Asthma control and asthma treatment adherence in primary care: results from the prospective, multicentre, non-interventional, observational cohort ASCOPE study in Malaysia.

INTRODUCTION: As the first point of contact for those presenting with asthma symptoms, primary healthcare plays a crucial role in asthma management. This is a nationwide study of assessment of asthma symptom control and adherence to asthma medication among outpatients in public health clinics in Malaysia. METHODS: This is a prospective, observational multicentre study (ASCOPE; NCT03804632). Data on asthma control, assessment of control symptoms, and adherence to treatment were collected from medical records and interviews of patients. The level of asthma control was assessed using the Global Initiative for Asthma (GINA) Assessment of Symptom Control. Adherence of patient to medication for asthma was assessed through interview of patients using four questions adapted from the Malaysian Medication Adherence Scale. RESULTS: Among the 1011 patients recruited, 416 (41%) had well controlled asthma, 388 (38%) were partly controlled, and 207 (21%) had uncontrolled asthma. Majority (81%) had mild asthma and all patients were on asthma medication. Most patients did not have spirometry data (97%) but underwent peak flow rate measurements (98%). Poor adherence occurred at all levels of asthma control but was worst among those with uncontrolled asthma. This was statistically significant across all four questions on adherence (p<0.05). For example, more patients with uncontrolled asthma forgot doses (56%) or stopped treatment (39%) than those with well-controlled asthma (44% and 27%respectively). CONCLUSIONS: Among Malaysian primary care patients with asthma, less than 50% had well-controlled asthma, and low adherence to treatment was common. More effort is needed to improve asthma control among patients in Malaysia, including those with mild asthma.

Early statin therapy in patients with acute intracerebral hemorrhage without prior statin use.

BACKGROUND AND PURPOSE: Statin therapy is beneficial for primary and secondary prevention of ischaemic stroke, but its influence in patients with intracerebral hemorrhage (ICH) is unclear. An assessment was made of the effect of early statin therapy on patients with acute ICH. METHODS: Taiwan's National Health Insurance Research Database was screened for patients without prior statin therapy admitted from January to December 2008 for newly diagnosed ICH. Patients taking statins during hospitalization or within 3 months post-discharge were the early statin group (n = 749); patients who were not were the control group (n = 7583). The study end-points were recurrent ICH and all-cause mortality during follow-up. RESULTS: All eligible patients were followed up until 31 December 2010. During the follow-up, 69 (9.2%) patients in the early statin group and 677 (8.9%) control group patients had recurrent ICH. Cox proportional hazards analyses showed that early statin use did not increase the risk of recurrent ICH (adjusted hazard ratio 1.044; 95% confidence interval 0.812-1.341). During the same period, 90 (12.0%) of the early statin group and 1519 (20.0%) control group patients died. All-cause mortality was lower in the early statin group (adjusted hazard ratio 0.742; 95% confidence interval 0.598-0.919) than in the control group. Matched propensity score analyses were consistent with findings in Cox proportional hazards analyses. CONCLUSIONS: Early statin group patients with acute ICH did not have a higher recurrent risk of ICH and might have lower all-cause mortality during follow-up. It is concluded that statin therapy might be beneficial for patients with ICH.

Impact of early statin therapy in patients with ischemic stroke or transient ischemic attack.

BACKGROUND: Statin therapy has demonstrated benefits in ischemic stroke patients. However, little is known about whether the timing of statin initiation affects clinical outcomes. The possible association of statin use and cerebral hemorrhage is also a concern for early statin therapy after stroke. The objective of this study was to evaluate the efficacy and safety of the initiation timing of statins in acute ischemic stroke. METHODS: A cohort study was performed using 5-year National Health Insurance Research Database in Taiwan. Patients without prior statin therapy admitted for their new ischemic stroke or transient ischemic attack (TIA) were enrolled. Patients were recognized as inhospital use group (2019 patients, statin initiation during hospitalization), intermediate use group (2266 patients, statin initiation within 1 year after discharge) or late use group (2958 patients, statin initiation 1 year later after discharge). The study endpoint was the composite outcome of ischemic stroke, TIA, hemorrhagic stroke, or acute coronary event. RESULTS: As compared with inhospital use, patients with late use had a 49% increased risk (adjusted HR: 1.49, 95% CI: 1.26-1.76) of composite endpoint. In contrast, patients with intermediate use had similar risk of endpoint as those with inhospital use. The risk of cerebral hemorrhage was similar in patients receiving inhospital, intermediate, or late statin treatment. CONCLUSIONS: In acute ischemic stroke, patients receiving late statin treatment carried a poorer clinical outcome than those with earlier statin initiation. Inhospital statin use after an acute ischemic stroke did not increase the risk of cerebral hemorrhage.

