Insights into COVID-19 epidemiology and control from temporal changes in serial interval distributions in Hong Kong.

The serial interval distribution is used to approximate the generation time distribution, an essential parameter to infer the transmissibility (${R}_t$) of an epidemic. However, serial interval distributions may change as an epidemic progresses. We examined detailed contact tracing data on laboratory-confirmed cases of COVID-19 in Hong Kong during the five waves from January 2020 to July 2022.

Patient's perceptions of buprenorphine use receiving treatment for cancer.

Objective: To assess knowledge and attitudes toward opioids and buprenorphine (BUP) of patients with cancer.

Design: Single-site, single-intervention telephone survey of patients under palliative care at the cancer center.

Outcomes: Forty percent of the participants recognized the word "buprenorphine," and 28 percent recognized BUP indication for addiction treatment.

FBXO11 governs macrophage cell death and inflammation in response to bacterial toxins.

causes severe infections such as pneumonia and sepsis depending on the pore-forming toxin Panton-Valentine leukocidin (PVL). PVL kills and induces inflammation in macrophages and other myeloid cells by interacting with the human cell surface receptor, complement 5a receptor 1 (C5aR1). C5aR1 expression is tighly regulated and may thus modulate PVL activity, although the mechanisms involved remain incompletely understood.

The Incubation Period Distribution of Coronavirus Disease 2019: A Systematic Review and Meta-analysis.

Incubation period is an important parameter to inform quarantine period and to study transmission dynamics of infectious diseases. We conducted a systematic review and meta-analysis on published estimates of the incubation period distribution of coronavirus disease 2019, and showed that the pooled median of the point estimates of the mean, median and 95th percentile for incubation period are 6.3 days (range, 1.

Serial Intervals and Case Isolation Delays for Coronavirus Disease 2019: A Systematic Review and Meta-Analysis.

Background: Estimates of the serial interval distribution contribute to our understanding of the transmission dynamics of coronavirus disease 2019 (COVID-19). Here, we aimed to summarize the existing evidence on serial interval distributions and delays in case isolation for COVID-19.

Methods: We conducted a systematic review of the published literature and preprints in PubMed on 2 epidemiological parameters, namely, serial intervals and delay intervals relating to isolation of cases for COVID-19 from 1 January 2020 to 22 October 2020 following predefined eligibility criteria.

COVID-19 transmission in Hong Kong despite universal masking.

Objectives: mask-wearing outside the home has been almost universal in Hong Kong since late January 2020 with very high compliance. Nevertheless, community spread of COVID-19 has still occurred. We aimed to assess the settings where COVID-19 transmission occurred and determine the fraction of transmission events that occurred in settings where masks are not usually worn.

Targeting NLRP3 and Staphylococcal pore-forming toxin receptors in human-induced pluripotent stem cell-derived macrophages.

Staphylococcus aureus causes necrotizing pneumonia by secreting toxins such as leukocidins that target front-line immune cells. The mechanism by which leukocidins kill innate immune cells and trigger inflammation during S. aureus lung infection, however, remains unresolved.

NtrBC Regulates Invasiveness and Virulence of During High-Density Infection.

is an opportunistic pathogen that is a major cause of nosocomial and chronic infections contributing to morbidity and mortality in cystic fibrosis patients. One of the reasons for its success as a pathogen is its ability to adapt to a broad range of circumstances. Here, we show the involvement of the general nitrogen regulator NtrBC, which is structurally conserved but functionally diverse across species, in pathogenic and adaptive states of .

IRF5 Promotes Influenza Virus-Induced Inflammatory Responses in Human Induced Pluripotent Stem Cell-Derived Myeloid Cells and Murine Models.

Recognition of influenza A virus (IAV) by the innate immune system triggers pathways that restrict viral replication, activate innate immune cells, and regulate adaptive immunity. However, excessive innate immune activation can exaggerate disease. The pathways promoting excessive activation are incompletely understood, with limited experimental models to investigate the mechanisms driving influenza virus-induced inflammation in humans.

