Prevalence of multidrug-resistant Gram-negative bacteria from blood cultures and rapid detection of beta-lactamase-encoding genes by multiplex PCR assay

Introduction This study aimed to determine the prevalence of multidrug-resistant Gram-negative bacteria (GNB) from blood cultures in a tertiary-care hospital and the multiplex PCR assay's ability to detect resistance genes. Methods A total of 388 GNB isolates obtained from hospitalized patients between November 2019 and November 2021 were included in the study. Antimicrobial susceptibility testing was done by VITEK 2 system and broth microdilution method. Beta-lactamase-encoding genes were detected by multiplex PCR assays, BioFire-Blood Culture Identification 2 (BCID2) panel (bioMerieux, France). Extended-spectrum beta-lactamases (ESBLs) were detected phenotypically with VITEK AST-GN71 card (bioMerieux, France). The isolates of GNB were classified into multidrug-resistant, extensively-drug-resistant, and pandrug-resistant categories, and their prevalence and distribution in different wards, including coronavirus diseases 2019 (COVID-19) intensive care units (ICU), were calculated. Results Results revealed that all isolates of Acinetobacter baumannii and Pseudomonas aeruginosa were multidrug-resistant as well as 91.6% of Enterobacter cloacae, 80.6% of Proteus mirabilis, and 76.1% of Klebsiella pneumoniae, respectively. In fermentative bacteria, blaOXA-48-like (58.1%), blaNDM (16.1%), blaKPC (9.7%) and blaVIM (6.5%) genes were detected. More than half of Enterobacter cloacae (58.3%) and Klebsiella pneumoniae (53.7%) produced ESBLs. Among non-fermenters, the blaNDM gene was carried by 55% of Pseudomonas aeruginosa and 19.5% of Acinetobacter baumannii. In the COVID-19 ICU, Acinetobacter baumannii was the most common isolate (86.1%). Conclusions This study revealed high proportions of multidrug-resistant blood isolates and various underlying resistance genes in Gram-negative strains. The BCID2 panel seems to be helpful for the detection of the most prevalent resistance genes of fermentative bacteria.Copyright © GERMS 2022.

Surface enhanced Raman spectroscopy based analysis of SARS-CoV-2 spike protein binding to ACE2 receptor

The SARS-CoV-2 virus is still a challenge because of its diversity and mutations. The binding interactions of the angiotensin converting enzyme 2 (ACE2) receptor and the spike protein are relevant for the SARS-CoV-2 virus to enter the cell. Consequently, it is important and helpful to analyze binding activities and the changes in the structure of the ACE2 receptor and the spike protein. Surface enhanced Raman spectroscopy is able to analyze small concentrations of the proteins without contact, non-invasively and label-free. In this work, we present a SERS based approach in the visible wavelength range to analyze and study the binding interactions of the ACE2 receptor and the spike protein. SERS measurements of the ACE2 receptor, the spike protein and the ACE2-spike complex were performed. Additionally, an inhibitor was used to prevent the spike protein from binding to ACE2 and to compare the results. The analysis of the measured SERS spectra reveals structural differences and changes due to binding activities. Thus, we show that the performed SERS based approach can help for rapid and non-invasive analysis of binding interactions of the ACE2-spike complex and also of protein binding in general. © 2023 SPIE.

A new strategy to integrate silver nanowires with waterborne coating to improve their antimicrobial and antiviral properties

