The coronavirus disease 2019 (COVID-19) pandemic has resulted in millions of patients infected worldwide and indirectly affecting even more individuals through disruption of daily living. Long-term ...adverse outcomes have been reported with similar diseases from other coronaviruses, namely Middle East Respiratory Syndrome (MERS) and Severe Acute Respiratory Syndrome (SARS). Emerging evidence suggests that COVID-19 adversely affects different systems in the human body. This review summarizes the current evidence on the short-term adverse health outcomes and assesses the risk of potential long-term adverse outcomes of COVID-19. Major adverse outcomes were found to affect different body systems: immune system (including but not limited to Guillain-Barré syndrome and paediatric inflammatory multisystem syndrome), respiratory system (lung fibrosis and pulmonary thromboembolism), cardiovascular system (cardiomyopathy and coagulopathy), neurological system (sensory dysfunction and stroke), as well as cutaneous and gastrointestinal manifestations, impaired hepatic and renal function. Mental health in patients with COVID-19 was also found to be adversely affected. The burden of caring for COVID-19 survivors is likely to be huge. Therefore, it is important for policy makers to develop comprehensive strategies in providing resources and capacity in the healthcare system. Future epidemiological studies are needed to further investigate the long-term impact on COVID-19 survivors.
Inspired by Karl Polanyi's argument that the institution of money offers an essential insight into the economy as an instituted process, I examine the extent to which the recent proposals presented ...in various countries to formulate their central bank digital currencies (CBDCs) actually represent the reactions of governments to the new development paths of their respective society in the digital age. To illustrate this, I scrutinize the particular social, political and economic dimensions of the instituted process which have led to the launch of the digital yuan by the Chinese government in 2021. I also argue that the formulation of the digital yuan is specific to the particular contextual settings of China and their progress. Finally, I argue that the evolving role and long-term influence of the digital yuan in a global context is largely subject to the competition of the world's major upcoming CBDCs like the U.S. dollar and euro.
Thioamides antithyroid‐drugs (ATDs) are important in hyperthyroid disease management. Identification of the susceptibility locus of ATD‐induced agranulocytosis is important for clinical management. ...We performed a genome‐wide association study (GWAS) involving 20 patients with ATD‐induced agranulocytosis and 775 healthy controls. The top finding was further replicated. A single‐nucleotide polymorphism (SNP), rs185386680, showed the strongest association with ATD‐induced agranulocytosis in GWAS (odds ratio (OR) = 36.4; 95% confidence interval (CI) = 12.8–103.7; P = 1.3 × 10‐24) and replication (OR = 37; 95% CI = 3.7–367.4; P = 9.6 × 10‐7). HLA‐B*38:02:01 was in complete linkage disequilibrium with rs185386680. High‐resolution HLA typing confirmed that HLA‐B*38:02:01 was associated with carbimazole (CMZ)/methimazole (MMI)‐induced agranulocytosis (OR = 265.5; 95% CI = 27.9–2528.0; P = 2.5 × 10‐14), but not associated with propylthiouracil (PTU). The positive and negative predictive values of HLA‐B*38:02:01 in predicting CMZ/MMI‐induced agranulocytosis were 0.07 and 0.999. Approximately 211 cases need to be screened to prevent one case. Screening for the risk allele will be useful in preventing agranulocytosis in populations in which the frequency of the risk allele is high.
Background There has been no study on antibiotic‐resistant Propionibacterium acnes in Hong Kong.
Objective We investigated the prevalence and pattern of antibiotic‐resistant P. acnes and to ...identify any associated factors for harbouring the resistant strains.
Methods Culture and sensitivity testing of P. acnes to commonly used antibiotics were performed. Resistance to tetracycline was defined at a minimal inhibitory concentration (MIC) of 2 μg/mL or more; erythromycin at an MIC of 0.5 μg/mL or more; clindamycin at an MIC of 0.25 μg/mL or more according to EUCAST. For breakpoints of doxycycline and minocycline, those with an MIC of 1 μg/mL or more were defined as resistant strains.
Results Among the 111 specimens collected from 111 patients, 86 strains of P. acnes were recovered, one from each specimen. Twenty‐five specimens had no growth. Forty‐seven (54.8%) strains were found to be resistant to one or more antibiotics. Forty‐six (53.5%), 18 (20.9%), 14 (16.3%), 14(16.3%) and 14 (16.3%) strains were resistant to clindamycin (CL), erythromycin (EM), tetracycline (TET), doxycycline (DOX) and minocycline (MR) respectively. Ten strains (11.6%) had cross resistance between the MLS antibiotics (erythromycin or clindamycin), one strain (1.2%) had cross resistance among the cyclines and 14 strains (16.4%) had cross resistance between the MLS and cycline antibiotics. Binary logistic regression showed an association between MLS antibiotic resistance with an increased age whereas cycline resistance was associated with the duration of treatment.
