Prevalence and risk factors of hyponatremia in hospitalized critically ill children: an observational study.

Critically ill children frequently encounter the most common and potentially life-threatening electrolyte disturbances, i.e., hyponatremia. It is an independent risk factor for prolonged hospitalization in the intensive care unit and increased in-hospital mortality. Hyponatremia occurs in up to 20%-30% of admissions in the pediatric intensive care unit (PICU). This observational study was conducted in the PICU of a tertiary care hospital in a developing country from September 2018 to September 2019. Admission criteria in our PICU are the need for mechanical ventilation, fulminant hepatic failure, vasopressor support, respiratory failure and poorly controlled seizure. We studied 256 children, aged 1 month to 18 years, with normal serum sodium at admission. In our study, 72 (28.1%) children developed hyponatremia, and about two third (n=48, 66.7%) of them developed within 72 hours of admission in PICU. The majority of children (n = 46, 63.9%) in the hyponatremic group were below 5 years. Wasted children (n = 68, 26.6%) in the hyponatremic and isonatremic groups were 20 (27.8%) and 48 (26%), respectively. The most common etiology of hyponatremia was cerebral salt wasting syndrome (n = 20, 27.8%) followed by drug-induced cases (n = 19, 26.4%). The drugs responsible were diuretics and anti-epileptics. In our study, multiorgan failure (OR = 5.05, 95%CI = 1.90-13.43; p = 0.0001), shock (OR = 7.38, 95%CI = 3.56-12.28; p = 0.0001), vasopressor use (OR = 6.74, 95%CI = 3.45-13.17; p = 0.0001) and coagulopathy (OR = 6.74, 95%CI = 3.45-13.17; p = 0.0001) were the risk factors for the development of hyponatremia. Mortality among the hyponatremic group (44.4%) was significantly higher than in the isonatremic group (21.7%). Hyponatremia is a common electrolyte disturbance found in critically ill patients and is associated with prolonged hospitalization and increased mortality.

Synthesis and active manipulation of magnetic liquid beads.

We report the fabrication and characterisation of magnetic liquid beads with a solid magnetic shell and liquid core using microfluidic techniques. The liquid beads consist of a fluorinated oil core and a polymer shell with magnetite particles. The beads are generated in a flow-focusing polydimethylsiloxane (PDMS) device and cured by photo polymerisation. We investigated the response of the liquid beads to an external magnetic field by characterising their motion towards a permanent magnet. Magnetic sorting of liquid beads in a channel was achieved with 90% efficiency. The results show that the liquid beads can be controlled magnetically and have potential applications in digital microfluidics including nucleic acid amplification, drug delivery, cell culture, sensing, and tissue engineering. The present paper also discusses the magnetophoretic behaviour of the liquid bead by varying its mass and magnetite concentration in the shell. We also demonstrated the two-dimensional self-assembly of magnetic liquid beads for potential use in digital polymerase chain reaction and digital loop mediated isothermal amplification.

Calcium alginate elastic capsules for microalgal cultivation.

Calcium alginate elastic capsules with a core-shell structure are versatile spherical solid beads that can be produced in large quantities using various techniques. This type of capsule is a promising platform for cell culture applications, owing to its mechanical elasticity and transparency. This paper reports the production of calcium alginate capsules with high consistency, and for the first time, demonstrates the feasibility of the capsules for microalgal cultivation. Cell growth analysis reveals that the vibrationally-shaken calcium alginate elastic capsule platform yielded a higher maximum cell number (4.86 × 108 cells per mL) during the cultivation period than the control solution platforms. Aquafeed and food supplements for humans are the targeted applications of this novel platform.

Isolated Bilateral Upper Limb Amelia - A Rare Case Report.

Introduction: Congenital upper limb amelia is one of the extremely rare conditions. It is defined as a complete absence of upper limbs. It may present as isolated or with other associated anomalies. Case Report: We present a case of a 2-year-old male child with congenital complete absence of bilateral upper limb. This male child was born after four female children. With the advancement in modern-era prenatal diagnostic facilities and a better understanding of fetal-maternal drug pharmacology, such cases are rare entity. Conclusion: Amelia is a very rare and challenging situation for clinicians. Regular prenatal checkup and knowledge of maternal and fetal drug interactions during pregnancy are key factors for prevention.

