Population health surveys are rarely comprehensive in addressing sexual health, and population-representative surveys often lack standardized measures for collecting comparable data across countries. We present a sexual health survey instrument and implementation considerations for population-level sexual health research. The brief, comprehensive sexual health survey and consensus statement was developed via a multi-step process (an open call, a hackathon, and a modified Delphi process). The survey items, domains, entire instruments, and implementation considerations to develop a sexual health survey were solicited via a global crowdsourcing open call. The open call received 175 contributions from 49 countries. Following review of submissions from the open call, 18 finalists and eight facilitators with expertise in sexual health research, especially in low and middle-income countries (LMICs), were invited to a 3-day hackathon to harmonize a survey instrument. Consensus was achieved through an iterative, modified Delphi process that included three rounds of online surveys. The entire process resulted in a 19-item consensus statement and a 10-minute sexual health survey instrument. This is the first global consensus on a sexual and reproductive health survey instrument that can be used to generate cross-national comparative data in both high-income and LMICs. The inclusive process identified priority domains for improvement and can inform the design of sexual and reproductive health programs and contextually relevant data for comparable research across countries.

Drug release from microparticle-based topical gels may affect their bioavailability, safety and efficacy. This work sought to elucidate spatial distribution of the drug within the microparticle matrix and how this impacts the product's critical performance attributes. The purpose of this research was to inform the development of in vitro characterization approaches to support a demonstration of bioequivalence. Drug-free microparticles were loaded with tretinoin or drug-loaded microparticles were separated from purchased Retin-A Micro? (tretinoin) topical gel drug products. The resultant microparticles were analyzed for tretinoin content, drug loading efficiency, morphology, surface topography, surface pore size distribution, particle size distribution and tretinoin release. The solid-state characteristics and chemical interaction of tretinoin with the microparticles were also investigated. Microparticles loaded with tretinoin made in-house and those separated from Retin-A Micro? (tretinoin) topical gel were spherical, polydisperse and free of aggregates. The surface porosity of the microparticles was a19.8% with an average pore size of a327 nm. Microparticles loaded with tretinoin in-house were smaller in size and exhibited faster drug release than those separated from Retin-A Micro? (tretinoin) topical gel. Tretinoin release was found to increase with an increase in the drug loading. Based on XRD and DSC data, tretinoin was present in an amorphous state. The FTIR spectra indicated a disappearance of carbonyl band of microparticles and shifting of the hydroxyl band of tretinoin due to hydrogen bonding. The extent of drug loading and the solid-state interaction of tretinoin with the microparticles may be critical for drug release. Additional characterization of the drug products is necessary to understand the effect of the factors examined in this work on the bioavailability and efficacy of tretinoin gels.

We present an oblique plane microscope (OPM) that uses a bespoke glass-tipped tertiary objective to improve the resolution, field of view, and usability over previous variants. Owing to its high numerical aperture optics, this microscope achieves lateral and axial resolutions that are comparable to the square illumination mode of lattice light-sheet microscopy, but in a user friendly and versatile format. Given this performance, we demonstrate high-resolution imaging of clathrin-mediated endocytosis, vimentin, the endoplasmic reticulum, membrane dynamics, and Natural Killer-mediated cytotoxicity. Furthermore, we image biological phenomena that would be otherwise challenging or impossible to perform in a traditional light-sheet microscope geometry, including cell migration through confined spaces within a microfluidic device, subcellular photoactivation of Rac1, diffusion of cytoplasmic rheological tracers at a volumetric rate of 14 Hz, and large field of view imaging of neurons, developing embryos, and centimeter-scale tissue sections.

Chromatin architect of muscle expression (Charme) is a muscle-restricted long noncoding RNA (lncRNA) that plays an important role in myogenesis. Earlier evidence indicates that the nuclear Charme isoform, named pCharme, acts on the chromatin by assisting the formation of chromatin domains where myogenic transcription occurs. By combining RNA antisense purification (RAP) with mass spectrometry and loss-of-function analyses, we have now identified the proteins that assist these chromatin activities. These proteinswhich include a sub-set of splicing regulators, principally PTBP1 and the multifunctional RNA/DNA binding protein MATR3bind to sequences located within the alternatively spliced intron-1 to form nuclear aggregates. Consistent with the functional importance of pCharme interactome in vivo, a targeted deletion of the intron-1 by a CRISPR-Cas9 approach in mouse causes the release of pCharme from the chromatin and results in cardiac defects similar to what was observed upon knockout of the full-length transcript.