Conclusions Antibiotic‐resistant P. acnes is prevalent in Hong Kong. Dermatologists should be more vigilant in prescribing antibiotics for acne patients.
Non-small cell lung cancer (NSCLC) represents about 85% of the reported cases of lung cancer. Acquired resistance to targeted therapy with epidermal growth factor receptor-tyrosine kinase inhibitors ...(EGFR-TKIs), such as gefitinib, is not uncommon. It is thus vital to explore novel strategies to restore sensitivity to gefitinib. Provided that microRNAs (miRNAs) negatively regulate their gene targets at the transcriptional level, it is speculated that miRNA mimetics may reduce the expression, activity and signal transduction of EGFR so that sensitization of tumour sites to gefitinib-induced cytotoxicity can be achieved. Indeed, a growing body of evidence has shown that the manipulation of endogenous levels of miRNA not only attenuates the EGFR/PI3K/Akt phosphorylation cascade, but also restores apoptotic cell death in in vitro models of experimentally-induced gefitinib resistance and provoked tumour regression/shrinkage in xenograft models. These data are in concordant with the clinical data showing that the differential expression profiles of miRNA in tumour tissues and blood associate strongly with drug response and overall survival. Furthermore, another line of studies indicate that the chemopreventive effects of a variety of natural compounds may involve miRNAs. The present review aims to discuss the therapeutic capacity of miRNAs in relation to recent discoveries on EGFR-TKI resistance, including chronic drug exposure and mutations.
Abstract
Background
Self-collected specimens have been advocated to avoid infectious exposure to healthcare workers. Self-induced sputum in those with a productive cough and saliva in those without a ...productive cough have been proposed, but sensitivity remains uncertain.
Methods
We performed a prospective study in 2 regional hospitals in Hong Kong.
Results
We prospectively examined 563 serial samples collected during the virus shedding periods of 50 patients: 150 deep throat saliva (DTS), 309 pooled-nasopharyngeal (NP) and throat swabs, and 104 sputum. Deep throat saliva had the lowest overall reverse-transcriptase polymerase chain reaction (RT-PCR)-positive rate (68.7% vs 89.4% sputum and 80.9% pooled NP and throat swabs) and the lowest viral ribonucleic acid (RNA) concentration (mean log copy/mL 3.54 vs 5.03 sputum and 4.63 pooled NP and throat swabs). Analyses with respect to time from symptom onset and severity also revealed similar results. Virus yields of DTS correlated with that of sputum (Pearson correlation index 0.76; 95% confidence interval, 0.62–0.86). We estimated that the overall false-negative rate of DTS could be as high as 31.3% and increased 2.7 times among patients without sputum.
Conclusions
Deep throat saliva produced the lowest viral RNA concentration and RT-PCR-positive rate compared with conventional respiratory specimens in all phases of illness. Self-collected sputum should be the choice for patients with sputum.
Deep throat saliva as a diagnostic specimen for COVID-19 has the advantage of being self-collected to minimize infectious exposure to healthcare workers. However, it is suboptimal in sensitivity. False-negative results may pose adverse impact on patient management and outbreak control.
A multicenter study was conducted to evaluate the diagnostic performance and the time to identifcation of the Verigene Blood Culture Test, the BC-GP and BC-GN assays, to identify both Gram-positive ...and Gram-negative bacteria and their drug resistance determinants directly from positive blood cultures collected in Hong Kong.
A total of 364 blood cultures were prospectively collected from four public hospitals, in which 114 and 250 cultures yielded Gram-positive and Gram-negative bacteria, and were tested with the BC-GP and BC-GN assay respectively. The overall identification agreement for Gram-positive and Gram-negative bacteria were 89.6% and 90.5% in monomicrobial cultures and 62.5% and 53.6% in polymicrobial cultures, respectively. The sensitivities for most genus/species achieved at least 80% except Enterococcus spp. (60%), K.oxytoca (0%), K.pneumoniae (69.2%), whereas the specificities for all targets ranged from 98.9% to 100%. Of note, 50% (7/14) cultures containing K.pneumoniae that were missed by the BC-GN assay were subsequently identified as K.variicola. Approximately 5.5% (20/364) cultures contained non-target organisms, of which Aeromonas spp. accounted for 25% and are of particular concern. For drug resistance determination, the Verigene test showed 100% sensitivity for identification of MRSA, VRE and carbapenem resistant Acinetobacter, and 84.4% for ESBL-producing Enterobacteriaceae based on the positive detection of mecA, vanA, blaOXA and blaCTXM respectively.
