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Rajendran JC Bose,1– 4,* Nagendran Tharmalingam,5,* Yonghyun Choi,1 Thiagarajan Madheswaran,6 Ramasamy Paulmurugan,2,3 Jason R McCarthy,4 Soo-Hong Lee,7 Hansoo Park1 1School of Integrative Engineering, Chung-Ang University, Seoul, South Korea; 2Molecular Imaging Program at Stanford (MIPS), Department of Radiology, School of Medicine, Stanford University, Stanford, CA 94305-5427, USA; 3Canary Center at Stanford for Cancer Early Detection, Department of Radiology, School of Medicine, Stanford University, Stanford, CA 94305-5427, USA; 4Masonic Medical Research Institute, Utica, NY, USA; 5Infectious Diseases Division, Warren Alpert Medical School of Brown University, Rhode Island Hospital, Providence, RI 02903, USA; 6Department of Pharmaceutical Technology, School of Pharmacy, International Medical University, Kuala Lumpur 57000, Malaysia; 7Department of Medical Biotechnology, Dongguk University, Seoul, Gyeonggi-do, South Korea*These authors contributed equally to this workCorrespondence: Soo-Hong Lee Department of Medical BiotechnologyDongguk University, Seoul, Gyeonggi-do, South KoreaTel +82-31-961-5153Email soohong@dongguk.eduHansoo ParkSchool of Integrative Engineering, Chung-Ang University, Seoul, South KoreaTel +82 2-820-5804Email heyshoo@cau.ac.krBackground: Lipid polymer hybrid nanoparticles (LPHNPs) have been widely investigated in drug and gene delivery as well as in medical imaging. A knowledge of lipid-based surface engineering and its effects on how the physicochemical properties of LPHNPs affect the cell–nanoparticle interactions, and consequently how it influences the cytological response, is in high demand.Methods: Herein, we have engineered antibiotic-loaded (doxycycline or vancomycin) LPHNPs with cationic and zwitterionic lipids and examined the effects on their physicochemical characteristics (size and charge), antibiotic entrapment efficiency, and the in vitro intracellular bacterial killing efficiency against Mycobacterium smegmatis or Staphylococcus aureus infected macrophages.Results: The incorporation of cationic or zwitterionic lipids in the LPHNP formulation resulted in a size reduction in LPHNPs formulations and shifted the surface charge of bare NPs towards positive or neutral values. Also observed were influences on the drug incorporation efficiency and modulation of the drug release from the biodegradable polymeric core. The therapeutic efficacy of LPHNPs loaded with vancomycin was improved as its minimum inhibitory concentration (MIC) (2 μg/mL) versus free vancomycin (4 μg/mL). Importantly, our results show a direct relationship between the cationic surface nature of LPHNPs and its intracellular bacterial killing efficiency as the cationic doxycycline or vancomycin loaded LPHNPs reduced 4 or 3 log CFU respectively versus the untreated controls.Conclusion: In our study, modulation of surface charge in the nanomaterial formulation increased macrophage uptake and intracellular bacterial killing efficiency of LPHNPs loaded with antibiotics, suggesting alternate way for optimizing their use in biomedical applications.Keywords: nanohybrids, intracellular bacterial infection, Mycobacterium smegmatis, Staphylococcus aureus, doxycycline, vancomycin

BackgroundInternet interventions for depression have shown less than optimal adherence. This study describes the feasibility trial of a multimodal e-mental health intervention designed to enhance adherence and outcomes for depression. The intervention required frequent brief log-ins for self-monitoring and feedback as well as email and brief telephone support guided by a theory-driven manualized protocol. ObjectiveThe objective of this feasibility trial was to examine if our Internet intervention plus manualized telephone support program would result in increased adherence rates and improvement in depression outcomes. MethodsThis was a single arm feasibility trial of a 7-week intervention. ResultsOf the 21 patients enrolled, 2 (9.5%) dropped out of treatment. Patients logged in 23.2 ± 12.2 times over the 7 weeks. Significant reductions in depression were found on all measures, including the Patient Health Questionnaire depression scale (PHQ-8) (Cohen’s d = 1.96, P < .001), the Hamilton Rating Scale for Depression (d = 1.34, P < .001), and diagnosis of major depressive episode (P < .001). ConclusionsThe attrition rate was far lower than seen either in Internet studies or trials of face-to-face interventions, and depression outcomes were substantial. These findings support the feasibility of providing a multimodal e-mental health treatment to patients with depression. Although it is premature to make any firm conclusions based on these data, they do support the initiation of a randomized controlled trial examining the independent and joint effects of Internet and telephone administered treatments for depression.

