A Cross-Sectional Study Examining the Relationship Between Malnutrition and Gross Motor Function in Cerebral Palsy.

Introduction Cerebral palsy (CP) characterizes a range of permanent, nonprogressive symptoms of postural and motor dysfunction caused by an insult to the developing central nervous system in a fetus or an infant. CP manifests early in life, often within the first two to three years of age. CP is associated with poor growth, that is the deviation from the normal growth parameters. The prevalence of CP ranges from 2.0 to 3.5 per 1000 live births in high-income countries which is comparable to the estimates from low-income countries. Antenatal and perinatal insults are among the most commonly reported causes of CP; however, a large number of cases do not have an identifiable etiology of CP. The current study aims to examine the relationship between malnutrition and gross motor function in children with CP. Materials and Methods This study was conducted at the Department of Pediatrics and Neonatology, Nehru Hospital, Baba Raghav Das (BRD) Medical College, Gorakhpur (UP) over a period of one year (August 2020 to July 2021) after obtaining ethical clearance from the College Research Council. Children of age 1-15 years with CP attending the pediatric outpatient and inpatient departments were enrolled as the study participants after obtaining informed consent from a legal guardian. Assessment of motor function was done using the gross motor function classification system (GMFCS). Associations of malnutrition across levels of gross motor function were tested using Chi-square or Fisher's exact test whichever was applicable. Statistical significance was set at p < 0.05 as significant. Data was analyzed using IBM SPSS Statistics for Windows, Version 21 (Released 2012; IBM Corp., Armonk, New York, United States). Result We analyzed 110 children with a diagnosis of CP (median age 6.5 years, interquartile range (IQR) 4.4-9.0 years). The majority (65/110; 59%) of the patients were male, and 68 (61.8%) delivered at term gestation. The most common presenting symptom among children with CP was seizures (79/110; 72.3%), the second most common being delayed milestones among 73 (66.8%), followed by difficulty in breathing among 63 (57.5%). The association between the anthropometric index of participants and GMFCS was found to be highly significant. Conclusion Most CP patients were facing gross motor disturbances. Spastic type of CP was most frequent, and more than half of the patients experienced feeding difficulty. A statistically significant association was found between gross motor functioning and the prevalence of malnutrition and stunting.

Dynamic metabolism of endothelial triglycerides protects against atherosclerosis in mice.

Blood vessels are continually exposed to circulating lipids, and elevation of ApoB-containing lipoproteins causes atherosclerosis. Lipoprotein metabolism is highly regulated by lipolysis, largely at the level of the capillary endothelium lining metabolically active tissues. How large blood vessels, the site of atherosclerotic vascular disease, regulate the flux of fatty acids (FAs) into triglyceride-rich (TG-rich) lipid droplets (LDs) is not known. In this study, we showed that deletion of the enzyme adipose TG lipase (ATGL) in the endothelium led to neutral lipid accumulation in vessels and impaired endothelial-dependent vascular tone and nitric oxide synthesis to promote endothelial dysfunction. Mechanistically, the loss of ATGL led to endoplasmic reticulum stress-induced inflammation in the endothelium. Consistent with this mechanism, deletion of endothelial ATGL markedly increased lesion size in a model of atherosclerosis. Together, these data demonstrate that the dynamics of FA flux through LD affects endothelial cell homeostasis and consequently large vessel function during normal physiology and in a chronic disease state.

Probing Interlayer Interactions and Commensurate-Incommensurate Transition in Twisted Bilayer Graphene through Raman Spectroscopy.

Twisted 2D layered materials have garnered much attention recently as a class of 2D materials whose interlayer interactions and electronic properties are dictated by the relative rotation/twist angle between the adjacent layers. In this work, we explore a prototype of such a twisted 2D system, artificially stacked twisted bilayer graphene (TBLG), where we probe, using Raman spectroscopy, the changes in the interlayer interactions and electron-phonon scattering pathways as the twist angle is varied from 0° to 30°. The long-range Moiré potential of the superlattice gives rise to additional intravalley and intervalley scattering of the electrons in TBLG, which has been investigated through their Raman signatures. Density functional theory (DFT) calculations of the electronic band structure of the TBLG superlattices were found to be in agreement with the resonant Raman excitations across the van Hove singularities in the valence and conduction bands predicted for TBLG due to hybridization of bands from the two layers. We also observe that the relative rotation between the graphene layers has a marked influence on the second order overtone and combination Raman modes signaling a commensurate-incommensurate transition in TBLG as the twist angle increases. This serves as a convenient and rapid characterization tool to determine the degree of commensurability in TBLG systems.

