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Synergistic bioassay-guided isolation of the extracts of Artemisia rupestris L, which belongs to the family Asteraceae, afforded two acetylenic spiroketal enol ethers, namely rupesdiynes A (1) and B (2). Their structures were determined based on spectroscopic analysis and experimental and calculated ECD investigations. The two compounds exhibited synergistic activity and were able to reduce the minimum inhibitory concentration (MIC) of oxacillin four-fold, with a fractional inhibitory concentration index (FICI) of 0.5 in combination with oxacillin against the oxacillin-resistant EMRSA-16. Biofilm formation inhibitory and Ethidium bromide (EtBr) efflux assay were further employed to verify the possible mechanism of the synergistic antibacterial effect. Additionally, molecular docking studies were conducted to investigate the binding affinities of the two compounds with penicillin-binding protein 2a (PBP2a) of EMRSA-16. Taken together, rupesdiynes A (1) and rupesdiyne B (2) showed moderate synergistic activity against EMRSA-16 with oxacillin via inhibiting biofilm formation and efflux pump activity, respectively.

BACKGROUND: Brain plasticity evoked by environmental enrichment through early mobilization may improve sensorimotor functions of patients with moderate-to-severe traumatic brain injury (TBI). Increasing evidence also suggests that early mobilization increases verticalization, which is beneficial to TBI patients in critical care. However, there are limited data on early mobilization interventions provided to patients with moderate-to-severe TBI. OBJECTIVE: We investigated the possible enhancing effects of revised progressive early mobilization on functional mobility and the rate of out-of-bed mobility attained by patients with moderate-to-severe TBI. METHODS: This is a quantitative study with a retrospective and prospective pre–post intervention design. We implemented a revised progressive early mobilization protocol for patients with moderate-to-severe TBI admitted to the trauma intensive care unit (ICU) within the previous seven days. The outcome parameters were the rate of patients attaining early mobilization (sitting on the edge of the bed) and the Perme ICU Mobility Score at discharge from the ICU. The outcome parameters in the intervention cohort were compared with those from a historical control cohort who received standard medical care a year previously. Differences in the Perme ICU Mobility Score between the two cohorts were assessed using univariate analysis of covariance. RESULTS: Forty-two patients were included in the progressive early mobilization program and were compared with 44 patients who underwent standard medical care. In the intervention cohort, 100% and 57.2% of the patients completed early rehabilitation and early mobilization, respectively, compared to 0% in the control cohort. The intervention cohort at ICU discharge showed significantly improved the Perme ICU Mobility Scores. CONCLUSIONS: The implementation of the revised progressive early mobilization program for patients with moderate-to-severe TBI resulted in significantly improved mobility at ICU discharge; however, the length of overall stay in the ICU may be not affected.

Antimicrobial susceptibility testing (AST) is a key measure in clinical microbiology laboratories to enable appropriate antimicrobial administration. During an AST, the determination of the minimum inhibitory concentration (MIC) is an important step in which the bacterial responses to an antibiotic at a series of concentrations obtained in separate bacterial growth chambers or sites are compared. However, the preparation of different antibiotic concentrations is time-consuming and labor-intensive. In this paper, we present a microfluidic device that generates a concentration gradient for antibiotics that is produced by diffusion in the laminar flow regime along a series of lateral microwells to encapsulate bacteria for antibiotic treatment. All the AST preparation steps (including bacterium loading, antibiotic concentration generation, buffer washing, and isolated bacterial growth with an antibiotic) can be performed in a single chip. The viable bacterial cells in each microwell after the antibiotic treatment are then quantified by their surface-enhanced Raman scattering (SERS) signals that are acquired after placing a uniform SERS-active substrate in contact with all the microwells. For proof-of-concept, we demonstrated the AST performance of this system on ampicillin (AMP)-susceptible and -resistant