Newregulations by the California Air Resources Board (CARB) demand a stringent 0.02 g/hp-hr tailpipe NOx limit by the year 2027, requiring Selective Catalytic Reduction (SCR) catalysts to provide high NOx conversions even at low (below 200°C) exhaust temperatures. This work describes utilizing an Electrically Heated Mixer System(EHMsystem) upstreamof a Light-Off SelectiveCatalytic Reduction (LO-SCR) catalyst followed by a conventional aftertreatment (AT) system containing DOC, DPF, and SCR, enabling high NOx conversions meeting CARB's NOx emission target. The AT catalysts were hydrothermally aged to Full Useful Life. Conventional unheated Diesel Exhaust Fluid (DEF) was injected upstream of both the LO-SCR and primary downstream SCR. The EHM system allowed for DEF to be injected as low as 130°C upstream of the LO-SCR, whereas, in previous studies, unheated DEF was injected at 180°C or dosed at 130°Cwith heatedDEF. The combination of unheated DEF, EHMsystem, LO-SCR, and downstream SCR enabled the needed increase in NOx efficiency in low exhaust temperatures, which was observed in drive cycles such as in cold-FTP, LLC, and World Harmonized Transient Cycle (WHTC). There were severalfold reductions in tailpipe NOx using this configuration compared to its baseline: 3.3-fold reduction in FTP, 22-fold in Low Load Cycle (LLC), 38-fold in Beverage Cycle, 8-fold in "Stay Hot" Cycle, and 10-fold inWHTC. Finally, it is shown that the EHM system can heat the exhaust gas, such as during a cold start, without needing additional heating hardware integrated into the system. These results were observed without performing changes in the engine base calibration. [ABSTRACT FROM AUTHOR]

Since the introduction of diesel urea SCR technology, aftertreatment thermal management has become critical for maintaining SCR catalyst light-off and thereby low cumulative cycle NOx emissions. A novel diesel engine aftertreatment thermal management strategy is proposed which utilizes a 2-stroke breathing variable value actuation strategy to increase the mass flow rate of exhaust gas. Experiments showed that when emissions are constrained to the same level as a state-of-the-art thermal management strategy, 2SB does not increase heat transfer to aftertreatment. However, if constraints are allowed to flex, temperatures comparable to a state-of-the-art thermal management calibration could be achieved with a 1.75× exhaust mass flow rate, potentially helping heat the SCR catalyst in a cold-start scenario. [ABSTRACT FROM AUTHOR]

Low air-flow diesel engine strategies are advantageous during low load operation to maintain temperatures of a warmed-up aftertreatment system (ATS) while reducing fuel consumption and engine-out emissions. This paper presents results at curb idle for internal EGR (iEGR) that demonstrate low airflow and reduced engine-out emissions during fuel-efficient ATS temperature maintenance operation. Internal EGR via reinduction and trapping using negative valve overlap (NVO) are compared to each other, conventional operation and to other low airflow approaches including cylinder deactivation (CDA). At 800 RPM/1.3 bar BMEP (curb idle) iEGR via reinduction enables 200°C engine-out temperature combined with 70% lower NO X , 35% lower fuel consumption, and 40% lower exhaust flow rate than conventional thermal management operation. Internal EGR via trapping using NVO resulted in an engine-out temperature of 185°C, with 56% lower NO X and 25% lower fuel consumption than conventional thermal management operation. Both iEGR strategies have lower engine-out temperatures and higher exhaust flow rates than CDA. No external EGR is required for either iEGR strategy. "iEGR via reinduction" outperforms "iEGR via NVO" as a result of higher open cycle efficiency (via less pumping work) and higher closed-cycle efficiency (via higher specific heat ratio). [ABSTRACT FROM AUTHOR]