PurposeThis study aims to focus on the preparation and characterization of the silver nanowire (AgNWs), as well as their application as antimicrobial and antivirus activities either with incorporation on the waterborne coating formulation or on their own.Design/methodology/approachPrepared AgNWs are characterized by different analytical instruments, such as ultraviolet-visible spectroscope, scanning electron microscope and X-ray diffraction spectrometer. All the paint formulation's physical and mechanical qualities were tested using American Society for Testing and Materials, a worldwide standard test procedure. The biological activities of the prepared AgNWs and the waterborne coating based on AgNWs were investigated. And, their effects on pathogenic bacteria, antioxidants, antiviral activity and cytotoxicity were also investigated.FindingsThe obtained results of the physical and mechanical characteristics of the paint formulation demonstrated the formulations' greatest performance, as well as giving good scrub resistance and film durability. In the antimicrobial activity, the paint did not have any activity against bacterial pathogen, whereas the AgNWs and AgNWs with paint have similar activity against bacterial pathogen with inhibition zone range from 10 to 14 mm. The development of antioxidant and cytotoxicity activity of the paint incorporated with AgNWs were also observed. The cytopathic effects of herpes simplex virus type 1 (HSV-1) were reduced in all three investigated modes of action when compared to the positive control group (HSV-1-infected cells), suggesting that these compounds have promising antiviral activity against a wide range of viruses, including DNA and RNA viruses.Originality/valueThe new waterborne coating based on nanoparticles has the potential to be promising in the manufacturing and development of paints, allowing them to function to prevent the spread of microbial infection, which is exactly what the world requires at this time.

Experiences of accumulated stress among aging parent caregivers of adults with autism spectrum disorder

With the continuing increased incidence rate of autism spectrum disorder over the decades, there are increasing numbers of adults with autism who require varying levels of lifelong care, typically from parents. It is necessary to understand parents' lived experience of lifelong caregiving, and how their own aging process further impacts life quality. Furthermore, greater understanding of stressors, resources, appraisals, and coping among parent caregivers of children with "high functioning autism" who are transitioning into young adulthood is particularly necessary as services, needs, and experiences for both are nuanced due to functional status, deficits in the service system, and demographic disparities. Given lifespan aspects past research has not addressed, the study focused on development of a measure of parent accumulated stressors, and on interrelations of stressors, perceived social support, future time perspective, burden, satisfaction, and coping on health-related quality of life and meaning in life among 28 parents of young adults with autism. Although proposed quantitative analyses were not completed due to sample size, qualitative analyses on parent experiences and stressors revealed common themes of concern for child's future quality of life, complicated dynamics of providing help to their child overtime, and increased stress related to others' lack of understanding of their child. In total, 10 themes and multiple subthemes were identified in relation to aspects of accumulated stressors. Findings suggest parent stress with this specific population is complex, manifesting in nuanced ways at different life stages. Impacts of the COVID-19 pandemic are also explored, and implications for scientific advancement and clinical services are discussed. (PsycInfo Database Record (c) 2023 APA, all rights reserved)

Optimization and Characterization of Quercetin Vitamin C Nano-Phytosome Formulation

Objective: To design an optimal formulation for quercetin and vitamin C nano-phytosome. Method(s): Nano-phytosomes are prepared by the thin layer hydration technique using a 2-level-5-factor design experimental. A total of 32 experimental formulas were used for data analysis. The ratio of quercetin: soy lecithin (X1), the ratio of quercetin: cholesterol (X2), stirring speed (X3), stirring temperature (X4), and stirring time (X5) were used as independent factors, while globule size as a dependent factor. Data analysis was carried out by Design Expert12 application. Characterization of the optimal formula included physicochemical evaluation, globule size analysis, zeta potential, polydispersity index, entrapment efficiency, Transition Electron Microscopy (TEM) analysis, and FTIR analysis. Result(s): The optimal formula consisted of quercetin: vitamin C: lecithin: cholesterol ratio of 1: 1: 1.046: 0.105 mol;stirring speed 763.986 rpm;stirring time of 59 min, at temperature 51.73 degreeC which produced 59.26 nm average globule size, PDI value 0.66;zeta potential value-35.93+/-0.95 mV and average SPAN value 0.61. This formulation showed entrapment efficiency of quercetin 91.69+/-0.18 % and vitamin C 90.82+/-0.13 %. The TEM and FITR analysis showed the morphological of the globules and interactions between the drugs, soy lecithin, and cholesterol to form nano-phytosomes. Conclusion(s): The conditions to obtain the optimal formula for quercetin vitamin C nano-phytosome consisted of quercetin: vitamin C: lecithin: cholesterol ratio of 1: 1: 1.046: 0.105 mol;stirring speed 763.986 rpm;stirring time of 59 min, and at temperature 51.73 degreeC.Copyright © 2023 The Authors.

