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1.
JCI Insight ; 2024 Sep 24.
Artículo en Inglés | MEDLINE | ID: mdl-39316445

RESUMEN

Extracellular vesicles (EVs) have emerged as important mediators of inter-tissue signaling and exercise adaptations. In this human study (n = 32), we provide evidence that muscle-specific microRNA-1 (miR-1) was transferred to adipose tissue via EVs following an acute bout of resistance exercise. Using a multi-model machine learning automation tool, we discovered muscle primary miR-1 transcript and CD63+ EV count in circulation as top explanatory features for changes in adipose miR-1 levels in response to resistance exercise. RNA-sequencing (RNA-seq) and in-silico prediction of miR-1 target genes identified caveolin 2 (CAV2) and tripartite motif containing 6 (TRIM6) as miR-1 target genes downregulated in the adipose tissue of a subset of participants with the highest increases in miR-1 levels following resistance exercise (n = 6). Overexpression of miR-1 in differentiated human adipocyte-derived stem cells downregulated these miR-1 targets and enhanced catecholamine-induced lipolysis. These data identify a potential EV-mediated mechanism by which skeletal muscle communicates to adipose tissue and modulates lipolysis via miR-1.

2.
Pediatr Radiol ; 2024 Aug 24.
Artículo en Inglés | MEDLINE | ID: mdl-39179930

RESUMEN

BACKGROUND: Micrognathia can be diagnosed in utero with ultrasound by measuring the jaw index and/or inferior facial angle, though it can be challenging due to fetal positioning. The jaw index can be measured with magnetic resonance imaging (MRI) using the masseter muscle, but indistinct margins can lead to inaccuracy; the easily visualized posterior teeth buds may be a better landmark. OBJECTIVE: We aimed to evaluate inter-reader variability, agreement with ultrasound, and association with postnatal outcomes using MRI to measure the inferior facial angle, jaw index by masseter muscle, and jaw index by posterior teeth buds. MATERIALS AND METHODS: A single-institution retrospective review was performed of singleton pregnancies with prenatally diagnosed micrognathia by ultrasound or MRI from September 2013-June 2022. Ultrasound measurements were obtained by a maternal-fetal medicine specialist and MRI measurements by two radiologists to evaluate inter-reader variability. Intraclass correlation coefficients (ICC) and Bland-Altman analysis were used to assess agreement between imaging methods and logistic regressions and ROC curves to assess associations with postnatal outcomes. RESULTS: Forty-three fetuses (median gestational age 26 weeks (IQR 22-31); 47% male (20/43)) were included. Ultrasound measurements could not be obtained for jaw index in 15/43 (35%) fetuses and inferior facial angle in 11/43 (26%); MRI measurements were obtained by at least one reader in all cases. Jaw index by teeth buds demonstrated lowest inter-reader variability (ICC = 0.82, P < 0.001) and highest agreement with ultrasound (bias -0.23, 95% CI -2.8-2.2). All MRI measurements, but not ultrasound, predicted need for mandibular distraction (inferior facial angle P = 0.02, jaw index by masseter muscle P = 0.04, jaw index by teeth buds P = 0.01). CONCLUSION: Fetal MRI measurements, particularly jaw index measured by posterior teeth buds, demonstrate low inter-reader variability and high agreement with ultrasound, and may predict need for mandibular distraction postnatally.

