Planning for a potential paediatric bronchiolitis surge: How Inter-Professional Education (IPE) was used to build a practice-ready clinical team

Introduction: Bronchiolitis is the most common cause for paediatric respiratory hospital admissions in young children in the UK.1 Following the relaxation of international SARS-Cov-2 lockdown measures a potential national surge in cases was predicted, highlighting a need for more collaborative working across core specialities.2 This prompted the use of the principles of Inter-Professional Education (IPE) to prepare and deliver an intervention to improve outcomes for these patients.3 Objectives: * To plan, deliver and evaluate an educational intervention focussed on improving the knowledge, skills and attitudes needed to care for a sick child with bronchiolitis * To utilise the principles of IPE to improve competence and confidence across core specialities involved in the care of a sick child with bronchiolitis Methods: A team from the Adult Intensive Care Unit (AICU) and the Paediatric High Dependency Unit (PHDU) from the Royal Berkshire Hospital in Reading delivered an inter-professional teaching session focussed on caring for the sick child with bronchiolitis. The patient journey was utilised as a framework to teach the core knowledge, skills and attitudes needed to clinically manage a child from the Emergency Department (ED) to the Intensive Care Unit (ICU). Each session included a lecture about bronchiolitis - describing pathophysiology and how to recognise the deteriorating child;a skills and drills tutorial - highlighting the need for weight-based calculations for high flow nasal oxygen, intravenous fluids and drugs;and a practical simulation scenario - focussing on the stabilisation and management of a sick child awaiting retrieval to the Paediatric Intensive Care Unit (PICU). Result(s): 135 healthcare professionals from a range of adult and paediatric disciplines involved in the care of children across the patient journey attended one of fourteen teaching sessions delivered between September to December 2021. Attendees completed a feedback questionnaire. One hundred and twenty-two (90%) reported an extremely high degree of satisfaction overall, with many saying they would recommend the teaching sessions to others. Areas of personal and professional development were highlighted across the following main themes: gaining theoretical knowledge;understanding key equipment;performing drug calculations;preparing for intubation and ventilation;assessing the need for chest physiotherapy techniques;and more collaborative team-working. Free text comments demonstrated that the attendees felt the teaching sessions: built confidence through the sharing of new or improved knowledge and skills;facilitated a safe space to practice using simulation;and provided the opportunity to learn about and from each other. Many of the attendees also commented on areas they wanted to reinforce and further develop in daily clinical practice as a direct result of the sessions. Conclusion(s): On-going evaluation is taking place as the teaching sessions continue throughout the year, facilitating the inclusion of additional inter-professional groups from across core specialities. These sessions have been used as a template for the development of further planned IPE with a more varied range of paediatric clinical cases and presentations. These will continue to build on the transferable knowledge and skills that increase competence and confidence in caring for the sick child whilst developing a more collaborative practice-ready workforce.

Gene Editing/Gene Therapies: BIOREACTOR RECOMBINANT PRODUCTION OF SARS-COV-2 VIRUS ANTIGENS IN CHO CELL CLONES BY USING NEW UCOE LENTIVIRAL VECTOR SYSTEM

Background & Aim: The new UCOE models we have recently developed, tested on many cell groups (including mouse ES and human iPS cells) and human mAb recombinant production studies as well, shows a powerful resistance to DNA methylation- mediated silencing and provides a higher and stable transfection profile. By the urgent need of vaccine development for COVID-19 during the pandemic, in this study we aimed to produce a potential recombinant vaccine by using the new generation UCOEs models of our own design. Methods, Results & Conclusion(s): Existing new-generation UCOE models and standard plasmid vectors to be used as control group were provided. Then, the sequences related to the PCR method were amplified for sufficient stock generation and cloning experiments. Verification in the plasmid vector was carried out in gel electrophoresis. Transfection of 293T cells was performed with clone plasmids carrying antigen genes and plasmids carrying genetic information of lentivirus units for the production of lentiviral vectors. Afterwards, 293T cells produced lentiviral vectors carrying antigen genes. Harvesting of these vectors was carried out during 48th and 72nd hours. Afterwards, CHO cells were transduced with appropriate quantity of lentiviral vectors. Isolation and purification of targeted proteins from the relevant medium were performed by HPLC and Q-TOF methods. A part of the spike and nucleocapsid gene sequences of COVID-19 were firstly cloned into our UCOE models. These UCOEs plasmids were then transferred into 293T cells along with plasmids carrying the genes that will form the lentivirus vectors (LVs). After harvesting and calculation of LV vector titers, the cloned vectors were then transfected into the CHO cells which the targeted recombinant production of the antigen proteins will be carried out. Antigenic structures were then isolated from the culture medium of CHO cells in following days for confirmation. Using HPLC and qTOF mass spectrometer methods, these structures in the medium were confirmed to be the units of spike and nucleocapsid proteins of the COVID-19 virus. In order to produce large amount of the recombinant antigens, the culture was then carried out with bioreactors in liters. At the final stage, these recombinantly produced antigen proteins were tested on rats to measure their immunogenic responses, and the study recently been completed successfully as a potential recombinant vaccine against COVID-19.Copyright © 2023 International Society for Cell & Gene Therapy

