Patterns of inpatient antibiotic use among public hospitals in Hong Kong from 2000 to 2015

Background: Studies have demonstrated that higher rates of antibiotic resistance are found in countries with higher antibiotic consumption. The global increase in antibiotic consumption is a major public health concern. Objectives: To describe the antibiotic dispensing patterns in public hospitals in Hong Kong from 2000-2015. Methods: We acquired data on all hospital admissions with any antibiotics dispensed from 2000-2015 from the Hong Kong public hospitals. The annual proportion of hospital admissions with antibiotic dispensed was estimated and stratified by age group. An interrupted time series analysis was conducted to examine any potential change in tetracycline dispensing after the release of the new clinical practice guideline. Results: A total of 35,535,506 antibiotic prescriptions were dispensed among 2,161,360 unique hospitalized patients from 2000 to 2015. Antibiotics were dispensed in 29.2% of all hospital admissions in the public hospitals, the annual proportions of hospital admissions with antibiotics dispensed increased over the study period from 27.87% in 2000 to 31.39% in 2015, ranging from 27.17 to 31.39%. However, a significant increase was only observed in age groups of 5-19, 20-44 and 85 years or above when stratifying by age. In the interrupted time series analysis, a change in trend was detected for tetracycline dispensing which coincided with the time of publication of the new clinical practice guideline. Conclusions: We found that the overall volume of antibiotic use increased between 2000 and 2015. The rise in dispensing of carbapenems in our study is concerning. The significant change in tetracycline use after being recommended as one of the preferred regimens demonstrated that the change in clinical practice guideline had an immediate effect on the antibiotic prescribing practice in Hong Kong public hospitals

Truncation of the Deubiquitinating Domain of CYLD in Myelomonocytic Cells Attenuates Inflammatory Responses

The cylindromatosis tumor suppressor (CYLD) is a deubiquitinating enzyme that has been implicated in various aspects of adaptive and innate immune responses. Nevertheless, the role of CYLD in the function of specific types of immune cells remains elusive. In this report we have used conditional gene targeting in mice to address the role of the deubiquitinating activity of CYLD in the myelomonocytic lineage. Truncation of the deubiquitinating domain of CYLD specifically in myelomonocytic cells impaired the development of lethal LPS-induced endotoxic shock and the accumulation of thioglycollate-elicited peritoneal macrophages. Our data establish CYLD as a regulator of monocyte-macrophage activation in response to inflammatory stimuli and identify it as a potential target for therapeutic intervention in relevant inflammatory disorders in humans

Lectins in Cervical Screening.

Cervical screening in low-resource settings remains an unmet need. Lectins are naturally occurring sugar-binding glycoproteins whose binding patterns change as cancer develops. Lectins discriminate between dysplasia and normal tissue in several precancerous conditions. We explored whether lectins could be developed for cervical screening via visual inspection. Discovery work comprised lectin histochemistry using a panel of candidate lectins on fixed-human cervix tissue (high-grade cervical intraepithelial neoplasia (CIN3, n = 20) or normal (n = 20)), followed by validation in a separate cohort (30 normal, 25 CIN1, 25 CIN3). Lectin binding was assessed visually according to staining intensity. To validate findings macroscopically, near-infra red fluorescence imaging was conducted on freshly-resected cervix (1 normal, 7 CIN3), incubated with topically applied fluorescently-labelled lectin. Fluorescence signal was compared for biopsies and whole specimens according to regions of interest, identified by the overlay of histopathology grids. Lectin histochemistry identified two lectins-wheat germ agglutinin (WGA) and Helix pomatia agglutinin (HPA)-with significantly decreased binding to CIN3 versus normal in both discovery and validation cohorts. Findings at the macroscopic level confirmed weaker WGA binding (lower signal intensity) in CIN3 vs. normal for biopsies (p = 0.0308) and within whole specimens (p = 0.0312). Our findings confirm proof-of-principle and indicate that WGA could potentially be developed further as a probe for high-grade cervical disease

Effect of influenza on cardiorespiratory and all-cause mortality in Hong Kong, Singapore and Guangzhou.

1. Using a common modelling approach, mortality attributable to influenza was higher in the two subtropical cities Guangzhou and Hong Kong than in the tropical city Singapore. 2. The virus activity appeared more synchronised in subtropical cities, whereas seasonality of influenza tended to be less marked in the tropical city. 3. High temperature was associated with increased mortality after influenza infection in Hong Kong, whereas relative humidity was an effect modifier for influenza in Guangzhou. No effect modification was found for Singapore. 4. Seasonal and environmental factors probably play a more important role than socioeconomic factors in regulating seasonality and disease burden of influenza. Further studies are needed in identifying the mechanism behind the regulatory role of environmental factors.published_or_final_versio

Selective-logging and oil palm: Multitaxon impacts, biodiversity indicators, and trade-offs for conservation planning

