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The elongation of C. elegans embryos allows examination of mechanical interactions between adjacent tissues. Muscle contractions during late elongation induce the remodelling of epidermal circumferential actin filaments through mechanotransduction. Force inputs from the muscles deform circumferential epidermal actin filament, which causes them to be severed, eventually reformed and shortened. This squeezing force drives embryonic elongation. We investigated the possible role of the non-muscle myosins NMY-1 and NMY-2 in this process using nmy-1 and nmy-2 thermosensitive alleles. Our findings show these myosins act redundantly in late elongation, since double nmy-2(ts); nmy-1(ts) mutants immediately stop elongation when raised to 25°C. Their inactivation does not reduce muscle activity, as measured from epidermis deformation, suggesting that they are directly involved in the multi-step process of epidermal remodeling. Furthermore, NMY-1 and NMY-2 inactivation is reversible when embryos are kept at the non-permissive temperature for a few hours. However, after longer exposure to 25°C double mutant embryos fail to resume elongation, presumable because NMY-1 was seen to form protein aggregates. We propose that the two C. elegans non-muscle myosin II act during actin remodeling either to bring severed ends or hold them.
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Polydimethyl silicone rubber-based polymer composites filled with molybdenum and bismuth were fabricated using simple open mold cast technique. The physical and chemical structure and gamma shielding parameters like attenuation coefficient, half-value layer (HVL) thickness and relaxation length have been investigated for the said novel materials using X-ray diffraction (XRD), Fourier transform Infrared spectroscopy (FTIR) and gamma ray spectrometer. XRD study reveals the crystalline nature of the composites. It is evident from FTIR studies that there is no chemical interaction between the polymer matrix and filler particles. The results of attenuation studies reveal that the linear attenuation coefficient increases with addition of Bi and Mo and is found to be 0.653, 1.341 and 1.017, 1.793 and 0.102, 0.152 cm-1 for 1MMB and 2MMB polymer composites at 80, 356 and 662 keV gamma rays, respectively. The HVL thickness of the materials is found to be 1.06, 0.51 and 0.68, 0.38 and 6.73, 4.532 cm for 1MMB (20Mo + 10Bi phr) and 2MMB (40Mo + 20Bi phr) at these energies, respectively. The mass attenuation coefficient of the novel composites 1MMB and 2MMB is found to be higher than the conventional materials like lead and barite for 356 keV gamma rays. In addition, the material is found to be light weight and flexible enabling to be molded in required forms, thus being a substitute for the material lead that is known to be heavy and toxic by nature.
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Bismuto , Molibdeno , Polímeros , Polímeros/química , Molibdeno/química , Molibdeno/efectos de la radiación , Bismuto/química , Rayos gamma , Radiación Ionizante , Protección Radiológica/métodos , Protección Radiológica/instrumentación , Ensayo de Materiales , Espectroscopía Infrarroja por Transformada de Fourier , Difracción de Rayos X , HumanosRESUMEN
Pearl millet (Pennisetum glaucum, also known as Cenchrus americanus) is a cereal crop that has a C4 photosynthesis system and that can grow and develop seeds even under stressed conditions including drought-stressed, high temperature-stressed and nutrient-poor conditions. In previous studies, transcriptomes of pearl millet were studied by RNA sequencing (RNA-Seq) to understand mechanisms regulating its development and tolerance to such stressed conditions. Here, RNA-Seq reads from 565 pearl millet samples from 25 projects in the NCBI (National Center for Biotechnology Information) BioProject database were collected and mapped to the pearl millet reference genome to obtain read counts and transcripts per million (TPM) for each pearl millet gene. The count and TPM data for all the 565 samples as well as the attributes of those samples and projects were deposited in the figshare repository (https://doi.org/10.6084/m9.figshare.24902100).