COVID-19 is a rapidly evolving public health emergency that has largely impacted the provision of healthcare services around the world. The challenge for electrophysiology teams is double; on one side preventing disease spread by limiting all nonessential face-to-face interactions, but at the same time ensuring continued care for patients who need it. These guidelines contain recommendations regarding triaging in order to define what procedures, device checks and clinic visits can be postponed during the pandemic. We also discuss best practices to protect patients and healthcare workers and provide guidance for the management of COVID-19 patients with arrhythmic conditions.

Interleukin-1 receptor activated kinases (IRAKs) play crucial roles in the Toll-like receptor (TLR) mediated signal transduction pathways that control host innate immune responses. Here we report the cloning of an IRAK1 cDNA (named ScIRAK1) from the mandarin fish. The predicted ScIRAK1 peptide contains a death domain and a serine/threonine-specific kinase domain. Quantitative RT-PCR showed that ScIRAK1 mRNA was primarily expressed in blood cells and posterior kidney. Seven days following infection with infectious spleen and kidney necrosis virus (ISKNV), the ScIRAK1 mRNA level was significantly higher in the blood cells of clinically symptomatic fish than in the blood cells of asymptomatic fish or control fish injected with phosphate-buffered saline. Additional experiments showed that overexpression of ScIRAK1 in the 293T cells could induce NF-B activation. These results suggest that ScIRAK1 may play a role in the pathology of ISKNV infection in the mandarin fish.

BACKGROUND: Community-acquired pneumonia (CAP) is a leading cause of morbidity and mortality worldwide. Antibiotics are losing their effectiveness due to the emerging infectious diseases, the scarcity of novel antibiotics, and the contributions of antibiotic misuse and overuse to resistance. Characterization of the lipidomic response to pneumonia and exploring the lipidomic phenotype can provide new insight into the underlying mechanisms of pathogenesis and potential avenues for diagnostic and therapeutic treatments. METHODS: Lipid profiles of bronchoalveolar lavage fluid (BALF) samples were generated through untargeted lipidomic profiling analysis using high-performance liquid chromatography with mass spectrometry (HPLC-MS). Principal component analysis (PCA) was applied to identify possible sources of variations among samples. Partitioning clustering analysis (k-means) was employed to evaluate the existence of distinct lipidomic clusters. RESULTS: PCA showed that BALF lipidomes differed significantly between CAP (n = 52) and controls (n = 68, including 35 healthy volunteers and 33 patients with non-infectious lung diseases); while no clear separation was found between severe CAP and non-severe CAP cases. Lactosylceramides were the most prominently elevated lipid constituent in CAP. Clustering analysis revealed three separate lipid profiles; subjects in each cluster exhibited significant differences in disease severity, incidence of hypoxemia, percentages of phagocytes in BALF, and serum concentrations of albumin and total cholesterol (all p < 0.05). In addition, SM (d34:1) was negatively related to macrophage (adjusted r = ? 0.462, p < 0.0001) and PE (18:1p/20:4) was positively correlated with polymorphonuclear neutrophil (PMN) percentages of BALF (adjusted r = 0.541, p < 0.0001). The 30-day mortality did not differ amongst three clusters (p < 0.05). CONCLUSIONS: Our data suggest that specific lower airway lipid composition is related to different intensities of host inflammatory responses, and may contribute to functionally relevant shifts in disease pathogenesis in CAP individuals. These findings argue for the need to tailor therapy based on specific lipid profiles and related inflammatory status. TRIAL REGISTRATION: ClinicalTrials.gov (NCT03093220). Registered on 28 March 2017 (retrospectively registered). ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12931-019-1028-8) contains supplementary material, which is available to authorized users.