Progress towards ending HIV transmission in England by 2030

Background: England is committed to ending HIV transmission by 2030. The HIV Action Plan (2021) set an interim ambition to reduce HIV transmission by 80% to 600 new diagnoses first made in England by 2025. Here we present the progress between 2019 (baseline) and 2021, interpreted in the context of the COVID-19 pandemic. Method(s): People newly diagnosed with HIV were reported to the HIV and AIDS Reporting Section (HARS). The annual number of people having an HIV test in all sexual health services (SHS) including online testing were reported using GUMCAD. HIV diagnoses among people previously diagnosed abroad were excluded (25%). Result(s): New HIV diagnoses first made in England fell by 32% from 2,986 in 2019 to 1,987 in 2020, but plateaued in 2021 (2,023). Among gay/bisexual men, HIV diagnoses plateaued in 2021 (721) after a fall of 45% between 2019 and 2020, from 1,262 to 699. After a fall in HIV testing in 2020 (from 156,631 in 2019 to 144,800 in 2020), the number of people tested in 2021 (178,466) exceeded pre-COVID-19 levels. This suggests a decline in HIV incidence supported by a CD4 back calculation model (80% probability of a decline for the period 2019-2021), but at a slowing rate. Among heterosexual adults, new HIV diagnoses first made in England in 2021 also plateaued (798) following a 31% decrease (from 1,109 in 2019 to 761 in 2020). However, HIV testing coverage has not recovered to pre- COVID-19 levels (628,607 in 2019, 441,017 in 2020 and 489,727 in 2021). This provides no evidence of a fall in incidence in this population. Conclusion(s): A reduction by 360 new diagnoses first made in England year on year from 2022 onwards is required to meet the HIV Action Plan ambition. Despite an estimated 4,500 people with undiagnosed HIV and extremely high levels of antiretroviral therapy and viral suppression, PrEP access remains unequal. HIV testing numbers, which were affected by COVID-19 pandemic, have recovered in gay/bisexual men, but not among heterosexual adults. While the interim ambition is within reach for gay/bisexual men, PrEP and testing levels must be scaled up in heterosexual adults.

Traffic Flow Forecasting in the COVID-19: A Deep Spatial-temporal Model Based on DiscreteWavelet Transformation

Traffic flowprediction has always been the focus of research in the field of Intelligent Transportation Systems, which is conducive to the more reasonable allocation of basic transportation resources and formulation of transportation policies. The spread of COVID-19 has seriously affected the normal order in the transportation sector. With the increase in the number of infected people and the government's anti-epidemic policy, human outgoing activities have gradually decreased, resulting in increasingly obvious discreteness and irregularities in traffic flow data. This article proposes a deep-space time traffic flow prediction model based on discrete wavelet transform (DSTM-DWT) to overcome the highly discrete and irregular nature of the new crown epidemic. First, DSTM-DWT decomposes traffic flow into discrete attributes, such as flow trend, discrete amplitude, and discrete baseline. Second, we design the spatial relationship of the transportation network as a graph and integrate the new crown pneumonia epidemic data into the characteristics of each transportation node. Then, we use the graph convolutional network to calculate the spatial correlation of each node, and the temporal convolutional network to calculate the temporal correlation of the data. In order to solve the problem of high discreteness of traffic flow data during the epidemic, this article proposes a graph memory network (GMN), which is used to convert discrete magnitudes separated by discrete wavelet transform into highdimensional discrete features. Finally, use DWT to segment the predicted traffic data, and then perform the inverse discrete wavelet transform between the newly segmented traffic trend and discrete baseline and the discrete model predicted by GMN to obtain the final traffic flow prediction result. In simulation experiments, this work was compared with the existing advanced baselines to verify the superiority of DSTM-DWT.

