Exploring a Solvent Dependent Strategy to Control Self-Assembling Behavior and Cellular Interaction in Laminin-Mimetic Short Peptide based Supramolecular Hydrogels.

Self-assembled hydrogels, fabricated through diverse non-covalent interactions, have been extensively studied in regenerative medicines. Inspired from bioactive functional motifs of ECM protein, short peptide sequences have shown remarkable abilities to replicate the intrinsic features of the natural extracellular milieu. In this direction, we have fabricated two short hydrophobic bioactive sequences derived from the laminin protein i. e., IKVAV and YIGSR. Based on the substantial hydrophobicity of these peptides, we selected a co-solvent approach as a suitable gelation technique that included different concentrations of DMSO as an organic phase along with an aqueous solution containing 0.1 % TFA. These hydrophobic laminin-based bioactive peptides with limited solubility in aqueous physiological environment showed significantly enhanced solubility with higher DMSO content in water. The enhanced solubility resulted in extensive intermolecular interactions that led to the formation of hydrogels with a higher-order entangled network along with improved mechanical properties. Interestingly, by simply modulating DMSO content, highly tunable gels were accessed in the same gelator domain that displayed differential physicochemical properties. Further, the cellular studies substantiated the potential of these laminin-derived hydrogels in enhancing cell-matrix interactions, thereby reinforcing their applications in tissue engineering.

Designing Pathway-Controlled Multicomponent Ultrashort Peptide Hydrogels with Diverse Functionalities at the Nanoscale for Directing Cellular Behavior.

Tuning self-assembling pathways by implementing different external stimuli has been extensively studied, owing to their effective control over structural and mechanical properties. Consequently, multicomponent peptide hydrogels with high structural tunability and stimuli responsiveness are crucial in dictating cellular behavior. Herein, we have implemented both coassembly approach and pathway-dependent self-assembly to design nonequilibrium nanostructures to understand the thermodynamic and kinetic aspects of peptide self-assembly toward controlling cellular response. Our system involved an ultrashort peptide gelator and a hydrophilic surfactant which coassembled through different pathways, i.e., heat-cool and sonication methods with variable energy input. Interestingly, it was possible to access diverse structural and mechanical properties at the nanoscale in a single coassembled system. Further, the hydrophilic surfactant provided additional surface functionalities, thus creating an efficient hydrophilic matrix for cellular interaction. Such diverse functionalities in a single coassembled system could lead to the development of advanced scaffolds, with applications in various biomedical fields.

Prognostic Significance of Programmed Cell Death-Ligand 1 Expression in Tobacco Associated Oral Squamous Cell Carcinoma: An Immunohistochemical Based Cross-Sectional Study.

BACKGROUND: Advancements in immuno-oncology have dramatically transformed cancer treatment. Immunotherapy, targeting immune check point proteins, notably Programmed cell death ligand 1 (PD-L1) and its receptor Programmed Cell Death-1 (PD-1) which modulate the activity of immune response in Head and Neck squamous cell carcinomas (HNSCC), is an area of much research. The immunohistochemical expression of PD-L1 in cancer cells has been proposed as a predictive biomarker for selecting candidates for immunotherapy. Thus, the present study was undertaken to study the expression of PD-L1 in the primary tumour cells and evaluate its correlation with various clinicopathological parameters and prognosis in tobacco associated oral squamous cell carcinomas (OSCC). METHODS: Expression of PD-L1 was investigated in 75 surgically resected cases of OSCC by immunohistochemistry and its association with different clinicopathological features and prognosis was analysed. RESULTS: PD-L1 protein was detected in 68% (51 cases) of cases. Tumour stage (p = 0.04), lymph node (LN) metastasis (p < 0.01) and moderate to marked tumour infiltrating lymphocytes (TILs) (p < 0.05), significantly correlated with the PD-L1 expression in the primary tumour. PD-L1 expression did not show a significant association with overall survival (OS) rate, however, patients with positive PD-L1 expression showed a poorer survival rate. Patients exhibiting nodal positivity had the worst prognosis (p < 0.005). CONCLUSION: These data demonstrated a significant association of ≥ 5% PD-L1 expression in the primary tumour and the presence of LN metastasis, moderate to marked TILs and advancing tumour stage, thus, making it a plausible immunotherapeutic target molecule in OSCC patients.

The left ventricle in atrial septal defect: Looking through 3D glasses.

