Systematic quantification of differences in shear wave elastography estimates between linear-elastic and viscoelastic material assumptionsa).

Quantitative, accurate, and standardized metrics are important for reliable shear wave elastography (SWE)-based biomarkers. For over two decades, the linear-elastic material assumption has been employed in SWE modes. In recent years, viscoelasticity estimation methods have been adopted in a few clinical systems. The current study aims to systematically quantify differences in SWE estimates obtained using linear-elastic and viscoelastic material assumptions. An acousto-mechanical simulation framework of acoustic radiation force impulse-based SWE was created to elucidate the effect of material viscosity and shear modulus on SWE estimates. Shear modulus estimates exhibited errors up to 72% when a numerical viscoelastic phantom was assessed as linearly elastic. Shear modulus estimates of polyvinyl alcohol phantoms between rheometry and SWE following the Kelvin-Voigt viscoelastic model assumptions were not significantly different. However, the percentage difference in shear modulus estimates between rheometry and SWE using the linear-elastic assumption was 50.1%-62.1%. In ex vivo liver, the percentage difference in shear modulus estimates between linear-elastic and viscoelastic methods was 76.1%. These findings provide a direct and systematic quantification of the potential error introduced when viscoelastic tissues are imaged with SWE following the linear-elastic assumption. This work emphasizes the need to utilize viscoelasticity estimation methods for developing robust quantitative imaging biomarkers.

VapC12 ribonuclease toxin modulates host immune response during Mycobacterium tuberculosis infection.

Mechanistic understanding of antibiotic persistence is a prerequisite in controlling the emergence of MDR cases in Tuberculosis (TB). We have reported that the cholesterol-induced activation of VapC12 ribonuclease is critical for disease persistence in TB. In this study, we observed that relative to the wild type, mice infected with ΔvapC12 induced a pro-inflammatory response, had a higher pathogen load, and responded better to the anti-TB treatment. In a high-dose infection model, all the mice infected with ΔvapC12 succumbed early to the disease. Finally, we reported that the above phenotype of ΔvapC12 was dependent on the presence of the TLR4 receptor. Overall, the data suggests that failure of a timely resolution of the early inflammation by the ΔvapC12 infected mice led to hyperinflammation, altered T-cell response and high bacterial load. In conclusion, our findings suggest the role of the VapC12 toxin in modulating the innate immune response of the host in ways that favor the long-term survival of the pathogen inside the host.

Exploration of functional relations among differentially co-expressed genes identifies regulators in glioblastoma.

The conventional computational approaches to investigating a disease confront inherent constraints as they often need to improve in delving beyond protein functional associations and grasping their deeper contextual significance within the disease framework. Such context-specificity can be explored using clinical data by evaluating the change in interaction between the biological entities in different conditions by investigating the differential co-expression relationships. We believe that the integration and analysis of differential co-expression and the functional relationships, primarily focusing on the source nodes, will open novel insights about disease progression as the source proteins could trigger signaling cascades, mostly because they are transcription factors, cell surface receptors, or enzymes that respond instantly to a particular stimulus. A thorough contextual investigation of these nodes could lead to a helpful beginning point for identifying potential causal linkages and guiding subsequent scientific investigations to uncover mechanisms underlying observed associations. Our methodology includes functional protein-protein Interaction (PPI) data and co-expression information and filters functional linkages through a series of critical steps, culminating in the identification of a robust set of regulators. Our analysis identified eleven key regulators-AKT1, BRCA1, CAMK2G, CUL1, FGFR3, KIF3A, NUP210, PRKACB, RAB8A, RPS6KA2 and TGFB3-in glioblastoma. These regulators play a pivotal role in disease classification, cell growth control, and patient survivability and exhibit associations with immune infiltrations and disease hallmarks. This underscores the importance of assessing correlation towards causality in unraveling complex biological insights.

Tethered spinal cord tension assessed via ultrasound elastography in computational and intraoperative human studies.

