A selectivity-enhanced colloidal crystal array for ribavirin sensing based on the synergistic effect of covalent and non-covalent interactions

Ribavirin is an important antiviral with demonstrated activity against coronaviruses such as severe acute respiratory syndrome coronavirus and coronavirus disease 2019 virus. However, abuse of ribavirin will cause great environmental damage and threaten human health owing to its reproductive toxicity and teratogenicity. Therefore, an innovative detection method is demanded for simple and sensitive detection of ribavirin. This work reports an imprinted colloidal crystal array (ICCA) for ribavirin sensing. The building blocks of the ICCA are ribavirin imprinted spheres, which possess superior binding efficiency toward ribavirin. Benefiting from the highly ordered structure, the ICCA exhibits optical properties which change upon binding ribavirin. The changes in reflectance wavelength enable a fast and label-free detection of ribavirin between 21 and 245 μmol L−1. Moreover, the sensor shows excellent selectivity for ribavirin detection in river water. Overall, all the results reported in this work demonstrate that the ICCA should be a promising detection tool for antivirals. © 2023 Society of Industrial Chemistry. © 2023 Society of Industrial Chemistry.

Co-exposure to urban particulate matter and aircraft noise adversely impacts the cerebro-pulmonary-cardiovascular axis in mice

Worldwide, up to 8.8 million excess deaths/year have been attributed to air pollution, mainly due to the exposure to fine particulate matter (PM). Traffic-related noise is an additional contributor to global mortality and morbidity. Both health risk factors substantially contribute to cardiovascular, metabolic and neuropsychiatric sequelae. Studies on the combined exposure are rare and urgently needed because of frequent co-occurrence of both risk factors in urban and industrial settings. To study the synergistic effects of PM and noise, we used an exposure system equipped with aerosol generator and loud-speakers, where C57BL/6 mice were acutely exposed for 3d to either ambient PM (NIST particles) and/or noise (aircraft landing and take-off events). The combination of both stressors caused endothelial dysfunction, increased blood pressure, oxidative stress and inflammation. An additive impairment of endothelial function was observed in isolated aortic rings and even more pronounced in cerebral and retinal arterioles. The increase in oxidative stress and inflammation markers together with RNA sequencing data indicate that noise particularly affects the brain and PM particularly affects the lungs. Noise also increased levels of circulating stress hormones adrenaline and noradrenaline, while PM increased levels of circulating cytokines CD68 and MCP-1. The combination of both stressors has additive adverse effects on the cardiovascular system that are based on PM-induced systemic inflammation and noise-triggered stress hormone signaling. We demonstrate an additive upregulation of ACE-2 in the lung, suggesting that there may be an increased vulnerability to COVID-19 infection. The data warrant further mechanistic studies to characterize the propagation of primary target tissue damage (lung, brain) to remote organs such as aorta and heart by combined noise and PM exposure.Copyright © 2023

Understanding nonlinear and synergistic effects of the built environment on urban vibrancy in metro station areas

Transit-oriented development (TOD) has long been recognized as a significant model for prospering urban vibrancy. However, most studies on TOD and urban vibrancy do not consider temporal differences or the nonlinear effects involved. This study applies the gradient boosting decision tree (GBDT) model to metro station areas in Wuhan to explore the nonlinear and synergistic effects of the built-environment features on urban vibrancy during different times. The results show that (1) the effects of the built-environment features on the vibrancy around metro stations differ over time;(2) the most critical features affecting vibrancy are leisure facilities, floor area ratio, commercial facilities, and enterprises;(3) there are approximately linear or complex nonlinear relationships between the built-environment features and the vibrancy;and (4) the synergistic effects suggest that multimodal is more effective at leisure-dominated stations, high-density development is more effective at commercial-dominated stations, and mixed development is more effective at employment-oriented stations. The findings suggest improved planning recommendations for the organization of rail transport to improve the vibrancy of metro station areas.

Combination of tps and tms in a patient with post covid-19 depression

Abstract In the case of a 76 year old patient with moderate depression and anxiosomatic symptoms the treatment was initiated with TMS. After 30 sessions, anxiety improved in the subjective perception around 30% but not the depressive mood. By changing the method to TPS, after 3 sessions the mood improved significantly and after the 6th session we effectuated a nearly complete and lasting remission of depressive symptoms with additionally slightly improved anxiosomatic symtoms.This may be the first reference of potentially synergistic effects of TPS and TMS in depressed patients and also the first description of treating a non-demented depressed patient with tps. Research Category and Technology and Methods Clinical Research: 10. Transcranial Magnetic Stimulation (TMS) Keywords: TPS, TMS, depression, combinationCopyright © 2023

Air quality changes in Taiwan over the past decades and during the COVID-19 crisis

Over the past decades, Taiwan has achieved remarkable goals in air pollution reduction with the concentrations of several common air pollutants such as CO, NOx, PM10, PM2.5, and SO2 going down. In contrast to these achievements, the mitigation of O3 remains extremely tough due to the complexity of its formation process involving synergistic effects of precursor reductions and meteorological influences. During the local COVID-19 crises in Taiwan and the Level 3 alert in 2021, air pollutants directly emitted from the traffic such as CO and NOx present clear relationships with the drop of the recorded freeway traffic volume due to the alert, while PM10 and PM2.5 which are also relevant to the traffic do not show indications of being greatly influenced by the decrease of the traffic flow. Although road traffic is not regarded as a main source of SO2 by current understanding, the unusual SO2 variation patterns found in this study suggest a prolonged impact for months from the changes of travel behavior during the epidemic. In contrast, the epidemic did not exert influences on industrial SO2 concentration which accounts for a large portion of total SO2 in Taiwan, and a similar scenario is also seen in each type of O3 monitoring. Although some results discussed in this study are not in line with current consensuses and understandings in terms of the nation of certain air pollutants, these findings may disclose new perspectives which could be a potential benefit to air quality improvement projects in the future.