OBJECTIVES: To identify left ventricular (LV) dyssynchrony and associated factors in atrial septal defect (ASD) patients, using real time three-dimensional echocardiogram (RT3DE). BACKGROUND: Left ventricular dysfunction has been observed in ASD. Few studies have utilized RT3DE to assess LV wall-motion abnormality in ASD. METHODS: Patients aged ≥1 year with ASD, with or without partial anomalous pulmonary venous drainage (PAPVD), were included over 1 year. Additional cardiac defects or abnormalities independently affecting LV function were excluded. 2DE and RT3DE-derived LV function data were recorded. Student's t test and Pearson's correlation were used for analysis. RESULTS: Of 104 patients (69 females) aged 1-57 years, ostium secundum ASD was present in 97 and sinus venosus ASD in 7. Maximum excursion increased significantly with age, weight, and body surface area (P < 0.001). Majority of children (58%) aged 3-5 years showed no delay in segmental excursion. Lateral wall excursional delay was greater beyond 5 years or with weight > 15 kg (42% as compared to 20% in <15 kg). In patients weighing < 15 kg, time to minimum systolic volume (Tmsv 16-SD) was higher with PAPVD and with indexed defect size > 40 mm/m2 , though not statistically significant. As compared to EF estimation by 2DE, EF derived using RT3DE was significantly lower (P < 0.001). CONCLUSION: Left ventricular dyssynchrony is least between 3 and 5 years. Beyond 5 years, delayed lateral wall excursion is seen. With an indexed defect size exceeding 40 mm/m2 , and in the presence of PAPVD, time to minimum systolic volume is higher.

Bioactive Hydrogels Inspired by Laminin: An Emerging Biomaterial for Tissue Engineering Applications.

Tissue or organ damage due to severe injuries or chronic diseases can adversely affect the quality of life. Current treatments rely on organ or tissue transplantation which has limitations including unavailability of donors, ethical issues, or immune rejection after transplantations. These limitations can be addressed by tissue regeneration which involves the development of bioactive scaffolds closely mimicking the extracellular matrix (ECM). One of the major components of ECM is the laminin protein which supports several tissues associated with important organs. In this direction, peptide-based hydrogels can effectively mimic the essential characteristics of laminin. While several reports have discussed the structure of laminin, the potential of laminin-derived peptide hydrogels as effective biomaterial for tissue engineering applications is yet to be discussed. In this context, the current review focuses on the structure of laminin and its role as an essential ECM protein. Further, the potential of short peptide hydrogels in mimicking the crucial properties of laminin is proposed. The review further highlights the significance of bioactive hydrogels inspired by laminin - in addressing numerous tissue engineering applications including angiogenesis, neural, skeletal muscle, liver, and adipose tissue regeneration along with a brief outlook on the future applications of these laminin-based hydrogels.

Immunohistochemical evaluation of yes-associated protein molecule in the odontogenic epithelium of different histopathological variants of ameloblastoma and unicystic ameloblastoma.

Background: Ameloblastoma is one of the major odontogenic neoplasms with an invasive and recurrence potential. Its tumourigenesis and proliferative capacity can be attributed to the activation or inactivation of certain molecular signalling pathways. Hippo signalling pathway is known to regulate diverse physiological processes related to mitosis and organ growth and is an emerging tumour suppressor pathway, the dysfunction of which is implicated in various diseases including cancers. Yes-associated protein1 (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) are the downstream effectors in the Hippo cascade, which on nuclear activation leads to cellular proliferation in various tumours. Aim: The current study was undertaken to evaluate the expression of YAP in various histopathological variants of ameloblastoma and unicystic ameloblastoma. Materials and Methods: Fifty formalin-fixed paraffin-embedded tissue samples of histopathologically diagnosed cases of ameloblastoma, and 10 histopathologically diagnosed cases of unicystic ameloblastoma were obtained from the departmental archives to evaluate the immunohistochemical expression of YAP both manually and by software analysis. Results: More than 90% of cases of conventional ameloblastoma and unicystic ameloblastoma elicited positive expression of YAP. No statistical difference was found among different histopathological variants of conventional ameloblastoma. Significant difference between the means of all four quantitative score groups was observed. Conclusion: In view of the modulating effect of YAP in tumourigenesis and its higher expression in ameloblastoma, further exploration of this molecule appears to be a promising area of research.

Evaluation of micrometastasis and isolated tumor cells in node-negative early-stage oral tongue squamous cell carcinoma: a cross-sectional study in tertiary-level hospitals in eastern India.