Background As effective management of sepsis requires timely administration of appropriate antibiotics, a reliable and rapid antimicrobial susceptibility testing (AST) is crucial. To meet clinical needs, we developed a novel AST, referred to as SERS-AST, based on the surface-enhanced Raman Scattering (SERS) technology. SERS-AST determines antibiotic susceptibility of bacteria based on variations in bacterial SERS signals derived from secreted purines and their derivatives. Methods SERS-AST was applied to blood culture samples of patients with bacteremia. Eight common causative organisms, including Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis, Enterococcus faecium, Escherichia coli, Enterobacter cloacae, Klebsiella pneumoniae, and Acinetobacter baumannii and seven most prescribed antibiotics, including oxacillin, levofloxacin, vancomycin, ampicillin, cefotaxime, ceftazidime, levofloxacin, and imipenem were tested. Receiver operating characteristic analysis was performed to obtain the optimal cutoff SERS signal value to determine the susceptibility of tested bacteria. The results of SERS-AST were compared with those of VITEK 2. Results A total of 164 bacterial isolates from blood samples were examined, and the agreement rates between SERS-AST and VITEK 2 results were 96% for Gram-positive bacteria and 97% for Gram-negative bacteria. Conclusions By directly assaying positive blood cultures without additional subcultures, SERS-AST can be completed within 4 hours with high accuracy. It can be an alternative AST method to provide critical information to clinicians for timely administration of appropriate antibiotics to treat patients with blood stream infections.

Effective management of sepsis requires timely administration of appropriate antibiotics; therefore, a reliable and rapid antimicrobial susceptibility test (AST) is crucial. To meet clinical needs, we developed a novel AST, referred to as SERS-AST, based on the surface-enhanced Raman Scattering (SERS) technology. In this study, we applied SERS-AST to eight most common pathogens causing bacteremia, including Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis, E. faecium, Escherichia coli, Enterobacter cloacae, Klebsiella pneumoniae, and Acinetobacter baumannii. Seven different antibiotics were tested, including oxacillin, levofloxacin, vancomycin, ampicillin, cefotaxime, ceftazidime, levofloxacin, and imipenem. SERS-AST determines antibiotic susceptibility of bacteria directly from positive blood cultures based on variations in bacterial SERS signals derived from secreted purines and their derivatives. The whole process could be completed within 4 hours, and the agreement rates between SERS-AST and VITEK 2 results were 96% for Gram-positive bacteria and 97% for Gram-negative bacteria.

Background: The injury severity score (ISS) is used in daily practice to evaluate the severity of trauma patients; however, the score is not always consistent with the prognosis. After injury, systemic inflammatory response syndrome (SIRS) and compensatory anti-inflammatory response syndrome (CARS) are related to the prognosis of trauma patients. Methods: Patients who admitted to the Trauma Intensive Care Unit (ICU) were eligible. Whole blood samples were collected at admission, and then 6, 12, 24, 48 and 72 hours after admission. Natural killer (NK) cells, lymphocyte subset population and cytokines release were identified using flow cytometry. We grouped patients by their ISS (≤ 25 and > 25 as very severe injury) and ICU stay (≤ 10 days as a short ICU stay and >10 days as a long ICU stay) for evaluation. Results: Fifty-three patients were enrolled. ICU stay but not ISS was close correlated with activity daily living (ADL) at discharge. Patients with a long ICU stay had an immediate increase in NK cells followed by lymphopenia which persisted for 48 hours. Immediate activation of CD8 + T cells and then exhaustion with a higher programmed cell death-1 (PD-1) expression and suppression of CD4 + T cells with a shift to an anti-inflammatory Th2 phenotype were also observed in the patients with a long ICU stay. When the patients were grouped by ISS, the dynamics of immune responses were inconsistent to those when the patients were grouped by ICU stay. Conclusion: Immune responses are associated with the prognosis of trauma patients, however the currently used clinical parameters may not accurately reflect immune responses. Further investigations are needed to identify accurate predictors of prognosis in trauma patients.

For cardiopulmonary bypass, the polyvinyl chloride (PVC) circuit which can initiate the activation of platelets and the coagulation cascade after blood cell contacting is the possible detrimental effect. Surface coating of the PVC tubing system can be an effective approach to enhance circuit's hemocompatibility. In this study, aluminum oxide (Al2 O3 ) thin films were deposited through thermal atomic layer deposition (T-ALD) or plasma-enhanced ALD (PE-ALD) on PVC samples, and the anticoagulation of the Al2 O3 -coated PVC samples was demonstrated. The results revealed that Al2 O3 deposition through ALD increased surface roughness, whereas T-ALD had a relative hydrophilicity compared with blank PVC and PE-ALD. Whole blood immersion tests showed that blood clots formed on blank PVC and that a large amount of red blood cells was found on PE-ALD substrates, whereas less blood cells were noted in T-ALD samples. Both T-ALD and PE-ALD Al2 O3 films did not cause activation of blood cells, as evidenced in CD3+ /CD4+ /CD8+ , CD61+ /CD62P+ , and CD45+ /CD42b+ populations. Analysis of serum coagulation factors showed that a lower amount of prothrombin was absorbed on T-ALD Al2 O3 samples than that on blank PVC. For albumin and fibrinogen immersion tests, immunostaining and scanning electron microscopy further revealed that a thin albumin layer was absorbed on T-ALD Al2 O3 substrates but not on PVC samples. This study revealed that deposition of Al2 O3 films by T-ALD can improve anticoagulation of the PVC tubing system.