BACKGROUND: Tension in the spinal cord is a trademark of tethered cord syndrome. Unfortunately, existing tests cannot quantify tension across the bulk of the cord, making the diagnostic evaluation of stretch ambiguous. A potential non-destructive metric for spinal cord tension is ultrasound-derived shear wave velocity (SWV). The velocity is sensitive to tissue elasticity and boundary conditions including strain. We use the term Ultrasound Tensography to describe the acoustic evaluation of tension with SWV. METHODS: Our solution Tethered cord Assessment with Ultrasound Tensography (TAUT) was utilized in three sub-studies: finite element simulations, a cadaveric benchtop validation, and a neurosurgical case series. The simulation computed SWV for given tensile forces. The cadaveric model with induced tension validated the SWV-tension relationship. Lastly, SWV was measured intraoperatively in patients diagnosed with tethered cords who underwent treatment (spinal column shortening). The surgery alleviates tension by decreasing the vertebral column length. RESULTS: Here we observe a strong linear relationship between tension and squared SWV across the preclinical sub-studies. Higher tension induces faster shear waves in the simulation (R2 = 0.984) and cadaveric (R2 = 0.951) models. The SWV decreases in all neurosurgical procedures (p < 0.001). Moreover, TAUT has a c-statistic of 0.962 (0.92-1.00), detecting all tethered cords. CONCLUSIONS: This study presents a physical, clinical metric of spinal cord tension. Strong agreement among computational, cadaveric, and clinical studies demonstrates the utility of ultrasound-induced SWV for quantitative intraoperative feedback. This technology is positioned to enhance tethered cord diagnosis, treatment, and postoperative monitoring as it differentiates stretched from healthy cords.

Tethered spinal cord syndrome occurs when surrounding tissue attaches to and causes stretching across the spinal cord. People with a tethered cord can experience weakness, pain, and loss of bladder control. Although increased tension in the spinal cord is known to cause these symptoms, evaluating the amount of stretching remains challenging. We investigated the ability of an ultrasound imaging approach to measure spinal cord tension. We studied our method in a computer simulation, a benchtop validation model, and in six people with tethered cords during surgery that they were undergoing to reduce tension. In each phase, the approach could detect differences between stretched spinal cords and spinal cords in a healthy state. Our method could potentially be used in the future to improve the care of people with a tethered cord.

Is Neck Pain Related to Sagittal Head and Neck Posture?: A Systematic Review and Meta-analysis.

Background: Neck pain (NP) is common in all age groups and adversely affects the patients' entire lifestyle. There exists inconclusive evidence relating faulty craniocervical posture with pain-related disability. This review aims to determine whether sagittal head and neck posture differs in NP and pain-free subjects, to critically appraise the correlation of posture with NP. Methods: Of 3796 articles identified at primary search from CINAHL, PubMed, Google Scholar, EMBASE, 26 were included based on eligibility criteria. Mean pooled difference (MPD) and effect size (ES) were calculated to establish relationship among studies, to assess postural correlation with NP measures [Visual Analogue Scale (VAS), Numeric Pain Rating Scale (NPRS), neck disability index (NDI), Northwick Park NP Questionnaire (NPQ)] and for age- and gender-wise variation. Risk of bias was assessed using Newcastle-Ottawa Quality Assessment Scale. Results: Craniovertebral angle (CVA) had a significant MPD of - 2.93(95% CI - 4.95 to - 0.91). Sagittal head angle (SHA) and forward head posture (FHP) had an insignificant MPD of 1.15 (95% CI - 1.16 to 3.46) and - 0.26 (95% CI - 1.89 to 1.36), respectively. Age- and gender-wise CVA difference was found to be 2.36° and 2.57°, respectively. ES was significant for correlation between CVA and pain intensity [NPRS: - 0.44 (95% CI - 0.61 to - 0.26); VAS: - 0.31 (95% CI - 0.46 to - 0.16)], and between CVA and disability [NDI: - 0.18 (95% CI - 0.31 to - 0.05); NPQ: - 0.47 (95% CI - 0.61 to - 0.320)]. Conclusion: CVA differs for age, gender, and pain vs pain-free subjects, and correlates negatively with NP measures. Other surrogate measures (SHA, cranial and cervical angles, FHP) warrant further research. PROSPERO Registration: PROSPERO 2021 CRD42021275485.