OBJECTIVE: The present study aimed to investigate the incidence of micrometastasis (MMs) and isolated tumor cells (ITCs) in node-negative early-stage oral tongue squamous cell carcinoma (T1-T2 N0). The secondary objective was to correlate the incidence with the clinicopathologic parameters of age, sex, depth of invasion, pattern of invasion, host lymphocytic response, and size and grade of primary tumor. STUDY DESIGN: Micrometastasis and ITCs in cervical nodes of 30 patients with early-stage oral tongue squamous cell carcinoma were detected and compared using 3 methods: routine hematoxylin and eosin staining, serial-sectioning at intervals of 150 microns employing hematoxylin and eosin, and serial sectioning pan-cytokeratin immunostaining. Associations with clinicopathological variables were analyzed. RESULTS: Metastatic tumor cells were detected in the cervical nodes of 2 patients using serial sectioning and immunohistochemistry, resulting in upstaging of 6.6% of all cases. Level I and II lymph nodes were primarily involved. CONCLUSIONS: Early-stage oral tongue squamous cell carcinoma has a significant potential for MMs that frequently go undetected in routine histopathologic examination. However, laborious and technique-sensitive, serial sectioning in combination with pan-cytokeratin staining (AE1/AE3) may aid in detecting MMs and ITCs in patients with early-stage OTSCC.

Multidrug-resistant tuberculosis in an HIV-infected girl.

Multidrug-resistant tuberculosis (MDR-TB) in patients with human immunodeficiency virus (HIV) infection poses multiple challenges for treatment, and has a high mortality. MDR-TB coinfection with HIV has been reported in African children. In India, we did not come across any report of HIV and MDRTB coinfection in children, though such coinfection has been reported in adults. A 9-year-old HIV-infected girl requiring antiretroviral therapy (ART) developed MDR-TB and responded to second-line antituberculous therapy.

Guidelines for physical activity in children with heart disease.

Justification: In recent years, there has been increasing recognition of children with heart disease in our country. These children belong to different age groups and have untreated, partially treated, or completely treated heart disease. The role of physical activity for optimal physical, emotional, and psychosocial well-being for children is well understood. There is a challenge for the parents and the medical professionals to take a decision regarding the type of physical activity safe for the child as heart disease may affect the hemodynamic demands. Most of the existing international guidelines focus on competitive sports in operated heart disease children. This may be of limited use when we have a mixed population of children with heart disease, different types of sports in our country and where a larger subset is looking for recommendations to leisure time activities. Process: The Pediatric Cardiac Society of India decided to formulate recommendations for physical activity in children with heart diseases. A committee of experts, who were well-versed with the subject of physical activity in children with heart disease, volunteered to take up the task of writing the guidelines. The recommendations emerged following deliberations of the committee members, on the virtual platform as well as mails. The final version of manuscript was approved by all committee members and all members are co-authors of this manuscript. The different types of physical activities were defined including leisure sports and competitive sports. The exercise was classified based on the mechanical action of muscles involved into dynamic and static components. Each type of exercise was then classified based on the intensity into low, medium, and high. Recommendations for the type of physical activity for individual heart lesions were decided based on the rationale available. Objectives: The recommendations here are made with an intention to provide general guidelines for physical activity in children with operated and unoperated heart diseases, not excluding a need for individualizing a plan, serial assessment, and comprehensive checkup in special situations. Recommendations: We hope the recommendations mentioned below would provide basic clarity in planning physical activity in children with heart disease. This is with the hope to encourage physically active life, at the same time ensuring a safety net.

Profile of Kawasaki disease at a tertiary care center in India.

BACKGROUND: Kawasaki disease (KD) is the most common cause of acquired heart disease in developed countries. KD is increasingly being reported from India; however, studies involving the large number of patients are few. METHODS: All children presenting to the center from January 2017 to December 2019, diagnosed to have KD, were retrospectively included in the study. Clinical and laboratory profiles, including echocardiograms, were reviewed. Factors contributing to intravenous immunoglobulin (IVIg) refractoriness and the development of coronary artery abnormalities (CAA) were assessed. RESULTS: A total of 39 children with KD presented to the center during the study. While 32 received initial treatment at our center, seven were referred after the initial IVIg infusion. The age range was 2 months to 11 years (mean 42.15 ± 38.51 months). More than two-thirds of the cohort was male (n = 27/39). Mucosal involvement was the commonest clinical abnormality for the group, followed by rash. Hemoglobin was significantly lower in the group with coronary artery involvement (P = 0.001). CAA (61.5%), incomplete KD, and atypical features were much more common in infants compared to the rest. Refractoriness to treatment was significantly more common in infants (P = 0.029). CONCLUSIONS: A significant proportion of infants with KD had cardiac involvement. Infants were more likely to have IVIg-resistant disease.

