Light-triggered cardiac microphysiological model.

Light is recognized as an accurate and noninvasive tool for stimulating excitable cells. Here, we report on a non-genetic approach based on organic molecular phototransducers that allows wiring- and electrode-free tissue modulation. As a proof of concept, we show photostimulation of an in vitro cardiac microphysiological model mediated by an amphiphilic azobenzene compound that preferentially dwells in the cell membrane. Exploiting this optical based stimulation technology could be a disruptive approach for highly resolved cardiac tissue stimulation.

Towards predicting shear-banding instabilities in lipid monolayers.

Langmuir monolayers are advantageous systems used to investigate how lipid membranes get involved in the physiology of many living structures, such as collapse phenomena in alveolar structures. Much work focuses on characterizing the pressure-bearing capacity of Langmuir films, expressed in the form of isotherm curves. These show that monolayers experience different phases during compression with an according evolution of their mechanical response, incurring into instability events when a critical stress threshold is overcome. Although well-known state equations, which establish an inverse relationship between surface pressure and area change, are able to properly describe monolayer behaviour during liquid expanded phase, the modelling of their nonlinear behaviour in the subsequent condensed region is still an open issue. In this regard, most efforts are addressed to explain out-of-plane collapse by modelling buckling and wrinkling mainly resorting to linearly elastic plate theory. However, some experiments on Langmuir monolayers also show in-plane instability phenomena leading to the formation of the so-called shear bands and, to date, no theoretical description of the onset of shear banding bifurcation in monolayers has been yet provided. For this reason, by adopting a macroscopic description, we here study material stability of the lipid monolayers and exploit an incremental approach to find the conditions that kindle shear bands. In particular, by starting from the widely assumed hypothesis that monolayers behave elastically in the solid-like region, in this work a hyperfoam hyperelastic potential is introduced as a new constitutive strategy to trace back the nonlinear response of monolayer response during densification. In this way, the obtained mechanical properties together with the adopted strain energy are successfully employed to reproduce the onset of shear banding exhibited by some lipid systems under different chemical and thermal conditions.

Improving surgical site infection prevention in Asia-Pacific through appropriate surveillance programs: Challenges and recommendation.

BACKGROUND: Surgical site infections (SSIs) represent a substantial clinical and economic burden on patients and the healthcare system. The prevention of SSIs entails surveillance activities which lead to effective mitigation strategies, which are lacking across Asia Pacific (APAC). This manuscript aims to document gaps and challenges across APAC that affect the undertaking of a successful SSI surveillance activities and to provide recommendations on overcoming such challenges. METHODS: A targeted literature review with relevance to APAC identified a series of salient points pertaining to SSI prevention guidelines, implementation, surveillance and outcomes, which was discussed in July 2019 at the APAC Surgical Site Infection Prevention Symposium. An expert panel, comprising eight multidisciplinary experts from APAC and the USA, subsequently amalgamated the key discussion points from the Symposium and their clinical experiences in developing this article. RESULTS: The barriers to implementing a successful and effective APAC SSI surveillance program were identified as: (a) lack of standardized definitions, reporting methodology and accountability, (b) lack of fiscal resources, (c) reporting variability and under-reporting, and (d) lack of safety culture. Implementing an effective surveillance program in APAC will require countries to develop a well-designed and robust surveillance plan and ensure adequate training for staffs involved. CONCLUSION: To improve SSI prevention in the region, it is imperative to encourage implementation of national programs with standardized methodologies and accountabilities. An ongoing APAC information exchange, including data and methodologies, will enable continuous learning within the APAC region.

Low Frequency Dielectric and Optical Behavior on Physicochemical Properties of Hydroxyapatite/Cornstarch Composite.

