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Deep brain stimulation (DBS) and other neuromodulatory techniques are being increasingly utilized to treat refractory neurologic and psychiatric disorders. /Hypothesis: To better understand the circuit-level pathophysiology of treatment-resistant depression (TRD) and treat the network-level dysfunction inherent to this challenging disorder, we adopted an approach of inpatient intracranial monitoring borrowed from the epilepsy surgery field. We implanted 3 patients with 4 DBS leads (bilateral pair in both the ventral capsule/ventral striatum and subcallosal cingulate) and 10 stereo-electroencephalography (sEEG) electrodes targeting depression-relevant network regions. For surgical planning, we used an interactive, holographic visualization platform to appreciate the 3D anatomy and connectivity. In the initial surgery, we placed the DBS leads and sEEG electrodes using robotic stereotaxy. Subjects were then admitted to an inpatient monitoring unit for depression-specific neurophysiological assessments. Following these investigations, subjects returned to the OR to remove the sEEG electrodes and internalize the DBS leads to implanted pulse generators. Intraoperative testing revealed positive valence responses in all 3 subjects that helped verify targeting. Given the importance of the network-based hypotheses we were testing, we required accurate adherence to the surgical plan (to engage DBS and sEEG targets) and stability of DBS lead rotational position (to ensure that stimulation field estimates of the directional leads used during inpatient monitoring were relevant chronically), both of which we confirmed (mean radial error 1.2±0.9 mm; mean rotation 3.6±2.6°). This novel hybrid sEEG-DBS approach allows detailed study of the neurophysiological substrates of complex neuropsychiatric disorders. • Used inpatient intracranial monitoring to study pathophysiology in depression. • Implanted DBS and sEEG electrodes targeting depression-relevant network regions. • Utilized interactive, holographic visualization platform to plan lead placement. • Performed neurophysiological assessments during patients' hospital admission. • Hybrid sEEG-DBS approach can be used to develop novel DBS therapeutic applications. [ABSTRACT FROM AUTHOR]

• Solar radiation exposure of sidewalks impacts the pedestrian experience. • Tools are needed to evaluate and design comfortable pedestrian paths. • The variability of solar radiation exposure must be included in mobility studies. • Users of diverse walking abilities experience pedestrian networks differently. • Adopting vulnerable people's perspective fosters the design of inclusive cities. The walking experience is impacted by solar radiation exposure of pedestrian paths; this is a critical consideration for walkability assessment. The presented systematic methodology evaluates the impact of solar radiation on the user experience of pedestrian networks. Simulations were performed modelling the urban morphology in 3D and evaluating the shading provision of sidewalks at key times of the year. Three issues were investigated: the variability in solar radiation exposure of sidewalks, the difference in path length if discomfort resulting from exposure to solar radiation was prioritised over distance, and the access to shading for pedestrians of diverse walking abilities. Four user profiles were characterised by walking speed and ability to climb the stairs; adopting the perspective of diverse users provided critical information to design cities meeting the needs of vulnerable pedestrians. The resulting maps illustrated the dynamic nature of solar radiation exposure of the pedestrian network, with a critical cue on the paths chosen for optimising comfort, and the time that pedestrians would spend in the sun before finding shade. This work is a first step forward in the systematic implementation of microclimatic analysis in the walkability assessment, aimed at supporting designers in proposing solutions for ameliorating thermal stress. [ABSTRACT FROM AUTHOR]

Shading pedestrian paths is strategically important to ensure accessibility and comfort for pedestrians in cities. Limited applicability in practice of previous research about the effectiveness of natural and artificial shading devices was found. This paper proposes a workflow to design effective installations of shading devices on sidewalks; it relies on a design tool developed prioritising compatibility with other software/processes for its application to urban design. The methodology was tested on the city of Milan; the performance of 60 % linear path in shade was set as the design goal. Based on solar radiation exposure of urban canyons, a time of the day was associated with each simulated summer scenario. A library of shading devices was compiled allowing designers to test various proposals. The workflow was applied at first to theoretical urban canyons, then to a real case study sidewalk. Results included a catalogue of solutions with installation guidelines, a table to estimate the recommended number of shading devices for each sidewalk location, and the opportunity to iteratively test master planning proposals. Four applications of the workflow were proposed in response to resources availability and increasing outcome suitability. The workflow would support urban designers in implementing solar radiation exposure analysis in their practice. [Display omitted] • Design tools are needed to apply microclimatic analysis to urban design. • An iterative workflow tests shading solutions within the design process. • Pedestrians benefit from shading devices when positioned effectively. • The presentation of solutions is adapted to distinct phases of the design process. [ABSTRACT FROM AUTHOR]

Nemaline rod myopathy (NRM) is a rare muscle disorder defined by muscle weakness, respiratory insufficiency, and dysphagia. Respiratory muscle involvement can lead to acute hypercapnic respiratory failure, posing significant challenges in management. Our patient is a 73-year-old male with a history of polymyositis, who presented with acute hypercapnic respiratory failure secondary to a suspected polymyositis flare. Despite initial management, the patient experienced complications, including dysphagia, thrombocytopenia, and altered mental status. Neurological consultations revealed conflicting opinions regarding the primary diagnosis, suggesting inclusion body myositis. The patient's condition continued to deteriorate, prompting discussions about prognosis and palliative care options. This case highlights the challenges in managing respiratory failure in patients with late-onset nemaline myopathy and the importance of multidisciplinary care in addressing complex medical needs. This case emphasises the complexity of managing respiratory failure in patients with late-onset nemaline myopathy and the significance of adopting a multidisciplinary approach. Timely interventions, including respiratory support, dysphagia management, and palliative care discussions, are vital in optimizing patient care and quality of life. Further research is warranted to elucidate optimal management strategies and improve outcomes in this patient population. [ABSTRACT FROM AUTHOR]

Fontan circulatory inefficiency can be addressed by replacing the missing subpulmonary power source to reverse the Fontan paradox. An implantable cavopulmonary assist device is described that will simultaneously reduce systemic venous pressure and increase pulmonary arterial pressure, improving preload and cardiac output, in a univentricular Fontan circulation on a long-term basis. A rotary blood pump that was based on the von Karman viscous pump was designed for implantation into the total cavopulmonary connection (TCPC). It will impart modest pressure energy to augment Fontan flow without risk of obstruction. In the event of rotational failure, it is designed to default to a passive flow diverter. Pressure-flow performance was characterized in vitro in a Fontan mock circulatory loop with blood analog. The pump performed through the fully specified operating range, augmenting flow in all 4 directions of the TCPC. Pressure rise of 6 to 8 mm Hg was readily achieved, ranging to 14 mm Hg at highest speed (5600 rpm). Performance was consistent across a wide range of cardiac outputs. In stalled condition (0 rpm), there was no discernible pressure loss across the TCPC. A blood pump technology is described that can reverse the Fontan paradox and may permit a surgical strategy of long-term biventricular maintenance of a univentricular Fontan circulation. The technology is intended for Fontan failure in which right-sided circulatory inefficiencies predominate and ventricular systolic function is preserved. It may also apply before clinical Fontan failure as health maintenance to preempt the progression of Fontan disease. [ABSTRACT FROM AUTHOR]

