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Background: Following the coronavirus disease-2019 (COVID-19) pandemic, a new entity emerged termed as multisystem inflammatory syndrome in children and adolescents temporally related to COVID-19 (MISC) by the World Health Organization (WHO). Infection with COVID-19 triggers the formation of antibodies to viral surface epitopes. It is believed that low titer non-neutralizing antibodies may accentuate virus-triggered immune responses. The study aimed to describe the various clinical presenting features, deranged laboratory parameters, echocardiographic findings, and immediate outcome and to categorize into 3 types of MISC and find any difference among the 3 types. Methodology: Children 29-days old to 12-years old who clinically satisfied the published WHO’s case definition for MISC were included in the study. All children were subjected to serological testing for total immunoglobulin to viral spike glycoprotein, relevant blood investigations, and echocardiography. Results: Out of 50 cases, we had 24(48%) cases of MISC without shock, 12(24%) cases of Kawasaki disease-like phenotype, and 14(28%) cases of MISC with shock. Fever (96%) and respiratory complaints (64%) predominate followed by gastrointestinal (45%) and red eye (32%). The inflammatory markers were notably elevated- the median CRP was 39.6mg/L, median ESR was 70mm 1sthr, median procalcitonin was 8.2 ng/ml. There is a significant drop in inflammatory markers post-treatment (p=0.019, p=0.000, p=0.016 respectively for CRP, ESR and procalcitonin). Abnormal echocardiographic findings were seen in 46% of cases in terms of decreased ejection fraction and coronary artery aneurysms (CAA). There were 7 deaths (14%), and 42(84%) patients were successfully discharged. Conclusion: Following the COVID-19 pandemic, MISC has emerged with its characteristic clinical pattern which needs early identification and prompt treatment to prevent mortality and morbidity.

Genomic interstrand crosslinks (ICLs) are formed by reactive species generated during normal cellular metabolism, produced by the microbiome, and employed in cancer chemotherapy. While there are multiple options for replication dependent and independent ICL repair, the crucial step for each is unhooking one DNA strand from the other. Much of our insight into mechanisms of unhooking comes from powerful model systems based on plasmids with defined ICLs introduced into cells or cell free extracts. Here we describe the properties of exogenous and endogenous ICL forming compounds and provide an historical perspective on early work on ICL repair. We discuss the modes of unhooking elucidated in the model systems, the concordance or lack thereof in drug resistant tumors, and the evolving view of DNA adducts, including ICLs, formed by metabolic aldehydes., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Published by Elsevier B.V.)

We have studied the structural and interfacial properties of CTAB/isooctane/alcohol/aqueous urea reverse micelles (RMs) for the first time using time-resolved fluorescence and small-angle X-ray scattering techniques. The chain length of alcohol, used as cosurfactant, has been varied to design three microemulsion systems: CTAB/1-butanol, CTAB/1-hexanol, and CTAB/1-octanol/isooctane/water, at a fixed water loading ratio, w 0 = 12. Time-resolved fluorescence anisotropy studies indicate that urea induces micellar aggregation in CTAB/1-butanol and CTAB/1-hexanol RMs but breaks down RM aggregates in CTAB/1-octanol RMs. Urea addition slows down solvation dynamics inside RMs at higher urea concentrations, evident from the longer lifetimes of solvent correlation decay. The underlying changes in microemulsion structure and intermicellar interactions are studied using small-angle X-ray scattering studies. The significant intermicellar interactions were modeled using the sticky hard sphere (SHS) for the CTAB/1-butanol and CTAB/1-hexanol RMs and by using the Macroion model for the CTAB/1-octanol RMs. The two different structural factors highlight the dominance of attractive and repulsive forces, respectively. Although there is no change in RM shape, the combination of urea addition and chain length variation in cosurfactants significantly alters the size and interface in these pseudoternary RMs.

