Discovery of Potent Isoindolinone Inhibitors that Target an Active Conformation of PARP1 Using DNA-Encoded Libraries.

Inhibition of poly (ADP-ribose) polymerase-1 (PARP1), a DNA repair enzyme, has proven to be a successful strategy for the treatment of various cancers. With the appropriate selection conditions and protein design, DNA-encoded library (DEL) technology provides a powerful avenue to identify small molecules with the desired mechanism of action towards a target of interest. However, DNA-binding proteins, such as PARP1, can be challenging targets for DEL screening due to non-specific protein-DNA interactions.

Posterior Sagittal Approach for Nonanorectal Malformation: Widening Spectrum.

Background: Posterior sagittal is a very well accepted approach in the treatment of anorectal malformations. This approach provides good access and exposure through the perineum to the deep pelvic structures. It reduces risk of injury to important structures as dissection remains in midline.

Initial experience with 3D laparoscopic choledochal cyst (CDC) excision and hepatico-duodenostomy (HD) in 21 children.

Introduction: Minimal access surgery has gradually become the standard of care in the management of choledochal cysts (CDC). Laparoscopic management of CDC is a technically challenging procedure that requires advanced intracorporeal suturing skills, and hence, has a steep learning curve. Robotic surgery has the advantages of 3D vision, articulating hand instruments making suturing easy and thus is ideal.

Phomoxanthone A Targets ATP Synthase.

Phomoxanthone A is a naturally occurring molecule and a powerful anti-cancer agent, although its mechanism of action is unknown. To facilitate the determination of its biological target(s), we used affinity-based labelling using a phomoxanthone A probe. Labelled proteins were pulled down, subjected to chemoproteomics analysis using LC-MS/MS and ATP synthase was identified as a likely target.

An Unusual Case of Type A Posterior Cloaca Associated with 46XX Disorder of Sexual Differentiation with Y Duplication of Urethra.

We report an infant reared as a girl who presented with ambiguous genitalia and urine coming per rectum. On examination, she had minimal clitoromegaly with labial fusion and Y urethral duplication. On investigations, genetic, metabolic, and endocrine causes for disorder of sexual differentiation were ruled out.

A phase transition enhances the catalytic activity of SARM1, an NAD glycohydrolase involved in neurodegeneration.

Sterile alpha and toll/interleukin receptor (TIR) motif-containing protein 1 (SARM1) is a neuronally expressed NAD glycohydrolase whose activity is increased in response to stress. NAD depletion triggers axonal degeneration, which is a characteristic feature of neurological diseases. Notably, loss of SARM1 is protective in murine models of peripheral neuropathy and traumatic brain injury.

Multidisciplinary Approach for Management of Pediatric Tumors: a Case Series.

Pediatric solid tumors have wide range of presentations. Multidisciplinary approach is often needed for their optimum management. There are no reports discussing such an approach to pediatric tumors involving pediatric surgeons, oncologists and cardiothoracic surgeons together for the management.

Identification of the first noncompetitive SARM1 inhibitors.

Sterile Alpha and Toll Interleukin Receptor Motif-containing protein 1 (SARM1) is a key therapeutic target for diseases that exhibit Wallerian-like degeneration; Wallerian degeneration is characterized by degeneration of the axon distal to the site of injury. These diseases include traumatic brain injury, peripheral neuropathy, and neurodegenerative diseases. SARM1 promotes neurodegeneration by catalyzing the hydrolysis of NAD to form a mixture of ADPR and cADPR.

Posterior Sagittal Approach for Uterovaginal Anastomosis in a Case of Congenital Cervical Atresia with Anorectal Malformation.

Cervical atresia is a rare association with anorectal malformation (ARM) which can be missed till puberty in the presence of normal vaginal orifice. A 12-year-old girl operated for ARM in neonatal age presented with primary amenorrhea. She had a normal vaginal opening, short perineal body, and prolapsed anteposed anus and was diagnosed with cervical agenesis.

Synthesis and Anticancer Activity of Structure Simplified Naturally-Inspired Dimeric Chromenone Derivatives.

Select dimeric chromenones exhibit low micromolar cyctotoxicity toward lymphoma and leukemia cell lines, L5178Y and HL60, respectively. The bioactive dimeric chromenones were identified from a focused library of structurally-simplified derivatives of naturally-occurring dimeric chromenones and tetrahydroxanthones that was prepared as part of this study. The simple dimeric chromenone scaffolds contain no stereogenic centers, are easily synthesized, and may be utilized as lead compounds in cancer research and drug discovery.

Calcium Regulates the Nuclear Localization of Protein Arginine Deiminase 2.

Protein arginine deiminases (PADs) are calcium-dependent enzymes that mediate the post-translational conversion of arginine into citrulline. Dysregulated PAD activity is associated with numerous autoimmune disorders and cancers. In breast cancer, PAD2 citrullinates histone H3R26 and activates the transcription of estrogen receptor target genes.

Ultra-modified rapid sequence induction with transnasal humidified rapid insufflation ventilatory exchange: Challenging convention.