Chloroquine is used in the treatment of patients with COVID-19 infection, although there is no substantial evidence for a beneficial effect. Chloroquine is known to prolong the QRS and QTc interval on the ECG. To assess the effect of chloroquine on QRS and QTc intervals in COVID-19 patients, we included all inpatients treated with chloroquine for COVID-19 in the Spaarne Gasthuis (Haarlem/Hoofddorp, the Netherlands) and had an ECG performed both in the 72 h before and during or at least 48 h after treatment. We analyzed the (change in) QRS and QTc interval using the one-sample t-test. Of the 106 patients treated with chloroquine, 70 met the inclusion criteria. The average change in QRS interval was 6.0 ms (95% CI 3.3-8.7) and the average change in QTc interval was 32.6 ms (95% CI 24.9-40.2) corrected with the Bazett's formula and 38.1 ms (95% CI 30.4-45.9) corrected with the Fridericia's formula. In 19 of the 70 patients (27%), the QTc interval was above 500 ms after start of chloroquine treatment or the change in QTc interval was more than 60 ms. A heart rate above 90 bpm, renal dysfunction, and a QTc interval below 450 ms were risk factors for QTc interval prolongation. Chloroquine prolongs the QTc interval in a substantial number of patients, potentially causing rhythm disturbances. Since there is no substantial evidence for a beneficial effect of chloroquine, these results discourage its use in COVID-19 patients.

As COVID-19 cases and deaths continue to expand globally, there is an urgent need to develop, test and approve effective antiviral therapies. Currently a majority of clinical trials are evaluating therapies in patients who are already hospitalized with SARS Co-V-2 infection. Given that the median time between development of symptoms and need for hospitalization is a week, a golden opportunity to intervene early is being missed. Indeed, for many other viral infections, early treatment soon after development of symptoms is associated with decreased mortality, lower hospitalization rates and lower likelihood of transmission to others. Here, we advocate for randomized double-blind placebo controlled clinical trials to evaluate promising agents early during SARS Co-V-2 infection.

The potential immune intersection between COVID-19 disease and cancer therapy raises important practical clinical questions and highlights multiple scientific gaps to be filled. Among available therapeutic approaches to be considered, immune checkpoint inhibitors (ICI) seem to require major attention as they may act at the crossroads between cancer treatment and COVID-19 disease, due to their profound immunomodulatory activity. On the basis of available literature evidence, we suggest guidance to consider for treating physicians, and propose areas of clinical and preclinical investigation. Comprehensively, although with the necessary caution, ICI therapy seems to remain a suitable therapeutic option for patients with cancer during the COVID-19 pandemic.

PurposeThis paper aims to underscore major opportunities for shared value innovation based on data management efficiency, which has often been overlooked so far. By integrating prior research about digital transformation, shared value creation, entrepreneurial marketing and the innovation-based view of firm performance, it addresses a major gap in the literature.Design/methodology/approachThe innovation-based arguments illustrate how efficient data management may lead to different types of innovation, which provide opportunities for growth and efficiency gains after the coronavirus pandemic.FindingsMany companies digitalization programs have concentrated on strengthening the efficiency of current business processes. Thus, these initiatives have contributed to the efficiency of traditional analog activities by using data and smart algorithms. In contrast, the efficiency of the underlying data management was largely neglected, but the COVID-19 pandemic has highlighted its importance. To overcome the limited emphasis on sustainability and efficiency in the digital context, this paper focuses on data management efficiency. After detailing this concept, it is linked to the growing literature about creating shared value, and a process segmentation for implementing shared value innovations in the field of digital efficiency is developed.Originality/valueThe paper extends research into digital transformation by emphasizing that the distinction of effectiveness and efficiency is as relevant in the digital context as in the traditional analog environment. It further provides new insights into creating shared value because it increases the awareness of researchers and managers to consider data management efficiency as a basis for shared value innovation with positive effects on the triple bottom line. The paper also contributes to entrepreneurial marketing research because data management efficiency provides significant opportunities for entrepreneurs, startup firms and innovators in established organizations to develop entirely new markets based on new services, solutions and business models. Finally, the paper deepens the understanding of the innovation-based view of firm performance.

This bibliometric review is aimed to analyze the top 100 most-cited publications in dentistry and to compare its outcomes. A literature search was performed using Elseviers Scopus, without any restriction of language, publication year, or study design. Of 336,381 articles, the top 100 were included based on their citation count, which ranged from 638 to 4728 citations (Feijoo et al., 326 to 2050). The most productive decade was the 2000s, with 40 articles on the list (Feijoo et al., 1980s: 26). Marx RE (7%) was the major contributor in this study (Feijoo et al., Socransky SS: 9%), and almost half (48%) of articles were from the USA. Of the top 100 articles, 26% focused on periodontology (Feijoo et al., periodontology: 43%), while 17% of the total were published in the Journal of Dental Research (Feijoo et al., Journal of Clinical Periodontology: 20%). Most of the publications were narrative reviews/expert opinion (36%), (Feijoo et al., case series: 22%), and were within the evidence level V (64%) (Feijoo et al., 54%). The citation count that a paper secures is not necessarily a reflection of researchs quality, however, the current analysis provides the latest citation trends in dentistry.