An investigation on relationship among the physicochemical, optical and dielectric properties of the hydroxyapatite/cornstarch (HA/Cs) composites with the starch proportion of 30, 40, 50, 60, 70, 80 and 90 wt% is presented in this work. The HA/Cs composites have been characterized via FTIR, XRD, DRS and impedance analyzer. This work depicts that the strong interaction is exhibited between the hydroxyapatite nanoparticles and starch as the starch proportion increases. This increment trend results in the higher crystallinity of the HA/Cs composites. The highly crystallized HA/Cs with hydroxyapatite nucleation center presents low optical properties (diffuse reflectance and optical band gap energy). The HA/Cs composite with 80 wt% starch proportion (H2C8) show higher dielectric properties (dielectric constant, loss factor and conductivity) due to the stronger interfacial interaction and close-packed HA/Cs crystalline structure. The relationship among the physicochemical, optical and dielectric properties of the HA/Cs composite is studied in this work for potential of instrumentation design.

Expert commentary on the challenges and opportunities for surgical site infection prevention through implementation of evidence-based guidelines in the Asia-Pacific Region.

INTRODUCTION: Surgical site infections (SSIs) are a significant source of morbidity and mortality in the Asia-Pacific region (APAC), adversely impacting patient quality of life, fiscal productivity and placing a major economic burden on the country's healthcare system. This commentary reports the findings of a two-day meeting that was held in Singapore on July 30-31, 2019, where a series of consensus recommendations were developed by an expert panel composed of infection control, surgical and quality experts from APAC nations in an effort to develop an evidence-based pathway to improving surgical patient outcomes in APAC. METHODS: The expert panel conducted a literature review targeting four sentinel areas within the APAC region: national and societal guidelines, implementation strategies, postoperative surveillance and clinical outcomes. The panel formulated a series of key questions regarding APAC-specific challenges and opportunities for SSI prevention. RESULTS: The expert panel identified several challenges for mitigating SSIs in APAC; (a) constraints on human resources, (b) lack of adequate policies and procedures, (c) lack of a strong safety culture, (d) limitation in funding resources, (e) environmental and geographic challenges, (f) cultural diversity, (g) poor patient awareness and (h) limitation in self-responsibility. Corrective strategies for guideline implementation in APAC were proposed that included: (a) institutional ownership of infection prevention strategies, (b) perform baseline assessments, (c) review evidence-based practices within the local context, (d) develop a plan for guideline implementation, (e) assess outcome and stakeholder feedback, and (f) ensure long-term sustainability. CONCLUSIONS: Reducing the risk of SSIs in APAC region will require: (a) ongoing consultation and collaboration among stakeholders with a high level of clinical staff engagement and (b) a strong institutional and national commitment to alleviate the burden of SSIs by embracing a safety culture and accountability.

Efficacy of a Comprehensive Dysphagia Intervention Program Tailored for the Residents of Nursing Homes.

Oropharyngeal dysphagia is a widespread condition in older people and thus poses a serious health threat to the residents of nursing homes. The management of dysphagia relies mainly on compensatory strategies, such as diet and environmental modification. This study investigated the efficacy of an intervention program using a single-arm interventional study design. Twenty-two participants from nursing homes were included and had an average of 26 hours of intervention, including oromotor exercises, orosensory stimulation and exercises to target dysphagia and caregiver training. Four of the 22 participants exhibited improvement in functional oral intake scale (FOIS) but was not statistically significant as a group. All oromotor function parameters, including the range, strength, and coordination of movements, significantly improved. These results indicate that this intervention program could potentially improve the oromotor function, which were translated into functional improvements in some participants' recommended diets. The validity of this study could be improved further by using standardized swallowing and feeding assessment methods or an instrumental swallowing assessment.

Association between body mass index and stroke severity in acute ischaemic stroke with non-valvular atrial fibrillation.

