Suramin, penciclovir, and anidulafungin exhibit potential in the treatment of COVID-19 via binding to nsp12 of SARS-CoV-2.

COVID-19, for which no confirmed therapeutic agents are available, has claimed over 48,14,000 lives globally. A feasible and quicker method to resolve this problem may be 'drug repositioning'. We investigated selected FDA and WHO-EML approved drugs based on their previously promising potential as antivirals, antibacterials or antifungals. These drugs were docked onto the nsp12 protein, which reigns the RNA-dependent RNA polymerase activity of SARS-CoV-2, a key therapeutic target for coronaviruses. Docked complexes were reevaluated using MM-GBSA analysis and the top three inhibitor-protein complexes were subjected to 100 ns long molecular dynamics simulation followed by another round of MM-GBSA analysis. The RMSF plots, binding energies and the mode of physicochemical interaction of the active site of the protein with the drugs were evaluated. Suramin, Penciclovir, and Anidulafungin were found to bind to nsp12 with similar binding energies as that of Remdesivir, which has been used as a therapy for COVID-19. In addition, recent experimental evidences indicate that these drugs exhibit antiviral efficacy against SARS-CoV-2. Such evidence, along with the significant and varied physical interactions of these drugs with the key viral enzyme outlined in this investigation, indicates that they might have a prospective therapeutic potential in the treatment of COVID-19 as monotherapy or combination therapy with Remdesivir.

Quality Improvement Audit on Multidisciplinary Transition Clinic

Aims The National Institute of Excellence (NICE) in 2016 guideline recommendations as per requirements of Care Act 2014, states to follow best practice for Transition from children to adults' services for young people who are using health or social care services. During this transition period the young people can be comprehensively prepared with adequate provision of information, services geared towards young people, person-centered planning, which is delivered by adequately trained professionals both in children's and adults' services, including support for parents and care providers. Our transition clinics are attended by Paediatrician, Rehabilitation medicine consultant, other relevant clinicians, and therapists. The aim of the study is to determine the quality of Transition Clinic Multidisciplinary Team proforma completed by Community Paediatrics team. Methods Retrospective data about Transition clinic, was retrieved from electronic health record database called systemone. The data collected from 4 clinics held over one year period between February 2020 to 2021. The clinic details are recorded on purpose-designed proforma for discussion in multidisciplinary meeting in transition clinic. The proforma captures these young people complex needs and comorbidities including learning disability, motor impairment, skeletal deformity, and feeding difficulties. The data was analysed and compared using Microsoft excel 2010. Results A total of 11 patients with age ranges from 15 to 19, were reviewed in Transition clinic from February 2020 to 2021. Among these cases, 6 patients had virtual consultation due to pandemic. There were higher proportion of girls about 63% compared to boys, who were about 36%, reviewed in these clinics. Among them 82% had Cerebral palsy and the rest 18% had complex congenital abnormality. There was 100% accuracy in the clinical data entry with regards to diagnosis, medication, and general health enquiry, except clinical examination which is close to 36%. This could be due to virtual clinics held during pandemic. Other professional and therapist involvement had been documented in a separate section. Also, there was 100% documentation on detailed plans, however only 30% had information about the relevant contact details for other services. The statistical calculation is not possible due to small sample size. Conclusion The study demonstrates that majority of these transition clinic entries followed MDT proforma. The clinical documentation does reflect the multidisciplinary discussion with focus on the young person's complex and multiple needs during transition period and to support before transition into adult care service. The professionals tried their best to deliver the care during the COVID pandemic, without any cancellation, also parental and carers concerns about pain and growth were taken into consideration during these virtual clinics. All children's and adults' services should give young people and their families or carers information about what to expect from services and what support is available to them. Therefore, we have introduced a standardised proforma incorporating the key areas specified by NICE, which include relevant details and contact information about the available adult services. The revised transition clinic format has been created as quality improvement project to improve clinical documentation.

Smart Vital Signs Monitoring System for Covid-19 Patients in Quarantine

A healthcare monitoring system based on the Internet of Things has been designed to monitor the vital signs of patients with COVID-19 while they are isolated at home. The complete system is designed using an embedded controller, medical sensors, a mobile application, and a cloud server. This Internet of Medical Things (IoMT) device is used to evaluate COVID-19 patients' critical levels during home isolation by monitoring their heart rate, body temperature, oxygen saturation (SpO2), cough intensity counts and geographic position. This approach enables physicians to assess COVID-19 patients without the need for direct contact, thereby minimizing the risk of infection. An embedded hardware device with internet connectivity collects and displays vital signs of COVID-19 patients and transmits the data to an IoT platform. The cloud layer and smartphone application store COVID-19 patient records via the API interface. Additionally, the Hospital Management System (HMS) is utilized to manage physician appointments and the prescriptions given to patients. Mobile applications and email notifications are sent to physicians and patients' families in case of an emergency, allowing them to respond quickly. The users can also view their vital signs and an alert message on the OLED screen. © 2022 IEEE.