Suppression of angiopoietin-like 4 reprograms endothelial cell metabolism and inhibits angiogenesis.

Angiopoietin-like 4 (ANGPTL4) is known to regulate various cellular and systemic functions. However, its cell-specific role in endothelial cells (ECs) function and metabolic homeostasis remains to be elucidated. Here, using endothelial-specific Angptl4 knock-out mice (Angptl4iΔEC), and transcriptomics and metabolic flux analysis, we demonstrate that ANGPTL4 is required for maintaining EC metabolic function vital for vascular permeability and angiogenesis. Knockdown of ANGPTL4 in ECs promotes lipase-mediated lipoprotein lipolysis, which results in increased fatty acid (FA) uptake and oxidation. This is also paralleled by a decrease in proper glucose utilization for angiogenic activation of ECs. Mice with endothelial-specific deletion of Angptl4 showed decreased pathological neovascularization with stable vessel structures characterized by increased pericyte coverage and reduced permeability. Together, our study denotes the role of endothelial-ANGPTL4 in regulating cellular metabolism and angiogenic functions of EC.

Loss of cis-PTase function in the liver promotes a highly penetrant form of fatty liver disease that rapidly transitions to hepatocellular carcinoma.

Obesity-linked fatty liver is a significant risk factor for hepatocellular carcinoma (HCC)1,2; however, the molecular mechanisms underlying the transition from non-alcoholic fatty liver disease (NAFLD) to HCC remains unclear. The present study explores the role of the endoplasmic reticulum (ER)-associated protein NgBR, an essential component of the cis-prenyltransferases (cis-PTase) enzyme3, in chronic liver disease. Here we show that genetic depletion of NgBR in hepatocytes of mice (N-LKO) intensifies triacylglycerol (TAG) accumulation, inflammatory responses, ER/oxidative stress, and liver fibrosis, ultimately resulting in HCC development with 100% penetrance after four months on a high-fat diet. Comprehensive genomic and single cell transcriptomic atlas from affected livers provides a detailed molecular analysis of the transition from liver pathophysiology to HCC development. Importantly, pharmacological inhibition of diacylglycerol acyltransferase-2 (DGAT2), a key enzyme in hepatic TAG synthesis, abrogates diet-induced liver damage and HCC burden in N-LKO mice. Overall, our findings establish NgBR/cis-PTase as a critical suppressor of NAFLD-HCC conversion and suggests that DGAT2 inhibition may serve as a promising therapeutic approach to delay HCC formation in patients with advanced non-alcoholic steatohepatitis (NASH).

Clinical Manifestations and Disability After Acute Encephalitis Syndrome Among Pediatric Patients in Eastern Uttar Pradesh: A Retrospective Analysis.

Introduction Acute encephalitis syndrome (AES) in pediatric patients can lead to a range of disabilities, affecting various aspects of their daily lives. The disease is caused by a diverse group of pathogens including viruses, bacteria, fungi, and protozoans. While significant progress has been made in combating the acute phase of the disease, the lingering effects on the physical, cognitive, and emotional well-being of survivors have yet to be comprehensively explored. The present retrospective study was conducted to investigate disabilities including neurological squeals and functional impairment challenges faced by AES survivors as they navigate life with disabilities. Methods We conducted a comprehensive retrospective analysis of medical records of pediatric patients diagnosed with AES and evaluated their follow-up visits at regular intervals during the study period. The Liverpool scoring system and clinical examinations were utilized to assess the presence and severity of disabilities in the patients. Results A total of 134 pediatric AES patients were included in the study; among them, 56% were males, and 44% were females. The mean age of the participants was 4.8 ± 3.1 years, and the mean number of days of hospitalization was 27.8 ± 30.8. Only 9.7% of the patients were found to be Japanese encephalitis (JE)-positive, and 87.5% of the participants were found to have disabilities in some or the other domain of the Liverpool Outcome Score (LOS). There were statistically significant correlations between the age of the patients and the LOS at follow-up. Post-recovery disabilities were more severe among patients who required a prolonged duration of hospitalization. Conclusion A considerable proportion of AES survivors are left with disabilities. Causes other than Japanese encephalitis are now more frequent in AES. The need for prolonged hospitalization is related to more severe disabilities. The early identification of disabilities through the Liverpool scoring system and clinical examination can aid in implementing appropriate intervention strategies.