Towards increasing synergistic effects of resilience strategies in supply chain network design

The recent COVID-19 pandemic showed that supply chain resilience is essential for continuity of many businesses, especially retail chains. However, there are still some challenges that have received little attention in the resilient supply chain network design (RSCND) literature. While numerous resilience strategies have been proposed to make supply chain networks resilient against disruptions, very few papers have discussed why and how those resilience strategies are selected out of many potential candidates given various sources of disruption, i.e., natural, man-made, and pandemic-oriented disruptions. The aim of this paper is to propose a multi-methodological approach, based on resource dependence theory and two-stage stochastic programming, for choosing the right resilience strategies in a RSCND problem considering their positive and negative synergistic effects under resource constraints. These interactions among resilience strategies can be referred to as supply chain dynamics. We then present a novel approach for determining the most suitable combination of candidate strategies with respect to these synergistic effects. The criticality of nodes and the susceptibility of the network in different echelons are also examined via simulating the disruptive risks in hidden and unexpected places. We provide a case study from the retail industry that illustrates the potentially significant impacts of network disruptions. Via extensive stress-testing, we show the benefits of applying multiple resilience capabilities simultaneously. Our findings demonstrate the importance of considering synergistic effects among resilience strategies under budget limitations for supply chain resilience. © 2022 Elsevier Ltd

Multimedia resources in pharmacy education: A lab experience

Introduction: During the COVID-19 pandemic crisis, teachers were forced to suddenly adjust their teaching methods. The phenomenon was particularly challenging for teaching laboratory classes at a time of full lockdown. Visual memory shows the personal ability to process images and this type of memory is very important for enhancing learning and processing of information. This experience aimed to develop pedagogical strategies to help the students' learning process in a particular moment, as well as to use the methods developed to enhance future learning of pharmaceutical techniques within pharmacy education. Method(s): Multimedia resources were used to produce short videos of the preparation of laboratory assignments for pharmaceutical technology classes. In synchronous online classes, the videos were watched, commented on, the compounding preparation record was performed and at the end of the class the video was shown once again to consolidate the compounding process. In a first approach, in 2019/2020, students did not repeat the assignments in person and carried out their assessment remotely. In a blended-learning approach, with different students in 2020/2021, they had the opportunity to return to the lab to repeat the experiment protocols viewed online and perform the assessment in person. Result(s): There was no relevant difference between the grades obtained with classical face-to-face teaching (before the pandemic) and with the use of e-learning/blended-learning methodologies. However, students with online exclusive learning reported that they would have liked to repeat the assignments face-to-face in the laboratory. The blended-learning students reported that seeing the videos before the experimental work helped their memory and execution, leading to the perception that the video resources are useful. Conclusion(s): A combination method of multimedia resources to stimulate visual memory and practical execution of the activity may have a synergistic effect on learning and acquisition of practical skills.

Influence of metal oxide catalyst on co-pyrolysis of biomass and COVID-19 waste.

The disposal of waste generated by the COVID-19 pandemic is still a challenge to the government in most countries. The present study shines its light on the catalytic effect of metal oxide on converting COVID-19 waste i.e. used face masks into valuable products through co-pyrolysis. The co-pyrolysis trial was carried out for a mixture of waste face mask (WFM) and Moringa oleifera (MO) biomass at a constant temperature of 450°C for 15 min of resident time. This investigation focuses on studying the catalytic effect of calcium oxide (CaO) on the by-products of the pyrolysis process. From the FT-IR studies, it is observed that the CaO catalyst assisted to reduce oxygen as well as sulphur and carboxylic acids in the bio-oil due to its strong basic nature. The FE-SEM images suggest the increase in porous structure with catalytic pyrolysis (CP) char compared to non-catalytic pyrolysis (NCP) char. The catalytic activity of CaO increased the alcoholic content with a reduction in aldehydes and ketones in the bio-oil. The addition of WFM to the biomass with CaO catalyst pyrolysis (CP) delivered a higher oil yield of 52% compared to non-catalytic pyrolysis (NCP).