Update on diversity and distribution of HIV-1 subtypes in Yunnan province.

The aim of this study was to characterize updated HIV subtypes in Yunnan to determine their origins and distribution within the population. RT-PCR of both the gag and env genes were sequenced from Yunnan province inhabitants newly diagnosed with HIV-1. Sequence data from 290 samples were used for statistical analysis of subtype distribution and phylogenetic tree construction. Distribution data were adjusted to account for different geographical distributions of HIV-1 subtypes in the population. Phylogenetic analysis revealed six HIV-1 subtypes in Yunnan, including eight types of unique recombination forms (URFs). The most prevalent subtypes in this province, CRF07_BC (18·9%), CRF08_BC (39·1%), CRF01_AE (22·4%), and URFs (subtype C, 5·9% and subtype B, 4·5%), were all recombinants. We found significant differences in the distribution of these HIV-1 subtypes not only geographically, but also between various ethnic groups and with respect to transmission routes. Our findings indicate a complex population of HIV-1 subtypes, URFs, and recombinant subtypes in Yunnan province. This diversity could make the prevention and control of HIV infection in Yunnan more difficult due to the possibility of virus recombination or infection by multiple subtypes.

Average Soil Water Retention Curves Measured by Neutron Radiography.

Water retention curves are essential for understanding the hydrologic behavior of partially saturated porous media and modeling flow and transport processes within the vadose zone. We directly measured the main drying and wetting branches of the average water retention function obtained using two-dimensional neutron radiography. Flint sand columns were saturated with water and then drained and rewetted under quasi-equilibrium conditions using a hanging water column setup. Digital images (2048 by 2048 pixels) of the transmitted flux of neutrons were acquired at each imposed matric potential (∼10-15 matric potential values per experiment) at the National Institute of Standards and Technology Center for Neutron Research BT-2 neutron imaging beam line. Volumetric water contents were calculated on a pixel-by-pixel basis using Beer-Lambert's law after taking into account beam hardening and geometric corrections. To account for silica attenuation and remove scattering effects at high water contents, the volumetric water contents were normalized (to give relative saturations) by dividing the drying and wetting sequences of images by the images obtained at saturation and satiation, respectively. The resulting pixel values were then averaged and combined with information on the imposed basal matric potentials to give average water retention curves. The average relative saturations obtained by neutron radiography showed an approximate one-to-one relationship with the average values measured volumetrically using the hanging water column setup. There were no significant differences (P < 0.05) between the parameters of the van Genuchten equation fitted to the average neutron radiography data and those estimated from replicated hanging water column data. Our results indicate that neutron imaging is a very effective tool for quantifying the average water retention curve.

Sequential expression of putative stem cell markers in gastric carcinogenesis.

BACKGROUND: Gastric carcinogenesis has been well documented in the step-wise histopathological model, known as Correa pathway. Several biomarkers including CD44, Musashi-1 and CD133 have been reported as putative stem cell (PSC) markers. METHODS: We investigated expression of PSC markers CD44, Musashi-1 and CD133 in relation to gastric carcinogenesis and prognosis and chemoresponse. Immunohistochemistry staining was performed in gastric cancer (GC) clinical specimens representing different steps of the Correa pathway. Gastric cancer samples taken before and after neoadjuvant chemotherapy with docetaxel, cisplatin and capecitabine (DCX) were also evaluated for PSC marker expression. RESULTS: We showed that the expression of three PSC markers was significantly elevated in GC relative to normal gastric mucosa (P<0.001 for each marker). Precancerous lesions, including intestinal metaplasia and dysplasia, demonstrated increased expression of CD44 and Musashi-1. CD133 was predominantly expressed along the border between intramucosal carcinoma and connective tissue at later stages. High CD44 and CD133 expression showed prognostic value for worse patient survival (P=0.014 and P=0.019, respectively). A small number of tumours with high expression of CD44 and CD133 showed pathological response to DCX-based neoadjuvant chemotherapy. CONCLUSION: CD44 and Musashi-1 are frequently expressed in both premalignant gastric lesions and invasive GC, whereas CD133 expression is restricted mainly to neoplastic tissues.

High bone marrow angiopoietin-1 expression is an independent poor prognostic factor for survival in patients with myelodysplastic syndromes.