Duplication of the genome requires the replication apparatus to overcome a variety of impediments, including covalent DNA adducts, the most challenging of which is on the leading template strand. Replisomes consist of two functional units, a helicase to unwind DNA and polymerases to synthesize it. The helicase is a multi-protein complex that encircles the leading template strand and makes the first contact with a leading strand adduct. The size of the channel in the helicase would appear to preclude transit by large adducts such as DNA: protein complexes (DPC). Here we discuss some of the extensively studied pathways that support replication restart after replisome encounters with leading template strand adducts. We also call attention to recent work that highlights the tolerance of the helicase for adducts ostensibly too large to pass through the central channel.

Immunofluorescence imaging is a standard experimental tool for monitoring the response of cellular factors to DNA damage. Visualizing the recruitment of DNA Damage Response (DDR) components requires high affinity antibodies, which are generally available. In contrast, reagents for the display of the lesions that induce the response are far more limited. Consequently, DDR factor accumulation often serves as a surrogate for damage, without reporting the actual inducing structure. This limitation has practical implications given the importance of the response to DNA reactive drugs such as those used in cancer therapy. These include interstrand crosslink (ICL) forming compounds which are frequently employed clinically. Among them are the psoralens, natural products that form ICLs upon photoactivation and applied therapeutically since antiquity. However, despite multiple attempts, antibodies against psoralen ICLs have not been developed. To overcome this limitation, we developed a psoralen tagged with an antigen for which there are commercial antibodies. In this report we describe our application of the tagged psoralen in imaging experiments, and the unexpected discoveries they revealed., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Published by Elsevier B.V.)

The pilot study evaluated contingency management (CM) for family-based obesity therapy (FBT). The secondary outcome assessed the association of the hepatic transient electrography (TE) parameters, including the controlled attenuation parameter (CAP) and liver stiffness (LSM), and changes in liver function blood tests and BMI changes in youth involved in intensive FBT. It included youth-parent dyads from an urban pediatric center randomized to weekly behavioral therapy (BT, n= 4) who received fixed financial compensation for attendance, or BT+CM (n= 5) who received an escalating monetary reward for weight loss. At week 30, all youth and parents had weight-loss trends without significant differences between groups. While the TE measures and blood tests were normal in the youth at baseline and week 30, the CAP changes correlated with BMI changes (R 2 = 0.86, P< 0.001) and LSM changes with alanine aminotransferase changes (R 2 = 0.79, P=0.005). In conclusion, BT+CM did not significantly add to the BMI improvement seen with BT alone in youth and their parents. However, in youth with obesity and normal liver blood tests, TE may be useful for monitoring changes in fatty liver disease., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Majumdar et al.)

This was a prospective observational study to evaluate abnormalities in lipid profile in 50 children with transfusion dependent thalassemia. Dyslipidemia characterized by high triglycerides, low high density lipoprotein (HDL), and high total cholesterol: HDL ratio was noted. These pro atherogenic risk factors may be lead to significant cardiovascular morbidity in these patients.

Chronic RV pacing may lead to pacing induced cardiomyopathy in some patients and results in a higher risk of development of LV systolic dysfunction, heart failure, mitral regurgitation and atrial fibrillation. His bundle pacing emerged as the most physiologic form of ventricular pacing. However, wide adoption of this technique in routine clinical practice is limited by higher capture thresholds at implant sometimes, lower R wave amplitudes, atrial over sensing and increased risk for late rise in pacing thresholds (resulting in the need for lead revisions). Some recent studies have focused on left bundle branch area pacing as a solution to these problems. In our study, we have compared left bundle branch area pacing (in 22 patients) with conventional right ventricular apical pacing (in 28 patients) who presented to us with conventional indications for pacemaker implantations in term of procedure and fluoroscopy time and short-term lead performance and left ventricular function. The results of our study showed that left bundle branch area pacing is associated with shortened QRS duration (22.36 ± 9.36 ms) and better LV function (higher left ventricular ejection fraction 64.00 ± 3.03 vs. 59.73 ± 6.73 with a p value of 0.013 and lower left ventricular diastolic internal diameter 4.58 ± 0.32 vs. 5.23 ± 0.40 cm with a p value of < 0.001) in comparison to right ventricular apical pacing. The total procedure time and fluoroscopy time was similar (63.15 ± 7.02 vs. 55.15 ± 6.16 min, p value 0.142 and 6.08 ± 1.42 vs. 5.06 ± 1.30 min, p value 0.332 respectively) in left bundle branch area pacing group. The results of this study indicate that left bundle branch area pacing may be an option for physiological pacing in patients requiring a high percentage of ventricular pacing.

