Surgical Management of Pediatric Obstructive Sleep Apnea Beyond Adenotonsillectomy: The Nose, Nasopharynx, and Palate.

While adenotonsillectomy is the primary treatment of pediatric obstructive sleep apnea (OSA), persistent OSA after surgery is common and may be due to residual obstruction at the nose, nasopharynx, and/or palate. Comprehensive evaluation for persistent pediatric OSA ideally includes clinical examination (with or without awake nasal endosocpy) as well as drug-induced sleep endoscopy in order to accurately identify sources of residual obstruction. Depending on the site of obstruction, some of the surgical management options include submucous inferior turbinate resection, septoplasty, adenoidectomy, and expansion sphincter pharyngoplasty.

Senescence in oral lichen planus as assessed by the immunohistochemical evaluation of senescence marker protein-30 (Regucalcin).

Background: Oral lichen planus is a T-cell-mediated chronic inflammatory disease affecting approximately 1% to 2% of the population, the etiology of which is currently unknown. The objectives of this study were to observe if senescence occurs in oral lichen planus, through the assessment of the immunohistochemical expression of a novel marker for senescence called Senescence marker protein-30 or regucalcin, and compare the expression to that in oral lichenoid reaction and non-specific inflammation. Subjects and Methods: The study material consisted of 30 cases of oral lichen planus, 15 cases of oral lichenoid reaction and 15 cases of non-specific inflammation. The number of positive cells in ten randomly selected high power fields were counted in the epithelium and the connective tissue separately and the mean was determined. Results: Mann-Whitney U test was used to statistically analyze if there was any significant difference in the expression of Senescence marker protein-30 between oral lichen planus, oral lichenoid reaction and non-specific inflammation. Even though a greater expression was seen in the oral lichen planus cases than oral lichenoid reaction, the difference in both the epithelium and connective tissue was not statistically significant. Conclusion: This study shows that in addition to the already known mechanisms like apoptosis and increased cell proliferation rates, the activated T-lymphocytes may also trigger a senescent change in the cells of oral lichen planus. As with the other mechanisms, this is also seen only in a small proportion of the cases.

Early Adverse Events Following Pediatric Mandibular Advancement: Analysis of the ACS NSQIP-Pediatric Database.

OBJECTIVE: This study aims to assess early adverse events and patient factors associated with complications following mandible distraction osteogenesis (MDO). MATERIALS AND METHODS: The American College of Surgeons National Surgical Quality Improvement Program-Pediatric (NSQIP-Pediatric) database, years 2012 to 2019, was queried for patients undergoing mandible advancement via relevant Current Procedural Terminology and postoperative diagnosis codes. Thirty-day adverse events and co-morbidities are assessed. RESULTS: A total of 208 patients were identified with 17.3% (n = 36) experiencing an adverse event, reoperation (n = 14), and readmission (n = 11) being most common. Patients < 365 days old at the time of operation were more likely to experience an adverse event (26.1% vs 10.8%; P = .005). However, among patients less than 1 year of age, differences in the complication rates between patients ≤ 28 days and >28 days (30.2% vs 22.2%; P = .47) and those weighing ≤ 4 kg and >4 kg (31.7% vs 11.5%; P = .063) did not reach statistical significance. CONCLUSIONS: Adverse events following mandible advancement are relatively common, though often minor. In our analysis of the NSQIP-Pediatric database, neonatal age ( ≤ 28 days) or weight ≤ 4 kg did not result in a statistically significant increase in complications among patients less than 1 year of age. Providers should consider early intervention in patients who may benefit from MDO.

Multitarget-directed therapeutics: (Urea/thiourea)2 derivatives of diverse heterocyclic-Lys conjugates.