BACKGROUND AND PURPOSE: The objective of this study was to investigate the association between body mass index (BMI) and both initial stroke severity at presentation and functional outcomes after acute ischaemic stroke (AIS) in patients with non-valvular atrial fibrillation (NVAF). METHODS: Patients were categorized on the basis of their BMI into underweight (BMI <18.5, n = 111), normal (18.5 ≤ BMI <25, n = 1036) and overweight to obese (BMI ≥25, n = 472) groups. Initial stroke severity was assessed using the National Institutes of Health Stroke Scale (NIHSS) score and functional outcomes were assessed using the modified Rankin Scale score at discharge. The differences in stroke severity and functional outcomes were compared between groups using robust log-linear regression with a Poisson distribution and binary logistic regression analysis. RESULTS: A total of 1619 AIS patients with NVAF from six hospitals were included. Compared with the NIHSS scores [median 5, interquartile range (IQR) 2-14] of normal-weight patients, the NIHSS scores (median 9, IQR 4-19) of underweight patients were more likely to be higher, whereas those of overweight to obese patients were lower (median 4, IQR 1-12) (P < 0.001). In terms of functional outcomes after stroke, underweight patients had a higher risk of poor functional outcomes (odds ratio 1.78, 95% confidence interval 1.09-2.56, P = 0.01) but overweight to obese patients had no significant difference in functional outcomes compared with normal-weight patients. CONCLUSION: An inverse association was found between BMI and stroke severity in AIS patients with NVAF. This suggests the presence of an obesity paradox for short-term outcomes in patients with NVAF.

Evaluation of the blend of organic acids and medium-chain fatty acids in matrix coating as antibiotic growth promoter alternative on growth performance, nutrient digestibility, blood profiles, excreta microflora, and carcass quality in broilers.

This study was conducted to evaluate the effects of the blend of organic acids (OAs) and medium-chain fatty acids (MCFAs) in broiler chickens. A total of 816 1-d-old male Ross 308 broiler chickens (35 ± 0.44 g) were randomly allocated into 1 of the following 6 dietary treatments (17 broilers per pen with 8 pens per treatment): dietary treatments consisted of corn-soybean meal-based basal diet and the basal diet supplemented with 0.02, 0.03, 0.04, 0.05, and 0.06% blend of OAs and MCFAs. The study lasted 5 wk during which growth performance was determined. In the current study, the inclusion of 0.02, 0.03, 0.04, 0.05, and 0.06% blend of OAs and MCFAs in the basal diet linearly increased (P < 0.05) body weight gain and improved feed conversion ratio (P < 0.0001) on day 7 to 14, day 14 to 35, as well as overall. Increasing inclusion of the blend of OAs and MCFAs levels in the diets also linearly increased (P = 0.001) the digestibility of dry matter on day 35. Broilers fed with different levels of the blend of OAs and MCFAs showed a linear increment (P = 0.042) in Lactobacillus concentration and decrease (P = 0.002) in Escherichia coli concentration. With regard to relative organ weight, a trend of linear reduction (P = 0.052) in bursa of Fabricius weight of broilers fed the blend of OAs and MCFAs was observed. There was a significant linear improvement (P = 0.011) in the IgG concentration associated with the inclusion of the blend of OAs and MCFAs levels in the diets. In conclusion, the blend of OAs and MCFAs supplementation positively influenced growth performance, nutrient digestibility, and excreta microflora in broiler chickens.

Performance, egg quality, nutrient digestibility, and excreta microbiota shedding in laying hens fed corn-soybean-meal-wheat-based diets supplemented with xylanase.