Late-Presenting Septic Arthritis of the Hip in Children: Variations in Presentation and a Review of 25 Hips After Surgical Debridement.

INTRODUCTION: The septic arthritis of the hip (SAH) is one of the most common musculoskeletal infections occurring in pediatric populations requiring urgent intervention. This study discusses the myriad of clinical and radiological presentations of late-presenting SAH in children and the outcomes of surgical management. METHODS: After ethical approval, we did retrospective reviews of children treated for late-presenting SAH (after five days of symptoms). We excluded late cases with established sequelae. We recorded age, duration of symptoms, clinical evaluation, and radiographs. We evaluated the final results clinically and radiologically. RESULTS: Twenty-four patients with 25 hips were eligible for evaluation. At presentation, all had decreased or painful hip movements, but none had a fever. Radiographs revealed the following changes: hip dislocation (four), capital femoral slip (seven), proximal femur/neck osteomyelitis (six), pathological fractured neck femur (two), iliac osteomyelitis (two), and early arthritic changes (two). Hip arthrotomy was done in all cases. Frank pus was found in 21 (84%) cases. Cases with capital slip and fractured neck femur required fixation with two smooth K-wires. Methicillin-resistant Staphylococcus aureus (MRSA) was isolated in three patients and tuberculosis in two cases. Clinical outcomes showed 14 patients with poor outcomes, eight with fair, and two with good. Avascular necrosis (AVN) of the femoral head was noted in 14 hips and complete femoral head resorption in nine. CONCLUSIONS: The late-presenting SAH in children has a myriad of presentations including dislocation and capital slip with unsatisfactory outcome. However, ongoing local infective processes may necessitate debridement. With limited salvage options available at the sequelae stage, awareness and training for early diagnosis and treatment may be the best way to improve the scenario. We recommend future multicenter randomized studies of predictive factors and indications of arthrotomy in late presenters.

Protein array processing software for automated semiquantitative analysis of serum antibody repertoires.

Effective immunotherapies activate natural antitumor immune responses in patients undergoing treatment. The ability to monitor immune activation in response to immunotherapy is critical in measuring treatment efficacy over time and across patient cohorts. Protein arrays are systematically arranged, large collections of annotated proteins on planar surfaces, which can be used for the characterization of disease-specific and treatment-induced antibody repertoires in individuals undergoing immunotherapy. However, the absence of appropriate image analysis and data processing software presents a substantial hurdle, limiting the uptake of this approach in immunotherapy research. We developed a first, automated semiquantitative open-source software package for the analysis of widely used protein macroarrays. The software allows accurate single array and inter-array comparative studies through the tackling of intra-array inconsistencies arising from experimental disparities. The innovative and automated image analysis process includes adaptive positioning, background identification and subtraction, removal of null signals, robust statistical analysis, and protein pair validation. The normalized values allow a convenient semiquantitative data analysis of different samples or timepoints. Enabling accurate characterization of sample series to identify disease-specific immune profiles or their relative changes in response to treatment may serve as a diagnostic or predictive tool of disease.

Microfluidic encapsulation of DNAs in liquid beads for digital PCR application.

Droplet-based microfluidics and digital polymerase chain reaction (PCR) hold significant promise for accurately detecting and quantifying pathogens. However, existing droplet-based digital PCR (ddPCR) applications have been relying exclusively on single emulsion droplets. Single emulsion droplets may not be suitable for applications such as identifying the source and pathways of water contamination where the templates must be protected against harsh environmental conditions. In this study, we developed a core-shell particle to serve as a protective framework for DNAs, with potential applications in digital PCR. We employed a high-throughput and facile flow-focusing microfluidic device to generate liquid beads, core-shell particles with liquid cores, which provided precise control over process parameters and consequently particle characteristics. Notably, the interfacial interaction between the core and shell liquids could be adjusted without adding surfactants to either phase. As maintaining stability is essential for ensuring the accuracy of digital PCR (dPCR), we investigated parameters that affect the stability of core-shell droplets, including surfactants in the continuous phase and core density. As a proof of concept, we encapsulated a series of human faecal DNA samples in the core-shell droplets and the subsequent liquid beads. The core-shell particles ensure contamination-free encapsulation of DNA in the core. The volume of the core droplets containing the PCR mixture is only 0.12 nL. Our experimental results indicate that the liquid beads formulated using our technique can amplify the encapsulated DNA and be used for digital PCR without interfering with the fluorescence signal. We successfully demonstrated the ability to detect and quantify DNA under varying concentrations. These findings provide new insights and a step change in digital PCR that could benefit various applications, including the detection and tracking of environmental pollution.