3.
bioRxiv ; 2024 Aug 10.
Artículo en Inglés | MEDLINE | ID: mdl-39149347

RESUMEN

MicroRNA-1 (miR-1) is the most abundant miRNA in adult skeletal muscle. To determine the function of miR-1 in adult skeletal muscle, we generated an inducible, skeletal muscle-specific miR-1 knockout (KO) mouse. Integration of RNA-sequencing (RNA-seq) data from miR-1 KO muscle with Argonaute 2 enhanced crosslinking and immunoprecipitation sequencing (AGO2 eCLIP-seq) from human skeletal muscle identified miR-1 target genes involved with glycolysis and pyruvate metabolism. The loss of miR-1 in skeletal muscle induced cancer-like metabolic reprogramming, as shown by higher pyruvate kinase muscle isozyme M2 (PKM2) protein levels, which promoted glycolysis. Comprehensive bioenergetic and metabolic phenotyping combined with skeletal muscle proteomics and metabolomics further demonstrated that miR-1 KO induced metabolic inflexibility as a result of pyruvate oxidation resistance. While the genetic loss of miR-1 reduced endurance exercise performance in mice and in C. elegans, the physiological down-regulation of miR-1 expression in response to a hypertrophic stimulus in both humans and mice causes a similar metabolic reprogramming that supports muscle cell growth. Taken together, these data identify a novel post-translational mechanism of adult skeletal muscle metabolism regulation mediated by miR-1.

4.
Children (Basel) ; 11(6)2024 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-38929246

RESUMEN

Solid organ injury (SOI) is common in children who experience abdominal trauma, and the management of such injuries has evolved significantly over the past several decades. In 2000, the American Pediatric Surgical Association (APSA) published the first societal guidelines for the management of blunt spleen and/or liver injury (BLSI), advocating for optimized resource utilization while maintaining patient safety. Nonoperative management (NOM) has become the mainstay of treatment for SOI, and since the publication of the APSA guidelines, numerous groups have evaluated how invasive procedures, hospitalization, and activity restrictions may be safely minimized in children with SOI. Here, we review the current evidence-based management guidelines in place for the treatment of injuries to the spleen, liver, kidney, and pancreas in children, including initial evaluation, inpatient management, and long-term care, as well as gaps that exist in the current literature that may be targeted for further optimization of protocols for pediatric SOI.

5.
bioRxiv ; 2024 May 26.
Artículo en Inglés | MEDLINE | ID: mdl-38903110

RESUMEN

Background: Alzheimer's disease (AD) is characterized by the presence of neurofibrillary tangles made of hyperphosphorylated tau and senile plaques composed of beta-amyloid. These pathognomonic deposits have been implicated in the pathogenesis, although the molecular mechanisms and consequences remain undetermined. UFM1 is an important, but understudied ubiquitin-like protein that is covalently attached to substrates. This UFMylation has recently been identified as major modifier of tau aggregation upon seeding in experimental models. However, potential alterations of the UFM1 pathway in human AD brain have not been investigated yet. Methods: Here we used frontal and temporal cortex samples from individuals with or without AD to measure the protein levels of the UFMylation pathway in human brain. We used multivariable regression analyses followed by Bonferroni correction for multiple testing to analyze associations of the UFMylation pathway with neuropathological characteristics, primary biochemical measurements of tau and additional biochemical markers from the same cases. We further studied associations of the UFMylation cascade with cellular stress pathways using Spearman correlations with bulk RNAseq expression data and functionally validated these interactions using gene-edited neurons that were generated by CRISPR-Cas9. Results: Compared to controls, human AD brain had increased protein levels of UFM1. Our data further indicates that this increase mainly reflects conjugated UFM1 indicating hyperUFMylation in AD. UFMylation was strongly correlated with pathological tau in both AD-affected brain regions. In addition, we found that the levels of conjugated UFM1 were negatively correlated with soluble levels of the deUFMylation enzyme UFSP2. Functional analysis of UFM1 and/or UFSP2 knockout neurons revealed that the DNA damage response as well as the unfolded protein response are perturbed by changes in neuronal UFM1 signaling. Conclusions: There are marked changes in the UFMylation pathway in human AD brain. These changes are significantly associated with pathological tau, supporting the idea that the UFMylation cascade might indeed act as a modifier of tau pathology in human brain. Our study further nominates UFSP2 as an attractive target to reduce the hyperUFMylation observed in AD brain but also underscores the critical need to identify risks and benefits of manipulating the UFMylation pathway as potential therapeutic avenue for AD.