Sizing Horizontal Geothermal Heat Exchangers for Community Greenhouses in Montreal

Community greenhouses are important for the production of local food and reduction of food supply insecurities within cities. As we've seen with Covid-19, pandemics highlight the criticality of local food access to underprivileged urban districts. Since almost 60 % of the energy used in greenhouses is spent in heating and cooling, ground heat exchangers (GHEs) can play a significant role in supplying temperature regulation, but geothermal heat pump systems tend to be expensive for community organizations. An efficient way to reduce GHEs installation costs is to dig trenches to install the system horizontally and cover a part of heating and cooling loads only. In order to ensure cost effectiveness and optimize operations, this type of system was studied for urban greenhouses where ground space can be limited. Sizing calculations were performed for GHEs of a 7.62 m x 15.24 m greenhouse located on the Island of Montreal where the annual, monthly, and hourly energy consumption were estimated from previous building simulations. Three scenarios were used to specify sizing of the system in terms of excavation dimensions and percentage of the greenhouse peak loads covered;(1) number and length of trenches required for a horizontal GHE (HGHE) covering 100% of cooling and heating loads;(2) number and length of trenches required for an HGHE to cover 100% of peak heating loads and 60% of peak cooling loads and;(3) the percentage of heating and cooling peak loads that can be covered by an HGHE located under the greenhouse with similar dimensions (around 116 m2). Estimated excavation dimensions for cases 1 and 2 are 51.8 m x 8 m (414.4 m2) and 40.8 m x 8 m (326.4 m2). Estimated percentage of peak loads covered for case 3 is 40% of heating peak loads and 30% of cooling peak loads. © 2022 Geothermal Resources Council. All rights reserved.

Using Novel Remote Electronic Monitoring to Measure and Manage the Rheumatology Clinic Backlog Generated by Covid-19

Background/Aims During the COVID-19 pandemic we were unable to provide regular outpatient services for patients with chronic rheumatic diseases. A ''backlog'' of 6812 patients without an allocated follow-up appointment accrued by September 2021. We quantified this cohort and analysed attempts to deliver care remotely (using video, telephone, and electronic remote management forms (RMFs)). Methods We selected a 12-month ''window'' (May 2020-May 2021) and analysed the number of patients awaiting follow-up during this period. This was initially 3259 patients out of the total backlog 6812. We revisited the number of patients remaining in that cohort on four occasions between September 2021 and September 2022: at baseline, then at 1-, 2-, 6- and 12-month intervals. Each audit cycle was conducted using the same methodology. Alongside usual follow up pathways, (face to face, video or telephone), we implemented remote management forms (RMFs) for different disease groups which were designed by the department;they contained a triage questionnaire, including calculation of disease severity scores, and questions about medications. These were sent out by clinicians to some patients in lieu of a telephone, video or face to face appointments. Data from RMFs was stored in a secure database for clinician review. Data analysis performed in Microsoft Excel and R (version 4.2.1). Results The number of patients without allocated follow-up appointments reduced from 3259 to 326 between Sep-21 and Sep-22. This is a 90% reduction in the backlog over a 12-month period, with a 71% reduction achieved by 6 months. There was a significant, progressive reduction in the number of patients over time (p<0.001 - Chi-square test for trend). Of the 1956 RMFs completed between Sep-21 - Mar-22, only 261 patients recorded a previous appointment date. 154/261 (59%) were completed by patients waiting in the ''window'' of May-20 - May- 21. This indicates a preferential use of RMFs targeting backlog patients. Between 2-8% of the total backlog patients were managed using RMFs based on available data. Conclusion We have significantly reduced the size of our backlog of outpatient follow-up due to COVID-19 over a 12-month period. In-addition these results likely underestimate the effect of RMFs due to this dataset being incomplete. Remote management made a sizeable contribution to this reduction, meaning some of this reduction was achieved without face-to-face encounters. The use of 1956 forms over a 6- month period shows robust integration of our RMFs into outpatient services disrupted by COVID-19 and provides evidence for remote management as a useful tool in outpatient management, with relevance to areas such as Patient Initiated Follow Up pathways. Further work is needed to clarify where remote management is best deployed and which patient groups benefit most from this.

COVID-19 airborne transmission risk calculation using CO2 concentrations in a 3D office environment

The ongoing COVID-19 pandemic has caused millions of deaths worldwide along with detrimental socioeconomic consequences. Existing evidence suggests that the rate of indoor transmission is directly linked with the Indoor Air Quality (IAQ) conditions. Most of the existing methodologies for virus transmissibility risk estimation are based on the well-known Wells-Riley equation and assume well-mixed, uniform conditions;so spatiotemporal variations within the indoor space are not captured. In this work, a novel fine-grained methodology for real-time virus transmission risk estimation is developed using a 3D model of a real office room with 31 occupants. CONTAM-CFD0 software is used to compute the airflow vectors and the resulting 3D CO2 concentration map (attributed to the exhalations from the occupants). Simulation results are also provided that demonstrate the efficacy of using CO2 sensors for estimating the infection risk in real-time in the 3D office environment. © 2022 17th International Conference on Indoor Air Quality and Climate, INDOOR AIR 2022. All rights reserved.