The synthesis of a new small library of molecules containing bis-urea/thiourea pendants in lysine conjugated to three different heterocycles is described. The heterocycles used in this study have benzisoxazole/piperazine/piperidine units. After a detailed antimicrobial, antioxidant, and anti-inflammatory evaluation, it was found that the most active compounds are 10, 11, 14, 15, 18, 19 and 10, 11, 19 and 8, 9, 12, 13, 16, 17, respectively. Further, it was observed that the presence of all three entities, that is, urea/thiourea, the substituent (OMe/F), as well as the heterocycle, is highly essential for exerting potent activity. Among the heterocycles, the presence of isoxazole seems to be highly beneficial for exerting good potency. In continuation, docking studies have revealed extraordinary binding efficiency for some of the active compounds. Given their potent biological results and docking score, some of the title compounds could be potential drug candidates for microbial-related diseases and provide a basis for future research into the development of molecules possessing multitask ability.

In-silico investigation of phytochemicals from Asparagus racemosus as plausible antiviral agent in COVID-19.

COVID-19 has ravaged the world and is the greatest of pandemics in human history, in the absence of treatment or vaccine the mortality and morbidity rates are very high. The present investigation was undertaken to screen and identify the potent leads from the Indian Ayurvedic herb, Asparagus racemosus (Willd.) against SARS-CoV-2 using molecular docking and dynamics studies. The docking analysis was performed on the Glide module of Schrödinger suite on two different proteins from SARS-CoV-2 viz. NSP15 Endoribonuclease and spike receptor-binding domain. Asparoside-C, Asparoside-D and Asparoside -F were found to be most effective against both the proteins as confirmed through their docking score and affinity. Further, the 100 ns molecular dynamics study also confirmed the potential of these compounds from reasonably lower root mean square deviations and better stabilization of Asparoside-C and Asparoside-F in spike receptor-binding domain and NSP15 Endoribonuclease respectively. MM-GBSA based binding free energy calculations also suggest the most favourable binding affinities of Asparoside-C and Asparoside-F with binding energies of -62.61 and -55.19 Kcal/mol respectively with spike receptor-binding domain and NSP15 Endoribonuclease. HighlightsAsparagus racemosus have antiviral potentialPhytochemicals of Shatavari showed promising in-silico docking and MD resultsAsparaoside-C and Asparoside-F has good binding with target proteinsAsparagus racemosus holds promise as SARS-COV-2 (S) and (N) proteins inhibitor Communicated by Ramaswamy H. Sarma.

The translational activator Sov1 coordinates mitochondrial gene expression with mitoribosome biogenesis.

Mitoribosome biogenesis is an expensive metabolic process that is essential to maintain cellular respiratory capacity and requires the stoichiometric accumulation of rRNAs and proteins encoded in two distinct genomes. In yeast, the ribosomal protein Var1, alias uS3m, is mitochondrion-encoded. uS3m is a protein universally present in all ribosomes, where it forms part of the small subunit (SSU) mRNA entry channel and plays a pivotal role in ribosome loading onto the mRNA. However, despite its critical functional role, very little is known concerning VAR1 gene expression. Here, we demonstrate that the protein Sov1 is an in bona fide VAR1 mRNA translational activator and additionally interacts with newly synthesized Var1 polypeptide. Moreover, we show that Sov1 assists the late steps of mtSSU biogenesis involving the incorporation of Var1, an event necessary for uS14 and mS46 assembly. Notably, we have uncovered a translational regulatory mechanism by which Sov1 fine-tunes Var1 synthesis with its assembly into the mitoribosome.

Experimental synthesis of size-controlled TiO2 nanofillers and their possible use as composites in restorative dentistry.