6.
Nat Commun ; 15(1): 2975, 2024 Apr 06.
Artículo en Inglés | MEDLINE | ID: mdl-38582938

RESUMEN

Indirect Drive Inertial Confinement Fusion Experiments on the National Ignition Facility (NIF) have achieved a burning plasma state with neutron yields exceeding 170 kJ, roughly 3 times the prior record and a necessary stage for igniting plasmas. The results are achieved despite multiple sources of degradations that lead to high variability in performance. Results shown here, for the first time, include an empirical correction factor for mode-2 asymmetry in the burning plasma regime in addition to previously determined corrections for radiative mix and mode-1. Analysis shows that including these three corrections alone accounts for the measured fusion performance variability in the two highest performing experimental campaigns on the NIF to within error. Here we quantify the performance sensitivity to mode-2 symmetry in the burning plasma regime and apply the results, in the form of an empirical correction to a 1D performance model. Furthermore, we find the sensitivity to mode-2 determined through a series of integrated 2D radiation hydrodynamic simulations to be consistent with the experimentally determined sensitivity only when including alpha-heating.

7.
Dev Psychopathol ; : 1-13, 2024 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-38506061

RESUMEN

Contemporary biological and contextually based theoretical frameworks have conceptualized how stress exposure may influence adaptation in youth. However, nearly all of this scholarship neglects the role of specific contextual features and/or biological processes that are involved in ethnic-racial minority youth's responses and adaptation to sociocultural stressors. Drawing on the theoretical principles of the developmental psychopathology framework and contemporary models of stress and adaptation, this article proposes a new multisystem model that explains how multiple levels and systems within and outside of individual youth influence their sociocultural adaptation. We provide empirical evidence to support components of this multisystem model. We propose that research based on our new theoretical framework will capture the sociocultural experiences of ethnic-racial minority youth by centering processes that are relevant to their lived experiences, coping, and adjustment. In doing so, this model will inform psychosocial interventions focused on promoting healthy adaptation among ethnic and racial diverse youth. Finally, we offer recommendations to guide future research on stress and adaptation among ethnic and racial diverse youth, in particular, and developmental psychopathology more broadly.

8.
Radiography (Lond) ; 30(1): 73-79, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37871368

RESUMEN

INTRODUCTION: An awareness of Professional Identity (PI), an individual's identity in relation to their professional group, and Role Perception (RP), an individual's view of their specific role, may enable safe and effective practice by providing an understanding of professional boundaries, behaviours and activities. This research aimed to explore and gain an understanding of the PI and RP of Radiographers and Clinical Technologists working as Nuclear Medicine Technologists (NMT's). METHODS: 10 NMT's were recruited from a large National Health Service (NHS) Trust. Utilising the established methodology of Qualitative Description, data was obtained using semi-structured interviews and analysed using inductive thematic analysis. RESULTS: Four themes were identified: "Becoming the Unexpected" which detailed various training pathways; "Caring with Science" which described the NMT's role and defined their PI; "Same View, Different Lens" which portrayed how Radiographers and Clinical Technologists practise as team of NMT's; and "Confirmation of Professional Self" which presented how individuals view their professional status. CONCLUSION: The study showed that the NMT role is highly specialised, multi-faceted and patient-centred. Their professional status is based on the nature of their role and their university level education and training. They work together under the umbrella title of NMT with a dual professional identity of "provider of care" and "user of science and technology". However, they may have an individual identity of Radiographer or Clinical Technologist that is determined by their training pathway. IMPLICATIONS FOR PRACTICE: This research has provided valuable understanding of the PI and RP of NMT's. By highlighting the differences in the regulatory status of this workforce, an insight into the future implications in the context of national healthcare planning has been provided, highlighting potentially significant issues that may impact on the manner in which NMT's can practice.