[Display omitted] Ficus racemosa has long been used as a treatment for bacterial and fungal infections by people in India. The search for a safe alternative therapy from plant resources has gained interest in recent years due to herb's more central place in contemporary medicine and their status as a vast global reservoir of potentially active pharmaceuticals. Using standard methods, we aim to evaluate the pharmacological and bioactive potential of F. racemosa compounds extracted from fruits. Our observation reveals that stigmasterol has the highest docking score across all targets, making it the most promising chemical overall. According to Lipinski's rule of thumb, the obtained compounds derived from F. racemosa were predicted to have high bioactivities, giving them a high drug-likeliness score. Target and compound docking scores provide insight into binding posture and critical amino acid residues in antibacterial and antifungal activity. This research confirms that F. racemosa fruit extract is effective against fungal infections. These findings will aid biochemists in their quest to produce effective phytochemicals by further testing multi-targeting drugs. [ABSTRACT FROM AUTHOR]

Microplastics were found to be the major pollutant across the globe. Plastic microbeads, like 0.5 mm, are very small and mainly used for exfoliation. The marine species cannot distinguish between their usual food and these microbeads. Microbeads have the potential to transfer up the food chain, which may lead to consumption by humans in the end. Activated carbon from inexpensive sources has greatly interested separation systems, especially in water treatment. In that view, carbon nanoparticles were produced, combined with polyvinylidene fluoride (PVDF) polymer, and used as a membrane to trap the microplastic particles. UV–Vis, FTIR, TEM, and powder X-ray diffraction (XRD) analysis confirmed the produced carbon nanoparticles. FT-RAMAN Spectroscopy studies, microbial viable cell count, and turbidity analysis followed the membrane preparation and post-treatment. The carbon nanoparticle fabricated nanofilm effectively eliminates the microbial count and microplastics and reduces the turbidity (0.13 NTU). This study confirms that the membrane effectively filters microplastics and other contaminants. Nowadays, nanofiltration technologies have been considered beneficial for eliminating microplastics to an efficiency of 95%. Further research is needed to determine a feasible low-cost, ecologically suitable, and effective solution to remove the microplastics in water. [Display omitted] • Microplastic pollution threatens human health and food safety. • Microplastics are most abundant in the marine environment. • Polymer film is conjugated with the carbon nanoparticles to remove microplastics. • Standard procedures were employed to characterize the microplastics. [ABSTRACT FROM AUTHOR]

The UK National Health Service (NHS) is continually under pressure to provide more bed spaces and to do this within a tight budget. Therefore, NHS Trusts may turn to modular buildings, which promise faster construction and low energy demands helping the NHS meet its stringent energy targets. However, there is growing evidence that thermally lightweight, well insulated and naturally ventilated dwellings are at risk of overheating during warm UK summers. This paper examines the energy demands and internal temperatures in two 16-bed hospital wards built in 2008 at Bradford Royal Infirmary in northern England using modular fast track methods. The two-storey building used ceiling-mounted radiant panels and a mix of natural and mechanical ventilation with heat recovery to condition patients' rooms. Monitoring showed that the annual energy demand was 289 kWh/m 2 ±16%, which is below the NHS guidelines for new hospital buildings. It was observed that the criterion given in Department of Health Technical Memorandum HTM03-01 can lead to the incorrect diagnosis of overheating risk in existing buildings. Assessment using other static and adaptive overheating criteria showed that patient rooms and the nurses' station overheated in summer. To maintain patient safety, temporary air conditioning units had to be installed during the warmest weather. It is concluded that thermally lightweight, well insulated, naturally ventilated hospital wards can be low-energy but are at risk of overheating even in relatively cool UK summer conditions and that this needs to be addressed before such buildings can be recommended for wider adoption. [ABSTRACT FROM AUTHOR]

Lighting contributes a significant portion to the overall energy consumption in an office building. It is thus important to reduce the energy consumption of lighting systems especially for Net Zero Energy Buildings (NZEB). Maximizing daylight harvesting can significantly increase the energy savings. With increase in demand for satisfying occupant preferences in visual comfort, the need for personalized lighting in the office space is also rising. In this paper, a novel lighting control system for Net Zero Energy Buildings (NZEB) is proposed which models the lighting system using Artificial Neural Network (ANN) and utilizes this model with the Internal Model Control (IMC) principle for controller design. Modeling the lighting system using ANN reduces the challenge of modeling a large and complex system with inherent process variability without the need to analyze extensive data-sets. The proposed ANN-IMC controller uses feedback from sensors on the task table to maintain desired illuminance, is easy to tune with just one parameter and is robust to process variability. The proposed control design is applicable to square systems where the number of lights and number of sensors are equal. However, the proposed architecture can also be extended for controlling other lighting accessories such as roller blinds. The performance of the proposed lighting control system to harvest the daylight effectively is demonstrated using both simulation results and an experimental setup in test-bed environment. The versatility of the proposed system will allow an operator to deploy personalized lighting in an office space. [ABSTRACT FROM AUTHOR]

The importance of studying tropical urban climate was recognised by the World Meteorological Organisation (WMO) as early as in 1981 but substantial improvements were seen only in the last two decades. However specific knowledge of tropical urban climate still lags behind that of temperate climate. In this paper, authors review the state of the art in tropical heat island intensity, its influence on building energy consumption and the effect of urban compactness in the tropics. The review is limited to peer-reviewed journal publications found on four databases: Web of Science, Scopus, Google Scholar and Science Direct. The review indicates that although the tropical belt has large variations in topography, forest cover, land mass and development patterns, much of the current work is confined largely to Far East Asia, South Asia and South America. Future studies should focus on protocol for parameterisation and standardisation of measurement, in depth and scientific understanding of the influence of vegetation, water and topography, survey and monitoring of the context specific relationship between UHI and energy consumption, development of database for numerical model validation and improvement, and the context specific development of LCZ based institutional framework to integrate UHI mitigation strategies with environmental design guidelines. [ABSTRACT FROM AUTHOR]

