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Small (Weinheim An Der Bergstrasse,... Jul 2024Abdominal aortic aneurysm (AAA) represents a critical cardiovascular condition characterized by localized dilation of the abdominal aorta, carrying a significant risk of...
Abdominal aortic aneurysm (AAA) represents a critical cardiovascular condition characterized by localized dilation of the abdominal aorta, carrying a significant risk of rupture and mortality. Current treatment options are limited, necessitating novel therapeutic approaches. This study investigates the potential of a pioneering nanodrug delivery system, RAP@PFB, in mitigating AAA progression. RAP@PFB integrates pentagalloyl glucose (PGG) and rapamycin (RAP) within a metal-organic-framework (MOF) structure through a facile assembly process, ensuring remarkable drug loading capacity and colloidal stability. The synergistic effects of PGG, a polyphenolic antioxidant, and RAP, an mTOR inhibitor, collectively regulate key players in AAA pathogenesis, such as macrophages and smooth muscle cells (SMCs). In macrophages, RAP@PFB efficiently scavenges various free radicals, suppresses inflammation, and promotes M1-to-M2 phenotype repolarization. In SMCs, it inhibits apoptosis and calcification, thereby stabilizing the extracellular matrix and reducing the risk of AAA rupture. Administered intravenously, RAP@PFB exhibits effective accumulation at the AAA site, demonstrating robust efficacy in reducing AAA progression through multiple mechanisms. Moreover, RAP@PFB demonstrates favorable biosafety profiles, supporting its potential translation into clinical applications for AAA therapy.
PubMed: 38953313
DOI: 10.1002/smll.202402141 -
The Journal of Obstetrics and... Jul 2024A 35-year-old woman (gravida 1, para 0) was admitted to our hospital at 28 weeks' gestation with vaginal bleeding from placenta previa. Severe fetal bradycardia was...
A 35-year-old woman (gravida 1, para 0) was admitted to our hospital at 28 weeks' gestation with vaginal bleeding from placenta previa. Severe fetal bradycardia was observed during fetal heart rate monitoring. Ultrasonography showed widely dilated veins on the fetal surface of the placenta and an extraordinarily low umbilical artery peak systolic velocity in the Doppler study. Umbilical cord torsion was suspected. On the subsequent day, we performed a cesarean section due to worsening fetal heart rate patterns. Umbilical artery blood gas analysis indicated severe acidemia (pH 7.063), and umbilical cord torsion was confirmed at the placental cord insertion site. Diagnosing UCT prenatally is challenging; however, it can be suspected by scanning for the widely dilated veins on the fetal placental surface, termed as the "Sunset Sign," an abnormally low umbilical artery peak systolic velocity, and other fetal Doppler abnormalities.
PubMed: 38953213
DOI: 10.1111/jog.16013 -
Pediatric Blood & Cancer Jul 2024Sickle cell disease (SCD)-related neurological effects are particularly devastating. Dilated perivascular spaces (dPVS) are a well-described component of cerebral small...
Sickle cell disease (SCD)-related neurological effects are particularly devastating. Dilated perivascular spaces (dPVS) are a well-described component of cerebral small vessel disease in older adults without SCD. However, the burden and association of dPVS with neurological complications in children with SCD have not been described. In this study, we used the international consensus criteria to quantify dPVS in the centrum semiovale and basal ganglia in T2-weighted magnetic resonance images (MRI) of children with SCD who were randomized as part of the Silent Cerebral Infarct Transfusion (SIT) trial. We examined the relationship between global and/or regional dPVS burden and presence or area of silent cerebral infarctions, hematological measures, demographic variables, and full-scale intelligence quotient (FSIQ) scores. The study included 156 SIT trial participants who had pre-randomization and study exit MRI. Their median age was 9.6 (5-15) years, 39% were female, and 94 (60%) participants had a high dPVS burden. Participants randomized to the blood transfusion arm and who had a high dPVS burden at baseline had a moderate decline in dPVS score over 36 months compared to no change in the observation group. On multivariable logistic regression, intelligence quotient was not associated with dPVS burden. Children with SCD included in the SIT trial have a high burden of dPVS compared to children without SCD. However, dPVS do not appear to have the same pathophysiology of silent cerebral infarcts. Further study is needed to determine both their etiology and clinical relevance.
PubMed: 38953143
DOI: 10.1002/pbc.31150 -
Cureus May 2024We present five cases of common variable immunodeficiency (CVID), comprising three women and two men with a mean age of 23.8 ± 9.2 years. All our patients suffered from...