Analysis of disease spectrum of hospitalized children during outbreak of coronavirus disease 2019 in pediatric department of a tertiary general hospital in Shanghai.

Objective To analyze the changes of disease spectrum in pediatric inpatients before and after the outbreak of coronavirus disease 2019 (COVID-19). Methods The data of gender, age, habitual residence, diagnosis and other relevant information of 1 931 hospitalized children in Department of Pediatrics, The First Affiliated Hospital of Naval Medical University (Second Military Medical University) from Feb. 2019 to Jan. 2020 (1 year before the COVID-19 epidemic) and 618 hospitalized children from Feb. 2020 to Jan. 2021 (1 year after the COVID-19 epidemic) were collected. The total number, habitual residence, gender and disease spectrum of hospitalized children 1 year before and 1 year after the COVID-19 epidemic were statistically analyzed. Results The number of hospitalized children decreased by 68.00% (1 313/1 931) 1 year after the COVID-19 epidemic. The number of hospitalized children from other provinces and cities was decreased (17.80%110/618vs 29.00%560/1 931) and there was significantly difference in the distribution of habitual residence of hospitalized children between 1 year before and 1 year after the COVID-19 epidemic (P<0.01). One year after the COVID-19 epidemic, the number of children with respiratory diseases decreased by 92.04% (971/1 055), and the proportion was also decreased (13.59%84/618vs 54.63%1 055/1 931);the number of children with endocrine system diseases increased by 20.71% (29/140), and the proportion was increased (27.35%169/618vs 7.25%140/1 931);the number of children with neonatal diseases decreased by 43.01% (166/386), but the proportion was increased (35.60%220/618 vs 19.99%386/1 931). Compared with 1 year before the COVID-19 epidemic, there were significant differences in the proportions of respiratory diseases, endocrine system diseases and neonatal diseases in hospitalized children 1 year after the COVID-19 epidemic (all P<0.01). The age distribution of hospitalized children 1 year before and 1 year after the epidemic of COVID-19 was different (P<0.01), and the number of hospitalized children was also different in different seasons (P<0.05). One year after the epidemic of COVID-19, the number of hospitalized children with respiratory diseases was decreased most significantly, and the number of children with pneumonia decreased by 93.71% (655/699), with a significant difference found in the proportions of pneumonia between 1 year before and 1 year after the COVID-19 epidemic (52.38%44/84vs 66.26% 699/1 055, P<0.05). Compared with 1 year before the COVID-19 epidemic, the proportion of endocrine system diseases such as short stature/growth retardation was decreased and the proportion of precocious puberty/early puberty development was increased 1 year after the COVID-19 epidemic (P<0.05). Conclusion The COVID-19 epidemic has led to a significant decrease in hospitalized children in department of pediatric, especially in the proportion of respiratory diseases, but it has led to an increase in hospitalized children with endocrine system diseases, suggesting that epidemic prevention and control measures can effectively reduce respiratory diseases requiring hospitalization, but may increase precocious puberty and early puberty development. These changes should be considered by department of pediatrics in general hospitals.Copyright © 2022, Second Military Medical University Press. All rights reserved.

Beyond the pandemic? Exploring the impact of COVID-19 on spectrum use and management

COVID-19 has influenced the way we utilise the radio spectrum in terms of increasing data rates, the localisation of usage, and the transfer of traffic from urban to rural areas. Most regulators have shown sympathy towards operator requirements, stipulating a range of mitigation actions including allowing technology neutrality and temporary assignments. Internationally, the ITU-R suspended all physical meetings and launched a new global network resiliency platform named 'REG4COVID' to share experiences including those related to spectrum management. It is argued in this chapter that the pandemic has supported the calls for additional unlicensed spectrum for Wi-Fi in the 6 GHz and accelerated the rollout of 5G. Moreover, despite of increasing use of streaming, it is quite difficult to assume that traditional linear TV will be replaced, at least in the near future for a variety of reasons. The pandemic has also raised the question as to whether an innovative assignment model could be used to assign the spectrum instead of auctions, and whether, in some countries where temporary assignments were made, frequencies are kept unutilised or reserved. Concerning international spectrum management, it is expected that WRC-23 will be held on time though there will be some implications for issues such as the regulatory time-limits for bringing into use satellite networks frequency assignments. Finally, it is argued that the pandemic has also demonstrated the importance of flexibility and agility in national spectrum management, and placed spectrum managers in a new position where they were forced to be proactive instead of their traditional reactive role. © 2023 the authors.