Basic monitoring mechanical ventilation in patients with COVID-19, rethinking what we know

During the COVID-19 pandemic, 15% of hospitalized patients have required mechanical ventilation and because the reorganization of health services at COVID-19 centers, a large percentage of health personnel have assumed new functions in the care of the critical patient;situation that makes evident the need to analyze the different techniques, maneuvers and calculations for an adequate assessment and decision-making. A bibliographic review of the topic was made searching for references in Elsevier, Pubmed, SciELO, Medline, Nature, New England Journal of Medicine using the words mechanical ventilation, COVID-19, acute respiratory distress syndrome, lung protection strategy, airway pressures, pulmonary mechanics, published from 2010 to 201 9 in English and Spanish. During the COVID-1 9 pandemic, mechanical ventilation has been a fundamental procedure in the management of severe acute respiratory distress syndrome, becoming indispensable that health personnel who work in COVID-1 9 areas know and understand the different techniques, maneuvers and calculations used to determine the state of the respiratory system in the ventilated patient and apply treatments accordingly.Copyright © 2022 Comunicaciones Cientificas Mexicanas S.A. de C.V.. All rights reserved.

Insights Into the Selective Imprinted Polymer of Voriconazole from Host-Guest Interaction Perspective

The incidence of fungal coinfections, such as Aspergillus spp., in patients with COVID-19 has been widely reported. Voriconazole is the first-line treatment for aspergillosis. A challenging sample preparation process is required to perform therapeutic drug monitoring of voriconazole. Recently, Molecularly Imprinted Polymers (MIP) have been shown to improve the separation selectivity for biological samples. Monomer selection in MIP is often performed by trial and error, without a design strategy. Therefore, this study aimed to construct a high-affinity MIP for voriconazole based on its interaction with functional monomers. All structures were optimized with B3LYP/6-311G++(d,p) and DFT-D3 dispersion correction method. Calculations of vacuum and solvated frequencies were carried out using a structure with maximum binding energy from molecular docking. The results showed that complex five was the most stable, exothermic, spontaneous, and enthalpy-driven among the complexes. In addition, there are nine intermolecular interactions and one moderate hydrogen bond in the QTAIM and NBO analysis, whereas hydrogen bonds, van der Waals interactions, and hydrophobic interactions were observed in the NCI-RDG analysis. The findings of this preliminary investigation showed that voriconazole possesses high stability when combined with functional monomers. It also provides information and assistance for further laboratory MIP synthesis.

Examining the Association of Air Quality on Covid-19 Patient Outcomes Using Area Level Data from the Electronic Health Record

Background: Within the coronavirus 2019 (COVID-19) pandemic, literature has found worsened patient outcomes and increased virus transmissibility associated with reduced air quality. This factor, a structural social determinant of health (SDOH), has shown great promise as a link between air quality and patient outcomes during the COVID-19 pandemic. Researching SDOH within our patient populations is often difficult and limited by poor documentation or extensive questionnaires or surveys. The use of demographic data derived from the electronic health record (EHR) to more accurately represent SDOH holds great promise. The use of area-level determinants of health outcomes has been shown to serve as a good surrogate for individual exposures. We posit that an area level measure of air quality, the county-level Air Quality Index (AQI), will be associated with disease worsening in intensive care unit (ICU) patients being treated for COVID-19. Method(s): We will calculate AQI using a combination of open-source records available via the United States Environmental Protection Agency (EPA) and manual calculations using geospatial informatics systems (GIS) methods. Subjects will be identified as adult (> 18 years) patients admitted to Vanderbilt University Medical Center's ICUs between January 1, 2020, and March 31, 2022 with a positive SARS-CoV-2 laboratory analysis result. We will exclude patients without a home address listed. Patient demographic and hospital data from ICU admission to 28 days following admission will include: age, sex, home address, race, insurance type, primary language, employment status, highest level of education, and hospital course data. Together these will be collated to produce our primary outcome variable of WHO Clinical Progression Scale score. These validated scores range from 0 (uninfected) to 10 (dead) to track clinically meaningful progression of COVID-19 infected patients. Our AQI variable will be obtained from the EPA available county-level monitoring station spatial data combined with open-source state/county center point spatial data. These data contain historic cataloguing to determine air quality at both specific time points and averages over time. Where a county's average yearly AQI is not available due to lack of a monitoring station, we will use spatial data tools to calculate an average based on data from nearby stations. We will utilize yearly averages of AQI in the year prior to COVID-19 diagnosis to describe overall impact of air quality on patients' respiratory outcomes as opposed to single day exposures. Linkage of patient data to AQI database will be performed using patient addresses. Discussion(s): By combining area level data with electronic health record (EHR) data, we will be positioned to understand the contribution of environmental and social determinants of health on patient outcomes. Our long-term goal is to elucidate which social and environmental determinants of health are associated with worse outcomes from COVID-19 and other respiratory viruses, using data extracted from the EHR.

