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1.
Artículo en Inglés | MEDLINE | ID: mdl-39104322

RESUMEN

Apoptosis, inflammation, and wound healing are critical pathophysiological events associated with various liver diseases. Currently, there is a lack of in vivo approaches to study hepatocyte apoptosis-induced liver injury and repair. To address this critical knowledge gap, we developed a unique genetically modified mouse model, namely, 3xTg-iHAP (3-Transgene with inducible Hepatocyte Apoptosis Phenotype) in this study. The 3xTg-iHAP mice possess three transgenes including Alb-Cre, Rosa26-rtTA, and tetO-Fasl on a B6 background. These mice are phenotypically normal, viable, and fertile. After subcutaneous administration of a single dose of doxycycline (5 mg/kg, Dox) to 3xTg-iHAP mice, we observed a complete histological spectrum of sterile liver wound-healing responses: asymptomatic hepatocyte apoptosis at 8 h, necrotic liver injury and sterile inflammation at 48 h, followed by hepatocyte mitosis and regeneration within 7 days. During the injury phase, the mice exhibited an increase in biomarkers of ALT, CXCL1, and IL-6 in peripheral blood and α-SMA protein in liver tissues. Conversely, the mice displayed a decrease in these markers in the recovery phase. Remarkably, this model shows that the sterile liver injury following elevated hepatocyte apoptosis is associated with an increase in myeloid cells in the liver. Within 7 days post-Dox administration, the liver of Dox-treated 3xTg-iHAP mice displays a normal histological structure, indicating completion of wound-healing. Together, we established a novel mouse model of injury and regeneration induced by hepatocyte apoptosis. This tool provides a robust in vivo platform for studying the pathophysiology of sterile liver inflammation, regeneration, and new therapeutic interventions for liver diseases.

2.
Mol Cell ; 84(15): 2935-2948.e7, 2024 Aug 08.
Artículo en Inglés | MEDLINE | ID: mdl-39019044

RESUMEN

Mitochondria are essential regulators of innate immunity. They generate long mitochondrial double-stranded RNAs (mt-dsRNAs) and release them into the cytosol to trigger an immune response under pathological stress conditions. Yet the regulation of these self-immunogenic RNAs remains largely unknown. Here, we employ CRISPR screening on mitochondrial RNA (mtRNA)-binding proteins and identify NOP2/Sun RNA methyltransferase 4 (NSUN4) as a key regulator of mt-dsRNA expression in human cells. We find that NSUN4 induces 5-methylcytosine (m5C) modification on mtRNAs, especially on the termini of light-strand long noncoding RNAs. These m5C-modified RNAs are recognized by complement C1q-binding protein (C1QBP), which recruits polyribonucleotide nucleotidyltransferase to facilitate RNA turnover. Suppression of NSUN4 or C1QBP results in increased mt-dsRNA expression, while C1QBP deficiency also leads to increased cytosolic mt-dsRNAs and subsequent immune activation. Collectively, our study unveils the mechanism underlying the selective degradation of light-strand mtRNAs and establishes a molecular mark for mtRNA decay and cytosolic release.


Asunto(s)
5-Metilcitosina , Citosol , Mitocondrias , Estabilidad del ARN , ARN Bicatenario , ARN Mitocondrial , Humanos , Citosol/metabolismo , 5-Metilcitosina/metabolismo , Mitocondrias/metabolismo , Mitocondrias/genética , ARN Bicatenario/metabolismo , ARN Bicatenario/genética , ARN Mitocondrial/genética , ARN Mitocondrial/metabolismo , Células HEK293 , Células HeLa , Metiltransferasas/metabolismo , Metiltransferasas/genética , Inmunidad Innata , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Animales , Proteínas de Unión al ARN/metabolismo , Proteínas de Unión al ARN/genética , Sistemas CRISPR-Cas
3.
J Alzheimers Dis ; 100(3): 791-797, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38905050