Characterizing Viscoelastic Polyvinyl Alcohol Phantoms for Ultrasound Elastography.

Ultrasound phantoms mimic the acoustic and mechanical properties of native tissues. Polyvinyl alcohol (PVA) phantoms are used extensively as models for validating ultrasound elastography approaches. However, the viscous properties of PVA phantoms have not been investigated adequately. Glycerol is a viscous liquid that has been reported to increase the speed of sound of phantoms. This study aims to assess the acoustic and viscoelastic properties of PVA phantoms and PVA mixed with glycerol at varying concentrations. The phantoms were fabricated with 10% w/v PVA in water with varying concentrations of glycerol (10%, 15% and 20% v/v) and 2% w/v silicon carbide particles as acoustic scatterers. The phantoms were subjected to either one, two, or three 24-h freeze-thaw cycles. The longitudinal sound speeds of all PVA phantoms were measured, and ranged from 1529 to 1660 m/s. Attenuation spectroscopy was performed in the range of 5 to 20 MHz. The measured attenuation followed a power-law relationship with frequency, wherein the power-law fit constants and exponents ranged from 0.02 to 0.1 dB/cm/MHzn and from 1.6 to 1.9, respectively. These results were in agreement with previous reports for soft tissues. Viscoelasticity of PVA phantoms was assessed using rheometry. The estimated values of shear modulus and viscosity using the Kelvin-Voigt and Kelvin-Voigt fractional derivative models were within the range of previously-reported tissue-mimicking phantoms and soft tissues. The number of freeze-thaw cycles were shown to alter the viscosity of PVA phantoms, even in the absence of glycerol. Scanning electron microscopy images of PVA phantoms without glycerol showed a porous hydrogel network, in contrast to those of PVA-glycerol phantoms with non-porous structure. Phantoms fabricated in this study possess tunable acoustic and viscoelastic properties within the range reported for healthy and diseased soft tissues. This study demonstrates that PVA phantoms can be manufactured with glycerol for applications in ultrasound elastography.

Elucidating the metabolic characteristics of pancreatic ß-cells from patients with type 2 diabetes (T2D) using a genome-scale metabolic modeling.

Diabetes is a global health problem caused primarily by the inability of pancreatic ß-cells to secrete adequate insulin. Despite extensive research, the identity of factors contributing to the dysregulated metabolism-secretion coupling in the ß-cells remains elusive. The present study attempts to capture some of these factors responsible for the impaired ß-cell metabolism-secretion coupling that contributes to diabetes pathogenesis. The metabolic-flux profiles of pancreatic ß-cells were predicted using genome-scale metabolic modeling for ten diabetic patients and ten control subjects. Analysis of these flux states shows reduction in the mitochondrial fatty acid oxidation and mitochondrial oxidative phosphorylation pathways, that leads to decreased insulin secretion in diabetes. We also observed elevated reactive oxygen species (ROS) generation through peroxisomal fatty acid ß-oxidation. In addition, cellular antioxidant defense systems were found to be attenuated in diabetes. Our analysis also uncovered the possible changes in the plasma metabolites in diabetes due to the ß-cells failure. These efforts subsequently led to the identification of seven metabolites associated with cardiovascular disease (CVD) pathogenesis, thus establishing its link as a secondary complication of diabetes.

Exploring gene knockout strategies to identify potential drug targets using genome-scale metabolic models.

Research on new cancer drugs is performed either through gene knockout studies or phenotypic screening of drugs in cancer cell-lines. Both of these approaches are costly and time-consuming. Computational framework, e.g., genome-scale metabolic models (GSMMs), could be a good alternative to find potential drug targets. The present study aims to investigate the applicability of gene knockout strategies to be used as the finding of drug targets using GSMMs. We performed single-gene knockout studies on existing GSMMs of the NCI-60 cell-lines obtained from 9 tissue types. The metabolic genes responsible for the growth of cancerous cells were identified and then ranked based on their cellular growth reduction. The possible growth reduction mechanisms, which matches with the gene knockout results, were described. Gene ranking was used to identify potential drug targets, which reduce the growth rate of cancer cells but not of the normal cells. The gene ranking results were also compared with existing shRNA screening data. The rank-correlation results for most of the cell-lines were not satisfactory for a single-gene knockout, but it played a significant role in deciding the activity of drug against cell proliferation, whereas multiple gene knockout analysis gave better correlation results. We validated our theoretical results experimentally and showed that the drugs mitotane and myxothiazol can inhibit the growth of at least four cell-lines of NCI-60 database.