We present five cases of common variable immunodeficiency (CVID), comprising three women and two men with a mean age of 23.8 ± 9.2 years. All our patients suffered from recurrent bronchopneumonitis, with complications of purulent pleurisy in two cases, requiring decortication in one case, and resulting in bronchiectasis in three cases. Digestive tract infections were observed in four patients, while two patients presented with ENT infections. One case was complicated by bacterial meningitis. All patients presented with global hypogammaglobulinemia, with CVID and granulomatous manifestation in one case. Treatment consisted of monthly immunoglobulin infusions.
PubMed: 38953064
DOI: 10.7759/cureus.61397 -
Iranian Journal of Medical Sciences Jun 2024Despite its rarity, pulmonary capillary hemangiomatosis (PCH) presents a significant diagnostic challenge. Due to its similarity to other pulmonary vascular diseases,...
Despite its rarity, pulmonary capillary hemangiomatosis (PCH) presents a significant diagnostic challenge. Due to its similarity to other pulmonary vascular diseases, such as pulmonary veno-occlusive disease, it is characterized by abnormal pulmonary capillary proliferation, which is a rare cause of primary pulmonary hypertension. This case was the first reported instance of PCH in Shahid Rajaee Heart Hospital in Tehran, Iran, in 2023, which was confirmed by genetic testing. It highlighted the importance of considering PCH among the differential diagnoses for pulmonary hypertension, even in adolescent patients. The 13-year-old patient's main complaints were progressive exertional dyspnea and chest pain. He had no previous medical history and had not taken any pharmaceutical or herbal medications. Critical clinical findings included a heart murmur, an electrocardiogram revealing right ventricular hypertrophy, and echocardiogram evidence of pulmonary hypertension. The main diagnosis was PCH, as shown by CT findings of pulmonary artery dilatation and diffuse nodular ground glass opacities. Genetic tests indicated pathogenic EIF2AK4 mutations and suspicion of PCH. Therapeutic intervention included vasodilator therapy, which exacerbated the patient's condition. This case emphasized the importance of maintaining a high index of suspicion for rare causes of pulmonary hypertension, such as PCH. The outcome was to prepare the patient for lung transplantation. To differentiate PCH from other pulmonary vascular diseases, a combination of clinical presentation, radiologic studies, genetic analysis, and response to treatment is required to determine appropriate management, particularly lung transplantation.
Topics: Humans; Adolescent; Male; Hemangioma, Capillary; Hypertension, Pulmonary; Lung Neoplasms; Protein Serine-Threonine Kinases
PubMed: 38952636
DOI: 10.30476/ijms.2024.101215.3385 -
Respiration; International Review of... Jun 2024Subglottic stenosis, manifested by granulation tissue hyperplasia, is challenging and requires multiple repeated treatments and stent maintenance at times....
INTRODUCTION
Subglottic stenosis, manifested by granulation tissue hyperplasia, is challenging and requires multiple repeated treatments and stent maintenance at times. Corticosteroids prevent severe subglottic stenosis development owing to their antifibrotic and antiinflammatory properties. Submucosal injection of glucocorticoids or mitomycin, a useful adjuvant therapeutic method, improves the mean interval between endoscopic procedures and reduces airway restenosis risks.
CASE PRESENTATION
We report a rare case of a man with complex subglottic stenosis who underwent balloon dilatation combined with cryotherapy, stent placement, and adjuvant submucosal triamcinolone injection. The drug was injected efficiently and safely into the submucosal layer under percutaneous ultrasound guidance, and subglottic stenosis was well-controlled at a low cost.
CONCLUSION
POCUS-guided medication injections may be a useful adjuvant medical therapy for subglottic stenosis.
PubMed: 38952129
DOI: 10.1159/000539974 -
Eye (London, England) Jun 2024This study aimed to investigate the change of choroidal venous overload in Vogt‒Koyanagi‒Harada (VKH) disease. Clinical records of 52 patients with VKH disease (52...
BACKGROUND/OBJECTIVES
This study aimed to investigate the change of choroidal venous overload in Vogt‒Koyanagi‒Harada (VKH) disease. Clinical records of 52 patients with VKH disease (52 eyes) and 24 control subjects (24 eyes) who underwent multimodal imaging, including fluorescein angiography (FA) and indocyanine green angiography (ICGA), were retrospectively reviewed.
SUBJECTS/METHODS
Imaging data were assessed for signs associated with choroidal venous overload, e.g., choroidal perfusion delay, choroidal vascular hyperpermeability, dilated choroidal veins, and intervortex venous anastomosis (IVA). Dual FA and ICGA scoring for active posterior segment inflammation was performed. Clinical and imaging features associated with choroidal venous overload were compared between early- and late-stage VKH disease.
