A Novel Single Domain Antibody Targeting FliC Flagellin of Salmonella enterica for Effective Inhibition of Host Cell Invasion

The enteric pathogen, Salmonella enterica is a major cause of human gastroenteritis globally and with increasing bacterial resistance to antibiotics, alternative solutions are urgently needed. Single domain antibodies (sdAbs), the smallest antibody fragments that retain antigen binding specificity and affinity, are derived from variable heavy-chain only fragments (VHH) of camelid heavy-chain-only immunoglobulins. SdAbs typically contain a single disulfide bond simplifying recombinant protein production in microbial systems. These factors make sdAbs ideally suited for the development of effective anti-bacterial therapeutics. To this end, we generated an anti-Salmonella VHH library from which we screened for high affinity sdAbs. We present a novel sdAb (Abi-Se07) that targets the Salmonella virulence factor, FliC, required for bacterial motility and invasion of host cells. We demonstrate that Abi-Se07 bound FliC with a KD of 16.2 ± 0.1 nM. In addition, Abi-Se07 exhibited cross-serovar binding to whole cells of S. enterica serovar Typhimurium, Heidelberg, and Hadar. Abi-Se07 significantly inhibited bacterial motility and significantly reduced S. enterica colonization in a more native environment of chicken jejunum epithelium. Taken together, we have identified a novel anti-Salmonella sdAb and discuss future efforts toward therapeutic development.Fil: Huen, Jennifer. AbCelex Technologies Inc.; Canadá. University of Toronto; CanadáFil: Yan, Zhun. AbCelex Technologies Inc.; CanadáFil: Iwashkiw, Jeremy. AbCelex Technologies Inc.; CanadáFil: Dubey, Shraddha. AbCelex Technologies Inc.; CanadáFil: Gimenez, Maria C.. University of Toronto; CanadáFil: Ortiz, María Eugenia. University of Toronto; Canadá. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Investigaciones para la Industria Química. Universidad Nacional de Salta. Facultad de Ingeniería. Instituto de Investigaciones para la Industria Química; ArgentinaFil: Patel, Saumil V.. AbCelex Technologies Inc.; CanadáFil: Jones, Michael D.. AbCelex Technologies Inc.; CanadáFil: Riazi, Ali. AbCelex Technologies Inc.; CanadáFil: Terebiznik, Mauricio. University of Toronto; CanadáFil: Babaei, Saeid. AbCelex Technologies Inc.; CanadáFil: Shahinas, Dea. AbCelex Technologies Inc.; Canad

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

β Receptors: role in cardiometabolic disorders

Pharmacological and molecular approaches have shown that an atypical β-adrenoceptor (AR), called β 3 -AR, that is distinct from β 1 -ARs and β 2 -ARs, exists in some tissues in heterogeneous populations such as β 3a -ARs and β 3b -ARs. β 3 -ARs belong to a superfamily of receptors linked to guanine nucleotide binding proteins (G proteins). The β 3 -AR gene contains two introns whereas the β 1 -AR and β 2 -AR genes are intronless, leading to splice variants. β 3 -ARs can couple to G i and G s and they are reported to be present in brown adipose tissue, vasculature, the heart, among other tissues. β 3 -ARs cause vasodilation of microvessels in the islets of Langerhans and may participate in the pathogenesis of cardiac failure, during which modification of β 1 -AR and β 2 -AR expression occurs. The development of β 3 -AR agonists has led to the elaboration of promising new drugs, including antiobesity and antidiabetic drugs. This article reviews the various pharmacological actions of β 3 -ARs and their clinical implications for diabetes and cardiovascular diseases

SAGES Update: Electronic Disease Surveillance in Resource-Limited Settings

The Suite for Automated Global Electronic bioSurveillance (SAGES) is a collection of modular, flexible, open source software tools for electronic disease surveillance in resource-limited settings. SAGES software development, funded by the US Armed Forces Health Surveillance Center, continues as we add new international collaborators