Elevated air movement produced by fans can offset air-conditioning energy requirements by allowing temperature setpoints to be raised without compromising thermal comfort. These advantages are even greater in hot and humid climates that inherently have large and sustained indoor cooling requirements. Few studies have assessed the in-situ benefits of fans in actual buildings. We installed ceiling and desk fans into a Zero Energy office building (675 m2) in Singapore. Across an 11-week period, 35 occupants alternated between two conditions (no fan vs. fan): 24 °C setpoint with fans off, and 26.5 °C setpoint with fans on. When the temperature setpoint was raised and elevated air movement was provided, a 32% energy reduction was obtained. The energy savings accrued without any negative impacts occurring on thermal satisfaction. Overcooling caused by thermal preference to slightly warmer and warmer conditions was substantially reduced from 33 to 9%. No changes in perceived air-staleness or self-reported alertness and ability to concentrate occurred either, indicating parity across the no fan and fan conditions. Although occupants primarily relied on ceiling fans at the 26.5 °C setpoint, they were by default on at the beginning of each day, giving less incentive to use the desk fans. Our study took place in a high-performance Zero Energy building, whereby thermal dissatisfaction was already low (7%). Therefore, notable changes did not occur, but significant improvements to thermal comfort could still occur in buildings that are unable to maintain high levels of thermal satisfaction. [Display omitted] • We raised the setpoint from 24 to 26.5 °C and provided supplementary air movement. • Elevated air movement reduced cooling energy requirements by 32%. • No negative impacts to thermal preference or thermal satisfaction were found. • Overcooling was reduced from 33 to 9%. • Perceived air-staleness and self-reported productivity were unaffected. [ABSTRACT FROM AUTHOR]

Frictional contact is commonly represented in the Material Point Method (MPM) by algorithms based on multi-velocity fields, in which the correction is performed at the background computational mesh. Typically for applications of various stiffness values, these algorithms show a non-physical variation in the contact stresses along the interface surface. The lack of a smoothening function in the detection procedure, which is essential in explicit finite element algorithms, contributes to the stress oscillation and causes a gap between the bodies in contact. For MPM versions with a finite particle size, like Convected Particle Domain Interpolation method (CPDI), the effect of the last shortcoming becomes more pronounced. Results can be improved by using denser mesh, however, the computational cost will increase considerably. In the present paper, the boundary of a continuum object is discretised separately from the MPM discretisation and traced accurately during the solution advancement. Therefore, contact forces among different boundaries are evaluated using a penalty function method commonly implemented in Lagrangian analyses. These forces are then mapped to the computational mesh, where the momentum equation is solved, as an external force. The suggested approach is validated with a benchmark problem, where the closed-form solution is available, and compared to the classical MPM contact algorithm. Furthermore, an application of two bodies collision with large deformation is demonstrated. [ABSTRACT FROM AUTHOR]

• A control system to enhance vascular pulsatility for rotary blood pump was proposed. • Switching two differential pump speed setpoints to raise vascular pulsatility. • The proposed control algorithm was only based on intrinsic pump speed measurements. • This algorithm augmented vascular pulsatility, provided flow rates, avoided suction. Continuous flow rotary blood pumps (RBP) operating clinically at constant rotational speeds cannot match cardiac demand during varying physical activities, are susceptible to suction, diminish vascular pulsatility, and have an increased risk of adverse events. A sensorless, physiologic feedback control strategy for RBP was developed to mitigate these limitations. The proposed algorithm used intrinsic pump speed to obtain differential pump speed (Δ RPM). The proposed gain-scheduled proportional-integral controller, switching of setpoints between a higher pump speed differential setpoint (Δ RPM Hr) and a lower pump speed differential setpoint (Δ RPM Lr), generated pulsatility and physiologic perfusion, while avoiding suction. The switching between Δ RPM Hr and Δ RPM Lr setpoints occurred when the measured Δ RPM reached the pump differential reference setpoint. In-silico tests were implemented to assess the proposed algorithm during rest, exercise, a rapid 3-fold pulmonary vascular resistance increase, rapid change from exercise to rest, and compared with maintaining a constant pump speed setpoint. The proposed control algorithm augmented aortic pressure pulsatility to over 35 mmHg during rest and around 30 mmHg during exercise. Significantly, ventricular suction was avoided, and adequate cardiac output was maintained under all simulated conditions. The performance of the sensorless algorithm using estimation was similar to the performance of sensor-based method. This study demonstrated that augmentation of vascular pulsatility was feasible while avoiding ventricular suction and providing physiological pump outflows. Augmentation of vascular pulsatility can minimize adverse events that have been associated with diminished pulsatility. Mock circulation and animal studies would be conducted to validate these results. [ABSTRACT FROM AUTHOR]

Objective Interleukin (IL)-18 is a pleotropic cytokine involved in various inflammatory disorders. The transcription factor, nuclear factor kappa-B (NF-κB), is thought to play an important role in IL-18 signaling. The present study proposes a novel role for IL-18 in cholesterol efflux and plaque stability and demonstrates that pyrrolidine dithiocarbamate (PDTC), a NF-κB inhibitor blocks IL-18 signaling in apolipoprotein (Apo) E−/− mice. Methods Three groups of normal chow-diet-fed, male Apo E−/− mice, aged 12 weeks ( n = 6/group) were employed: Gp I, PBS (2 mo); Gp II, recombinant (r)IL-18 (1 mo) followed by PBS (1 mo); Gp III, rIL-18 (1 mo) followed by PDTC (1 mo). Results Significantly augmented expression of IL-18 receptor (R)α by fluorescence-activated cell sorting analysis and plasma IL-18 was observed in Gp II. There was a significant increase in total cholesterol and low-density lipoprotein cholesterol whereas high-density lipoprotein cholesterol was significantly decreased in Gp II. However, this pattern was reversed in Gp III. Significantly augmented mRNA expression of IL-18, CD36, matrix metalloproteinase (MMP)-9, and NF-κB was observed in Gp II but liver X receptor alpha (LXR-α) gene was significantly reduced. A significant increase in frequency of atherosclerotic lesions was observed in Gp II animals, whereas there was a significant decrease in the Gp III. Conclusion IL-18 administration initiates inflammatory cascade by binding with IL-18 Rα via NF-κB which is involved in progression and destabilization of atherosclerotic plaques in Apo E−/− mice. This study also reveals that NF-κB blockade with PDTC, blocks IL-18 signaling through down-regulation of IL-18, IL-18 Rα, CD36, and MMP-9, thus reducing inflammation and restoring plaque instability via upregulation of LXR-α. [ABSTRACT FROM AUTHOR]

