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1.
Catheter Cardiovasc Interv ; 103(1): 238-242, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-37971094

RESUMEN

A 75-year-old female was found to have mechanical mitral valve thrombosis complicated by severe mitral stenosis, pulmonary edema, and right heart failure. She was at prohibitive risk for surgical intervention. She did not tolerate thrombolysis due to bleeding. We performed percutaneous intervention with cerebral protection with subsequent restoration of mechanical mitral valve function, resolution of the mitral valve stenosis, and no neurologic complications.


Asunto(s)
Implantación de Prótesis de Válvulas Cardíacas , Prótesis Valvulares Cardíacas , Estenosis de la Válvula Mitral , Trombosis , Femenino , Humanos , Anciano , Válvula Mitral/diagnóstico por imagen , Válvula Mitral/cirugía , Resultado del Tratamiento , Estenosis de la Válvula Mitral/diagnóstico por imagen , Estenosis de la Válvula Mitral/cirugía , Implantación de Prótesis de Válvulas Cardíacas/efectos adversos , Trombosis/diagnóstico por imagen , Trombosis/etiología , Trombosis/terapia , Prótesis Valvulares Cardíacas/efectos adversos
2.
Curr Genomics ; 25(2): 105-119, 2024 Apr 08.
Artículo en Inglés | MEDLINE | ID: mdl-38751600

RESUMEN

Background: The plasma virome represents the overall composition of viral sequences present in it. Alteration in plasma virome has been reported in treatment naïve and immunocompromised (CD4 count < 200) people with HIV (PWH). However, the effect of ART on virome composition in PWH on ART with preserved CD4 counts is poorly understood. Objectives: We aimed to assess the alterations in plasma virome in PWH on ART in comparison to HIV-negative uninfected controls and to further investigate possible associations of plasma viruses with inflammation and immune dysfunction, namely, immunosenescence and immune exhaustion. Methods: Plasma viral DNA from PWH on ART and controls was used for sequencing on the Illumina Nextseq500 platform, followed by the identification of viral sequences using an automated pipeline, VIROMATCH. Multiplex cytokine assay was performed to measure the concentrations of various cytokines in plasma. Immunophenotyping was performed on PBMCs to identify T cell markers of immunosenescence and immune exhaustion. Results: In our observational, cross-sectional pilot study, chronically infected PWH on ART had significantly different viral species compositions compared to controls. The plasma virome of PWH showed a significantly high relative abundance of species Human gammaherpesvirus 4, also known as Epstein-Barr virus (EBV). Moreover, EBV emerged as a significant viral taxon differentially enriched in PWH on ART, which further correlated positively with the exhaustion phenotype of T cells and significantly increased TNF-α in PWH on ART. Additionally, a significantly increased proportion of senescent T cells and IL-8 cytokine was detected in PWH on ART. Conclusion: Altered plasma virome influenced the inflammatory response and T-cell phenotype in PWH on ART.

3.
BMC Nephrol ; 25(1): 16, 2024 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-38200454

RESUMEN

BACKGROUND: Plasma proenkephalin A (PENK-A) is a precursor of active enkephalins. Higher blood concentrations have been associated with estimated glomerular filtration rate (eGFR) decline in European populations. Due to the significant disparity in incident chronic kidney disease (CKD) between White and Black people, we evaluated the association of PENK-A with incident CKD and other kidney outcomes among a biracial cohort in the U.S. METHODS: In a nested cohort of 4,400 participants among the REasons for Geographic And Racial Differences in Stroke, we determined the association between baseline PENK-A concentration and incident CKD using the creatinine-cystatin C CKD-EPI 2021 equation without race coefficient, significant eGFR decline, and incident albuminuria between baseline and a follow-up visit 9.4 years later. We tested for race and sex interactions. We used inverse probability sampling weights to account for the sampling design. RESULTS: At baseline, mean (SD) age was 64 (8) years, 49% were women, and 52% were Black participants. 8.5% developed CKD, 21% experienced ≥ 30% decline in eGFR and 18% developed albuminuria. There was no association between PENK-A and incident CKD and no difference by race or sex. However, higher PENK-A was associated with increased odds of progressive eGFR decline (OR: 1.12; 95% CI 1.00, 1.25). Higher PENK-A concentration was strongly associated with incident albuminuria among patients without diabetes mellitus (OR: 1.29; 95% CI 1.09, 1.53). CONCLUSION: While PENK-A was not associated with incident CKD, its associations with progression of CKD and incident albuminuria, among patients without diabetes, suggest that it might be a useful tool in the evaluation of kidney disease among White and Black patients.