A review: The phytochemistry, pharmacology, and pharmacokinetics of Curcumae Longae Rhizoma (Turmeric)

Curcumae Longae Rhizoma (CLR) is the rhizome of Curcuma longa L. Pharmacological studies show that CLR can be used to treat cervical cancer, lung cancer, lupus nephritis, and other conditions. In this paper, we review botany, traditional application, phytochemistry, pharmacological activity, and pharmacokinetics of CLR. The literature from 1981 to date was entirely collected from online databases, such as Web of Science, Google Scholar, China Academic Journals full-text database (CNKI), Wiley, Springer, PubMed, and ScienceDirect. The data were also obtained from ancient books, theses and dissertations, and Flora Reipublicae Popularis Sinicae. There are a total of 275 compounds that have been isolated from CLR, including phenolic compounds, volatile oils, and others. The therapeutic effect of turmeric has been expanded from breaking blood and activating qi in the traditional sense to antitumor, anti-inflammatory, antioxidation, neuroprotection, antibacterial, hypolipidemic effects, and other benefits. However, the active ingredients and mechanisms of action related to relieving disease remain ill defined, which requires more in-depth research and verification at a clinical level.

Our experience of using Dexmedetomidine-Propofol sedation in patients undergoing treatment planning Magnetic resonance imaging scan for Deep brain stimulator insertion surgery during Covid 19 pandemic

Introduction: Patients undergoing Deep brain stimulator (DBS) insertion require a high-resolution MRI for treatment planning prior to DBS surgery. This group of patients has movement disorders therefore traditionally the planning MRI is done under General anaesthesia to ensure patient immobility and to obtain good quality MRI images. Providing sedation/anaesthesia for MRI procedure during COVID-19 pandemic was challenging. When we restarted elective surgery during Covid-19 pandemic we were worried about aerosol generating procedures, therefore we looked at the feasibility of using Dexmedetomidine-Propofol sedation for treatment planning MRI as an alternative to General anaesthesia to prevent aerosol generating procedure. Method(s): We conducted retrospective review of anaesthetic records of all patients who underwent MRI under sedation for DBS planning from August 2020 to July 2021. We collected the data on patient demographics, Indication & target site for DBS, duration of sedation, complications during the scan, cardiovascular side effects like hypotension and bradycardia during scan, quality of image, duration of PACU stay and post scan complications. The quality of MRI imaging was assessed by the neurosurgeon who did the treatment planning. Sedation protocol: sedation was commenced with Propofol target controlled infusion (TCI) using Schneider model with effector site concentration (Cet) of 2 to 3 and Dexmedetomidine bolus dose of 1 microgram per kilogram was infused over 10 minutes. All the patients were induced to a Ramsay Sedation Scale of at least 5 or 6. Sedation was maintained with Dexmedetomidine infusion at 0.5 mcg/kg/hr and Propofol TCI (Schneider model Cet of 2 mcg/mL). Result(s): During our study period 15 patients underwent MRI under sedation with Propofol-Dexmedetomidine for DBS treatment planning. Of this 7 were males and 8 were females. Age range was from 39 to 75 years. The target site was Subthalamic nucleus in 9 patients, Thalamic nuclei in 4 patients and Globus pallidus internus in 2 patients. Duration of sedation ranged from 40 minutes to 100 minutes with a median of 45 minutes. 2 patients developed movement artefacts during scanning and were converted to GA, 3 patients developed hypotension (20% reduction from pre-induction blood pressure) requiring treatment with ephedrine. Five patients had sinus bradycardia (20% reduction from pre-induction heart rate) but did not require treatment. The qualities of images were classified as good in 11 patients and acceptable in 2 patients by the neurosurgeon involved in treatment planning. None of the patients needed repeat MRI scanning. Patient's stay in PACU ranged from 20-50 minutes with a mean of 26.5 minutes. Discussion(s): Dexmedetomidine-Propofol sedation has been widely used for sedation to perform MRI scans in paediatric patients, its use in adult patients is not well documented in the literature. Propofol enables smooth induction of sedation and rapid recovery however it may cause hypotension, decreased respiratory drive and upper airway obstruction. Dexmedetomidine has been used as a single sedative agent for MRI however its onset of action is slow and when used as a sole sedative agent large dose of dexmedetomidine is required and this may contribute to delayed recovery after sedation. Propofol-Dexmedetomidine combination has synergistic effects and is advantageous. Propofol can induce sedation smoothly, Dexmedetomidine can reduce dose required for sedation and suppression of motor response in healthy subjects (1). Combination of Dexmedetomidine- Propofol infusion reduced total Propofol dose and decreased the incidence of airway complications in a paediatric study (2). During our study period 2 patients sedation were converted to General anaesthesia, both patients had raised BMI and had laboured breathing under sedation causing transmitted head movement, therefore patient selection is important for successful scan under sedation. Propofol-Dexmedetomidine sedation can be used safely for treatment planning MRI in selective movement disorder patients.

