Indian Guidelines for Indications and Timing of Intervention for Common Congenital Heart Diseases: Revised and Updated Consensus Statement of the Working Group on Management of Congenital Heart Diseases. Abridged Secondary Publication.

Justification: A number of guidelines are available for management of congenital heart diseases from infancy to adult life. However, these guidelines are for patients living in high income countries. Separate guidelines, applicable to Indian children, are required when recommending an intervention for congenital heart diseases, as often these patients present late in the course of the disease and may have co-existing morbidities and malnutrition.

Alterations to dual stream connectivity predicts response to aphasia therapy following stroke.

Background: Predicting aphasia recovery is difficult due to a high variability in treatment response. Detailed measures of treatment response are compounded by a dearth of information that examine brain connections that contribute to clinical improvement. In this study we measure alterations to cortical connectivity pathways during a therapy paradigm to detect whether key brain connections that contribute to language recovery can be detected prior to therapy.

Protein corona formation moderates the release kinetics of ion channel antagonists from transferrin-functionalized polymeric nanoparticles.

Transferrin (Tf)-functionalized p(HEMA--GMA) nanoparticles were designed to incorporate and release a water-soluble combination of three ion channel antagonists, namely zonampanel monohydrate (YM872), oxidized adenosine triphosphate (oxATP) and lomerizine hydrochloride (LOM) identified as a promising therapy for secondary degeneration that follows neurotrauma. Coupled with a mean hydrodynamic size of 285 nm and near-neutral surface charge of -5.98 mV, the hydrophilic nature of the functionalized polymeric nanoparticles was pivotal in effectively encapsulating the highly water soluble YM872 and oxATP, as well as lipophilic LOM dissolved in water-based medium, by a back-filling method.

Overcoming Fungal Echinocandin Resistance through Inhibition of the Non-essential Stress Kinase Yck2.

New strategies are urgently needed to counter the threat to human health posed by drug-resistant fungi. To explore an as-yet unexploited target space for antifungals, we screened a library of protein kinase inhibitors for the ability to reverse resistance of the most common human fungal pathogen, Candida albicans, to caspofungin, a widely used antifungal. This screen identified multiple 2,3-aryl-pyrazolopyridine scaffold compounds capable of restoring caspofungin sensitivity.

Bi-allelic Mutations in NADSYN1 Cause Multiple Organ Defects and Expand the Genotypic Spectrum of Congenital NAD Deficiency Disorders.

Birth defects occur in up to 3% of all live births and are the leading cause of infant death. Here we present five individuals from four unrelated families, individuals who share similar phenotypes with disease-causal bi-allelic variants in NADSYN1, encoding NAD synthetase 1, the final enzyme of the nicotinamide adenine dinucleotide (NAD) de novo synthesis pathway. Defects range from the isolated absence of both kidneys to multiple malformations of the vertebrae, heart, limbs, and kidney, and no affected individual survived for more than three months postnatally.

Tobacco - Use Prevalence, Exposure, Attitudes, Behaviour/Cessation, Curriculum among Health Professional Students in Mangalore City, Karnataka, India.

Background: Tobacco use is one of the leading preventable causes of premature death, disease and disability around the world. Medical and Dental graduates have an important role to play in tobacco cessation and prevention. Hence, the present study was undertaken to assess the tobacco use prevalence, practice, attitudes towards policy making and curriculum in medical and dental interns (house surgeons).

Functional genomics and gene-environment interaction highlight the complexity of congenital heart disease caused by Notch pathway variants.

Congenital heart disease (CHD) is the most common birth defect and brings with it significant mortality and morbidity. The application of exome and genome sequencing has greatly improved the rate of genetic diagnosis for CHD but the cause in the majority of cases remains uncertain. It is clear that genetics, as well as environmental influences, play roles in the aetiology of CHD.

Silent synapses dictate cocaine memory destabilization and reconsolidation.