Clinico-Etiological Profile of Pediatric Syncope: A Single Center Experience.

OBJECTIVE: To describe the clinical profile of children with syncope. METHODS: Hospital records were reviewed for clinical and laboratory details of children presenting with real or apparent syncope. Five diagnostic categories were identified: neurocardiogenic syncope (NCS), psychogenic pseudosyncope (PPS), cardiac, neurological and indeterminate. RESULTS: 30 children (aged 4 to 17 years)were included. The commonest cause of syncope was NCS (63.3%), followed by PPS (13.3%), cardiac (10%), neurological (10%) and indeterminate (3.3%). Exercise, loud noise or emotional triggers and family history were associated with cardiac etiology, and electrocardiogram (ECG) was diagnostic in the majority. Children with PPS and cardiacsyncope had frequent episodes when compared with other groups. Indiscriminate antiepileptic use was found in 5 children, including two cardiac cases. CONCLUSIONS: Frequent recurrences of syncope may suggest PPS or cardiac cause. Cardiac etiology may be readily identified on history and ECG alone.

Modern computational intelligence based drug repurposing for diabetes epidemic.

BACKGROUND AND AIM: Objectives are to explore recent advances in discovery of new antidiabetic agents using repurposing strategies and to discuss modern technologies used for drug repurposing highlighting diabetic specific web portal. METHODS: Recent literature were studied and analyzed from various sources such as Scopus, PubMed, and IEEE Xplore databases. RESULTS: Drugs like Niclosamideethanolamine, Methazolamide, Diacerein, Berberine, Clobetasol, etc. with possibility of repurposing to curb diabetes can be potential late-stage clinical candidates, providing access to information on pharmacology, formulation, and probable toxicity if any. CONCLUSIONS: With collaboration of artificial intelligence (AI) with pharmacology, the efficiency of drug repurposing can improve significantly.

Effect of Lysyl Oxidase G473 A Polymorphism on Lysyl Oxidase and Total Soluble Collagen Expression in Oral Submucous Fibrosis.

BACKGROUND: Oral submucous fibrosis (OSF) is a debilitating collagen-metabolic disorder leading to submucosal fibrosis and trismus. Lysyl oxidase (LOX), a critical collagen biosynthetic enzyme, is up-regulated in OSF. Polymorphisms in the Lysyl oxidase gene have been associated with increased risk of OSF and might affect normal collagen synthesis, accumulation, or degradation, crucial in determining fibrosis severity. METHODS: One hundred OSF cases and 100 controls were genotyped for LOX G473A(Arg158Gln) polymorphism by polymerase chain reaction-restriction fragment length polymorphism. The expression of LOX was estimated both by quantitative mRNA analysis and western blot. Total soluble collagen was evaluated from mucosal tissue obtained from OSF cases. Immunohistochemical (IHC) localization of type 1 collagen was performed in mucosal tissue obtained from patients carrying various genotypes. RESULTS: Heterozygous G473A genotype was significantly higher in OSF cases [2.063(95% CI =1.059-4.016)], among 26-40 years age-group [4.375(95% CI=1.323-14.267),p=0.029] and in male patients [2.38 (95% CI= 1.107-5.121), p= 0.042]. LOX expression was significantly higher in cases of the heterozygous or homozygous carrier (p <0.001). We found the total soluble collagen level significantly (p <0.001) higher among patients carrying GA or AA genotype. IHC revealed focal deposition of type1 collagen in the submucosal tissue; comparatively higher deposition was evident in mucosal tissue of OSF patients carrying AA genotype. CONCLUSIONS: These findings suggest LOX G473A polymorphism confers an increased risk of OSF and may affect collagen accumulation in OSF cases.

Subacute combined degeneration of the spinal cord in an adolescent girl.

Subacute combined degeneration of the spinal cord (SACD), a condition resulting from vitamin B12 deficiency, generally affects elderly people. We present a 12-year-old girl, who, despite a non-vegetarian diet and no obvious etiological factors, developed SACD.