The aim of this work was to obtain an efficient protocol with a green, fast and facile way to synthesize TiO2 NPs and its application as fillers for enhancement of desired dental properties of light curing dental composites. A comparative study comprised the fabrication of light curing restorative composite materials with incorporating different fillers with varying wt%, varying resin material composition, to determine optimal dental restoration by focusing on the physical properties of dental materials. It was observed that the as-prepared green synthesized TiO2 nanohybrid particles contributed to the improvement in physical properties, thus promoting the green and rapid synthesis of nanohybrid fillers. In addition, mechanical values for experimental cured resin materials with bare and surface modified fillers were obtained. The experimental light curing nanocomposites with 5 wt% (wt%) nanohybrid surface modified filler particles with BisGMA (60 wt%), TEGDMA (20 wt%) and UDMA (20 wt%) resin composition provided increased physical strength and durability with higher compressive stress 195.56 MPa and flexural stress 83.30 MPa. Furthermore, the dental property, such as polymerization shrinkage (PS) obtained from volumetric method was decreased up to 3.4% by the addition of nano-hybrid fillers. In addition to this, the biocompatible and antimicrobial nature of TiO2 and its aesthetics properties such as tooth-like color makes TiO2 favorable to use as fillers. This study presents a green and facile method for the synthesis of TiO2 nanohybrid particles that can be successfully used as fillers in an experimental light curing resin matrix for enhancing its dental properties. This describes the potential of the green synthesized TiO2 nanohybrid particles to use as fillers in restorative dentistry.

Imidazolo and tryptophan-imidazolo hybrid derived ureas/thioureas as potent bioactive agents - SAR and molecular modelling studies.

Herein, we used an imidazole derivative (IMD) which showed promising antibacterial, antifungal and antioxidant properties in our earlier investigation. Prompted by this, we converted IMD to hydrazide (IMH) by hydrazinolysis which was derivatized to various ureas (3-7) and thioureas (8-12). On the other hand, IMH was conjugated to Boc-Trp-OH as it has been shown in the past that hybridization of two molecules produced promising biologically active compounds. Boc of the conjugate was removed and further converted into several urea (14-18) and thiourea (19-23) derivatives. All the title compounds so also the starting materials and intermediates were assessed for potential biological applications. The results showed that compounds 3, 4, 8, 9, 14, 15, 19 and 20 were excellent antioxidants as revealed by DPPH, DMPD and ABTS assays. Further, certain analogues like 5-7, 10-12, 16-18 and 21-23 were found to be potent antimicrobials against pathogenic bacteria and fungi whereas good anti-inflammatory activity was obtained for molecules 5-7, 10-12, 16-18 and 21-23. All together, derivatives of the conjugates have shown superior activity over non-conjugated compounds and the former have exhibited potent activity against standard drugs in all the assays. In a quest to understand the binding interactions of the compounds with active site of tyrosine kinase (PDB ID: 2HCK), glucosamine-6-phosphate (GlcN-6-P) synthase (PDB ID: 2VF5) and cyclooxygenase-2 (PDB ID: 1CX2) enzymes, the correlation studies were conducted using molecular modelling which showed good receptor binding interactions with several amino acids of the enzymes. Overall, the current investigation may be considered for the discovery of lead compound(s) for treating multiple disorder conditions using singular molecular entity.

A correlation study of biological activity and molecular docking of Asp and Glu linked bis-hydrazones of quinazolinones.

The present investigation involves the synthesis and spectroscopic and biological activity studies of the bis-hydrazones of quinazolinones derived from aspartic acid and glutamic acid. The antioxidant activities of the compounds were evaluated using DPPH, DMPD and ABTS radical scavenging assays whose results revealed that the IC50 of compounds 6, 7, 11, 12, 20, 21, 25 and 26 was lower than those of the standard references. The anti-inflammatory activity was evaluated with a haemolysis assay using a human blood erythrocytes suspension and the results demonstrated that compounds 8, 9, 13, 14, 22, 23, 27 and 28 were excellent anti-inflammatory agents. In addition, the antibacterial and antifungal activities against various clinical pathogens of human origin revealed that compounds 7, 9, 12, 14, 21, 23, 26 and 28 possessed potent antimicrobial properties. Furthermore, to understand the correlation between biological activity and drug-receptor interaction, molecular docking was performed on the active sites of tyrosine kinase (PDB ID: 2HCK), cyclooxygenase-2 (PDB ID: 1CX2) and glucosamine-6-phosphate (GlcN-6-P) synthase (PDB ID: 2VF5) which showed good binding profiles with the targets that can potentially hold the title compounds. The correlation study revealed that compounds containing EDGs (-OH, -OCH3) were excellent antioxidants, compounds with EWGs (-Cl, -NO2) exhibited good anti-inflammatory activity and compounds bearing -OH and -NO2 groups were very good antimicrobials.