Cold swaging of zirconium (ZR4) rods: Force analysis using CATIA-V5 and practical force measurement method

Zirconium alloys are used in various components of a nuclear fuel due to its irradiation strength and very less neutron absorption, these are used for production of clad tubes, end caps, end plates, spacer pads and bearing pads which are used in nuclear fuel cladding which are further used in the Boiling Water Reactor (BWR) and Pressurized Heavy Water Reactor (PHWR). The rods before going for production of end caps should undergo swaging in order to reduce the diameter from 24mm to 16 mm. Swaging process includes the reduction of cross section of zirconium rods with annealing process at regular intervals to relieve stresses, so the operation is performed in a number of passes. It is preferred for production of rods over the other cold working process such as wire drawing and pilgering due to its unique advantages over crack formation and line defects. The rod which is being swaged undergoes centrifugal force due to the roller action and hammers in radial direction so force analysis is done in CATIA V5 R19. Apart from centrifugal action the rod undergoes various other forces which constitute to the production of rod by swaging, so in order to calculate the total load suitable practical measurements are suggested and one method is specified due to the constraint nature of the machine. Patient lines are frequent in medical care, and one indicator of access to healthcare is waiting time. We explain queuing theory - an empirical method that provides service providers with a lot of experience in the design and management of existing services. This paper focuses on the pattern of arrival and the facilities available in the hospital in Vijayanagara District. The most important purpose of this research was to provide policymakers with knowledge to contribute to the well-being of the population by reducing waiting time for service, in this study, the waiting time of patients in the ambient department was first analyzed with the M / M/ 1 queuing method. The entire world is spreading of coronavirus-COVID-19 has increased exponentially across the globe, and still, no vaccine is available for the treatment of patients. The crowd has grown tremendously in the hospitals where the facilities are minimal. The queue theory is applied for the Single-server system and its self-similarity existence in a queue used to identify the queue time, waiting time, and Hurst parameter by different patient arrivals methods Health care center in our local area located in Hospet, Vijayanagara district, Karnataka. © 2022 Author(s).

Forecasting the spread of Covid-19 pandemic outbreak in India using ARIMA time series modelling

COVID-19 is the infectious disease caused by the most recently discovered corona virus. This new virus and disease were unknown before the outbreak began in Wuhan, China, in December 2019. This paper focuses on a Time Series Model to predict COVID-19 Outbreaks in India. Every day data of fresh COVID-19 confirmed cases act as an exogenous factor in this frame. Our data envelops the time period from 01st Sep, 2020 to 9th Dec, 2020. COVID-19 Corona virus disease has been recognized as a worldwide hazard, and most of the studies are being conducted using diverse mathematical techniques to forecast the probable evolution of this outbreak. These mathematical models based on various factors and analyses are subject to potential bias. Here, we put forward a natural Times Series (TS) model that could be very useful to predict the spread of COVID-19. Here, a popular method Auto Regressive Integrated Moving Average (ARIMA) TS model is performed on the real COVID-19 data set to predict the outbreak trend of the prevalence and incidence of COVID-19 in.India. The time series under study is a non-stationary. Results obtained in the study revealed that the ARIMA model has a strong potential for prediction. The model predicted maximum COVID-19 cases in India at around 14, 22,337 with an interval (12, 80,352 - 15, 69, 817) during 1st Sep to 9th Dec period cumulatively. As per the model, the number of new cases shall fluctuate drastically in India. The results will help governments to make necessary arrangements as per the estimated cases. This kind of analysis and implications of ARIMA models and fitting procedures are useful in forecasting COVID-19 Outbreaks in India. © 2022 Author(s).

Analysis of patient arrivals for COVID-19 test at healthcare center in Vijayanagara District

Patient queues are frequent in medical care, and one indicator of access to healthcare is waiting time. We explain queuing theory - an empirical method that provides service providers with a lot of experience in the design and management of existing services. This paper focuses on the pattern of arrival and the facilities available in the hospital in Vijayanagara District. The most important purpose of this research was to provide policymakers with knowledge to contribute to the well-being of the population by reducing waiting time for service, since long queues in exceeding cases will delay effective decisions about a particular disease that may cause death while waiting for service by patients. In this study, the waiting time of patients in the ambient department was first analyzed with the M / M/1 queuing method after measuring the mean number of patients served per hour and their median number in the hour. Additional findings of the workers questionnaire were evaluated to know. © 2022 Author(s).

Discovery and Use of Long dsRNA Mediated RNA Interference to Stimulate Antiviral Protection in Interferon Competent Mammalian Cells.

