ healthy individuals, especially in AA. Ribonucleoprotein high population (HNRNPH1 elevated, heterogeneous nuclear ribonucleoprotein, RNP-Hi) of proliferating Naïve B cells were more prevalent in SLE patients, specifically in EA. Interferon-induced protein high population (IFIT-Hi) of Naive B cells are increased in EA ANA- individuals. The proportion of memory B cells and plasma cells clusters tend to be expanded in SLE patients. As anticipated, we observed a higher signature of cytokine-related pathways, especially interferon, in SLE individuals. Pathway analysis among AA individuals revealed an NRF2-mediated Oxidative Stress response signature in the transitional B cell cluster, not seen in EA individuals. TNFR1/2 and Sirtuin Signaling pathway genes were higher in AA IFIT-Hi Naive B cells, whereas they were not detected in EA individuals. Interferon signaling was observed in B cells in both ethnicities. Oxidative phosphorylation was found in age-related B cells (ABCs) for both ethnicities, whereas Death Receptor Signaling was found only in EA patients in these cells. Interferon-related transcription factors were elevated in ABCs and IFIT-Hi Naive B cells in SLE subjects of both ethnicities. Conclusions: ANA+ healthy individuals have altered gene expression pathways in B cells that might drive apoptosis and subsequent clinical autoimmune pathogenesis. Increases in certain regulatory pathways may delay progression to SLE. Further, AA individuals have more elevated activation pathways that may make them more susceptible to SLE.

Keywords:

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59 Kinematic Gait Analysis Is a Non-Invasive, More Objective and Earlier Measurement of Impairment in the Mdx Mouse Model of Duchenne Muscular Dystrophy

Authors: P. J. Sweeney, T. Ahtoniemi, J. Puoliväli, T. Laitinen, K. Lehtimäki, A. Nurmi, D. Wells

Abstract:

Duchenne muscular dystrophy (DMD) is caused by an X linked mutation in the dystrophin gene; lack of dystrophin causes a progressive muscle necrosis which leads to a progressive decrease in mobility in those suffering from the disease. The MDX mouse, a mutant mouse model which displays a frank dystrophinopathy, is currently widely employed in pre clinical efficacy models for treatments and therapies aimed at DMD. In general the end-points examined within this model have been based on invasive histopathology of muscles and serum biochemical measures like measurement of serum creatine kinase (sCK). It is established that a “critical period” between 4 and 6 weeks exists in the MDX mouse when there is extensive muscle damage that is largely sub clinical but evident with sCK measurements and histopathological staining. However, a full characterization of the MDX model remains largely incomplete especially with respect to the ability to aggravate of the muscle damage beyond the critical period. The purpose of this study was to attempt to aggravate the muscle damage in the MDX mouse and to create a wider, more readily translatable and discernible, therapeutic window for the testing of potential therapies for DMD. The study consisted of subjecting 15 male mutant MDX mice and 15 male wild-type mice to an intense chronic exercise regime that consisted of bi-weekly (two times per week) treadmill sessions over a 12 month period. Each session was 30 minutes in duration and the treadmill speed was gradually built up to 14m/min for the entire session. Baseline plasma creatine kinase (pCK), treadmill training performance and locomotor activity were measured after the “critical period” at around 10 weeks of age and again at 14 weeks of age, 6 months, 9 months and 12 months of age. In addition, kinematic gait analysis was employed using a novel analysis algorithm in order to compare changes in gait and fine motor skills in diseased exercised MDX mice compared to exercised wild type mice and non exercised MDX mice. In addition, a morphological and metabolic profile (including lipid profile), from the muscles most severely affected, the gastrocnemius muscle and the tibialis anterior muscle, was also measured at the same time intervals. Results indicate that by aggravating or exacerbating the underlying muscle damage in the MDX mouse by exercise a more pronounced and severe phenotype in comes to light and this can be picked up earlier by kinematic gait analysis. A reduction in mobility as measured by open field is not apparent at younger ages nor during the critical period, but changes in gait are apparent in the mutant MDX mice. These gait changes coincide with pronounced morphological and metabolic changes by non-invasive anatomical MRI and proton spectroscopy (1H-MRS) we have reported elsewhere. Evidence of a progressive asymmetric pathology in imaging parameters as well as in the kinematic gait analysis was found. Taken together, the data show that chronic exercise regime exacerbates the muscle damage beyond the critical period and the ability to measure through non-invasive means are important factors to consider when performing preclinical efficacy studies in the MDX mouse.