Multi Targeting Deep Brain Stimulation for Treatment-Resistant Depression: A 22 Month Follow up Case Report: Track 2: Brain Stimulation for Treatment Resistant Depression, Pain, and Parkinson's Disease

Introduction: According to WHO, there are more than 300,000,000 people worldwide suffering from depression. It is the world's leading cause of disability and contributes significantly to the overall global burden of disease. 30% of the patients are refractory, being possible candidates for surgical treatment by means of Deep Brain Stimulation (DBS). We present the follow up at 22 months of a patient with Treatment Refractory Depression (TRD) operated on with a new combination of targets. Materials / Methods: The diagnostic criteria used are those established by Mayberg et al: DSM IV-TR criteria for major depressive disorder with a major depressive episode of at least 1 year duration, with a minimum score of 20 on the 17-item Hamilton Depression Scale (HAM-D). Result(s): 55-year-old male. HAM-D: 26-point. It was decided to simultaneously implant Area 25 (SCG/Cg 25) and the Inferior Thalamic Peduncle (ITP) in order to contemplate the synergistic effect of stimulation of both structures. On December 5, 2018, it was successfully implanted, with previously published techniques, using a deep brain micro register system and stereotactic planning to define the coordinates of each selected target for the implantation of the four tetrapolar electrodes, model 6145 (Abbott) for Area 25 and model 6149 for ITP (Abbott). The electrode implanted in Area 25 was kept lit for 3 months, then only the corresponding to the ITP for an additional 3 months, and finally the four electrodes simultaneously maintaining the stimulation parameters reported in the literature. Post-surgical HAM-D scales were performed, with the following results: * Exclusively Area 25 (21/03/19) = 10 points * Exclusively ITP (13/06/19) = 9 points * Area 25 + ITP (08/08/19) = 14 points. * Area 25 + ITP (19/12/19) = 5 points. * Area 25 + ITP (08/10/20) = 5 points. Discussion(s): The possibility of multiple targets is technically possible and appropriate in very well selected cases. Conclusion(s): The patient showed a statistically significant improvement. Despite maintaining a rating of 5, it is worth mentioning that the patient refers feeling "better" than the previous year considering the time of year (spring), and the burden of the COVID-19 pandemic. This confirms some reports that mention the maintenance of the effect in the long term, even at 8 years, or even an improvement after almost two years can be seen. We consider that the synergism obtained by simultaneous stimulation of both targets could be more effective in terms of control of the depressive state at the long term. Supplemental Data: none. Learning Objectives: 1- To present a new therapeutic modality of multitargeting DBS for major depression. 2- To demonstrate that the combination of surgical targets is a possible option in carefully selected patients. 3- To demonstrate that the therapeutic effect is maintained over the time. Keywords: depression, deep brain stimulation, Area 25, inferior thalamic peduncle, multitargeting Copyright © 2022

PERSISTENT COVID-19 INFECTION IN A PATIENT WITH CASTLEMAN DISEASE

SESSION TITLE: Rare Pulmonary Infections SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/18/2022 01:35 pm - 02:35 pm INTRODUCTION: Castleman's Disease (CD) includes a group of rare and heterogenous lymphoproliferative disorders that share characteristic histopathological features. The etiology of CD is unknown. The condition results in episodic regional lymphadenopathy. Symptoms are driven by episodic cytokine excess. Clinical presentation can include fevers, night sweats, weight loss and fatigue. Life expectancy is not affected, however patients are at risk of developing various other conditions including amyloidosis, cryptogenic organizing pneumonia and lymphoma. COVID-19 is known to have periods of cytokine excess. In severe instances in can lead to cytokine storm, characterized by bilateral pulmonary infiltrates, worsening hypoxemia, and organ failure. We present the case of a 48 year-old female with CD who endured prolonged COVID-19 and cytokine storm. CASE PRESENTATION: A 48-year-old female with CD presented to the emergency department for shortness of breath. Six months prior to admission she had received one dose of the mRNA-1273 (Moderna) vaccine against SARS-CoV-2. Unfortunately, she contracted COVID-19 prior to the second dose. At that time she was hospitalized at a separate institution for COVID-19 and hypoxemia. The patient was treated with systemic glucocorticoids and remdesivir, and subsequently discharged home on supplemental oxygen via nasal cannula at 2 l/min. Unfortunately her respiratory status progressively declined over the following two months. During this time PCR testing for SARS-CoV-2 was positive on multiple occasions. She subsequently presented to our ER for dyspnea and hypoxemia. She once again tested positive by PCR. Inflammatory markers including fibrin degradation products, c-reactive protein and fibrinogen were severely elevated. Chest radiograph revealed bilateral infiltrates. The patient was placed on high flow oxygen and admitted to the ICU. Treatment was initiated with remdesivir, systemic glucocorticoids, and tocilizumab. Unfortunately, she continued to decline and was eventually placed on mechanical ventilation. The patient was then transferred to another institution for evaluation of extracorporeal membrane oxygenation. DISCUSSION: Both CD and COVID-19 are characterized by cytokine excess. Our patient with CD presented with persistent COVID-19. She remained symptomatic for close to six months. Her course was waxing and waning for the first few months and then progressively declined. Multiple PCR tests for SARS-CoV-2 were positive during this interval. We postulate that the proclivity of CD to cytokine excess had a synergistic effect on the inflammatory components of COVID-19 infection. This may have contributed to the protracted infection. CONCLUSIONS: More research is needed in patients with lymphoproliferative disorders and the impact of COVID-19 infection on their outcomes. Reference #1: Van Rhee, Frits, et al. "International, Evidence-Based Consensus Treatment Guidelines for Idiopathic Multicentric Castleman Disease.” American Society of Hematology, American Society of Hematology, 15 Nov. 2018, https://ashpublications.org/blood/article/132/20/2115/39506/International-evidence-based-consensus-treatment. Reference #2: "Castleman Disease: Symptoms, Causes, Treatments and Tests.” Cleveland Clinic, https://my.clevelandclinic.org/health/diseases/17920-castleman-disease. Reference #3: "Castleman Disease.” NORD (National Organization for Rare Disorders), 10 July 2017, https://rarediseases.org/rare-diseases/castlemans-disease/. DISCLOSURES: No relevant relationships by Wajahat Khan No relevant relationships by Nashwa Yosry