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Computed tomography (CT) is known for its non-invasiveness, fast procedure, and also for providing detailed diagnostic information to physicians. It also utilises low-dose-rate ionising radiation (X-rays) as a source for imaging. Multidetector computed tomography (MDCT) is an advanced system that uses iodinated contrast media for more accurate diagnostic results. Studies suggest using these contrasts will lead to greater radiation adsorption with significant DNA damage. No studies have been taken comparing the physical dose with the biological effect. The present study sheds light on the same by assessing the biological effect of CT with and without contrast intervention. The present study is timebound; thus, 21 participants attending for CT thorax and abdomen with no history of any cancer were included. The same participants underwent both pre-contrast and post-contrast studies. The blood sample was taken before the procedure and used as a control. Physical parameters like DLP and CTDI obtained from the instrument were compared with the MN frequency obtained (CBMN Assay). The study showed a significant increase (p-value < 0.05) in the Physical and MN frequency in the Post-Contrast group compared to the pre-contrast group. Although a positive correlation was observed between pre and post-contrast groups, the results were not found to be statistically significant (p-value < 0.05). The study confirms increased physical dose and MN frequency upon contrast intervention. This study recommends the judicial use of MDCT in disease diagnostics.
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INTRODUCTION: Zinner Syndrome (ZS), a rare congenital malformation of the mesonephric duct, combines seminal vesicle cyst (SVC) with ipsilateral upper urinary tract abnormalities. Typically asymptomatic in childhood, ZS manifests between 2nd to 4th decades with bladder symptoms, perineal pain and infertility. Diagnostic confirmation with additional imaging is needed when either renal or seminal abnormalities are identified. MATERIALS AND METHODS: A retrospective study spanning 22 years identified 20 pediatric ZS cases through clinical analytics. Demographic, clinical, and radiological data were analyzed, including presenting complaints, imaging modalities (ultrasound, CT, MRI), and surgical findings. The study was HIPAA-compliant and IRB-approved. RESULTS: Among 20 cases (mean age: 7.3 years), clinical presentations included asymptomatic cases, urinary symptoms, and abdominal pain. Imaging revealed renal anomalies (agenesis, multicystic dysplastic kidney) and seminal vesicle abnormalities. Surgical interventions (n = 12) addressed symptomatic cases, often involving robotic or laparoscopic procedures. DISCUSSION: ZS, though rare, presents with varied clinical features, necessitating a multidisciplinary approach. Early diagnosis is facilitated by prenatal identification of renal abnormalities. Surgical intervention is reserved for symptomatic cases, with techniques such as vesiculectomy and resection of remnant structures employed. CONCLUSION: This study highlights ZS's diverse clinical and radiological spectrum, emphasizing the need for vigilance in detecting overlapping entities. Timely identification, utilizing advanced imaging techniques, is crucial for accurate diagnosis and appropriate management of Zinner Syndrome in the pediatric population.
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Vesículas Seminales , Humanos , Estudios Retrospectivos , Masculino , Niño , Vesículas Seminales/anomalías , Vesículas Seminales/diagnóstico por imagen , Preescolar , Síndrome , Femenino , Adolescente , Anomalías Múltiples/diagnóstico , Conductos Mesonéfricos/anomalías , Quistes/diagnóstico , Quistes/cirugía , LactanteRESUMEN
Pearl millet (Cenchrus americanus) is a cereal crop that can tolerate high temperatures, drought, and low-fertility conditions where other crops lose productivity. However, genes regulating this ability are largely unknown. Transcription factors (TFs) regulate transcription of their target genes, regulate downstream biological processes, and thus are candidates for regulators of such tolerance of pearl millet. PgWRKY74 encodes a group IIc WRKY TF in pearl millet and is downregulated by drought. PgWRKY74 may have a role in drought tolerance. The objective of this study was to gain insights into the physiological and biochemical functions of PgWRKY74. Yeast one-hybrid and gel shift assays were performed to examine transcriptional activation potential and deoxyribonucleic acid (DNA)-binding ability, respectively. Transgenic Arabidopsis thaliana plants overexpressing PgWRKY74-green fluorescent protein (GFP) fusion gene were generated and tested for growth and stress-responsive gene expression under mannitol and NaCl-stressed conditions. A construct with PgWRKY74 enabled yeast reporter cells to survive on test media in the yeast one-hybrid assays. The electrophoretic mobility of DNA with putative WRKY TF-binding motifs was lower in the presence of a recombinant PgWRKY74 protein than its absence. The PgWRKY74-GFP-overexpressing Arabidopsis plants exhibited smaller rosette areas than did wild-type plants under mannitol-stressed and NaCl-stressed conditions, and exhibited weaker expression of RD29B, which is induced by the stress-related phytohormone abscisic acid (ABA), under the mannitol-stressed condition. PgWRKY74 have transcriptional activation potential and DNA-binding ability, and can negatively regulate plant responses to mannitol and NaCl stresses, possibly by decreasing ABA levels or ABA sensitivity.