Asunto(s)
Medicina Nuclear , Humanos , Medicina Estatal , Técnicos Medios en Salud , Cintigrafía , Percepción
9.
J Surg Res ; 295: 168-174, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38016270

RESUMEN

INTRODUCTION: Necrotizing enterocolitis (NEC) is a significant cause of morbidity and mortality among extremely premature infants. Approximately 50% of cases progress to surgery, frequently resulting in resection of necrotic bowel and ostomy creation. Premature neonates are at risk for bronchopulmonary dysplasia and feeding failure; surgery in these patients is higher risk. We evaluated the incidence of gastrostomy tube (GT) placement after ostomy reversal in surgical NEC to define a subset of patients who would benefit from concurrent ostomy reversal and GT placement. METHODS: A single-center retrospective study of infants with surgical NEC requiring ostomy creation between 2007 and 2021 was performed. RESULTS: Eighty patients met inclusion criteria. A GT was placed in 45/80 (56.3%), of which 3/45 (6.7%) were placed before, 20/45 (44.4%) concurrently with, and 22/45 (48.9%) after ostomy reversal. Between those who did and did not require GT placement, there were no significant differences in gestational age (27 versus 27 wk, P = 0.94) or birth weight (830 g versus 1055 g, P = 0.36). Hospital length of stay was longer in the GT group (128.2 versus 70.9 d, P < 0.0001). Time from ostomy reversal to hospital discharge was shorter when performed concurrently with GT (56 versus 77 d, P = 0.02). There were no differences in short-term or long-term GT related complications based on timing of GT placement. CONCLUSIONS: GT placement occurred in approximately 50% of patients with surgical NEC and GT may be accomplished safely at the time of ostomy reversal thus reducing the need for an additional procedure.


Asunto(s)
Enterocolitis Necrotizante , Enfermedades del Recién Nacido , Estomía , Lactante , Recién Nacido , Humanos , Gastrostomía/efectos adversos , Enterocolitis Necrotizante/epidemiología , Enterocolitis Necrotizante/cirugía , Estudios Retrospectivos , Morbilidad
10.
J Pediatr Surg ; 59(5): 969-974, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38042733

RESUMEN

BACKGROUND: Open fetal resection for large lung lesions has virtually been replaced by maternal steroid administration. Despite this paradigm shift, little is known about the effects steroids have on lung lesion growth in utero. METHODS: A 10-year retrospective review of all prenatally diagnosed lung lesions cared for at our fetal care center was performed. We evaluated the effects of prenatal steroids on congenital pulmonary airway malformation (CPAM)-volume-ratio (CVR), distinguishing change in CVR among CPAMs, bronchopulmonary sequestrations (BPS), and bronchial atresias. We also correlated fetal ultrasound and MRI findings with pathology to determine the accuracy of prenatal diagnosis. RESULTS: We evaluated 199 fetuses with a prenatal lung lesion. Fifty-four (27 %) were treated with prenatal steroids with a subsequent 21 % mean reduction in the CVR (2.1 ± 1.4 to 1.1 ± 0.4, p = 0.003). Fetuses with hydrops and mediastinal shift who were treated with steroids rarely had resolution of these radiographic findings. Postnatal pathology was available for 91/199 patients (45.7 %). The most common diagnosis was CPAM (42/91, 46 %), followed by BPS (30/91, 33 %), and bronchial atresia (14/91, 15 %). Fetuses who received steroids and had pathology consistent with CPAM were more likely to have a reduction in their CVR (p = 0.02). Fetal ultrasound correctly diagnosed the type of lung lesion in 75 % of cases and fetal MRI in 81 % of cases. CONCLUSIONS: Prenatally diagnosed CPAMs are more likely to respond to maternal steroids than BPS or bronchial atresias. Knowing the diagnosis in utero could aid to steward steroid usage, however, fetal imagining modalities are not perfect in distinguishing subtype. LEVEL OF EVIDENCE: III.