Loss of IL-10 signaling in macrophages limits bacterial killing driven by prostaglandin E2.

Loss of IL-10 signaling in macrophages (Mφs) leads to inflammatory bowel disease (IBD). Induced pluripotent stem cells (iPSCs) were generated from an infantile-onset IBD patient lacking a functional IL10RB gene. Mφs differentiated from IL-10RB-/- iPSCs lacked IL-10RB mRNA expression, were unable to phosphorylate STAT3, and failed to reduce LPS induced inflammatory cytokines in the presence of exogenous IL-10.

A Genome-Wide Knockout Screen in Human Macrophages Identified Host Factors Modulating Infection.

A genome-scale CRISPR knockout library screen of THP-1 human macrophages was performed to identify loss-of-function mutations conferring resistance to uptake. The screen identified 183 candidate genes, from which 14 representative genes involved in actin dynamics (, , , , , , and ), glycosaminoglycan metabolism (), receptor signaling ( and ), lipid raft formation (), calcium transport ( and ), and cholesterol metabolism () were analyzed further. For some of these pathways, known chemical inhibitors could replicate the resistance phenotype, indicating their potential as targets for host-directed therapy.

Using a Systems Biology Approach To Study Host-Pathogen Interactions.

The rapid development of genomics and other "-omics" approaches has significantly impacted how we have investigated host-pathogen interactions since the turn of the millennium. Technologies such as next-generation sequencing, stem cell biology, and high-throughput proteomics have transformed the scale and sensitivity with which we interrogate biological samples. These approaches are impacting experimental design in the laboratory and transforming clinical management in health care systems.

Interleukin-22 promotes phagolysosomal fusion to induce protection against Typhimurium in human epithelial cells.

Intestinal epithelial cells (IECs) play a key role in regulating immune responses and controlling infection. However, the direct role of IECs in restricting pathogens remains incompletely understood. Here, we provide evidence that IL-22 primed intestinal organoids derived from healthy human induced pluripotent stem cells (hIPSCs) to restrict serovar Typhimurium SL1344 infection.

Broad-Spectrum Adaptive Antibiotic Resistance Associated with Pseudomonas aeruginosa Mucin-Dependent Surfing Motility.

Surfing motility is a novel form of surface adaptation exhibited by the nosocomial pathogen in the presence of the glycoprotein mucin, which is found in high abundance at mucosal surfaces, especially those of the lungs of cystic fibrosis and bronchiectasis patients. Here, we investigated the adaptive antibiotic resistance of under conditions in which surfing occurs compared that in to cells undergoing swimming. surfing cells were significantly more resistant to several classes of antibiotics, including aminoglycosides, carbapenems, polymyxins, and fluoroquinolones.

Novel roles for two-component regulatory systems in cytotoxicity and virulence-related properties in .

The rapid adaptation of the opportunistic bacterial pathogen to various growth modes and environmental conditions is controlled in part through diverse two-component regulatory systems. Some of these systems are well studied, but the majority are poorly characterized, even though it is likely that several of these systems contribute to virulence. Here, we screened all available strain PA14 mutants in 50 sensor kinases, 50 response regulators and 5 hybrid sensor/regulators, for contributions to cytotoxicity against cultured human bronchial epithelial cells, as assessed by the release of cytosolic lactate dehydrogenase.

Exploiting induced pluripotent stem cell-derived macrophages to unravel host factors influencing Chlamydia trachomatis pathogenesis.

Chlamydia trachomatis remains a leading cause of bacterial sexually transmitted infections and preventable blindness worldwide. There are, however, limited in vitro models to study the role of host genetics in the response of macrophages to this obligate human pathogen. Here, we describe an approach using macrophages derived from human induced pluripotent stem cells (iPSdMs) to study macrophage-Chlamydia interactions in vitro.

Induced pluripotent stem cell derived macrophages as a cellular system to study salmonella and other pathogens.

