The emergence of the novel H7N9 influenza A virus (IAV) has caused global concerns about the ability of this virus to spread between humans. Analysis of the receptor-binding properties of this virus using a recombinant protein approach in combination with fetuin-binding, glycan array and human tissue-binding assays demonstrates increased binding of H7 to both 2-6 and 2-8 sialosides as well as reduced binding to 2-3-linked SIAs compared to a closely related avian H7N9 virus from 2008. These differences could be attributed to substitutions Q226L and G186V. Analysis of the enzymatic activity of the neuraminidase N9 protein indicated a reduced sialidase activity, consistent with the reduced binding of H7 to 2-3 sialosides. However, the novel H7N9 virus still preferred binding to 2-3- over 2-6-linked SIAs and was not able to efficiently bind to epithelial cells of human trachea in contrast to seasonal IAV, consistent with its limited human-to-human transmission.

Immune protection of the body cavities depends on the swift activation of innate and adaptive immune responses in nonclassical secondary lymphoid organs known as fat-associated lymphoid clusters (FALCs). Compared with classical secondary lymphoid organs such as lymph nodes and Peyer's patches, FALCs develop along distinct differentiation trajectories and display a reduced structural complexity. Although it is well established that fibroblastic reticular cells (FRCs) are an integral component of the immune-stimulating infrastructure of classical secondary lymphoid organs, the role of FRCs in FALC-dependent peritoneal immunity remains unclear. Using FRC-specific gene targeting, we found that FRCs play an essential role in FALC-driven immune responses. Specifically, we report that initiation of peritoneal immunity was governed through FRC activation in a myeloid differentiation primary response 88 (MYD88)-dependent manner. FRC-specific ablation of MYD88 blocked recruitment of inflammatory monocytes into FALCs and subsequent CD4+ T cell-dependent B-cell activation and IgG class switching. Moreover, containment of Salmonella infection was compromised in mice lacking MYD88 expression in FRCs, indicating that FRCs in FALCs function as an initial checkpoint in the orchestration of protective immune responses in the peritoneal cavity.

COVID-19 has drastically altered our lives in an unprecedented manner, shuttering industries and leaving most of the country in isolation as we adapt to the evolving crisis Orthopedic surgery has not been spared from these effects, with the postponement of elective procedures in an attempt to mitigate disease transmission and preserve hospital resources as the pandemic continues to expand During these turbulent times, it is crucial to understand that although patients' and care-providers' safety is paramount, canceling or postponing essential surgical care is not without consequences and may be irreversibly detrimental to patients' health and quality of life in some cases The optimal solution to how to balance effectively the resumption of standard surgical care while doing everything possible to limit the spread of COVID-19 is undetermined and could include such strategies as social distancing, screening forms and tests, including temperature screening, segregation of inpatient and outpatient teams, proper use of protective gear, and the use of ambulatory surgery centers (ASCs) to provide elective, yet ultimately essential, surgical care while conserving resources and protecting the health of patients and health care providers Of importance, these recommendations do not and should not supersede evolving United States Centers for Disease Control and Prevention and relevant federal, state and local public health guidelines Level of Evidence: Level V Copyright ? 2020 Arthroscopy Association of North America

COVID-19 presents an existential challenge for millions of people and a generational challenge for the globe. Scientific research is the primary vehicle in humanity's attempts to understand the virus and mitigate its effects. Research on the pathogen is critically important. At the same time, COVID-19's consequences are due to more than the pathogen. Social and behavioral science research is essential in understanding how to achieve the highest possible health and safety levels, and how to preserve and improve quality of life, within complex and interdependent societies. This article describes the social sciences' role in this challenge and offers examples of its insights.

The development of different molecular biology techniques in the past decade has led to an explosion of new research in molecular pathology with consequent important applications to diagnosis, prognosis, and therapeutics, as well as a clearer concept of the disease pathogenesis. Many methods used in molecular pathology are now validated and used in several areas of pathological diagnosis, particularly on infectious and neoplastic diseases. The spectrum of infectious diseases, especially lung infective diseases, is now broadening and modifying, thus the pathologist is increasingly involved in the diagnosis of these pathologies. The precise tissue characterization of lung infections has an important impact on specific therapeutic treatment. Increased knowledge of significant alterations in lung cancer has led today to a better understanding of the pathogenic substrate underlying the development, progression and metastasis of neoplastic processes. Molecular tests are now routinely performed in different lung tumors allowing a more precise patient stratification in terms of prognosis and therapy. This review focuses on molecular pathology of the principal infective lung diseases and tumors.

