1,456 research outputs found

    High prevalence of Escherichia coli sequence type 131 among antimicrobial-resistant E. coli isolates from geriatric patients

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    Previous work on the subclones within Escherichia coli ST131 predominantly involved isolates from Western countries. This study assessed the prevalence and antimicrobial resistance attributed to this clonal group. A total of 340 consecutive, non-duplicated urinary E. coli isolates originating from four clinical laboratories in Hong Kong in 2013 were tested. ST131 prevalence among the total isolates was 18.5 % (63/340) and was higher among inpatient isolates (23.0 %) than outpatient isolates (11.8 %, P<0.001), and higher among isolates from patients aged ≥65 years than from patients aged 18–50 years and 51–64 years (25.4 vs 3.4 and 4.0 %, respectively, P<0.001). Of the 63 ST131 isolates, 43 (68.3 %) isolates belonged to the H30 subclone, whereas the remaining isolates belonged to H41 (n = 17), H54 (n = 2) and H22 (n = 1). All H30 isolates were ciprofloxacin-resistant, of which 18.6 % (8/43) belonged to the H30-Rx subclone. Twenty-six (41.3 %) ST131 isolates were ESBL-producers, of which 19 had bla CTX-M-14 (12 non-H30-Rx, two H30-Rx and five H41), six had bla CTX-M-15 (five non-H30-Rx and one H30-Rx) and one was bla CTX-M-negative (H30). In conclusion, ST131 accounts for a large share of the antimicrobial-resistant E. coli isolates from geriatric patients. Unlike previous reports, ESBL-producing ST131 strains mainly belonged to non-H30-Rx rather than the H30-Rx subclone, with bla CTX-M-14 as the dominant enzyme type.postprin

    Understanding the Spatial Clustering of Severe Acute Respiratory Syndrome (SARS) in Hong Kong

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    We applied cartographic and geostatistical methods in analyzing the patterns of disease spread during the 2003 severe acute respiratory syndrome (SARS) outbreak in Hong Kong using geographic information system (GIS) technology. We analyzed an integrated database that contained clinical and personal details on all 1,755 patients confirmed to have SARS from 15 February to 22 June 2003. Elementary mapping of disease occurrences in space and time simultaneously revealed the geographic extent of spread throughout the territory. Statistical surfaces created by the kernel method confirmed that SARS cases were highly clustered and identified distinct disease “hot spots.” Contextual analysis of mean and standard deviation of different density classes indicated that the period from day 1 (18 February) through day 16 (6 March) was the prodrome of the epidemic, whereas days 86 (15 May) to 106 (4 June) marked the declining phase of the outbreak. Origin-and-destination plots showed the directional bias and radius of spread of superspreading events. Integration of GIS technology into routine field epidemiologic surveillance can offer a real-time quantitative method for identifying and tracking the geospatial spread of infectious diseases, as our experience with SARS has demonstrated

    Help-seeking behaviours for psychological distress amongst Chinese patients

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    The Contribution of Ageing to Hospitalisation Days in Hong Kong: A Decomposition Analysis

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    Background: Ageing has become a serious challenge in Hong Kong and globally. It has serious implications for health expenditure, which accounts for nearly 20% of overall government expenditure. Here we assess the contribution of ageing and related factors to hospitalisation days in Hong Kong. We used hospital discharge data from all publicly funded hospitals in Hong Kong between 2001 and 2012. Methods: A decomposition method was used to examine the factors that account for the change of total hospitalisation days during the two periods, 2001-2004 and 2004-2012. The five factors include two demographic factors – population size and age-gender composition – and three service components – hospital discharge rate, number of discharge episodes per patient, and average length of stay (LOS) – which are all measured at age-gender group level. In order to assess the health cost burden in the future, we also project the total hospitalisation days up to 2041, for a range of scenarios. Results: During the decreasing period of hospitalisation days (2001-2004), the reduction of LOS contributed to about 60% of the reduction. For the period of increase (2004-2012), ageing is associated with an increase in total hospitalisation days of 1.03 million, followed by an increase in hospital discharge rates (0.67 million), an increase in the number of discharge episodes per patient (0.62 million), and population growth (0.43 million). The reduction of LOS has greatly offset these increases (-2.19 million days), and has become one of the most significant factors in containing the increasing number of hospitalisation days. Projected increases in total hospitalisation days under different scenarios have highlighted that the contribution of ageing will become even more prominent after 2022. Conclusion: Hong Kong is facing increasing healthcare burden caused by the rapid increase in demand for inpatient services due to ageing. Better management of inpatient services with the aim of increasing efficiency and reducing LOS, avoidable hospitalisation and readmission, without compromising patient satisfaction and quality of service, are crucial for containing the rapid and enormous increases in total hospitalisation days for Hong Kong. The results would be relevant to many rapidly ageing societies in this region

