Bipolar disorder prevalence and psychotropic medication utilisation in Hong Kong and the United Kingdom

PURPOSE: Bipolar disorder (BPD) is often an under-addressed mental disorder. Limited studies have investigated its epidemiology and drug utilisation in Hong Kong (HK) and the United Kingdom (UK) and thus local prescribing practices remain unclear. This study aimed to determine the prevalence of BPD and the prescribing of psychotropic medications as maintenance treatment from 2001-2018 in HK and the UK. METHOD: A retrospective study using the data from Clinical Data Analysis and Reporting System in HK and IQVIA Medical Research Data in the UK. RESULTS: The prevalence of BPD diagnosis in HK and the UK more than doubled during the study period. Some distinct changes in prescribing patterns over time were observed. Lithium use declined by 2.46% and 14.58% in HK and the UK, respectively. By 2018, patients were 4.6 times more likely to receive antidepressant monotherapy in the UK versus HK (15.62% vs. 3.42%). In HK, 38.41% of women of childbearing age were prescribed valproate in 2018 compared with 8.46% in the UK. CONCLUSION: The prevalence of BPD diagnosis has been increasing in HK and the UK. The disparity in prescribing patterns of BPD maintenance treatment in two regions reflected three major issues in clinical practice: (1) under-prescribing of lithium in both regions, (2) antidepressant monotherapy in the UK and (3) overprescribing of valproate to women of childbearing age in HK. A review of current clinical treatment guidelines and regulations of prescribing practice by local clinicians should be immediately implemented to ensure the safe use of medications in patients with BPD

Sideways walk test: reliability and association with lower limb motor function after stroke

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A new species of Dermopristis Kearn, Whittington & Evans-Gowing, 2010 (Monogenea: Microbothriidae), with observations on associations between the gut diverticula and reproductive system and on the presence of denticles in the nasal fossae of the host Glaucostegus typus (Bennett) (Elasmobranchii: Rhinobatidae)

Dermopristis cairae n. sp. (Microbothriidae) is described from the skin and possibly from the nasal fossae of the giant shovelnosed ray Glaucostegus typus (Bennett). The new species is distinguished from D. paradoxus Kearn, Whittington & Evans-Gowing, 2010 by its larger size, body shape, lack of transverse ridges on the ventral surface and absence of a seminal receptacle. Extensive short gut branches lie dorsal to the testes and adjacent to the coiled region of the vas deferens and the oo¨type, possibly reflecting high metabolic demand in these areas. Denticles are present in the lining of the nasal fossae of G. typus, providing a firm substrate for the cement-based attachment of a microbothriid. However, confirmation that D. cairae inhabits the nasal fossae of G. typus is required

Comparative Outcomes Between Direct Oral Anticoagulants, Warfarin, and Antiplatelet Monotherapy Among Chinese Patients With Atrial Fibrillation: A Population-Based Cohort Study

Introduction: Outcomes associated with suboptimal use of antithrombotic treatments (antiplatelets, warfarin, direct oral anticoagulants [DOACs]) are unclear in Chinese patients with atrial fibrillation (AF). Objectives: Our objective was to assess the prescription patterns, quality, effectiveness, and safety of antithrombotic treatments. Methods: This was a population-based cohort study using electronic health records in Hong Kong. Patients newly diagnosed with AF during 2010–2016 were followed up until 2017. Patients at high stroke risk (CHA2DS2-VASc score ≥ 2) and receiving antithrombotic treatments were matched using propensity scoring. We used Cox proportional hazards regression to compare the risks of ischemic stroke, intracranial hemorrhage (ICH), gastrointestinal bleeding (GIB), and all-cause mortality between groups. Results: Of the 52,178 high-risk patients with AF, 27,614 (52.9%) received antithrombotic treatment and were included in the analyses. Between 2010 and 2016, prescribing of antiplatelets and warfarin declined and that of DOACs increased dramatically (from 1 to 32%). Two-thirds of warfarin users experienced poor anticoagulation control. Warfarin and DOACs were associated with lower risks of ischemic stroke (warfarin, hazard ratio [HR] 0.51 [95% confidence interval (CI) 0.36–0.71]; DOACs, HR 0.69 [95% CI 0.51–0.94]) and all-cause mortality (warfarin, HR 0.47 [95% CI 0.39–0.57]; DOACs, HR 0.45 [95% CI 0.37–0.55]) than were antiplatelets. DOACs were associated with a lower risk of ICH than was warfarin (HR 0.53 [95% CI 0.34–0.83]). GIB risks were similar among all groups. Conclusion: Antiplatelet prescribing and suboptimal warfarin management remain common in Chinese patients with AF at high risk of stroke. DOAC use may be associated with a lower risk of ischemic stroke and all-cause mortality when compared with antiplatelets and with a lower risk of ICH when compared with warfarin