Evaluating the Use of Patient Reported Outcome Measures to Assess Intra-Pandemic Psoriatic Arthritis Disease Activity and Comparing Them with Pre-Pandemic Clinical Assessments

Background/Aims In our department, patient reported outcome measures (PROMs), including RAPID-3 and PSAID12, were employed during the COVID-19 pandemic in asynchronous consultations for patients with psoriatic arthritis (PsA). We compared pre-pandemic DAS28-CRP with intrapandemic PROMs to assess changes in disease activity since the pandemic. Whilst previous studies have primarily compared PsA PROMs with clinician-assessed scores (e.g. PASDAS), we compare PsA PROMs with clinicians' overall assessment of disease activity;this judgement considers PROMs, serology studies and individual patient feedback. Finally, we assess whether patients with PROMs indicating active disease were followed up appropriately. Methods Clinician-assessed scores were collected between 01/01/2019-01/03/ 2020 (''pre-pandemic''). Between 01/12/2020-31/03/2022 (''intrapandemic''), patient data from electronic surveys were analysed in a secure database for calculation of PROMs. These data, alongside blood results and patient comments, informed clinicians' triage decisions. Clinical outcome data were collected from electronic patient records;>=3 months follow-up appointment allocation was the target for patients with active disease (moderate/high disease activity). Data analysis was performed using r (version 4.2.2). Results In our pre-pandemic cohort (n=393), 79.8% of patients were in remission (per DAS28-CRP). Conversely, the intra-pandemic cohort (n=231) showed remission rates of 14.3% (per PSAID12) and 0% (RAPID-3). Indeed, 33.7% (based on PSAID12) vs 75.8% (RAPID-3) had moderate/ high disease activity. These results were validated in a paired cohort (n=38, score recorded in both windows). Disease activity worsened during the pandemic for 63.2% (PSAID12) and 97.4% (RAPID-3) of patients. PSAID-12 correlated positively with RAPID-3 (r=0.52, p<0.001), especially when RAPID-3 >=6.5 (r=0.75, p<0.001). When comparing PROMs with clinicians' assessment of PsA activity in our paired cohort, PSAID12 and RAPID-3 accurately reflected disease status in 70.6% and 58.8% of patients respectively. 3/9 and 9/27 patients with active disease, based on PSAID12 and RAPID-3 respectively, were seen within three months. Conversely, 7/10 patients who clinicians had deemed to have active disease were seen within three months. Conclusion Despite approximately 80% of patients being in pre-pandemic remission, the majority reported active intra-pandemic PsA. Whilst RAPID-3 skewed patients towards active disease, PSAID12 skewed patients towards remission/low disease activity. PSAID-12 and RAPID- 3 have been previously correlated;however, here we suggest that they could be used interchangeably in patients with high disease activity. PSAID-12 was a better predictor of clinicians' assessment of disease activity, although neither PROM correlated well with >=3 months followup appointment allocation. Although RAPID-3 and PSAID12 helped inform clinicians' decisions, neither alone sufficiently reflects patients' disease states. Remote management is practicable, but future studies should validate these findings across a larger cohort and assess the utility of different PROMs across PsA disease activity categories. Furthermore, multivariate analysis is warranted to ascertain which (combination of) variable(s) (e.g., PROMs, serology results, tender/ swollen joint count) best correlates with clinician judgement.

Probability of hospitalization for chronic degenerative diseases in patients with COVID-19.

OBJECTIVE: To determine the probability of hospitalization for chronic degenerative disease in patients with COVID-19. MATERIALS AND METHODS: A retrospective cohort in patients with COVID-19, confirmed by RT-PCR. Two study groups were integrated, the exposed group made up of 3 subgroups, exclusively diabetes mellitus, exclusively arterial hypertension and exclusively obesity;the unexposed group was the one in which any chronic comorbidity was ruled out. Relative risk, multiple logistic regression and probability calculation of the event (hospitalization) were used. RESULT(S): The relative risk for hospitalization in diabetes was of 3.59 (95%CI;2.44-5.29), 3.20 (95%CI;2.10-4.87) in hypertension and 2.56 (95%CI;1.72-3.81) in obesity. The multiple regression equation was y = -1358 + 2388 (diabetes mellitus) + 2005 (systemic arterial hypertension) + 1458 (obesity). The probability of hospitalization when there was no chronic disease was of 20.6%, when there was a chronic disease the probability fluctuated between 52.5% and 73.5%, when there were two chronic diseases it varied from 89.1% to 95.4%, and when there were three diseases the probability of hospitalization was of 98.9%. CONCLUSION(S): In the context of the probability of hospitalization when there is a chronic degenerative disease or it is absent, the research shows the difference in these two scenarios, as revealed by the more than 70 percentage points identified in the extreme scenarios, a condition that, led to the clinical field, reaffirms the presence of chronic degenerative disease as a risk factor for hospitalization.Copyright © 2023 Comunicaciones Cientificas Mexicanas S.A. de C.V.. All rights reserved.

