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There is emerging evidence that α1-blockers can be safely used in the treatment of hypertension. These drugs can be used in almost all hypertensive patients for blood pressure control. However, there are several special indications. Benign prostatic hyperplasia is a compelling indication of α1-blockers, because of the dual treatment effect on both high blood pressure and lower urinary tract symptoms. Many patients with resistant hypertension would require α1-blockers as add-on therapy. Primary aldosteronism screen is a rapidly increasing clinical demand in the management of hypertension, where α1-blockers are useful for blood pressure control in the preparation for the measurement of plasma aldosterone and renin. Nonetheless, α1-blockers have to be used under several considerations. Among the currently available agents, only long-acting α1-blockers, such as doxazosin gastrointestinal therapeutic system 4-8 mg daily and terazosin 2-4 mg daily, should be chosen. Orthostatic hypotension is a concern with the use of α1-blockers especially in the elderly, and requires careful initial bedtime dosing and avoiding overdosing. Fluid retention is potentially also a concern, which may be overcome by combining an α1-blocker with a diuretic.

FDA regulations state print ads for prescription drugs must provide a true statement of information "in brief summary" describing "side effects, contraindications and effectiveness." To fulfill these requirements, these ads typically display risk information both as important safety information (ISI) on the "main" ad page with the product claims and on a separate "brief summary" page. The ISI can be lengthy and may repeat brief summary content.The authors tested two versions of the ISI (short versus long) and the presence or absence of a brief summary in direct-to-consumer prescription drug print ads for two medical conditions: overactive bladder (N = 181) and rheumatoid arthritis (N = 179). Attention was measured with eye-tracking and self-report methods. Risk retention and perceptions were self-reported.Participants spent more time viewing ads with a long ISI or a brief summary and in some instances, recalled more risks. The combination of a long ISI and a brief summary did not increase or decrease attention to or retention of risk information.A long ISI and a brief summary may perform similar functions.

We extend the well-known $\beta$-model for directed graphs to dynamic network setting, where we observe snapshots of adjacency matrices at different time points. We propose a kernel-smoothed likelihood approach for estimating $2n$ time-varying parameters in a network with $n$ nodes, from $N$ snapshots. We establish consistency and asymptotic normality properties of our kernel-smoothed estimators as either $n$ or $N$ diverges. Our results contrast their counterparts in single-network analyses, where $n\to\infty$ is invariantly required in asymptotic studies. We conduct comprehensive simulation studies that confirm our theory's prediction and illustrate the performance of our method from various angles. We apply our method to an email data set and obtain meaningful results.

Emerging evidence suggests white matter network abnormalities in patients with schizophrenia (SZ) and bipolar disorder (BD), but the alterations in dynamics of the white matter network in patients with SZ and BD are largely unknown. The white matter network of patients with SZ (n = 45) and BD (n = 47) and that of healthy controls (HC, n = 105) were constructed. We used dynamics network control theory to quantify the dynamics metrics of the network, including controllability and synchronizability, to measure the ability to transfer between different states. Experiments show that the patients with SZ and BD showed decreasing modal controllability and synchronizability and increasing average controllability. The correlations between the average controllability and synchronizability of patients were broken, especially for those with SZ. The patients also showed alterations in brain regions with supercontroller roles and their distribution in the cognitive system. Finally, we were able to accurately discriminate and predict patients with SZ and BD. Our findings provide novel dynamic metrics evidence that patients with SZ and BD are characterized by a selective disruption of brain network controllability, potentially leading to reduced brain state transfer capacity, and offer new guidance for the clinical diagnosis of mental illness.

Transnational policy transfer through cross-border government-to-government collaboration projects has been widely adopted as a tool to facilitate economic growth, especially by developing countries. Why did some transnational projects of policy transfer succeed while others fail? What are the facilitating and constraining factors in shaping their fates? What are their theoretical and policy implications for public administration and economic development in a globalizing world? This article examines the case of the China–Singapore Suzhou Industrial Park which has been in operation since its establishment in 1994. Challenging the previous studies and adopting a mixed research method utilizing a wide range of quantitative and qualitative data, we identify three major factors affecting the results of policy transfer: (1) a systemic combination of “hardware” and “software” in the conceptualization of transnational policy transfer; (2) localization of transnational policy and its enforcement; and mostly importantly, (3) institutionalization of key processes in both ends of policy exchanges and implementation. Ministry of Education (MOE) Nanyang Technological University Published version This study is funded by the Singapore Ministry of Education AcRF Tier 2 Grant (MOE2016-T2-02-87) and Nanyang Technological University Strategic Initiative (04INS000132C430; 04INS000136C430).