This article is presenting a first attempt on a proposed fuzzy fractal control method for efficiently controlling nonlinear dynamic systems. The main goal is to combine the main advantages of fractal theoretical concepts and fuzzy logic theory for achieving efficient control of nonlinear dynamic systems. The concept coming from Fractal theory, known as the fractal dimension, can be utilized to measure the complexity of the dynamic behavior of a non-linear plant. On the other hand, fuzzy logic theory can be used to represent and capture the expert knowledge in controlling a plant. In addition, fuzzy logic enables to manage the uncertainty involved in the decision-making process for achieving efficient control of a non-linear plant. We illustrate the proposed fuzzy fractal control method with the current worldwide situation that requires achieving an efficient control of the COVID-19 pandemics.

The rapid spread of the highly contagious Omicron variant of SARS-CoV-2 globally will challenge the accessibility and the delivery of physical and rehabilitation medicine (PRM) services. Many health care systems throughout the world performed effective reforms such as the transition to telerehabilitation (TR). In Bulgaria, TR is still not regulated by law, and terms such as teleconsultation and tele-education have not yet been introduced. The adoption of TR in the Bulgarian health care system will undoubtedly increase the accessibility to rehabilitation treatment for a larger group of Bulgarian patients with various neurological, cardiorespiratory, musculoskeletal, and oncological conditions and will significantly contribute to the PRM services modernization in Bulgaria.

Children infected with COVID-19 have a critical part in community-based viral transmission. This study aimed to evaluate knowledge, awareness, attitudes, and behaviors of parents of pediatric dental patients on COVID-19 and to present required actions to prevent its spreading. A total of 524 parents took part in this cross-sectional study. A self-administered questionnaire was prepared for determining sociodemographic characteristics and socioeconomic status of parents, along with their COVID-19-related knowledge, awareness, attitudes, and behaviors. In total, 90.6% of parents were unaware that disease may show no symptoms; 61.1% and 32.6% did not know roles of "close contact with asymptomatic patients" and "dentistry practices" in transmission, respectively; 30.2% thought it could be transmitted to their children at dental clinics, and only 16.4% stated their children as carriers. Parents need to be informed on COVID-19 transmission through contact with asymptomatic individuals, risks associated with dentistry practices, and role of children in transmission.

The US Department of Health and Human Services (HHS) has developed and is implementing an agency-wide Digital Communications Strategy. A robust strategy to coordinate digital communications is vital at times of crisis, such as the COVID-19 pandemic - and will be needed as part of an effective HHS campaign to motivate individuals who are hesitant to accept coronavirus vaccines. Using science-based principles of systems change, a four-phase approach was developed in alignment with the 21st Century Integrated Digital Experience Act (IDEA). Phase I involved announcing a plan for creating and implementing the HHS Digital Communications Strategy, including support for it from the HHS Secretary. Phase II involved gathering information and stakeholder support, with an interview research study as the central component for providing input and encouraging stakeholder engagement. Phase III focused on building the Strategy through an iterative process. Phase IV, which is ongoing, concentrates on implementing the Strategy, measuring the impact of digital communications and supporting the budget required to modernize Federal digital communications approaches to meet the American public's needs. Learnings from the work so far are consistent with those from prior HHS systems change efforts in communications - and are helping to improve the Strategy in real time.