Burnout remains an emerging challenge in healthcare. Burnout in these settings has been associated with compromised personal wellbeing, decreased work productivity, higher healthcare costs, decreased patient satisfaction, and deteriorating quality of patient care. As pharmacist roles on healthcare teams expand, health-system pharmacy leaders should be cognizant of burnout, including risk factors and identification. Coordinated efforts should foster pharmacist wellbeing and resilience, individualized work-related responsibilities to ensure professional ambitions are met, promotion of upper leadership expectation transparency, and cultivation of relationships within the pharmacy department. [ABSTRACT FROM AUTHOR]

Modern diesel engine aftertreatment systems require elevated temperatures for effective reduction of engine-out emissions. Maintaining elevated aftertreatment temperatures in a fuel-efficient manner is a challenge, especially at low-load engine operation where engine-outlet temperatures are low; therefore, higher engine-outlet temperatures are typically achieved via increased fuel consumption. Previous studies have demonstrated that strategies such as cylinder deactivation (method where there is neither valve motion nor fuel injection in a subset of cylinders, thereby isolating the deactivated cylinders from the gas exchange process) and cylinder cutout (method where there is no fuel injection in a subset of cylinders, implemented with high recirculated gas rates) reduce fuel consumption while elevating engine-outlet temperatures, by reducing the overall airflow through the engine. This article introduces and characterizes ‘‘non-fired cylinder ventilation’’ as alternate means to achieve fuel-efficient aftertreatment thermal management, by reduction of overall airflow through the engine. Fuel injection is deactivated from a subset of cylinders during non-fired cylinder ventilation, and the non-firing cylinders participate in the gas exchange process with the same manifold at a time, thereby reducing the intake-to-exhaust manifold gas exchange through the cylinders. It is demonstrated that non-fired cylinder ventilation shows similar fuel efficiency and thermal management as cylinder deactivation when the valves of the non-firing ventilated cylinders are open by at least 4 mm, due to similar, negligible, gas-exchange losses, while non-fired cylinder ventilation with lower valve lifts enables elevated engine-outlet temperatures with relatively higher fuel consumption than cylinder deactivation. Non-fired cylinder ventilation strategies demonstrate 75 °C higher temperatures at fuel-neutral conditions, and up to 35% fuel savings at similar temperatures, compared to six-cylinder operation. [ABSTRACT FROM AUTHOR]

Aftertreatment thermal management is critical for regulating emissions in modern diesel engines. Elevated engine-out temperatures and mass flows are effective at increasing the temperature of an aftertreatment system to enable efficient emission reduction. In this effort, experiments and analysis demonstrated that increasing the idle speed, while maintaining the same idle load, enables improved aftertreatment "warm-up" performance with engine-out NOx and particulate matter levels no higher than a state-of-the-art thermal calibration at conventional idle operation (800 rpm and 1.3 bar brake mean effective pressure). Elevated idle speeds of 1000 and 1200 rpm, compared to conventional idle at 800 rpm, realized 31%-51% increase in exhaust flow and 25 °C-40 °C increase in engine-out temperature, respectively. This study also demonstrated additional engine-out temperature benefits at all three idle speeds considered (800, 1000, and 1200 rpm, without compromising the exhaust flow rates or emissions, by modulating the exhaust valve opening timing. Early exhaust valve opening realizes up to ;51% increase in exhaust flow and 50 °C increase in engine-out temperature relative to conventional idle operation by forcing the engine to work harder via an early blowdown of the exhaust gas. This early blowdown of exhaust gas also reduces the time available for particulate matter oxidization, effectively limiting the ability to elevate engine-out temperatures for the early exhaust valve opening strategy. Alternatively, late exhaust valve opening realizes up to ;51% increase in exhaust flow and 91 °C increase in engine-out temperature relative to conventional idle operation by forcing the engine to work harder to pump in- cylinder gases across a smaller exhaust valve opening. In short, this study demonstrates how increased idle speeds, and exhaust valve opening modulation, individually or combined, can be used to significantly increase the "warm-up" rate of an aftertreatment system. [ABSTRACT FROM AUTHOR]