Asunto(s)
Precursores de Proteínas , Insuficiencia Renal Crónica , Accidente Cerebrovascular , Humanos , Femenino , Persona de Mediana Edad , Masculino , Albuminuria/epidemiología , Factores Raciales , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/epidemiología , Accidente Cerebrovascular/epidemiología , Encefalinas
4.
Curr Opin Nephrol Hypertens ; 32(4): 330-334, 2023 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-37195253

RESUMEN

PURPOSE OF REVIEW: Recent studies have shed light on factors influencing FGF23 regulation in terms of its production and cleavage. However, less is known about FGF23 elimination from circulation. The kidney's role in FGF23 elimination will be the focus of this review. RECENT FINDINGS: Marked abnormalities in FGF23 physiology have been observed in persons with reduced kidney function compared with healthy persons and raise the question of whether the kidney may be directly regulating FGF23 concentrations. FGF23 concentrations rise dramatically after onset of acute kidney injury and early chronic kidney disease and are associated with poor clinical outcomes. New studies leveraging measurements of FGF23 in the aorta and renal veins concurrently demonstrate that the human kidney efficiently extracts both intact and C-terminal FGF23 from the circulation independent of kidney function and catabolize the hormone. Additionally, the kidney's reduction of PTH predicts the amount it will reduce both C-terminal and intact FGF23. SUMMARY: The human kidney removes both intact FGF23 and its C-terminal fragments. FGF23 catabolism within the kidney may be influenced by PTH concentrations, and other factors. Future studies to understand regulation of these hormones and the kidney's role in this interplay are timely.


Asunto(s)
Lesión Renal Aguda , Insuficiencia Renal Crónica , Humanos , Factor-23 de Crecimiento de Fibroblastos , Factores de Crecimiento de Fibroblastos/metabolismo , Riñón/metabolismo , Insuficiencia Renal Crónica/metabolismo , Lesión Renal Aguda/metabolismo
5.
Pediatr Blood Cancer ; 70(11): e30650, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37638812

RESUMEN

PURPOSE: A comprehensive operative report for cancer surgery is crucial for accurate disease staging, risk stratification, and therapy escalation/de-escalation, which affects the outcome. Narrative operative reports may fail to include some critical findings. Furthermore, standardized operative reports can form the basis of a local registry, which is often lacking in limited-resource settings (LRSs). In adult literature, synoptic operative reports (SOR) contain more key findings than narrative operative reports. In the LRSs, where the capacity of diagnostic pathology services is typically suboptimal, the value of a thorough operative report is even greater. The aim of this study was to develop a SOR template to help standardize childhood cancer surgery reporting in LRSs. METHODS: Twenty-three experts in pediatric cancer with extensive experience practicing in LRSs were invited to participate in a modified Delphi procedure. SOR domains for pediatric oncology surgery were drafted based on a literature search and then modified based on experts' opinions. The experts anonymously answered multiple rounds of online questionnaires until all domains and subdomains reached a consensus, which was predefined as 70% agreement. RESULTS: Sixteen experts participated in the study, and two rounds of the survey were completed. Twenty-one domains were considered relevant, including demographics, diagnosis, primary site, preoperative disease stage, previous tumor biopsy or surgery, preoperative tumor rupture, neoadjuvant therapy, surgical access, type of resection, completeness of resection, tumor margin assessment, locoregional tumor extension, organ resection, intraoperative tumor spillage, vascular involvement, lymph node sampling, estimated blood loss, intraoperative complications and interventions to address them, specimen names, and specimen orientation. CONCLUSION: We developed a SOR template for pediatric oncology surgery in LRSs. Consensus for all 21 domains and associated subdomains was achieved using a modified Delphi procedure.