    Alternative-Splicing in the Exon-10 Region of GABAA Receptor β2 Subunit Gene: Relationships between Novel Isoforms and Psychotic Disorders

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    BACKGROUND: Non-coding single nucleotide polymorphisms (SNPs) in GABRB2, the gene for beta(2)-subunit of gamma-aminobutyric acid type A (GABA(A)) receptor, have been associated with schizophrenia (SCZ) and quantitatively correlated to mRNA expression and alternative splicing. METHODS AND FINDINGS: Expression of the Exon 10 region of GABRB2 from minigene constructs revealed this region to be an "alternative splicing hotspot" that readily gave rise to differently spliced isoforms depending on intron sequences. This led to a search in human brain cDNA libraries, and the discovery of two novel isoforms, beta(2S1) and beta(2S2), bearing variations in the neighborhood of Exon-10. Quantitative real-time PCR analysis of postmortem brain samples showed increased beta(2S1) expression and decreased beta(2S2) expression in both SCZ and bipolar disorder (BPD) compared to controls. Disease-control differences were significantly correlated with SNP rs187269 in BPD males for both beta(2S1) and beta(2S2) expressions, and significantly correlated with SNPs rs2546620 and rs187269 in SCZ males for beta(2S2) expression. Moreover, site-directed mutagenesis indicated that Thr(365), a potential phosphorylation site in Exon-10, played a key role in determining the time profile of the ATP-dependent electrophysiological current run-down. CONCLUSION: This study therefore provided experimental evidence for the importance of non-coding sequences in the Exon-10 region in GABRB2 with respect to beta(2)-subunit splicing diversity and the etiologies of SCZ and BPD

    Neonatal-onset multisystem inflammatory disease responsive to interleukin-1 beta inhibition

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    BACKGROUND:Neonatal-onset multisystem inflammatory disease is characterized by fever, urticarial rash, aseptic meningitis, deforming arthropathy, hearing loss, and mental retardation. Many patients have mutations in the cold-induced autoinflammatory syndrome 1 (CIAS1) gene, encoding cryopyrin, a protein that regulates inflammation.METHODS:We selected 18 patients with neonatal-onset multisystem inflammatory disease (12 with identifiable CIAS1 mutations) to receive anakinra, an interleukin-1-receptor antagonist (1 to 2 mg per kilogram of body weight per day subcutaneously). In 11 patients, anakinra was withdrawn at three months until a flare occurred. The primary end points included changes in scores in a daily diary of symptoms, serum levels of amyloid A and C-reactive protein, and the erythrocyte sedimentation rate from baseline to month 3 and from month 3 until a disease flare.RESULTS:All 18 patients had a rapid response to anakinra, with disappearance of rash. Diary scores improved (P<0.001) and serum amyloid A (from a median of 174 mg to 8 mg per liter), C-reactive protein (from a median of 5.29 mg to 0.34 mg per deciliter), and the erythrocyte sedimentation rate decreased at month 3 (all P<0.001), and remained low at month 6. Magnetic resonance imaging showed improvement in cochlear and leptomeningeal lesions as compared with baseline. Withdrawal of anakinra uniformly resulted in relapse within days; retreatment led to rapid improvement. There were no drug-related serious adverse events.CONCLUSIONS:Daily injections of anakinra markedly improved clinical and laboratory manifestations in patients with neonatal-onset multisystem inflammatory disease, with or without CIAS1 mutations

    Generation and physiological roles of linear ubiquitin chains

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    Ubiquitination now ranks with phosphorylation as one of the best-studied post-translational modifications of proteins with broad regulatory roles across all of biology. Ubiquitination usually involves the addition of ubiquitin chains to target protein molecules, and these may be of eight different types, seven of which involve the linkage of one of the seven internal lysine (K) residues in one ubiquitin molecule to the carboxy-terminal diglycine of the next. In the eighth, the so-called linear ubiquitin chains, the linkage is between the amino-terminal amino group of methionine on a ubiquitin that is conjugated with a target protein and the carboxy-terminal carboxy group of the incoming ubiquitin. Physiological roles are well established for K48-linked chains, which are essential for signaling proteasomal degradation of proteins, and for K63-linked chains, which play a part in recruitment of DNA repair enzymes, cell signaling and endocytosis. We focus here on linear ubiquitin chains, how they are assembled, and how three different avenues of research have indicated physiological roles for linear ubiquitination in innate and adaptive immunity and suppression of inflammation
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