Seroprevalence and attainment of herd immunity against SARS CoV-2: A modelling study.

OBJECTIVE: The present study aims to predict the likelihood of and likely time required to attain herd immunity against COVID-19 in New Delhi due to natural infection. METHOD: An ODE-based mathematical model was constructed by extending the classical SEIR model to predict the seroprevalence rate. We estimated the parameter values for Delhi using available data (reported cases and the seroprevalence rate) and used them for future prediction. Also, changes in the seroprevalence rate with different possibilities of reinfection were predicted. RESULTS: Maximum seroprevalence rate obtained through our model is 31.65% and also a reduction in the seroprevalence rate was observed for the upcoming one month (month of January, 2021) due to the reduced transmission rate. After increasing the transmission rate to the value same as the third wave in New Delhi, we obtained a maximum value of 54.96%. This maximum value significantly decreased with the reduction in the reinfection possibilities. Also, a little impact of the duration of persistence of antibodies, 180 vs 105 days, was observed on the maximum seroprevalence. CONCLUSION: This modelling study suggests that natural infection alone, as gauged by serial sero-surveys, may not result in attainment of herd immunity in the state of Delhi.

7-Alkoxy-appended coumarin derivatives: synthesis, photo-physical properties, aggregation behaviours and current-voltage (I-V) characteristic studies on thin films.

In this study, we designed and synthesised a series of coumarin derivatives appended with a long alkoxy chain on the seventh position of the coumarin-3-carboxylate/carboxylic acid core to make thin film materials. Synthesised compounds were characterized by their UV and fluorescence spectra in solutions as well as their films prepared by both LB and spin-coated methods. The surface morphology and electrical behaviour of thin films were judged by AFM, SEM and I-V characteristic mapping respectively. Isotherm, UV-Vis absorption and fluorescence spectroscopic investigations revealed the formation of aggregates on thin films. The result of SEM and AFM images provides the information about the length and height of aggregates on the thin films of coumarin derivatives. From I-V characteristics, it was found that at room temperature, the spin-coated films of coumarin derivatives containing an ester functional group exhibited a threshold switching behaviour, whereas derivatives containing the carboxylic acid functional group showed both threshold and bipolar switching behaviours. We also noticed that the I-V characteristic features of synthesized materials depended on the length of the alkyl chain of individual series.

Synthesis of 3-alkenylindoles through regioselective C-H alkenylation of indoles by a ruthenium nanocatalyst.

3-Alkenylindoles are biologically and medicinally very important compounds, and their syntheses have received considerable attention. Herein, we report the synthesis of 3-alkenylindoles via a regioselective alkenylation of indoles, catalysed by a ruthenium nanocatalyst (RuNC). The reaction tolerates several electron-withdrawing and electron-donating groups on the indole moiety. Additionally, a "robustness screen" has also been employed to demonstrate the tolerance of several functional groups relevant to medicinal chemistry. With respect to the Ru nanocatalyst, it has been demonstrated that it is recoverable and recyclable up to four cycles. Also, the catalyst acts through a heterogeneous mechanism, which has been proven by various techniques, such as ICPMS and three-phase tests. The nature of the Ru nanocatalyst surface has also been thoroughly examined by various techniques, and it has been found that the oxides on the surface are responsible for the high catalytic efficiency of the Ru nanocatalyst.

Computational study of photo-thermal ablation of large blood vessel embedded tumor using localized injection of gold nanoshells.