Cocaine-associated memories are persistent, but, on retrieval, become temporarily destabilized and vulnerable to disruptions, followed by reconsolidation. To explore the synaptic underpinnings for these memory dynamics, we studied AMPA receptor (AMPAR)-silent excitatory synapses, which are generated in the nucleus accumbens by cocaine self-administration, and subsequently mature after prolonged withdrawal by recruiting AMPARs, echoing acquisition and consolidation of cocaine memories. We show that, on memory retrieval after prolonged withdrawal, the matured silent synapses become AMPAR-silent again, followed by re-maturation ~6 h later, defining the onset and termination of a destabilization window of cocaine memories.

Default mode network anatomy and function is linked to pediatric concussion recovery.

Objective: To determine whether anatomical and functional brain features relate to key persistent post-concussion symptoms (PPCS) in children recovering from mild traumatic brain injuries (mTBI), and whether such brain indices can predict individual recovery from PPCS.

Methods: One hundred and ten children with mixed recovery following mTBI were seen at the concussion clinic at Neurology department Alberta Children's Hospital. The primary outcome was the Post-Concussion Symptom Inventory (PCSI, parent proxy).

Macromolecular approach for targeted radioimmunotherapy in non-Hodgkin's lymphoma.

Polymers are an attractive anchoring platform for the synthesis of radioimmunoconjugates. They enable independent control over the amount of radioisotope loading and antibody attachment, which is pivotal in developing tailorable formulations for personalised medicine. Herein, we report the synthesis of p(HEMA-ran-GMA) for the conjugation of lutetium ions and rituximab as a functional platform for radioimmunotherapy.

Ion Manipulation in Open Air Using 3D-Printed Electrodes.

Ambient ionization techniques provide a way to sample materials via creation of ions in the air. However, transferring and focusing of these ions is typically done in the reduced pressure environment of the mass spectrometer. Spray-based ambient ionization sources require relatively large distances between the source and mass spectrometer inlet for effective desolvation, resulting in a small fraction of the ions being collected.

Nontransplant Surgery for Intestinal Failure.

Insufficient absorptive mucosal surface is the fundamental problem in the short bowel state. Intestinal adaptation has been well studied, and it is well recognized that it may lead to dilatation of the bowel with increased thickness of the bowel wall, resulting from both mucosal hypertrophy and hyperplasia. Autologous reconstructive surgery exploits bowel dilatation in short bowel syndrome and maximizes the absorptive potential of the available mucosal surface.

Novel Hydrophilic Copolymer-Based Nanoparticle Enhances the Therapeutic Efficiency of Doxorubicin in Cultured MCF-7 Cells.

Nanoparticle drug delivery applications have predominantly focused on the entrapment and delivery of hydrophobic molecules with poor water solubility. However, benefits can also be obtained from nanoparticle-based delivery of hydrophilic therapeutics. This study reports on the development of a p(HEMA--GMA)-based nanoparticle synthesized via a spontaneous water-in-oil inverse nanoemulsion to deliver doxorubicin, a water-soluble chemotherapeutic.

Tumour suppression by targeted intravenous non-viral CRISPRa using dendritic polymers.

Aberrant gene expression is a hallmark of cancer. Although transcription is traditionally considered 'undruggable', the development of CRISPR-associated protein 9 (Cas9) systems offers enormous potential to rectify cancer-associated transcriptional abnormalities in malignant cells. However delivery of this technology presents a critical challenge to overcome in order to realize clinical translation for cancer therapy.

Interlude of metastability in the melting of polymer crystals.

We have studied the process of melting of polymer crystals using Langevin dynamics simulations with a coarse-grained united atom model. We have considered two ideal situations: one in which a single crystal melts and the other in which a multichain crystal melts. We show that the melting of the single crystal proceeds through a globular metastable state, which is followed by expansion to a more random coil-like state.

Guidelines for the management of common congenital heart diseases in India: A consensus statement on indications and timing of intervention.

Introduction: A number of guidelines are available for management of congenital heart diseases from infancy to adult life. However, these guidelines are for patients living in high-income countries. Separate guidelines, applicable to Indian children, are required when recommending an intervention for congenital heart diseases, as often these patients present late in the course of the disease and may have co-existing morbidities and malnutrition.

Modulators of platelet function in aging.