INVESTIGATION OF THE ANTIBIOTIC RESISTANCE PROFILE OF KLEBSIELLA PNEUMONIAE ISOLATES ISOLATED FROM DIFFERENT CLINICAL SPECIMENS: ONE-YEAR DATA DURING THE COVID-19 PANDEMIC PROCESS.

Objective: In recent years, the rapid spread of resistance caused by the production of extended-spectrum beta-lactamase (ESBL) among bacteria has increased the importance of K. pneumoniae bacteria. Regular monitoring of antibiotic resistance rates of bacteria is very important for the treatment of infections and new treatment methods that can be developed. In the study, it was aimed to determine the antibiotic resistance profiles and ESBL positivity rates of K. pneumoniae isolated from patients who applied to Biruni University Hospital between March 2020 and March 2021, covering the COVID-19 Pandemic. Material(s) and Method(s): In the study, antibiogram test results and ESBL presences of K. pneumoniae bacteria isolated from samples sent from different outpatient clinics and services were evaluated retrospectively. GraphPad InStat V. 3.05 was used for statistical analysis. Result and Discussion: In the study, 423 K. pneumoniae bacteria were isolated from different clinical samples. Of the isolates, 161 (38%) were obtained from the endotracheal aspirate (ETA) sample, and 349 (82.5%) were obtained from the intensive care clinic. In addition, 358 (84.63%) of the isolates were ESBL positive and 65 (15.36%) ESBL negative. It was observed that the majority of the isolates obtained were resistant to ampicillin, and almost all of the ESBL positive isolates were resistant to ceftazidime. Both the studies and the results of the study show that the number of K. pneumoniae strains showing multiple antibiotic resistance has increased over time and this increase continues exponentially.Copyright © 2023 University of Ankara. All rights reserved.

Quantification of oil and gas methane emissions in the Delaware and Marcellus basins using a network of continuous tower-based measurements

According to the United States Environmental Protection Agency (US EPA), emissions from oil and gas infrastructure contribute 30 % of all anthropogenic methane (CH4) emissions in the US. Studies in the last decade have shown emissions from this sector to be substantially larger than bottom-up assessments, including the EPA inventory, highlighting both the increased importance of methane emissions from the oil and gas sector in terms of their overall climatological impact and the need for independent monitoring of these emissions. In this study we present continuous monitoring of regional methane emissions from two oil and gas basins using tower-based observing networks. Continuous methane measurements were taken at four tower sites in the northeastern Marcellus basin from May 2015 through December 2016 and five tower sites in the Delaware basin in the western Permian from March 2020 through April 2022. These measurements, an atmospheric transport model, and prior emission fields are combined using an atmospheric inversion to estimate monthly methane emissions in the two regions. This study finds the mean overall emission rate from the Delaware basin during the measurement period to be 146–210 Mg CH4 h-1 (energy-normalized loss rate of 1.1 %–1.5 %, gas-normalized rate of 2.5 %–3.5 %). Strong temporal variability in the emissions was present, with the lowest emission rates occurring during the onset of the COVID-19 pandemic. Additionally, a synthetic model–data experiment performed using the Delaware tower network shows that the presence of intermittent sources is not a significant source of uncertainty in monthly quantification of the mean emission rate. In the Marcellus, this study finds the overall mean emission rate to be 19–28 Mg CH4 h-1 (gas-normalized loss rate of 0.30 %–0.45 %), with relative consistency in the emission rate over time. These totals align with aircraft top-down estimates from the same time periods. In both basins, the tower network was able to constrain monthly flux estimates within ±20 % uncertainty in the Delaware and ±24 % uncertainty in the Marcellus. The results from this study demonstrate the ability to monitor emissions continuously and detect changes in the emissions field, even in a basin with relatively low emissions and complex background conditions.