Purpose: Efficacy of multi-disciplinary weight management (MDM) in youth has not been compared to their routine care., Objectives: To compare body mass index z-score (zBMI) and blood test (lab) changes (Δ) in youth before and after MDM and to correlate bio-impedance analysis (BIA) and lab measurements., Methods: We compared zBMI Δ (from referring providers' records), within 3 months prior to MDM, to monthly zBMI Δ after MDM, in a retrospective cohort of youth at a tertiary MDM center. BIA and lab measurements after 6 months, MDM were compared to baseline., Results: We reviewed 316 records (12.9 ± 3.5 years, 49% males, 104.8 ± 35.1 kgs). The pre-MDM zBMI Δ (0.02 ± 0.1) was reversed after MDM (-0.03 ± 0.09, visit 2, P < 0.001). The zBMI Δ progressed on follow-up (-0.14 ± 0.05, visit 6). Baseline BIA components correlated with Homeostatic Model Assessment of Insulin resistance (HOMA-IR), triglycerides, and systolic blood pressure. HbA1c, HOMA-IR, and liver functions significantly improved on follow-up. MDM participation showed progressive attrition and dropped to 11.6% at visit 6., Conclusion: MDM in youth resulted in zBMI and lab improvements compared to their pre-MDM measurements. BIA provided additional outcome measures that correlated with metabolic markers. MDM follow-up was limited by the progressive participant drop-out. Behavioral economic strategies are needed to improve adherence.

Dorsal dermal sinus (DDS) represents the spectrum of spinal dysraphism. Children may present with features of meningitis. A 13-month male child presented with features of meningitis and quadriparesis. Clinical examination revealed a small pit over the thoracic spine. MRI was suggestive of a DDS. Initially, the patient responded to antibiotics and methylprednisolone, which was given for resolving the mass effect. However, he had a recurrence of symptoms and underwent surgical exploration and resection of DSS with resolution of symptoms. Careful examination of the back is extremely essential in children with meningitis. Radiological investigation helps in visualisation of the DSS. Although rare in children, they may present with recurrent meningitis., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Competing Interests: Competing interests: None declared.

Obesity in pediatric patients is rising with nearly one third of children in the USA classified as overweight and up to 16-18% of the adolescent population obese with at least one comorbid condition. Consequently, bariatric procedures in this population have increased without consistent recommendations for follow-up and transition to adult providers. This review describes the known and potential long-term consequences of bariatric surgery in pediatric patients, reviews the current literature on transitions of care for adolescent patients with chronic illnesses. Additionally, this review summarizes recommendations from the literature for developing a standardized program for transitioning care for post-bariatric surgical patients and offers useful tools and guidelines for doing so.

Cytosolic pattern recognition receptors play key roles in innate immune response. Nucleotide binding and oligomerisation domain containing protein 1 (NOD1) belonging to the Nod-like receptor C (NLRC) sub-family of Nod-like receptors (NLRs) is important for detection and clearance of intra-cellular Gram negative bacteria. NOD1 is involved in activation of pro-inflammatory pathways. Limited structural data is available for NOD1. Using different templates for each domain of NOD1, we determined the full-length homology model of NOD1. ADP binding amino acids within the nucleotide binding domain (NBD) of NOD1 were also predicted. Key residues in inter-domain interaction were identified by sequence comparison with Oryctolagus cuniculus NOD2, a related protein. Interactions between NBD and winged helix domain (WHD) were found to be conserved in NOD1. Functional and structural effect of single nucleotide polymorphisms within the NOD1 NBD domain associated with susceptibility risk to Ulcerative colitis (UC), an inflammatory disorder of the colon was evaluated by in silico studies. Mutations W219R and L349P were predicted to be damaging and disease associated by prediction programs SIFT, PolyPhen2, PANTHER, SNP&GO, PhD SNP and SNAP2. We further validated the effect of W219R and L349P mutation on NOD1 function in vitro. Elevated mRNA expression of pro-inflammatory cytokines IL8 and IL-1β was seen as compared to the wild type NOD1 in intestinal epithelial cell line HT29 when stimulated with NOD1 ligand. Thus, these mutations may indeed have a bearing on pathogenesis of inflammation during UC., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