BACKGROUND: Angiogenic factors have an essential role in normal and pathologic angiogenesis. However, the clinical implication of angiogenic factor expression in myelodysplastic syndromes (MDS) remains unclear. METHODS: In this study, we sought to investigate the prognostic impact of the expression of genes encoding angiopoietin-1 (Ang-1), Ang-2, the receptor Tie2, vascular endothelial growth factor-A (VEGF-A) and VEGF-C in the bone marrow (BM) in 208 patients with newly diagnosed primary MDS. RESULTS: BM Ang-1 expression was significantly higher in MDS patients, especially those with higher-risk subtypes, than in normal controls. With a median follow-up time of 32.9 months, the disease transformed to acute leukaemia more frequently in the patients bearing higher Ang-1 expression than in those with lower expression (31.5% vs 18.6%, P=0.023). The MDS patients with higher Ang-1 expression had shorter overall survival than those with lower expression (median 20.8±4.5 months vs 63.3±17.8 months, P<0.001). Multivariate analyses showed that higher Ang-1 expression was an independent unfavourable prognostic factor for overall survival. There was no impact of the expression of other angiogenic factors on survival. CONCLUSION: BM Ang-1 expression may serve as a new biomarker to predict clinical outcome in MDS patients.

Characterizing protein activities on the lysozyme and nanodiamond complex prepared for bio applications.

Recently, nanodiamond particles have attracted increasing attention as a promising nanomaterial for its biocompatibility, easy functionalization and conjugation with biomolecules, and its superb physical/chemical properties. Nanodiamonds are mainly used as markers for cell imaging, using its fluorescence or Raman signals for detection, and as carriers for drug delivery. For the success of these applications, the biomolecule associated with the nanodiamond has to retain its functionality. In this work, the protein activities of egg white lysozyme adsorbed on nanodiamond particles of different sizes is investigated. The lysozyme nanodiamond complex is used here as a protein model for analyzing its structural conformation changes and, correspondingly, its enzymatic activity after the adsorption. Fourier-transform infrared spectroscopy (FTIR) is used for the analysis of the sensitive protein secondary structure. To access the activities of the adsorbed lysozyme, a fluorescence-based assay is used. The process of adsorption is also analyzed using UV-visible spectroscopic measurements in combination with analysis of nanodiamond properties with FTIR, Raman spectroscopy, and ζ-potential measurements. It is found that the activity of lysozyme upon adsorption depends on the nanodiamond's size and surface properties, and that the nanodiamond particles can be selected and treated, which do not alter the lysozyme functional properties. Such nanodiamonds can be considered convenient nanoparticles for various bioapplications.

Demonstrating the pharmacogenetic effects of angiotensin-converting enzyme inhibitors on long-term prognosis of diastolic heart failure.

The objective of this study was to evaluate the effects of angiotensin-converting enzyme (ACE) inhibitors and pharmacogenetic interaction on the survival of the patients with diastolic heart failure (DHF). A total of 285 subjects with DHF confirmed by echocardiography were recruited in the period between 1995 and 2003. Baseline characteristics (age, sex, prior history, medication, and echocardiographic findings) and genetic polymorphisms (ACE gene insertion/deletion (I/D) polymorphism; T174M, M235T, G-6A, A-20C, G-152A, and G-217A polymorphisms of the angiotensinogen (AGT) gene; and A1166C polymorphisms of the angiotensin II type I receptor (AT1R)) were collected and matched (by propensity score) in those who received and those who did not receive ACE inhibitors. The patients were followed up to 10 years. Kaplan-Meier curves and Cox regression models were used to demonstrate the survival trend. The 85 patients who received ACE inhibitors and the other 85 patients who did not were found to have comparable baseline characteristics and polymorphism distribution. Prescription of ACE inhibitors was associated with a significant decrease in overall mortality (hazard ratio (HR), 0.45; 95% confidence interval (CI), 0.24-0.83; P=0.01), and a lower rate of cardiovascular events at 4000 days (HR, 0.53; 95% CI, 0.32-0.90; P=0.02). In addition, ACE I/D gene D allele was associated with higher overall mortality as compared with the I allele (HR, 2.04; P=0.003). This effect was diminished in those who received ACE inhibitors. The use of ACE inhibitor was associated with a significant decrease in long-term mortality and cardiovascular events in the patients with DHF. Genetic variants in the renin-angiotensin system genes were also associated, but their effects could be modified by the use of ACE inhibitors.

Direct peroral cholangioscopy using an ultraslim endoscope and overtube balloon-assisted technique: a case series.

