LAAM

Objectives: The World Health Organization (WHO) had designated the SARS-CoV-2 lineage B.1.1.529 as the new Variant of Concern Omicron (VOC-Omicron) on 26th November 20211 . Real-time reverse transcription polymerase chain reaction (RT-PCR), single nucleotide polymorphisms (SNP) and whole genome sequencing (WGS) tests were widely employed to detect SARS-CoV-2 and its variant. Yet, the SARS-CoV-2 Omicron detection performance of commercial real-time RT-PCR platforms and SARS-CoV-2 spike SNP assays remain to be elucidated...

OBJECTIVES: To evaluate the inhibitory effect of a novel mussel-inspired monomer (N-(3,4-dihydroxyphenethyl)methacrylamide (DMA) on the soluble and matrix-bound proteases. METHODS: The inhibitory effect of DMA (0, 1, 5, and 10 mM) and 1 mM chlorhexidine (CHX) dissolved in 50% ethanol/water on soluble recombinant human matrix metalloproteinases (rhMMP-2, -8, and -9), as well as cysteine cathepsins (B and K) were evaluated using both fluorometric assay kits and molecular docking...

BACKGROUND: Walk tests are the most common, simple, and easy-to-administer tests to measure walking ability, monitor changes in gait performance and evaluate the effects of interventions in clinical settings. To apply walk tests with confidence, clinicians need to understand their psychometrically properties (e.g., reliability and validity) for a particular population. This systematic review aimed to analyze the reliability and validity of clinically-oriented walk tests for older adults with dementia...

BACKGROUND: Patients boarding in the emergency department (ED) as a result of delays in bed placement are associated with increased morbidity and mortality. Prior literature on ED boarding does not explore the impact of boarding on patients admitted to the hospital from the ED. The objective of this study was to evaluate the impact of patient boarding on ED length of stay for all patients admitted to the hospital. METHODS: This was an institutional review board-approved, retrospective review of all patients from January 1, 2015, through June 30, 2019, presenting to 2 large EDs in a single health system in Pennsylvania...

The occurrence and spatial distribution of bisphenol A (BPA) and analogues bisphenol B (BPB), bisphenol F (BPF) and bisphenol S (BPS) were investigated in microplastic on 11 beaches in Hong Kong. At 10 sites, BPA was the only detected chemical with concentrations ranged from 82.4-989 ng g-1 microplastic. BPA, BPB and BPS co-occurred at only one site, where it is located close proximity to the outfall of a sewage treatment plant. There was no significant spatial difference of BPA concentrations in microplastic when all the sites were considered, indicating that some remote and presumably cleaner beaches have been contaminated...

Commercial and private deployment of airborne drones is revolutionising many ecosystems. To identify critical issues and research gaps, our systematic literature review findings suggest that historic issues such as privacy, acceptance and security are increasingly replaced by operational considerations including interaction with and impacts on other airspace users. Recent incidents show that unrestricted drone use can inflict problems on other airspace users like airports and emergency services. Our review of current regulatory approaches shows a need for further policy and management response to both manage rapid and efficient drone usage growth, and facilitate innovation (e...

INTRODUCTION: Heated tobacco products (HTPs) are increasingly popular worldwide, but whether they aid or undermine cigarette abstinence remains uncertain. We examined the predictors of HTP initiation and the prospective association of HTP use with cigarette abstinence in community-based smokers in Hong Kong. DESIGN: Secondary analysis of a randomised clinical trial aimed to evaluate the effectiveness of brief advice and referral for smoking cessation. The interventions were not related to HTP use...

WAP-8294A2 is a cyclic peptide antibiotic with novel structure and excellent activity against Gram-positive pathogens. Herein, we report the total synthesis of complex macrocyclic peptide WAP-8294A2 (W1), ent-analogue W2, deoxy analogue W3 and de-methyl analogue W4 using a solid-phase synthetic route followed by a final stage solution-phase cyclization reaction. Exploitation of this process allowed the synthesis of eleven alanine-scanning analogues and eight lysine-scanning analogues. The antimicrobial activity of these analogues was evaluated in vitro against Gram-positive bacteria...

Background: Cerebellar ataxia affects the coordination and balance of patients. The impact of this disease increases burden in patients, caregivers and society. Costs and the burden of this disease have not been investigated in Hong Kong. Objectives: (1) To estimate the socioeconomic cost of cerebellar ataxia in Hong Kong for the base year 2019, (2) to assess the health-related quality of life (HRQoL) and severity of ataxia, and (3) to establish the correlation between the severity and cost of cerebellar ataxia and to examine the correlation between the severity of cerebellar ataxia and HRQoL...

The development of novel antibiotics is critical to combating the growing emergence of drug-resistant pathogens. Malacidin A is a new member of the calcium-dependent antibiotic (CDAs) family with activity against antibiotic-resistant pathogens. Its mode of action is distinct from classical CDAs. However, the absolute structure of malacidin A has not been established. Herein, the total syntheses of malacidin A and its analogues are reported by a combination of Fmoc-based solid-phase peptide synthesis (SPPS) and β-hydroxyaspartic acid ligation-mediated peptide cyclization...