RESUMEN

Background: Evidence from previous observational studies suggest that infection by herpes simplex virus (HSV) and varicella zoster virus (VZV) increase the risk of dementia. Objective: To investigate if older adults exposed to HSV treatment have lower risk of dementia than the rest of the population. Methods: We used the 10% Australian Pharmaceutical Benefits Scheme (PBS) database from 2013 to 2022 to ascertain the cross-sectional, time-series and longitudinal association between exposure to HSV treatment and the dispensing of antidementia medicines. Participants were men and women aged 60 years or older. We used Anatomical Therapeutic Chemical (ATC) codes to identify medicines dispensed for the treatment of HSV and dementia. Results: During the year 2022 6,868 (1.2%) of 559,561 of participants aged 60 years or over were dispensed antidementia agent. The odds ratio (OR) of being dispensed an antidementia agent among individuals dispensed treatment for HSV was 0.73 (99% CI = 0.56-0.95). Multilevel logistic regression for the 2013-2022 period for those dispensed HSV treatment was 0.87 (99% CI = 0.75-1.00). Split-time span series from 2013 was associated with hazard ratio of 0.98 (99% CI = 0.89-1.07) for individuals dispensed relative to those not dispensed HSV treatment. All analyses were adjusted for age, sex, and the dispensing of medicines for the treatment of diabetes, hyperlipidemia, hypertension, and ischemic heart disease. Conclusions: The dispensing of antiviral medicines for the treatment of HSV and VZV is consistently, but not conclusively, associated with decreased dispensing of antidementia medicines. This suggests that treatment of HSV and VZV infections may contribute to reduce the risk of dementia.


Asunto(s)
Demencia , Humanos , Masculino , Femenino , Estudios Transversales , Anciano , Persona de Mediana Edad , Australia/epidemiología , Estudios Longitudinales , Demencia/tratamiento farmacológico , Demencia/epidemiología , Anciano de 80 o más Años , Antivirales/uso terapéutico , Nootrópicos/uso terapéutico , Herpes Simple/tratamiento farmacológico , Herpes Simple/epidemiología , Infecciones por Herpesviridae/tratamiento farmacológico , Infecciones por Herpesviridae/epidemiología
4.
Int J Dermatol ; 63(9): 1164-1171, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38727148

RESUMEN

Eosinophilic dermatosis of hematologic malignancy (EDHM) is a cutaneous manifestation seen in patients with hematoproliferative and lymphoproliferative disorders, most commonly chronic lymphocytic leukemia. This systematic review aimed to summarize the therapeutic interventions of EDHM. A comprehensive search yielded 71 studies, predominantly case reports and series. The most frequently reported modalities were systemic and topical corticosteroids, as well as treatment of the underlying malignancy. Responses to these treatments varied. Targeted therapies, including dupilumab and omalizumab, showed promise, as did other modalities such as montelukast, dapsone, doxycycline, and phototherapy. Higher-quality studies should be conducted to facilitate higher-quality management recommendations for EDHM.


Asunto(s)
Eosinofilia , Humanos , Eosinofilia/diagnóstico , Eosinofilia/tratamiento farmacológico , Eosinofilia/terapia , Anticuerpos Monoclonales Humanizados/uso terapéutico , Sulfuros , Omalizumab/uso terapéutico , Neoplasias Hematológicas/complicaciones , Neoplasias Hematológicas/terapia , Fototerapia/métodos , Ciclopropanos/uso terapéutico , Ciclopropanos/administración & dosificación , Quinolinas/uso terapéutico , Dapsona/uso terapéutico , Doxiciclina/uso terapéutico , Corticoesteroides/uso terapéutico , Leucemia Linfocítica Crónica de Células B/complicaciones , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Administración Cutánea , Acetatos
5.
Cell Mol Gastroenterol Hepatol ; 18(3): 101364, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38788898