Precise, wide field, and low-cost imaging and analysis of core-shell beads for digital polymerase chain reaction.

Digital droplet reactors have become a valuable tool for the analysis of single cells, organisms, or molecules by discretising reagents into picolitre or nanolitre volumes. However, DNA-based assays typically require processing of samples on the scale of tens of microlitres, with the detection of as few as one or as many as a hundred thousand fragments. Through the present work, we introduce a flow-focusing microfluidic device that produces 120 picolitre core-shell beads, which are assembled into a monolayer in a Petri dish for visualization and analysis. The bead assembly is subjected to polymerase chain reaction (PCR) amplification and fluorescence detection to digitally quantify the DNA concentration of the sample. We use a low-cost 21-megapixel digital camera and macro lens to capture wide-field fluorescence images with a 10-30 mm2 field-of-view at magnifications ranging from 5× to 2.5×. A customised Python script analysed the acquired images. Our study demonstrates the ability to perform digital PCR analysis of the entire bead assembly through end-point imaging and compare the results with those obtained through RT-qPCR.

Biodegradable Polymers for Micro Elastofluidics.

Micro elastofluidics is an emerging research field that encompasses characteristics of conventional microfluidics and fluid-structure interactions. Micro elastofluidics is expected to enable practical applications, for instance, where direct contact between biological samples and fluid handling systems is required. Besides design optimization, choosing a proper material is critical to the practical use of micro elastofluidics upon interaction with biological interface and after its functional lifetime. Biodegradable polymers are one of the most studied materials for this purpose. Micro elastofluidic devices made of biodegradable polymers possess exceptional mechanical elasticity, excellent bio compatibility, and structural degradability into non-toxic products. This article provides an insightful and systematic review of the utilization of biodegradable polymers in digital and continuous-flow micro elastofluidics.

Core-Shell Particles: From Fabrication Methods to Diverse Manipulation Techniques.

Core-shell particles are micro- or nanoparticles with solid, liquid, or gas cores encapsulated by protective solid shells. The unique composition of core and shell materials imparts smart properties on the particles. Core-shell particles are gaining increasing attention as tuneable and versatile carriers for pharmaceutical and biomedical applications including targeted drug delivery, controlled drug release, and biosensing. This review provides an overview of fabrication methods for core-shell particles followed by a brief discussion of their application and a detailed analysis of their manipulation including assembly, sorting, and triggered release. We compile current methodologies employed for manipulation of core-shell particles and demonstrate how existing methods of assembly and sorting micro/nanospheres can be adopted or modified for core-shell particles. Various triggered release approaches for diagnostics and drug delivery are also discussed in detail.

Dynamic Behaviours of Monodisperse Double Emulsion Formation in a Tri-Axial Capillary Device.

We investigated experimentally, analytically, and numerically the formation process of double emulsion formations under a dripping regime in a tri-axial co-flow capillary device. The results show that mismatches of core and shell droplets under a given flow condition can be captured both experimentally and numerically. We propose a semi-analytical model using the match ratio between the pinch-off length of the shell droplet and the product of the core growth rate and its pinch-off time. The mismatch issue can be avoided if the match ratio is lower than unity. We considered a model with the wall effect to predict the size of the matched double emulsion. The model shows slight deviations with experimental data if the Reynolds number of the continuous phase is lower than 0.06 but asymptotically approaches good agreement if the Reynolds number increases from 0.06 to 0.14. The numerical simulation generally agrees with the experiments under various flow conditions.

Crustwater: Modeling Hydrophobic Solvation.

We describe Crustwater, a statistical mechanical model of nonpolar solvation in water. It treats bulk water using the Cage Water model and introduces a crust, i.e., a solvation shell of coordinated partially structured waters. Crustwater is analytical and fast to compute. We compute here solvation vs temperature over the liquid range, and vs pressure and solute size. Its thermal predictions are as accurate as much more costly explicit models such as TIP4P/2005. This modeling gives new insights into the hydrophobic effect: (1) that oil-water insolubility in cold water is due to solute-water (SW) translational entropy and not water-water (WW) orientations, even while hot water is dominated by WW cage breaking, and (2) that a size transition at the Angstrom scale, not the nanometer scale, takes place as previously predicted.

