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Nature Apr 2024The eye, an anatomical extension of the central nervous system (CNS), exhibits many molecular and cellular parallels to the brain. Emerging research demonstrates that...
The eye, an anatomical extension of the central nervous system (CNS), exhibits many molecular and cellular parallels to the brain. Emerging research demonstrates that changes in the brain are often reflected in the eye, particularly in the retina. Still, the possibility of an immunological nexus between the posterior eye and the rest of the CNS tissues remains unexplored. Here, studying immune responses to herpes simplex virus in the brain, we observed that intravitreal immunization protects mice against intracranial viral challenge. This protection extended to bacteria and even tumours, allowing therapeutic immune responses against glioblastoma through intravitreal immunization. We further show that the anterior and posterior compartments of the eye have distinct lymphatic drainage systems, with the latter draining to the deep cervical lymph nodes through lymphatic vasculature in the optic nerve sheath. This posterior lymphatic drainage, like that of meningeal lymphatics, could be modulated by the lymphatic stimulator VEGFC. Conversely, we show that inhibition of lymphatic signalling on the optic nerve could overcome a major limitation in gene therapy by diminishing the immune response to adeno-associated virus and ensuring continued efficacy after multiple doses. These results reveal a shared lymphatic circuit able to mount a unified immune response between the posterior eye and the brain, highlighting an understudied immunological feature of the eye and opening up the potential for new therapeutic strategies in ocular and CNS diseases.
Topics: Animals; Female; Humans; Male; Mice; Rabbits; Bacteria; Brain; Dependovirus; Eye; Glioblastoma; Herpesvirus 2, Human; Intravitreal Injections; Lymphatic System; Lymphatic Vessels; Macaca mulatta; Meninges; Optic Nerve; Swine; Zebrafish; Vascular Endothelial Growth Factor C
PubMed: 38418880
DOI: 10.1038/s41586-024-07130-8 -
Insights Into Imaging Feb 2024To investigate whether T2-weighted imaging (T2WI)-based intratumoral and peritumoral radiomics can predict extranodal extension (ENE) and prognosis in patients with...
OBJECTIVE
To investigate whether T2-weighted imaging (T2WI)-based intratumoral and peritumoral radiomics can predict extranodal extension (ENE) and prognosis in patients with resectable rectal cancer.
METHODS
One hundred sixty-seven patients with resectable rectal cancer including T3T4N + cases were prospectively included. Radiomics features were extracted from intratumoral, peritumoral 3 mm, and peritumoral-mesorectal fat on T2WI images. Least absolute shrinkage and selection operator regression were used for feature selection. A radiomics signature score (Radscore) was built with logistic regression analysis. The area under the receiver operating characteristic curve (AUC) was used to evaluate the performance of each Radscore. A clinical-radiomics nomogram was constructed by the most predictive radiomics signature and clinical risk factors. A prognostic model was constructed by Cox regression analysis to identify 3-year recurrence-free survival (RFS).
RESULTS
Age, cT stage, and lymph node-irregular border and/or adjacent fat invasion were identified as independent clinical risk factors to construct a clinical model. The nomogram incorporating intratumoral and peritumoral 3 mm Radscore and independent clinical risk factors achieved a better AUC than the clinical model in the training (0.799 vs. 0.736) and validation cohorts (0.723 vs. 0.667). Nomogram-based ENE (hazard ratio [HR] = 2.625, 95% CI = 1.233-5.586, p = 0.012) and extramural vascular invasion (EMVI) (HR = 2.523, 95% CI = 1.247-5.106, p = 0.010) were independent risk factors for predicting 3-year RFS. The prognostic model constructed by these two indicators showed good performance for predicting 3-year RFS in the training (AUC = 0.761) and validation cohorts (AUC = 0.710).
CONCLUSION
The nomogram incorporating intratumoral and peritumoral 3 mm Radscore and clinical risk factors could predict preoperative ENE. Combining nomogram-based ENE and MRI-reported EMVI may be useful in predicting 3-year RFS.