RESUMEN

BACKGROUND & AIMS: Necrotizing enterocolitis (NEC) is a life-threatening disease affecting mostly the ileum of preemies. Intestinal epithelial cell (IEC) apoptosis contributes to NEC pathogenesis. However, how scattered crypt IEC apoptosis leads to NEC with excessive villus epithelial necrosis remains unclear. METHODS: A novel triple-transgenic mouse model, namely, 3xTg-iAPcIEC (inducible apoptosis phenotype in crypt-IEC), was developed to induce IEC-specific overexpression of Fasl transgene using doxycycline (Dox)-inducible tetO-rtTA system and villin-cre technology. The 3-days-old neonatal 3xTg-iAPcIEC mice and their littermate controls were subcutaneously (s.c.) challenged with a single dose of Dox. Intestinal tissues were processed at different time points to examine scattered crypt IEC apoptosis-mediated NEC development. Gene knockout technology, antibody-mediated cell depletion, and antibiotic-facilitated Gram-positive bacteria depletion were used to study mechanisms. RESULTS: Treatment of 3xTg-iAPcIEC mouse pups with Dox induces scattered crypt IEC apoptosis followed by crypt inflammation and excessive villous necrosis resembling NEC. This progression correlated with elevated Ifng, Rip3, CD8+ T cells, and Gram-positive bacteria in the ileum. Mechanistically, IFN-γ and RIP3-activated signals mediate the effect of scattered crypt IEC apoptosis on the induction of intestinal crypt inflammation and villous necrosis. Meanwhile, pathophysiological events of CD8+ T cell infiltration and dysbiosis with Gram-positive bacteria primarily contribute to excessive villous inflammation and necrosis. Notably, blocking any of these events protects against NEC development in 3xTg-iAPcIEC mouse pups, underlining their central roles in NEC pathogenesis. CONCLUSIONS: Scattered crypt IEC apoptosis induces NEC in mouse pups via IFN-γ, RIP3, CD8+ T cells, and Gram-positive bacteria-mediated comprehensive pathophysiological events. Our findings may advance knowledge in the prevention and treatment of NEC.


Asunto(s)
Apoptosis , Modelos Animales de Enfermedad , Enterocolitis Necrotizante , Proteína Ligando Fas , Interferón gamma , Mucosa Intestinal , Ratones Transgénicos , Animales , Enterocolitis Necrotizante/patología , Enterocolitis Necrotizante/metabolismo , Ratones , Mucosa Intestinal/patología , Mucosa Intestinal/microbiología , Mucosa Intestinal/inmunología , Interferón gamma/metabolismo , Proteína Ligando Fas/metabolismo , Proteína Serina-Treonina Quinasas de Interacción con Receptores/metabolismo , Proteína Serina-Treonina Quinasas de Interacción con Receptores/genética , Células Epiteliales/patología , Células Epiteliales/metabolismo , Linfocitos T CD8-positivos/inmunología , Necrosis , Animales Recién Nacidos , Doxiciclina/farmacología , Humanos , Íleon/patología , Íleon/inmunología
6.
Clin Endocrinol (Oxf) ; 100(2): 170-180, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-38059618

RESUMEN

OBJECTIVE: Prevalence of subclinical thyroid disease increases with age, but optimal detection and surveillance strategies remain unclear particularly for older men. We aimed to assess thyroid stimulating hormone (TSH) and free thyroxine (FT4) concentrations and their longitudinal changes, to determine the prevalence and incidence of subclinical thyroid dysfunction in older men. DESIGN, PARTICIPANTS AND MEASUREMENTS: Longitudinal study of 994 community-dwelling men aged ≥70 years without known or current thyroid disease, with TSH and FT4 concentrations assessed at baseline and follow-up (after 8.7 ± 0.9 years). Factors associated with incident subclinical thyroid dysfunction were examined by logistic regression and receiver operating characteristic analyses. RESULTS: At baseline, 85 men (8.6%) had subclinical hypothyroidism and 10 (1.0%) subclinical hyperthyroidism. Among 899 men euthyroid at baseline (mean age 75.0 ± 3.0 years), 713 (79.3%) remained euthyroid, 180 (20.0%) developed subclinical/overt hypothyroidism, and 6 (0.7%) subclinical/overt hyperthyroidism. Change in TSH correlated with baseline TSH (r = .16, p < .05). Change in FT4 correlated inversely with baseline FT4 (r = -0.35, p < .05). Only higher age and baseline TSH predicted progression from euthyroid to subclinical/overt hypothyroidism (fully-adjusted odds ratio [OR] per year=1.09, 95% confidence interval [CI] = 1.02-1.17, p = .006; per 2.7-fold increase in TSH OR = 65.4, CI = 31.9-134, p < .001). Baseline TSH concentration ≥2.34 mIU/L had 76% sensitivity and 77% specificity for predicting development of subclinical/overt hypothyroidism. CONCLUSIONS: In older men TSH concentration increased over time, while FT4 concentration showed little change. Subclinical or overt hypothyroidism evolved in one fifth of initially euthyroid men, age and higher baseline TSH predicted this outcome. Increased surveillance for thyroid dysfunction may be justified in older men, especially those with high-normal TSH.