Calcium Ion Binding to the Mutants of Calmodulin: A Structure-Based Computational Predictive Model of Binding Affinity Using a Charge Scaling Approach in Molecular Dynamics Simulation.

The binding of calcium ions (Ca2+) to the calcium-binding proteins (CBPs) controls a plethora of regulatory processes. Among the roles played by CBPs in several diseases, the onset and progress of some cardiovascular diseases are caused by mutations in calmodulin (CaM), an important member of CBPs. Rationalization and prediction of the binding affinity of Ca2+ ions to the CaM can play important roles in understanding the origin of cardiovascular diseases. However, there is no robust structure-based computational method for predicting the binding affinity of Ca2+ ions to the different forms of CBPs in general and CaM in particular. In the current work, we have devised a fast yet accurate computational technique to accurately calculate the binding affinity of Ca2+ to the different forms of CaM. This method combines the well-known molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) method and a charge scaling approach developed by previous authors that takes care of the polarization of CaM and Ca2+ ions. Our detailed analysis of the different components of binding free energy shows that subtle changes in electrostatics and van der Waals contribute to the difference in the binding affinity of mutants from that of the wild type (WT), and the charge scaling approach is superior in calculating these subtle changes in electrostatics as compared to the nonpolarizable force field used in this work. A statistically significant regression model made from our binding free energy calculations gives a correlation coefficient close to 0.8 to the experimental results. This structure-based predictive model can open up a new strategy to understand and predict the binding of Ca2+ to the mutants of CBPs, in general.

Analytical 2-Dimensional Model of Nonpolar and Ionic Solvation in Water.

A goal in computational chemistry is computing hydration free energies of nonpolar and charged solutes accurately, but with much greater computational speeds than in today's explicit-water simulations. Here, we take one step in that direction: a simple model of solvating waters that is analytical and thus essentially instantaneous to compute. Each water molecule is a 2-dimensional dipolar hydrogen-bonding disk that interacts around small circular solutes with different nonpolar and charge interactions. The model gives good qualitative agreement with experiments. As a function of the solute radius, it gives the solvation free energy, enthalpy and entropy as a function of temperature for the inert gas series Ne, Ar, Kr, and Xe. For anions and cations, it captures relatively well the trends versus ion radius. This approach should be readily generalizable to three dimensions.

Clinical characteristic and epidemiological features of SARS CoV -2 disease patients from a COVID 19 designated Hospital in New Delhi.

SARS CoV -2 infection is rapidly evolving as a serious global pandemic. The present study describes the clinical characteristics of SARS CoV-2 infection patients. The Samples were subjected to RT - PCR or Rapid Antigen test for diagnosis of SARS CoV- 2. A cohort of 3745 patients with confirmed diagnosis of SARS CoV -2 infection in a tertiary care center in New Delhi, India were included in this study. Data was collected from offline and online medical records over a period of six months. Amongst 3745 SARS CoV -2 infected patients, 2245 (60%) were symptomatic and 1500 (40%) were asymptomatic. Most common presenting symptom was cough (49.3%) followed febrile episodes (47.1%), breathlessness (42.7%) and sore throat (35.1%). Cough along with breathlessness (24.1) was the most common combination of symptoms followed by fever with cough (22.7). The most common comorbidity found among symptomatic group was diabetes (42.5%) followed by hypertension (21.4%) and chronic kidney disease (18%). Comorbidities like diabetes mellitus, chronic diseases of lungs, heart and kidneys were found to be common in symptomatic group and this was found to be statistically significant (p<0.05). COVID-19 is an evolving disease and data from our study help in understanding the clinic-epidemiological profile of patients. This article is protected by copyright. All rights reserved.

Simple and Continuous Fabrication of Janus Liquid Marbles with Tunable Particle Coverage Based on Controlled Droplet Impact.