Assessment of Tumor Associated Tissue Eosinophilia (TATE) in Oral Squamous Cell Carcinoma Using Carbol Chromotrope Stain / Evaluación de la Eosinofilia Tisular Asociada al Tumor (TATE) en el Carcinoma Oral de Células Escamosas Mediante la Tinción de Carbol Cromótropo

Tumor related tissue eosinophilia (TATE) is a known phenomenon but its role in prognostics and correlation with size of the primary tumor is still controversial. Using a stain, like Carbol chromotrope, that targets eosinophils exclusively and vividly, offers an advantage over haematoxylin and eosin, which was used in most of the studies. Forty-nine cases of oral squamous cell carcinoma, where the TNM staging has been recorded in their history, was taken and stained with Lendrum's carbol chromotrope. Significant difference in the eosinophil count with varying size of the tumor and a parallel increase in the number noted, with increase in size. There is a corresponding increase in the number of eosinophils infiltrating the tumor with increase in size of oral squamous cell carcinoma.

La eosinofilia tisular asociada a tumores (TATE) es un fenómeno conocido, sin embargo su pronóstico y correlación con el tamaño del tumor primario aún es tema de controversia. El uso de cromotropo como tinción dirigida exclusivamente a los eosinófilos, ofrece una ventaja sobre la hematoxilina-eosina, que ha sido utilizada en la mayoría de los estudios. Se estudiaron células escamosas en 49 casos de carcinoma oral, con registro del estadio TNM. Las células fueron teñidas con carbol cromotropo de Lendrum. Se observó una diferencia significativa en el recuento de eosinófilos con el tamaño del tumor y un aumento paralelo en número, con el aumento de tamaño. Hay un aumento correspondiente en el número de eosinófilos que infiltran el tumor con aumento en el tamaño de carcinoma de células escamosas orales.

Pectineal Ligament Hysteropexy for Uterine Prolapse in Premenopausal Women by Open and Laparoscopic Approach in Indian Urban and Rural Centers.

OBJECTIVE: The aim of this study was to evaluate (a) the surgical outcomes of pectineal ligament hysteropexy (PLH) for uterine prolapse by laparotomy and (b) the feasibility and safety of the procedure by laparoscopic route. METHODS: This is a retrospective consecutive case series of women who underwent PLH from January 1998 to December 2011. The prolapsed uterus was suspended with polyester tape to pectineal ligament on either side through a Cherney incision or laparoscopically at 3 urban and 3 rural hospitals in India. RESULTS: In 194 women who underwent PLH (176 open and 18 laparoscopic), there were no intraoperative complications. The mean follow-up was 6.5 years (range, 0.5-12 years) for open method and 1 year (range, 0.5-2 years) for laparoscopic approach. There were 46 births in 40 women after the procedure including 32 vaginal and 14 cesarean deliveries. Overall, 10 women (5.1%) had uterine prolapse recurrence; 7 of these occurred after vaginal delivery. One woman had tape erosion into the bladder because of pelvic tuberculosis. At follow-up, 12 women developed cystocele, and 7 women developed portio vaginalis elongation. There were no postoperative enteroceles. Overall reoperation rate was 14.9%. Laparoscopic PLH had minimal morbidity with no recurrence over 2 years. CONCLUSIONS: Open PLH for uterine prolapse may be safely performed and gives durable support to the prolapsed uterus with low recurrence risk.

Implications of N-capped urea/thiourea and C-capped 3-(1-piperazinyl)-1,2-benzisothiazole with bridging Gly-Val/Phe-Gly-Val-Pro as therapeutic targets.

