Recent advancements in critical care: Part I.

Medical colleges are now developing or refurbishing their anaesthesia intensive care units. In most teaching colleges, the residency post includes working in the critical care unit (CCU). Critical care is a rapidly evolving and popular super-speciality for postgraduate students. In some hospitals, anaesthesiologists play a key role in the management of the CCU. As perioperative physicians, all anaesthesiologists should be aware of the recent advancements in diagnostic and monitoring gadgets and investigations in critical care so that they may manage perioperative events effectively. Haemodynamic monitoring gives us warning signs about the change in the internal milieu of the patient. Point-of-care ultrasonography helps in rapid differential diagnosis. Point-of-care diagnostics give us instant bed-side information on the condition of a patient. Biomarkers help in confirming diagnosis, in monitoring, treatment, and providing prognosis. Molecular diagnostics guide anaesthesiologists in providing specific treatment to a causative agent. This article touches upon all of these management strategies in critical care and attempts to put forth the recent advancements in this speciality.

Aligned human cardiac syncytium for in vitro analysis of electrical, structural, and mechanical readouts.

Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) have emerged as an exciting new tool for cardiac research and can serve as a preclinical platform for drug development and disease modeling studies. However, these aspirations are limited by current culture methods in which hPSC-CMs resemble fetal human cardiomyocytes in terms of structure and function. Herein we provide a novel in vitro platform that includes patterned extracellular matrix with physiological substrate stiffness and is amenable to both mechanical and electrical analysis. Micropatterned lanes promote the cellular and myofibril alignment of hPSC-CMs while the addition of micropatterned bridges enable formation of a functional cardiac syncytium that beats synchronously over a large two-dimensional area. We investigated the electrophysiological properties of the patterned cardiac constructs and showed they have anisotropic electrical impulse propagation, as occurs in the native myocardium, with speeds 2x faster in the primary direction of the pattern as compared to the transverse direction. Lastly, we interrogated the mechanical function of the pattern constructs and demonstrated the utility of this platform in recording the strength of cardiomyocyte contractions. This biomimetic platform with electrical and mechanical readout capabilities will enable the study of cardiac disease and the influence of pharmaceuticals and toxins on cardiomyocyte function. The platform also holds potential for high throughput evaluation of drug safety and efficacy, thus furthering our understanding of cardiovascular disease and increasing the translational use of hPSC-CMs.

Caregivers' perception of speech and language status and related needs in children with cleft lip and palate.

BACKGROUND AND PURPOSE: Comprehensive management for communication disorders in individuals with CLP was provided in a community based program in two rural districts in Tamilnadu, India. This program provides services at the community to empower the families about CLP and treatment options. OBJECTIVE: To document the caregiver perceptions' of communication status and needs in children with repaired CLP. METHOD: Six Focus Group Discussions were conducted in Thiruvannamalai and Cuddalore districts in Tamil Nadu, India. Participants were 55 Caregivers of children (5-12 years of age) with repaired CLP. RESULTS: Most participants were concerned about their child's communication and few expressed concerns about specific errors in speech observed in their children. The caregivers recognized the need for and were willing to avail speech correction services. The focus group discussions highlighted some factors that need to be considered while planning a service delivery program for speech correction. The caregivers' expressed inability to independently carryout home training programs attributing it the lack of cooperation from their children. However they were open to receiving services if it was logistically convenient. CONCLUSION: This study provided the caregiver perceptions' of needs relating to communication in children with CLP. These need to be incorporated in the existing program to develop a model for speech intervention that would be feasible, sustainable and have good compliance.

Studying the implementation of iterative impedance control for assistive hand rehabilitation using an exoskeleton.

A positive training synergy can be obtained when two individuals attempt to learn the same motor task while mechanically coupled to one another. In this paper, we have studied how mimicking this interaction through impedance control can be exploited to improve assistance delivered by hand exoskeleton devices during rehabilitation. In this context, the machine and user take complementary roles akin to two coupled individuals. We present the derivation of a dynamic model of the human hand for the purpose of controller development for new hand exoskeleton platforms. Using this model, we have simulated the behavior of an iterative impedance controller programmed for rehabilitative training. The controller interacts with cylindrical objects to be grasped by means of an inverse kinematic mapping and tuning of mechanical impedance characteristic of the finger joints. Through fusion of concepts from motor control theory, muscle impedance and task oriented control, the controller is capable of iteratively learn to accomplish simple tasks involving grasping and lifting while cooperating with a user. The controller is also capable of adapting to more complex dynamics for more dexterous tasks, such as pulling on a hand-bar or loosening the cap of a jar. We believe the human-robot synergy established in this investigation has benefits to therapy. It can be combined with a broad range of training exercises and represents an incremental step towards mimicking natural human motor responses.