IN VITRO TO IN VIVO: COMBATING MULTIDRUG-RESISTANT ENTEROBACTERIACAE IN THE AGE OF COVID-19

SESSION TITLE: COVID-19 Co-Infections SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/19/2022 12:45 pm - 1:45 pm INTRODUCTION: The COVID-19 pandemic has highlighted the emergence of multidrug-resistant bacterial pathogens. Here we present a case of the successful treatment of a COVID-19 superinfection with Citrobacter freundii, which produced both a Klebsiella pneumoniae carbapenemase (KPC) as well as a New Delhi Metallo-Beta-Lactamase (NDM-1). CASE PRESENTATION: A 53-year-old male without significant past medical history was admitted to the intensive care unit for acute hypoxemic respiratory failure due to COVID-19 pneumonia. His hospital course was complicated by progressive hypoxia requiring intubation and mechanical ventilation. Due to persistent fevers and increased respiratory secretions, he was placed on empiric antibiotic therapy including vancomycin, cefepime, and briefly meropenem. Blood cultures were periodically drawn and ultimately demonstrated no growth. However, a respiratory culture via bronchoalveolar lavage was positive for multidrug-resistant Citrobacter freundii. Susceptibilities showed high level of resistance to meropenem, Imipenem, Ceftazidime-Avibactam as well as Aztreonam. Molecular testing confirmed the presence of both KPC and NDM-1 β-lactamases. The patient was treated with a combination of Aztreonam 2g plus Ceftazidime-Avibactam 2.5g IV every eight hours via simultaneous infusion for fourteen days, resulting in clinical improvement and discharge to a rehabilitation facility. DISCUSSION: The emergence of carbapenem-resistant enterobacteria has been identified as a major clinical problem. The high rates and high mortality of carbapenem-resistant enterobacteria complicating the course of COVID patients during the pandemic highlighted the importance of this issue. Among the Enterobacteriaceae, β-lactam resistance is primarily caused by enzymatic degradation by β-lactamases. Two carbapenemase subclasses are especially problematic: KPC and NDM-1. Horizontal gene transfer and clonal expansion have enabled KPC and NDM-1 to spread worldwide. However, coexistence of these two resistant mechanisms within the same pathogen has rarely been reported. Recently, high stability, non-inferior fitness, and transferability among patients of KPC-2-NDM-1-CRKPs have been documented, raising further concerns about the risk for further spread and increasing rates [1]. Therapeutic options are limited. We used a combination of Ceftazidime/Avibactam plus Aztreonam for treatment, based on limited in vitro studies demonstrating a synergistic effect and superior clearance rather than either antibiotic alone or administered in sequence [2,3]. CONCLUSIONS: Superinfections with carbapenem-resistant enterobacteria have increased in the context of the COVID-19 pandemic and are likely to become more prevalent in our hospitals. Prompt recognition and appropriate therapeutic selection are paramount for treating these highly resistant organisms. Reference #1: Gao H, Liu Y, Wang R, Wang Q, Jin L, Wang H. The transferability and evolution of NDM-1 and KPC-2 co-producing Klebsiella pneumoniae from clinical settings. EBioMedicine. 2020 Jan;51:102599. doi: 10.1016/j.ebiom.2019.102599. Epub 2020 Jan 3. PMID: 31911273;PMCID: PMC6948161. Reference #2: Marshall S, Hujer AM, Rojas LJ, Papp-Wallace KM, Humphries RM, Spellberg B, Hujer KM, Marshall EK, Rudin SD, Perez F, Wilson BM, Wasserman RB, Chikowski L, Paterson DL, Vila AJ, van Duin D, Kreiswirth BN, Chambers HF, Fowler VG Jr, Jacobs MR, Pulse ME, Weiss WJ, Bonomo RA. Can Ceftazidime-Avibactam and Aztreonam Overcome β-Lactam Resistance Conferred by Metallo-β-Lactamases in Enterobacteriaceae? Antimicrob Agents Chemother. 2017 Mar 24;61(4):e02243-16. doi: 10.1128/AAC.02243-16. PMID: 28167541;PMCID: PMC5365724. Reference #3: Lodise TP, Smith NM, O'Donnell N, et al. Determining the optimal dosing of a novel combination regimen of ceftazidime/avibactam with aztreonam against NDM-1-producing Enterobacteriaceae using a hollow-fibre infection model. J Antimicrob Chemother 202 ;75(9): 2622-32 DISCLOSURES: No relevant relationships by wisam daoud No relevant relationships by Christopher Walker No relevant relationships by Amanda Westbrook No relevant relationships by Nicola Zetola