11.
Ann R Coll Surg Engl ; 106(2): 185-194, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37128857

RESUMEN

INTRODUCTION: This study examined to what extent supervised aerobic and resistance exercise combined with continued unsupervised exercise training improves cardiorespiratory fitness and corresponding perioperative risk in peripheral artery disease (PAD) patients with intermittent claudication. METHODS: A total of 106 patients (77% male) were enrolled into the study, alongside 155 healthy non-PAD control participants. Patients completed supervised exercise therapy (aerobic and resistance exercises of the upper and lower limbs) twice a week for 10 weeks. Thereafter, 52 patients completed 12 weeks of an unsupervised tailored home-based exercise. Pain-free walking distance (PWD), maximum walking distance (MWD), peak oxygen uptake ([Formula: see text]) and perioperative risk were assessed before and after both exercise interventions. RESULTS: Patients were highly unconditioned relative to healthy controls ([Formula: see text]=11.9 vs 24.2ml/kg/min, p=<0.001) with 91% classified as high perioperative risk (peak oxygen uptake <15ml/kg/min). Supervised exercise increased PWD (+44±81m, p=<0.001), MWD (+44±71m, p=<0.001) and [Formula: see text] (+1.01±1.63ml/kg/min, p=<0.001) and lowered perioperative risk (91% to 85%, p=<0.001). When compared with supervised exercise, the improvements in PWD were maintained following unsupervised exercise (+11±91m vs supervised exercise, p=0.572); however, MWD and [Formula: see text] decreased (-15±48m, p=0.030 and -0.34±1.11ml/kg/min, p=0.030, respectively) and perioperative risk increased (+3%, p=<0.001) although still below baseline (p=<0.001). CONCLUSIONS: Supervised aerobic and resistance exercise training and, to a lesser extent, unsupervised tailored exercise improves walking capacity and cardiorespiratory fitness and reduces perioperative risk in PAD patients with intermittent claudication.


Asunto(s)
Capacidad Cardiovascular , Enfermedades Pulmonares , Enfermedad Arterial Periférica , Humanos , Masculino , Femenino , Claudicación Intermitente/terapia , Enfermedad Arterial Periférica/complicaciones , Ejercicio Físico , Terapia por Ejercicio , Oxígeno , Resultado del Tratamiento
12.
J Pediatr Surg ; 59(5): 962-968, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38160185

RESUMEN

INTRODUCTION: Prosthetic patches (patch) and muscle flaps (flap) are techniques used for repair of congenital diaphragmatic hernia (CDH) with a large defect unamenable to primary closure. We hypothesized that the flap technique for CDH repair while on extra-corporeal membrane oxygenation (on-ECMO) would have decreased bleeding complications compared to patch due to the hemostatic advantage of native tissue. METHODS: A single-center retrospective comparative study of patients who underwent on-ECMO CDH repair between 2008 and 2022 was performed. RESULTS: Fifty-two patients met inclusion criteria: 18 patch (34.6%) and 34 flap (65.4%). There was no difference in CDH severity between groups. On univariate analysis, reoperation for surgical bleeding was lower following flap repair compared to patch (23.5% vs 55.6%, respectively; p = 0.045), 48-h postoperative blood product transfusion was lower after flap repair (132 mL/kg vs 273.5 mL/kg patch; p = 0.006), and two-year survival was increased in the flap repair group compared to patch (53.1% vs 17.7%, respectively; p = 0.036). On multivariate analysis adjusting for CDH side, day on ECMO repaired, and day of life CDH repaired, flap repair was significantly associated with lower five-day postoperative packed red blood cell transfusion amount, improved survival to hospital discharge, and improved two-year survival. CONCLUSIONS: Our experience suggests that the muscle flap technique for on-ECMO CDH repair is associated with reduced bleeding complications compared to prosthetic patch repair, which may in part be responsible for the improved survival seen in the flap repair group. These results support the flap repair technique as a favored method for on-ECMO CDH repair. LEVEL OF EVIDENCE: Level III.