Experiences of Parents and Practitioners Working with Middle School Students with ASD during the COVID-19 School Shutdown

People with Autism Spectrum Disorders (ASD) may be especially vulnerable to the effects of the COVID-19 pandemic due to their unique characteristics. This qualitative case study used interviews with instructional staff and parents to understand the experiences of both families and practitioners during the COVID-19 pandemic, and how this can inform the use of virtual instruction for students with ASD. Through the lens of Bronfenbrenner's ecological systems theory (1979) we examined how the different layers of our world shifted due to the pandemic, and what influence this had on our students with a diagnosis of ASD. Findings revealed several themes of among the interview transcripts, five main themes were observed: COVID-19, conflict of no control versus freedom, setting, technology use and preparation, and perspective.

Online Availability of a Robot Therapy for Children with Autism

In this paper we will present a case in which a robot therapy for children with autism was transferred from clinic to home conditions. The developed application enables the children to continue with the interventions in home conditions. This proved especially important in the COVID-19 pandemic. The application also allows monitoring of the child's activities, through which the therapist can later analyze the patient's behavior and offer appropriate therapy. The application shows reliable results and gives promise to develop beyond the user case we are considering. © 2023 IEEE.

Preface

The title of the ConferenceXXII Conference of PhD Students and Young Scientists "Interdisciplinary topics in mining and geology”The location and the date of the conferencevirtual event – online conference, June 29th to July 1st, 2022 in Wrocław, PolandXXIInd Conference of PhD Students and Young Scientists "Interdisciplinary topics in mining and geology” continues a series of events that started in 2000 at Wrocław University of Science and Technology. Scientific programme of the Conference focuses on four thematic panels:1. Mining Engineering: sustainable development, digitalisation in mining, problems of securing, protecting and using remnants of old mining works, underground mining, opencast mining, mineral processing, waste management, mining machinery, mine transport, economics in mining, mining aeronautics, ventilation and air conditioning in mines,2. Earth and Space Sciences: geology, hydrogeology, environmental protection, extraterrestrial resources, groundwater and medicinal waters, engineering and environmental protection, geotourism,3. Geoengineering: environmental protection, applied geotechnics, rock and soil mechanics, geohazards,4. Geoinformation: mining geodesy, GIS, photogrammetry and remote sensing, geodata modeling and analysis.The XXII Conference of PhD Students and Young Scientists was held as a virtual event, that is as a virtual, online conference in real-time. The reason why the Organizing Committee decided to change the traditional formula of the event to online formula was related to the concern for the health of the participants due to the COVID-19 epidemic.The XXII Conference of PhD Students and Young Scientists took place from June 29th to July 1st, 2022 in Wroclaw, Poland. That is the organizers worked and managed the event from the Wrocław University of Science and Technology Geocentre building. Because the conference focused on four thematic panels, four different special opening lectures were delivered by wellknown scientists- Professor Jan Zalasiewicz (University of Leicester, England)- Associate Professor Artur Krawczyk (AGH University of Science and Technology, Poland)- Professor Biljana Kovacević-Zelić (University of Zagreb, Croatia)- Assistant Professor Eduard Kan (Tashkent Institute of Irrigation and Agricultural Mechanizations Engineers, Uzbekistan).The Conference was divided into 8 oral sessions (with 33 presentations) and 1 poster session (with 33 posters). The amount of time provided to one presentation was 15 minutes, after presentation there was 5 minutes available for discussion. The poster session was available throughout the event, and the posters were available for online viewing on the Conference's website with the possibility of make discussion and ask questions in real time via zoom meeting application as well. Every day of the Conference one "virtual coffee break” was devoted for discussion between participants and question and answer session for the Organizers.There were 96 registered participants from 13 countries. The online XXII Conference of PhD Students and Young Scientists was conducted using the Zoom meeting platform with commemorative screen shots taken. By tradition two competitions, for the best oral presentation and for the best poster were held. The award for the best oral presentation was given ex aequo to Julia Tiganj (TH Georg Agricola University of Applied Sciences, Germany) for the presentation entitled Post-mining goes international: hurdles to climate neutrality using the example of China and Oksana Khomiak, Jörg Benndorf (TU Bergakademie Freiberg, Germany) for the presentation entitled Spectral analysis of ore hyperspectral images at different stages of the mining value chain, whereas the best poster was awarded to Adam Wróblewski, Jacek Wodecki, Paweł Trybała, Radosław Zimroz (Wrocław University of Science and technology, Poland) for the poster entitled Large underground structures geometry evaluation based on point cloud data analysis.List of Scientific Committee, Organizing Committee, Editorial Team are available i this pdf.

