Comparison of diurnal blood pressure and urine production between people with and without chronic spinal cord injury.

STUDY DESIGN: Observational study. OBJECTIVES: To quantify diurnal blood pressure (BP) patterns and nocturnal hypertension and to measure diurnal urine production in people with chronic spinal cord injury (SCI), compared with controls without SCI. SETTING: Chronic SCI population in the community in Victoria, Australia. METHODS: Participants were recruited by advertisement, and sustained SCI at least a year prior or were healthy able-bodied volunteers. Participants underwent ambulatory BP monitoring (ABPM), measurement of urine production, and completed questionnaires regarding orthostatic symptoms. Comparisons were made between participants with tetraplegia or paraplegia and able-bodied controls. Participants with night:day systolic BP < 90% were classified as dippers, 90-100% as nondippers, and >100% as reverse dippers. RESULTS: Groups with tetraplegia (n = 51) and paraplegia (n = 33) were older (42.1 ± 15 and 41.1 ± 15 vs. 32.4 ± 13 years, mean ± s.d.) and had a higher prevalence of males (88 and 85% vs. 60%) than controls (n = 52). The average BP was 110.8 ± 1.5/64.4 ± 1.2 mmHg, 119.4 ± 2.1/69.8 ± 1.5 mmHg, and 118.1 ± 1.4/69.8 ± 1.0 mmHg in tetraplegia, paraplegia, and controls, respectively. Of participants with tetraplegia, paraplegia and controls, reverse dipping was observed in 45, 13, and 2% (p < 0.001), while nocturnal hypertension was observed in 13, 23, and 18%, respectively (p = 0.48). A reduction in nocturnal urine flow rate compared with the day was observed in paraplegia and controls, but not tetraplegia. CONCLUSIONS: Similar to the effects of acute SCI, chronic SCI, specifically tetraplegia, also causes isolated nocturnal hypertension, reverse dipping, orthostatic intolerance, and nocturnal polyuria. Cardiovascular risk management and assessment of orthostatic symptoms should include ABPM.

Novel Extended-Release Multiple-Unit System of Imidafenacin Prepared by Fluid-Bed Coating Technique.

The objective of this study was to formulate once-a-day extended-release (ER) pellet system of imidafenacin (IDN), a recently approved urinary antispasmodic agent with twice-a-day dosing regimen. The sugar sphere pellets were firstly layered with IDN and hypromellose and then coated with Eudragit RS (copolymers of acrylic and methacrylic acid esters), employed as a release modifier, using a fluid-bed coater. Solid-state characterizations using solid-state X-ray diffraction and differential scanning calorimeter indicated that the antispasmodic agent was homogeneously layered onto the pellets in an amorphous state. Drug release from multiple-unit ER system was effectively retarded in proportion to the amount of Eudragit RS in the outer layer, with a high correlation value above 0.86. In a pharmacokinetic evaluation in beagle dogs, the plasma concentration profile of IDN was markedly protracted by ER pellets, exhibiting delayed the time needed to reach the maximum drug concentration and the elimination half-life in plasma, compared to the commercial immediate release form (Uritos® tablet, Kyorin Pharmaceutical Co., Ltd., Japan). Therefore, the novel ER pellets can be a promising tool for oral IDN therapy, providing a once-a-day dosing regimen, and thus, improving patient compliance.

Preparation of Ultrathin Two-Dimensional Tix Ta1-x Sy Oz Nanosheets as Highly Efficient Photothermal Agents.

Although two-dimensional (2D) metal oxide/sulfide hybrid nanostructures have been synthesized, the facile preparation of ultrathin 2D nanosheets in high yield still remains a challenge. Herein, we report the first high-yield preparation of solution-processed ultrathin 2D metal oxide/sulfide hybrid nanosheets, that is, Tix Ta1-x Sy Oz (x=0.71, 0.49, and 0.30), from Tix Ta1-x S2 precursors. The nanosheet exhibits strong absorbance in the near-infrared region, giving a large extinction coefficient of 54.1 L g-1 cm-1 at 808 nm, and a high photothermal conversion efficiency of 39.2 %. After modification with lipoic acid-conjugated polyethylene glycol, the nanosheet is a suitable photothermal agent for treatment of cancer cells under 808 nm laser irradiation. This work provides a facile and general method for the preparation of 2D metal oxide/sulfide hybrid nanosheets.