Texture Evolution during Isothermal, Isostrain and Isobaric Loading of Polycrystalline Shape Memory NiTi.

In situ neutron diffraction was used to provide insight into martensite variant microstructures during isothermal, isobaric, and isostrain loading in shape memory NiTi. Results show variant microstructures were equivalent for the corresponding strain and more importantly, the reversibility and equivalency was immediately evident in variant microstructures that were first formed isobarically but then reoriented to a near random self-accommodated microstructure following isothermal deformation. Variant microstructures formed isothermally were not significantly affected by a subsequent thermal cycle under constant strain. In all loading cases considered, the resulting variant microstructure correlated with strain and did not correlate with stress. Based on the ability to select a variant microstructure for a given strain despite thermomechanical loading history, the results demonstrated here can be obtained by following any sequence of thermomechanical loading paths over multiple cycles. Thus for training shape memory alloys (repeating thermomechanical cycling to obtain the desired variant microstructure), optimal paths can be selected so as to minimize the number of training cycles required thereby increasing the overall stability and fatigue life of these alloys in actuator or medical applications.

Engineered Solution-Liquid-Solid Growth of a "Treelike" 1D/1D TiO2 Nanotube-CdSe Nanowire Heterostructure: Photoelectrochemical Conversion of Broad Spectrum of Solar Energy.

This work presents a hitherto unreported approach to assemble a 1D oxide-1D chalcogenide heterostructured photoactive film. As a representative system, bismuth (Bi) catalyzed 1D CdSe nanowires are directly grown on anodized 1D TiO2 nanotube (T_NT). A combination of the reductive successive-ionic-layer-adsorption-reaction (R-SILAR) and the solution-liquid-solid (S-L-S) approach is implemented to fabricate this heterostructured assembly, reported in this 1D/1D form for the first time. XRD, SEM, HRTEM, and elemental mapping are performed to systematically characterize the deposition of bismuth on T_NT and the growth of CdSe nanowires leading to the evolution of the 1D/1D heterostructure. The resulting "treelike" photoactive architecture demonstrates UV-visible light-driven electron-hole pair generation. The photoelectrochemical results highlight: (i) the formation of a stable n-n heterojunction between TiO2 nanotube and CdSe nanowire, (ii) an excellent correlation between the absorbance vis-à-vis light conversion efficiency (IPCE), and (iii) a photocurrent density of 3.84 mA/cm2. This proof-of-concept features the viability of the approach for designing such complex 1D/1D oxide-chalcogenide heterostructures that can be of interest to photovoltaics, photocatalysis, environmental remediation, and sensing.

Movement decoding using neural synchronization and inter-hemispheric connectivity from deep brain local field potentials.

OBJECTIVE: Correlating electrical activity within the human brain to movement is essential for developing and refining interventions (e.g. deep brain stimulation (DBS)) to treat central nervous system disorders. It also serves as a basis for next generation brain-machine interfaces (BMIs). This study highlights a new decoding strategy for capturing movement and its corresponding laterality from deep brain local field potentials (LFPs). APPROACH: LFPs were recorded with surgically implanted electrodes from the subthalamic nucleus or globus pallidus interna in twelve patients with Parkinson's disease or dystonia during a visually cued finger-clicking task. We introduce a method to extract frequency dependent neural synchronization and inter-hemispheric connectivity features based upon wavelet packet transform (WPT) and Granger causality approaches. A novel weighted sequential feature selection algorithm has been developed to select optimal feature subsets through a feature contribution measure. This is particularly useful when faced with limited trials of high dimensionality data as it enables estimation of feature importance during the decoding process. MAIN RESULTS: This novel approach was able to accurately and informatively decode movement related behaviours from the recorded LFP activity. An average accuracy of 99.8% was achieved for movement identification, whilst subsequent laterality classification was 81.5%. Feature contribution analysis highlighted stronger contralateral causal driving between the basal ganglia hemispheres compared to ipsilateral driving, with causality measures considerably improving laterality discrimination. SIGNIFICANCE: These findings demonstrate optimally selected neural synchronization alongside causality measures related to inter-hemispheric connectivity can provide an effective control signal for augmenting adaptive BMIs. In the case of DBS patients, acquiring such signals requires no additional surgery whilst providing a relatively stable and computationally inexpensive control signal. This has the potential to extend invasive BMI, based on recordings within the motor cortex, by providing additional information from subcortical regions.