Platelets are small, anucleated effector cells that play an important role in linking the hemostatic and inflammatory processes in the body. Platelet function is known to be altered under various inflammatory conditions including aging. A gain in platelet function during aging can increase the risk of thrombotic events, such as stroke and acute myocardial infarction.

Indian guidelines for indications and timing of intervention for common congenital heart diseases: Revised and updated consensus statement of the Working group on management of congenital heart diseases.

A number of guidelines are available for the management of congenital heart diseases (CHD) from infancy to adult life. However, these guidelines are for patients living in high-income countries. Separate guidelines, applicable to Indian children, are required when recommending an intervention for CHD, as often these patients present late in the course of the disease and may have coexisting morbidities and malnutrition.

Electron cryomicroscopy observation of acyl carrier protein translocation in type I fungal fatty acid synthase.

During fatty acid biosynthesis, acyl carrier proteins (ACPs) from type I fungal fatty acid synthase (FAS) shuttle substrates and intermediates within a reaction chamber that hosts multiple spatially-fixed catalytic centers. A major challenge in understanding the mechanism of ACP-mediated substrate shuttling is experimental observation of its transient interaction landscape within the reaction chamber. Here, we have shown that ACP spatial distribution is sensitive to the presence of substrates in a catalytically inhibited state, which enables high-resolution investigation of the ACP-dependent conformational transitions within the enoyl reductase (ER) reaction site.

Prospects of siRNA cocktails as tools for modifying multiple gene targets in the injured spinal cord.

Unlabelled: Gene silencing through RNA interference (RNAi) has been touted as a boon for identifying potential therapies for difficult-to-treat pathologies. In this regard, siRNA-mediated gene silencing for tackling the multifaceted pathophysiology of spinal cord injury seemed promising. The genes caspase 3 and sarm1 were targeted in the present study, using siRNAs in a rodent model of spinal cord injury, as the feasibility of concomitant silencing of more than one gene had not been previously attempted.

Reaction Acceleration in Electrospray Droplets: Size, Distance, and Surfactant Effects.

Phenylhydrazone formation from isatin is used to examine the effects on the reaction rate of (i) electrospray emitter distance from the mass spectrometer (MS) inlet, (ii) emitter tip diameter, and (iii) presence of surfactant. Reaction rates are characterized through measurement of conversion ratios. It is found that there is an increase in the conversion ratio as (i) the electrospray source is moved further from the inlet of the mass spectrometer, (ii) smaller sprayer diameters are used, and (iii) when surfactants are present.

Screening of the Suzuki Cross-Coupling Reaction Using Desorption Electrospray Ionization in High-Throughput and in Leidenfrost Droplet Experiments.

Suzuki cross-coupling is a widely performed reaction, typically using metal catalysts under heated conditions. Acceleration of the Suzuki cross-coupling reaction has been previously explored in microdroplets using desorption electrospray ionization mass spectrometry (DESI-MS). Building upon previous work, presented here is the use of a high-throughput DESI-MS screening system to identify optimal reaction conditions.

Self-Similar Subgrid-Scale Models for Inertial Range Turbulence and Accurate Measurements of Intermittency.

A class of spectral subgrid models based on a self-similar and reversible closure is studied with the aim to minimize the impact of subgrid scales on the inertial range of fully developed turbulence. In this manner, we improve the scale extension where anomalous exponents are measured by roughly 1 order of magnitude when compared to direct numerical simulations or to other popular subgrid closures at the same resolution. We find a first indication that intermittency for high-order moments is not captured by many of the popular phenomenological models developed so far.

Routine surveillance endoscopy and biopsy after isolated intestinal transplantation-Revisiting the gold standard.

The value of endoscopy and biopsy after intestinal transplantation in the absence of clinical concerns has never been investigated. We examined clinical yield of routine surveillance endoscopy and biopsy (control group, n = 28, Jan 2011 to Jun 2014). Most episodes of acute rejection were diagnosed when there were clinical symptoms or signs such as increased stoma output, fever, or bacteremia, but not by routine surveillance endoscopy and biopsy.