Background Ex vivo lung perfusion (EVLP) has the potential to increase the donor pool for lung transplantation by facilitating resuscitation and extended evaluation of marginal organs. Current EVLP methodology employs continuous flow (CF) pumps that produce non-pulsatile EVLP hemodynamics. In this feasibility study, we tested the hypothesis that a pulsatile flow (PF) pump will provide better EVLP support than a CF pump through delivery of physiologic hemodynamics. Methods Porcine lungs were supported in an EVLP model by centrifugal CF (n = 3) or PF (n = 4) left ventricular assist devices. Lungs were ventilated at 4 to 5 mL/kg, 0.21 fraction of inspired oxygen (FiO 2 ), and perfused with an acellular, albumin-based solution corrected for osmolarity, acid-base balance, and carbon dioxide pressure (≤20 hours at 30 ° C) for a minimum of 12 hours support. Prostaglandin E 1 and 30% albumin were infused continuously. Hemodynamic, respiratory, and blood gas parameters were continuously monitored and digitally recorded hourly. Parenchymal biopsies were used for quantification of wet to dry weight ratio. Results All lungs maintained function in the EVLP circuit for a minimum of 12 hours (mean 14.7 ± 1 hours) and demonstrated minimal edema formation. The PF EVLP produced higher pulsatility as demonstrated by greater energy equivalent pressure and surplus hemodynamic energy compared with CF EVLP ( p < 0.05). There were no statistically significant differences in pulmonary impedance, arterial partial pressure of oxygen/fraction of inspired oxygen, wet to dry weight ratio, and peak airway pressure between CF and PF EVLP. Conclusions The CF and PF EVLP systems successfully maintained lungs 12+ hours using a modified Steen perfusate (XVIVO Perfusion, Inc, Goteborg, Sweden); however, there were no statistically significant differences between CF and PF groups despite higher pulsatility, suggesting that PF may not offer immediate benefits over CF for prolonged ex vivo lung preservation. [ABSTRACT FROM AUTHOR]

The aim of this work was to study corrosion behavior of magnesium (Mg) alloys (MgZnCa plates and AZ31 stents) under varied fluid flow conditions representative of the vascular environment. Experiments revealed that fluid hydrodynamics, fluid flow velocity and shear stress play essential roles in the corrosion behavior of absorbable magnesium-based stent devices. Flow-induced shear stress (FISS) accelerates the overall corrosion (including localized, uniform, pitting and erosion corrosions) due to the increased mass transfer and mechanical force. FISS increased the average uniform corrosion rate, the localized corrosion coverage ratios and depths and the removal rate of corrosion products inside the corrosion pits. For MgZnCa plates, an increase of FISS results in an increased pitting factor but saturates at an FISS of ∼0.15 Pa. For AZ31 stents, the volume loss ratio (31%) at 0.056 Pa was nearly twice that (17%) at 0 Pa before and after corrosion. Flow direction has a significant impact on corrosion behavior as more severe pitting and erosion corrosion was observed on the back ends of the MgZnCa plates, and the corrosion product layer facing the flow direction peeled off from the AZ31 stent struts. This study demonstrates that flow-induced corrosion needs be understood so that Mg-based stents in vascular environments can be effectively designed. [ABSTRACT FROM AUTHOR]

Combinatorial drug delivery is an attractive, but challenging requirement of next generation cancer nanomedicines. Here, we report a transferrin-targeted core-shell nanomedicine formed by encapsulating two clinically used single-agent drugs, doxorubicin and sorafenib against liver cancer. Doxorubicin was loaded in poly(vinyl alcohol) nano-core and sorafenib in albumin nano-shell, both formed by a sequential freeze-thaw/coacervation method. While sorafenib from the nano-shell inhibited aberrant oncogenic signaling involved in cell proliferation, doxorubicin from the nano-core evoked DNA intercalation thereby killing > 75% of cancer cells. Upon targeting using transferrin ligands, the nanoparticles showed enhanced cellular uptake and synergistic cytotoxicity in ~ 92% of cells, particularly in iron-deficient microenvironment. Studies using 3D spheroids of liver tumor indicated efficient penetration of targeted core-shell nanoparticles throughout the tissue causing uniform cell killing. Thus, we show that rationally designed core-shell nanoparticles can effectively combine clinically relevant single-agent drugs for exerting synergistic activity against liver cancer. From the Clinical Editor Transferrin-targeted core-shell nanomedicine encapsulating doxorubicin and sorafenib was studied as a drug delivery system against hepatocellular carcinoma, resulting in enhanced and synergistic therapeutic effects, paving the way towards potential future clinical applications of similar techniques. [ABSTRACT FROM AUTHOR]

Abstract: Aberrant epigenetics play a key role in the onset and progression of acute myeloid leukemia (AML). Herein we report in silico modelling based development of a novel, protein-vorinostat nanomedicine exhibiting selective and superior anti-leukemic activity against heterogeneous population of AML patient samples (n=9), including refractory and relapsed cases, and three representative cell lines expressing CD34+/CD38− stem cell phenotype (KG-1a), promyelocytic phenotype (HL-60) and FLT3-ITD mutation (MV4-11). Nano-vorinostat having ~100nm size exhibited enhanced cellular uptake rendering significantly lower IC50 in AML cell lines and patient samples, and induced enhanced HDAC inhibition, oxidative injury, cell cycle arrest and apoptosis compared to free vorinostat. Most importantly, nanomedicine showed exceptional single-agent activity against the clonogenic proliferative capability of bone marrow derived leukemic progenitors, while remaining non-toxic to healthy bone marrow cells. Collectively, this epigenetics targeted nanomedicine appears to be a promising therapeutic strategy against various French-American-British (FAB) classes of AML. From the Clinical Editor: Through the use of a protein-vorinostat agent, exceptional single-agent activity was demonstrated against the clonogenic proliferative capability of bone marrow derived leukemic progenitors, while remaining non-toxic to healthy bone marrow cells. The studied epigenetics targeted nanomedicine approach is a promising therapeutic strategy against various French-American-British classes of acute myeloid leukemia. [Copyright &y& Elsevier]

Abstract: A multifunctional core-shell nanomedicine capable of inhibiting the migratory capacity of metastatic cancer cells followed by imparting cytotoxic stress by photodynamic action is reported. Based on in silico design, we have developed a core-shell nanomedicine comprising of ~80nm size poly(lactic-co-glycolic acid) (PLGA) nano-core encapsulating photosensitizer, m-tetra(hydroxyphenyl)chlorin (mTHPC), and ~20nm size albumin nano-shell encapsulating tyrosine kinase inhibitor, Dasatinib, which impair cancer migration. This system was prepared by a sequential process involving electrospray of polymer core and coacervation of protein shell. Cell studies using metastatic breast cancer cells demonstrated disruption of Src kinase involved in the cancer migration by albumin–dasatinib nano-shell and generation of photoactivated oxidative stress by mTHPC-PLGA nano-core. This unique combinatorial photo-chemo nanotherapy resulted synergistic cytotoxicity in ~99% of the motility-impaired metastatic cells. This approach of blocking cancer migration followed by photodynamic killing using rationally designed nanomedicine is a promising new strategy against cancer metastasis. From the Clinical Editor: A multifunctional core-shell nanomedicine capable of inhibiting metastatic cancer cell migration, in addition to inducing photodynamic effects, is described in this paper. The authors document cytotoxicity in approximately 99% of the studied metastatic breast cancer cells. Similar approaches would be a very welcome addition to the treatment protocols of advanced metastatic breast cancer and other types of neoplasms. [Copyright &y& Elsevier]