PURPOSE: To assess if early multiple-inhaler triple therapy (MITT) initiation in patients with chronic obstructive pulmonary disease (COPD) reduces subsequent healthcare resource utilization (HCRU), direct medical costs, and acute exacerbations of COPD (AECOPDs). PATIENTS AND METHODS: This retrospective, longitudinal cohort study used electronic health records and linked hospital administrative data in England. COPD patients with an AECOPD between July 2012 and May 2016 (index), and who subsequently started MITT within 180 days were eligible. Patients with an AECOPD 6 months prior to index were excluded. HCRU, direct healthcare costs, and AECOPDs were assessed in the following 24-month period for early (30 days) and delayed (31C180 days) MITT initiators. RESULTS: A total of 934 patients were included in the analysis and categorized as early (n=367, 39%) or delayed (n=567, 61%) MITT initiators. Mean patient age was 68.5 years and 53.2% were male. A significantly higher proportion of delayed MITT initiators required 1 outpatient appointment (all-cause) compared with early MITT initiators (87% vs 79%; p=0.0016). A significantly higher proportion of delayed MITT initiators required 1 COPD?related inpatient stay versus early MITT initiators (47% vs 40%; p=0.0262). Over the 24-month follow-up, mean all-cause and COPD-related total healthcare costs were significantly higher in delayed MITT initiators compared with early MITT initiators (all?cause: 11,348 vs 8126; p=0.0011; COPD-related: 7307 vs 4535; p=0.0009). CONCLUSION: Delayed initiation of multiple-inhaler triple therapy was associated with higher all-cause and COPD-related costs, suggesting that earlier initiation of triple therapy in COPD patients may help reduce the economic burden on the healthcare system.

Generic drug development is a complex process that involves development of formulation similar to Reference Listed Drug (RLD). Because of the complexity associated with generic drug development, many regulatory agencies have come up with various guidelines. Out of many guidelines, the Biopharmaceutics classification system (BCS) that was introduced in 1995 based on aqueous solubility and permeability helped many pharmaceutical scientists across the globe to utilize the tool for formulation development, waiver of in vivo studies. Later on in vitro guidelines based on dissolution and IVIVC were introduced by many regulatory agencies with an intent to reduce number of in vivo human testing thereby facilitating shorter development time and faster approvals and launch. Most recently understanding the importance in silico approaches such as PBPK modelling, regulatory agencies such as USFDA and EMA came up with modelling guidance documents. Even though consensus exists between guidance documents from various regulatory agencies, still there are many minor to major differences exists between these guidance documents that needs to be considered while submitting a generic drug application. This review aims to compare all the in vitro and in silico guidance documents from major regulatory agencies with emphasis on latest trends and technologies combined with regulatory acceptability with an intention to harmonize regulations. Guidance documents from major regulatory agencies such as USFDA, EMA, WHO, ICH and other emerging markets were compared. Similarities &differences among these guidance documents are critically reviewed to provide the reader a detailed overview of these guidance documents at one place. This article is protected by copyright. All rights reserved.

Biomaterials have been the subject of numerous studies to pursue potential therapeutic interventions for a wide variety of disorders and diseases. The physical and chemical properties of various materials have been explored to develop natural, synthetic, or semi-synthetic materials with distinct advantages for use as drug delivery systems for the central nervous system (CNS) and non-CNS diseases. In this review, an overview of popular biomaterials as drug delivery systems for neurogenerative diseases is provided, balancing the potential and challenges associated with the CNS drug delivery. As an effective drug delivery system, desired properties of biomaterials are discussed, addressing the persistent challenges such as targeted drug delivery, stimuli responsiveness, and controlled drug release in vivo. Finally, we discuss the prospects and limitations of incorporating extracellular vesicles (EVs) as a drug delivery system and their use for biocompatible, stable, and targeted delivery with limited immunogenicity, as well as their ability to be delivered via a non-invasive approach for the treatment of neurodegenerative diseases.

The accidental contamination of food and food packaging surfaces with SARS-CoV-2 is of increasing concern among scientists and consumers, particularly in relation to fresh foods that are consumed without further cooking The use of chemical sanitizers is often not suitable for these kinds of commodities;therefore, a non-thermal sanitation technology could help to increase safety in relation to the food supply chain Cold plasma has proven to be a promising strategy for virus inactivation This research is aimed at evaluating the ability of a cold plasma sanitation system to inactivate SARS-CoV-2 RNA on packaged foods Two different plastic materials were investigated and subjected to 5- and 10-min exposure to plasma after experimental inoculum of the RNA In addition to viral degradation, possible changes in the performance of the materials were evaluated Shelf-life of the foods, after exposure of the packages to plasma, was also investigated Results showed that 10 min of exposure was sufficient to almost completely eliminate the viral RNA from package surfaces The treatment did not produce any significant variation in packaging material performance or the shelf-life of the tested packaged products, indicating the potentiality of this treatment for the decontamination of packaged products