Aims/Introduction Emerging evidence shows that epigenetic modifications occurring during fetal development in response to intrauterine exposures could be one of the mechanisms involved in the early determinants of adult metabolic disorders. This study aimed to investigate whether the placental maternally expressed gene 3 (MEG3) deoxyribonucleic acid (DNA) methylation profile is associated with maternal gestational diabetes mellitus status and newborn birthweight. Materials and Methods Samples for measurement were collected from 23 women with gestational diabetes mellitus and 23 healthy controls. MEG3 gene expression and DNA methylation levels were assessed using quantitative real‐time polymerase chain reaction and MethylTargetTM, respectively. Pearson correlation analyses were used to examine associations between placental DNA methylation levels and clinical variables of interest. The associated results were adjusted by multivariate linear regression for maternal age, body mass index, height, gestational age and newborn sex as confounders. Results We found that the DNA methylation levels in the MEG3 differentially methylated region were significantly different between the gestational diabetes mellitus and control groups on the maternal side of the placenta (40.64 ± 2.15 vs 38.33 ± 2.92; P = 0.004). Furthermore, the mean MEG3 DNA methylation levels were correlated positively with maternal fasting glucose concentrations (R = 0.603, P, The placental deoxyribonucleic acid methylation status in the maternally expressed gene 3 differentially methylated region was correlated with maternal fasting glucose concentrations and the newborn birthweight. These epigenetic adaptations might contribute to late‐onset obesity, underlining the adverse intrauterine environment.

Influenza virus cause seasonal influenza epidemic and seriously sporadic influenza pandemic outbreaks. Hemagglutinin (HA) is an important target in the therapeutic treatment and diagnostic detection of the influenza virus. Variation in the sialic acid receptor binding site leads to strain-specific binding and results in different binding modes to the host receptors. Here, we evaluated the neutralizing activity and hemagglutination inhibition activity of a prepared murine anti-H1N1 monoclonal antibody PR8-23. Then we identified the epitope peptide of antibody PR8-23 by phage display technique from phage display peptide libraries. The identified epitope, 63-IAPLQLGKCNIA-74, containing two α-helix and two β-fold located at the footprint of the sialoglycan receptor on the RBS in the globular head domain of HA. It broads the growing arsenal of motifs for the amino acids on the globular head domain of HA in sialic acid receptor binding site and neutralizing antibody production.

Schizophrenia (SC) and bipolar disorder (BP) share elements of symptoms and the underlying neural mechanisms for both remain unclear. Recently, the complexity of spontaneous functional MRI (fMRI) signals in brain activity has been investigated in SC and BP using multiscale sample entropy (MSE) with inconsistent results.To perform MSE analysis across five time scales to assess differences in resting-state fMRI signal complexity in SC, BP, and normal controls (NC).Retrospective.Fifty SC, 49 BP, and 49 NC.A 3 T, T2* weighted echo planar imaging (EPI) sequence.The mean MSEs of all gray matter (GM) and of 12 regions of interest (ROIs) were extracted using masks across the five scales. The regional homogeneity (ReHo) and amplitude of low-frequency fluctuation (ALFF) in these ROIs were also determined and the relationship between the three measures was investigated. The correlations between cognitive assessment scores and MSE values were also explored.Bonferroni correction, One-way ANOVA, Spearman rank correlation coefficient (r), Gaussian random field (GRF) correction.There were decreased GM MSE values in the patient groups (F = 9.629, P 0.05). SC and BP patients demonstrated lower complexity than NCs in the calcarine fissure, precuneus, inferior occipital gyrus, lingual gyrus and cerebellum, and higher complexity in the median cingulate, thalamus, hippocampus, middle temporal gyrus and middle frontal gyrus. There were significant differences between SC and BP patients in the precuneus (F = 4.890, P 0.05) and inferior occipital gyrus (F = 5.820, P 0.05). Calcarine fissure, cingulate, temporal gyrus, occipital gyrus, hippocampus, precuneus, frontal gyrus, and lingual gyrus MSE values were significantly correlated with both ReHo (r 0.282, P 0.05) and ALFF (r 0.278, P 0.05). Furthermore, median temporal MSE (r = -0.321, P 0.05) on scale 3 and (r = -0.307, P 0.05) on scale 4 and median cingulate MSE (r = -0.337, P 0.05) on scale 5 was significantly negatively correlated with cognitive assessment scores.These data highlight different patterns of brain signal intensity complexity in SC and BP.1 TECHNICAL EFFICACY: Stage 1.