Abstract: Simultaneous inhibition of deregulated cancer kinome using rationally designed nanomedicine is an advanced therapeutic approach. Herein, we have developed a polymer-protein core-shell nanomedicine to inhibit critically aberrant pro-survival kinases (mTOR, MAPK and STAT5) in primitive (CD34+/CD38−) Acute Myeloid Leukemia (AML) cells. The nanomedicine consists of poly-lactide-co-glycolide core (~250nm) loaded with mTOR inhibitor, everolimus, and albumin shell (~25nm thick) loaded with MAPK/STAT5 inhibitor, sorafenib and the whole construct was surface conjugated with monoclonal antibody against CD33 receptor overexpressed in AML. Electron microscopy confirmed formation of core-shell nanostructure (~290nm) and flow cytometry and confocal studies showed enhanced cellular uptake of targeted nanomedicine. Simultaneous inhibition of critical kinases causing synergistic lethality against leukemic cells, without affecting healthy blood cells, was demonstrated using immunoblotting, cytotoxicity and apoptosis assays. This cell receptor plus multi-kinase targeted core-shell nanomedicine was found better specific and tolerable compared to current clinical regime of cytarabine and daunorubicin. From the Clinical Editor: These authors demonstrate simultaneous inhibition of critical kinases causing synergistic lethality against leukemic cells, without affecting healthy blood cells by using rationally designed polymer-protein core-shell nanomedicine, provoding an advanced method to eliminate cancer cells, with the hope of future therapeutic use. [Copyright &y& Elsevier]

Objective: The anatomic and physiologic constraints for pediatric cavopulmonary assist differ markedly from adult Fontan circulations owing to smaller vessel sizes and risk of elevated pulmonary resistance. In this study, hemodynamic and hemolysis performance of a catheter-based viscous impeller pump (VIP) to power the Fontan circulation is assessed at a pediatric scale (∼15 kg) and performance range (0-30 mm Hg). Methods: Computer simulation and mock circulation studies were conducted to assess the hydraulic performance, acute hemodynamic response to different levels VIP support, and the potential for vena caval collapse. Computational fluid dynamics simulations were used to estimate VIP hydraulic performance, shear rates, and potential for hemolysis. Hemolysis was quantified in a mock loop with fresh bovine blood. Results: A VIP augmented 4-way total cavopulmonary connection flow at pediatric scales and restored systemic pressures and flows to biventricular values, without causing flow obstruction or suction. VIP generated flows up to 4.1 L/min and pressure heads of up to 38 mm Hg at 11,000 rpm. Maximal shear rate was 160 Pa, predicting low hemolysis risk. Observed hemolysis was low with plasma free hemoglobin of 11.4 mg · dL−1 · h−1. Conclusions: A VIP will augment Fontan cavopulmonary flow in the proper pressure and flow ranges, with low hemolysis risk under more stringent pediatric scale and physiology compared with adult scale. This technology may be developed to simultaneously reduce systemic venous pressure and improve cardiac output after stage 2 or 3 Fontan repair. It may serve to compress surgical staging, lessening the pathophysiologic burden of repair. [ABSTRACT FROM AUTHOR]

Abstract: The National Health Service (NHS) Estate in England includes 18.83 Mm2 of acute hospital accommodation, distributed across 330 sites. Vulnerability to overheating is clear with 15,000 excess deaths occurring nationally during the July 2003 heatwave. The installation of mechanical cooling in existing hospitals appears to be the inevitable recommendation from NHS patient safety risk assessments but the carbon implications would undermine the NHS Carbon Reduction Strategy. NHS CO2 emissions constitute 25% of all public sector emissions, equivalent to 3% of the UK total. In the post-2008 economic climate, the likelihood of wholesale replacement of the NHS Estate is significantly diminished; refurbishment is now of increasing interest to the Trusts that together make up the NHS. The research project ‘Design and Delivery of Robust Hospital Environments in a Changing Climate’ seeks to understand the environmental performance of the current NHS Estate and, from this, to establish its resilience. To this end, hospital buildings operated by four NHS Trusts are being monitored and simulated using dynamic thermal models calibrated against measured data. Adaptive refurbishment options are proposed and their relative performance predicted against the existing internal conditions, energy demands and CO2 emissions. This paper presents findings relating to one representative type building, a medium-rise ward block dating from the late 1960s. It shows that this particular type may have more resilience in the current climate than might have been expected, that it will remain resilient into the 2030s, and that relatively non-invasive measures would extend and increase its resilience whilst saving energy. [Copyright &y& Elsevier]

Abstract: In view of the warming climate, there is increasing concern about the likelihood of overheating inside UK buildings that are not mechanically cooled. A number of studies are examining this matter, of which the DeDeRHECC project is one. The recent availability of the UKCP09 future climate data projections has acted as a stimulus to such work. This paper illustrates how field measurement, thermal modelling and the generation of current and future typical and extreme weather years, can be used to provide a picture of the resilience of buildings to climate change. The unified framework for assessing both measurements and current and future predictions that is offered by the BSEN15251 thermal comfort standard is a crucial component. The paper focuses on internal temperatures during the day and at night in wards within the tower building at Addenbrooke’s hospital, which has a hybrid ventilation strategy. The maintenance of thermal comfort in such spaces is critically important and installing air-conditioning in response to climate change is expensive and potentially energy intensive. Fans appear to be a simple retrofit measure that may substantially improve the wards’ resilience to climate change even in extreme years. Whilst healthcare provides the back cloth, the methodology developed has a much wider utility for assessing thermal comfort in buildings in the current and future climate of the UK. [Copyright &y& Elsevier]

Objective: An ectopic coronary artery that courses between the aortic root and the pulmonary trunk may lead to sudden cardiac death, especially in athletes. It has been speculated that during exercise, compression of the coronary artery between the great vessels may impair coronary blood flow and produce myocardial ischemia and fatal arrhythmia. However, this hypothesis cannot be tested in humans, and little experimental data exist to explain this phenomenon. To this end, in a calf with an anomalous left coronary artery that coursed from the right sinus of Valsalva between the great vessels, we assessed for myocardial ischemia during pharmacologically induced tachycardia and hypertension. Methods: We identified a juvenile male calf (103 kg) with an anomalous left coronary artery from the right sinus of Valsalva that coursed between the great vessels. Via thoracotomy, the animal was instrumented for hemodynamic measurements. Intravenous dobutamine increased heart rate and myocardial metabolic demands. Intravenous phenylephrine produced arterial hypertension and increased myocardial metabolic demands. Fluorescent-labeled microspheres were used to map regional myocardial blood flow, and hemodynamics were recorded during each condition. Masson’s trichrome staining for fibrosis, wheat-germ agglutinin staining for myocyte size, terminal deoxynucleotidyl transferase dUTP nick end-label staining for apoptosis, and isolectin-B4 staining for capillary density were performed. Results: For the first time, empiric data documented that an ectopic coronary artery produced myocardial ischemia during elevated myocardial metabolic demands. Left coronary artery resistance increased in a cardiac cycle–dependent pattern that was consistent with systolic compression between the great vessels. Increased cardiac fibrosis, myocyte hypertrophy, cardiac apoptosis, and capillary density indicated that regional ischemic, inflammatory-mediated myocardial remodeling was present. Conclusions: These findings confirm the proposed mechanism of sudden death and support early surgical repair of coronary arteries that course between the aortic root and the pulmonary trunk. [Copyright &y& Elsevier]