Investigating allied health professionals' attitudes, perceptions and acceptance of an electronic medical record using the Unified Theory of Acceptance and Use of Technology.

Objective This study aimed to investigate allied health professionals' (AHPs') perspectives pre- and post-implementation of an electronic medical record (EMR) in a tertiary health service in Australia and examine factors influencing user acceptance. Methods Data were collected pre- and post-EMR implementation via cross-sectional online surveys based on the Unified Theory of Acceptance and Usage of Technology (UTAUT). All AHPs at a large tertiary hospital were invited to complete the surveys. Data analysis included descriptive analysis, Mann-Whitney U tests for pre-post item- and construct-level comparison and content analysis of free-text responses. The theoretical model was empirically tested using partial least squares structural equation modelling. Results AHPs had positive attitudes toward EMR use both pre- and post-implementation. Compared to pre-implementation, AHPs felt more positive post-implementation about system ease of use and demonstrated decreased anxiety and apprehension regarding EMR use. AHPs felt they had adequate resources and knowledge to use EMR and reported real-time data accessibility as a main advantage. Disadvantages of EMR included an unfriendly user interface, system outages and decreased efficiency. Conclusions As AHPs increase EMR system familiarity, their positivity towards its use increases. An understanding of what influences AHPs when implementing new compulsory technology can inform change management strategies to improve adoption.

Hypertension - the difficult decisions.

BACKGROUND: Although management of hypertension is a daily activity of primary care practitioners, it remains one of the most demanding areas of medicine. Reasons for this include the imprecision of blood pressure measurement, the complexity of assessing cardiovascular risk, and the need to use multiple agents to control blood pressure. OBJECTIVE: This article discusses clinical scenarios that force clinicians to make decisions about blood pressure measurement techniques and methods of treatment. DISCUSSION: We consider ambulatory compared to office based blood pressure measurement, the types of clinical scenarios in which ambulatory blood pressure monitoring is likely to be beneficial, what to consider when there is nocturnal elevated blood pressure, and the assessment and management of resistant hypertension.

Electronic medical record platform enhancements during COVID-19 to support identify-isolate-inform strategy for initial detection and management of patients.

Singapore was one of the earliest countries affected by COVID-19, outside China. EDs in Singapore faced a surge of confirmed cases of COVID-19 patients, which stretched their resources. Here we describe how we adopted strategic changes using the identify-isolate-inform tool to improve the evaluation, treatment and management of COVID-19 patients. During this pandemic, information technology integration, modifications to the electronic medical record and essential enhancements to the dashboard were implemented in a timely manner to match the clinical needs. Considerations for an isolation facility within an ED are especially important for future outbreaks.

Heterophase fcc-2H-fcc gold nanorods.

The crystal phase-based heterostructures of noble metal nanomaterials are of great research interest for various applications, such as plasmonics and catalysis. However, the synthesis of unusual crystal phases of noble metals still remains a great challenge, making the construction of heterophase noble metal nanostructures difficult. Here, we report a one-pot wet-chemical synthesis of well-defined heterophase fcc-2H-fcc gold nanorods (fcc: face-centred cubic; 2H: hexagonal close-packed with stacking sequence of "AB") at mild conditions. Single particle-level experiments and theoretical investigations reveal that the heterophase gold nanorods demonstrate a distinct optical property compared to that of the conventional fcc gold nanorods. Moreover, the heterophase gold nanorods possess superior electrocatalytic activity for the carbon dioxide reduction reaction over their fcc counterparts under ambient conditions. First-principles calculations suggest that the boosted catalytic performance stems from the energetically favourable adsorption of reaction intermediates, endowed by the unique heterophase characteristic of gold nanorods.

Aging amorphous/crystalline heterophase PdCu nanosheets for catalytic reactions.

Phase engineering is arising as an attractive strategy to tune the properties and functionalities of nanomaterials. In particular, amorphous/crystalline heterophase nanostructures have exhibited some intriguing properties. Herein, the one-pot wet-chemical synthesis of two types of amorphous/crystalline heterophase PdCu nanosheets is reported, in which one is amorphous phase-dominant and the other one is crystalline phase-dominant. Then the aging process of the synthesized PdCu nanosheets is studied, during which their crystallinity increases, accompanied by changes in some physicochemical properties. As a proof-of-concept application, their aging effect on catalytic hydrogenation of 4-nitrostyrene is investigated. As a result, the amorphous phase-dominant nanosheets initially show excellent chemoselectivity. After aging for 14 days, their catalytic activity is higher than that of crystalline phase-dominant nanosheets. This work demonstrates the intriguing properties of heterophase nanostructures, providing a new platform for future studies on the regulation of functionalities and applications of nanomaterials by phase engineering.