A PATIENT WITH COVID-19 PNEUMONIA, PULMONARY EMBOLISM, AND OSA

SESSION TITLE: Global Case Reports in Critical Care SESSION TYPE: Global Case Reports PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: Thrombotic complications in patients diagnosed with COVID-19 pneumonia are emerging as an important and significant morbidity and mortality burden, with overwhelming inflammation, hypoxia, immobilization, and diffuse intravascular coagulation among possible causes of a procoagulant state (1). Obstructive sleep apnea (OSA), with intermittent arterial oxygen desaturation, may in its turn contribute to a procoagulant state, causing hemodynamic alterations as polycythemia and sluggish blood flow (2). Here we report on a case of sudden and massive non-lethal pulmonary thromboembolism (PTE) in a patient with COVID-19 severe pneumonia, for whom OSA was suspected and documented as a possible concurrent mechanism of thromboembolic complication during follow-up. CASE PRESENTATION: A 55-year-old male non-smoker obese (BMI 33 Kg/m2) was admitted to our hospital after 9 days of fever. In the Emergency Room, a chest HRCT scan showed bilateral diffuse ground glass opacities. He was treated with subcutaneous Tocilizumab (324 mg) single shot, Remdesivir (200 mg/day for first day and 100/daily for further 4 days), methyl-prednisolone 40 mg/daily, Enoxaparin 6000 UI/twice daily, azithromycin 500 mg/daily, high flow nasal cannula oxygen (50 L/min, TC 34°C, FiO2 35%) for moderate acute respiratory failure due to COVID-19 pneumonia (pO2: 58 mmHg, PCO2 34 mmHg pH 7.50, P/F 275). After 10 days, patient's clinical conditions worsened, needing non-invasive respiratory support;D-dimer increased abruptly, rising to 10 ng/mL, with findings consistent with PTE at a computed tomographic angiography (CTA, Fig 1). The patient was successfully treated with 10 mg/daily subcutaneous fondaparinux for 12 days, while assisted in the Intensive Care Unit, being discharged home in room air shortly later with oral anticoagulants. At the 3-month follow-up visit, OSA was suspected due to reported excessive daytime sleepiness and weakness, snoring, disturbed night sleep, morning headache in the last 4 years. The patient underwent a home sleep apnea test (HSAT) overnight. Test results revealed an AHI of 50 events/h, with several prolonged episodes of obstructive sleep apnea (307 apnea and hypopnea (A+H) events, 70 obstructive apnea and 233 hypopnea events, with a mean duration of 10% and an average arterial saturation of 93% (Fig. 2). He was adapted to CPAP therapy, with benefit and good correction of polygraphic indexes. DISCUSSION: The pathogenetic mechanisms of COVID 19 and OSA could have played a synergistic effect on endothelial damage, thus increasing the risk of thromboembolism. CONCLUSIONS: The presence of underdiagnosed comorbidities may well worsen the clinical course and complication of COVID-19;an earlier diagnosis of OSA is a prerequisite for timely treatment and, potentially, improved long-term clinical outcomes. Reference #1: Suh YJ, et al. Pulmonary embolism and deep vein thrombosis in COVID 19: a systematic review and meta-analysis. Radiology 2021;298 (2): E70-E80. Reference #2: Alfonso-Fernandez A., Garcia Surquia A., de la Pena M. OSA is a risk factor for recurrent VTE Chest. 2016;150 (6): 1291-1301. DISCLOSURES: no disclosure on file for Antonietta Esposito;no disclosure on file for Antonella Frattari;no disclosure on file for Giustino Parruti;no disclosure on file for Giorgia Patrizio;no disclosure on file for Pierpaolo Prosperi;no disclosure on file for Giorgia Rapacchiale;No relevant relationships by ANTONELLA SPACONE no disclosure on file for Giacomo Zuccarini;

Formulation And Evaluation Of Ayurvedic Immuno Booster Rasayan Kwath

Objective: In the wake of covid19 outbreak, all mankind of entire world if suffering. As we all know prevention is better than cure. Hence, to take care of diet and nutrients can help in building a strong immune system. When an immune system response is low, weak or damage it become an open invitation for infections. The present study was aimed for preparation of immunity booster as a Kwath or Kadha using natural ingredients by decoction process and also evaluation of the formulation. Method: The present study was conducted in Department of Pharmacy, Hygia Institute of Pharmacy, Lucknow. The preparation obtained by boiling the drugs with water called Kwath (Decoction). The method of Kwath preparation is very much similar to the decoction method of extraction from herbs. It is water soluble and heat stable constituents of crude drugs by boiling in water for 15 min, cooling, straining, and passing sufficient cold water through the drugs to produce the required volume. Result: This preliminary in-vitro study demonstrated that immunity boosting Rasayan Kwath was effective against pathogenic bacteria. From the result we can say that the Rasayan Kwath is good in appearance, stable and acceptable. Kwath has been designed by ancient scholars aimed at the synergistic action of the herbs to cure infections and boosting up immune system. This project based Kwath or kadha works as antioxidant, antipyretic seem to be effective in regulating immunity for the prevention and reduction of viral disease complications. This herbal preparations suggested quantity improve the immunity level naturally with speedy recovery in COVID-19 cases as well as in healthy persons and suspected cases it minimizes the chance of infections. Conclusion: On the basis of the results we can further conclude that the present formulation may be effective against various respiratory pathogenic microbes like available formulation in the market. No doubt further research like toxicity study and supporting preclinical trials for immunity boosting required to claiming present work in the market. But in research in this field use, this work as a primary step in this direction.