This observational, descriptive study was conducted on 260 dengue patients diagnosed as per the revised 2009 WHO guidelines in a tertiary-care hospital of eastern India between June and November 2015. Children were evaluated for clinical symptoms, signs, and laboratory parameters. Clinical variables viz., rash, nausea/vomiting, bleeding, oliguria, capillary leak and liver enlargement; and laboratory variables viz., rising haemoglobin, haematocrit, thrombocytopenia, blood urea, serum Creatinine, ALT, hypo albuminemia and cholesterol were found to be significantly associated with outcome.

Ulcerative colitis (UC), an inflammatory disorder of the colon arises from dysregulated immune response towards gut microbes. Transcription factor NFκB is a major regulatory component influencing mucosal inflammation. We evaluated expression of Tumor Necrosis Factor Alpha Induced Protein3 (TNFAIP3), the inhibitor of NFκB activation and its associated partners ITCH, RNF11 and Tax1BP1 in inflamed mucosa of UC patients. We found highly significant up-regulated mRNA expression of TNFAIP3 that negatively correlated with disease activity in UC. mRNA levels of ITCH, RNF11 and Tax1BP1 were significantly down-regulated. Significant positive correlation with disease activity was noted for Tax1BP1. All four genes showed significant down-regulation at protein level. mRNA levels of inducers of TNFAIP3 expression, NFκB p65 subunit and MAST3 was determined. There was significant increase in p65 mRNA expression and down-regulated MAST3 expression. This suggested that increase in NFκB expression regulates TNFAIP3 levels. Deficiency of TNFAIP3 expression resulted in significant up-regulation of NFκB p65 sub-unit as well as its downstream genes such as iNOS, an inflammatory marker, inhibitors of apoptosis like cIAP2 and XIAP and mediators of anti-apoptotic signals TRAF1 and TRAF2. Taken together, decreased expression of TNFAIP3 and its partners contribute to inflammation and up-regulation of apoptosis inhibitors that may create microenvironment for colorectal cancer.

Youth with type 1 diabetes (T1DM) gain weight after insulin therapy initiation. We aimed to study the effects of Enhanced Dietary Counseling (EDC) compared to Standard of Care Dietary Counseling (SDC) on BMI trajectory in youth with new-onset T1DM. Youth with new-onset T1DM (n = 47; 8.9 + 4.2 years) were randomized 6 weeks post-diagnosis to either SDC per American Diabetes Association guidelines (n = 25) or EDC (n = 22: SDC plus monthly nutritional education and 3-day food records (FRs) at 6 and 24 weeks). Weights and heights were measured at diagnosis, 6 weeks, 3, 6, and 12 months post-diagnosis; pre-diagnosis BMI was obtained from pediatricians' records. BMI Z score was used to track BMI change. Knowledge of recommended daily energy intake (DEI) and daily carbohydrate intake was assessed at follow-up visits. Changes in BMI Z scores were similar in SDC versus EDC subjects from pre-diagnosis to 12 months post-diagnosis. BMI Z score at 12 months exceeded pre-diagnosis level in 58.5 % subjects (54.5 % EDC vs. 63.1 % SDC, p = 0.75). From 6 weeks to 6 months, percentage of subjects correctly recalling recommended DEI increased in EDC along with percentage of subjects meeting recommended daily fruit servings intake from 25 % (6 weeks) to 64 % (6 months), p = 0.047). EDC did not prevent BMI Z score increases in youth with new-onset T1DM, and BMI Z score exceeded pre-diagnosis levels in >50 % 12 months post-diagnosis. A family-based approach and/or additional intervention may be needed to prevent excessive weight gain.