Asunto(s)
Oxigenación por Membrana Extracorpórea , Hernias Diafragmáticas Congénitas , Humanos , Hernias Diafragmáticas Congénitas/cirugía , Estudios Retrospectivos , Diafragma , Colgajos Quirúrgicos
13.
Nat Commun ; 14(1): 7846, 2023 Dec 06.
Artículo en Inglés | MEDLINE | ID: mdl-38057298

RESUMEN

For trace gas sensing and precision spectroscopy, optical cavities incorporating low-loss mirrors are indispensable for path length and optical intensity enhancement. Optical interference coatings in the visible and near-infrared (NIR) spectral regions have achieved total optical losses below 2 parts per million (ppm), enabling a cavity finesse in excess of 1 million. However, such advancements have been lacking in the mid-infrared (MIR), despite substantial scientific interest. Here, we demonstrate a significant breakthrough in high-performance MIR mirrors, reporting substrate-transferred single-crystal interference coatings capable of cavity finesse values from 200 000 to 400 000 near 4.5 µm, with excess optical losses (scatter and absorption) below 5 ppm. In a first proof-of-concept demonstration, we achieve the lowest noise-equivalent absorption in a linear cavity ring-down spectrometer normalized by cavity length. This substantial improvement in performance will unlock a rich variety of MIR applications for atmospheric transport and environmental sciences, detection of fugitive emissions, process gas monitoring, breath-gas analysis, and verification of biogenic fuels and plastics.

14.
Mol Ther Nucleic Acids ; 34: 102081, 2023 Dec 12.
Artículo en Inglés | MEDLINE | ID: mdl-38111915

RESUMEN

MicroRNAs (miRNAs) control the expression of diverse subsets of target mRNAs, and studies have found miRNA dysregulation in failing hearts. Expression of miR-29 is abundant in heart, increases with aging, and is altered in cardiomyopathies. Prior studies demonstrate that miR-29 reduction via genetic knockout or pharmacologic blockade can blunt cardiac hypertrophy and fibrosis in mice. Surprisingly, this depended on specifically blunting miR-29 actions in cardiomyocytes versus fibroblasts. To begin developing more translationally relevant vectors, we generated a novel transgene-encoded miR-29 inhibitor (TuD-29) that can be incorporated into a viral-mediated gene therapy for cardioprotection. Here, we corroborate that miR-29 expression and activity is higher in cardiomyocytes versus fibroblasts and demonstrate that TuD-29 effectively blunts hypertrophic responses in cultured cardiomyocytes and mouse hearts. Furthermore, we found that adeno-associated virus (AAV)-mediated miR-29 overexpression in mouse hearts induces early diastolic dysfunction, whereas AAV:TuD-29 treatment improves cardiac output by increasing end-diastolic and stroke volumes. The integration of RNA sequencing and miRNA-target interactomes reveals that miR-29 regulates genes involved in calcium handling, cell stress and hypertrophy, metabolism, ion transport, and extracellular matrix remodeling. These investigations support a likely versatile role for miR-29 in influencing myocardial compliance and relaxation, potentially providing a unique therapeutic avenue to improve diastolic function in heart failure patients.

15.
Prenat Diagn ; 43(12): 1514-1519, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37807606

RESUMEN

OBJECTIVE: Giant omphaloceles (GO) have associated pulmonary hypoplasia and respiratory complications. Total lung volumes (TLV) on fetal MRI can prognosticate congenital diaphragmatic hernia outcomes; however, its applicability to GO is unknown. We hypothesize that late gestation TLV and observed-to-expected TLV (O/E TLV) on fetal MRI correlate with postnatal pulmonary morbidity in GO. METHOD: A single-institution retrospective review of GO evaluated between 2012 and 2022 was performed. Fetal MRI TLV between 32 and 36 weeks' gestation and O/E TLV throughout gestation were calculated and correlated with postnatal outcomes. RESULTS: 86 fetuses with omphaloceles were evaluated; however, only 26 met strict inclusion criteria. MRIs occurred between 18 and 36 weeks' gestation. Those requiring delivery room intubation had significantly lower late gestation TLV and O/E TLV. O/E TLV predicted tracheostomy placement and survival. Neither TLV nor O/E TLV predicted the length of hospitalization or supplemental oxygen after discharge. Three fetuses had a TLV less than 35 mL: one died of respiratory failure, and the other two required tracheostomy. CONCLUSIONS: Fetal MRI TLV measured between 32 and 36 weeks' gestation and O/E TLV predict the need for delivery room intubation and tracheostomy. O/E TLV correlated with survival. These data support fetal MRI as a prognostic tool to predict GO associated pulmonary morbidity.