In this paper we conceptually identify the gap in the literature about lack of business's awareness in non \financial activities, especially biodiversity, which can be responsible for crisis like Covid\19 which can adversely affect the global economy. We recommend approaches to existing business about how to enhance the quality of reporting by considering non\human element in reporting and making it more comprehensive for the stakeholders. We adopt Actor Network Theory (ANT) and the Natural Inventory Model to support our argument that nature consists of both human and non\human. From our observation about the Covid\19 crisis and by consulting the existing relevant literature on CSR, Covid\19, non\financial reporting and integrated reports (IR), we propose the implication of non\financial reporting by companies based on a theoretical framework. We recommend that companies should implement/adopt Circular Economy concept for sustainable business model and report on biodiversity and extinction accounting in more structured and mandatory way via producing IR to create value on short, medium and long terms. This is the first paper to tackle the Covid\19 crisis and offer solution for future reporting. The findings will add value in the academia and society.

Introduction The coronavirus disease 2019 (COVID-19) vaccine is available across various countries worldwide, with public-private partnerships ensuring all individuals are vaccinated through a phased approach. Irrespective of the geographical spread, several myths pertaining to the COVID-19 vaccine have stemmed, ultimately limiting the national administration of vaccines and rollouts. This study assessed the acceptance of the COVID-19 vaccine among the general public in Pakistan. Methods A pre-validated questionnaire was administered from January 2021 to February 2021 to assess the public attitude and acceptance of the COVID-19 vaccine. Logistic regression analyses were run to identify factors associated with the acceptance among the population. Results A total of 936 responses were elicited, where 15% perceived their risk of being infected at 20-30% with an overall 70% agreeing to be vaccinated if recommended. Multivariate analysis identified higher acceptance in the male gender, healthcare workers, and students. Of all, 66% respondents chose healthcare workers and public officials, whereas 15.6% chose scientific literature, and 12.9% chose social media as the most reliable source of COVID-19 information. Conclusion Given the relatively greater trust in healthcare providers for information regarding COVID-19, healthcare workers ought to be on the frontline for vaccine campaigns and public outreach efforts, with governmental efforts in addition to the promotion of scientific materials for population-level understanding.

The coronavirus disease 2019 (COVID-19) pandemic has highlighted the need for different types of diagnostics, comparative validation of new tests, faster approval by federal agencies, and rapid production of test kits to meet global demands. In this Perspective, we discuss the utility and challenges of current diagnostics for COVID-19.

A case of the absorption of corona virus disease 2019 (COVID-19) promoted by professor Xu ZOU's acupuncture technique for "benefiting kidney and strengthening anti-pathogenic qi" is introduced. A female patient suffered from COVID-19, 64 years old, had been treated with acupuncture and Chinese herb granules for 10 days on the base of the oral administration of moxifloxacin. In the re-examination, the chest CT image indicated that the absorption of COVID-19 was obvious as compared with before, the nucleic acid test of novel corona virus was negative and the patient narrated no obvious discomfort. Acupuncture therapy plays its active adjuvant effect in the whole process of the treatment of COVID-19.

The study provides a comparative analysis of the impact of the pandemic on the situation of the e-commerce market in various countries and also identifies areas for improving the structure of the e-commerce market in Russia in the long term. The authors have established the prerequisites for the intensification of the development of the e-commerce market, including the expansion of access to the Internet, the growth of users of mobile devices and social networks;the gradually weakening offline retail sector;the implemented state policy of regulating the e-commerce market. The advantages of e-commerce over other forms of offline retail are established. It is shown that China and the United States are leaders in terms of the volume of the e-commerce market and its share in the retail segment. The authors analyzed the dynamics of the development of the e-commerce market in some countries during the COVID-2019 pandemic. It is proved that during the pandemic, the increase in Internet connections, quarantine measures and institutional restrictions of states provoked the growth of the e-commerce market in most countries. It is emphasized that the largest growth of the e-commerce market during the pandemic occurred in the United States, Great Britain, Poland, and Russia. The authors justified the directions of the state policy on improving the e-commerce market in Russia. ? 2022, The Author(s), under exclusive license to Springer Nature Switzerland AG.