Asunto(s)
Neoplasias , Adulto , Humanos , Niño , Técnica Delphi , Oncología Médica , Biopsia , Consenso
6.
Phys Chem Chem Phys ; 25(34): 23081-23091, 2023 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-37602388

RESUMEN

Amyotrophic lateral sclerosis (ALS) is a debilitating neurodegenerative disease commonly caused due to the aggregation of superoxide dismutase 1 (SOD1) protein. Finding inhibitors of SOD1 aggregation is of prime concern, but understanding the mechanistic action of inhibitors is equally important. Recent experiments found that two polyphenols, curcumin, and quercetin, have the ability to inhibit SOD1 aggregation. Quercetin was experimentally proven to break pre-formed fibrils into shorter segments, while curcumin did not significantly affect the pre-formed species. Here, we delve deeper into understanding the mechanism of action of quercetin and curcumin on pre-formed octameric fibrils of SOD1 (28PVKVWGSIKGL38: chains A-H) with the help of molecular dynamics (MD) simulations of a fibril docked polyphenol complex. Our results suggest that quercetin shows π-π stacking interaction with one of the key residues for toxic amyloid formation, Trp 32 of chains D, E, and F, and breaks the peptide chains G, and H from the rest of the fibril. On the other hand, curcumin binds to the hydrophobic amino acids of almost all the chains B-H and stabilizes the fibril rather than destabilizing it. Binding free energy calculations using MM/PBSA showed that curcumin binds more strongly to the SOD1 fibril due to greater van der Waals interactions compared to quercetin. These findings provide insights for the development of potential ALS treatments.


Asunto(s)
Esclerosis Amiotrófica Lateral , Curcumina , Enfermedades Neurodegenerativas , Humanos , Curcumina/farmacología , Quercetina/farmacología , Superóxido Dismutasa-1 , Polifenoles
7.
Phys Chem Chem Phys ; 25(8): 6232-6246, 2023 Feb 22.
Artículo en Inglés | MEDLINE | ID: mdl-36756854

RESUMEN

Pathology of superoxide dismutase 1 (SOD1) aggregation is linked to a neurodegenerative disease known as amyotrophic lateral sclerosis (ALS). Without suitable post-translational modifications (PTMs), the protein structure tends to become aggregation-prone. Understanding the role of PTMs and targeting the aggregation-prone SOD1 with small molecules can be used to design a strategy to inhibit its aggregation. Microsecond long molecular dynamics (MD) simulations followed by free energy surface (FES) analyses show that the loss of structure in the apo monomer happens locally and stepwise. Removing the disulfide bond from apoprotein leads to further instability in the zinc-binding loop, giving rise to non-native protein conformations. Further, it was found that these non-native conformations have a higher propensity to form a non-native dimer. We chose three structurally similar polyphenols based on their binding energies and investigated their impact on SOD1 aggregation kinetics. MD simulations of apo-SOD1SH/corkscrew fibril-polyphenol complexes were also carried out. The effect of polyphenols was seen on fibril elongation as well. Based on the experiments and MD simulation results, it can be inferred that the choice of inhibitors is influenced not only by the binding energy but also by dimer interface stabilization, the proclivity to form non-native dimers, the propensity to break fibrils, and the propensity to decrease the rate of elongation. The polyphenols with 3' and 4' hydroxyl groups are better inhibitors of SOD1 aggregation.


Asunto(s)
Enfermedades Neurodegenerativas , Humanos , Superóxido Dismutasa-1/química , Superóxido Dismutasa-1/metabolismo , Superóxido Dismutasa/metabolismo , Amiloide/química , Conformación Proteica , Proteínas Amiloidogénicas , Mutación
8.
Pediatr Nephrol ; 38(7): 2179-2187, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-36508050