In invertebrate cells, RNA interference (RNAi) acts as a powerful immune defense that stimulates viral gene knockdown thereby preventing infection. With this pathway, virally produced long dsRNA (dsRNA) is cleaved into short interfering RNA (siRNA) by Dicer and loaded into the RNA-induced silencing complex (RISC) which can then destroy/disrupt complementary viral mRNA sequences. Comparatively, in mammalian cells it is believed that the type I interferon (IFN) pathway is the cornerstone of the innate antiviral response. In these cells, dsRNA acts as a potent inducer of the IFN system, which is dependent on dsRNA length, but not sequence, to stimulate an antiviral state. Although the cellular machinery for RNAi is intact and functioning in mammalian cells, its role to trigger an antiviral response using long dsRNA (dsRNAi) remains controversial. Here we show that dsRNAi is not only functional but has a significant antiviral effect in IFN competent mammalian cells. We found that pre-soaking mammalian cells with concentrations of sequence specific dsRNA too low to induce IFN production could significantly inhibit vesicular stomatitis virus expressing green fluorescent protein (VSV-GFP), and the human coronaviruses (CoV) HCoV-229E and SARS-CoV-2 replication. This phenomenon was shown to be dependent on dsRNA length, was comparable in effect to transfected siRNAs, and could knockdown multiple sequences at once. Additionally, knockout cell lines revealed that functional Dicer was required for viral inhibition, revealing that the RNAi pathway was indeed responsible. These results provide the first evidence that soaking with gene-specific long dsRNA can generate viral knockdown in mammalian cells. We believe that this novel discovery provides an explanation as to why the mammalian lineage retained its RNAi machinery and why vertebrate viruses have evolved methods to suppress RNAi. Furthermore, demonstrating RNAi below the threshold of IFN induction has uses as a novel therapeutic platform, both antiviral and gene targeting in nature.

How real is a virtual interview? Perspectives of orthopaedic surgery residency directors.

OBJECTIVE: As a result of COVID-19 pandemic, the 2021 US residency MATCH was devoid of the traditional in-person interviews. Herein, we assess the impact of Virtual Interviews (VIs) on resident selection, from the perspectives of Orthopedic Surgery (OS) Program Directors (PDs). MATERIALS AND METHODS: A 14-item survey was sent to PDs of ACGME-accredited OS residencies. Questions were designed to assess the pros, cons, and robustness of VIs compared to their antecedent in-person format. RESULTS: Forty-seven PDs responded to our survey. VIs antagonized PDs' ability to assess applicants' fit to program (76.6%), commitment to specialty (64%), and interpersonal skills (68.1%). This led to heavier dependence upon applicants' portfolios (64%). Almost all respondents (97.9%) found VIs to be more cost-efficient, saving a median of $3000 in interview-related expenses. Overall, only 8.5% of PDs were willing to conduct exclusive VIs in future cycles, compared to the majority in favor of dual formats (51.5%) or exclusive in-person interviews (40.4%). CONCLUSIONS: VIs have been an overall success, making most PDs opt for dual interview formats in future cycles. How this technology is further implemented in the future remains to be seen.

Impact of the virtual interview format on urology residency interviews: A survey of program directors

INTRODUCTION AND OBJECTIVE: The COVID-19 pandemic has profoundly changed the 2020-2021 residency application cycle, with the introduction of the virtual interview (VI) format being among the most significant of implemented changes. While employed by all urology residencies this past application cycle, no studies have investigated how VIs have impacted the interview process from programs' perspective. The purpose of this study is to assess the impact of VIs to serve as a guide for programs when determining their interview procedures in future residency application cycles. METHODS: Web-based surveys with questions regarding the VI format's impact on varying aspects of the residency interview process were sent out to program directors (PDs) of ACGME-accredited urology residency programs. Elements of the residency interview process covered in the questions included costs, time commitment, candidate evaluation, technical difficulties, and overall thoughts about the VI format. RESULTS: A total of 38 PDs responded to our survey. All responding PDs agreed or strongly agreed that VIs were less expensive than in-person interviews with an average cost reduction of $3,244 per program. Despite switching to a VI format, only 34% of PDs reported that interviews were less time-consuming than in-person interviews. Regarding the evaluation of candidates, the majority of PDs stated that VIs were detrimental for the assessment of candidates' fit with a program (74%), their personality and communication skills (74%), and their commitment to the specialty as well as their ability to function as a urology resident (68%). Consequentially, 53% of urology residencies relied more heavily on candidates' objective metrics when developing their rank list. Technical difficulties that interfered with interviewing candidates occurred in 5% of interviews. Overall, the majority of programs (53%) stated that VIs were inferior to in-person interviews. Despite their decreased satisfaction with the VI format, 61% of programs were open to hosting virtual and in-person interviews. At the same time, 34% and 5% of the PDs reported that they would prefer to exclusively host in-person or virtual interviews in the 2021-2022 application cycle, respectively. CONCLUSIONS: Despite their associated reduction in interview-related costs, VIs are not as reliable as in-person interviews to assess residency candidates for urology residency positions. Despite this, VIs exhibit significant potential upon further refinement of the format. More studies are needed to determine their impact in future application cycles.