Asunto(s)
Hipertiroidismo , Hipotiroidismo , Enfermedades de la Tiroides , Masculino , Humanos , Anciano , Estudios Longitudinales , Hipotiroidismo/diagnóstico , Tirotropina , Tiroxina
7.
Radiographics ; 43(9): e230043, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37651277

RESUMEN

Cirrhosis is the end stage of chronic liver disease and causes architectural distortion and perfusional anomalies. It is a major risk factor for developing hepatocellular carcinoma (HCC). Common disease entities in noncirrhotic livers, such as hemangiomas, can be rare in cirrhotic livers, and benign entities such as confluent hepatic fibrosis and focal nodular hyperplasia-like lesions may mimic the appearance of malignancies,. HCC usually has typical imaging characteristics, such as the major features established by the Liver Imaging Reporting and Data System. However, HCC can also have a spectrum of atypical or uncommon appearances, such as cystic HCC, hypovascular HCC, or macroscopic fat-containing HCC. HCCs with certain genetic mutations such as CTNNB-1-mutated HCC can harbor unique imaging features not seen in other types of HCC. In addition, malignancies that are less common than HCC, such as cholangiocarcinoma and metastases, which can be difficult to differentiate, can still occur in cirrhotic livers. Atypical imaging features of benign and malignant lesions can be challenging to accurately diagnose. Therefore, familiarity with these features and an understanding of the prevalence of disease entities in cirrhotic livers are key in the daily practice of radiologists for evaluation of cirrhotic livers. The authors illustrate the typical and atypical features of benign and malignant lesions in cirrhosis and discuss the technical pitfalls and unique advantages associated with various imaging modalities in assessing cirrhotic livers, including noncontrast and contrast-enhanced US, CT, and MRI. Work of the U.S. Government published under an exclusive license with the RSNA. Quiz questions for this article are available in the supplemental material.


Asunto(s)
Neoplasias de los Conductos Biliares , Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico por imagen , Neoplasias Hepáticas/diagnóstico por imagen , Cirrosis Hepática/diagnóstico por imagen , Conductos Biliares Intrahepáticos
8.
CJC Open ; 5(6): 415-420, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37397610

RESUMEN

This study assesses the impact of contrast-enhanced chest and abdominal computed tomography (CT) and 18F-fluorodeoxyglucose positron emission tomography (FDG-PET)/CT in preoperative screening of heart transplantation or ventricular assist device candidates. Patients who underwent both studies within a 6-month interval at our institution between 2014 and 2021 were reviewed for significant findings, defined as possible contraindications or actionable findings. Among the 79 included patients, significant findings were found in 38 (48.1%) with CT and in 18 (22.8%) with FDG-PET/CT (P = 0.0015). FDG-PET/CT identified 10 additional significant findings, but none of these precluded patient listing for heart transplantation. Use of FDG-PET/CT may lead to unnecessary investigations when performed indiscriminately in all patients.