Asunto(s)
Hernia Umbilical , Hernias Diafragmáticas Congénitas , Lactante , Femenino , Embarazo , Humanos , Hernia Umbilical/complicaciones , Pulmón/diagnóstico por imagen , Mediciones del Volumen Pulmonar , Hernias Diafragmáticas Congénitas/complicaciones , Hernias Diafragmáticas Congénitas/diagnóstico por imagen , Feto , Estudios Retrospectivos , Imagen por Resonancia Magnética , Morbilidad
16.
Pharmaceutics ; 15(9)2023 Aug 26.
Artículo en Inglés | MEDLINE | ID: mdl-37765178

RESUMEN

Acute respiratory distress syndrome (ARDS) has approximately 40% in-hospital mortality, and treatment is limited to supportive care. Pneumonia is the underlying etiology in many cases with unrestrained inflammation central to the pathophysiology. We have previously shown that CNP-miR146a, a radical scavenging cerium oxide nanoparticle (CNP) conjugated to the anti-inflammatory microRNA(miR)-146a, reduces bleomycin- and endotoxin-induced acute lung injury (ALI) by decreasing inflammation. We therefore hypothesized that CNP-miR146a would decrease inflammation in murine infectious ALI. Mice were injured with intratracheal (IT) MRSA or saline followed by treatment with IT CNP-miR146a or saline control. Twenty-four hours post-infection, bronchoalveolar lavage fluid (BALF) and whole lungs were analyzed for various markers of inflammation. Compared to controls, MRSA infection significantly increased proinflammatory gene expression (IL-6, IL-8, TNFα, IL-1ß; p < 0.05), BALF proinflammatory cytokines (IL-6, IL-8, TNFα, IL-1ß; p < 0.01), and inflammatory cell infiltrate (p = 0.03). CNP-miR146a treatment significantly decreased proinflammatory gene expression (IL-6, IL-8, TNFα, IL-1ß; p < 0.05), bronchoalveolar proinflammatory protein leak (IL-6, IL-8, TNFα; p < 0.05), and inflammatory infiltrate (p = 0.01). CNP-miR146a decreases inflammation and improves alveolar-capillary barrier integrity in the MRSA-infected lung and has significant promise as a potential therapeutic for ARDS.

17.
J Surg Res ; 292: 234-238, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37657141

RESUMEN

INTRODUCTION: Fetal growth restriction (FGR) is associated with impaired angiogenesis and chronic inflammation. MicroRNAs (miRs) are short noncoding RNAs that regulate gene expression at the post-transcriptional level by targeting messenger RNA (mRNA) for degradation or by suppressing translation. We hypothesize that dysregulation of miR-15b, an antiangiogenic miR, and miR-146a, an anti-inflammatory miR, are associated with the FGR's pathogenesis. METHODS: Pregnant mice were provided ad libitum access to food between E1 and E8. From E9-E18, dams received either a 50% caloric restricted diet (FGR) or continued ad libitum access (controls). Placentas were harvested at E18.5 and total RNA was extracted. Gene expression levels of miRs and mRNAs were compared between FGR and control placentas. RESULTS: Placentas affected by FGR demonstrated increased expression of miR-15b. Vascular endothelial growth factor alpha, which is downregulated in response to increased levels of miR-15b, was suppressed. The anti-inflammatory miR, miR-146a, was downregulated, resulting in upregulation of proinflammatory (IL-6, IL-8, and NFkB1) and oxidative stress (HIF-1α, SOD2, and Nox2) mediators. CONCLUSIONS: Aberrant angiogenesis and chronic inflammation seen in FGR appear to be associated with dysregulated miR-15b and miR-146a gene expression, respectively. This observation suggests these miRs play a post-transcriptional regulatory role in FGR, providing an insight into possible therapeutic targets.