Energy Harvesting Using ZnO Nanosheet-Decorated 3D-Printed Fabrics.

In this work, we decorated piezoresponsive atomically thin ZnO nanosheets on a polymer surface using additive manufacturing (three-dimensional (3D) printing) technology to demonstrate electrical-mechanical coupling phenomena. The output voltage response of the 3D-printed architecture was regulated by varying the external mechanical pressures. Additionally, we have shown energy generation by placing the 3D-printed fabric on the padded shoulder strap of a bag with a load ranging from ∼5 to ∼75 N, taking advantage of the excellent mechanical strength and flexibility of the coated 3D-printed architecture. The ZnO coating layer forms a stable interface between ZnO nanosheets and the fabric, as confirmed by combining density functional theory (DFT) and electrical measurements. This effectively improves the output performance of the 3D-printed fabric by enhancing the charge transfer at the interface. Therefore, the present work can be used to build a new infrastructure for next-generation energy harvesters capable of carrying out several structural and functional responsibilities.

Physics of moderately stretched electrified jets in electrohydrodynamic jet printing.

Electrohydrodynamic (EHD) jet printing involves the deposition of a liquid jet issuing from a needle stretched under the effect of a strong electric field between the needle and a collector plate. Unlike the geometrically independent classical cone-jet observed at low flow rates and high applied electric fields, at a relatively high flow rate and moderate electric field, EHD jets are moderately stretched. Jetting characteristics of such moderately stretched EHD jets differ from the typical cone-jet due to the nonlocalized cone-to-jet transition. Hence, we describe the physics of the moderately stretched EHD jet applicable to the EHD jet printing process through numerical solutions of a quasi-one-dimensional model of the EHD jet and experiments. Through comparison with experimental measurements, we show that our simulations correctly predict the jet shape for varying flow rates and applied potential difference. We present the physical mechanism of inertia-dominated slender EHD jets based on the dominant driving and resisting forces and relevant dimensionless numbers. We show that the slender EHD jet stretches and accelerates primarily due to the balance of driving tangential electric shear and resisting inertia forces in the developed jet region, whereas in the vicinity of the needle, driving charge repulsion and resisting surface tension forces govern the cone shape. The findings of this study can help in operational understanding and better control of the EHD jet printing process.

Spontaneous hydrogen production using gadolinium telluride.

Developing materials for controlled hydrogen production through water splitting is one of the most promising ways to meet current energy demand. Here, we demonstrate spontaneous and green production of hydrogen at high evolution rate using gadolinium telluride (GdTe) under ambient conditions. The spent materials can be reused after melting, which regain the original activity of the pristine sample. The phase formation and reusability are supported by the thermodynamics calculations. The theoretical calculation reveals ultralow activation energy for hydrogen production using GdTe caused by charge transfer from Te to Gd. Production of highly pure and instantaneous hydrogen by GdTe could accelerate green and sustainable energy conversion technologies.

Mesenchymal stromal cells, metabolism, and mitochondrial transfer in bone marrow normal and malignant hematopoiesis.

Hematopoietic stem cell (HSC) transplantation-based treatments are in different phases of clinical development, ranging from current therapies to a promise in the repair and regeneration of diseased tissues and organs. Mesenchymal stromal/stem cells (MSCs), which are fibroblast-like heterogeneous progenitors with multilineage differentiation (osteogenic, chondrogenic, and adipogenic) and self-renewal potential, and exist in the bone marrow (BM), adipose, and synovium, among other tissues, represent one of the most widely used sources of stem cells in regenerative medicine. MSCs derived from bone marrow (BM-MSCs) exhibit a variety of traits, including the potential to drive HSC fate and anti-inflammatory and immunosuppressive capabilities via paracrine activities and interactions with the innate and adaptive immune systems. The role of BM-MSC-derived adipocytes is more controversial and may act as positive or negative regulators of benign or malignant hematopoiesis based on their anatomical location and functional crosstalk with surrounding cells in the BM microenvironment. This review highlights the most recent clinical and pre-clinical findings on how BM-MSCs interact with the surrounding HSCs, progenitors, and immune cells, and address some recent insights on the mechanisms that mediate MSCs and adipocyte metabolic control through a metabolic crosstalk between BM microenvironment cells and intercellular mitochondrial transfer in normal and malignant hematopoiesis.