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The search for mechanism-based anti-inflammatory therapies is of fundamental importance to avoid undesired off-target effects. Phospholipase A2 (PLA2) activity is a potential molecular target for anti-inflammatory drugs because it fuels arachidonic acid needed to synthesize inflammation mediators, such as prostaglandins. Herein, we aim to investigate the molecular mechanism by which ß-keto amyrin isolated from a methanolic extract of Cryptostegia grandiflora R. Br. Leaves can inhibit inflammation caused by Daboia russellii viper (DR) venom that mainly contains PLA2. We found that ß-keto amyrin neutralizes DR venom-induced paw-edema in a mouse model. Molecular docking of PLA2 with ß-keto amyrin complex resulted in a higher binding energy score of -8.86 kcal/mol and an inhibition constant of 611.7 nM. Diclofenac had a binding energy of -7.04 kcal/mol and an IC50 value of 620 nM, which predicts a poorer binding interaction than ß-keto amyrin. The higher conformational stability of ß-keto amyrin interaction compared to diclofenac is confirmed by molecular dynamics simulation. ß-keto amyrin isolated from C. grandiflora inhibits the PLA2 activity contained in Daboia russellii viper venom. The anti-inflammatory property of ß-keto amyrin is due to its direct binding into the active site of PLA2, thus inhibiting its enzyme activity.
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Apocynaceae , Daboia , Inflamación , Ácido Oleanólico , Venenos de Víboras , Animales , Ratones , Antiinflamatorios/farmacología , Apocynaceae/química , Diclofenaco/farmacología , Diclofenaco/uso terapéutico , Inflamación/inducido químicamente , Inflamación/tratamiento farmacológico , Simulación del Acoplamiento Molecular , Ácido Oleanólico/análogos & derivados , Ácido Oleanólico/farmacología , Ácido Oleanólico/uso terapéutico , Fosfolipasas A2/efectos de los fármacos , Fosfolipasas A2/metabolismo , Venenos de Víboras/química , Venenos de Víboras/toxicidadRESUMEN
Pearl millet (Pennisetum glaucum) is a cereal crop that can grow and set seeds even under drought, high temperatures and nutrient-poor conditions. Panicles of two pearl millet cultivars that differ in seed-setting rates were exposed to two different high-temperature treatments at three different developmental stages with three replicates, and RNA was prepared from these panicles. The resulting RNA samples were subjected to sequencing with the Illumina NovaSeq 6000 sequencer. The obtained data were 150-base-paired-end reads and were approximately 5 Gb/sample in total. These read data were deposited as those for a project in the NCBI (National Center for Biotechnology Information) BioProject database.