Selection and Utilization of Multiple Teaching Tools in Blended Classrooms from the Perspective of Synergistic Effect

Teaching tools are playing an increasingly important role in modern education, especially in this post-pandemic era, the outbreak of Covid-19 pandemic and the social distancing policy have brought fundamental changes to the education mode in China. Fully and rationally making use of multiple teaching tools in blended classrooms is helpful in realizing teaching goals, moreover, it can increase students’ interest in learning and activate classroom atmosphere. However, current studies on the teaching tools of blended classrooms fail to well exhibit teaching content in the classrooms, the existing tools only have limited functions, and such classrooms couldn’t effectively train students’ abilities to communicate or make self-evaluations. In view of these problems, this paper aims to study the selection and utilization of multiple teaching tools in blended classrooms from the perspective of synergistic effect. At first, this paper built an Evaluation Index System (EIS) for assessing the degree of synergy of multiple teaching tools when they are used in blended classrooms;then, it calculated the degree of order of these tools in the said classrooms;at last, this paper analyzed the effectiveness of the synergistic effect of different teaching tools. © 2022. International Journal of Emerging Technologies in Learning.All Rights Reserved

Computational screening for investigating the synergistic regulatory potential of drugs and phytochemicals in combination with 2-deoxy-D-glucose against SARS-CoV-2.

COVID-19 disease caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) was declared a global pandemic by the World Health Organization (WHO) in March 2020. Since then, the SARS-CoV-2 virus has impacted millions of lives worldwide. Various preclinical and clinical trials on the treatment of COVID-19 disease have revealed that the drugs that work in combination are more likely to reduce reinfection and multi-organ failure. Considering the combination drug therapy, herein, we performed a systematic computational study starting with the formation of sixty-two combinations of drugs and phytochemicals with 2-deoxy-D-glucose (2-DG). The top nineteen combinations resulting from Drug-Drug Interaction (DDI) analysis were selected for individual and multiple-ligand-simultaneous docking (MLSD) study with a host target Serine Protease (TMPRSS2; PDB ID: 7MEQ) and two viral targets, Main Protease (3CLpro; PDB ID: 6LU7) and Uridylate-Specific Endoribonuclease (NSP15; PDB ID: 6VWW). We found that the resulting drugs and phytochemicals in combination with 2-DG shows better binding than the individual compounds. We performed the re-docking of the top three drug combinations by utilizing the polypharmacology approach to validate the binding patterns of drug combinations with multiple targets for verifying the best drug combinatorial output obtained by blind docking. A strong binding affinity pattern was observed for 2-DG + Ruxolitinib (NIH-recommended drug), 2-DG + Telmisartan (phase 4 clinical trial drug), and 2-DG + Punicalagin (phytochemical) for all the selected targets. Additionally, we conducted multiple-ligand-simultaneous molecular dynamics (MLS-MD) simulations on the selected targets with the 2-DG + Ruxolitinib combination. The MLS-MD analysis of the drug combinations shows that stabilization of the interaction complexes could have significant inhibition potential against SARS CoV-2. This study provides an insight into developing drug combinations utilizing integrated computational approaches to uncover their potential in synergistic drug therapy. Supplementary Information: The online version contains supplementary material available at 10.1007/s11224-022-02049-0.

In-vivo reprogramming macrophages and dendritic cells with Allocetra-OTS: Successful mono- and combination-antitumor therapy

Background: Chimeric antigen receptor (CAR) T cells can activate an immune response to a cancer-specific antigen but is less effective in solid tumors. Immune check point inhibitors (ICI) revolutionized the treatment of solid tumors, however, in many tumors only partial response is achieved. Here we questioned the role of synergistic effect of Allocetra-OTS (cellular therapy for in-vivo reprogramming macrophages and dendritic cells, Enlivex Therap.) on solid tumor progression. Methods: To follow tumor growth in vivo, HeLa-CD19 cells were stably transduced with pLenti-PGK-V5-Luc-Neo. For CAR preparation, fresh mononuclear cells (MNC) were transfected with CD19-CAR plasmids. For the intraperitoneal solid tumor model, SCID-Bg mice were injected intraperitoneally (IP) with human HeLa- CD19 or HeLa-CD19-luciferase cells, 10×106 allocetra-OTS or vehicle, and 10×106 CD19-CAR T cells or mock T cells. In an immune-competent model, Balb/c mice were treated IP with AB12 (mesothelioma) with pLenti-PGK-V5-Luc-Neo and treated with anti-CTLA4 with or without Allocetra-OTS. Mice were monitored daily for clinical signs and peritoneal fluid accumulation and weekly for tumor growth. Kaplan-Meier log rank test was done for survival. Peritoneal cells were evaluated using single cell analysis and flow cytometry. Tumors were examined for bacterial presence by immunohistochemistry staining with antilipoteichoic acid (LTA) and antilipopolysaccharide (LPS). For allocetra-OTS preparation, enriched mononuclear fractions were collected by leukapheresis from healthy eligible human donors and induced to undergo early apoptosis. Results: SCID mice survived 30±5 days (range 27-37) and were sacrificed or died from solid tumor in the peritoneal cavity after accumulation of bloody peritoneal fluid and clinical deterioration. Results were verified using IVIS of intraperitoneal HeLaCD19- Luc cells. CAR T cell therapy significantly ameliorated survival to 55±11 days (p < 0.05 vs MOCK) but Alloctra-OTS further ameliorated survival to 75±10 (p < 0.001) with 20-40% complete remission. In AB12 model, anti CTLA4 therapy significantly ameliorated survival from 26±5 to 38 ±9 days (p < 0.05). However, Allocetra-OTS monotherapy ameliorated survival to 45 ±12 days (p < 0.02) and combinational therapy to 75±9 days (p < 0.0001) with complete remission in 60-75% of mice. Single cell analysis revealed that restoration of large peritoneal macrophages (LPM), were associated with antitumor activity. Conclusions: During intraperitoneal tumor progression, allocetra-OTS as monotherapy or combinational therapy with CAR or anti-CTLA4 significantly reduced tumor size and enable complete remission in up to 75% treated mice. Based on excellent safety profile in > 30 patients treated for sepsis and Covid19, human phase I/II of allocetra-OTS plus ICI, for peritoneal metastases, is planned for 2022.