Strong global demand for tropical timber and agricultural products has driven large-scale logging and subsequent conversion of tropical forests. Given that the majority of tropical landscapes have been or will likely be logged, the protection of biodiversity within tropical forests thus depends on whether species can persist in these economically exploited lands, and if species cannot persist, whether we can protect enough primary forest from logging and conversion. However, our knowledge of the impact of logging and conversion on biodiversity is limited to a few taxa, often sampled in different locations with complex land-use histories, hampering attempts to plan cost-effective conservation strategies and to draw conclusions across taxa. Spanning a land-use gradient of primary forest, once- and twice-logged forests, and oil palm plantations, we used traditional sampling and DNA metabarcoding to compile an extensive data set in Sabah, Malaysian Borneo for nine vertebrate and invertebrate taxa to quantify the biological impacts of logging and oil palm, develop cost-effective methods of protecting biodiversity, and examine whether there is congruence in response among taxa. Logged forests retained high species richness, including, on average, 70% of species found in primary forest. In contrast, conversion to oil palm dramatically reduces species richness, with significantly fewer primary-forest species than found on logged forest transects for seven taxa.Using a systematic conservation planning analysis, we show that efficient protection of primary-forest species is achieved with land portfolios that include a large proportion of logged-forest plots. Protecting logged forests is thus a cost-effective method of protecting an ecologically and taxonomically diverse range of species, particularly when conservation budgets are limited. Six indicator groups (birds, leaf-litter ants, beetles, aerial hymenopterans, flies, and true bugs) proved to be consistently good predictors of the response of the other taxa to logging and oil palm. Our results confidently establish the high conservation value of logged forests and the low value of oil palm. Cross-taxon congruence in responses to disturbance also suggests that the practice of focusing on key indicator taxa yields important information of general biodiversity in studies of logging and oil palm

Role of cardiac mitofusins in cardiac conduction following simulated ischemia–reperfusion

Mitochondrial dysfunction induced by acute cardiac ischemia–reperfusion (IR), may increase susceptibility to arrhythmias by perturbing energetics, oxidative stress production and calcium homeostasis. Although changes in mitochondrial morphology are known to impact on mitochondrial function, their role in cardiac arrhythmogenesis is not known. To assess action potential duration (APD) in cardiomyocytes from the Mitofusins-1/2 (Mfn1/Mfn2)-double-knockout (Mfn-DKO) compared to wild-type (WT) mice, optical-electrophysiology was conducted. To measure conduction velocity (CV) in atrial and ventricular tissue from the Mfn-DKO and WT mice, at both baseline and following simulated acute IR, multi-electrode array (MEA) was employed. Intracellular localization of connexin-43 (Cx43) at baseline was evaluated by immunohistochemistry, while Cx-43 phosphorylation was assessed by Western-blotting. Mfn-DKO cardiomyocytes demonstrated an increased APD. At baseline, CV was significantly lower in the left ventricle of the Mfn-DKO mice. CV decreased with simulated-ischemia and returned to baseline levels during simulated-reperfusion in WT but not in atria of Mfn-DKO mice. Mfn-DKO hearts displayed increased Cx43 lateralization, although phosphorylation of Cx43 at Ser-368 did not differ. In summary, Mfn-DKO mice have increased APD and reduced CV at baseline and impaired alterations in CV following cardiac IR. These findings were associated with increased Cx43 lateralization, suggesting that the mitofusins may impact on post-MI cardiac-arrhythmogenesis

Comparative analysis of long-haul system based on SSB modulation utilising dual parallel Mach–Zehnder modulators

In this paper, we have proposed a long-haul optical transmission system, based on a single sideband (SSB) modulation scheme. Analytical and simulation models have been developed, optimised and demonstrated for the proposed SSB system configurations. The SSB modulation scheme was proposed to overcome dispersion in the fibre. We have shown that the related link losses can be minimized by increasing the quality of the optical signal at the modulation. We have optimised the radio over fibre configuration scheme based on dual parallel dual drive Mach–Zehnder Modulator, thereby increasing transmission length of the fibre. With the proposed SSB, by suppressing some of the harmonics and cancelling one of the sidebands, we have halved the RF power fading and interference. The developed analytical (theoretical/mathematical) model agrees very well with the simulation results using two (both) different commercial simulation tools. The optical signal is boosted while minimizing the number of repeaters. We report a SSB configuration, compensation and amplification with individual spans of 150 km, by extending the length of the link up to 3250 km. The proposed system configuration exhibits high performance with less complexity and lower cost

“<i>I do it because they do it</i>”:social-neutralisation in information security practices of Saudi medical interns

Successful implementation of information security policies (ISP) and IT controls play an important role in safeguarding patient privacy in healthcare organizations. Our study investigates the factors that lead to healthcare practitioners' neutralisation of ISPs, leading to non-compliance. The study adopted a qualitative approach and conducted a series of semi-structured interviews with medical interns and hospital IT department managers and staff in an academic hospital in Saudi Arabia. The study's findings revealed that the MIs imitate their peers' actions and employ similar justifications when violating ISP dictates. Moreover, MI team superiors' (seniors) ISP non-compliance influence MIs tendency to invoke neutralisation techniques. We found that the trust between the medical team members is an essential social facilitator that motivates MIs to invoke neutralisation techniques to justify violating ISP policies and controls. These findings add new insights that help us to understand the relationship between the social context and neutralisation theory in triggering ISP non-compliance

Dengue Virus Infection-Enhancing Activity in Serum Samples with Neutralizing Activity as Determined by Using FcγR-Expressing Cells

Dengue has become a major international public health concern in recent decades. There are four dengue virus serotypes. Recovery from infection with one serotype confers life-long protection to the homologous serotype but only partial protection to subsequent infection with other serotypes. Secondary infection with a serotype different from that in primary infection increases the risk of development of severe complications. Antibodies may play two competing roles during infection: virus neutralization that leads to protection and recovery, or infection-enhancement that may cause severe complications. Progress in vaccine development has been hampered by limited understanding on protective immunity against dengue virus infection. We report the neutralization activity and infection-enhancement activity in individuals with dengue in Malaysia. We show that infection-enhancement activity is present when neutralizing activity is absent or low, and cross-reactive neutralizing activity may be hampered by infection-enhancing activity. Conventional assays for titration of neutralizing antibody do not consider infection-enhancement activity. We used an alternative assay that determines the sum of neutralizing and infection-enhancement activity in sera from dengue patients. In addition to providing insights into antibody responses during infection, the alternative assay provides a new platform for the study of immune responses to vaccine