There are many epidemiological models at hand to cope with the present pandemic; it is, however, difficult to calibrate these models when data are noisy, partial or observed only indirectly. It is also difficult to distinguish relevant data from noise, and to distinguish the impact of individual determinants of the epidemic. In mathematical statistics, the tools to handle all of these phenomena exist; however, they are seldom used for epidemiological models. The goal of this paper is to start filling this gap by proposing a general stochastic epidemiological model, which we call SEIR Filter. Technically our model is a heterogeneous partially observable vector auto-reg-ression model, in which we are able to express closed form formulas for the distribution of compartments and observations, so both maximum likelihood and least square estimators are analytically tractable. We give conditions for vanishing, explosion and stationary behaviour of the epidemic and we are able to express a closed form formula for reproduction number. Finally, we present several examples of the model's application. We construct an estimate age-cohort model of the COVID-19 pandemic in the Czech Republic. To demonstrate the strengths of the model, we employ it to analyse and compare three vaccination scenarios.

This seminar reviews important features and management issues of community-acquired pneumonia (CAP) that are especially relevant to immunocompetent adults in light of new information about cause, clinical course, diagnostic testing, treatment, and prevention. Streptococcus pneumoniae remains the most important pathogen; however, emerging resistance of this organism to antimicrobial agents has affected empirical treatment of CAP. Atypical pathogens have been quite commonly identified in several prospective studies. The clinical significance of these pathogens (with the exception of Legionella spp) is not clear, partly because of the lack of rapid, standardised tests. Diagnostic evaluation of CAP is important for appropriate assessment of severity of illness and for establishment of the causative agent in the disease. Until better rapid diagnostic methods are developed, most patients will be treated empirically. Antimicrobials continue to be the mainstay of treatment, and decisions about specific agents are guided by several considerations that include spectrum of activity, and pharmacokinetic and pharmacodynamic principles. Several factors have been shown to be associated with a beneficial clinical outcome in patients with CAP. These factors include administration of antimicrobials in a timely manner, choice of antibiotic therapy, and the use of a critical pneumonia pathway. The appropriate use of vaccines against pneumococcal disease and influenza should be encouraged. Several guidelines for management of CAP have recently been published, the recommendations of which are reviewed.

OBJECTIVES: To describe the importance of critical care clinical research that is not pandemic-focused during pandemic times; outline principles to assist in the prioritization of nonpandemic research during pandemic times; and propose a guiding framework for decisions about whether, when and how to continue nonpandemic research while still honoring the moral and scientific imperative to launch research that is pandemic-focused. DESIGN/DATA SOURCES: Using in-person, email, and videoconference exchanges, we convened an interprofessional clinical research group, conducted a literature review of empirical studies, ethics documents and expert commentaries (2010 to present), and viewed traditional and social media posts (March 2020 to May 2020). Stakeholder consultation involved scientific, ethics, clinical, and administrative leaders. SETTING: Clinical research in the ICU. PATIENTS: Patients with and without coronavirus disease 2019. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: While clinical research should be prioritized to advantage patients with coronavirus disease 2019 in order to care for affected patients, it ideally would not unduly disadvantage patients without coronavirus disease 2019. Thus, timely, rigorous, relevant, and ethical clinical research is needed to improve the care and optimize outcomes for both patients with and without coronavirus disease 2019, acknowledging how many studies that are not exclusively focused on coronavirus disease 2019 remain relevant to patients with coronavirus disease 2019. Considerations to continue nonpandemic-focused research include the status of the pandemic, local jurisdictional guidance, capacity and safety of bedside and research personnel, disposition of patients already enrolled in nonpandemic studies, analyzing characteristics of each nonpandemic-focused study, research oversight, and final reporting requirements. CONCLUSIONS: Deliberation about continuing nonpandemic research should use objective, transparent criteria considering several aspects of the research process such as bedside and research staff safety, infection control, the informed consent model, protocol complexity, data collection, and implementation integrity. Decisions to pause or pursue nonpandemic research should be proportionate, transparent, and revisited as the pandemic abates.