Attaining a precise necrosis of tumor sparing normal tissue during carcinomas thermo-therapy via nominally invasive scheme like irradiation of laser is a recent challenge. In this study, a combined diffusion and convective energy equations were solved using COMSOL Multiphysics to predict the tissue thermal profile during laser assisted thermo-therapy with different tissue vascular networks. A comparative analysis between intratumoral and intravenous loading scheme of silica-gold nanoshells (AuNs) was also performed. AuNs cluster position and alignment was altered to achieve precise ablation of a large tumor with minimum damage to healthy tissue and improvement in necrosis in the vicinity of large blood vessels (LBV). A modified Beer-Lambert law and Arrhenius equation was applied to model laser heat propagation and to compute thermal damage respectively. Simulation results suggests the dominance of targeted nanostructure injection in cluster form over intravenous scheme in terms of precise control over spreading of necrotic zone due to selective laser dose delivery into the tumor. An effective tumor ablation, sparing normal tissue is best revealed for Type-A intratumoral scheme comparing Type-B and C as the reallocation of cluster position can help to achieve an irregular shaped necrotic zone. In addition a comparative analysis between dual-phase-lag (DPL) and classical Fourier approach within a tumor-blood inhomogeneous inner structure was made to access the effect of relaxation time onto biological thermal response. Numerical results show a difference in temperature profile between these two approaches during non-equilibrium condition i.e at the prior phases of laser heating and cooling whereas the results overlaps at higher instants. Since the DPL based bioheat conduction model can predict the inherent wave nature of the thermal front which is propagating at a finite speed. This study may improve the real clinical invasive schemes applied to ablate malignant tumor during hyperthermia treatment.

Valvular heart disease and anaesthesia.

Valvular heart disease presents as mixed spectrum lesion in healthcare settings in the third-world and developing countries. Rheumatic heart disease still forms the bulk of the aetiopathology of valve lesions. Mitral and aortic valve lesions top the list of valvular pathology. A thorough understanding of the pathophysiology of valvular heart disease is essential while planning anaesthesia and perioperative care for such patients. Meticulous use of optimal fluids, close monitoring of the changing haemodynamics and avoidance of situations that can cause major reduction of cardiac output and fluid shifts are mandatory to achieve good clinical outcome. We searched MEDLINE using combinations of the following: anaesthesia, aortic, mitral, regurgitation, stenosis and valvular heart disease. We also hand searched textbooks and articles on valvular heart disease and anaesthesia. This article mainly focuses on the understanding the pathophysiology of valvular heart disease in patients presenting for non-cardiac surgeries in secondary and tertiary care setting.

Postoperative analgesia for cleft lip and palate repair in children.

Acute pain such as postoperative pain during infancy was ignored approximately three decades ago due to biases and misconceptions regarding the maturity of the infant's developing nervous system, their inability to verbally report pain, and their perceived inability to remember pain. More recently, these misconceptions are rarely acknowledged due to enhanced understanding of the developmental neurobiology of infant pain pathways and supraspinal processing. Cleft lip and palate is one of the most common congenital abnormalities requiring surgical treatment in children and is associated with intense postoperative pain. The pain management gets further complicated due to association with postsurgical difficult airway and other congenital anomalies. Orofacial blocks like infraorbital, external nasal, greater/lesser palatine, and nasopalatine nerve blocks have been successively used either alone or in combinations to reduce the postoperative pain. Since in pediatric population, regional anesthesia is essentially performed under general anesthesia, association of these two techniques has dramatically cut down the risks of both procedures particularly those associated with the use of opioids and nonsteroidal anti-inflammatory drugs. Definitive guidelines for postoperative pain management in these patients have not yet been developed. Incorporation of multimodal approach as an institutional protocol can help minimize the confusion around this topic.

Time Resolved Spectroscopic Studies on a Novel Synthesized Photo-Switchable Organic Dyad and Its Nanocomposite Form in Order to Develop Light Energy Conversion Devices.