A series of urea/thiourea derivatives were synthesized by using peptides conjugated to 3-(1-piperazinyl)-1,2-benzisothiazole and their structure was characterized by analytical and spectral ((1)H, (13)C NMR and Mass) methods. These compounds were screened for antimicrobial and antiglycating activity as well as urease and H(+)/K(+)-ATPase inhibition. Preliminary structure-activity relationship studies revealed that the compounds possessing fluoro moiety were excellent antimicrobial agents. Furthermore, for other biological activities methoxy substituent was found to be the most active particularly upon substitution at para position.

Association of homocysteine with global DNA methylation in vegetarian Indian pregnant women and neonatal birth anthropometrics.

OBJECTIVE: The present study was designed to evaluate if plasma maternal folate, vitamin B-12 and homocysteine levels had an effect on maternal global DNA methylation and neonatal anthropometrics in Indian pregnant women. METHODS: A total of 49 participants having completed ≥36 weeks of pregnancy were enrolled in the study. Estimation of folate was by Ion capture assay, vitamin B-12 by microparticle enzyme immunoassay, total homocysteine by fluorescence polarization immunoassay and global DNA methylation using Cayman's DNA methylation enzyme immunoassay (EIA) kit. RESULTS: Folate and vitamin B-12 were inversely correlated to homocysteine in pregnant women consuming vegetarian and non-vegetarian diet. No difference in global DNA methylation was found between the vegetarian and non-vegetarian pregnant women. Folate and vitamin B-12 did not show association with global DNA methylation, however plasma total homocysteine of the vegetarian group showed significant correlation to global DNA methylation (r(2 )= 0.49, p = 0.011). Plasma total homocysteine was inversely related to tricep skinfold (r(2 )= -0.484, p = 0.01) and chest circumference (r(2 )= -0.104, p = 0.04) of neonates in vegetarian group. CONCLUSION: Moderate vitamin B-12 deficiency in vegetarian pregnant women might be the cause of hyperhomocystinemia, hypermethylation when compared to vitamin B-12 sufficient non-vegetarian group.

Design and synthesis of amino acids-conjugated heterocycle derived ureas/thioureas as potent inhibitors of protein glycation.

Protein glycation is believed to play an important role in the development of long-term disorders associated with diabetic complications. In view of the wide occurrence of advanced glycation end products (AGE's) and the oxidative stress derived from them in a variety of diabetic complications, it would be of great interest to identify and develop AGE inhibitors. In this study, synthesis and in vitro antiglycation activity of a small library of forty urea/thiourea derivatives of Phe/Tyr/Glu/Lys-benzisoxazole hybrids are reported. Structures of the compounds were confirmed by IR, NMR, mass spectrometry, and elemental analysis. Most of the title compounds exhibited promising activity. Best antiglycation activity was found for Tyr analogue with methoxy group as a substituent particularly at the para position with IC50 value of 1.9 microM against the positive control, Rutin, with IC50 = 41.9 microM. Thus, the title compounds represent novel class of potent antiglycating agents.

Pectineal ligament suspension of prolapsed vaginal vault.

OBJECTIVE: To report on a collective pectineal ligament suspension experience acquired over 12 years in India with 119 women who presented with prolapsed vaginal vault. The feasibility and effectiveness of the procedure was assessed for the open and laparoscopic routes. METHODS: The prolapsed vaginal vault was suspended unilaterally to the pectineal ligament using polyester tape at 3 urban and 3 rural hospitals. The procedure was done through a Cherney incision in 104 women. In the remaining 15 women, it was done laparoscopically at a single urban center. RESULTS: There were no intraoperative complications. The mean follow-up was 5.5 years (range, 0.5-12 years). Only 2 women had vaginal prolapse recurrence, at 3 and 5 years. Two had asymptomatic tape erosion, at 2 and 5 years, and a mild cystocele appeared in 5 women and a low rectocele in 4. However, none of these women required further vaginal surgery during their follow-up period. CONCLUSION: The present study demonstrates the long-term safety and effectiveness of pectineal ligament suspension for vaginal vault prolapse by the open and the laparoscopic routes. As it was done by surgeons of varying experience at centers with varying resources, the procedure can be readily mastered by any gynecologic surgeon.

tert-Butyl 1,5-bis(4-(benzo[d]isothiazol-3-yl)piperazin-1-yl)-1,5-dioxopentan-2-ylcarbamate urea/thiourea derivatives as potent H+/K(+)-ATPase inhibitors.