Hemodialysis patients are susceptible to coronavirus disease 2019 (COVID‐19). The aim of this study was to describe the epidemiological, clinical characteristics, and mortality‐related risk factors for those who undergoing hemodialysis with COVID‐19. We conducted a retrospective study. A total of 49 hemodialysis patients with COVID‐19 (Group 1) and 74 uninfected patients (Group 2) were included. For patients in Group 1, we found the median age was 62 years (36‐89 years), 59.3% were male, and the median dialysis vintage was 26 months. Twenty‐eight patients (57%) had three or more comorbidities and two patients (4%) died. The most common symptoms were fever (32.7%) and dry cough (46.9%), while nine patients (18.4%) were asymptomatic. Blood routine tests indicated lymphocytopenia, the proportion of lymphocyte subsets was generally reduced, and chest CT scans showed ground‐glass opacity (45.8%) and patchy shadowing (35.4%). However, these findings were not specific to hemodialysis patients with COVID‐19, and similar manifestations could be found in patients without SARS‐CoV‐2 infection. In conclusion, for hemodialysis patients with COVID‐19, lymphocytopenia and ground‐glass opacities or patchy opacities were common but not specific to them, early active treatment and interventions against nosocomial infection can significantly reduce the mortality and the risk of SARS‐CoV‐2 infection.

Photothermal therapy (PTT) has attracted wide attention due to its noninvasiveness and its thermal ablation ability. As photothermal agents are crucial factor in PTT, those with the characteristics of biocompatibility, non-toxicity and high photothermal stability have attracted great interest. In this work, new indocyanine green (IR-820) was utilized as a photothermal agent and near-infrared (NIR) fluorescence imaging nanoprobe. To improve the biocompatibility, poly(styrene-co-maleic anhydride) (PSMA) was utilized to encapsulate the IR-820 molecules to form novel IR-820@PSMA nanoparticles (NPs). Then, the optical and thermal properties of IR-820@PSMA NPs were studied in detail. The IR-820@PSMA NPs showed excellent photothermal stability and biocompatibility. The cellular uptaking ability of the IR-820@PSMA NPs was further confirmed in HeLa cells by the NIR fluorescent confocal microscopic imaging technique. The IR-820@PSMA NPs assisted PTT of living HeLa cells was conducted under 793 nm laser excitation, and a high PTT efficiency of 73.3% was obtained.

Background Recently, new evidence from large scale trials and updated guidelines have emerged on the risks and benefits of extended dual antiplatelet therapy (DAPT) for patients with acute coronary syndrome (ACS). Aims To discuss, clarify and advise on the application of the evidences and guidelines on individual patient selection for extended DAPT, with regard to balancing risk factors, particularly in Asian populations. Methods A total of 14 local cardiologists from Hong Kong with extensive experience in cardiology and cardiac interventions convened in a series of 3 advisory board meetings from October 2016 to September 2017, which included reviews of new evidence in the literature and discussions of the latest clinical trends, using an anonymous, electronic voting system for arriving at consensuses. Results Recommendations were produced for the following nine risk factors: old age (>65), chronic kidney disease (CKD), diabetes mellitus (DM), recurrent myocardial infarction (MI), multi-vessel disease (MVD), multiple stents, bioresorbable vascular scaffold (BVS) stent, left main stenting and peripheral artery disease (PAD). Strong ischaemic risk factors include DM, recurrent MI, MVD and/or >3 stents; less-strong ischaemic factors include CKD, left main stenting, BVS stent and PAD. Old age can be an unclear risk factor due to variations in physical fitness even among patients of identical age. Discussion The strengths and limitations of the results were acknowledged. Conclusion ACS patients with ischaemic risk factors could be considered for extended DAPT beyond 12 months, while balancing the risk of bleeding.

Free fatty acid 1 (FFA1/GPR40) has attracted extensive attention as a novel target for the treatment of type 2 diabetes for its role in the enhancement of insulin secretion with glucose dependency. Aiming to develop novel potent FFA1 agonists, a new series of phenylpropionic acid derivatives were designed and synthesized on the basis of the modification of chemical cement of TAK-875, AMG-837, and LY2881835. Among them, most promising compounds 7, 14, and 15 were obtained with EC50 values of 82, 79, and 88 nM, exhibiting a powerful agonistic activity compared to TAK-875 (95.1 nM). During Oral glucose tolerance test in normal mice, compound 7, 14, and 15 had significant glucose-lowering effect at the dose of 50 mg/kg. Furthermore, compound 15 (50 mg/kg) also significantly improved in glucose tolerance in type 2 diabetic mice. Herein, we reported the discovery and optimization of a series of potent FFA1 agonists. The discovery supported further exploration surrounding this scaffold.