La présente étude se penche sur l'incidence du recours à une tomodensitométrie (TDM) thoracique et abdominale avec produit de contraste et à une tomographie par émission de positrons au fluorodésoxyglucose marqué au fluor 18 (TEP-18FDG) lors d'évaluation préopératoire de candidats à une transplantation cardiaque ou à l'implantation d'un dispositif d'assistance ventriculaire. Les résultats obtenus de 79 patients qui ont subi ces deux examens dans un intervalle maximal de six mois à notre établissement entre 2014 et 2021 ont été analysés à la recherche de conclusions pertinentes, définies comme des contre-indications possibles à l'intervention ou des résultats ayant un impact direct sur la prise en charge du patient. De telles conclusions ont été constatées chez 38 participants (48,1 %) suite à une TDM et 18 participants (22,8 %) suite à une TEP-18FDG (p = 0,0015). La TEP-18FDG a permis de relever 10 résultats d'importance supplémentaires, mais aucun d'entre eux n'aurait entraîné l'inadmissibilité du patient à une transplantation cardiaque. L'utilisation de la TEP-18FDG pourrait donner lieu à des examens non nécessaires lorsqu'elle est réalisée sans distinction chez tous les patients.

9.
Autophagy ; 19(7): 2094-2110, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-36708254

RESUMEN

Mitochondrial impairment is a hallmark feature of neurodegenerative disorders, such as Parkinson disease, and PRKN/parkin-mediated mitophagy serves to remove unhealthy mitochondria from cells. Notably, probiotics are used to alleviate several symptoms of Parkinson disease including impaired locomotion and neurodegeneration in preclinical studies and constipation in clinical trials. There is some evidence to suggest that probiotics can modulate mitochondrial quality control pathways. In this study, we screened 49 probiotic strains and tested distinct stages of mitophagy to determine whether probiotic treatment could upregulate mitophagy in cells undergoing mitochondrial stress. We found two probiotics, Saccharomyces boulardii and Lactococcus lactis, that upregulated mitochondrial PRKN recruitment, phospho-ubiquitination, and MFN degradation in our cellular assays. Administration of these strains to Drosophila that were exposed to paraquat, a mitochondrial toxin, resulted in improved longevity and motor function. Further, we directly observed increased lysosomal degradation of dysfunctional mitochondria in the treated Drosophila brains. These effects were replicated in vitro and in vivo with supra-physiological concentrations of exogenous soluble factors that are released by probiotics in cultures grown under laboratory conditions. We identified methyl-isoquinoline-6-carboxylate as one candidate molecule, which upregulates mitochondrial PRKN recruitment, phospho-ubiquitination, MFN degradation, and lysosomal degradation of damaged mitochondria. Addition of methyl-isoquinoline-6-carboxylate to the fly food restored motor function to paraquat-treated Drosophila. These data suggest a novel mechanism that is facilitated by probiotics to stimulate mitophagy through a PRKN-dependent pathway, which could explain the potential therapeutic benefit of probiotic administration to patients with Parkinson disease.


Asunto(s)
Lactococcus lactis , Enfermedad de Parkinson , Saccharomyces boulardii , Animales , Mitofagia , Lactococcus lactis/metabolismo , Saccharomyces boulardii/metabolismo , Proteínas Quinasas/metabolismo , Autofagia , Paraquat , Ubiquitina-Proteína Ligasas/metabolismo , Drosophila/metabolismo
10.
Semin Roentgenol ; 57(4): 313-323, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-36265983

RESUMEN

Pulmonary CTA is a commonly performed study and the radiologist's role is not limited to simply producing a report. The process from identifying the appropriate patients who will benefit from the study to improving performance in the radiology department requires the radiologist's involvement, expertise, and leadership. The focus of this narrative review is to highlight the different steps and the ways to improve the quality in the assessment of thromboembolic disease where the radiologists can have an impact. This article provides an update on the commonly used and more recently published clinical decision tools, specific parameter adjustments of pulmonary CTA for more challenging patients and potential improvement for the radiology department.