A dePEGylated Lipopeptide-Based Pan-Coronavirus Fusion Inhibitor Exhibits Potent and Broad-Spectrum Anti-HIV-1 Activity without Eliciting Anti-PEG Antibodies.

We previously identified a lipopeptide, EK1C4, by linking cholesterol to EK1, a pan-CoV fusion inhibitory peptide via a polyethylene glycol (PEG) linker, which showed potent pan-CoV fusion inhibitory activity. However, PEG can elicit antibodies to PEG in vivo, which will attenuate its antiviral activity. Therefore, we designed and synthesized a dePEGylated lipopeptide, EKL1C, by replacing the PEG linker in EK1C4 with a short peptide. Similar to EK1C4, EKL1C displayed potent inhibitory activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and other coronaviruses. In this study, we found that EKL1C also exhibited broad-spectrum fusion inhibitory activity against human immunodeficiency virus type 1 (HIV-1) infection by interacting with the N-terminal heptad repeat 1 (HR1) of viral gp41 to block six-helix bundle (6-HB) formation. These results suggest that HR1 is a common target for the development of broad-spectrum viral fusion inhibitors and EKL1C has potential clinical application as a candidate therapeutic or preventive agent against infection by coronavirus, HIV-1, and possibly other class I enveloped viruses.

Broad-spectrum pan-genus and pan-family virus vaccines.

Although the development and clinical application of SARS-CoV-2 vaccines during the COVID-19 pandemic demonstrated unprecedented vaccine success in a short time frame, it also revealed a limitation of current vaccines in their inability to provide broad-spectrum or universal protection against emerging variants. Broad-spectrum vaccines, therefore, remain a dream and challenge for vaccinology. This review will focus on current and future efforts in developing universal vaccines targeting different viruses at the genus and/or family levels, with a special focus on henipaviruses, influenza viruses, and coronaviruses. It is evident that strategies for developing broad-spectrum vaccines will be virus-genus or family specific, and it is almost impossible to adopt a universal approach for different viruses. On the other hand, efforts in developing broad-spectrum neutralizing monoclonal antibodies have been more successful and it is worth considering broad-spectrum antibody-mediated immunization, or "universal antibody vaccine," as an alternative approach for early intervention for future disease X outbreaks.

A Web Tool to Estimate Baseline Anti-Spike Monoclonal Antibody Efficacy Based on Regional Genomic Surveillance.

Drug appropriateness is a pillar of modern evidence-based medicine, but the turnaround times of genomic sequencing are not compatible with the urgent need to deliver treatments against microorganisms. Massive worldwide genomic surveillance has created an unprecedented landscape for exploiting viral sequencing for therapeutic purposes. When it comes to therapeutic antiviral antibodies, using IC50 against specific polymorphisms of the target antigen can be calculated in vitro, and a list of mutations leading to drug resistance (immune escape) can be compiled. The author encountered this type of knowledge (available from the Stanford University Coronavirus Antiviral Resistance Database,) in a publicly accessible repository of SARS-CoV-2 sequences. The author used a custom function of the CoV-Spectrum.org web portal to deliver up-to-date, regional prevalence estimates of baseline efficacy for each authorized anti-spike mAb across all co-circulating SARS-CoV-2 sublineages at a given time point. This publicly accessible tool can inform therapeutic choices that would otherwise be blind.

SARS-CoV-2 bivalent mRNA vaccine with broad protection against variants of concern.