Experiment and Simulation of a Selective Subwavelength Filter with a Low Index Contrast.

Subwavelength gratings have been of great interest recently due to their ability to eliminate multiple orders. However, high index contrast ( Δ n ∼ 3 ) is typically achieved using metals or high-index dielectrics surrounded by vacuum in order to maintain good optical selectivity. Here, we theoretically propose and experimentally realize a selective subwavelength grating using an index contrast of Δ n ∼ 1.2 without vacuum. Despite its low index contrast, our simulation and experiments show that good optical selectivity is achieved using the same physics as subwavelength gratings made of high-index contrast. Such polymer-based encapsulated gratings are easier to scale up for use in large-area applications such as photovoltaics and lighting.

Investigation on Surface Integrity of Rapidly Solidified Aluminum RSA 905 by Magnetic Field-Assisted Finishing.

RSA 905, a rapidly solidified aluminum alloy, has been widely utilized in optical, automotive, and aerospace industries owing to its superior mechanical properties such as hardness and strength compared to conventional aluminum alloys. However, the surface finishing of RSA 905 to achieve submicron surface roughness is quite challenging and was rarely addressed. This paper presents an experimental and analytical study on magnetic field-assisted finishing (MFAF) of RSA 905 through a systematic investigation on surface integrity in relation to the MFAF process parameters. The effect of abrasive and polishing speed conditions on material removal and surface roughness was quantitatively investigated. The surface and subsurface quality were evaluated by optical microscope and scanning electron microscope (SEM) observations, residual stress measurement, surface microhardness and tribology test. The results show that relatively high material removal and low surface roughness were obtained under conditions using the SiC abrasive with a grit size of 12 µm at polishing speed of 400 rpm or using the Al2O3 abrasive with a grit size of 5 µm at polishing speed of 800 rpm. Heat melt layer caused by wire electrical discharge machining (EDM) during the sample preparation was removed by MFAF without inducing new subsurface damage. The MFAF process also helps release the surface residual stress and improve the tribological performance although the surface microhardness was slightly reduced.

Applying macromolecular crowding to 3D bioprinting: fabrication of 3D hierarchical porous collagen-based hydrogel constructs.

Native tissues and/or organs possess complex hierarchical porous structures that confer highly-specific cellular functions. Despite advances in fabrication processes, it is still very challenging to emulate the hierarchical porous collagen architecture found in most native tissues. Hence, the ability to recreate such hierarchical porous structures would result in biomimetic tissue-engineered constructs. Here, a single-step drop-on-demand (DOD) bioprinting strategy is proposed to fabricate hierarchical porous collagen-based hydrogels. Printable macromolecule-based bio-inks (polyvinylpyrrolidone, PVP) have been developed and printed in a DOD manner to manipulate the porosity within the multi-layered collagen-based hydrogels by altering the collagen fibrillogenesis process. The experimental results have indicated that hierarchical porous collagen structures could be achieved by controlling the number of macromolecule-based bio-ink droplets printed on each printed collagen layer. This facile single-step bioprinting process could be useful for the structural design of collagen-based hydrogels for various tissue engineering applications.

Relationship between autonomic cardiovascular control and obstructive sleep apnoea in persons with spinal cord injury: a retrospective study.