Bloodstream infection (BSI) is a serious public health issue worldwide. Timely and effective antibiotics for controlling infection are crucial towards patient outcomes. However, the current culture-based methods of identifying bacteria and antimicrobial susceptibility testing (AST) remain labor-intensive and time-consuming, and are unable to provide early support to physicians in critical hours. To improve the effectiveness of early antibiotic therapy, Surface-enhanced Raman scattering (SERS) technology, has been used in bacterial detection and AST based on its high specificity and label-free features. To simplify sample preparation steps in SERS-AST, we proposed an automated microfluidic control system to integrate all required procedures into a single device. Our preliminary results demonstrated the system can achieve on-chip reagent replacement, bacteria trapping, and buffer exchange. Finally, in-situ SERS-AST was performed within 3.5 h by loading isolates of ampicilin susceptible and resistant E. coli and clear discrimination of two strains under antibiotic treatment was demonstrated. Overall, our system can standardize and simplify the SERS-AST protocol and implicate parallel bacterial detection. This prototypical integration demonstrates timely microbiological support to optimize early antibiotic therapy for fighting bacteremia.

Trehalose, a glucose disaccharide, has been reported to play a role in stabilizing the cell envelope of Escherichia coli under numerous forms of abiotic stress. The exact manner by which trehalose contributes to this stability remains under investigation, though a recent paper suggested that it stabilizes the outer membrane component of the cell envelope in response to a variety of environmental stressors, including the presence of SDS and EDTA. We sought to validate these findings with a more robust approach to the SDS-EDTA assay. A key enzyme in the biosynthetic pathway of trehalose is OtsA, a trehalose-6-phosphate synthase, as otsA mutants are unable to synthesize trehalose. We hypothesized that otsA deletion mutants would be hindered in their ability to stabilize the outer membrane, increasing their susceptibility to SDS-EDTA-induced stress. To test this hypothesis, we performed basal growth rate analyses and SDS-EDTA assays. We report that mutants with a disrupted trehalose biosynthesis pathway were not more sensitive to either form of membrane stress (SDS or EDTA) relative to the wild type. These findings suggest that trehalose may not promote outer membrane stability of E. coli during SDS-EDTA stress., Undergraduate Journal of Experimental Microbiology and Immunology, Vol. 6 (2020): Undergraduate Journal of Experimental Microbiology and Immunology (UJEMI+)

NiTi shape memory alloys (SMAs) have been widely applied in biomedical fields owing to their excellent shape memory effect, super-elasticity, biomedical properties and fatigue performance. These applications include the cardiovascular stent, guidewire, stone extractors used in the cystic duct, artificial heart valve and orthodontic wire, etc. However, NiTi alloys might release out the Ni atoms in the physiological environment, which will induce the serious problems of allergic reaction, poisoning and causing cancer. This study employs the atomic layer deposition (ALD) technique to deposit Al2O3 films on the surfaces of NiTi SMAs. Experimental results show that the chemical compositions of ALD-Al2O3 films are well homogeneous. The ALD-Al2O3 films exhibit a fair adhesion with the NiTi substrates and sustain a suitable deformation strain. The ALD-Al2O3 films can also effectively inhibit the release out of Ni atoms from the NiTi SMAs. Meanwhile, the corrosion resistance of NiTi SMAs can be improved by the ALD-Al2O3 films.