A Prospective Randomized Study Comparing the Bolus Doses of Norepinephrine and Phenylephrine for the Treatment of Spinal Induced Hypotension in Cesarean Section.

BACKGROUND: Spinal anesthetic-induced hypotension is the most worrisome complication for patients undergoing cesarean section under spinal anesthesia. The present study compares norepinephrine and phenylephrine bolus for the treatment of hypotension during spinal anesthesia for cesarean section. METHODS: One hundred twenty- six women aged between 22 and 40 years with singleton pregnancy classified to the American Society of Anesthesiologists (ASA) physical class I and II posted for elective cesarean section under spinal anesthesia were randomly divided into two groups of 63 each. Group I patients received phenylephrine 50 mcg (microgram) as an intravenous bolus, and Group II received 4 mcg of norepinephrine as an intravenous bolus to treat spinal hypotension. RESULTS: On comparing the demographic data of the patients in terms of age, weight, height, ASA Grade, level of block and surgery time no significant differences were found between the groups. Similarly, the fetal parameters were found to be not significantly different between the groups. However, the number of bolus doses of vasopressors required for the treatment of spinal-induced hypotension was significantly reduced in Group II (p=0.02). The frequency of bradycardia was found to be higher in patients who were given phenylephrine as compared to patients administered noradrenaline boluses (p=0.03). Five (7.93%) patients had shivering in Group I, while similar episodes were observed in 10 (15.87%) patients (p=0.05). Moreover, no significant difference was observed in comparing the heart rate and mean arterial pressure between the groups. CONCLUSION: Intermittent boluses of norepinephrine are found to be effective in the management of spinal­induced hypotension during caesarean section.

Interfacial layers between ion and water detected by terahertz spectroscopy.

Dynamic fluctuations in the hydrogen-bond network of water occur from femto- to nanosecond timescales and provide insight into the structural/dynamical aspects of water at ion-water interfaces. Employing terahertz spectroscopy assisted with molecular dynamics simulations, we study aqueous chloride solutions of five monovalent cations, namely, Li, Na, K, Rb, and Cs. We show that ions modify the behavior of the surrounding water molecules and form interfacial layers of water around them with physical properties distinct from those of bulk water. Small cations with high charge densities influence the kinetics of water well beyond the first solvation shell. At terahertz frequencies, we observe an emergence of fast relaxation processes of water with their magnitude following the ionic order Cs > Rb > K > Na > Li, revealing an enhanced population density of weakly coordinated water at the ion-water interface. The results shed light on the structure breaking tendency of monovalent cations and provide insight into the properties of ionic solutions at the molecular level.

Strong Anharmonicity-Induced Low Thermal Conductivity and High n-type Mobility in the Topological Insulator Bi1.1 Sb0.9 Te2 S.

Intrinsically low lattice thermal conductivity (κlat ) while maintaining the high carrier mobility (µ) is of the utmost importance for thermoelectrics. Topological insulators (TI) can possess high µ due to the metallic surface states. TIs with heavy constituents and layered structure can give rise to high anharmonicity and are expected to show low κlat . Here, we demonstrate that Bi1.1 Sb0.9 Te2 S (BSTS), which is a 3D bulk TI, exhibits ultra-low κlat of 0.46 Wm-1 K-1 along with high µ of ≈401 cm2  V-1 s-1 . Sound velocity measurements and theoretical calculations suggest that chemical bonding hierarchy and high anharmonicity play a crucial role behind such ultra-low κlat . BSTS possesses low energy optical phonons which strongly couple with the heat carrying acoustic phonons leading to ultra-low κlat . Further, Cl has been doped at the S site of BSTS which increases the electron concentration and reduces the κlat resulting in a promising n-type thermoelectric figure of merit (zT) of ≈0.6 at 573 K.