Liquid marbles are gaining increased attention because of their added advantages such as low evaporation rates, less friction, and ease of manipulation over the pristine liquid drop. Their functionalities could be further enhanced by incorporating different types of particles (size, hydrophobicity, chemical properties, etc.), commonly called Janus liquid marbles (JLMs). However, their fabrication process remains a challenge, especially when we require continuous production. Here, we present a simple and fast approach for the fabrication of JLMs covered with nano- and microparticles in an additive-free environment based on the controlled impact of a water drop over the particle beds. The fabrication process involves collection of polyvinylidene difluoride particles (PVDF, particle type 1) by a water drop followed by its impact over an uncompressed bed of black toner particles (BTP, particle type 2). The whole process takes a time of approximately 30 ms only. The drop impact and the condition of the JLM formation were explained based on the Weber number (We) and maximum spread (ßm) analysis. A theoretical model based on the energy balance analysis is performed to calculate the maximum spreading (ßm), and the experimental and theoretical analyses are found to be in good agreement. Tunability in particle coverage is demonstrated by varying the droplet volume in the range of 5-15 µL. We further extend this strategy for the fast and continuous production of nearly identical JLMs, which could enhance the capabilities of open-surface microfluidic applications.

Surfactant-Mediated Collapse of Liquid Marbles and Directed Assembly of Particles at the Liquid Surface.

Extensive research is being devoted to both the fundamental and applied aspects of liquid marbles (LMs). However, influence of the surface tension of the liquid substrate on the stability of the LMs and LM-mediated capillary interaction remains unexplored. In this work, we unveil the role of the surface tension of the liquid substrate on the collapse of multilayered LMs and apply this knowledge for realizing a dense planar assembly of microparticles triggered by LM-mediated capillary interactions. Experiments and analysis show that the required surface tension for the collapse is dependent on the volume of the LMs. The larger LMs are less stable, and thus collapse at a higher surface tension than that required for smaller LMs. The results are explained on the basis of the balance between surface tension forces acting on the LM ( Fs) and its weight ( Fw). Force analysis reveals that the collapse of the LM on the liquid substrate occurs when the surface tension force approaches to its weight, that is, when Fs ≈ Fw. This has been verified for LMs having volume in the range 6-10 µL. The experiments with different surfactants (an anionic and a cationic) lead to similar results which indicate that the collapse condition of the LMs is mainly dependent on their weight and the surface tension of the liquid substrate. Further, we demonstrate the LM-mediated assembly of particles at the liquid surface, and interestingly, the LM can be collapsed once the assembly is completed, leading to a denser well-packed assembled structure. We believe that the presented results could provide new insights in the fields of microfluidics, particle patterning, and assembly.

Physical Growth, Morbidity Profile and Mortality Among Healthy Late Preterm Neonates.

OBJECTIVE: To compare the physical growth outcomes, morbidity profile and mortality at an age of 12 months among late preterm (34 0/7to 36 6/7) neonates to term (37 0/7to 41 6/7) neonates. STUDY DESIGN: Prospective cohort study. SETTING: A tertiary care center of Northern India during 2014-2015. PARTICIPANTS: 200 apparently healthy late preterms and term infants, followed up to 12 months of age. MAIN OUTCOME MEASURES: Physical growth parameters, morbidity profile and mortality. RESULTS: At mean age of 12 months, mean (SD) weight, length and head circumference of late preterms were 7.4 (0.8) kg, 69.2 (2.5) cm and 43.0 (1.1) cm, respectively; which were significantly lower than that of the full term infants [8.7 (1.6) kg, 72.2 (3.1) cm and 44.2 (1.1) cm] (P< 0.001). On univariate analysis, late preterm group was associated with higher odds (95% CI) of being underweight [5.6 (3.4, 5.5)], stunted [3.5 (2.1, 5.8)] and wasted [3.6 (1.9, 6.9)]. On multivariate analysis, only adjusted odds of late preterms becoming underweight by one year was significant [OR 4.1; 95% CI (1.6, 10.4)]. Feeding difficulties, jaundice and re-hospitalization rates were significantly higher in the late preterm group. The median (IQR) episodes per baby for late preterms as compared to terms for diarrhea [1.84 (0,3) vs 1.14 (0,2) (P <0.001)], and fever [1.33 (0,2) vs. 0.95 (0,2) (P = 0.01)] were higher. CONCLUSION: Healthy late preterms are at significantly higher risk of being underweight in the first year of life, in addition to having significantly higher morbidity.