Complete sequencing of an IncX3 plasmid carrying blaNDM-5 allele reveals an early stage in the dissemination of the blaNDM gene.

PURPOSE: The aim of the present study was to perform molecular characterisation of the blaNDM plasmids and to understand the mechanism of its spread among pathogenic bacteria. MATERIALS AND METHODS: Seventy-six non-repetitive carbapenem-resistant isolates which were collected during Nov 2011 to April 2013 from four hospitals in Chennai were analyzed for the presence of the blaNDM gene by PCR. Further, the genetic context of the blaNDM gene was analyzed by PCR specific to ISAba125 and bleMBL gene. One of the blaNDM plasmid was completely sequenced in the Illumina HiSeq platform. RESULTS: Twenty-three isolates consisting of 8 Escherichia coli, 8 Klebsiella pneumoniae, 3 Klebsiella oxytoca, 3 Acinetobacter baumanii and 1 Pseudomonas aeruginosa were found to carry the blaNDM gene. In 18 isolates the blaNDM gene was associated with a bleMBL gene and the ISAba125 element. The complete sequencing of pNDM-MGR194 revealed an IncX3 replication type plasmid, with a length of 46,253 bp, an average GC content of 47% and 59 putative ORFs. The iteron region contained the blaNDM5 gene and the bleMBL , trpF and dsbC genes downstream and an IS5 inserted within the ISAba125 element upstream. CONCLUSION: This is the first report where the blaNDM gene insertion in a plasmid is not accompanied by other resistance gene determinants. These observations suggest that the IncX3 plasmid pNDM-MGR194 is an early stage in the dissemination of the blaNDM .

Laser surface modification of medical grade alloys for reduced heating in a magnetic resonance imaging environment.

Nanoscale surface modification of medical grade metallic alloys was conducted using a neodymium-doped yttrium aluminum garnet laser-based dopant diffusion technique. The objective of this approach was to minimize the induction heating by reducing the absorbed radio frequency field. Such an approach is advantageous in that the dopant is diffused into the alloy and is not susceptible to detachment or spallation as would an externally applied coating, and is expected to not deteriorate the mechanical and electrical properties of the base alloy or device. Experiments were conducted using a controlled environment laser system with the ability to control laser properties (i.e., laser power, spot size, and irradiation time) and dopant characteristics (i.e., temperature, concentration, and pressure). The reflective and transmissive properties of both the doped and untreated samples were measured in a radio frequency (63.86 MHz) magnetic field using a system comprising a high power signal generator, a localized magnetic field source and sensor, and a signal analyzer. The results indicate an increase in the reflectivity of the laser-treated samples compared to untreated samples. The effect of reflectivity on the heating of the alloys is investigated through a mathematical model incorporating Maxwell's equations and heat conduction.

Design and implementation of a multiaxial loading capability during heating on an engineering neutron diffractometer.

A gripping capability was designed, implemented, and tested for in situ neutron diffraction measurements during multiaxial loading and heating on the VULCAN engineering materials diffractometer at the spallation neutron source at Oak Ridge National Laboratory. The proposed capability allowed for the acquisition of neutron spectra during tension, compression, torsion, and/or complex loading paths at elevated temperatures. The design consisted of age-hardened, Inconel(®) 718 grips with direct attachment to the existing MTS load frame having axial and torsional capacities of 100 kN and 400 N·m, respectively. Internal cooling passages were incorporated into the gripping system for fast cooling rates during high temperature experiments up to ∼1000 K. The specimen mounting couplers combined a threaded and hexed end-connection for ease of sample installation/removal without introducing any unwanted loads. Instrumentation of this capability is documented in this work along with various performance parameters. The gripping system was utilized to investigate deformation in NiTi shape memory alloys under various loading/control modes (e.g., isothermal, isobaric, and cyclic), and preliminary results are presented. The measurements facilitated the quantification of the texture, internal strain, and phase fraction evolution in NiTi shape memory alloys under various loading/control modes.

Multi-modal locomotion: from animal to application.