UV-vis absorption, steady state and time resolved spectroscopic investigations in pico and nanosecond time domain were made in the different environments on a novel synthesized dyad, 3-(2-methoxynaphthalen-1-yl)-1-(4-methoxyphenyl)prop-2-en-1-one (MNTMA) in its pristine form and when combined with gold (Au) nanoparticles i.e., in its nanocomposite structure. Both steady state and time resolved measurements coupled with the DFT calculations performed by using Gaussian 03 suit of software operated in the linux operating system show that though the dyad exhibits mainly the folded conformation in the ground state but on photoexcitation the nanocomposite form of dyad prefers to be in elongated structure in the excited state indicating its photoswitchable nature. Due to the predominancy of elongated isomeric form of the dyad in the excited state in presence of Au Nps, it appears that the dyad MNTMA may behave as a good light energy converter specially in its nanocomposite form. As larger charge separation rate (kcs ~ 4 x 10(8) s-1) is found relative to the rate associated with the energy wasting charge recombination processes (kcR ~ 3 x 10(5) s-1) in the nanocomposite form of the dyad, it demonstrates the suitability of constructing the efficient light energy conversion devices with Au-dyad hybrid nanomaterials.

Enantiomeric organogelators from D-/L-arabinose for phase selective gelation of crude oil and their gel as a photochemical micro-reactor.

Enantiomeric D- or L-arabinose based low molecular-weight organogelators (LMOGs), accessible in a single synthetic step from D-/L-arabinose have been found to be efficient gelators for aromatic solvents and refined and crude oil. The organogel has also been successfully used as a micro-reactor for a photochemical reaction.

Primary malignant fibrous histiocytoma involving the left pulmonary vein presenting as a left atrial tumor.

A 35-year-old woman presented with 4 months history of progressively increasing intermittent dyspnea and hemoptysis. Transthoracic echocardiography revealed a loculated mass in the left atrium (LA). A provisional diagnosis of LA myxoma was made. Intraoperatively the tumor was found extending into and closely adherent to the left pulmonary vein and could not be completely cleared off from the pulmonary venous wall. The histopathological examination of the tumor revealed it to be a myxoid malignant fibrous histiocytoma.

A transesophageal echocardiography technique to locate the kidney and monitor renal perfusion.

Monitoring the renal arterial Doppler flow velocity indices, the resistive index and pulsatility index, with ultrasound may help predict renal dysfunction. However, such monitoring has been done intermittently by transcutaneous ultrasound in the postoperative intensive care setting. In the operating room, transesophageal echocardiography (TEE) is an alternative to transcutaneous ultrasound for obtaining indices of renal perfusion. However, it is difficult to locate the right kidney using TEE. We propose a new technique to locate the left kidney that, in our experience, is simple and easy to perform. We believe, starting from a transgastric left ventricular short-axis view, turning left to locate the abdominal aorta, and following it to the origin of the left renal artery may help locate the left kidney faster than previously described techniques. We also propose a new technique to monitor these Doppler indices using TEE during the intraoperative period.

Creating awareness of an evidence-based approach to urban design.

Urban Design is a framework of urban studies that helps to understand the behavior of a city and, thus, the reasoning of its formation in a multidisciplinary way. Appropriate design policies help to attain solutions to urban problems by minimizing development impacts and by optimizing socioeconomic values of inner-city environments. However, development impacts and socio-economic values of an urban built-environment have a strong relationship with its spatial and organizational characteristics. That is, the pattern of the space organization itself helps to understand how the space is being used, and perhaps, what changes will make the space more interactive, usable, and environment-friendly. This study explores the spatial and organizational characteristics of urban morphology in evaluating urban development impacts by using the theory of space syntax. Conclusions suggest that space syntax simulates the likely effects of urban development solutions and, consequently, helps to evaluate urban design policies with data-based evidence before making recommendations for capital investments.

Aquaculture in artificially developed wetlands in urban areas: an application of the bivariate relationship between soil and surface water in landscape ecology.

Wetlands show a strong bivariate relationship between soil and surface water. Artificially developed wetlands help to build landscape ecology and make built environments sustainable. The bheries, wetlands of eastern Calcutta (India), utilize the city sewage to develop urban aquaculture that supports the local fish industries and opens a new frontier in sustainable environmental planning research.