RESUMEN

BACKGROUND: FGF23 mediates cardiac fibrosis through the activation of pro-fibrotic factors in in vitro models and is markedly elevated in kidney disease. Left atrial global longitudinal strain (LA GLS) derived by echocardiographic speckle-tracking measures longitudinal shortening of the LA walls, quantifies atrial performance and may enable detection of early LA remodeling in the setting of normal ventricular function. We hypothesized that LA GLS is abnormal in children on hemodialysis (HD) compared to healthy controls of comparable age/sex distribution and that, among HD patients, greater FGF23 levels are associated with abnormal LA GLS. METHODS: Clinical and echocardiographic data from 29 children receiving HD and 13 healthy controls were collected in a cross-sectional single-center study. Plasma FGF23 concentrations were measured using ELISA. The primary outcome was LA GLS measured using 2D speckle-tracking strain analysis. Linear regression analysis was used to investigate predictors of LA GLS in HD. RESULTS: Median dialysis vintage was 1.5 (IQR 0.5-4.3) years. Median intact FGF23 levels were substantially higher in the HD vs. control group (1206 [215, 4707] vs. 51 [43, 66.5] pg/ml; P = 0.0001), and LA GLS was 39.9% SD 11.6 vs. 32.8% SD 5.7 (P = 0.04). Among HD patients, higher FGF23 was associated with lower LA GLS (ß per unit Ln-FGF23: - 2.7; 95% CI slope - 5.4, - 0.1; P = 0.04 after adjustment for age, body size, and HD vintage. FGF23 was not associated with LA phasic reservoir, conduit, or contractile strain. CONCLUSIONS: In children on HD and preserved left ventricular ejection fraction, greater FGF23 is associated with lower LA GLS (indicative of impaired atrial performance). A higher resolution version of the Graphical abstract is available as Supplementary information.


Asunto(s)
Fibrilación Atrial , Remodelación Atrial , Disfunción Ventricular Izquierda , Humanos , Niño , Función Ventricular Izquierda , Volumen Sistólico , Estudios Transversales , Diálisis Renal/efectos adversos
9.
Bioorg Chem ; 136: 106544, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37116324

RESUMEN

Piperazine derivatives have been of great interest to medicinal chemists in the development of antidepressant drugs due to their distinct molecular and structural features along with their pharmacological profile. In this study, we have designed and synthesized a series of 10 compounds of piperazine clubbed oxadiazole derivatives (5a-j) and screened for their MAO inhibitory activity. Compound 5f and 5 g were found to be the most potent MAO-A inhibitors of the series with IC50 values of 0.96 ± 0.04 µM µM and 0.81 ± 0.03 µM, respectively with a selectivity index of 18-folds and 9-folds over MAO-B isoform. The compounds were found to be reversible inhibitors of MAO-A with no cytotoxicity against SH-SY5Y neuronal cells. The compounds also displayed good antioxidant activity. Further, in vivo TST studies revealed that both the compounds 5f and 5 g possessed good anti-depressant-like activity and reduced the immobility time significantly although were found inactive in FST studies. The molecular docking studies revealed that both compounds fit well at the active site of MAO-A enzyme as similar to clorgyline and form a stable complex. The results were confirmed via molecular dynamic studies which demonstrate the stable complex formation between MAO-A and 5f & 5 g. The appropriate drug-like characteristics with favourable ADMET profile, these molecules presented this piperazine clubbed oxadiazole structural framework as a key pharmacophore for the development of new antidepressant molecules along with strong candidature for further clinical investigations.


Asunto(s)
Inhibidores de la Monoaminooxidasa , Neuroblastoma , Humanos , Inhibidores de la Monoaminooxidasa/química , Simulación del Acoplamiento Molecular , Relación Estructura-Actividad , Antidepresivos/química , Monoaminooxidasa/metabolismo , Piperazina/farmacología , Estructura Molecular
10.
Exp Cell Res ; 418(2): 113274, 2022 09 15.
Artículo en Inglés | MEDLINE | ID: mdl-35810774

RESUMEN

Mesenchymal stem cell-derived exosomes (MSC-Exos) have been utilized as medicinal agents or as delivery vehicles in cartilage injuries and cartilage-based diseases. Given the ongoing emergence of evidence on the effector mechanisms and methods of the utility of the MSC-Exos in knee osteoarthritis, a comprehensive review of the current evidence is the need of the hour. Hence, in this article, we review the current understanding of the role of MSC-Exos in the management of knee osteoarthritis in view of their classification, characterization, biogenesis, mechanism of action, pathways involved in their therapeutic action, in-vitro evidence on cartilage regeneration, in-vivo evidence in OA knee models and recent advances in using MSC-Exos to better streamline future research from bench to bedside for OA knee.