BACKGROUND/AIM To evaluate the antitumor effects of Plitidepsin against clear cell carcinoma (CCC) of the ovary. MATERIALS AND METHODS The expression of eEF1A2 in ovarian cancer was assessed by immunohistochemistry. Using ovarian CCC cell lines, the antitumor effect of Plitidepsin was assessed both in vitro and in vivo. By over-expressing or knocking down the eEF1A2 expression, we investigated the role of eEF1A2 in the sensitivity of CCC cells to Plitidepsin. RESULTS Immunoreactivity to eEF1A2 was observed in 76.2% of CCC, which was significantly higher than other histological subtypes of ovarian cancer. Plitidepsin exhibited significant antitumor activity toward chemonaive and chemoresistant CCC cells both in vitro and in vivo. Ectopic expression of eEF1A2 in CCC cells resulted in increased sensitivity to Plitidepsin. In contrast, eEF1A2 knockdown decreased sensitivity of CCC cells to plitidepsin. CONCLUSION Plitidepsin, a novel anti-cancer agent that targets eEF1A2, may be a promising agent for treating ovarian CCC.

Sepsis brain injury (SBI) is a major cause of death in critically ill patients. The present study aimed to investigate the role of emodin in SBI development. Human astrocyte 1321N1 cells were stimulated with 100 ng/mL lipopolysaccharide (LPS) to establish an SBI model in vitro. Flow cytometry was performed to measure the cell pyroptosis. The protein expression levels of syndecan-1 (SDC-1), NLR family pyrin domain containing 3 (NLRP3), Caspase-1, and the N-terminal fragment of gasdermin D (GSDMD-N) were measured using Western blotting. Interleukin (IL)-1?, IL-6, IL-10, and tumor necrosis factor (TNF)- levels in cells were measured using enzyme-linked immunosorbent assay kits. The N6-methyladenosine (m6A) modification was analyzed using the methylated RNA immunoprecipitation assay. NLRP3 activator, nigericin, was used to overexpress NLRP3. LPS treatment significantly enhanced the pyroptosis in 1321N1 cells, increased the levels of TNF-, IL-1?, and IL-6, and decreased the levels of IL-10. The protein expression levels of NLRP3, SDC-1, GSDMD-N, and Caspase-1 were also increased. Emodin treatment decreased the levels of TNF-, IL-1?, IL-6, NLRP3, SDC-1, GSDMD-N, and Caspase-1, while increasing the levels of IL-10 in LPS-treated 1321N1 cells. Nigericin reversed the effects of emodin. Furthermore, emodin upregulated m6A levels in NLRP3 by increasing the expression of methyltransferase-like 3 (METTL3). Meanwhile, knockdown of METTL3 reversed the effects of emodin on the mRNA expression and stability of NLRP3. Therefore, emodin inhibits the inflammation and pyroptosis of LPS-treated 1321N1 cells by inactivating METTL3-mediated NLRP3 expression.

This chapter presents a conceptual framework and setting for the book. This is informed by the desire to link three critical thematic areas, namely, (i) the global tourism value chains, (ii) COVID-19 and (iii) the 2030 Agenda for Sustainable Development (AfSD) and the 17 embedded sustainable development goals (SDGs). Bringing in the SDGs adds value given that there are three SDGs (SDGs 8, 12 and 14) that make specific reference to tourism. Furthermore, COVID-19 negatively impacted many SDGs leading to governments, civic and private organisations revising budgets to channel resources towards flattening both the COVID-19 and economic curves. Understanding the global tourism value chains assists in opening up the complex tourism space and to systematically document COVID-19 impacts along with the industries within the value chain nodes. To this end, this chapter comes across mainly as an essay with heavy dependence on value add from the document and critical discourse analysis, as well as a meta-analysis of secondary data sources. The chapter is useful from both a theoretical and practical application points of view. A section bringing the nexus of the thematic focus areas is slotted in towards the end, with a critique of how the tourism sector should address shortfalls in relation to the SDGs within the COVID-19 pandemic.

