The recent outbreak of severe acute respiratory syndrome (SARS) provided an opportunity to study the antibody response of infected individuals to the causative virus, SARS coronavirus. We examined ...serum samples obtained from 46 patients with SARS, 40 patients with non-SARS pneumonia, and 38 healthy individuals, by use of Western blotting (WB), enzyme-linked immunoassay (ELISA), and immunofluorescence assay, using both native and bacterially produced antigens of the virus. We found a highly restricted, immunoglobulin G-dominated antibody response in patients with SARS, directed most frequently (89% by ELISA) and predominantly at the nucleocapsid. Almost all of the subjects without SARS had no antinucleocapsid antibodies. The spike protein was the next most frequently targeted, but only 63% of the patients (by ELISA) responded. Other targets of the response identified by use of WB included antigens of 80 and 60 kDa. Several nonstructural proteins cloned were not antigenic, and the culture-derived nucleocapsid appeared to be specifically degraded.
Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) and asthma are associated with a variety of precipitating factors including infection. This study assessed the infective viral ...etiologies by real-time multiplex polymerase chain reaction of patients hospitalized with AECOPD and asthma exacerbations. In addition, infective etiologies were assessed for association with the clinical outcome of the patients.
Adults admitted with AECOPD and asthma exacerbations between August 2016 and July 2017 were recruited. Nasopharyngeal aspirate (NPA) samples were obtained from the patients within 1-2 days of admission and subjected to pathogen detection and human rhinovirus (HRV) typing.
Altogether 402 patients with AECOPD, 80 stable COPD, 100 asthma exacerbation and 21 stable asthma subjects were recruited. Among those admitted for AECOPD and asthma exacerbations, 141(35.1%) and 45(45.0%) respectively had pathogens identified in the NPA specimens. The commonest virus identified was influenza A followed by HRV. HRV typing identified HRV-A and HRV-C as the more common HRV with a wide variety of genotypes. Identification of pathogens in NPA or HRV typing otherwise did not affect clinical outcomes including the hospital length of stay, readmission rates and mortality except that identification of pathogens in asthma exacerbation was associated with a lower rate of readmissions at 30 and 60 days.
Many respiratory viruses were associated with AECOPD and asthma exacerbation. HRV-A and HRV-C were the more common HRV associated with exacerbations. Identification of pathogens in NPA was associated with less readmissions for asthma patients at 30 and 60 days.
ClinicalTrials.gov NCT02866357 .
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Oseltamivir represents one of the most successful neuraminidase (NA) inhibitors in the current anti-influenza therapy. The 150-cavity of NA was identified as an additional binding pocket, and novel ...NA inhibitors have been designed to occupy the 150-cavity based on the structure information of oseltamivir carboxylate (OC) in complex with NA. In this study, a series of C-5-NH2-acyl derivatives of OC containing the pyrazole moiety were synthesized. Several derivatives exhibited substantial inhibitory activity against NA. Moreover, in silico ADME evaluation indicated that the derivatives were drug-like with higher oral absorption rates and greater cell permeability than OC. Additionally, molecular docking studies revealed that the derivatives interacted with both the NA enzyme active site and 150-cavity as expected. The results provided useful information for further structural optimization of OC.
Cancer arising from the uterine cervix is the fourth most common cause of cancer death among women worldwide. Almost 90% of cervical cancer mortality has occurred in low- and middle-income countries. ...One of the major aetiologies contributing to cervical cancer is the persistent infection by the cancer-causing types of the human papillomavirus. The disease is preventable if the premalignant lesion is detected early and managed effectively. In this review, we outlined the standard guidelines that have been introduced and implemented worldwide for decades, including the cytology, the HPV detection and genotyping, and the immunostaining of surrogate markers. In addition, the staging system used to classify the premalignancy and malignancy of the uterine cervix, as well as the safety and efficacy of the various treatment modalities in clinical trials for cervical cancers, are also discussed. In this millennial world, the advancements in computer-aided technology, including robotic modules and artificial intelligence (AI), are also incorporated into the screening, diagnostic, and treatment platforms. These innovations reduce the dependence on specialists and technologists, as well as the work burden and time incurred for sample processing. However, concerns over the practicality of these advancements remain, due to the high cost, lack of flexibility, and the judgment of a trained professional that is currently not replaceable by a machine.
Discovery of antimicrobial agents with a novel model of action is in urgent need for the clinical management of multidrug-resistant bacterial infections. Recently, we reported the identification of a ...first-in-class bacterial ribosomal RNA synthesis inhibitor, which interrupted the interaction between the bacterial transcription factor NusB and NusE. In this study, a series of diaryl derivatives were rationally designed and synthesized based on the previously established pharmacophore model. Inhibitory activity against the NusB-NusE binding, circular dichroism of compound treated NusB, antimicrobial activity, cytotoxicity, hemolytic property and cell permeability using Caco-2 cells were measured. Structure-activity relationship and quantitative structure–activity relationship were also concluded and discussed. Some of the derivatives demonstrated improved antimicrobial activity than the hit compound against a panel of clinically important pathogens, lowering the minimum inhibition concentration to 1–2 μg/mL against Staphylococcus aureus, including clinical strains of methicillin-resistant Staphylococcus aureus at a level comparable to some of the marketed antibiotics. Given the improved antimicrobial activity, specific inhibition of target protein-protein interaction and promising pharmacokinetic properties without significant cytotoxicity, this series of diaryl compounds have high potentials and deserve for further studies towards a new class of antimicrobial agents in the future.