Asunto(s)
Exosomas , Células Madre Mesenquimatosas , Osteoartritis de la Rodilla , Cartílago , Condrocitos/metabolismo , Exosomas/metabolismo , Humanos , Células Madre Mesenquimatosas/metabolismo , Osteoartritis de la Rodilla/metabolismo , Osteoartritis de la Rodilla/terapia
11.
World J Surg ; 47(12): 3408-3418, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37311874

RESUMEN

BACKGROUND: Congenital anomalies are a leading cause of morbidity and mortality worldwide. We aimed to review the common surgically correctable congenital anomalies with recent updates on the global disease burden and identify the factors affecting morbidity and mortality. METHOD: A literature review was done to assess the burden of surgical congenital anomalies with emphasis on those that present within the first 8000 days of life. The various patterns of diseases were analyzed in both low- and middle-income countries (LMIC) and high-income countries (HIC). RESULTS: Surgical problems such as digestive congenital anomalies, congenital heart disease and neural tube defects are now seen more frequently. The burden of disease weighs more heavily on LMIC. Cleft lip and palate has gained attention and appropriate treatment within many countries, and its care has been strengthened by global surgical partnerships. Antenatal scans and timely diagnosis are important factors affecting morbidity and mortality. The frequency of pregnancy termination following prenatal diagnosis of a congenital anomaly is lower in many LMIC than in HIC. CONCLUSION: Congenital heart disease and neural tube defects are the most common congenital surgical diseases; however, easily treatable gastrointestinal anomalies are underdiagnosed due to the invisible nature of the condition. Current healthcare systems in most LMICs are still unprepared to tackle the burden of disease caused by congenital anomalies. Increased investment in surgical services is needed.


Asunto(s)
Labio Leporino , Fisura del Paladar , Anomalías Congénitas , Cardiopatías Congénitas , Defectos del Tubo Neural , Femenino , Humanos , Embarazo , Labio Leporino/cirugía , Fisura del Paladar/cirugía , Cardiopatías Congénitas/cirugía , Morbilidad , Anomalías Congénitas/cirugía
12.
Pediatr Surg Int ; 39(1): 277, 2023 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-37777986

RESUMEN

PURPOSE: Perioperative and early post-operative outcomes of Primary Posterior sagittal anorectoplasty (P-PSARP) were evaluated. METHOD: Retrospective analysis of cases who underwent P-PSARP from 2004 to 2019 was done. Perioperative care, management, complications, voluntary bowel movement, soiling and constipation, graded by Krickenbeck criteria were studied. RESULTS: One hundred fifty six patients (134 girls) underwent P-PSARP at median age of 5 months (3 months to 14 years) in girls and 5(1-10) days in 21 boys. One male cloaca was operated at 5 months age. Of 20 boys, 5, 8, 4, 3 had rectobulbar urethral fistula, rectoprostatic urethral fistula, bladder neck fistula and male cloaca. Girls had vestibular fistula, rectovaginal fistula, vulval anus, anterior ectopic anus, pouch perineal fistulae and posterior anus with H type fistula in 114, 7, 6, 5, 1 and 1. Complications included wound infection, excoriation, oedema, mucosal prolapse, anal stricture, anal retraction and mortality in 6, 4, 5, 4, 4, 1 and 1, respectively. 35/155(12 neonates) required postoperative dilatations for 5(1-12) months. At follow-up, 96/114(84.2%) had voluntary bowel movements. 46/155 (29.7%) and 9/155 had constipation and soiling. 32:14:0 had grade 1:2:3 constipation, treated with diet (grade 1) and laxatives (grade 2) respectively. 4:3:2 had grade 1:2:3 soiling for initial 3 months, treated with bowel management programme. CONCLUSION: P-PSARP is feasible, subject to proper case selection and good perioperative care, once learning curve is achieved.


Asunto(s)
Malformaciones Anorrectales , Enfermedades de la Próstata , Fístula Rectal , Fístula de la Vejiga Urinaria , Recién Nacido , Femenino , Humanos , Masculino , Lactante , Malformaciones Anorrectales/cirugía , Estudios Retrospectivos , Recto/cirugía , Fístula Rectal/cirugía , Canal Anal/cirugía , Canal Anal/anomalías , Estreñimiento/etiología , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/cirugía , Resultado del Tratamiento , Estudios de Seguimiento
13.
Pediatr Surg Int ; 39(1): 107, 2023 Feb 09.
Artículo en Inglés | MEDLINE | ID: mdl-36757502