Keywords: Gait, muscular dystrophy, Kinematic analysis, neuromuscular disease

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58 Plasma Levels of Collagen Triple Helix Repeat Containing 1 (CTHRC1) as a Potential Biomarker in Interstitial Lung Disease

Authors: Rijnbout-St.James Willem, Lindner Volkhard, Scholand Mary Beth, Ashton M. Tillett, Di Gennaro Michael Jude, Smith Silvia Enrica

Abstract:

Introduction: Fibrosing lung diseases are characterized by changes in the lung interstitium and are classified based on etiology: 1) environmental/exposure-related, 2) autoimmune-related, 3) sarcoidosis, 4) interstitial pneumonia, and 4) idiopathic. Among interstitial lung diseases (ILD) idiopathic forms, idiopathic pulmonary fibrosis (IPF) is the most severe. Pathogenesis of IPF is characterized by an increased presence of proinflammatory mediators, resulting in alveolar injury, where injury to alveolar epithelium precipitates an increase in collagen deposition, subsequently thickening the alveolar septum and decreasing gas exchange. Identifying biomarkers implicated in the pathogenesis of lung fibrosis is key to developing new therapies and improving the efficacy of existing therapies. The transforming growth factor-beta (TGF-B1), a mediator of tissue repair associated with WNT5A signaling, is partially responsible for fibroblast proliferation in ILD and is the target of Pirfenidone, one of the antifibrotic therapies used for patients with IPF. Canonical TGF-B signaling is mediated by the proteins SMAD 2/3, which are, in turn, indirectly regulated by Collagen Triple Helix Repeat Containing 1 (CTHRC1). In this study, we tested the following hypotheses: 1) CTHRC1 is more elevated in the ILD cohort compared to unaffected controls, and 2) CTHRC1 is differently expressed among ILD types. Material and Methods: CTHRC1 levels were measured by ELISA in 171 plasma samples from the deidentified University of Utah ILD cohort. Data represent a cohort of 131 ILD-affected participants and 40 unaffected controls. CTHRC1 samples were categorized by a pulmonologist based on affectation status and disease subtypes: IPF (n = 45), sarcoidosis (4), nonspecific interstitial pneumonia (16), hypersensitivity pneumonitis (n = 7), interstitial pneumonia (n=13), autoimmune (n = 15), other ILD - a category that includes undifferentiated ILD diagnoses (n = 31), and unaffected controls (n = 40). We conducted a single-factor ANOVA of plasma CTHRC1 levels to test whether CTHRC1 variance among affected and non-affected participants is statistically significantly different. In-silico analysis was performed with Ingenuity Pathway Analysis® to characterize the role of CTHRC1 in the pathway of lung fibrosis. Results: Statistical analyses of CTHRC1 in plasma samples indicate that the average CTHRC1 level is significantly higher in ILD-affected participants than controls, with the autoimmune ILD being higher than other ILD types, thus supporting our hypotheses. In-silico analyses show that CTHRC1 indirectly activates and phosphorylates SMAD3, which in turn cross-regulates TGF-B1. CTHRC1 also may regulate the expression and transcription of TGFB-1 via WNT5A and its regulatory relationship with CTNNB1. Conclusion: In-silico pathway analyses demonstrate that CTHRC1 may be an important biomarker in ILD. Analysis of plasma samples indicates that CTHRC1 expression is positively associated with ILD affectation, with autoimmune ILD having the highest average CTHRC1 values. While characterizing CTHRC1 levels in plasma can help to differentiate among ILD types and predict response to Pirfenidone, the extent to which plasma CTHRC1 level is a function of ILD severity or chronicity is unknown.