Asunto(s)
Embolia Pulmonar , Humanos , Embolia Pulmonar/diagnóstico por imagen , Radiólogos , Enfermedad Aguda
11.
Antibiotics (Basel) ; 11(9)2022 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-36139951

RESUMEN

Excessive antibiotic consumption is still common among critically ill patients admitted to intensive care units (ICU), especially during the coronavirus disease 2019 (COVID-19) period. Moreover, information regarding antimicrobial consumption among ICUs in South-East Asia remains scarce and limited. This study aims to determine antibiotics utilization in ICUs by measuring antibiotics consumption over the past six years (2016−2021) and specifically evaluating carbapenems prescribed in a COVID-19 ICU and a general intensive care unit (GICU) during the second year of the COVID-19 pandemic. (2) Methods: This is a retrospective cross-sectional observational analysis of antibiotics consumption and carbapenems prescriptions. Antibiotic utilization data were estimated using the WHO Defined Daily Doses (DDD). Carbapenems prescription information was extracted from the audits conducted by ward pharmacists. Patients who were prescribed carbapenems during their admission to COVID-19 ICU and GICU were included. Patients who passed away before being reviewed by the pharmacists were excluded. (3) Results: In general, antibiotics consumption increased markedly in the year 2021 when compared to previous years. Majority of carbapenems were prescribed empirically (86.8%). Comparing COVID-19 ICU and GICU, the reasons for empirical carbapenems therapy in COVID-19 ICU was predominantly for therapy escalation (64.7% COVID-19 ICU vs. 34% GICU, p < 0.001), whereas empirical prescription in GICU was for coverage of extended-spectrum beta-lactamases (ESBL) gram-negative bacteria (GNB) (45.3% GICU vs. 22.4% COVID-19 ICU, p = 0.005). Despite microbiological evidence, the empirical carbapenems were continued for a median (interquartile range (IQR)) of seven (5−8) days. This implies the need for a rapid diagnostic assay on direct specimens, together with comprehensive antimicrobial stewardship (AMS) discourse with intensivists to address this issue.

12.
J Biol Chem ; 298(10): 102473, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-36089064

RESUMEN

WalKR is a two-component system that is essential for viability in Gram-positive bacteria that regulates the all-important autolysins in cell wall homeostasis. Further investigation of this essential system is important for identifying ways to address antibiotic resistance. Here, we show that a T101M mutation in walR confers a defect in autolysis, a thickened cell wall, and decreased susceptibility to antibiotics that target lipid II cycle, a phenotype that is reminiscent of the clinical resistance form known as vancomycin intermediate-resistant Staphylococcus aureus. Importantly, this is accompanied by dramatic sensitization to tunicamycin. We demonstrate that this phenotype is due to partial collapse of a pathway consisting of autolysins, AtlA and Sle1, a transmembrane sugar permease, MurP, and GlcNAc recycling enzymes, MupG and MurQ. We suggest that this causes a shortage of substrate for the peptidoglycan biosynthesis enzyme MraY, causing it to be hypersensitive to competitive inhibition by tunicamycin. In conclusion, our results constitute a new molecular model for antibiotic sensitivity in S. aureus and a promising new route for antibiotic discovery.


Asunto(s)
Farmacorresistencia Microbiana , Staphylococcus aureus Resistente a Meticilina , Humanos , Antibacterianos/farmacología , Antibacterianos/metabolismo , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Pared Celular/genética , Pared Celular/metabolismo , Farmacorresistencia Microbiana/genética , Staphylococcus aureus Resistente a Meticilina/metabolismo , Pruebas de Sensibilidad Microbiana , N-Acetil Muramoil-L-Alanina Amidasa/genética , N-Acetil Muramoil-L-Alanina Amidasa/metabolismo , Infecciones Estafilocócicas/microbiología , Staphylococcus aureus/metabolismo , Tunicamicina/farmacología
14.
Genes Dis ; 9(5): 1194-1207, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-35873033