RESUMEN

PURPOSE: The search for an ideal Hypospadias repair dressing continues. We aimed to develop a hypoallergenic optimized biocompatible dressing (BD). METHOD: BD with a multi-layered structure of hydrophilic treated Polypropylene with three-layered technologies; Absorbent-spunlaced hydroentangled polyester/viscose blend, outer Polypropylene, Polyester, Acrylic, and Spandex, with super Absorbent Polymer and Acrylic adhesive. Wistar rat abdominal wound model was divided into two groups: control (normal gauze dressing with adhesive) and Study (BD). The physical properties and wound characteristics were compared. RESULTS: Average mass: thickness of BD was 626.7 ± 5.6 g m-2: 2.6 ± 0.015 mm. Absorption was 1425.2 ± 127.6%. Percentage desorption of solution A from dressings at 24:40 h was 1249 ± 150%:1417 ± 230%. BD was hydrophilic with no particles/residue after immersion and pH neutral. The average air permeability was 11.6 ± 1.6 cm3/cm2/sec. The tensile force was 200N-220N with an extension on the breaking point at 24 mm. BD was superior for ease of removability on Day 6 (p = 0.012) and sticking quality (p = 0.036), absorption (p = 0.036), ease of removability(p = 0.036), and sustenance (p = 0.030) on Day 10. BD dressing demonstrated better wound healing (p = 0.015) and decreased redness (p = 0.002) on Day 10. Histopathological healing was better with BD on Day 14(p = 0.025) and Day 20 (p = 0.034). CONCLUSION: BD demonstrated better desirable physical and wound healing qualities with less inflammation compared with control normal dressing.


Asunto(s)
Hipospadias , Cicatrización de Heridas , Humanos , Masculino , Ratas , Animales , Hipospadias/cirugía , Polipropilenos , Ratas Wistar , Vendajes , Poliésteres
14.
Prep Biochem Biotechnol ; 53(10): 1187-1198, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-36799667

RESUMEN

The GH3 ß-glucosidase gene of Myceliophthora thermophila (MtBgl3c) has been cloned and heterologously expressed in E. coli for the first time. This study highlights the important characteristics of recombinant MtBgl3c (rMtBgl3c) which make it a promising candidate in industrial applications. Optimization of the production of rMtBgl3c led to 28,000 U L-1. On purification, it has a molecular mass of ∼100 kDa. It is a broad substrate specific thermostable enzyme that exhibits pH and temperature optima at 5.0 and 55 °C, respectively. The amino acid residues Asp287 and Glu514 act as nucleophile and catalytic acid/base, respectively in the enzyme catalysis. Its low Km value (1.28 mM) indicates a high substrate affinity as compared to those previously reported. The rMtBgl3c displays a synergistic action with the commercial enzyme cocktail in the saccharification of sugarcane bagasse suggesting its utility in the cellulose bioconversion. Tolerance to solvents, detergents as well as glucose make this enzyme applicable in wine, detergent, paper and textile industries too.


Asunto(s)
Celulosa , Saccharum , Celulosa/química , beta-Glucosidasa/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Saccharum/metabolismo
15.
Mol Biol Rep ; 49(6): 5567-5576, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35581509

RESUMEN

BACKGROUND: Picrorhiza kurroa has been reported as an age-old ayurvedic hepato-protection to treat hepatic disorders due to the presence of iridoids such as picroside-II (P-II), picroside-I, and kutkoside. The acylation of catalpol and vanilloyl coenzyme A by acyltransferases (ATs) is critical step in P-II biosynthesis. Since accumulation of P-II occurs only in roots, rhizomes and stolons in comparison to leaves uprooting of this critically endangered herb has been the only source of this compound. Recently, we reported that P-II acylation likely happen in roots, while stolons serve as the vital P-II storage compartment. Therefore, developing an alternate engineered platform for P-II biosynthesis require identification of P-II specific AT/s. METHODS AND RESULTS: In that direction, egg-NOG function annotated 815 ATs from de novo RNA sequencing of tissue culture based 'shoots-only' system and nursery grown shoots, roots, and stolons varying in P-II content, were cross-compared in silico to arrive at ATs sequences unique and/or common to stolons and roots. Verification for organ and accession-wise upregulation in gene expression of these ATs by qRT-PCR has shortlisted six putative 'P-II-forming' ATs. Further, six-frame translation, ab initio protein structure modelling and protein-ligand molecular docking of these ATs signified one MBOAT domain containing AT with preferential binding to the vanillic acid CoA thiol ester as well as with P-II, implying that this could be potential AT decorating final structure of P-II. CONCLUSIONS: Organ-wise comparative transcriptome mining coupled with reverse transcription real time qRT-PCR and protein-ligand docking led to the identification of an acyltransferases, contributing to the final structure of P-II.