Keywords: interstitial lung disease, CTHRC1, idiopathic pulmonary fibrosis, pathway analyses

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57 Systematic Review of Technology-Based Mental Health Solutions for Modelling in Low and Middle Income Countries

Authors: Mukondi Esther Nethavhakone

Abstract:

In 2020 World Health Organization announced the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), also known as Coronavirus disease 2019 (COVID-19) pandemic. To curb or contain the spread of the novel coronavirus (COVID 19), global governments implemented social distancing and lockdown regulations. Subsequently, it was no longer business as per usual, life as we knew it had changed, and so many aspects of people's lives were negatively affected, including financial and employment stability. Mainly, because companies/businesses had to put their operations on hold, some had to shut down completely, resulting in the loss of income for many people globally. Finances and employment insecurities are some of the issues that exacerbated many social issues that the world was already faced with, such as school drop-outs, teenage pregnancies, sexual assaults, gender-based violence, crime, child abuse, elderly abuse, to name a few. Expectedly the majority of the population's mental health state was threatened. This resulted in an increased number of people seeking mental healthcare services. The increasing need for mental healthcare services in Low and Middle-income countries proves to be a challenge because it is a well-known fact due to financial constraints and not well-established healthcare systems, mental healthcare provision is not as prioritised as the primary healthcare in these countries. It is against this backdrop that the researcher seeks to find viable, cost-effective, and accessible mental health solutions for low and middle-income countries amid the pressures of any pandemic. The researcher will undertake a systematic review of the technology-based mental health solutions that have been implemented/adopted by developed countries during COVID 19 lockdown and social distancing periods. This systematic review study aims to determine if low and middle-income countries can adopt the cost-effective version of digital mental health solutions for the healthcare system to adequately provide mental healthcare services during critical times such as pandemics (when there's an overwhelming diminish in mental health globally). The researcher will undertake a systematic review study through mixed methods. It will adhere to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The mixed-methods uses findings from both qualitative and quantitative studies in one review study. It will be beneficial to conduct this kind of study using mixed methods because it is a public health topic that involves social interventions and it is not purely based on medical interventions. Therefore, the meta-ethnographic (qualitative data) analysis will be crucial in understanding why and which digital methods work and for whom does it work, rather than only the meta-analysis (quantitative data) providing what digital mental health methods works. The data collection process will be extensive, involving the development of a database, table of summary of evidence/findings, and quality assessment process lastly, The researcher will ensure that ethical procedures are followed and adhered to, ensuring that sensitive data is protected and the study doesn't pose any harm to the participants.

Keywords: digital, mental health, covid, low and middle-income countries

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56 Water Monitoring Sentinel Cloud Platform: Water Monitoring Platform Based on Satellite Imagery and Modeling Data

Authors: Alberto Azevedo, Ricardo Martins, André B. Fortunato, Anabela Oliveira

Abstract:

Water is under severe threat today because of the rising population, increased agricultural and industrial needs, and the intensifying effects of climate change. Due to sea-level rise, erosion, and demographic pressure, the coastal regions are of significant concern to the scientific community. The Water Monitoring Sentinel Cloud platform (WORSICA) service is focused on providing new tools for monitoring water in coastal and inland areas, taking advantage of remote sensing, in situ and tidal modeling data. WORSICA is a service that can be used to determine the coastline, coastal inundation areas, and the limits of inland water bodies using remote sensing (satellite and Unmanned Aerial Vehicles - UAVs) and in situ data (from field surveys). It applies to various purposes, from determining flooded areas (from rainfall, storms, hurricanes, or tsunamis) to detecting large water leaks in major water distribution networks. This service was built on components developed in national and European projects, integrated to provide a one-stop-shop service for remote sensing information, integrating data from the Copernicus satellite and drone/unmanned aerial vehicles, validated by existing online in-situ data. Since WORSICA is operational using the European Open Science Cloud (EOSC) computational infrastructures, the service can be accessed via a web browser and is freely available to all European public research groups without additional costs. In addition, the private sector will be able to use the service, but some usage costs may be applied, depending on the type of computational resources needed by each application/user. Although the service has three main sub-services i) coastline detection; ii) inland water detection; iii) water leak detection in irrigation networks, in the present study, an application of the service to Óbidos lagoon in Portugal is shown, where the user can monitor the evolution of the lagoon inlet and estimate the topography of the intertidal areas without any additional costs. The service has several distinct methodologies implemented based on the computations of the water indexes (e.g., NDWI, MNDWI, AWEI, and AWEIsh) retrieved from the satellite image processing. In conjunction with the tidal data obtained from the FES model, the system can estimate a coastline with the corresponding level or even topography of the inter-tidal areas based on the Flood2Topo methodology. The outcomes of the WORSICA service can be helpful for several intervention areas such as i) emergency by providing fast access to inundated areas to support emergency rescue operations; ii) support of management decisions on hydraulic infrastructures operation to minimize damage downstream; iii) climate change mitigation by minimizing water losses and reduce water mains operation costs; iv) early detection of water leakages in difficult-to-access water irrigation networks, promoting their fast repair.