Naphtho[2,1-b]furan derived triazole-pyrimidines as highly potential InhA and Cytochrome c peroxidase inhibitors: Synthesis, DFT calculations, drug-likeness profile, molecular docking and dynamic studies

Napthofuran and its fused heterocyclic derivatives evaluated with varied biological activity functional groups comprise an important class of compounds for new chemical entities. We here in reporting synthesis of new 3-(4-substituted phenyl)naphtho[1′,2′:4,5]furo[2,3-e][1,2,4]triazolo[4,3-c]pyrimidines 6(a-f). Structures of the newly synthesized compounds were confirmed by making use of spectroscopic techniques like IR, NMR and Mass. The DFT calculations were taken for the selected molecules using B3LYP hybrid functional with a 6–31+G (d, p) all-electron basis set using the Gaussian 09 package. The bioactivity predictions were evaluated for the synthesized compounds. The In vitro biological activities were reported for the all compounds 6(a-f). The compound 6a showed high activity of anti-TB and antioxidant activity with at MIC 1.6 μg/ml and at percentage of inhibition (72.54±0.21) at 10μg/ml respectively. The compound 6f (73.21±0.11) showed antioxidant activity better than standard drug BHA (71.32±0.13) at 10 μg/ml. Furthermore, the docking studies for the newly synthesized molecules were carried out by Auto dock software with proteins InhA (4TZK),Cytochrome c peroxidase (2 × 08) and protease (Mpro) of SARS-CoV-2 Omicron (PDB ID: 7TOB). All the compounds showed a strong binding affinity for the docked proteins. The outcome of docking results showed that compound 6ahad excellent binding energies -10.8, -9.4, and -9.0 kcal/mol with 4TZK, 2 × 08, and 7TOB respectively. Lastly, the protein stability, fluctuations of APO-Protein, protein-ligand complexes were investigated through Molecular Dynamics (MD) simulations studies using Desmond Maestro 11.3 and potential lead molecules were identified. © 2023

Fast-responsive and multi-applicable fluorescent turn-off chemodosimeter for monitoring hypochlorite: application to test strips, water samples, disinfectants and bioimaging

Due to the twin-demic of COVID-19 and flu virus, disinfectants containing ClO- have been widely used nowadays. Therefore, it is urgent to develop a sensor capable of efficiently detecting toxic hypochlorite. We present the invention and assessment of a fast-responsive and multi-applicable chemodosimeter sensor ETA (2-(2-((1E,2E)-3-(4-(dimethylamino)phenyl)allylidene)hydrazineyl)-N,N,N-trimethyl-2-oxoethan-1-aminium chloride) for monitoring ClO‑. In pure water, adding ClO- to ETA caused a turn-off fluorescence within 2 sec. These changes made it possible to quickly detect ClO- with a high level of selectivity. ETA displayed a low detection limit (0.68 μM) to ClO-. Using UV-vis titrations, ESI-MS and DFT calculations, we were able to demonstrate the detection mechanism, in which ETA was cleaved by ClO-. In particular, we established the possibility for reliable ClO- detection in environmental systems such as actual water samples, disinfectants, living cells, zebrafish and celery, in addition to confirming the practicality of ETA utilizing test strips.

Semen Quality in Males Suffering From COVID-19

Background: It is well knowledge that various viral illnesses may interfere with a man's ability to father children. Through the angiotensin-converting enzyme-2 receptor, which is highly concentrated in testicular tissue, the corona virus illness known as COVID-19 may cause harm to several organs. On the other hand, there is a paucity of data about the transmission of severe acute respiratory syndrome corona virus-2 (SARS-CoV-2) in sperm, as well as the virus's influence on spermatogenesis and the capacity for fertility. We intended to look into whether or not COVID-19 guys' sperm contained SARS-CoV-2 as well as examine how COVID-19 affected the overall quality of the sperm and the degree to which it's DNA was fragmented. Material(s) and Method(s): The survey was conducted between May 2022 to October 2022, with the participation of 40 male COVID-19 patients who were between the ages of 19 and 45 and enrolled at the RSDKS, Government Medical College, Ambikapur, Chhattisgarh. We tested each sample of sperm with a real-time reverse transcriptase and found no abnormalities. At the time of the initial sample, which took place during COVID-19, a comprehensive examination of the sperm was carried out. This analysis included the calculation of the sperm DNA Fragmentation Index. After 74 days had passed since the first sample, we were able to get the second specimen and carried out the aforementioned tests once again. Result(s): All of the sperm samples that were examined using real-time reverse transcription-polymerase chain reaction (RT-PCR) came back negative for SARS-CoV-2. These samples were taken during the first and second sampling. The initial sample had considerably lower levels of fructose, semen volume, vitality, total motility, sperm concentration, total sperm count, percentage of normal morphology, and cytoplasmic droplet percentage than the subsequent samples. On the other hand, the agglutination of the semen, the percentage of head defects, the DNA Fragmentation Index, the liquefaction time, the viscosity of the semen, and the number of leukocytes all rose. At the second sample, these results were inverted, but not to the level that would be considered optimal. These results all had a p-value less than 0.05, meaning they were statistically significant. As a result, COVID-19 has a detrimental impact on the characteristics of the sperm, including the sperm DNA fragmentation index. Conclusion(s): The quality of the semen remained low up until the second time it was sampled, despite the fact that we were unable to discover SARS-CoV-2 in the sample. It is recommended that assisted reproductive technology (ART) clinics and sperm banking facilities evaluate the quality of the sperm produced by males infected with COVID-19 and exclude men who have a history of being infected with SARS-CoV-2 until the men's sperm quality recovers to normal.Copyright © 2023 Ubiquity Press. All rights reserved.