Overtube balloon-assisted direct peroral cholangioscopy (POC) using an ultraslim endoscope may be an effective alternative to the conventional mother-baby endoscope system. A total of 14 patients with biliary diseases underwent direct POC with an ultraslim endoscope. The endoscope was successfully advanced into the bile duct in all 14 patients (100 %). The success rate of the POC was 92.9 % (13/14) on the criterion of reaching the hilum or stricture site. Endoscopic biopsy was performed in six patients. Cystic duct or residual common bile duct stones were removed successfully under direct endoscopic visualization in three patients. A diagnosis of malignant or indeterminate bile duct stricture was changed to benign lesion or stricture or normal biliary mucosa in eight of ten patients. Procedure-related biliary tract infection occurred in one patient. This series demonstrated that direct POC using an ultraslim endoscope is useful for both diagnosis and treatment.

Assessment of the clinical outcomes and cost-effectiveness of the management of systolic heart failure in Chinese patients using a home-based intervention.

This study was designed to assess the clinical effect of a home-based telephone intervention in Chinese heart failure patients. A total of 550 Chinese heart failure patients were enrolled into either (i) a group that received the usual standard of care (UC group); or (ii) a group that received a home-based heart failure centre management programme using nursing specialist-led telephone consultations (HFC group). The impact of the home-based intervention on admission rate, admission length and medical costs over 6 months was measured. Although the mean left ventricular ejection fraction in HFC patients was 29.3% compared with 34.8% in UC patients, the home-based intervention resulted in a significantly lower all-cause admission rate per person (HFC 0.60 +/- 0.77 times/person; UC 0.96 +/- 0.85 times/person), a shorter all-cause hospital stay (reduced by 8 days per person) and lower total 6-month medical costs (reduced by US$2682 per patient). These results suggest that the home-based intervention with nursing specialist-led telephone consultations may improve the clinical outcome and provide cost-savings for Chinese patients with heart failure.

Au nanostar nanoparticle as a bio-imaging agent and its detection and visualization in biosystems.

In the present work, we report the imaging of Au nanostars nanoparticles (AuNSt) and their multifunctional applications in biomedical research and theranostics applications. Their optical and spectroscopic properties are considered for the multimodal imaging purpose. The AuNSt are prepared by the seed-meditated method and characterized for use as an agent for bio-imaging. To demonstrate imaging with AuNSt, penetration and localization in different biological models such as cancer cell culture (A549 lung carcinoma cell), 3D tissue model (multicellular tumor spheroid on the base of human oral squamous carcinoma cell, SAS) and murine skin tissue are studied. AuNSt were visualized using fluorescence lifetime imaging (FLIM) at two-photon excitation with a pulse duration 140 fs, repetition rate 80 MHz and 780 nm wavelength femtosecond laser. Strong emission of AuNSt at two-photon excitation in the near infrared range and fluorescence lifetime less than 0.5 ns were observed. It allows using AuNSt as a fluorescent marker at two-photon fluorescence microscopy and lifetime imaging (FLIM). It was shown that AuNSt can be observed inside a thick sample (tissue and its model). This is the first demonstration using AuNSt as an imaging agent for FLIM at two-photon excitation in biosystems. Increased scattering of near-infrared light upon excitation of AuNSt surface plasmon oscillation was also observed and rendered using a possible contrast agent for optical coherence tomography (OCT). AuNSt detection in a biological system using FLIM is compared with OCT on the model of AuNSt penetrating into animal skin. The AuNSt application for multimodal imaging is discussed.

An effective surface-enhanced Raman scattering template based on a Ag nanocluster-ZnO nanowire array.

An effective surface-enhanced Raman scattering (SERS) template based on a 3D hybrid Ag nanocluster (NC)-decorated ZnO nanowire array was fabricated through a simple process of depositing Ag NCs on ZnO nanowire arrays. The effects of particle size and excitation energy on the Raman scattering in these hybrid systems have been investigated using rhodamine 6G as a standard analyte. The results indicate that the hybrid nanosystem with 150 nm Ag NCs produces a larger SERS enhancement factor of 3.2 x 10(8), which is much higher than that of 10 nm Ag NCs (6.0 x 10(6)) under 532 nm excitation energy. The hybrid nanowire arrays were further applied to obtain SERS spectra of the two-photon absorption (TPA) chromophore T7. Finite-difference time-domain simulations reveal the presence of an enhanced field associated with inter-wire plasmon coupling of the 150 nm Ag NCs on adjacent ZnO nanowires; such a field was absent in the case of the 10 nm Ag NC-coated ZnO nanowire. Such hybrid nanosystems could be used as SERS substrates more effectively than assembled Ag NC film due to the enhanced light-scattering local field and the inter-wire plasmon-enhanced electromagnetic field.

White-light electroluminescence from ZnO nanorods/polyfluorene by solution-based growth.