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•Diarylimines and –amines were designed to target the specific NusB-NusE interaction in bacteria.•Representative compounds displayed excellent antimicrobial activity against MRSA strains.•Representative compounds showed low cytotoxicity to Human A549 and HaCaT cells.•Compounds 27 and 28 demonstrated excellent pharmacokinetic properties.
Coronavirus disease 2019 (COVID-19) is increasing worldwide, with complications due to frequent viral mutations, an intricate pathophysiology, and variable host immune responses. Biomarkers with ...predictive and prognostic value are crucial but lacking.
Serum samples from authentic and D614G variant (non-Omicron), and Omicron-SARS-CoV-2 infected patients were collected for METRNβ detection and longitudinal cytokine/chemokine analysis. Correlation analyses were performed to compare the relationships between serum METRNβ levels and cytokines/chemokines, laboratory parameters, and disease severity. Receiver operating characteristic (ROC) curves and Kaplan-Meier survival curves were used to evaluate the predictive value of METRNβ in COVID-19.
The serum level of METRNβ was highly elevated in non-Omicron-SARS-CoV-2 infected patients compared to healthy individuals, and the non-survivor displayed higher METRNβ levels than survivors among the critical ones. METRNβ concentration showed positive correlation with viral load in NAPS. ROC curve showed that a baseline METRNβ level of 1886.89 pg/ml distinguished COVID-19 patients from non-infected individuals with an AUC of 0.830. Longitudinal analysis of cytokine/chemokine profiles revealed a positive correlation between METRNβ and pro-inflammatory cytokines such as IL6, and an inverse correlation with soluble CD40L (sCD40L). Higher METRNβ was associated with increased mortality. These findings were validated in a second and third cohort of COVID-19 patients identified in a subsequent wave.
Our study uncovered the precise role of METRNβ in predicting the severity of COVID-19, thus providing a scientific basis for further evaluation of the role of METRNβ in triage therapeutic strategies.
Altered microbiome composition and aberrant promoter hypermethylation of tumor suppressor genes (TSGs) are two important hallmarks of colorectal cancer (CRC). Here we performed concurrent 16S rRNA ...gene sequencing and methyl-CpG binding domain-based capture sequencing in 33 tissue biopsies (5 normal colonic mucosa tissues, 4 pairs of adenoma and adenoma-adjacent tissues, and 10 pairs of CRC and CRC-adjacent tissues) to identify significant associations between TSG promoter hypermethylation and CRC-associated bacteria, followed by functional validation of the methylation-associated bacteria.
Fusobacterium nucleatum and Hungatella hathewayi were identified as the top two methylation-regulating bacteria. Targeted analysis on bona fide TSGs revealed that H. hathewayi and Streptococcus spp. significantly correlated with CDX2 and MLH1 promoter hypermethylation, respectively. Mechanistic validation with cell-line and animal models revealed that F. nucleatum and H. hathewayi upregulated DNA methyltransferase. H. hathewayi inoculation also promoted colonic epithelial cell proliferation in germ-free and conventional mice.
Our integrative analysis revealed previously unknown epigenetic regulation of TSGs in host cells through inducing DNA methyltransferase by F. nucleatum and H. hathewayi, and established the latter as CRC-promoting bacteria. Video abstract.
Focal Colors Are Universal after All Regier, Terry; Kay, Paul; Cook, Richard S.
Proceedings of the National Academy of Sciences - PNAS,
06/2005, Letnik:
102, Številka:
23
Journal Article
Recenzirano
Odprti dostop
It is widely held that named color categories in the world's languages are organized around universal focal colors and that these focal colors tend to be chosen as the best examples of color terms ...across languages. However, this notion has been supported primarily by data from languages of industrialized societies. In contrast, recent research on a language from a nonindustrialized society has called this idea into question. We examine color-naming data from languages of 110 nonindustrialized societies and show that (i) best-example choices for color terms in these languages cluster near the prototypes for English white, black, red, green, yellow, and blue, and (ii) best-example choices cluster more tightly across languages than do the centers of category extensions, suggesting that universal best examples (foci) may be the source of universal tendencies in color naming.
To examine the level of resilience among the frontline healthcare workers (HCWs) in four different Southeast Asian jurisdictions and identify the potential factors that may enhance healthcare workers ...resilience.
An online cross-sectional survey was carried out among 3,048 eligible healthcare workers in Hong Kong, Nepal, Vietnam, and Taiwan from May 2021 to July 2022, and information on individual resilience, socio-demographic characteristics, organizational supports, and personal exposures were collected. A binary logistic regression model was used to identify the factors that were associated with a high resilience level.
The resilience score was the highest among healthcare workers of Vietnam, followed by Taiwan and Hong Kong, with Nepal scoring the lowest. Participants with old age, part-time work, higher education level, more satisfaction with workplace policy, better organizational supports, and fewer COVID-specific worries were associated with higher resilience. Healthcare workers who were satisfied with the overall organizational policy support had an OR of 1.48 (95% CI: 1.25-1.76) for a high resilience level.
Implementing satisfying organizational policies and establishing supportive work environments for frontline healthcare workers can increase individual resilience and organizational stability.
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