Asunto(s)
Picrorhiza , Plantas Medicinales , Aciltransferasas/genética , Aciltransferasas/metabolismo , Cinamatos/metabolismo , Glicósidos , Glucósidos Iridoides/metabolismo , Iridoides/metabolismo , Ligandos , Simulación del Acoplamiento Molecular , Picrorhiza/genética , Picrorhiza/metabolismo , Plantas Medicinales/genética , Plantas Medicinales/metabolismo
16.
Genomics ; 113(5): 3381-3394, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-34332040

RESUMEN

Picrorhiza kurroa is a medicinal herb rich in hepatoprotective iridoid glycosides, picroside-I (P-I) and picroside-II (P-II). The biosynthetic machinery of picrosides is poorly understood, therefore, 'no-direction' gene co-expression networks were used to extract linked/closed and separated interactions in terpenoid glycosides-specific sub-networks. Transcriptomes generated from different organs, varying for P-I and P-II contents such as shoots grown at 15 and 25 °C and nursery-grown shoots, stolons, and roots resulted in 47,726, 44,958, 40,117, 66,979, and 55,578 annotated transcripts, respectively. Occurrence of 2810 ± 136 nodes and 15,626 ± 696 edges in these networks indicated intense, co-expressed, closed loop interactions. Either deregulation/inhibition of abscisic acid (ABA) biosynthesis/signaling or constitutive degradation of ABA resulted in organ-specific accumulation of P-I and P-II. Biosynthesis, condensation and glucosylation of isoprene units may occur in shoots, roots or stolons; but addition of phenylpropanoid moiety and further modification/s of the iridoid backbone occurs mainly inside vacuoles in roots.


Asunto(s)
Picrorhiza , Perfilación de la Expresión Génica , Genes de Plantas , Glicósidos Iridoides/metabolismo , Picrorhiza/genética , Picrorhiza/metabolismo , Transcriptoma
17.
Pediatr Surg Int ; 38(7): 963-983, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35567628

RESUMEN

PURPOSE: Heteropagus twinning (HT) is a rare anomaly. Six new cases along with a systematic review are described. METHODS: Six cases of HT managed at two tertiary care teaching hospitals over the last 26 years are described. A PubMed search with words: Heteropagus AND/ OR parasitic twins from 2001 to 2021 hit 183 articles. 36 were added from non-PubMed sources. Finally, 120 cases including 114 from 69 articles and 6 new cases were analysed. RESULTS: Of the new cases, 2/6 had an antenatal diagnosis. Five were males. 4 autosites had omphaloceles. Split notochord and 2 parasites attached to a single autosite were encountered. 5/6 autosites survived. On systematic review, the most frequent variant seen was rachipagus (n = 50) followed by omphalopagus (n = 46). Limbs were reported in 75 cases. Congenital heart disease was seen in 17/120(14.2%) autosites. Omphalocele and meningomyelocele were the most common extracardiac anomalies in autosites. Weight along with the anatomy and position of heteropagus twins was a better determinant of the mode of delivery than weight alone. Mortality was reported in 12 cases. CONCLUSION: Autosites in HT generally carry a good prognosis, however, final outcome depends mainly on associated major cardiac anomalies. Meticulous antenatal assessment and preoperative planning are of paramount importance. LEVEL OF EVIDENCE: IV.


Asunto(s)
Cardiopatías Congénitas , Hernia Umbilical , Gemelos Siameses , Femenino , Hernia Umbilical/diagnóstico , Hernia Umbilical/cirugía , Humanos , Masculino , Embarazo , Diagnóstico Prenatal , Gemelos Siameses/cirugía
18.
J Indian Assoc Pediatr Surg ; 27(2): 209-215, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35937127