We report bright white-light electroluminescence (EL) from a diode structure consisting of a ZnO nanorod (NR) and a p-type conducting polymer of poly(fluorine) (PF) fabricated using a hydrothermal method. ZnO NRs are successfully grown on an organic layer of PF using a modified seeding layer. The EL spectrum shows a broad emission band covering the entire visible range from 400 to 800 nm. White-light emission is possible because the ZnO-defect-related emission from the ZnO NR/PF heterostructure is enhanced to become over thousand times stronger than that from the usual ZnO NR structure. This strong green-yellow emission associated with the ZnO defects, combined with the blue PF-related emission, results in the white-light emission. Enhancement of the ZnO-defect emission is caused by the presence of Zn(OH)(2) at the interface between the ZnO NRs and PF. Fourier transform infrared spectroscopy reveals that the absorption peaks at 3441, 3502, and 3574 cm(-1) corresponding to the OH group are formed at the ZnO NR/PF heterostructure, which confirms the enhancement of defect emission from the ZnO NR/PF heterostructure. The processing procedure revealed in this work is a convenient and low-cost way to fabricate ZnO-based white-light-emitting devices.

Laser action in Tb(OH)3/SiO2 photonic crystals.

Photonic crystals of Tb(OH)(3)/SiO(2) core/shell nanospheres with different periodicities were used as a resonant cavity to explore laser action. By changing the particle size, the optical stop band of the photonic crystals can be tuned to coincide with the multiple emission bands of terbium ions. An overlap of the stop band on the multiple emissions of the active materials embedded inside the photonic crystals offered a good chance for resonance. Lasing emissions arising from terbium ions occurred near the band edge of the PCs were demonstrated.

Communication using eye roll reflective signalling.

Body reflections in the ultraviolet (UV) are a common occurrence in nature. Despite the abundance of such signals and the presence of UV cones in the retinas of many vertebrates, the function of UV cones in the majority of taxa remains unclear. Here, we report on an unusual communication system in the razorback sucker, Xyrauchen texanus, that involves flash signals produced by quick eye rolls. Behavioural experiments and field observations indicate that this form of communication is used to signal territorial presence between males. The flash signal shows highest contrast in the UV region of the visual spectrum (lambdamax approximately 380 nm), corresponding to the maximum wavelength of absorption of the UV cone mechanism in suckers. Furthermore, these cones are restricted to the dorsal retina of the animal and the upwelling light background is such that their relative sensitivity would be enhanced by chromatic adaptation of the other cone mechanisms. Thus, the UV cones in the sucker have optimal characteristics (both in terms of absorbance and retinal topography) to constitute the main detectors of the flash signal. Our findings provide the first ecological evidence for restricted distribution of UV cones in the retina of a vertebrate.

Giant enhancement of band edge emission based on ZnO/TiO(2) nanocomposites.

Enhancement of band edge emission of ZnO nanorods up to a factor of 120 times has been observed in the composite consisting of ZnO nanorods and TiO(2) nanoparticles, while the defect emission of ZnO nanorods is quenched to noise level. Through a detailed investigation, it is found that the large enhancement mainly arises from fluorescence resonance energy transfer between the band edge transition of ZnO nanorods and TiO(2) nanoparticles. Our finding opens up new possibilities for the creation of highly efficient solid state emitters.

Phagocytosis and immune response studies of Macrophage-Nanodiamond Interactions in vitro and in vivo.

The applications of nanodiamond as drug delivery and bio-imaging can require the relinquishing ND-drug conjugate via blood flow, where interaction with immune cells may occur. In this work, we investigated the ND penetration in macrophage and the immune response using the tissue-resident murine macrophages (RAW 264.7). Confocal fluorescence imaging, immunofluorescence analysis of nuclear translocation of interferon regulatory factor IRF-3 and transcriptional factor NF-κΒ, analysis of pro-inflammatory cytokines production IL-1ß, IL-6 IL-10 with a reverse transcription-polymerase chain reaction technique were applied. The TNF-α factor production has been studied both in vitro at ND interaction with the macrophage and in vivo after ND injection in the mice blood system using immunoassay. The macrophage antibacterial function was estimated through E. coli bacterial colony formation. ND didn't stimulate the immune response and functionality of the macrophage was not altered. Using MTT test, ND was found negligibly cytotoxic to macrophages. Thus, ND can serve as a biocompatible platform for bio-medical applications. Left: Graphic representation of Nanodiamond internalization in macrophage. Right: (a) Fluorescence images of lysosomes, (b) nanodiamond and (c) merged image of nanodiamond internalization in macrophage.