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Information on genetic diversity and population structure is helpful to strategize enhancing the genetic base of hybrid parental lines in breeding programs. The present study determined the population structure and genetic diversity of 109 pearl millet hybrid parental lines, known for their better adaptation and performance in drought-prone environments, using 16,472 single nucleotide polymorphic (SNP) markers generated from GBS (genotyping-by-sequencing) platforms. The SNPs were distributed uniformly across the pearl millet genome and showed considerable genetic diversity (0.337), expected heterozygosity (0.334), and observed heterozygosity (0.031). Most of the pairs of lines (78.36%) had Identity-by-State (IBS) based genetic distances of more than 0.3, indicating a significant amount of genetic diversity among the parental lines. Bayesian model-based population stratification, neighbor-joining phylogenetic analysis, and principal coordinate analysis (PCoA) differentiated all hybrid parental lines into two clear-cut major groups, one each for seed parents (B-lines) and pollinators (R-lines). Majority of parental lines sharing common parentages were found grouped in the same cluster. Analysis of molecular variance (AMOVA) revealed 7% of the variation among subpopulations, and 93% of the variation was attributable to within sub-populations. Chromosome 3 had the highest number of LD regions. Genomic LD decay distance was 0.69 Mb and varied across the different chromosomes. Genetic diversity based on 11 agro-morphological and grain quality traits also suggested that the majority of the B- and R-lines were grouped into two major clusters with few overlaps. In addition, the combined analysis of phenotypic and genotypic data showed similarities in the population grouping patterns. The present study revealed the uniqueness of most of the inbred lines, which can be a valuable source of new alleles and help breeders to utilize these inbred lines for the development of hybrids in drought-prone environments.
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Pennisetum , Pennisetum/genética , Filogenia , Sequías , Teorema de Bayes , Fitomejoramiento , Variación Genética , Polimorfismo de Nucleótido SimpleRESUMEN
Genome-wide association studies in inflammatory bowel disease have identified risk loci in the orosomucoid-like protein 3/ORMDL sphingolipid biosynthesis regulator 3 (ORMDL3) gene to confer susceptibility to ulcerative colitis (UC), but the underlying functional relevance remains unexplored. Here, we found that a subpopulation of the UC patients who had higher disease activity shows enhanced expression of ORMDL3 compared to the patients with lower disease activity and the non-UC controls. We also found that the patients showing high ORMDL3 mRNA expression have elevated interleukin-1ß cytokine levels indicating positive correlation. Further, knockdown of ORMDL3 in the human monocyte-derived macrophages resulted in significantly reduced interleukin-1ß release. Mechanistically, we report for the first time that ORMDL3 contributes to a mounting inflammatory response via modulating mitochondrial morphology and activation of the NLRP3 inflammasome. Specifically, we observed an increased fragmentation of mitochondria and enhanced contacts with the endoplasmic reticulum (ER) during ORMDL3 over-expression, enabling efficient NLRP3 inflammasome activation. We show that ORMDL3 that was previously known to be localized in the ER also becomes localized to mitochondria-associated membranes and mitochondria during inflammatory conditions. Additionally, ORMDL3 interacts with mitochondrial dynamic regulating protein Fis-1 present in the mitochondria-associated membrane. Accordingly, knockdown of ORMDL3 in a dextran sodium sulfate -induced colitis mouse model showed reduced colitis severity. Taken together, we have uncovered a functional role for ORMDL3 in mounting inflammation during UC pathogenesis by modulating ER-mitochondrial contact and dynamics.