Probing Adaptation of Hydration and Protein Dynamics to Temperature.

Protein dynamics is strongly influenced by the surrounding environment and physiological conditions. Here we employ broadband megahertz-to-terahertz spectroscopy to explore the dynamics of water and myoglobin protein on an extended time scale from femto- to nanosecond. The dielectric spectra reveal several relaxations corresponding to the orientational polarization mechanism, including the dynamics of loosely bound, tightly bound, and bulk water, as well as collective vibrational modes of protein in an aqueous environment. The dynamics of loosely bound and bulk water follow non-Arrhenius behavior; however, the dynamics of water molecules in the tightly bound layer obeys the Arrhenius-type relation. Combining molecular simulations and effective-medium approximation, we have determined the number of water molecules in the tightly bound hydration layer and studied the dynamics of protein as a function of temperature. The results provide the important impact of water on the biochemical functions of proteins.

Targeting the vasculature in cardiometabolic disease.

Obesity has reached epidemic proportions and is a major contributor to insulin resistance (IR) and type 2 diabetes (T2D). Importantly, IR and T2D substantially increase the risk of cardiovascular (CV) disease. Although there are successful approaches to maintain glycemic control, there continue to be increased CV morbidity and mortality associated with metabolic disease. Therefore, there is an urgent need to understand the cellular and molecular processes that underlie cardiometabolic changes that occur during obesity so that optimal medical therapies can be designed to attenuate or prevent the sequelae of this disease. The vascular endothelium is in constant contact with the circulating milieu; thus, it is not surprising that obesity-driven elevations in lipids, glucose, and proinflammatory mediators induce endothelial dysfunction, vascular inflammation, and vascular remodeling in all segments of the vasculature. As cardiometabolic disease progresses, so do pathological changes in the entire vascular network, which can feed forward to exacerbate disease progression. Recent cellular and molecular data have implicated the vasculature as an initiating and instigating factor in the development of several cardiometabolic diseases. This Review discusses these findings in the context of atherosclerosis, IR and T2D, and heart failure with preserved ejection fraction. In addition, novel strategies to therapeutically target the vasculature to lessen cardiometabolic disease burden are introduced.

Supramolecular Engineering of Alkylated, Fluorinated, and Mixed Amphiphiles.

The rational design of perfluorinated amphiphiles to control the supramolecular aggregation in an aqueous medium is still a key challenge for the engineering of supramolecular architectures. Here, the synthesis and physical properties of six novel non-ionic amphiphiles are presented. The effect of mixed alkylated and perfluorinated segments in a single amphiphile is also studied and compared with only alkylated and perfluorinated units. To explore their morphological behavior in an aqueous medium, dynamic light scattering (DLS) and cryogenic transmission electron microscopy/electron microscopy (cryo-TEM/EM) measurements are used. The assembly mechanisms with theoretical investigations are further confirmed, using the Martini model to perform large-scale coarse-grained molecular dynamics simulations. These novel synthesized amphiphiles offer a greater and more systematic understanding of how perfluorinated systems assemble in an aqueous medium and suggest new directions for rational designing of new amphiphilic systems and interpreting their assembly process.

Electroreduction of CO2 with Tunable Selectivity on Au-Pd Bimetallic Catalyst: A First Principle Study.

The electroreduction of CO2 exhibits great promise in mitigating CO2 from the atmosphere. However, it is quite challenging to produce C1 products selectively on metal surfaces due to inefficient binding of CO with a metal surface. Here, using density functional theory, we studied an experimentally viable system of gold alloyed with a high CO-binding metal palladium. It is observed that the selectivity toward formic acid and methane can be tuned on Au-Pd bimetallic catalysts. Pd-rich alloy surfaces such as Pd deposited on the (211) surface of Au (Pd@Au) are found to be highly selective toward formic acid with an ultralow limiting potential of -0.23 V vs SHE. Interestingly, as the surface of the alloy become Au-rich, the selectivity toward methane increases. Among all the Au-Pd bimetallic systems, the Au-rich (211) surface of Au3Pd alloy has a very low limiting potential of -0.9 V vs SHE for CO2 electroreduction to methane. The selectivity toward methane on this surface is enhanced due to its optimum CO* binding and the ease of CO* protonation to CHO*. The higher feasibility of CO* protonation is a result of the stabilization of adsorbed CHO*. This stabilization is attributed to the interaction of both C and O of the CHO* molecule with the surface Au and Pd. It is found that the selectivity of a catalyst depends upon the stability of various intermediates, which can be regulated by modifying the composition of Au and Pd in the alloy. The results presented here demonstrate broad opportunities to tune the selectivity of the catalyst with varying alloy compositions, which will help to develop novel catalysts for CO2 electroreduction.