Daptomycin is effective in treating infections caused by antibiotic-resistant Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococci (VRE), and vancomycin-resistant S. aureus (VRSA). Due to its distinct mechanism of action toward multidrug-resistant bacteria, daptomycin provides an attractive structural motif to generate new daptomycin-based antibiotics to combat the problem of bacterial resistance. In this study, we used the total synthesis method to produce daptomycin analogues with a variety in terms of types and sites of modifications...

New support was fabricated to enhance the enzyme activity of cellulase following immobilization. Functionalized core-shell magnetic gold nanoparticles were prepared and characterized by X-ray diffraction (XRD), vibrating sample magnetometer (VSM), scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Cellulase enzyme was immobilized on support via covalent bonding. The successful binding of the enzyme was chemically confirmed by Fourier-transform infrared spectroscopy (FTIR). The binding efficiency was 84% determined by Bradford assay...

A convergent synthesis via the late-stage serine ligation of naturally occurring calcium-dependent antibiotic CDA3a and its analogues has been developed, which allowed us to readily synthesize the analogues with the variation on the lipid tail. Some analogues were found to show 100-500-fold higher antimicrobial activity than the natural compound CDA3a against drug resistant bacteria. This study will enhance our understanding of CDA3a and provide valuable antibacterial lead candidates for further development...

Circulating adiponectin (APN) levels decrease with age and obesity. On the other hand, a reduction in APN levels is associated with neurodegeneration and neuroinflammation. We previously showed that aged adiponectin knockout (APN-/- ) mice developed Alzheimer's like pathologies, cerebral insulin resistance, and cognitive impairments. More recently, we also demonstrated that APN deficiency increased Aβ-induced microglia activation and neuroinflammatory responses in 5xFAD mice. There is compelling evidence that deregulated insulin activities or cerebral insulin resistance contributes to neuroinflammation and Alzheimer's disease (AD) pathogenesis...

Increased usage of daptomycin to treat infections caused by Gram-positive bacterial pathogens has resulted in emergence of resistant mutants. In a search for more effective daptomycin analogues through medicinal chemistry studies, we found that methylation at the nonproteinogenic amino acid kynurenine in daptomycin could result in significant enhancement of antibacterial activity. Termed "kynomycin," this new antibiotic exhibits higher antibacterial activity than daptomycin and is able to eradicate methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus ( VRE) strains, including daptomycin-resistant strains...

BACKGROUND: The notable discrepancy between platelet count and bleeding manifestations in immune thrombocytopenia (ITP) patients with acquired Glanzmann thrombasthenia (GT) has been described. OBJECTIVES: We aimed to examine the mechanisms responsible for thrombocytopenia and the bleeding phenotype in a patient with acquired GT. PATIENT, METHODS, AND RESULTS: A patient with primary ITP underwent splenectomy due to steroid intolerance...

A54145 is a family of antibacterial cyclic lipodepsipeptides structurally resembling daptomycin. Since its discovery in 1990, only the ambiguous structures of the methoxy-aspartic acid (MeO-Asp) and the hydroxy-asparagine (HO-Asn) have been reported. We have developed efficient routes to obtain the fully protected l-MeO-Asp and l-HO-Asn building blocks compatible with Fmoc-SPPS, and a total synthesis of A54145 that enabled us to establish its structure, consisting of l-3 S -HO-Asn and l-3 R -MeO-Asp, revising the wrongly proposed structure of l-3 S -MeO-Asp...

BACKGROUND: Microglia-mediated neuroinflammation is important in Alzheimer's disease (AD) pathogenesis. Extracellular deposition of β-amyloid (Aβ), a major pathological hallmark of AD, can induce microglia activation. Adiponectin (APN), an adipocyte-derived adipokine, exerts anti-inflammatory effects in the periphery and brain. Chronic APN deficiency leads to cognitive impairment and AD-like pathologies in aged mice. Here, we aim to study the role of APN in regulating microglia-mediated neuroinflammation in AD...

Legionella pneumophila, among other bacteria, may enter a viable but non-culturable state as a means for survival in stressful conditions. Bacterial cells in the viable but non-culturable state cannot grow on standard medium; however, they continue to exhibit characteristics that are associated with live cells, such as respiration, transcription, and cell wall integrity. The present paper outlines a detailed protocol for the detection of viable but non-culturable L. pneumophila cells via Syto® 9 and propidium iodide staining coupled with flow cytometry...

In mammals, urorectal development starts at early embryonic stage, defective urorectal development results in anorectal malformations, which are common congenital developmental defects of the anus and the urethra in newborns. The etiology and embryology of the defects are still largely unknown. Platelet-derived growth factor receptor alpha (Pdgfra) is a cell surface receptor tyrosine kinase, upon binding to its ligands (Pdgfa-d), mediates intracellular signaling and regulates embryonic development. The expression of Pdgfra is tightly regulated in the developing urorectal mesenchyme, and its dysregulation is associated with urorectal defects in animals with urorectal defects...