Poloxomer 188 Has a Deleterious Effect on Dystrophic Skeletal Muscle Function

Duchenne muscular dystrophy (DMD) is an X-linked, fatal muscle wasting disease for which there is currently no cure and limited palliative treatments. Poloxomer 188 (P188) is a tri-block copolymer that has been proposed as a potential treatment for cardiomyopathy in DMD patients. Despite the reported beneficial effects of P188 on dystrophic cardiac muscle function, the effects of P188 on dystrophic skeletal muscle function are relatively unknown. Mdx mice were injected intraperitoneally with 460 mg/kg or 30 mg/kg P188 dissolved in saline, or saline alone (control). The effect of single-dose and 2-week daily treatment was assessed using a muscle function test on the Tibialis Anterior (TA) muscle in situ in anaesthetised mice. The test comprises a warm up, measurement of the force-frequency relationship and a series of eccentric contractions with a 10% stretch that have previously been shown to cause a drop in maximum force in mdx mice. After 2 weeks of P188 treatment at either 30 or 460 mg/kg/day the drop in maximum force produced following eccentric contractions was significantly greater than that seen in saline treated control mice (P = 0.0001). Two week P188 treatment at either dose did not significantly change the force-frequency relationship or maximum isometric specific force produced by the TA muscle. In conclusion P188 treatment increases susceptibility to contraction-induced injury following eccentric contractions in dystrophic skeletal muscle and hence its suitability as a potential therapeutic for DMD should be reconsidered

Breakdown of the adiabatic limit in low dimensional gapless systems

It is generally believed that a generic system can be reversibly transformed from one state into another by sufficiently slow change of parameters. A standard argument favoring this assertion is based on a possibility to expand the energy or the entropy of the system into the Taylor series in the ramp speed. Here we show that this argumentation is only valid in high enough dimensions and can break down in low-dimensional gapless systems. We identify three generic regimes of a system response to a slow ramp: (A) mean-field, (B) non-analytic, and (C) non-adiabatic. In the last regime the limits of the ramp speed going to zero and the system size going to infinity do not commute and the adiabatic process does not exist in the thermodynamic limit. We support our results by numerical simulations. Our findings can be relevant to condensed-matter, atomic physics, quantum computing, quantum optics, cosmology and others.Comment: 11 pages, 5 figures, to appear in Nature Physics (originally submitted version

Export of functional Streptomyces coelicolor alditol oxidase to the periplasm or cell surface of Escherichia coli and its application in whole-cell biocatalysis

Streptomyces coelicolor A3(2) alditol oxidase (AldO) is a soluble monomeric flavoprotein in which the flavin cofactor is covalently linked to the polypeptide chain. AldO displays high reactivity towards different polyols such as xylitol and sorbitol. These characteristics make AldO industrially relevant, but full biotechnological exploitation of this enzyme is at present restricted by laborious and costly purification steps. To eliminate the need for enzyme purification, this study describes a whole-cell AldO biocatalyst system. To this end, we have directed AldO to the periplasm or cell surface of Escherichia coli. For periplasmic export, AldO was fused to endogenous E. coli signal sequences known to direct their passenger proteins into the SecB, signal recognition particle (SRP), or Twin-arginine translocation (Tat) pathway. In addition, AldO was fused to an ice nucleation protein (INP)-based anchoring motif for surface display. The results show that Tat-exported AldO and INP-surface-displayed AldO are active. The Tat-based system was successfully employed in converting xylitol by whole cells, whereas the use of the INP-based system was most likely restricted by lipopolysaccharide LPS in wild-type cells. It is anticipated that these whole-cell systems will be a valuable tool for further biological and industrial exploitation of AldO and other cofactor-containing enzymes.

An exact expression to calculate the derivatives of position-dependent observables in molecular simulations with flexible constraints

In this work, we introduce an algorithm to compute the derivatives of physical observables along the constrained subspace when flexible constraints are imposed on the system (i.e., constraints in which the hard coordinates are fixed to configuration-dependent values). The presented scheme is exact, it does not contain any tunable parameter, and it only requires the calculation and inversion of a sub-block of the Hessian matrix of second derivatives of the function through which the constraints are defined. We also present a practical application to the case in which the sought observables are the Euclidean coordinates of complex molecular systems, and the function whose minimization defines the constraints is the potential energy. Finally, and in order to validate the method, which, as far as we are aware, is the first of its kind in the literature, we compare it to the natural and straightforward finite-differences approach in three molecules of biological relevance: methanol, N-methyl-acetamide and a tri-glycine peptideComment: 13 pages, 8 figures, published versio