The majority of robotic vehicles that can be found today are bound to operations within a single media (i.e. land, air or water). This is very rarely the case when considering locomotive capabilities in natural systems. Utility for small robots often reflects the exact same problem domain as small animals, hence providing numerous avenues for biological inspiration. This paper begins to investigate the various modes of locomotion adopted by different genus groups in multiple media as an initial attempt to determine the compromise in ability adopted by the animals when achieving multi-modal locomotion. A review of current biologically inspired multi-modal robots is also presented. The primary aim of this research is to lay the foundation for a generation of vehicles capable of multi-modal locomotion, allowing ambulatory abilities in more than one media, surpassing current capabilities. By identifying and understanding when natural systems use specific locomotion mechanisms, when they opt for disparate mechanisms for each mode of locomotion rather than using a synergized singular mechanism, and how this affects their capability in each medium, similar combinations can be used as inspiration for future multi-modal biologically inspired robotic platforms.

Identification of plasmid-mediated quinolone resistance genes qnrA1, qnrB1 and aac(6')-1b-cr in a multiple drug-resistant isolate of Klebsiella pneumoniae from Chennai.

PURPOSE: Resistance to fluoroquinolones, a commonly prescribed antimicrobial for Gram-negative and Gram-positive microorganisms, is of importance in therapy. The purpose of this study was to screen for the presence of Plasmid-Mediated Quinolone Resistance (PMQR) determinants in clinical isolates of Klebsiella pneumoniae. MATERIALS AND METHODS: Extended-Spectrum Beta-Lactamase (ESBL) isolates of K. pneumoniae collected during October 2009 were screened by the antimicrobial susceptibility test. The plasmids from these isolates were analysed by specific Polymerase chain Reaction (PCR) for qnrA, qnrB and aac(6')-1b. The amplified products were sequenced to confirm the allele. RESULTS: Our analysis showed that 61% out of the 23 ESBL K. pneumoniae isolates were resistant to ciprofloxacin and 56% to levofloxacin. The PMQR was demonstrated by transforming the plasmids from two isolates P12 and P13 into E. coli JM109. The PMQR gene qnrA was found in 16 isolates and qnrB in 11 isolates. The plasmid pKNMGR13 which conferred an minimum inhibitory concentration (MIC) of more than 240 µg/ml in sensitive E. coli was found to harbour the qnrA1 and qnrB1 allele. Furthermore, the gene aac(6')-1b-cr encoding a variant aminoglycoside 6'-N Acetyl transferase which confers resistance to fluoroquinolones was found in the same plasmid. CONCLUSIONS: Our report shows the prevalence of PMQR mediated by qnrA and qnrB in multidrug-resistant K. pneumoniae isolates from Chennai. A multidrug-resistant plasmid conferring high resistance to ciprofloxacin was found to harbour another PMQR gene, aac(6')-1b-cr mutant gene. This is the first report screening for PMQR in K. pneumoniae isolates from India.

Development of a parametric kinematic model of the human hand and a novel robotic exoskeleton.

This paper reports the integration of a kinematic model of the human hand during cylindrical grasping, with specific focus on the accurate mapping of thumb movement during grasping motions, and a novel, multi-degree-of-freedom assistive exoskeleton mechanism based on this model. The model includes thumb maximum hyper-extension for grasping large objects (~> 50 mm). The exoskeleton includes a novel four-bar mechanism designed to reproduce natural thumb opposition and a novel synchro-motion pulley mechanism for coordinated finger motion. A computer aided design environment is used to allow the exoskeleton to be rapidly customized to the hand dimensions of a specific patient. Trials comparing the kinematic model to observed data of hand movement show the model to be capable of mapping thumb and finger joint flexion angles during grasping motions. Simulations show the exoskeleton to be capable of reproducing the complex motion of the thumb to oppose the fingers during cylindrical and pinch grip motions.

Design, implementation, and testing of a cryogenic loading capability on an engineering neutron diffractometer.

A novel capability was designed, implemented, and tested for in situ neutron diffraction measurements during loading at cryogenic temperatures on the spectrometer for materials research at temperature and stress at Los Alamos National Laboratory. This capability allowed for the application of dynamic compressive forces of up to 250 kN on standard samples controlled at temperatures between 300 and 90 K. The approach comprised of cooling thermally isolated compression platens that in turn conductively cooled the sample in an aluminum vacuum chamber which was nominally transparent to the incident and diffracted neutrons. The cooling/heat rate and final temperature were controlled by regulating the flow of liquid nitrogen in channels inside the platens that were connected through bellows to the mechanical actuator of the load frame and by heaters placed on the platens. Various performance parameters of this system are reported here. The system was used to investigate deformation in Ni-Ti-Fe shape memory alloys at cryogenic temperatures and preliminary results are presented.