NiTi shape memory alloys (SMAs) have been widely applied in biomedical fields due to their excellent shape memory effect, super-elasticity, and biocompatibility. In this study, the plasma- enhanced atomic layer deposition was applied to deposit TiO2 film on the surface of Ni50Ti50 substrate. The characterization and surface properties of TiO2 film, bending strain test, corrosion resistance, nickel release and in vitro biocompatibility were studied to evaluate the performance of ALD-TiO2 film. The results show that the ALD-TiO2 film is uniform and exhibits an amorphous structure. The ALD-TiO2 films are less hydrophilic than the Ni50Ti50 substrate. As the deposition cycle increases, the water contact angle of ALD-TiO2 film only changes slightly. The ALD-TiO2 film exhibits an adequate adhesion to the Ni50Ti50 substrate and can withstand proper bending strain. ALD-TiO2 film can effectively inhibit the release of nickel ions. After being immersed in the simulated body fluid for 30 days, the amount of nickel ions released decreases from 60 ppb for Ni50Ti50 substrate to 20–20 ppb for Ni50Ti50 with 200-cycle ALD-TiO2 film. Meanwhile, Ni50Ti50 with ALD-TiO2 films have better corrosion resistance than the Ni50Ti50 substrate. In vitro biocompatibility reveals that the ALD-TiO2 film can enhance cell adhesion, promote cell proliferation and reduce cytotoxicity. After 5 days of culture, the 200-cycle ALD-TiO2 film can enhance the cell proliferation by 2.7 times and reduce the cytotoxicity from 48% for Ni50Ti50 substrate to 37% for Ni50Ti50 with 200-cycle ALD-TiO2 film. These results indicate that the TiO2 films deposited by PE-ALD technique can effectively improve the biocompatibility of NiTi SMAs.

Summary Background & aims Patients admitted to intensive care units (ICUs) often need enteral nutrition (EN) support. For patients with type 2 diabetes (T2D), standard EN formulas may not provide ideal nutrients. The purpose was to investigate whether use of a diabetes-specific formula (DSF) could provide clinical and health economic benefits (compared to standard formulas) in critically ill patients with T2D. Methods This study was a retrospective analysis of medical records and expenditure data covering a 5-year period (2009–2013) from the hospitalization database of the National Taiwan University Hospital. Records of ICU patients who had T2D and were receiving enteral feeding with either the DSF or non-diabetes-specific formula (non-DSF) for at least 5 days were included in the analysis. Mortality, ICU length of stay (LOS), diabetes-related medications, and total costs of care (including all costs covered by the National Health Insurance and private expenses) were considered as the primary outcomes. Results A total of 158 patient records were analyzed in the DSF group and 794 in the non-DSF group. The baseline demographics including age, gender, weight, body mass index (BMI), and comorbidity patterns were mostly comparable between the groups. Compared to those receiving non-DSF, patients with T2D receiving DSF were found to have significantly decreased mortality (5.1% vs. 12.3%, P = 0.0118) and reduced need for insulin prescription (29.1% vs. 38.4%, P = 0.0269). ICU LOS was shorter for DSF patients, but no statistical difference was found (13.0 days vs. 15.1 days, P = 0.1843). However, significantly lower total ICU costs were reported for DSF patients (6700 USD vs. 9200 USD, P Conclusions The use of DSF in ICU patients with T2D is correlated with significant reduction in mortality and improved health economic outcomes.

Blood stream infection is one of the major public health issues characterized with high cost and high mortality. Timely effective antibiotics usage to control infection is crucial for patients’ survival. The standard microbiological diagnosis of infection however can last days. The delay in accurate antibiotic therapy would lead to not only poor clinical outcomes, but also to a rise in antibiotic resistance due to widespread use of empirical broad-spectrum antibiotics. An important measure to tackle this problem is fast determination of bacterial antibiotic susceptibility to optimize antibiotic treatment. We show that a protocol based on surface-enhanced Raman spectroscopy can obtain consistent antibiotic susceptibility test results from clinical blood-culture samples within four hours. The characteristic spectral signatures of the obtained spectra of Staphylococcus aureus and Escherichia coli—prototypic Gram-positive and Gram-negative bacteria—became prominent after an effective pretreatment procedure removed strong interferences from blood constituents. Using them as the biomarkers of bacterial metabolic responses to antibiotics, the protocol reported the susceptibility profiles of tested drugs against these two bacteria acquired from patients’ blood with high specificity, sensitivity and speed.

Thermal ALD (T-ALD) and plasma-enhanced ALD (PE-ALD) processes were employed to prepare the Al 2 O 3 thin films on plasticized polyvinyl chloride (PVC) surfaces at a low deposition temperature of 80 °C. The water contact angle test shows that the T-ALD Al 2 O 3 films exhibited a hydrophobic surface, while the PE-ALD Al 2 O 3 films were hydrophilic. The difference in the surface hydrophobicity is attributed to the carbon residue in Al 2 O 3 films, as revealed by the X-ray photoelectron and Fourier transform infrared spectroscopies. The trend of hydrophobicity follows with the evolution of surface roughness of the T-Al 2 O 3 films, indicating that the surface roughness contributed to the hydrophobicity as predicted by the Wenzel's mode. The result indicates that the surface hydrophilicity/hydrophobicity of the Al 2 O 3 thin films can be modified and controlled by the deposition conditions of the ALD process.