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Colitis Ulcerosa , Retículo Endoplásmico , Inflamasomas , Macrófagos , Proteínas de la Membrana , Mitocondrias , Proteína con Dominio Pirina 3 de la Familia NLR , Colitis Ulcerosa/metabolismo , Colitis Ulcerosa/patología , Colitis Ulcerosa/genética , Humanos , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Proteínas de la Membrana/metabolismo , Proteínas de la Membrana/genética , Mitocondrias/metabolismo , Mitocondrias/patología , Macrófagos/metabolismo , Macrófagos/patología , Inflamasomas/metabolismo , Animales , Retículo Endoplásmico/metabolismo , Ratones , Interleucina-1beta/metabolismo , Interleucina-1beta/genética , Masculino , Sulfato de Dextran/toxicidadRESUMEN
The COVID-19 influenza emerged and proved to be fatal, causing millions of deaths worldwide. Vaccines were eventually discovered, effectively preventing the severe symptoms caused by the disease. However, some of the population (elderly and patients with comorbidities) are still vulnerable to severe symptoms such as breathlessness and chest pain. Identifying these patients in advance is imperative to prevent a bad prognosis. Hence, machine learning and deep learning algorithms have been used for early COVID-19 severity prediction using clinical and laboratory markers. The COVID-19 data was collected from two Manipal hospitals after obtaining ethical clearance. Multiple nature-inspired feature selection algorithms are used to choose the most crucial markers. A maximum testing accuracy of 95% was achieved by the classifiers. The predictions obtained by the classifiers have been demystified using five explainable artificial intelligence techniques (XAI). According to XAI, the most important markers are c-reactive protein, basophils, lymphocytes, albumin, D-Dimer and neutrophils. The models could be deployed in various healthcare facilities to predict COVID-19 severity in advance so that appropriate treatments could be provided to mitigate a severe prognosis. The computer aided diagnostic method can also aid the healthcare professionals and ease the burden on already suffering healthcare infrastructure.
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Inteligencia Artificial , COVID-19 , Anciano , Humanos , COVID-19/diagnóstico , Pronóstico , Algoritmos , Hidrolasas , BiomarcadoresRESUMEN
Primary pediatric lung tumors are uncommon and have many overlapping clinical and imaging features. In contrast to adult lung tumors, these rare pediatric neoplasms have a relatively broad histologic spectrum. Informed by a single-institution 13-year retrospective record review, we present an overview of the most common primary pediatric lung neoplasms, with a focus on the role of positron emission tomography (PET), specifically 18F-fluorodeoxyglucose (FDG) PET and 68Ga-DOTATATE PET, in the management of primary pediatric lung tumors. In addition to characteristic conventional radiographic and cross-sectional imaging findings, knowledge of patient age, underlying cancer predisposition syndromes, and PET imaging features may help narrow the differential. While metastases from other primary malignancies remain the most commonly encountered pediatric lung malignancy, the examples presented in this pictorial essay highlight many of the important conventional radiologic and PET imaging features of primary pediatric lung malignancies.
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Fluorodesoxiglucosa F18 , Neoplasias Pulmonares , Tomografía de Emisión de Positrones , Radiofármacos , Humanos , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/terapia , Niño , Tomografía de Emisión de Positrones/métodos , Adolescente , Estudios Retrospectivos , Compuestos Organometálicos , Diagnóstico DiferencialRESUMEN
OBJECTIVES: To determine the added diagnostic value of contrast-enhanced ultrasound (CEUS) in pediatric chest abnormalities by comparing interpretation of CEUS studies and confidence level to conventional US studies. METHODS: CEUS studies in patients with a variety of clinically suspected chest abnormalities performed between 2016 and 2020 were reviewed and compared to same-day conventional US studies. Examinations were independently interpreted by 4 radiologists blinded to clinical and other imaging data. Rater confidence was classified as low, moderate, or high. Diagnostic accuracy was determined by comparing image interpretation to patient outcome as the ground truth. Interobserver agreement was also assessed. RESULTS: Sixteen patients (10 male) with 18 CEUS studies were included. Median rater agreement with ground truth was significantly higher for CEUS (100%) than conventional US (50%; P = .004). Median rater confidence was high (3.0) for CEUS, and low-moderate (1.5) for conventional US (P < .001). CEUS sensitivity (54.6-81.8%) and specificity (63.4-100.0%) were greater than conventional US (45.5-72.7% and 12.5-63.5%, respectively). CEUS false positives (0-4) and false negatives (2-5) were fewer than conventional US (4-7 and 3-6, respectively). Except for one rater pair where agreement was substantial (κ = .78, P < .01), inter-rater agreement for CEUS for all other rater pairs was nonsignificant (κ = .25-0.51, P ≥ .07). Agreement for conventional US was moderate and statistically significant for 3 rater pairs (κ = .55-0.78) and nonsignificant for the remaining 3 rater pairs (P ≥ .06). CONCLUSIONS: CEUS adds diagnostic value to the assessment of a variety of chest abnormalities. The data support further evaluation of the role of CEUS as a non-invasive, problem-solving technique in children.