Amino acids are known to possess variable efficacy against ulceration. Considering the good antiulcer activity of amino acids, a series of urea/thiourea derivatives of glutamic acid conjugated benzisothiazole analogue 3a-u with various substituents on aryl ring were synthesized, spectroscopically characterized and evaluated for in vitro H(+)/K(+)-ATPase inhibition. Majority of the compounds possessed potency compared to that of omeprazole, a reference drug. In particular, methoxy derivatives 3p-u were the most active compounds possessing a significant 15-fold increase for para substituent thus, contributing positively to gastric H(+)/K(+)-ATPase inhibition.

Inhibition of protein glycation by urea and thiourea derivatives of glycine/proline conjugated benzisoxazole analogue - synthesis and structure-activity studies.

Synthesis of a new series of urea/thiourea derivatives of Gly/Pro conjugated benzisoxazole has been reported. Structure of the compounds was characterized by physical and spectroscopical data and has been screened for their in vitro antiglycation activity. Several compounds showed promising activity with IC(50) < 5 µM compared to standard rutin (IC(50) = 41.9 µM). Further, it was found that compounds containing methoxy and bromine substituents have exerted highly potent activity. Thus, the title compounds represent novel class of potent antiglycating agents.

Novel urea and thiourea derivatives of thiazole-glutamic acid conjugate as potential inhibitors of microbes and fungi.

Since discovery and development of effective as well as safe drugs has brought a progressive era in human healthcare that is accompanied by the appearance of drug resistant bacterial strains, there is constant need of new antibacterial agent having novel mechanisms of action to act against the harmful pathogens. In the present study, several N-terminal substituted urea/thiourea derivatives were synthesized by the reaction of glutamic acid and 3-(1-piperazinyl)-1,2-benzisothiazole with various substituted phenyl isocyanates/isothiocyanates. Elemental analysis, IR, 1H NMR, 13C NMR and mass spectral data confirmed the structure of the newly synthesized compounds. The derivatives were investigated for their antibacterial and antifungal activities against various pathogens of human origin by agar well diffusion method and microdilution method. The preliminary antimicrobial bioassay reveals that the compounds containing fluoro and bromo as substituents showed promising antimicrobial activity.

Synthesis of quinazolinone conjugated shorter analogues of Bactenecin7 as potent antimicrobials.

A series of shorter peptide analogues of Bactenecin7 (RP, PRP, GPRP and RPRP) were synthesized and conjugated to 3-(4-oxo-3,4-dihydroquinazolin-2-yl)propanoic acid to study the effect of conjugation. All the peptides and their conjugates were characterized by analytical and spectroscopic techniques. The synthesized compounds viz., peptides, heterocyclic conjugates and the hydrogenolyzed products were evaluated for antimicrobial activity against a panel of pathogens. The results revealed that all the conjugates have shown enhanced activity than their counterparts. Further, hydrogenolyzed tetrapeptide conjugates (10 and 13) have exerted highly potent activity nearly 3-4 times than the standard drugs used.

Design and synthesis of tryptophan containing peptides as potential analgesic and anti-inflammatory agents.

A new series of smaller peptides with tryptophan at C-terminal and varying N-protected amino acids/peptides were designed, synthesized and characterized by analytical and spectroscopic techniques. Analgesic and anti-inflammatory properties of these peptides were carried out in vivo using tail-flick method and carrageenan-induced paw edema method, respectively, at different doses and different time intervals. Most of the peptides synthesized displayed enhanced activity, and particularly tetra and hexapeptides 29-31 were found to be even more potent than the reference standards used. Moreover, some peptides have exhibited promising activity even after 24 h of administration, whereas the reference standards were active only up to 3 h. Further, the compounds did not present any ulcerogenic liability.