Background: Left ventricular assist devices are increasingly used to treat patients with advanced and otherwise refractory heart failure as bridge to transplant or destination therapy. We evaluated a new miniaturized left ventricular assist device that requires minimal surgery for implantation, potentially allowing implantation in earlier stage heart failure. Methods: HeartWare (Miami Lakes, Fla) developed transapical miniaturized ventricular assist device. Acute (n = 4), 1-week (n = 2), and 30-day (n = 4) bovine model experiments evaluated hemodynamic efficacy and biocompatibility of the device, which was implanted through small left thoracotomy with single insertion at apex of left ventricle without cardiopulmonary bypass. The device outflow cannula was positioned across the aortic valve. The international normalized ratio was maintained between 2.0 and 2.5 with warfarin. Hemodynamic, echocardiographic, fluoroscopic, hematologic, and blood chemistry measurements were evaluated. Results: The device was successfully implanted through the left ventricular apex in all 10 animals. The device was operated at 15,000 ± 1000 rpm (power consumption, 3.5–6.0 W). The device maintained normal end-organ perfusion with no significant hemolysis (0–30 mg/dL). There were no pump failures or device-related complications. At autopsy, no abnormalities were seen in endocardium, aortic valve leaflets, or aortic root. There was no evidence of thromboembolism or abnormalities in any peripheral end organs. Conclusions: We successfully demonstrated feasibility of a novel intraventricular assist device that can be completely implanted through left ventricular apex. This transapical surgical approach eliminates needs for sternotomy, device pocket, cardiopulmonary bypass, ventricular coring, and construction of an outflow graft anastomosis. [ABSTRACT FROM AUTHOR]

Since the Fontan/Kreutzer procedure was introduced, evolutionary clinical advances via a staged surgical reconstructive approach have markedly improved outcomes for patients with functional single ventricle. However, significant challenges remain. Early stage mortality risk seems impenetrable. Serious morbidities – construed as immutable consequences of palliation – have hardly been addressed. Late functional status is increasingly linked to pathophysiologic consequences of prior staged procedures. As more single-ventricle patients survive into adulthood, Fontan failure is emerging as an intractable problem for which there is no targeted therapy. Incremental solutions to address these ongoing problems have not had a measurable impact. Therefore, a fundamental reconsideration of the overall approach is reasonable and warranted. The ability to provide a modest pressure boost (2 to 6 mmHg) to existing blood flow at the total cavopulmonary connection can effectively restore more stable biventricular status. This would impact not only treatment of late Fontan failure, but also facilitate early surgical repair. A realistic means to provide such a pressure boost has never been apparent. Recent advances are beginning to unravel the unique challenges that must be addressed to realize this goal, with promise to open single-ventricle palliation to new therapeutic vistas. [ABSTRACT FROM AUTHOR]

Objective: In a univentricular Fontan circulation, modest augmentation of existing cavopulmonary pressure head (2–5 mm Hg) would reduce systemic venous pressure, increase ventricular filling, and thus substantially improve circulatory status. An ideal means of providing mechanical cavopulmonary support does not exist. We hypothesized that a viscous impeller pump, based on the von Kármán viscous pump principle, is optimal for this role. Methods: A 3-dimensional computational model of the total cavopulmonary connection was created. The impeller was represented as a smooth 2-sided conical actuator disk with rotation in the vena caval axis. Flow was modeled under 3 conditions: (1) passive flow with no disc; (2) passive flow with a nonrotating disk, and (3) induced flow with disc rotation (0–5K rpm). Flow patterns and hydraulic performance were examined for each case. Hydraulic performance for a vaned impeller was assessed by measuring pressure increase and induced flow over 0 to 7K rpm in a laboratory mock loop. Results: A nonrotating actuator disc stabilized cavopulmonary flow, reducing power loss by 88%. Disk rotation (from baseline dynamic flow of 4.4 L/min) resulted in a pressure increase of 0.03 mm Hg. A further increase in pressure of 5 to 20 mm Hg and 0 to 5 L/min flow was obtained with a vaned impeller at 0 to 7K rpm in a laboratory mock loop. Conclusions: A single viscous impeller pump stabilizes and augments cavopulmonary flow in 4 directions, in the desired pressure range, without venous pathway obstruction. A viscous impeller pump applies to the existing staged protocol as a temporary bridge-to-recovery or -transplant in established univentricular Fontan circulations and may enable compressed palliation of single ventricle without the need for intermediary surgical staging or use of a systemic-to-pulmonary arterial shunt. [ABSTRACT FROM AUTHOR]

Abstract: This paper investigates the impact of on-site variables on the influence of vegetation in lowering outdoor temperature. The study uses six critical on-site variables such as surface albedo, sky view factor, altitude, shrub cover, tree cover and average height to floor area ratio to carry out analysis in five data sets. The climatic parameters and physical characteristics were measured and surveyed, respectively in 216 stations in high-rise high-density residential developments of coastal Hong Kong. The data set is mainly categorised into peak summer clear sky days (PSCS-days), peak summer partially cloudy days (PSPC-days) and late summer days to address the issues related to cloudy sky conditions in Hong Kong. The trend analysis shows that at a lower sky view factor, ranging from 0.1 to 0.25, shrub cover as low as 10–15% in a 1000m2 open area is more effective in reducing outdoor temperature than the same level of tree cover in a location with a higher sky view factor (0.4 or above). The regression models used in this study were able to explain the influence of on-site variables on vegetation in lowering the outdoor temperature within the respective urban settings. In high-rise high-density environments, on-site variables such as sky view factor and altitude have a substantial impact on the influence of vegetation in lowering outdoor temperature. However, off-site variables such as high urban density and anthropogenic heat could negate the behaviour of sky view factor and altitude. The study suggests that increasing the tree cover from 25% to 40% in the pocket parks in coastal area residential developments of Hong Kong could reduce daytime urban heat island intensity (UHI) by further 0.5°C. [Copyright &y& Elsevier]