SAGES Update: Electronic Disease Surveillance in Resource-Limited Settings

OBJECTIVE: The Suite for Automated Global Electronic bioSurveillance (SAGES) is a collection of modular, flexible, open-source software tools for electronic disease surveillance in resource-limited settings. This demonstration will illustrate several new innovations and update attendees on new users in Africa and Asia. INTRODUCTION: The new 2005 International Health Regulations (IHR), a legally binding instrument for all 194 WHO member countries, significantly expanded the scope of reportable conditions and are intended to help prevent and respond to global public health threats. SAGES aims to improve local public health surveillance and IHR compliance with particular emphasis on resource-limited settings. More than a decade ago, in collaboration with the US Department of Defense (DoD), the Johns Hopkins University Applied Physics Laboratory (JHU/APL) developed the Electronic Surveillance System for the Early Notification of Community-based Epidemics (ESSENCE). ESSENCE collects, processes, and analyzes non-traditional data sources (i.e. chief complaints from hospital emergency departments, school absentee data, poison control center calls, over-the-counter pharmaceutical sales, etc.) to identify anomalous disease activity in a community. The data can be queried, analyzed, and visualized both temporally and spatially by the end user. The current SAGES initiative leverages the experience gained in the development of ESSENCE, and the analysis and visualization components of SAGES are built with the same features in mind. METHODS: SAGES tools are organized into four categories: 1) data collection, 2) analysis & visualization, 3) communications, and 4) modeling/simulation/evaluation. Within each category, SAGES offers a variety of tools compatible with surveillance needs and different types or levels of information technology infrastructure. SAGES tools are built in a modular nature, which allows for the user to select one or more tools to enhance an existing surveillance system or use the tools en masse for an end-to-end electronic disease surveillance capability. Thus, each locality can select tools from SAGES based upon their needs, capabilities, and existing systems to create a customized electronic disease surveillance system. New OpenESSENCE developments include improved data query ability, improved mapping functionality, and enhanced training materials. New cellular phone developments include the ability to concatenate single SMS messages sent by simple or Smart Android cell phones. This ‘multiple-SMS’ message ability allows use of SMS technology to send and receive health information exceeding normal SMS message length in a manner transparent to the users. CONCLUSIONS: The SAGES project is intended to enhance electronic disease surveillance capacity in resource-limited settings around the world. We have combined electronic disease surveillance tools developed at JHU/APL with other freely-available, interoperable software tools to create SAGES. We believe this suite of tools will facilitate local and regional electronic disease surveillance, regional public health collaborations, and international disease reporting. SAGES development, funded by the US Armed Forces Health Surveillance Center, continues as we add new international collaborators. SAGES tools are currently deployed in locations in Africa, Asia and South America, and are offered to other interested countries around the world

Loschmidt echo and dynamical fidelity in periodically driven quantum systems

We study the dynamical fidelity F(t) and the Loschmidt echo L(t), following a periodic driving of the transverse magnetic field of a quantum Ising chain (back and forth across the quantum critical point) by calculating the overlap between the initial ground state and the state reached after n periods tau. We show that [log F(n tau)]/L (the logarithm of the fidelity per site) reaches a steady value in the asymptotic limit n -> infinity, and we derive an exact analytical expression for this quantity. Remarkably, the steady-state value of [log F(n tau -> infinity)]/L shows memory of non-trivial phase information which is instead hidden in the case of thermodynamic quantities; this conclusion, moreover, is not restricted to 1-dimensional models

A Saliva-Based Serological and Behavioral Analysis of SARS-CoV-2 Antibody Prevalence in Howard County, Maryland

ABSTRACT The objective of the study was to estimate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seroprevalence in the Howard County, Maryland, general population and demographic subpopulations attributable to natural infection or coronavirus disease 2019 (COVID-19) vaccination and to identify self-reported social behaviors that may affect the likelihood of recent or past SARS-CoV-2 infection. A cross-sectional, saliva-based serological study of 2,880 residents of Howard County, Maryland, was carried out from July through September 2021. Natural SARS-CoV-2 infection prevalence was estimated by inferring infections among individuals according to anti-nucleocapsid immunoglobin G levels and calculating averages weighted by sample proportions of various demographics. Antibody levels between BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) recipients were compared. Antibody decay rate was calculated by fitting exponential decay curves to cross-sectional indirect immunoassay data. Regression analysis was carried out to identify demographic factors, social behaviors, and attitudes that may be linked to an increased likelihood of natural infection. The estimated overall prevalence of natural infection in Howard County, Maryland, was 11.9% (95% confidence interval, 9.2% to 15.1%), compared with 7% reported COVID-19 cases. Antibody prevalence indicating natural infection was highest among Hispanic and non-Hispanic Black participants and lowest among non-Hispanic White and non-Hispanic Asian participants. Participants from census tracts with lower average household income also had higher natural infection rates. After accounting for multiple comparisons and correlations between participants, none of the behavior or attitude factors had significant effects on natural infection. At the same time, recipients of the mRNA-1273 vaccine had higher antibody levels than those of BNT162b2 vaccine recipients. Older study participants had overall lower antibody levels compared with younger study participants. The true prevalence of SARS-CoV-2 infection is higher than the number of reported COVID-19 cases in Howard County, Maryland. A disproportionate impact of infection-induced SARS-CoV-2 positivity was observed across different ethnic/racial subpopulations and incomes, and differences in antibody levels across different demographics were identified. Taken together, this information may inform public health policy to protect vulnerable populations. IMPORTANCE We employed a highly innovative noninvasive multiplex oral fluid SARS-CoV-2 IgG assay to ascertain our seroprevalence estimates. This laboratory-developed test has been applied in NCI’s SeroNet consortium, possesses high sensitivity and specificity according to FDA Emergency Use Authorization guidelines, correlates strongly with SARS-CoV-2 neutralizing antibody responses, and is Clinical Laboratory Improvement Amendments-approved by the Johns Hopkins Hospital Department of Pathology. It represents a broadly scalable public health tool to improve understanding of recent and past SARS-CoV-2 exposure and infection without drawing any blood. To our knowledge, this is the first application of a high-performance salivary SARS-CoV-2 IgG assay to estimate population-level seroprevalence, including identifying COVID-19 disparities. We also are the first to report differences in SARS-CoV-2 IgG responses by COVID-19 vaccine manufacturers (BNT162b2 [Pfizer-BioNTech] and mRNA-1273 [Moderna]). Our findings demonstrate remarkable consistency with those of blood-based SARS-CoV-2 IgG assays in terms of differences in the magnitude of SARS-CoV-2 IgG responses between COVID-19 vaccines