During positive pressure ventilation, gastric inflation and subsequent pulmonary aspiration can occur. Rapid sequence induction (RSI) technique is an age-old formula to prevent this. We adopted a novel approach of RSI for patients with high risk of aspiration and evaluated it further in patients undergoing laparoscopic surgeries.

Photochemical Control of Protein Arginine Deiminase (PAD) Activity.

Protein arginine deiminases (PADs) play an important role in the pathogenesis of various diseases, including rheumatoid arthritis, multiple sclerosis, lupus, ulcerative colitis, and breast cancer. Therefore, the development of PAD inhibitors has drawn significant research interest in recent years. Herein, we describe the development of the first photoswitchable PAD inhibitors.

Video-Assisted Thoracoscopic Surgery for Pediatric Empyema by Two-Port Technique: A Single-Center Experience with 167 Consecutive Cases.

Background/purpose: The aim of our study is to determine efficacy, safety, and feasibility of video-assisted thoracoscopic surgery (VATS) in childhood empyema with a technique of only two ports and open instruments at a tertiary care center in India.

Methods: This is a retrospective study of patients below 18 years, with empyema presenting to the Department of Pediatric Surgery of a Tertiary Care Referral Hospital in India, over a period of 9 years who underwent VATS decortication. Only two ports with open surgical instruments were used.

Tc-99m Ethylenedicysteine and Tc-99m Dimercaptosuccinic Acid Scintigraphy-Comparison of the Two for Detection of Scarring and Differential Cortical Function.

Context: The differential cortical function obtained by Tc-99m EC is comparable to that of Tc-99m DMSA. However, identification of scars on Tc-99m EC images needs to be studied.

Aims: The aim of the study is to evaluate role of Tc-99m EC for detection of scarring and differential cortical function by comparing with Tc-99m DMSA.

A Study of Morbidity and Cost of Peripheral Venous Cannulation in Neonates Admitted to Paediatric Surgical Intensive Care Unit.

Introduction: Peripheral venous access in sick neonates is indicated for administration of fluids, drugs or nutrients.

Aim: We conducted an audit of peripheral venous access in neonates admitted to paediatric surgical intensive care unit to study the morbidity, time spent on cannulation and cost with its use.

Materials And Methods: One hundred consecutive neonates requiring hospital admission to paediatric surgical intensive care unit in a period of one year were included in the study.

Development of a Selective Inhibitor of Protein Arginine Deiminase 2.

Protein arginine deiminase 2 (PAD2) plays a key role in the onset and progression of multiple sclerosis, rheumatoid arthritis, and breast cancer. To date, no PAD2-selective inhibitor has been developed. Such a compound will be critical for elucidating the biological roles of this isozyme and may ultimately be useful for treating specific diseases in which PAD2 activity is dysregulated.

Dispersing Zwitterions into Comb Polymers for Nonviral Transfection: Experiments and Molecular Simulation.

Polymer-based gene delivery vehicles benefit from the presence of hydrophilic groups that mitigate the inherent toxicity of polycations and that provide tunable polymer-DNA binding strength and stable complexes (polyplexes). However, hydrophilic groups screen charge, and as such can reduce cell uptake and transfection efficiency. We report the effect of embedding zwitterionic sulfobetaine (SB) groups in cationic comb polymers, using a combination of experiments and molecular simulations.

OVOTESTICULAR DISORDER OF SEX DEVELOPMENT: A SINGLE-CENTER EXPERIENCE.

Objective: Ovotesticular disorder of sex development (OT DSD) is a rare disorder of sex development characterized by the presence in the same individual of both histologically proven testis and ovary. There are scant data from the Indian subcontinent regarding this disorder. The aim of this study was to describe the clinical, biochemical, imaging, cytogenetic, surgical, and histopathologic findings and outcomes of patients with OT DSD from Western India.

Surgical checklist application and its impact on patient safety in pediatric surgery.

Background: Surgical care is an essential component of health care of children worldwide. Incidences of congenital anomalies, trauma, cancers and acquired diseases continue to rise and along with that the impact of surgical intervention on public health system also increases. It then becomes essential that the surgical teams make the procedures safe and error proof.

Design, synthesis, and biological evaluation of tetrazole analogs of Cl-amidine as protein arginine deiminase inhibitors.

Protein arginine deiminases (PADs) catalyze the post-translational hydrolysis of arginine residues to form citrulline. This once obscure modification is now known to play a key role in the etiology of multiple autoimmune diseases (e.g.

Pyloric atresia--three cases and review of literature.

Pyloric atresia (PA) is a rare congenital anomaly that constitutes approximately 1% of all intestinal atresias, and its incidence is approximately 1 in 100,000 live births. PA may occur as an isolated condition or associated with other abnormalities, the most common being Junctional epidermolysis bullosa (JEB). Evidence suggests that PA-EB (Pyloric Atresia - Epidermolysis Bullosa) Syndrome is a distinct entity.

Two-port laparoscopic management of a giant pseudocyst complicating ventriculoperitoneal shunt.

Insertion of a ventriculo-peritoneal (VP) shunt is the most common operative procedure for the treatment of hydrocephalus in children. Of the several causes of shunt malfunction, cerebrospinal fluid (CSF) pseudocyst is relatively uncommon. There are several modalities to treat a CSF pseudocyst.