Abstract: Previous research on Urban Heat Island Intensity (UHI) in Hong Kong was limited to 4 weeks of field measurements during the summer in 3 major coastal housing estates. The current study extends this work to 6 months enveloping 3 “seasons” and 7 different locations within the coastal area. Variations in UHI in the range −1.3° to 3.4°C were recorded. The study reveals seasonal changes are in general more influential on UHI than changes due to geographical characteristics. Among the seasonal models, the peak summer clear sky day''s daytime and nocturnal models examined separately were found to provide the clearest indicators of the impact of urban design variables on UHI with R 2 value of 0.7 and 0.8, respectively. Sky view factor, surface albedo, altitude, vegetation above 1m in height, average height to floor area ratio, location quotient and proximity to sea are critical variables in mitigating both daytime and nocturnal UHI. Combining daytime and nocturnal data dilutes the impact of extreme values on UHI, by up to 50%, and is not useful for design solutions. Ideally design solutions may respond to the adverse impacts recorded in peak summer clear sky daytime at the concept design stage, and then have the design manipulated and validated for other seasons. [Copyright &y& Elsevier]

Objective: We sought to investigate differences in indices of pulsatility between patients with normal ventricular function and patients with heart failure studied at the time of implantation with continuous-flow or pulsatile-flow left ventricular assist devices. Methods: Eight patients with normal ventricular function and 22 patients with heart failure were studied. A high-fidelity aortic and left ventricular pressure catheter was inserted retrograde through the aortic valve into the left ventricle, and transit-time flow probes were placed on the aorta and device outflow graft. Hemodynamic waveforms were recorded at native heart rate before cardiopulmonary bypass and over a range of device flow rates controlled by adjusting beat rate or rpm. These data were used to calculate vascular input impedance and 2 indices of vascular pulsatility: energy-equivalent pressure and surplus hemodynamic energy. Results: At low support levels, pulsatile support restored surplus hemodynamic energy to within 2.5% of normal values, whereas continuous support diminished surplus energy by more than 93%. At high support levels, pulsatile support augmented surplus energy by 49% over normal values, whereas continuous support further diminished surplus energy by 97%. Pulsatile support diminished vascular impedance from baseline failure values, whereas continuous support increased impedance. Vascular impedances at baseline for patients undergoing pulsatile and continuous support and during pulsatile support revealed normal vascular compliance, whereas impedance during continuous support indicated a loss of compliance (or “stiffening”) of the vasculature. Conclusion: These results suggest that selection of device type and flow rate can influence vascular pulsatility and input impedance, which might affect clinical outcomes. [Copyright &y& Elsevier]

The urban canyon albedo (UCA) quantifies the ability of street canyons to reflect solar radiation back to the sky. The UCA is controlled by the solar reflectance of road and façades and the street geometry. This study investigates the variability of UCA in a typical residential area of London and its impact on outdoor and indoor microclimates. The results are based on radiation measurements in real urban canyons and on a 1:10 physical model and simulations using ENVImet v 4.4.6 and EnergyPlus. Different scenarios with increased solar reflectance of roads and façades were simulated to investigate the impact on UCA and street level microclimate. The results showed that increasing the road reflectance has high absolute and relative impact on UCA in wide canyons. In deeper canyons, the absolute impact of the road reflectance is reduced while the relative impact of the walls' reflectance is increased. Results also showed that increasing surface reflectance in urban canyons has a detrimental impact on outdoor thermal comfort, due to increased interreflections between surfaces leading to higher mean radiant temperatures. Increasing the road reflectance also increases the incident diffuse radiation on adjacent buildings, producing a small increase in indoor operative temperatures. The findings were used to discuss the best design strategies to improve the urban thermal environment by using reflective materials in urban canyons without compromising outdoor thermal comfort or indoor thermal environments. [Display omitted] • High reflectance roads are effective in increasing urban albedo in wide canyons. • Façade reflectivity has more potential to increase urban albedo in deep canyons. • High reflectance materials worsen outdoor thermal comfort in urban canyons. • Reducing the façades reflectivity has a positive impact on outdoor thermal comfort. • High reflectance on roads has a negative impact on indoor operative temperatures. [ABSTRACT FROM AUTHOR]

• A new control algorithm for cavopulmonary pump in Fontan circulation was proposed. • Switching two cavopulmonary head setpoints to raise pulmonary vascular pulsatility. • The cavopulmonary head was estimated only with intrinsic pump speed measurements. • This method augmented pulmonary vascular pulsatility and provided needed flow rates. Fontan failure can be potentially addressed with an implantable pump in the cavopulmonary junction (cavopulmonary assist device, CPAD) to replace the missing subpulmonary power source. Fontan pulmonary circulation lacks pulsatility due to the absence of the right ventricle, which has adverse physiological consequences. CPAD can augment pulmonary flow and improve Fontan hemodynamics. However, CPAD operating at a constant pump speed does not provide pulmonary arterial pulsatility, provide physiologic flow to match cardiac demand, or avoid suction. To overcome these limitations, a sensorless control strategy for CPAD is proposed. CPAD pump speed measurement, an intrinsic pump parameter, was used to estimate cavopulmonary pressure head (CPPH). A gain scheduled proportional-integral controller alternates CPPH between high/low setpoints (CPPH Hr / CPPH Lr) that generates pulsatility, while simultaneously adapting to cardiac demand and avoiding suction. Computer simulations were performed to quantify the overall performance of the proposed algorithm at rest and exercise, rapid transition from exercise to rest, and doubling of the vena caval resistance. The performance was compared against CPPH measured using pressure sensors, and a constant pump speed control strategy. The sensorless algorithm generated a pulmonary vascular pulsatility of approximately 10 mmHg, and matched the cardiac demand at rest and exercise. The frequency of pump speed modulation was 10–15 cycles per minute and no suction was observed. The sensorless strategy outperformed constant CPAD speed control algorithm for improvement of pulmonary vascular pulsatility and physiologic perfusion. Further validation is needed using mock loop and animal tests. [ABSTRACT FROM AUTHOR]

Heavy metal content in water, sediment, and tissues of six commonly used edible fishes from Adyar estuary, southeast coast of India, was assessed for metal bioaccumulation. The enrichment of metals in estuarine sediment is due to the discharge of contaminated water from the Chennai Metropolis. The enrichment factor indicated that metals such as Cr (EF=30.9) and Cu (EF=31.9) are highly enriched and fall under the very severe category. Bioaccumulation factor (BAF) revealed that the concentration of heavy metals viz. Ni, Cr, Pb, Cu, Co, Zn, Fe, and Mn in different tissues of fishes was several times higher than their concentrations in water. Moreover, high concentration of heavy metals, especially Cu and Cr was noticed in the muscle and liver tissues of the fishes which are higher than the WHO standards. Among the studied fishes, Arius parkii and Gerres oyena showed higher levels of bioaccumulation in terms of toxic metals. • Heavy metals in fish tissues, water and sediment from Adyar estuary was assessed. • Enrichment factor revealed metals like Cr and Cu are highly enriched. • Sources from geogenic and anthropogenic origin are the cause for contamination. • Arius parkii and Gerres oyena shows higher level of metal bioaccumulation. [ABSTRACT FROM AUTHOR]