Introduction: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant has rapidly spread around the globe. With a substantial number of mutations in its Spike protein, the SARS-CoV-2 Omicron variant is prone to immune evasion and led to the reduced efficacy of approved vaccines. Thus, emerging variants have brought new challenges to the prevention of COVID-19 and updated vaccines are urgently needed to provide better protection against the Omicron variant or other highly mutated variants. Materials and methods: Here, we developed a novel bivalent mRNA vaccine, RBMRNA-405, comprising a 1:1 mix of mRNAs encoding both Delta-derived and Omicron-derived Spike proteins. We evaluated the immunogenicity of RBMRNA-405 in BALB/c mice and compared the antibody response and prophylactic efficacy induced by monovalent Delta or Omicron-specific vaccine with the bivalent RBMRNA-405 vaccine in the SARSCoV-2 variant challenge. Results: Results showed that the RBMRNA-405 vaccine could generate broader neutralizing antibody responses against both Wuhan-Hu-1 and other SARS-CoV-2 variants, including Delta, Omicron, Alpha, Beta, and Gamma. RBMRNA-405 efficiently blocked infectious viral replication and lung injury in both Omicron- and Delta-challenged K18-ACE2 mice. Conclusion: Our data suggest that RBMRNA-405 is a promising bivalent SARS-CoV-2 vaccine with broad-spectrum efficacy for further clinical development.

Immunoadsorption as maintenance therapy for refractory neuromyelitis optica spectrum disorder.

Background: Neuromyelitis optica spectrum disorder (NMOSD) is a rare relapsing autoimmune disease of the central nervous system, affecting mainly optic nerves and spinal cord. NMOSD pathophysiology is associated with anti-aquaporin-4 (AQP4) immunoglobulin G (IgG) autoantibodies. Rapid extracorporeal elimination of autoantibodies with apheresis techniques, such as immunoadsorption (IA), was proven to be an effective treatment of NMOSD attacks. Data on the long-term use of IA to prevent attacks or progression of NMOSD are lacking. Objectives: The aim of this study was to evaluate efficacy and safety of maintenance IA for preventing recurrence of NMOSD attacks in patients refractory to other immunotherapies. Design: Case study. Methods: Retrospective analysis of two female patients with severe NMOSD refractory to conventional immunotherapies was performed. Both patients had responded to tryptophan IA (Tr-IA) as attack therapy and subsequently were treated with biweekly maintenance Tr-IA. Results: Patient 1 (AQP4-IgG seropositive, age 42 years) had 1.38 attacks of optic neuritis per year within 10.1 years before commencing regular Tr-IA. With maintenance Tr-IA for 3.1 years, one mild attack occurred, which was responsive to steroid pulse therapy. Expanded Disability Status Scale (EDSS) was stable at 5.0. Visual function score of the last eye improved from 3 to 1. Patient 2 (AQP4-IgG seronegative, age 43 years) experienced 1.7 attacks per year, mainly acute myelitis and optic neuritis, during the period of 10.0 years before the start of Tr-IA. During regular Tr-IA treatment, no further NMOSD attack occurred. The patient was clinically stable without any additional immunosuppressive treatment for 5.3 years. EDSS improved from 6.0 to 5.0, and the ambulation score from 7 to 1. Tolerability of Tr-IA was good in both patients. No serious adverse events occurred during long-term clinical trajectories. Conclusion: Tr-IA was well tolerated as maintenance treatment and resulted in clinical stabilization of two patients with highly active NMOSD, who were refractory to standard drug therapy.

The challenges of screen time in children with typical development and children with developmental disorders during COVID-19 pandemic.