Synergistic effect and kinetic analysis of catalytic co-pyrolysis of waste cotton swabs and non-woven masks

In the context of the COVID-19, the co-pyrolysis of waste cotton swabs and non-woven masks is a promising way of biomass utilization. On the one hand, it alleviates the energy crisis to some extent, and on the other hand, it is conducive to the proper disposal of medical waste. In this paper, the pyrolysis process and kinetic behavior of two materials under different conditions including mixing ratios, heating rates and catalyst additions were studied. The results show that the heating rate has little effect on the pyrolysis process. Mask has better pyrolysis performance than cotton swabs and could promote the decomposition of biomass as an auxiliary material. All the blends show a certain synergistic effect. The difference between the actual mass loss and the theoretical mass loss (ΔW) is positive and the activation energy is lower than that of any single component. The addition of catalyst can further promote the pyrolysis reaction, and the residual mass is greatly reduced. This paper aims to provide some suggestions for further exploration in related fields.

IT'S ALWAYS COCAINE: A RARE CASE OF LEVAMISOLEINDUCED COCAINE ASSOCIATED VASCULITIS WITH PULMONARY AND RENAL INVOLVEMENT

CASE: 58 year old woman presents with 1 month of dyspnea and productive cough. She also reported loss of smell and hematuria for 1 week. History was notable for hypertension, COPD, substance abuse, specifically crack cocaine, and unstable housing. On admission she was tachypneic and hypoxic, requiring supplemental O2. Exam revealed bilateral crackles, elevated JVP, and mild lower extremity edema, but no skin changes or rashes. Laboratory studies showed an elevated creatine of 7.9. CT chest imaging showed extensive bilateral ground glass opacities with increased septal lines. Infectious work-up, including SARSCoV-2 PCR, was negative. Dialysis was initiated for new renal failure. To determine the etiology of the renal failure, autoimmune studies were obtained and showed a positive ANA and p-ANCA (1:640) and a negative MPO and PR3. Kidney biopsy was consistent with levamisole-induced vasculitis (LIV) from cocaine use. Treatment with steroids was initiated. She was discharged on steroid therapy and outpatient hemodialysis. She had repeated admissions for volume overload due to missed dialysis, and she developed heart failure within the year. She was unable to make appointments to start outpatient rituximab therapy. IMPACT/DISCUSSION: Levamisole-induced vasculitis (LIV) is a complication of use of cocaine adulterated with levamisole. Levamisole is an antihelminthic medication with well known immunomodulatory effects. Increasingly used as a cocaine adulterant, it is believed to be a component of over 80% of cocaine samples in the US. Its use is thought to be driven by levamisole's synergistic effect on the dopaminergic effects of cocaine. Levamisole-induced vasculitis is a p-ANCA associated vasculitis associated with long-term use of cocaine mixed with levamisole. It has been reported with both inhaled cocaine and smoking crack cocaine. Levamisole is thought to induce production of autoantibodies including p-ANCA, ANA, and lupus anticoagulant leading to immune complex deposition and secondary hypercoagulability. The most commonly reported presentation is cutaneous purpuric lesions, most notably the ear, tip of the nose, and malar eminence. LIV can occur without skin involvement and renal and pulmonary involvement including nephritis, renal failure, and hypersensitivity pneumonitis, has been reported. LIV with significant organ involvement is often treated with steroids. Additional immunosuppressive therapies including rituximab, cyclophosphamide, and plasmapheresis have been reported in severe cases. CONCLUSION: This case illustrates a rare presentation of LIV marked by with renal failure and absence of skin lesions. While the health effects of cocaine are well known, the adverse effects of agents used to cut cocaine are less readily considered. LIV should be considered in a patient with substance use disorder presenting with new vasculitis. As this case illustrates, factors like unstable housing and ongoing substance use disorder can complicate management.