Herein we have stepped-up on a strategic spectroscopic modality by utilizing label free ultrasensitive surface enhanced Raman scattering (SERS) technique to generate a differential spectral fingerprint for the prediction of normal (NRML), high-grade intraepithelial lesion (HSIL) and cervical squamous cell carcinoma (CSCC) from exfoliated cell samples of cervix. Three different approaches i.e. single-cell, cell-pellet and extracted DNA from oncology clinic as confirmed by Pap test and HPV PCR were employed. Gold nanoparticles as the SERS substrate favored the increment of Raman intensity exhibited signature identity for Amide III/Nucleobases and carotenoid/glycogen respectively for establishing the empirical discrimination. Moreover, all the spectral invention was subjected to chemometrics including Support Vector Machine (SVM) which furnished an average diagnostic accuracy of 94%, 74% and 92% of the three grades. Combined SERS read-out and machine learning technique in field trial promises its potential to reduce the incidence in low resource countries. Pap smear test is the existing diagnostic method used for the cervical cancer detection which mainly looks upon the abnormal morphological characteristics in exfoliated cells. The inter-observer variability and less sensitivity demands ancillary techniques to be introduced. We have established a label-free surface enhanced Raman spectroscopy based differential diagnosis for the healthy, pre-cancerous lesion and invasive stages of cervical cancer using exfoliated cell samples for the first time. The resultant spectra were evaluated empirically as well as chemometrically and identified an average diagnostic accuracy of 94%, 74% and 92% for single cell, cell pellet and extracted DNA respectively. This study is more advantageous than label free SERS of blood based analysis where early molecular changes will not be as prevalent as in the exfoliated cell samples collected from the cervix. Unlabelled Image • Label free surface enhanced Raman spectroscopy (SERS) was introduced for differential diagnosis of the healthy, pre-cancerous lesion and invasive stages of cervical cancer using exfoliated cell samples. • Gold nanoparticles as a SERS substrate, a strategy developed achieved for the first time to generate a differential spectral classification using single cell, cell pellet and extracted DNA • SERS analysis together with conventional cytopathological investigations, Pap test and HPV DNA based analysis, HPV PCR • The resultant spectra have been classified empirically as well chemometrically using PCA, LDA as well as SVM analysis and identified well-found an average diagnostic accuracy of 94%, 74% and 92% of the three clinical grades. [ABSTRACT FROM AUTHOR]

• A novel suction index based control algorithm for rotary blood pumps was developed. • The suction index was extracted from the intrinsic pump speed measurements. • The SI control algorithm does not require a model, or pressure or flow sensors. • Blood pump flow matched perfusion demand for rest and exercise. • Suction was avoided for all test conditions Rotary blood pumps (RBP) are long-term mechanical circulatory support devices that support a failing heart by pumping blood. Ventricular collapse and suction, which can lead to myocardial damage and arrhythmias, is a significant risk factor during RBP support. The RBP also needs to maintain pump flow to match perfusion demand over a wide range of physiologic conditions. We have developed a novel sensorless control algorithm to maintain physiologic perfusion while avoiding ventricular suction, using a suction index (SI) extracted from the intrinsic pump speed measurements. The objective of the proposed control algorithm is to maintain an SI setpoint. Using nonlinear mathematical models of a human circulatory system and a RBP, efficacy and robustness of the proposed algorithm with 2% RPM measurement were tested in-silico by comparing it to differential pump speed control, differential pump pressure control, constant speed control, and mean aortic pressure control during (1) rest and exercise conditions, (2) a rapid eight-fold increase in pulmonary vascular resistance for rest and exercise, and (3) transition from exercise to rest. The proposed control algorithm provided physiologic perfusion while simultaneously preventing ventricular suction for all test conditions. The performance of the proposed control algorithm was superior to other tested control strategies in avoiding suction. Maintaining a reference SI effectively provided physiologic perfusion and prevented ventricular suction. The proposed SI control approach can meet physiologic circulatory demand and avoid suction in RBP without requiring the use of unreliable pressure or flow sensors or a pump model. [ABSTRACT FROM AUTHOR]

• A new sensorless physiologic control algorithm for the Fontan pump was developed. • A cavopulmonary pressure head was proposed to provide physiologic perfusion. • The approach uses only intrinsic pump parameters and does not need external sensors. • The proposed algorithm maintained physiologic perfusion while avoiding suction. Mechanical circulatory support devices using continuous flow blood pump technologies are currently being developed to provide cavopulmonary support in patients with Fontan circulation. While cavopulmonary support can functionally replace the missing native right ventricle and biventricularize the Fontan circulation, there is a need for the pump to adapt to variable physiologic demands. A constant pump speed limits the ability to provide sufficient physiologic perfusion over a range of physiologic conditions. To address this challenge, a physiologic control algorithm for a Fontan pump was developed. The proposed algorithm uses a gain-scheduled, proportional-integral controller that generates a user defined cavopulmonary pressure head (CPPH = pulmonary artery pressure - vena caval pressure), to provide physiologic pressure rise while avoiding suction. The approach uses only intrinsic pump parameters and does not require the use of pressure or flow sensors. Performance and robustness of the sensorless control algorithm was quantified in-silico by simulating the following conditions: (1) Directly measured CPPH with pressure sensors; (2) CPPH estimation using the intrinsic pump measurement of pump speed and extended Kalman filter (EKF); (3) constant speed control algorithm; and (4) rapid four-fold increase in vena caval resistance (VCR) for (1) to (3). The results demonstrated that the sensorless control algorithm maintained physiologic perfusion while simultaneously preventing vena caval suction without the need for pressure sensors. The proposed algorithm was superior to the constant speed control strategy for physiologic perfusion and suction prevention, and warranted further investigation in vitro and in-vivo. [ABSTRACT FROM AUTHOR]

Abstract: The present study is on the growth inhibitory effect of Withania somnifera methanolic leaf extract and its active component, withanolide on HL-60 promyelocytic leukemia cells. The decrease in survival rate of HL-60 cells was noted to be associated with a time dependent decrease in the Bcl-2/Bax ratio, leading to up regulation of Bax. Both the crude leaf extract and the active component activated the apoptotic cascade through the cytochrome c release from mitochondria. The activation of caspase 9, caspase 8 and caspase 3 revealed that caspase was a key mediator in the apoptotic pathway. DNA fragmentation analysis revealed typical ladders as early as 12h indicative of caspase 3 role in the apoptotic pathway. Flow cytometry data demonstrated an increase of sub-G1 peak upon treatment by 51% at 24h, suggesting the induction of apoptotic cell death in HL-60 cells. [Copyright &y& Elsevier]