Background: The significant lifestyle changes that occurred during the lockdown period associated with the COVID-19 pandemic may have had many potential adverse effects on children, in particular, sedentary screen exposure among children, including those with developmental disorders. We conducted a cross-sectional study to investigate and compare the screen time and outdoor activity time of children with typically development (TD) and those with developmental disorders during and before the emergence of COVID-19, and identified the risk factors related to screen time during the COVID-19 pandemic. Methods: A total of 496 children were surveyed via online questionnaires. Parents or/and children filled in the online questionnaire, including basic characteristics, screen time, outdoor activity time, and other related factors. The Statistical Product and Service Solutions software was used to analyze all data. Results: Children spent less time outdoors (t=14.774, P<0.001) and more time on electronic screens (t=-14.069, P<0.001) during the lockdown period of COVID-19, compared to the periods before COVID-19. Age (P=0.037), pre-COVID-19 screen time (P=0.005), screen time used for learning/education (P<0.001), screen time of siblings (P=0.007), and use of screen devices as electronic babysitters (P=0.005) were risk factors for screen time during the COVID-19 pandemic, while restrictive use of electronic devices by parents (P<0.05) was a protective factor. The screen time of children with autism spectrum disorder (ASD) or attention deficit hyperactivity disorder (ADHD) was significantly longer than children with TD before COVID-19 pandemic, but there is no statistical difference during the COVID-19 pandemic. Conclusions: During the COVID-19 pandemic, children's screen exposure time increased, and outdoor activities decreased significantly. This represents a significant challenge, and we should focus our efforts on managing children's screen time and promoting healthier lifestyles, including children with typical development, as well as those with developmental disorders.

Neurodegenerative and Neurodevelopmental Diseases and the Gut-Brain Axis: The Potential of Therapeutic Targeting of the Microbiome.

The human gut microbiome contains the largest number of bacteria in the body and has the potential to greatly influence metabolism, not only locally but also systemically. There is an established link between a healthy, balanced, and diverse microbiome and overall health. When the gut microbiome becomes unbalanced (dysbiosis) through dietary changes, medication use, lifestyle choices, environmental factors, and ageing, this has a profound effect on our health and is linked to many diseases, including lifestyle diseases, metabolic diseases, inflammatory diseases, and neurological diseases. While this link in humans is largely an association of dysbiosis with disease, in animal models, a causative link can be demonstrated. The link between the gut and the brain is particularly important in maintaining brain health, with a strong association between dysbiosis in the gut and neurodegenerative and neurodevelopmental diseases. This link suggests not only that the gut microbiota composition can be used to make an early diagnosis of neurodegenerative and neurodevelopmental diseases but also that modifying the gut microbiome to influence the microbiome-gut-brain axis might present a therapeutic target for diseases that have proved intractable, with the aim of altering the trajectory of neurodegenerative and neurodevelopmental diseases such as Alzheimer's disease, Parkinson's disease, multiple sclerosis, autism spectrum disorder, and attention-deficit hyperactivity disorder, among others. There is also a microbiome-gut-brain link to other potentially reversible neurological diseases, such as migraine, post-operative cognitive dysfunction, and long COVID, which might be considered models of therapy for neurodegenerative disease. The role of traditional methods in altering the microbiome, as well as newer, more novel treatments such as faecal microbiome transplants and photobiomodulation, are discussed.

Remote autism assessments - lessons learned from the Covid-19 pandemic: a service evaluation

PurposeThe COVID-19 pandemic has resulted in health services adapting the delivery of routine assessments, with many operating remotely. This paper aims to explore the lived experiences of individuals undertaking remote autism assessments during the COVID-19 pandemic. Design/methodology/approachA mixed-methods service evaluation was completed in an adult autism and neurodevelopmental service based in the north of England. A total of 24 participants, who had undergone remote autism assessments between March 2020 and July 2020, completed a questionnaire about their experiences. Thematic analysis was performed, and additional quantitative data were analysed descriptively to allow contextual information to be included. FindingsThe evaluation identified three main themes. The first, practical and sensory issues of remote assessment, indicated that internet connectivity problems were common and sometimes impeded a successful assessment. Additionally, participants identified some elements of the videocall impacted their sensory sensitivities. The second theme, emotional responses to remote assessment, demonstrated relief and exhaustion to be common following sessions. The ability to complete assessments from a safe space were favoured by most. The final theme, pros and cons of different assessment methods, highlighted the preference for video assessments above telephone and in person sessions. Originality/valueThis study provides an original contribution to the literature by gathering autistic adults' perspectives on remote autism assessments. The findings suggest that video assessments were the most preferable, over face-to-face and then telephone. Services should offer video and face-to-face assessments while keeping telephone assessments to a minimum.