A number of pathogens, including several human-restricted organisms, persist and replicate within macrophages (Mφs) as a key step in pathogenesis. The mechanisms underpinning such host-restricted intracellular adaptations are poorly understood, in part, due to a lack of appropriate model systems. Here we explore the potential of human induced pluripotent stem cell derived macrophages (iPSDMs) to study such pathogen interactions.

Performance of the VITEK MS matrix-assisted laser desorption ionization-time of flight mass spectrometry system for rapid bacterial identification in two diagnostic centres in China.

Matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) MS systems was not officially launched for diagnostic use in clinical microbiology laboratories in China until 2012. Here, we report the findings from the first large-scale evaluation study of VITEK MS for routine bacterial identification in two major diagnostic centres in Beijing and Hong Kong. A total of 2266 unique isolates representing 56 genera and 127 species were analysed, and results were compared to those obtained by VITEK 2.

Antibiotic resistance in Pseudomonas aeruginosa biofilms: towards the development of novel anti-biofilm therapies.

The growth of bacteria as structured aggregates termed biofilms leads to their protection from harsh environmental conditions such as physical and chemical stresses, shearing forces, and limited nutrient availability. Because of this highly adapted ability to survive adverse environmental conditions, bacterial biofilms are recalcitrant to antibiotic therapies and immune clearance. This is particularly problematic in hospital settings where biofilms are a frequent cause of chronic and device-related infections and constitute a significant burden on the health-care system.

Requirement of the Pseudomonas aeruginosa CbrA sensor kinase for full virulence in a murine acute lung infection model.

Pseudomonas aeruginosa is an opportunistic pathogen that is a major cause of respiratory tract and other nosocomial infections. The sensor kinase CbrA is a central regulator of carbon and nitrogen metabolism and in vitro also regulates virulence-related processes in P. aeruginosa.

TypA is involved in virulence, antimicrobial resistance and biofilm formation in Pseudomonas aeruginosa.

Background: Pseudomonas aeruginosa is an important opportunistic human pathogen and is extremely difficult to treat due to its high intrinsic and adaptive antibiotic resistance, ability to form biofilms in chronic infections and broad arsenal of virulence factors, which are finely regulated. TypA is a GTPase that has recently been identified to modulate virulence in enteric Gram-negative pathogens.

Results: Here, we demonstrate that mutation of typA in P.

Mucin promotes rapid surface motility in Pseudomonas aeruginosa.

Unlabelled: An important environmental factor that determines the mode of motility adopted by Pseudomonas aeruginosa is the viscosity of the medium, often provided by adjusting agar concentrations in vitro. However, the viscous gel-like property of the mucus layer that overlays epithelial surfaces is largely due to the glycoprotein mucin. P.

Therapeutic potential of host defense peptides in antibiotic-resistant infections.

The emergence of infections caused by multi-drug resistant (MDR) pathogens pose a major burden to modern healthcare. Exacerbating this issue is the substantial decline in development of new classes of antibiotics by pharmaceutical companies. This has led to renewed interest in the therapeutic potential of natural anti-infective agents such as host defense peptides (HDPs).

Plasma-modified biomaterials for self-antimicrobial applications.

The surface compatibility and antibacterial properties of biomaterials are crucial to tissue engineering and other medical applications, and plasma-assisted technologies have been employed to enhance these characteristics with good success. Herein, we describe and review the recent developments made by our interdisciplinary team on self-antimicrobial biomaterials with emphasis on plasma-based surface modification. Our results indicate that a self-antibacterial surface can be produced on various types of materials including polymers, metals, and ceramics by plasma treatment.

Multifunctional cationic host defence peptides and their clinical applications.

With the rapid rise in the emergence of bacterial strains resistant to multiple classes of antimicrobial agents, there is an urgent need to develop novel antimicrobial therapies to combat these pathogens. Cationic host defence peptides (HDPs) and synthetic derivatives termed innate defence regulators (IDRs) represent a promising alternative approach in the treatment of microbial-related diseases. Cationic HDPs (also termed antimicrobial peptides) have emerged from their origins as nature's antibiotics and are widely distributed in organisms from insects to plants to mammals and non-mammalian vertebrates.