Objective: We report on the development and characterization of a UV-C light-emitting diode (LED) 280 nm cluster prototype device designed for the rapid disinfection of SARS-CoV-2 coronaviruses. The device was evaluated against the Betacoronavirus mouse hepatitis virus-3 strain, and its virucidal capacity was probed as a function of different applied UV-C doses versus different situations concerning irradiation distances. Background: UV-C LEDs are light emitters that offer advantages over low-pressure mercury lamps, such as quasimonochromaticity, lower electrical power consumption, instant on/off with the instant full-power operation, unlimited on/off cycles for disinfection schemes, and a much longer lifetime operation, in addition to portability aspects, as well as UV-C LEDs do not contain heavy metal in its composition such as mercury, found in ultraviolet germicidal irradiation (UVGI) lamps. Results: This novel device reached a 99.999% elimination rate at a distance of 9 cm at all the tested irradiation times (dose dependence), demonstrating that it took only 30 sec to achieve this inactivation rate. Its virucidal effectivity in rapid virus inactivation was demonstrated. Conclusions: We conclude that the HHUVCS cluster device (p = 280 nm) provides a rapid virucidal effect against the SARS-CoV-2 coronavirus. The current research should encourage further advances in UV-C LED-based devices designed for the inactivation of SARS-CoV-2 virus on surfaces, in air, and in liquids.

The continued presence of COVID-19 has significantly disrupted most church practices, including the ability to gather in person for worship. This has greatly altered church life, and with no clear timeline established yet on if-and-when churches will be able to operate in ways similar to before, the calls for reopening churches began well in advance of any evidence of decreasing infection rates. While within this conversation are discussions to be had concerning the relationship between Church and State, as well as an acknowledgement of the privileging of economic systems over relational systems, this article responds to the lack of disability awareness within the mainstream conversation as an act of pastoral justice. A history of how the church has engaged with disability is used to provide context otherwise missing from these accounts, and a critique of their argumentation is offered.

This paper looks at how Macao, the world's most densely populated city, deals with the COVID-19 disease, with a focus on government interventions and responses of the gaming concessionaires who operate integrated resorts. Macao was selected as the case not only because of the background of the authors, but also because Macao has been cited in many media coverage as a "good practice" example when it comes to fighting against this COVID-19 pandemic situation. Since there are already ample of articles on the background, development timeline, and overall commentary, this paper adopts a mixed approach by combining supplementary secondary data on the COVID-19 timeline in Macao (focusing on government interventions that can affect the tourism and hospitality industry) and primary qualitative in-depth interviews with senior management personnel (holding positions of Director or above) from major integrated resorts in Macao to get insights on industry strategic responses and expectation on future. A total of seven interviews were conducted with senior management members of five integrated resorts in May 2020. Four areas of responses were identified. They are 1. Survival; 2. The New Business Norm; 3. Business Rebound Strategies and 4. Corporate Social Responsibility (CSR). The findings indicate a seemingly utopian scenario among the major integrated resorts and gaming concessionaires in Macao towards their compliance and autonomous actions. The mechanism of this utopian-like scenario is explained by adopting the neo-institutional theory.

Aim The damage caused by the COVID-19 pandemic has made the prevention of its further spread at the top of the list of priorities of many governments and state institutions responsible for health and civil protection around the world. This prevention implies an effective system of epidemiological surveillance and the application of timely and effective control measures. This research focuses on the application of techniques for modelling and geovisualization of epidemic data with the aim of simple and fast communication of analytical results via geoportal. Methods The paper describes the approach applied through the project of establishing the epidemiological location-intelligence system for monitoring the effectiveness of control measures in preventing the spread of COVID-19 in Bosnia and Herzegovina. Results Epidemic data were processed and the results related to spatio-temporal analysis of the infection spread were presented by compartmental epidemic model, reproduction number R, epi-curve diagrams as well as choropleth maps for different levels of administrative units. Geovisualization of epidemic data enabled the release of numerous information from described models and indicators, providing easier visual communication of the spread of the disease and better recognition of its trend. Conclusion The approach involves the simultaneous application of epidemic models and epidemic data geovisualization, which allows a simple and rapid evaluation of the epidemic situation and the effects of control measures. This contributes to more informative decision-making related to control measures by suggesting their selective application at the local level.