The aim of this study was to evaluate the effects of dietary levels of xylanase on production performance, egg quality, nutrient digestibility, and excreta microbiota shedding of laying hens in a 12-week trial. Two-hundred-forty Hy-Line brown laying hens (44 wk old) were distributed according to a randomized block experimental design into one of 4 dietary treatments with 10 replicates of 6 birds each. The 4 dietary treatments were corn-soybean-meal-wheat-based diets supplemented with 0, 225, 450, or 900 U/kg xylanase. Daily feed intake, egg production, egg weight, egg mass, feed conversion ratio, and damaged egg rate showed no significant response to increasing xylanase supplementation during any phase (P > 0.05). No significant responses were observed for apparent total tract digestibility of dry matter, nitrogen, or gross energy (P > 0.05). A significant linear increase to increasing xylanase supplementation was seen for lactic acid bacteria numbers, although coliforms and Salmonella counts were not affected. Increasing the dietary xylanase resulted in a significant linear increase in eggshell thickness in wk 3, 6, 9, and 12 (P < 0.05). In addition, a significant linear increase occurred for Haugh unit and albumen height in wk 12 (P < 0.05). In summary, the inclusion of xylanase in corn-soybean-meal-wheat-based diets increased eggshell thickness, Haugh unit, albumen height, and excreta lactic acid bacteria count but had no effect on production performance or nutrient digestibility.

Comparison of rocuronium-induced neuromuscular blockade in second trimester pregnant women and non-pregnant women.

BACKGROUND: This study set out to compare the onset and duration of rocuronium-induced neuromuscular blockade in second trimester pregnant women and non-pregnant women receiving general anesthesia. METHODS: Forty-seven pregnant (Group P) and forty-seven non-pregnant (Group C) women were enrolled. Anesthesia was induced with propofol 2.0 mg/kg and rocuronium 0.6 mg/kg, and neuromuscular blockade was assessed with an accelerometric sensor using train-of-four stimulation (TOF-Watch® SX). Tracheal intubation was performed at maximum depression of the first twitch (T1) and anesthesia was maintained with sevoflurane 1.5-2.5% and 50% oxygen in air. We recorded the times to maximum T1 depression and 5% and 25% T1 recovery, as well as the mean arterial pressure and heart rate at baseline, injection of rocuronium, intubation, and 5% and 25% T1 recovery. RESULTS: The onset of rocuronium-induced neuromuscular blockade (time to maximum T1 depression) did not differ significantly between the groups. The duration (time to 25% T1 recovery) was significantly longer in Group P than in Group C (45.7 ±â€¯12.9 min vs 40.6 ±â€¯10.4 min, P <0.037). During the recovery period from the blockade, the mean arterial pressure was significantly lower in Group P than in Group C. CONCLUSION: Our data showed that the rocuronium-induced neuromuscular blockade did not significantly differ in onset but lasted significantly longer in second trimester pregnant women compared with non-pregnant women.

High resolution Thomson scattering system for steady-state linear plasma sources.

The high resolution Thomson scattering system with 63 points along a 25 mm line measures the radial electron temperature (Te) and its density (ne) in an argon plasma. By using a DC arc source with lanthanum hexaboride (LaB6) electrode, plasmas with electron temperature of over 5 eV and densities of 1.5 × 1019 m-3 have been measured. The system uses a frequency doubled (532 nm) Nd:YAG laser with 0.25 J/pulse at 20 Hz. The scattered light is collected and sent to a triple-grating spectrometer via optical-fibers, where images are recorded by an intensified charge coupled device (ICCD) camera. Although excellent in stray-light reduction, a disadvantage comes with its relatively low optical transmission and in sampling a tiny scattering volume. Thus requires accumulating multitude of images. In order to improve photon statistics, pixel binning in the ICCD camera as well as enlarging the intermediate slit-width inside the triple-grating spectrometer has been exploited. In addition, the ICCD camera capture images at 40 Hz while the laser is at 20 Hz. This operation mode allows us to alternate between background and scattering shot images. By image subtraction, influences from the plasma background are effectively taken out. Maximum likelihood estimation that uses a parameter sweep finds best fitting parameters Te and ne with the incoherent scattering spectrum.

Expression patterns of members of the isocitrate dehydrogenase gene family in murine inner ear.