Rational exploration of efficient, inexpensive, and robust electrocatalysts is critical for the efficient water splitting. Conjugated conductive metal-organic frameworks (cMOFs) with multicomponent layered double hydroxides (LDHs) to construct bifunctional heterostructure catalysts are considered as an efficient but complicated strategy. Here, the fabrication of a cMOF/LDH hetero-nanotree array catalyst (CoNiRu-NT) coupled with monodispersed ruthenium (Ru) sites via a controllable grafted-growth strategy is reported. Rich-amino hexaiminotriphenylene linkers coordinate with the LDH nanotrunk to form cMOF nanobranches, providing numerous anchoring sites to precisely confine and stabilize RuN

OBJECTIVE This study aimed to evaluate the effects of the combined use of external therapeutic ultrasound (ETUS) and the specific glycoprotein IIb/IIIa inhibitor tirofiban on myocardial no-reflow in a canine model of acute myocardial infarction after reperfusion. METHODS The canine myocardial no-reflow model was established by a 3-hour occlusion of the left anterior desecending coronary artery followed by a 2-hour reperfusion. Twenty-four canines were divided into four groups (6/group): (1) control, (2) tirofiban alone, (3) ETUS combined with tirofiban (ETUS + tirofiban), and (4) ETUS alone. RESULTS The area of no-reflow in each of the three treatment groups was significantly decreased, compared with the control group, with the ETUS + tirofiban group having the smallest area. Also, the ETUS + tirofiban group had the highest recanalized rate of microvessels in the no-reflow area and fewer impaired cellular organelles. The recovery rates of the endocardial and middle circumferential strain as well as longitudinal strain in the ETUS + tirofiban group were significantly greater than those of the tirofiban group. Moreover, the expression of hypoxia-inducible factor-1α (HIF-1α) was significantly increased in the ETUS + tirofiban group, compared with the other groups. CONCLUSIONS The combined use of ETUS and tirofiban offers synergistic benefits for the treatment of myocardial no-reflow.

Microbial symbionts are essential or important partners to phloem-feeding insects. Antibiotics have been used to selectively eliminate symbionts from their host insects and establish host lines with or without certain symbionts for investigating functions of the symbionts. In this study, using the antibiotic rifampicin we attempted to selectively eliminate certain symbionts from a population of the Middle East-Asia Minor 1 whitefly of the Bemisia tabaci species complex, which harbors the primary symbiont "Candidatus Portiera aleyrodidarum" and two secondary symbionts "Candidatus Hamiltonella defensa" and Rickettsia. Neither the primary nor the secondary symbionts were completely depleted in the adults (F0) that fed for 48 h on a diet treated with rifampicin at concentrations of 1-100 μg/mL. However, both the primary and secondary symbionts were nearly completely depleted in the offspring (F1) of the rifampicin-treated adults. Although the F1 adults produced some eggs (F2), most of the eggs failed to hatch and none of them reached the second instar, and consequently the rifampicin-treated whitefly colony vanished at the F2 generation. Interestingly, quantitative polymerase chain reaction assays showed that in the rifampicin-treated whiteflies, the density of the primary symbiont was reduced at an obviously slower pace than the secondary symbionts. Mating experiments between rifampicin-treated and untreated adults demonstrated that the negative effects of rifampicin on host fitness were expressed when the females were treated by the antibiotic, and whether males were treated or not by the antibiotic had little contribution to the negative effects. These observations indicate that with this whitefly population it is not feasible to selectively eliminate the secondary symbionts using rifampicin without affecting the primary symbiont and establish host lines for experimental studies. However, the extinction of the whitefly colony at the second generation after rifampicin treatment indicates the potential of the antibiotic as a control agent of the whitefly pest.

This study aimed to detect the interactions of several single nucleotide polymorphisms (SNPs) and alcohol consumption on blood pressure levels. Genotypes of 10 SNPs in the ATP-binding cassette transporter A1 (ABCA-1), acyl-CoA:cholesterol acyltransferase-1 (ACAT-1), low density lipoprotein receptor (LDLR), hepatic lipase gene (LIPC), endothelial lipase gene (LIPG), methylenetetrahydrofolate reductase (MTHFR), the E3 ubiquitin ligase myosin regulatory light chain-interacting protein (MYLIP), proprotein convertase subtilisin-like kexin type 9 (PCSK9), peroxisome proliferator-activated receptor delta (PPARD), and Scavenger receptor class B type 1 (SCARB1) genes were determined in 616 nondrinkers and 608 drinkers. The genotypic frequencies of LDLR rs5925, LIPC rs2070895, MTHFR rs1801133, and MYLIP rs3757354 SNPs were significantly different between nondrinkers and drinkers. The levels of systolic blood pressure (ABCA-1 rs2066715 and rs2070895), diastolic blood pressure (rs2070895), and pulse pressure (PP) (rs2066715, ACAT-1 rs1044925, and rs1801133) in nondrinkers, and systolic blood pressure (rs1044925 and SCARB1 rs5888), diastolic blood pressure (rs1044925 and LIPG rs2000813), and PP (PCSK9 rs505151 and rs5888) in drinkers were different among the genotypes (P