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Medios de Contraste , Aumento de la Imagen , Humanos , Masculino , Adolescente , Niño , Proyectos Piloto , Ultrasonografía/métodos , Aumento de la Imagen/métodos , Examen Físico , Sensibilidad y EspecificidadAsunto(s)
Progresión de la Enfermedad , Enfermedades Pulmonares Intersticiales , Pulmón , Tomografía Computarizada por Rayos X , Humanos , Enfermedades Pulmonares Intersticiales/diagnóstico por imagen , Enfermedades Pulmonares Intersticiales/complicaciones , Tomografía Computarizada por Rayos X/métodos , Pulmón/diagnóstico por imagen , Miositis/diagnóstico por imagen , Miositis/complicaciones , Masculino , Persona de Mediana Edad , Femenino , Radiografía Torácica/métodos , AdultoRESUMEN
Regulation of RNA stability and translation by RNA-binding proteins (RBPs) is a crucial process altering gene expression. Musashi family of RBPs comprising Msi1 and Msi2 is known to control RNA stability and translation. However, despite the presence of MSI2 in the heart, its function remains largely unknown. Here, we aim to explore the cardiac functions of MSI2. We confirmed the presence of MSI2 in the adult mouse, rat heart, and neonatal rat cardiomyocytes. Furthermore, Msi2 was significantly enriched in the heart cardiomyocyte fraction. Next, using RNA-seq data and isoform-specific PCR primers, we identified Msi2 isoforms 1, 4, and 5, and two novel putative isoforms labeled as Msi2 6 and 7 to be expressed in the heart. Overexpression of Msi2 isoforms led to cardiac hypertrophy in cultured cardiomyocytes. Additionally, Msi2 exhibited a significant increase in a pressure-overload model of cardiac hypertrophy. We selected isoforms 4 and 7 to validate the hypertrophic effects due to their unique alternative splicing patterns. AAV9-mediated overexpression of Msi2 isoforms 4 and 7 in murine hearts led to cardiac hypertrophy, dilation, heart failure, and eventually early death, confirming a pathological function for Msi2. Using global proteomics, gene ontology, transmission electron microscopy, seahorse, and transmembrane potential measurement assays, increased MSI2 was found to cause mitochondrial dysfunction in the heart. Mechanistically, we identified Cluh and Smyd1 as direct downstream targets of Msi2. Overexpression of Cluh and Smyd1 inhibited Msi2-induced cardiac malfunction and mitochondrial dysfunction. Collectively, we show that Msi2 induces hypertrophy, mitochondrial dysfunction, and heart failure.
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Insuficiencia Cardíaca , Animales , Ratones , Ratas , Cardiomegalia , Proteínas de Unión al ADN/metabolismo , Insuficiencia Cardíaca/metabolismo , Mitocondrias/metabolismo , Proteínas Musculares/genética , Miocitos Cardíacos/metabolismo , Isoformas de Proteínas/metabolismo , Isoformas de Proteínas/farmacología , ARN Mensajero/metabolismo , ARN Mensajero/farmacología , Proteínas de Unión al ARN/genética , Proteínas de Unión al ARN/metabolismo , Factores de Transcripción/metabolismo , Factores de Transcripción/farmacologíaRESUMEN
PURPOSE: To evaluate complications associated with cryoablation in a pediatric population and review preventive measures to mitigate these complications. MATERIAL AND METHODS: Retrospective study including all the image guided cryoablations performed on pediatric population. Immediate and delayed complications were analyzed, and we identified the different protective measures used and the clinical outcomes from follow-up. Point estimates for the percentage of complications were calculated by maximum likelihood, and 95% confidence intervals for the true percentages were calculated using the Clopper-Pearson exact method. RESULTS: Eighty-seven ablations were performed on 68 patients (age range of 2-18 years, mean 12.4 years) for non-neoplastic (70%) and neoplastic (30%) lesions. The percentage of ablations resulting in complications was 18% (95% confidence interval (CI) 11% to 28%). Of these, 5% (95% CI 1% to 11%) were grade 3 complications, and 14% (95% CI 7% to 23%) were grade 2 complications. Thermal protection was performed in 27.6% of ablations (n = 24). The mean clinical follow-up duration was 348 days. CONCLUSION: Cryoablation in pediatric patients is relatively safe, with a major complication rate per ablation of 5%. Thermal protective measures can be considered to mitigate these complications.