Overall, the Verigene test provided acceptable accuracy for identification of bacteria and resistance markers with a range of turnaround time 40.5 to 99.2 h faster than conventional methods in our region.
MicroRNAs (miRNAs) regulate mRNA stability and protein expression, and certain miRNAs have been demonstrated to act either as oncogenes or tumor suppressors. Differential miRNA expression signatures ...have been documented in many human cancers but the role of miRNAs in endometrioid endometrial cancer (EEC) remains poorly understood. This study identifies significantly dysregulated miRNAs of EEC cells, and characterizes their impact on the malignant phenotype. We studied the expression of 365 human miRNAs using Taqman low density arrays in EECs and normal endometriums. Candidate differentially expressed miRNAs were validated by quantitative real‐time PCR. Expression of highly dysregulated miRNAs was examined in vitro through the effect of anti‐/pre‐miRNA transfection on the malignant phenotype. We identified 16 significantly dysregulated miRNAs in EEC and 7 of these are novel findings with respect to EEC. Antagonizing the function of miR‐7, miR‐194 and miR‐449b, or overexpressing miR‐204, repressed migration, invasion and extracellular matrix‐adhesion in HEC1A endometrial cancer cells. FOXC1 was determined as a target gene of miR‐204, and two binding sites in the 3′‐untranslated region were validated by dual luciferase reporter assay. FOXC1 expression was inversely related to miR‐204 expression in EEC. Functional analysis revealed the involvement of FOXC1 in migration and invasion of HEC1A cells. Our results present dysfunctional miRNAs in endometrial cancer and identify a crucial role for miR‐204‐FOXC1 interaction in endometrial cancer progression. This miRNA signature offers a potential biomarker for predicting EEC outcomes, and targeting of these cancer progression‐ and metastasis‐related miRNAs offers a novel potential therapeutic strategy for the disease.
Repeated isolation of multidrug-resistant Acinetobacter baumannii (MDRAB) from respiratory secretions poses a great challenge for infection control. We conducted a retrospective case-control study to ...evaluate the efficacy and adverse effect of inhaled colistin methanesulfonate (CMS) in the eradication of MDRAB from the respiratory tract. Patients who were admitted to Taipei Veterans General Hospital between February 2009 and June 2010, had at least two sets of monomicrobial culture of MDRAB from respiratory secretions, and remained in hospital for at least 14 days after the first isolation of MDRAB (index day) were included. Patients who received intravenous CMS were excluded. Patients who received CMS inhalation for ≥3 days were selected as cases whereas the controls were matched for age and Acute Physiology and Chronic Health Evaluation II score. Thirty-nine cases and controls were identified. The duration of CMS inhalation was 10.9 ± 3.6 days. The use of inhaled CMS was the only independent factor associated with the eradication of MDRAB within 14 days after the index day (OR 266.33; 95% CI 11.26–6302.18, p <0.001), and shortened the duration of MDRAB recovery from the respiratory tract by 13.3 ± 1.45 days. The adverse effects were similar for both groups. The increase of colistin minimal inhibitory concentrations in the last isolate compared with the index isolate from the same patient did not differ between the two groups. In conclusion, our study demonstrated that inhaled CMS enhanced the eradication of MDRAB from the respiratory tract without significant clinical adverse effect or impact on colistin resistance.
In this article, I first recap the major downsides of globalization which clearly inhibit the development of a more just and stable world, hence setting the stage for its transition ...(re-globalization). Then, I examine the changing role and influence of China in the course of globalization and its current transition by following an analytical framework of institutional change. Specifically, I describe the process where China has evolved from a selective follower/imitator of international criteria/orders to an active innovator in proposing alternatives like the Belt and Road Initiative and internationalization of the yuan to the Global South. These actions have unarguably accelerated the process of re-globalization. Nevertheless, while the initial results are positive, whether a more just and stable world could be ultimately realized will be determined by whether the compatibility of the economic culture of China with other societies could be sustained through recognition by their mass communities, and also consensus from the other world powers.
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