Keywords: remote sensing, coastline detection, water detection, satellite data, sentinel, Copernicus, EOSC

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55 Nanocomposite Effect Based on Silver Nanoparticles and Anemposis Californica Extract as Skin Restorer

Authors: Maria Zulema Morquecho Vega, Fabiola CarolinaMiranda Castro, Rafael Verdugo Miranda, Ignacio Yocupicio Villegas, Ana lidia Barron Raygoza, Martin enrique MArquez Cordova, Jose Alberto Duarte Moller

Abstract:

Background: Anemopsis californica, also called (tame grass) belongs to the Saururaceae family small, green plant. The blade is long and wide. Gives a white flower. The plant population is only found in humid, swampy habitats, it grows where there is water, along the banks of streams and water holes. In the winter, it dries up. The leaves, rhizomes, or roots of this plant have been used to treat a range of diseases. Some of its healing properties are used to treat wounds, cold and flu symptoms, spasmodic cough, infection, pain and inflammation, burns, swollen feet, as well as lung ailments, asthma, circulatory problems (varicose veins), rheumatoid arthritis, purifies blood, helps in urinary and digestive tract diseases, sores and healing, for headache, sore throat, diarrhea, kidney pain. The tea made from the leaves and roots is used to treat uterine cancer, womb cancer, relieves menstrual pain and stops excessive bleeding after childbirth. It is also used as a gynecological treatment for infections, hemorrhoids, candidiasis and vaginitis. Objective: To study the cytotoxicity of gels prepared with silver nanoparticles in AC extract combined with chitosan, collagen and hyaluronic acid as an alternative therapy for skin conditions. Methods: The Ag NPs were synthesized according to the following method. A 0.3 mg/mL solution is prepared in 10 ml of deionized water, adjust to pH 12 with NaOH, stirring is maintained constant magnetic and a temperature of 80 °C. Subsequently, 100 ul of a 0.1 M AgNO3 solution and kept stirring constantly for 15 min. Once the reaction is complete, measurements are performed by UV-Vis. A gel was prepared in a 5% solution of acetic acid with the respective nanoparticles and AC extract of silver in the extract of AC. Chitosan is added until the process begins to occur gel. At that time, collagen will be added in a ratio of 3 to 5 drops, and later, hyaluronic acid in 2% of the total compound formed. Finally, after resting for 24 hours, the cytotoxic effect of the gels was studied. in the presence of highly positive bacteria Staphylococcus aureus and highly negative for Escherichia coli. Cultures will be incubated for 24 hours in the presence of the compound and compared with the reference. Results: Silver nanoparticles obtained had a spherical shape and sizes among 20 and 30 nm. UV-Vis spectra confirm the presence of silver nanoparticles showing a surface plasmon around 420 nm. Finally, the test in presence of bacteria yield a good antibacterial property of this nanocompound and tests in people were successful. Conclusion: Gel prepared by biogenic synthesis shown beneficious effects in severe acne, acne vulgaris and wound healing with diabetic patients.

Keywords: anemopsis californica, nanomedicina, biotechnology, biomedicine

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