Application of Artificial Intelligence in COVID-19 drug repurposing.

BACKGROUND AND AIM: COVID-19 outbreak has created havoc and a quick cure for the disease will be a therapeutic medicine that has usage history in patients to resolve the current pandemic. With technological advancements in Artificial Intelligence (AI) coupled with increased computational power, the AI-empowered drug repurposing can prove beneficial in the COVID-19 scenario. METHODS: The recent literature is studied and analyzed from various sources such as Scopus, Google Scholar, PubMed, and IEEE Xplore databases. The search terms used are 'COVID-19', ' AI ', and 'Drug Repurposing'. RESULTS: AI is implemented in the field design through the generation of the learning-prediction model and performs a quick virtual screening to accurately display the output. With a drug-repositioning strategy, AI can quickly detect drugs that can fight against emerging diseases such as COVID-19. This technology has the potential to improve the drug discovery, planning, treatment, and reported outcomes of the COVID-19 patient, being an evidence-based medical tool. CONCLUSIONS: Thus, there are chances that the application of the AI approach in drug discovery is feasible. With prior usage experiences in patients, few of the old drugs, if shown active against SARS-CoV-2, can be readily applied to treat the COVID-19 patients. With the collaboration of AI with pharmacology, the efficiency of drug repurposing can improve significantly.

Exposure and Use of Mobile Media Devices by Young Children.

BACKGROUND AND OBJECTIVES: Research on children's use of mobile media devices lags behind its adoption. The objective of this study was to examine young children's exposure to and use of mobile media devices. METHODS: Cross-sectional study of 350 children aged 6 months to 4 years seen October to November 2014 at a pediatric clinic in an urban, low-income, minority community. The survey was adapted from Common Sense Media's 2013 nationwide survey. RESULTS: Most households had television (97%), tablets (83%), and smartphones (77%). At age 4, half the children had their own television and three-fourths their own mobile device. Almost all children (96.6%) used mobile devices, and most started using before age 1. Parents gave children devices when doing house chores (70%), to keep them calm (65%), and at bedtime (29%). At age 2, most children used a device daily and spent comparable screen time on television and mobile devices. Most 3- and 4-year-olds used devices without help, and one-third engaged in media multitasking. Content delivery applications such as YouTube and Netflix were popular. Child ownership of device, age at first use, and daily use were not associated with ethnicity or parent education. CONCLUSIONS: Young children in an urban, low-income, minority community had almost universal exposure to mobile devices, and most had their own device by age 4. The patterns of use suggest early adoption, frequent and independent use, and media multitasking. Studies are urgently needed to update recommendations for families and providers on the use of mobile media by young children.

Two-ventricle repair for complex congenital heart defects palliated towards single-ventricle repair.

OBJECTIVES: Complex congenital heart defects that present earlier in life are sometimes channelled towards single-ventricle repair, because of anatomical or logistic challenges involved in two-ventricle correction. Given the long-term functional and survival advantage, we have been consciously exploring the feasibility of a biventricular repair in these patients when they present later for Fontan completion. METHODS: Since June 2009, 71 patients were referred for staged completion of the Fontan procedure. Following detailed evaluation that included three-dimensional echocardiography and magnetic resonance imaging, 10 patients (Group 1-median age 6 years) were identified and later underwent complex biventricular repair with takedown of Glenn shunt, while completion of extracardiac Fontan repair was done in 61 patients (Group 2-median age 7 years). RESULTS: Two-ventricle repair was accomplished in all the 10 Group 1 patients. One patient developed complete heart block requiring permanent pacemaker insertion. Late patch dehiscence occurred in another (awaiting repair). At a median follow-up of 15 months, there was no mortality among the Group 1 patients and all except for 1 patient were symptom free. There were 2 early deaths (3.3%) in the Group 2 patients. CONCLUSIONS: Two-ventricular repair, although surgically challenging, should be considered in all patients with two functional ventricles who come for Fontan completion. Comprehensive preoperative imaging and meticulous planning helps in identifying suitable candidates.

Anti-platelet agents in pediatric cardiac practice.

Pediatric patients with a variety of congenital and acquired cardiac conditions receive antithrombotic therapy. Many of the indications are empirical, and have either not been proven in controlled studies or are extrapolated from adult studies. This article reviews the current available literature regarding the use of anti-platelet drugs in the pediatric cardiac population.