STUDY DESIGN: Retrospective study. OBJECTIVE: To determine if there is an association between obstructive sleep apnoea (OSA) and blood pressure (BP) pattern or heart rate variability (HRV) in people with spinal cord injury (SCI). SETTING: A state-based spinal cord service in Victoria, Australia. METHODS: We identified 42 subjects who had ambulatory BP monitoring (ABPM) within 6 months of a diagnostic sleep study at Austin Hospital between 2009 and 2014. Markers for autonomic function, including circadian BP pattern and HRV were extracted from the ABPM study database. Apnoea/hypopnoea index (AHI), arousals/hour and oxygen desaturation index were extracted from the sleep study database. Subjects with a nocturnal systolic BP dipping more than 10% of daytime value were defined as dippers, between 10 and 0% were non-dippers and those with a higher night than day systolic BP were reverse dippers. Severity of OSA is classified as non-OSA (AHI < 5), mild (AHI 5-15), moderate (AHI 15-30) and severe (AHI > 30). RESULTS: Subjects (n = 42) were predominantly male (85.7%), aged 44 ± 15.4 (mean ± SD), with a BMI of 24.4 ± 5.7 (mean ± SD) and mainly tetraplegic (92.9%). There was no difference in AHI, oxygen desaturation index or arousals/hour between dippers, non-dippers and reverse dippers. None of the HRV parameters differed between dippers, non-dippers and reverse dippers. No differences were found in 24 h, night-time, daytime or nocturnal dip in BP between subjects with non-OSA, mild, moderate and severe OSA. CONCLUSION: We found no relationship between BP pattern or HRV and the severity of OSA in persons with SCI.

pH-sensitive PEGylation of RIPL peptide-conjugated nanostructured lipid carriers: design and in vitro evaluation.

BACKGROUND: RIPL peptide (IPLVVPLRRRRRRRRC)-conjugated nanostructured lipid carriers (RIPL-NLCs) can facilitate selective drug delivery to hepsin (Hpn)-expressing cancer cells, but they exhibit low stability in the blood. Generally, biocompatible and nontoxic poly(ethylene glycol) surface modification (PEGylation) can enhance NLC stability, although this may impair drug delivery and NLC clearance. To attain RIPL-NLC steric stabilization without impairing function, pH-sensitive cleavable PEG (cPEG) was grafted onto RIPL-NLCs (cPEG-RIPL-NLCs). METHODS: Various types of NLC formulations including RIPL-NLCs, PEG-RIPL-NLCs, and cPEG-RIPL-NLCs were prepared using the solvent emulsification-evaporation method and characterized for particle size, zeta potential (ZP), and cytotoxicity. The steric stabilization effect was evaluated by plasma protein adsorption and phagocytosis inhibition studies. pH-sensitive cleavage was investigated using the dialysis method under different pH conditions. Employing a fluorescent probe (1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate [DiI]), in vitro drug delivery capacity of the cPEG-RIPL-NLCs under different pH conditions was also performed on Hpn-expressing SKOV3 cells and 3D-tumor spheroids. RESULTS: All prepared NLCs showed homogenous dispersion (<220 nm in size) with a negative ZP (-18 to -22 mV), except for positively charged RIPL-NLCs (~10 mV), revealing no significant cytotoxicity in either SKOV3 or RAW 264.7 cell lines. cPEG-RIPL-NLC protein adsorption was 1.75-fold less than that of RIPL-NLCs, and PEGylation significantly reduced the macrophage uptake. PEG detachment from the cPEG-RIPL-NLCs was pH-sensitive and time dependent. At 2 hours incubation, cPEG-RIPL-NLCs and PEG-RIPL-NLCs exhibited comparable cellular uptake at pH 7.4, whereas cPEG-RIPL-NLC uptake was increased over 2-fold at pH 6.5. 3D-spheroid penetration also demonstrated pH-sensitivity: at pH 7.4, cPEG-RIPL-NLCs could not penetrate deep into the spheroid core region during 2 hours, whereas at pH 6.5, high fluorescence intensity in the core region was observed for both cPEG-RIPL-NLC-and RIPL-NLC-treated groups. CONCLUSION: cPEG-RIPL-NLCs are good candidates for Hpn-selective drug targeting in conjunction with pH-responsive PEG cleavage.

RIPL peptide-conjugated nanostructured lipid carriers for enhanced intracellular drug delivery to hepsin-expressing cancer cells.