Age-related hearing loss (ARHL) is characterized by an age-dependent decline of auditory function characterized by with loss of sensory hair cells, spiral ganglion neurons, and stria vascularis (SV) cells in the cochlea of the inner ear. Aging and age-related diseases result from accumulated oxidative damage caused by reactive oxygen species (ROS) generated by mitochondria. The isocitrate dehydrogenase (IDH) family includes three enzymes in human cells: IDH1, IDH2, and IDH3. Although all three enzymes catalyze the same enzymatic reaction, that is, oxidative decarboxylation of isocitrate to produce α-ketoglutarate, each IDH enzyme has unique features. We identified and characterized IDH expression in the cochlea and vestibule of the murine inner ear. We examined the mRNA expression levels of Idh family members in the cochlea and vestibule using reverse transcription-PCR (RT-PCR) and detected expression of IDH family members in both tissues. We also used immunohistochemistry to localize IDH family members within the cochlea and vestibule of the adult mouse inner ear. IDH1 was detected throughout the cochlea. IDH2 was expressed specifically in the hair cells, spiral ganglion, and stria vascularis. IDH3α was found in the cell bodies of neurons of the spiral ganglion, the stria vascularis, and in types II, IV, and V cells of the spiral ligament in a pattern that resembled the location of the Na+, K+-ATPase ion channel. We postulate that the IDH family participates in transporting K+ ions in the cochlea. In the vestibule, all IDH family members were detected in both hair cells and the vestibular ganglion. We hypothesize that IDH1, IDH2, and IDH3 function to protect proteins in the inner ear from oxidative stress during K+ recycling.

The role of carbon chain length in the attachment between microbubbles and aqueous solutions of ionic liquid.

HYPOTHESIS: The effects of varying carbon chain lengths (CCLs) and concentrations of aqueous solutions of imidazolium based ionic liquids on bubble particle attachment (BPA) will provide a better understanding in catering for the varying degrees of surface activities in the application of the flotation technology. The general trends of this study should also be applicable to homologous series of other cationic surfactants and ionic liquids. EXPERIMENTS: Zeta potentials of small air bubbles and bunker oil drops dispersed in aqueous solutions of n-methylimidazolium chloride ionic liquids (n=0, 2, 3, 6, 8, 10, 12) of concentrations ranging from 1000PPM to 8000PPM, as were interfacial tensions of these solutions with bunker oil (180cst) and contact angles made by air bubbles at interfaces between these solutions and thin layers of bunker oil on flat solid surfaces were investigated. Finally, interparticle forces analysis using the Derjaguin-Landau, Verwey-Overbeek (DLVO) theory is also included. FINDINGS: Analysis using the DLVO theory showed attractive forces between the oil particles and micro-bubbles are significantly more prevalent in short CCLs solutions of imidazolium-based ILs in low concentrations, namely [C0mim][Cl] and [C2mim][Cl] at a maximum zeta potential difference of 75.3mV. The results from CA measurements follows similarly whereby low concentrations of ILs with short CCLs were in favor for the bubble-particle attachment process with angles ranging between 93.95° for [C0mim][Cl] and 97.28° for [C2mim][Cl]. IFT which is important in reducing coalescence for the preferential BPA process to occur in flotation decreases with an increase of CCL and concentration of IL.

Genome-wide loss-of-function genetic screening identifies opioid receptor µ1 as a key regulator of L-asparaginase resistance in pediatric acute lymphoblastic leukemia.