Decreased Utilization of Low-Value Health Care Services during the Covid-19 Pandemic

INTRODUCTION AND OBJECTIVE: Low value health care is defined as care in which the potential to cause harm is greater than benefit. We hypothesize that rationing of health care services during the pandemic decreased the delivery of low value services. METHOD(S): Data was retrieved from the Mass General Brigham Research Patient Data Registry. High value care services were defined by U.S. Preventive Services Task Force guidelines, while low value care services were adapted for claims as described in the literature. Twenty-one services (4 high value and 17 low value) had adequate volume for analysis. Three month periods were considered, consisting of the pandemic period (Q4: 3/2/20 to 6/1/20) and control periods preceding the pandemic (Q1: 12/1/18 to 3/1/19;Q2: 3/2/19 to 6/1/19;and Q3: 12/1/19 to 3/1/20). Ratio measures of services per period were used to account for seasonality and differences in frequency.The 2019 high value (H) care ratio (Y0H = NHQ2/NHQ1) illustrates relative service counts during a typical year and the 2020 ratio (Y1H = NHQ4/NHQ3) represents the change due to the pandemic. Difference in ratios YH=Y1H-Y0H less than zero reflects a reduction in high value services during the pandemic. The same calculation was made for low value (L) procedures;YL=Y1LY0L. The difference between YL and YH is the difference in differences (DID) estimator and illustrates the differential decline in services. YH- YL greater than zero suggests that low value care declined to a greater degree than high value care. Subdivision DID in ratio analyses were performed for cancer and non-cancer care. RESULT(S): Included in this analysis were 3,271,957 patients. Mean age was 51.4 years, 59.1% of patients were female, and 71.7% were non-Hispanic. Of 21 identified services, 18 had a reduction in volume during the pandemic. The YL for PSA testing in men older than 75 was -0.81. The DID in ratios of all care was 0.08 (p<0.01), suggesting a modest decline in low-value care (Figure 1). The reduction was more pronounced for cancer care with a DID in ratios of 3.39 (p<0.01). CONCLUSION(S): We observed a reduction in both low and high value care with a greater reduction in low value services, especially for cancer care. Limitations include use of data from a single health system, limited number of services, and short time periods given the rapid onset of the pandemic.

Predictive value of central venous-to-arterial carbon dioxide tension in patients with ARDS treated with veno - venous extracorporeal membrane oxygenation (ECMO)

Introduction: Central venous-to-arterial carbon dioxide tension ( PvaCO2) can be useful for monitoring adequacy of tissue perfusion in patients with ARDS supported with veno-venous Extracorporeal Membrane Oxygenation (VV-ECMO). However, in theory, the unavoidable mixing of venous blood with blood after the oxygenator can affect PvaCO2 values by increasing central venous oxygen saturation and substantially decreasing CO2 concentration. This study aimed to evaluate acute changes in PvaCO2 after VV-ECMO installation and determine its association with patient outcomes. Method(s): Retrospectively evaluated coronavirus disease 2019 (COVID-19) ARDS patients with at least one concurrent arterial and central venous blood gas analysis before and after VV-ECMO installation as standard care. The primary outcome was intensive care unit (ICU) mortality at 28 days. Result(s): 29 patients were enrolled in the study. All the patients had a 25 F drainage multistage femoral cannula and a 21 F internal jugular infusion cannula. The median distance between the central venous sampling point and the tip of the infusion cannula was 39 [23-73] mm. No statistically significant changes in PvaCO2frelative changes calculated. After were observed 24-48 h after VV-ECMO installation (5 [4-7] mmHg to 6.5 [5-8.2] mmHg, p = 0.12). Hemoglobin concentration decreased 24 to 48 h after VVECMO installation (10.7 [9.5-12.7] g/dl to 9.6 [8.8-11.6] g/dl, p < 0.01) but neither central venous (75 [70-81]% to 73 [67-78]%, p = 0.46) nor arterial oxygen saturation (95 [92-97]% to 95 [93-96]%, p = 0.81) changed significantly. Elevated PvaCO2 after VV-ECMO installation had a good predictive value for 28 day ICU mortality (calculated area under the ROC curve 0.81) (Fig. 1 veno-venous). Conclusion(s): VV-ECMO support appears to have little effect on the PvaCO2 calculation. PvaCO2 can be used to evaluate patients with ARDS supported with VV-ECMO, as persistently elevated values can be associated with poor outcomes.