BACKGROUND: To facilitate selective and enhanced drug delivery to hepsin (Hpn)-expressing cancer cells, RIPL peptide (IPLVVPLRRRRRRRRC, 16-mer)-conjugated nanostructured lipid carriers (RIPL-NLCs) were developed. METHODS: NLCs were prepared using a solvent emulsification-evaporation method and the RIPL peptide was conjugated to the maleimide-derivatized NLCs via the thiol-maleimide reaction. Employing a fluorescent probe (DiI), in vitro target-selective intracellular uptake behaviors were observed using fluorescence microscopy and flow cytometry. Separately, docetaxel (DTX) was encapsulated by pre-loading technique, then cytotoxicity and drug release were evaluated. In vivo antitumor efficacy was investigated in BALB/c nude mice with SKOV3 cell tumors after intratumoral injections of different DTX formulations at a dose equivalent to 10 mg/kg DTX. RESULTS: RIPL-NLCs showed positively charged nanodispersion, whereas NLCs were negatively charged. DTX was successfully encapsulated with an encapsulation efficiency and drug loading capacity of 95-98% and 44-46 µg/mg, respectively. DTX release was diffusion-controlled, revealing the best fit to the Higuchi equation. Cellular uptake of DiI-loaded RIPL-NLCs was 8.3- and 6.2-fold higher than that of DiI-loaded NLCs, in Hpn(+) SKOV3 and LNCaP cells, respectively. The translocation of RIPL-NLCs into SKOV3 cells was time-dependent with internalization within 1 h and distribution throughout the cytoplasm after 2 h. DTX-loaded RIPL-NLCs (DTX-RIPL-NLCs) revealed dose-dependent in vitro cytotoxicity, while drug-free formulations were non-cytotoxic. In SKOV3-bearing xenograft mouse model, DTX-RIPL-NLCs significantly inhibited tumor growth: the inhibition ratios of the DTX solution-treated and DTX-RIPL-NLC-treated groups were 61.4% and 91.2%, respectively, compared to those of the saline-treated group (control). CONCLUSION: RIPL-NLCs are good candidates for Hpn-selective drug targeting with a high loading capacity of hydrophobic drug molecules.

Preparation of High-Percentage 1T-Phase Transition Metal Dichalcogenide Nanodots for Electrochemical Hydrogen Evolution.

Nanostructured transition metal dichalcogenides (TMDs) are proven to be efficient and robust earth-abundant electrocatalysts to potentially replace precious platinum-based catalysts for the hydrogen evolution reaction (HER). However, the catalytic efficiency of reported TMD catalysts is still limited by their low-density active sites, low conductivity, and/or uncleaned surface. Herein, a general and facile method is reported for high-yield, large-scale production of water-dispersed, ultrasmall-sized, high-percentage 1T-phase, single-layer TMD nanodots with high-density active edge sites and clean surface, including MoS2 , WS2 , MoSe2 , Mo0.5 W0.5 S2 , and MoSSe, which exhibit much enhanced electrochemical HER performances as compared to their corresponding nanosheets. Impressively, the obtained MoSSe nanodots achieve a low overpotential of -140 mV at current density of 10 mA cm-2 , a Tafel slope of 40 mV dec-1 , and excellent long-term durability. The experimental and theoretical results suggest that the excellent catalytic activity of MoSSe nanodots is attributed to the high-density active edge sites, high-percentage metallic 1T phase, alloying effect and basal-plane Se-vacancy. This work provides a universal and effective way toward the synthesis of TMD nanostructures with abundant active sites for electrocatalysis, which can also be used for other applications such as batteries, sensors, and bioimaging.

Poly(D,L-lactic acid)-glycerol-based nanoparticles for curcumin delivery.

Poly(D,L-lactic acid)-glycerol (PDLLA-G)-based nanoparticles (NPs) were fabricated for the intravenous delivery of curcumin (CUR). NPs with a mean diameter of approximately 200 nm, a narrow size distribution, and capable of efficient drug encapsulation were prepared using an emulsification-solvent evaporation method. The stability of NPs was verified in water, phosphate buffered saline (PBS), and serum after 24-h incubation. A sustained drug release pattern was observed, and the amount of CUR released in acidic media (pH 5.5) was higher than in media at physiological pH (pH 7.4). Blank NPs (without drug loading) did not exhibit severe cytotoxicity in MDA-MB-231 human breast adenocarcinoma cells. The in vitro anti-tumor efficacy of CUR-loaded NPs in MDA-MB-231 cells was comparable to that of a solution of CUR. Pharmacokinetic studies in rats showed that the in vivo clearance (CL) of CUR in the NP-treated group was lower than the group treated with CUR solution. Therefore, encapsulation of CUR in PDLLA-G NPs was shown to enable prolonged circulation of the drug in the blood stream and guarantee improved anticancer activity after intravenous injection. These biocompatible NPs could be an efficient nano-sized injectable formulation for CUR delivery.