RESUMEN

Macrophages are dominant innate immune cells. They demonstrate remarkable heterogeneity and plasticity that are essential for homeostasis and host defense. The heterogeneity of tissue macrophages is shaped by the ontogeny, tissue factors, and environmental signals, a pattern in a tissue-associated latitudinal manner. At the same time, macrophages have long been considered as mainly plastic cells. These cells respond to stimulation quickly and in a stimulus-specific way by utilizing a longitudinal cascaded activation, including coordination of signal transducer, epigenetic elements, and transcription factors, conclusively determine the macrophage phenotypes and functions. With the development of cutting-edge technologies, such as fate-mapping, single-cell transcriptomics, ipsc platform, nanotherapeutic materials, etc., our understanding of macrophage biology and the roles in the pathogenesis of diseases is much advanced. This review summarizes recent progress on the latitudinal and longitudinal regulation of tissue macrophages in inflammatory diseases. The latitudinal regulation covers the tissue macrophage origins, tissue factors, and environmental signals, reflecting the macrophage heterogeneity. The longitudinal regulation focuses on how multiple factors shape the phenotypes and functions of macrophage subsets to gain plasticity in inflammatory diseases (i.e., inflammatory bowel disease). In addition, how to target macrophages as a potential therapeutic approach and cutting edge-technologies for tissue macrophage study are also discussed in this review.

15.
Am J Physiol Gastrointest Liver Physiol ; 323(3): G205-G218, 2022 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-35819158

RESUMEN

Feeding modes influence the gut microbiome, immune system, and intestinal barrier homeostasis in neonates; how feeding modes impact susceptibility to neonatal gastrointestinal (GI) diseases is still uncertain. Here, we investigated the impact of dam feeding (DF) and formula feeding (FF) on features of the gut microbiome and physiological inflammation during the first 2 days of postnatal development and on the susceptibility to intestinal injury related to the inflammatory state in neonatal mouse pups. 16S rRNA sequencing data revealed microbiome changes, lower α-diversity, and a distinct pattern of ß-diversity including expansion of f_Enterobacteriaceae and f_Enterococcaceae in the ileum of FF pups compared with DF pups by postnatal day (P)2. Together with gut dysbiosis, the FF cohort also had greater ileal mucosa physiological inflammatory activity compared with DF pups by P2 but maintained normal histological features. Interestingly, FF but not DF mouse pups developed necrotizing enterocolitis (NEC)-like intestinal injury within 24 h after anti-CD3 mAb treatment, suggesting that FF influences the susceptibility to intestinal injury in neonates. We further found that NEC-like incidence in anti-CD3 mAb-treated FF neonatal pups was attenuated by antibiotic treatment. Collectively, our data suggest that FF predisposes mouse pups to anti-CD3 mAb-induced intestinal injury due to abnormal f_Enterobacteriaceae and f_Enterococcaceae colonization. These findings advance our understanding of FF-associated microbial colonization and intestinal inflammation, which may help inform the development of new therapeutic approaches to GI diseases like NEC in infants.NEW & NOTEWORTHY This report shows that a feeding mode profoundly affects gut colonization in neonatal mice. Furthermore, our results demonstrate that formula feeding predisposes mouse pups to anti-CD3 mAb-induced necrotizing enterocolitis (NEC)-like intestinal injury upon inadequate microbial colonization. The study suggests the role of the combined presence of formula feeding-associated dysbiosis and mucosal inflammation in the pathogenesis of NEC and provides a new mouse model to study this disease.


Asunto(s)
Enterocolitis Necrotizante , Microbioma Gastrointestinal , Animales , Animales Recién Nacidos , Disbiosis , Enterocolitis Necrotizante/tratamiento farmacológico , Humanos , Inflamación/patología , Mucosa Intestinal/patología , Ratones , ARN Ribosómico 16S
17.
JACC Basic Transl Sci ; 7(2): 131-142, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-35257040

RESUMEN

Stents can be effectively implemented with no x-rays or contrast medium. Modified stents were successfully implanted in 9 of 11 attempted targets (82%) (7 carotid and 4 coronary arteries) using an impedance-sensitive navigation system and optical coherence tomography. Electroanatomical navigation systems can be used to assist interventionalists in performing arterial stenting while minimizing x-ray and contrast use, thereby potentially enhancing safety for both patients and catheterization laboratory staff members.