Brown adipose TRX2 deficiency activates mtDNA-NLRP3 to impair thermogenesis and protect against diet-induced insulin resistance.

Brown adipose tissue (BAT), a crucial heat-generating organ, regulates whole-body energy metabolism by mediating thermogenesis. BAT inflammation is implicated in the pathogenesis of mitochondrial dysfunction and impaired thermogenesis. However, the link between BAT inflammation and systematic metabolism remains unclear. Herein, we use mice with BAT deficiency of thioredoxin-2 (TRX2), a protein that scavenges mitochondrial reactive oxygen species (ROS), to evaluate the impact of BAT inflammation on metabolism and thermogenesis and its underlying mechanism. Our results show that BAT-specific TRX2 ablation improves systematic metabolic performance via enhancing lipid uptake, which protects mice from diet-induced obesity, hypertriglyceridemia, and insulin resistance. TRX2 deficiency impairs adaptive thermogenesis by suppressing fatty acid oxidation. Mechanistically, loss of TRX2 induces excessive mitochondrial ROS, mitochondrial integrity disruption, and cytosolic release of mitochondrial DNA, which in turn activate aberrant innate immune responses in BAT, including the cGAS/STING and the NLRP3 inflammasome pathways. We identify NLRP3 as a key converging point, as its inhibition reverses both the thermogenesis defect and the metabolic benefits seen under nutrient overload in BAT-specific Trx2-deficient mice. In conclusion, we identify TRX2 as a critical hub integrating oxidative stress, inflammation, and lipid metabolism in BAT, uncovering an adaptive mechanism underlying the link between BAT inflammation and systematic metabolism.

The origin and impact of bound water around intrinsically disordered proteins.

Proteins and water couple dynamically over a wide range of time scales. Motivated by their central role in protein function, protein-water dynamics and thermodynamics have been extensively studied for structured proteins, where correspondence to structural features has been made. However, properties controlling intrinsically disordered protein (IDP)-water dynamics are not yet known. We report results of megahertz-to-terahertz dielectric spectroscopy and molecular dynamics simulations of a group of IDPs with varying charge content along with structured proteins of similar size. Hydration water around IDPs is found to exhibit more heterogeneous rotational and translational dynamics compared with water around structured proteins of similar size, yielding on average more restricted dynamics around individual residues of IDPs, charged or neutral, compared with structured proteins. The on-average slower water dynamics is found to arise from excess tightly bound water in the first hydration layer, which is related to greater exposure to charged groups. The more tightly bound water to IDPs correlates with the smaller hydration shell found experimentally, and affects entropy associated with protein-water interactions, the contribution of which we estimate based on the dielectric measurements and simulations. Water-IDP dynamic coupling at terahertz frequencies is characterized by the dielectric measurements and simulations.

Feature Blending: An Approach toward Generalized Machine Learning Models for Property Prediction.

From studying the atomic structure and chemical behavior to the discovery of new materials and investigating properties of existing materials, machine learning (ML) has been employed in realms that are arduous to probe experimentally. While numerous highly accurate models, specifically for property prediction, have been reported in the literature, there has been a lack of a generalized framework. Herein we propose a novel feature selection approach that enables the development of a unified ML model for property prediction for several classes of materials. It involves an ingenious blending of selected features from various classes of data such that the resultant feature set equips the model with global data descriptors capturing both class-specific as well as global traits. We took accurate band gaps of three distinct classes of 2D materials as our target property to develop the proposed feature blending approach. Using Gaussian process regression (GPR) with the blended features, the ML model developed here resulted in an average root-mean-squared error of 0.12 eV for unseen data belonging to any of the participating classes. The feature blending approach proposed here can be extended to additional classes of materials and also to predict other properties.