2020 Advances in Inflammatory Bowel Diseases Annual Meeting Abstracts

The proceedings contain 78 papers. The topics discussed include: work disability, indirect costs and risk factors in patients with Crohn's disease in a Rio De Janeiro tertiary care center;proton pump inhibitors are associated with less severe periodontal disease: considerations for IBD patients;impact of COVID-19 pandemic in treatment adherence in inflammatory bowel disease patients;impact of COVID-19 in a cohort of patients with inflammatory intestinal disease;utilization of biologic therapy in patients with microscopic colitis not responding to standard therapy;restrictive eating symptoms may persist in children adolescents with treated IBD: case series;power calculations in randomized controlled trials of inflammatory bowel disease;measuring patient-reported outcomes in Crohn's disease patients during the outbreak of COVID-19;Tofacitinib and ileal pouch anal anastomosis. a single-center case series;corticosteroids, aminosalicylates and gastrointestinal symptoms are associated with the need of hospitalization in patients with inflammatory bowel diseases and COVID-19;and manometric study and the role of the perianal disease and the clinical activity in anorectal dysfunction in Crohn's disease.

Computational Screening of Inhibitory Compounds for SARS-Cov-2 3CL Protease with a Database Consisting of Approved and Investigational Chemicals.

Computational screening is one of the fundamental techniques in drug discovery. Each compound in a chemical database is bound to the target protein in virtual, and candidate compounds are selected from the binding scores. In this work, we carried out combinational computation of docking simulation to generate binding poses and molecular mechanics calculation to estimate binding scores. The coronavirus infectious disease has spread worldwide, and effective chemotherapy is strongly required. The viral 3-chymotrypsin-like (3CL) protease is a good target of low molecular-weight inhibitors. Hence, computational screening was performed to search for inhibitory compounds acting on the 3CL protease. As a preliminary assessment of the performance of this approach, we used 51 compounds for which inhibitory activity had already been confirmed. Docking simulations and molecular mechanics calculations were performed to evaluate binding scores. The preliminary evaluation suggested that our approach successfully selected the inhibitory compounds identified by the experiments. The same approach was applied to 8820 compounds in a database consisting of approved and investigational chemicals. Hence, docking simulations, molecular mechanics calculations, and re-evaluation of binding scores including solvation effects were performed, and the top 200 poses were selected as candidates for experimental assays. Consequently, 25 compounds were chosen for in vitro measurement of the enzymatic inhibitory activity. From the enzymatic assay, 5 compounds were identified to have inhibitory activities against the 3CL protease. The present work demonstrated the feasibility of a combination of docking simulation and molecular mechanics calculation for practical use in computational virtual screening.

Curcumin as a potential multiple-target inhibitor against SARS-CoV-2 Infection: A detailed interaction study using quantum chemical calculations

Curcumin is one of the important naturally occurring compounds having several medicinal properties such as: antiviral, antioxidant, antifibrotic, antineoplastic as well as anti-inflammatory. SARS-CoV-2 has emerged as inf-ectious virus, which severely infected a large number of people all over the world. Many efforts have been made to prepare novel antiviral compound, but it is still challenging. Naturally occurring compound, curcumin, can be used as an alternative to antiviral compound against SARS-CoV-2. Its effect against SARS-CoV-2 is already highlighted in the literature. But the quantitative study of its interaction with various precursors of SARS-CoV-2 is not reported till date. This paper reports the interaction of curcumin with angiotensin-convert-ing enzyme2, transmembrane serine protease 2, 3-chymotrypsin-like protease and papain-like protease through molecular docking and quantum chemistry calculations to achieve quantitative understanding of underlying interactions. Here the conformational flexibility of curcumin is also highlighted, which helps it to accommodate in the four different docking sites. The study has been performed using calculations of geometrical parameter, atomic charge, electron density, Laplacian of electron density, dipole moment and the energy gap between highest occupied and lowest unoccupied molecular orbitals. The non--covalentinteraction (NCI) analysis is performed to visualize the weak inter-action present in the active sites. Combinedly molecular docking and detailed quantum chemistry calculations revealed that curcumin can be adopted as a potential multiple-target inhibitor against SARS-CoV-2.