RESULTS
Choroidal perfusion delay, choroidal vascular hyperpermeability, dilated choroidal veins, and IVA were more prevalent in eyes with VKH disease (69.2%, 67.3%, 61.5%, and 65.4%, respectively) than in control eyes (25.0%, 20.8%, 25.0%, and 37.5%, respectively) (p < 0.05). All eyes with IVA in the early-stage of VKH disease had got other 3 signs. All choroidal venous overload signs were more prevalent in patients with early-stage (20 eyes) than in those with late-stage VKH disease (32 eyes) (p < 0.05). The number of choroidal venous overload signs were inversely related to disease duration (p < 0.001) and proportionally related to the total ICGA score (p < 0.001). IVA was significantly associated with the total ICGA score in logistic regression (p = 0.014).
CONCLUSIONS
Choroidal venous overload occurs early in VKH disease. Angiographic signs of choroidal venous overload may be useful markers to assess the status of VKH disease.
PubMed: 38951674
DOI: 10.1038/s41433-024-03198-8 -
Nature Methods Jul 2024Glycans constitute the most complicated post-translational modification, modulating protein activity in health and disease. However, structural annotation from tandem...
Glycans constitute the most complicated post-translational modification, modulating protein activity in health and disease. However, structural annotation from tandem mass spectrometry (MS/MS) data is a bottleneck in glycomics, preventing high-throughput endeavors and relegating glycomics to a few experts. Trained on a newly curated set of 500,000 annotated MS/MS spectra, here we present CandyCrunch, a dilated residual neural network predicting glycan structure from raw liquid chromatography-MS/MS data in seconds (top-1 accuracy: 90.3%). We developed an open-access Python-based workflow of raw data conversion and prediction, followed by automated curation and fragment annotation, with predictions recapitulating and extending expert annotation. We demonstrate that this can be used for de novo annotation, diagnostic fragment identification and high-throughput glycomics. For maximum impact, this entire pipeline is tightly interlaced with our glycowork platform and can be easily tested at https://colab.research.google.com/github/BojarLab/CandyCrunch/blob/main/CandyCrunch.ipynb . We envision CandyCrunch to democratize structural glycomics and the elucidation of biological roles of glycans.
PubMed: 38951670
DOI: 10.1038/s41592-024-02314-6 -
Nature Communications Jul 2024ANKRD11 (Ankyrin Repeat Domain 11) is a chromatin regulator and a causative gene for KBG syndrome, a rare developmental disorder characterized by multiple organ...
ANKRD11 (Ankyrin Repeat Domain 11) is a chromatin regulator and a causative gene for KBG syndrome, a rare developmental disorder characterized by multiple organ abnormalities, including cardiac defects. However, the role of ANKRD11 in heart development is unknown. The neural crest plays a leading role in embryonic heart development, and its dysfunction is implicated in congenital heart defects. We demonstrate that conditional knockout of Ankrd11 in the murine embryonic neural crest results in persistent truncus arteriosus, ventricular dilation, and impaired ventricular contractility. We further show these defects occur due to aberrant cardiac neural crest cell organization leading to outflow tract septation failure. Lastly, knockout of Ankrd11 in the neural crest leads to impaired expression of various transcription factors, chromatin remodelers and signaling pathways, including mTOR, BMP and TGF-β in the cardiac neural crest cells. In this work, we identify Ankrd11 as a regulator of neural crest-mediated heart development and function.
Topics: Animals; Neural Crest; Mice, Knockout; Mice; Heart; Repressor Proteins; Heart Defects, Congenital; Gene Expression Regulation, Developmental; Chromatin; Signal Transduction; Myocardium; Female
PubMed: 38951500
DOI: 10.1038/s41467-024-48955-1 -
Abdominal Radiology (New York) Jul 2024Peribiliary cysts (PC) are dilatations of the extramural peribiliary glands, with a very characteristic imaging pattern in the contexts of hepatobiliary diseases,... (Review)
Review
Peribiliary cysts (PC) are dilatations of the extramural peribiliary glands, with a very characteristic imaging pattern in the contexts of hepatobiliary diseases, idiopathic portal hypertension, adult-type polycystic disease of the liver and kidneys, solitary nonparasitic cysts, and systemic infections. The clinical relevance of PC is related to the fact that their presence may indicate underlying pathologies (such as those mentioned above) and may be considered as a potential marker of liver disease progression. Although imaging findings are quite characteristic, recognizing their main differential diagnoses, including malignancies, can be challenging but are essential to avoiding diagnostic errors.
PubMed: 38951232
DOI: 10.1007/s00261-024-04472-9