RESUMEN

Aim: The aim is to study the impact of nutritional status on outcomes and treatment-related complications in patients of neuroblastoma. Materials and Methods: Anthropometry (height, weight, weight for height [in <5 years], mid-arm circumference [MAC] [in <5 years], and body mass index [BMI]), hemoglobin level, and serum albumin level were recorded. Results: Twenty-four neuroblastoma patients, 16 males and 8 females, with a mean age of 42.7 months were treated and followed up over a period of 0.03-170 months. Of 24 patients, 16 survived (complete response - 9, partial response - 2, no response - 2, progressive disease - 3). Height <2 standard deviation [SD] was seen in 12.5% (3/24). Mortality and complications were found in 66.7% (2/3) and 100% (3/3), respectively. Weight <2SD was seen in 37.5% (9/24). Mortality and complications were found in 33.3% (3/9) and 67% (6/9), respectively. Weight for height <2 SD was seen in 35% (7/20). Mortality and complications were found in 42.9% (3/7) and 71.4% (5/7), respectively. MAC <2 SD was seen in 15.8% (3/19). Mortality and complications were found in 66.7% (2/3) and 66.7% (2/3). BMI <2SD was seen in 29.2% (7/24). Mortality and complications were found in 42.8% (3/7) and 28.6% (2/7). Anemia was seen in 62.5% (15/24), of which nine survived. Complications were seen in 58.3% (14/24) (P = 0.001). Hypoproteinemia was seen in 20.8% (5/24). Mortality and complications were 40% (2/5) and 80% (4/5). Conclusion: Neuroblastoma has poor outcome in Indian children, and there does not appear to be a major role played by nutrition in determining the response to treatment and survival.

19.
Catheter Cardiovasc Interv ; 97(1): 74-77, 2021 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-31876350

RESUMEN

OBJECTIVE: The aim is to evaluate the feasibility of using mechanical circulatory support, specifically the Impella device, in spontaneous coronary artery dissection (SCAD) patients with cardiogenic shock. BACKGROUND: The therapeutic options for managing SCAD complicated by cardiogenic shock are limited. Risky revascularization procedures are often necessary. METHODS: This was a multicenter case series in the United States. Approximately 20 cases of Impella implantation in patients with SCAD are known. The implanting physician for each of these cases was contacted and de-identified records were requested. The records were analyzed for Impella indications, outcomes, and complications. RESULTS: Records from four cases were received. All patients survived to hospital discharge and no major complications were observed. In two cases, cardiogenic shock developed in the absence of ongoing ischemia, suggesting a Takotsubo-like cardiomyopathy. In these cases, the Impella provided hemodynamic support until the patient's cardiac function recovered. CONCLUSION: Although a small case series, given the scarcity of SCAD cases complicated by cardiogenic shock and the limited therapies available to treat these patients, these data are of clinical value in highlighting the feasibility of Impella use in SCAD. The Impella can be valuable for procedural support and in cardiogenic shock, especially in cases without evidence of ongoing ischemia.


Asunto(s)
Corazón Auxiliar , Choque Cardiogénico , Vasos Coronarios , Disección , Humanos , Estudios Retrospectivos , Choque Cardiogénico/diagnóstico , Choque Cardiogénico/etiología , Choque Cardiogénico/terapia , Resultado del Tratamiento , Estados Unidos
20.
Pediatr Surg Int ; 37(11): 1627-1632, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34313820

RESUMEN

BACKGROUND: Surgery residents often consider learning from the operative videos on YouTube, however, the quality of these videos is questionable. We aim to compare the quality and reliability of operative videos on thoracoscopic lobectomy (TL) in children available on YouTube (YT) and WebSurg (WS). METHODS: Using a defined search strategy, the most-viewed YT videos and all available WS videos on TL in children were identified. The quality and reliability of the two groups of videos were compared using the video popularity index (VPI), Journal of American Medical Association (JAMA) benchmark criteria, and LAP-VEGaS quality assessment tool. On the basis of the LAP-VEGaS score, the videos were divided into acceptable quality (score ≥ 11) or poor quality (score < 11). RESULTS: Ten most-viewed YT videos were compared with six relevant videos on WS. The median %VPI among the WS and YT videos were 83.3 (range 71.5-404.4) and 49.4 (range 0-270), respectively (p = 0.017). The median JAMA score of the WS videos was also significantly higher than the YT videos (p = 0.0003). In terms of the LAP-VEGaS scores, all WS videos versus only three YT had an acceptable quality. CONCLUSIONS: As compared to the WS videos, the quality and reliability of the YT videos on TL were significantly poorer.


Asunto(s)
Medios de Comunicación Sociales , Niño , Humanos , Reproducibilidad de los Resultados , Grabación en Video
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