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Criocirugía , Humanos , Niño , Preescolar , Adolescente , Criocirugía/métodos , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
OBJECTIVE: To delineate pediatric interventional radiology (IR) inpatient consult growth and resulting collections after implementation of a pediatric IR consult service. METHODS: An inpatient IR consult process was created at a single academic children's hospital in October 2019. IR consult note templates were created in Epic (Epic Systems Corporation, Verona, Wisconsin) and utilized by 4 IR physicians. Automatic charge generation was linked to differing levels of evaluation and management (E&M) service relating to current procedural terminology (CPT) inpatient consult codes 99251-99255. The children's hospital informatics division identified IR consult notes entered from the implementation of the consult service: October 2019 to January 2022. The university radiology department billing office provided IR service E&M charge, payment, and relative value units (RVU) information during this study period. A chart review was performed to determine the IR procedure conversion rate. Mann-Whitney and a two-sample t-test statistical analyses compared use of the 25-modifier, monthly consult growth and monthly payment growth. P-value < 0.05 was considered statistically significant. RESULTS: Within this 27-month period, a total of 2153 inpatient IR consults were performed during 1757 Epic hospital encounters; monthly consult peak was reached 5 months into the study period. Consult level breakdown by CPT codes: 99251-8.7%, 99252-81.7%, and 99253-8.8%. 69.7% of IR consults had consult-specific billing with payments in 96.4% resulting in $143,976 new revenue. From 2020 to 2021, IR consult volume trended upward by 13.4% (P =0.069), and consult-specific payments increased by 84.1% (P<0.001). IR consult procedure conversion rate was 96.5%. CONCLUSION: An inpatient pediatric IR consult service was quickly established and maintained by four physicians over a 27-month study period. Annual IR consult volume trended upward and consult-specific payments increased, resulting in previously uncaptured IR service revenue.
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Médicos , Radiología Intervencionista , Niño , Humanos , Pacientes Internos , Derivación y ConsultaRESUMEN
Altered mitochondrial function without a well-defined cause has been documented in patients with ulcerative colitis (UC). In our efforts to understand UC pathogenesis, we observed reduced expression of clustered mitochondrial homolog (CLUH) only in the active UC tissues compared with the unaffected areas from the same patient and healthy controls. Stimulation with bacterial Toll-like receptor (TLR) ligands similarly reduced CLUH expression in human primary macrophages. Further, CLUH negatively regulated secretion of proinflammatory cytokines IL-6 and TNF-α and rendered a proinflammatory niche in TLR ligand-stimulated macrophages. CLUH was further found to bind to mitochondrial fission protein dynamin related protein 1 (DRP1) and regulated DRP1 transcription in human macrophages. In the TLR ligand-stimulated macrophages, absence of CLUH led to enhanced DRP1 availability for mitochondrial fission, and a smaller dysfunctional mitochondrial pool was observed. Mechanistically, this fissioned mitochondrial pool in turn enhanced mitochondrial ROS production and reduced mitophagy and lysosomal function in CLUH-knockout macrophages. Remarkably, our studies in the mouse model of colitis with CLUH knockdown displayed exacerbated disease pathology. Taken together, this is the first report to our knowledge explaining the role of CLUH in UC pathogenesis, by means of regulating inflammation via maintaining mitochondrial-lysosomal functions in the human macrophages and intestinal mucosa.