18.
AJR Am J Roentgenol ; 218(3): 396-404, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-34612678

RESUMEN

Pulmonary CTA is a ubiquitous study interpreted by radiologists with different levels of experience in a variety of practice settings. Pulmonary embolism (PE) can range from an incidental and clinically insignificant finding to a clinically significant thrombus that can be managed on an outpatient basis to a potentially fatal condition requiring immediate medical or invasive management. Accordingly, a clear and concise pulmonary CTA report should effectively communicate the most pertinent findings to help the treating medical team diagnose or exclude PE and provide information to guide appropriate management. In this Expert Panel Narrative Review, we discuss the purpose of the radiology report for pulmonary CTA, the optimal report format, and the relevant findings that need to be addressed and their clinical significance.


Asunto(s)
Embolia Pulmonar/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Humanos , Arteria Pulmonar/diagnóstico por imagen
19.
Anesth Analg ; 133(3): 630-647, 2021 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-34086617

RESUMEN

The use of transesophageal echocardiography (TEE) in the operating room and intensive care unit can provide invaluable information on cardiac as well as abdominal organ structures and function. This approach may be particularly useful when the transabdominal ultrasound examination is not possible during intraoperative procedures or for anatomical reasons. This review explores the role of transgastric abdominal ultrasonography (TGAUS) in perioperative medicine. We describe several reported applications using 10 views that can be used in the diagnosis of relevant abdominal conditions associated with organ dysfunction and hemodynamic instability in the operating room and the intensive care unit.


Asunto(s)
Abdomen/diagnóstico por imagen , Anestesia , Cuidados Críticos , Ecocardiografía Transesofágica , Complicaciones Intraoperatorias/diagnóstico por imagen , Atención Perioperativa , Complicaciones Posoperatorias/diagnóstico por imagen , Hemodinámica , Humanos , Unidades de Cuidados Intensivos , Complicaciones Intraoperatorias/etiología , Complicaciones Intraoperatorias/fisiopatología , Quirófanos , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/fisiopatología , Valor Predictivo de las Pruebas
20.
J Med Imaging Radiat Oncol ; 65(7): 841-845, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33779045

RESUMEN

INTRODUCTION: Lower gastrointestinal haemorrhage (LGIH) is a challenging phenomenon in a comorbid, elderly population. CT mesenteric angiography (CTMA) allows localisation of the site of haemorrhage, and provides a target for interventional techniques, but the intermittent nature of LGIH makes it challenging to reliably demonstrate extravasation. This study aimed to identify objective factors that may predict scan outcomes. METHODS: In this retrospective cohort study, all patients undergoing CTMA for LGIH at Monash Health from January 2011 to December 2019 (n = 854) were included. Baseline patient characteristics included age, bowel resection/endoscopic intervention within the past 14 days, known bowel malignancy, anticoagulant/antiplatelet use, duration of symptoms, vital signs, transfusion requirements in the past 24 h and investigation results (recent haemoglobin levels, platelet count, international normalised ratio and creatinine levels). Univariate analysis was performed, and significant factors were entered into a multivariate model. RESULTS: The final multivariate model was statistically significant (P < 0.001) and consisted of bowel resection/endoscopic intervention within the past 14 days (OR = 2.15), use of antiplatelet agents (OR = 2.03), blood transfusion requirement greater than 3 units per 24 h (OR = 1.79), systolic blood pressure less than 100 mmHg (OR = 1.56) and heart rate greater than 100 beats per minute (OR = 1.52). CONCLUSION: The factors identified above are objective, independently associated with positive scan outcomes, readily available to radiologists and are useful for more judicious patient selection.


Asunto(s)
Embolización Terapéutica , Hemorragia Gastrointestinal , Anciano , Angiografía , Angiografía por Tomografía Computarizada , Hemorragia Gastrointestinal/diagnóstico por imagen , Hemorragia Gastrointestinal/terapia , Humanos , Estudios Retrospectivos
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