Plasmonic enhancement of photoluminescence from bulk silicon was achieved by spectrally tailoring coupled localized surface plasmon resonance (LSPR) in the Al2O3 cover/nanostructured platinum (nano-Pt)/Al2O3 spacer/silicon multilayer structures prepared by atomic layer deposition (ALD). Agreement between the simulation and experimental data indicates that the plasmonic activity originates from absorption enhancement due to coupled LSPR. Because of the optimized dielectric environment deposited by ALD around the nano-Pt layer, absorption of the multilayer structure was enhanced by the precise tuning of coupled LSPR to coincide with the excitation wavelength. This accurate plasmonic multilayer structure grown by ALD with high precision, tunability, uniformity, and reproducibility can be further applied in efficient light-emitting devices.

High-performance plasmonic ZnO/Al2O3 spacer/nano-Pt/Al2O3/substrate multilayer structures were prepared by atomic layer deposition, in which the localized surface plasmons (LSP) were supported by the uniformly dispersed nanostructured Pt (nano-Pt) layer and a precise Al2O3 spacer was introduced to suppress luminescence quenching. Over 100-fold enhancement of photoluminescence from the ZnO emitter, which facilitates the observation of significant quantum confinement effect in the nanoscale ZnO layer as thin as ∼2 nm, was achieved. The giant plasmonic enhancement can be deduced from the optimized Al2O3 spacer thickness, which leads to the reduced coupling with nonradiative high-order LSP modes as well as the overlap between the LSP resonance wavelength and the luminescence/absorbance spectra of the ZnO emitter. This plasmonic multilayer structure with high enhancement, accuracy, tunability, uniformity, and reproducibility can be further applied in sensitive bioassays/biosensing and efficient solid-state lig...

Rapid bacterial antibiotic susceptibility test (AST) and minimum inhibitory concentration (MIC) measurement are important to help reduce the widespread misuse of antibiotics and alleviate the growing drug-resistance problem. We discovered that, when a susceptible strain of Staphylococcus aureus or Escherichia coli is exposed to an antibiotic, the intensity of specific biomarkers in its surface-enhanced Raman scattering (SERS) spectra drops evidently in two hours. The discovery has been exploited for rapid AST and MIC determination of methicillin-susceptible S. aureus and wild-type E. coli as well as clinical isolates. The results obtained by this SERS-AST method were consistent with that by the standard incubation-based method, indicating its high potential to supplement or replace existing time-consuming methods and help mitigate the challenge of drug resistance in clinical microbiology.

The benefit of ω-3 fatty acids in fat emulsion remains controversial. This study evaluated the effect of ω-3 fatty acids on immune and inflammatory modulation in surgical intensive care unit (SICU) patients.Thirty-eight patients admitted to the SICU after major surgery were enrolled in this prospective controlled study and randomized to receive parenteral nutrition (PN) with equal volume and calories from glucose, nitrogen, and fat but different lipid components for 7 postoperative days. Group A (n = 12) received a mixture of soybean and medium-chain triglyceride oils; group B (n = 18) received a fat emulsion with part of the lipid replaced by fish oil. Blood tests, including lipid profile, routine biochemistry, inflammatory cytokines, and lymphocyte subpopulations, were evaluated preoperatively and on postoperative days 4 and 7.Both lipid regimens were well tolerated. There was a trend toward reduced serum inflammatory cytokines in group B vs group A with significant differences regarding interleukin (IL)-1, IL-8, and interferon (IFN)-γ on postoperative day 4 (P.05) and IL-1, IL-8, IFN-γ, IL-6, and tumor necrosis factor-α on postoperative day 7 (P.05). There was a reduction in postoperative liver dysfunction (A vs B: 50% vs 33.3%) and infection rate (A vs B: 41.7% vs 27.8%) in group B, although this was not statistically significant. There was no mortality in either group.This study suggests that supplementation of parenteral ω-3 fatty acids in PN is safe and may improve immune and hyperinflammatory response for SICU patients after major surgery.