L-asparaginase is a critical chemotherapeutic agent for acute lymphoblastic leukemia (ALL). It hydrolyzes plasma asparagine into aspartate and NH3, causing asparagine deficit and inhibition of protein synthesis and eventually, leukemic cell death. However, patient relapse often occurs due to development of resistance. The molecular mechanism by which ALL cells acquire resistance to L-asparaginase is unknown. Therefore, we sought to identify genes that are involved in L-asparaginase resistance in primary leukemic cells. By unbiased genome-wide RNAi screening, we found that among 10 resistant ALL clones, six hits were for opioid receptor mu 1 (oprm1), two hits were for carbonic anhydrase 1 (ca1) and another two hits were for ubiquitin-conjugating enzyme E2C (ube2c). We also found that OPRM1 is expressed in all leukemic cells tested. Specific knockdown of OPRM1 confers L-asparaginase resistance, validating our genome-wide retroviral shRNA library screening data. Methadone, an agonist of OPRM1, enhances the sensitivity of parental leukemic cells, but not OPRM1-depleted cells, to L-asparaginase treatment, indicating that OPRM1 is required for the synergistic action of L-asparaginase and methadone, and that OPRM1 loss promotes leukemic cell survival likely through downregulation of the OPRM1-mediated apoptotic pathway. Consistent with this premise, patient leukemic cells with relatively high levels of OPRM1 are more sensitive to L-asparaginase treatment compared to OPRM1-depleted leukemic cells, further indicating that OPRM1 loss has a crucial role in L-asparaginase resistance in leukemic patients. Thus, our study demonstrates for the first time, a novel OPRM1-mediated mechanism for L-asparaginase resistance in ALL, and identifies OPRM1 as a functional biomarker for defining high-risk subpopulations and for the detection of evolving resistant clones. Oprm1 may also be utilized for effective treatment of L-asparaginase-resistant ALL.

Safety and efficacy of warfarin in patients with moderate thrombocytopenia.

INTRODUCTION: Patients with moderate thrombocytopenia and comorbidities requiring anticoagulation are currently sub-optimally treated because of bleeding concerns. Guidance on anticoagulating such patients is currently lacking because of limited data on safety and efficacy of anticoagulation in such patients. METHODS: This retrospective study compared the incidence of bleeding and thrombosis in a cohort of warfarinized patients with sustained platelet counts below 100×109/L against a cohort with normal platelet counts (>140×109/L). Primary outcomes of safety and efficacy were determined by incidence rate ratios (IRR) of bleeding and thrombotic events. International normalized ratio (INR) and platelet counts during adverse events in thrombocytopenic arm were secondary outcomes. RESULTS: 137 thrombocytopenic patients (104,985 patient-exposure days) were compared against 939 normal patients (715,193 patient-exposure days). IRR of minor, major bleeding and thrombosis among thrombocytopenic patients were 3.03 (95% CI: 1.57-5.60), 1.48 (95% CI: 0.44-3.98), and 0.807 (95% CI: 0.09-3.43) respectively. Median INR and platelet count readings during minor and major bleeds were 3.60 (IQR: 2.70-4.12) and 3.12 (IQR: 2.82-4.22), and 99×109/L (IQR: 77.0-147.0×109/L) and 115×109/L (IQR: 107.5-169.5×109/L) respectively. CONCLUSION: Warfarinized thrombocytopenic patients are at higher risk of minor bleeding complications with a higher tendency for major bleeding but derive similar benefits against thrombotic events compared to normal patients. Bleeding events are associated with higher INRs. A narrow INR target with an upper limit below 2.5 together with closer anticoagulation monitoring may improve safety of patients.

Interfacial rheology of coexisting solid and fluid monolayers.

Biologically relevant monolayer and bilayer films often consist of micron-scale high viscosity domains in a continuous low viscosity matrix. Here we show that this morphology can cause the overall monolayer fluidity to vary by orders of magnitude over a limited range of monolayer compositions. Modeling the system as a two-dimensional suspension in analogy with classic three-dimensional suspensions of hard spheres in a liquid solvent explains the rheological data with no adjustable parameters. In monolayers with ordered, highly viscous domains dispersed in a continuous low viscosity matrix, the surface viscosity increases as a power law with the area fraction of viscous domains. Changing the phase of the continuous matrix from a disordered fluid phase to a more ordered, condensed phase dramatically changes the overall monolayer viscosity. Small changes in the domain density and/or continuous matrix composition can alter the monolayer viscosity by orders of magnitude.