Trabecular scaffolds created using micro CT guided fused deposition modeling.

Free form fabrication and high resolution imaging techniques enable the creation of biomimetic tissue engineering scaffolds. A 3D CAD model of canine trabecular bone was produced via micro CT and exported to a fused deposition modeler, to produce polybutylene terephthalate (PBT) trabeculated scaffolds and four other scaffold groups of varying pore structures. The five scaffold groups were divided into subgroups (n=6) and compression tested at two load rates (49 N/s and 294 N/s). Two groups were soaked in a 25 °C saline solution for 7 days before compression testing. Micro CT was used to compare porosity, connectivity density, and trabecular separation of each scaffold type to a canine trabecular bone sample. At 49 N/s the dry trabecular scaffolds had a compressive stiffness of 4.94±1.19 MPa, similar to the simple linear small pore scaffolds and significantly more stiff (p<0.05) than either of the complex interconnected pore scaffolds. At 294 N/s, the compressive stiffness values for all five groups roughly doubled. Soaking in saline had an insignificant effect on stiffness. The trabecular scaffolds matched bone samples in porosity; however, achieving physiologic connectivity density and trabecular separation will require further refining of scaffold processing.

Left atrial myxoma presenting as acute inferior wall infarction-a case report.

Acute myocardial infarction is a rare form of presentation in patients with left atrial myxoma. With wider availability of echocardiography, more and more patients with atrial myxomas will be diagnosed. This report describes a patient with left atrial myxoma who presented features of acute myocardial infarction and had surgical removal of LA myxoma.

An instrumented scaffold can monitor loading in the knee joint.

No technique has been consistently successful in the repair of large focal defects in cartilage, particularly in older patients. Tissue-engineered cartilage grown on synthetic scaffolds with appropriate mechanical properties will provide an implant, which could be used to treat this problem. A means of monitoring loads and pressures acting on cartilage, at the defect site, will provide information needed to understand integration and survival of engineered tissues. It will also provide a means of evaluating rehabilitation protocols. A "sensate" scaffold with calibrated strain sensors attached to its surface, combined with a subminiature radio transmitter, was developed and utilized to measure loads and pressures during gait. In an animal study utilizing six dogs, peak loads of 120N and peak pressures of 11 MPa were measured during relaxed gait. Ingrowth into the scaffold characterized after 6 months in vivo indicated that it was well anchored and bone formation was continuing. Cartilage tissue formation was noted at the edges of the defect at the joint-scaffold interfaces. This suggested that native cartilage integration in future formulations of this scaffold configured with engineered cartilage will be a possibility.

Reversible inhibition of contractions of mammalian cardiomyocytes and of smooth muscle by the protistan parasite Leishmania major.

Myotropic neuropeptides have been isolated from vertebrates and invertebrates. Recently, a myoinhibitory peptide from the protist Leishmaniamajor was isolated, and its function in the sand fly vector was described. Similar lysates of cultured L. major were tested for their ability to inhibit contractions in mammalian cell and tissue preparations. L. major proteins (LMP) (34 microg/ml) completely stopped spontaneous contractions of cultured rat cardiomyocytes; cells resumed contracting after a saline wash. An application of 880 microg/ml LMP significantly decreased force of contractions (36%) in strips of guinea pig ileum precontracted with nicotine (p<0.01) but not with acetylcholine (p>0.01). Ileal strips rinsed with Tyrode's solution and again stimulated with nicotine contracted normally. Contractile force of ileal strips electrically stimulated with 40 V was reduced in a dose-dependent manner (30, 76, and 100%) (p<0.01) by increasing concentrations of LMP (220, 440, and 880 microg/ml). This ileal preparation resumed contracting after rinsing with Tyrode's solution. Oxytocin-induced contractions of guinea pig uterine strips were reduced significantly in a dose-dependent manner (21 and 55%) (p<0.01) by increasing concentrations (170 and 310 microg/ml) of LMP and resumed contracting normally after rinsing with Tyrode's solution. Modes of action for L. major myoinhibitory factors may include either decreasing Ca(2+) influx or increasing Ca(2+) efflux in susceptible muscle. Protistan-induced inotropism is discussed in light of exacerbating pathology of disease.