18.
Faraday Discuss ; 245(0): 368-379, 2023 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-37306220

RESUMEN

We report direct frequency comb spectroscopy of the 2ν1 band of H13CN in the short-wave infrared (λ = 1.56 µm) towards experimental validation of molecular line lists that support observatories like JWST. The laboratory measurements aim to test spectral reference data generated from an experimentally accurate potential energy surface (PES) and an ab initio dipole moment surface (DMS) calculated from quantum chemistry theory. Benchmarking theory with experiment will improve confidence in new astrophysics and astrochemistry inferred from spectroscopic observations of HCN and HNC. Here we describe our instrumentation and initial results using a cross-dispersed spectrometer with a virtually imaged phased array (VIPA).

19.
J Pediatr Surg ; 58(11): 2171-2180, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37353392

RESUMEN

INTRODUCTION: Appendicitis is the most common indication for emergency general surgery in the pediatric population. Computed tomography (CT) or magnetic resonance imaging (MRI) may be used for diagnosis when ultrasound findings are equivocal. However, CT involves unnecessary radiation exposure if MRI is available. After introducing a rapid sequence MRI (rsMRI) appendicitis protocol at our institution, CT was still preferentially used. We therefore implemented a quality improvement (QI) campaign to reduce the rate of CTs and increase the rate of rsMRI. Here, we assess the effectiveness of the QI campaign while evaluating potential barriers to using rsMRI. METHODS: We conducted a mixed methods study, first performing stakeholder interviews which informed the design of a QI campaign initiated in May 2021 and a midway feedback survey in December 2021. A retrospective cohort study was then performed of children evaluated for appendicitis at our institution between January 1, 2016, and April 30, 2022. CT and rsMRI rates were compared before and after QI campaign implementation. RESULTS: There was a significant decrease in rate of CTs and increase in rate of rsMRIs performed following the initiation of the QI campaign (p < 0.0001). The rate of CT scans decreased by a factor of 0.4 while the rate of rsMRI increased by a factor of 9.5. CONCLUSION: A successful QI campaign was initiated at our institution, resulting in decreased utilization of CT and increased use of rsMRI for the evaluation of suspected appendicitis. These results highlight the potential impact of QI projects. LEVEL OF EVIDENCE: III.

20.
Occup Med (Lond) ; 73(4): 208-210, 2023 05 18.
Artículo en Inglés | MEDLINE | ID: mdl-37061840

RESUMEN

BACKGROUND: Mortuaries are predominantly staffed by anatomical pathology technologists (APTs) and pathologists, and the work they undertake carries implicit health risk due to its nature. Until now there has not been a nationwide assessment of the occupational health of these essential workers in the UK. AIMS: To assess the current occupational health status and needs of the mortuary workforce in the UK. METHODS: We created a bespoke, brief online survey which was approved by the professional bodies representing APTs and pathologists in the UK. The survey was disseminated electronically using these organizations' targeted mailing lists. RESULTS: Two hundred and thirty participants completed the survey, comprising 108 (47%) APTs and 122 (53%) pathologists. Most (89%) respondents reported that they have suffered from occupational health issues, the largest subcategory being musculoskeletal problems (77%). Almost half (48%) of APTs and around one-quarter (26%) of pathologists who responded have taken time off work in the last year because of occupational health problems, with almost one-fifth (19%) of the APTs having taken at least 4 weeks off. CONCLUSIONS: A significant number of workhours are lost per year to sick leave resulting from occupational health problems. Respondents' comments highlight issues in workspaces, rest facilities and staffing, and variability in working conditions across the country. We suggest that future workforce planning should prioritize good occupational health, with nationwide improvements in mortuary design.


Asunto(s)
Enfermedades Profesionales , Salud Laboral , Humanos , Encuestas y Cuestionarios , Encuestas Epidemiológicas , Recursos Humanos , Enfermedades Profesionales/epidemiología , Reino Unido
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