CRITICAL RELEVANCE STATEMENT
A clinical-radiomics nomogram could help preoperative predict ENE, and a prognostic model constructed by the nomogram-based ENE and MRI-reported EMVI could predict 3-year RFS in patients with resectable rectal cancer.
KEY POINTS
• Intratumoral and peritumoral 3 mm Radscore showed the most capability for predicting ENE. • Clinical-radiomics nomogram achieved the best predictive performance for predicting ENE. • Combining clinical-radiomics based-ENE and EMVI showed good performance for 3-year RFS.
PubMed: 38411722
DOI: 10.1186/s13244-024-01625-8 -
ACS Omega Feb 2024The process of reconstructing an arterial graft is a complex and dynamic process that is subject to the influence of various mechanical factors, including tissue...
The process of reconstructing an arterial graft is a complex and dynamic process that is subject to the influence of various mechanical factors, including tissue regeneration and blood pressure. The attainment of favorable remodeling outcomes is contingent upon the biocompatibility and biomechanical properties of the arterial graft. A promising strategy involves the emulation of the three-layer structure of the native artery, wherein the inner layer is composed of polycaprolactone (PCL) fibers aligned with blood flow, exhibiting excellent biocompatibility that fosters endothelial cell growth and effectively prevents platelet adhesion. The middle layer, consisting of PCL and polyurethane (PU), offers mechanical support and stability by forming a contractile smooth muscle ring and antiexpansion PU network. The outer layer, composed of PCL fibers with an irregular arrangement, promotes the growth of nerves and pericytes for long-term vascular function. Prioritizing the reconstruction of the inner and outer layers establishes a stable environment for intermediate smooth muscle growth. Our three-layer arterial graft is designed to provide the blood vessel with mechanical support and stability through nondegradable PU, while the incorporation of degradable PCL generates potential spaces for tissue ingrowth, thereby transforming our graft into a living implant.
PubMed: 38405546
DOI: 10.1021/acsomega.3c06628 -
Journal of Cardiothoracic Surgery Feb 2024Calcified right atrial thrombus is rare and commonly occurs secondary to atrial fibrillation and long-term central venous catheterization which present risk for...
BACKGROUND
Calcified right atrial thrombus is rare and commonly occurs secondary to atrial fibrillation and long-term central venous catheterization which present risk for embolization. Treatment typically involves anticoagulation and antiplatelet therapy but rarely surgical excision can be performed, especially in patients with venous obstruction or concomitant valvular dysfunction.
CASE PRESENTATION
We present the case of a 69 year old symptomatic female with a history of atrial fibrillation and long-term venous catheterization found to have a large calcified right atrial thrombus causing inferior vena cava obstruction and severe tricuspid regurgitation. Patient underwent full median sternotomy with ascending arterial cannulation with superior vena cava and femoral venous cannulation. Intraoperatively, extensive right atrial calcified thrombus was found extending into the inferior vena cava and involving the septal portion of the tricuspid valve annulus causing regurgitation. The calcified thrombus was removed which resolved the inferior vena cava obstruction and the tricuspid valve was repaired by transecting septal leaflet chordae, commissuroplasty, and ring annuloplasty. Postoperative course was uncomplicated and pathology confirmed a calcified right atrial thrombus. At 6 month follow up, the patient was asymptomatic with echocardiogram showing no inferior vena cava stenosis and trivial tricuspid regurgitation.
CONCLUSIONS
Surgical excision of calcified right atrial thrombus is rare and is often indicated for symptomatic patients with extensive involvement causing venous inflow obstruction or valvular dysfunction. Sufficient preoperative imaging and a multi-disciplinary approach are essential for accurate diagnosis to guide targeted treatment. When the tricuspid valve is involved, repair is preferred over replacement in this patient population given their propensity for calcification and thrombus formation which may result in an increased risk of early bioprosthetic valve degeneration or mechanical valve thrombosis.
Topics: Humans; Female; Aged; Tricuspid Valve Insufficiency; Tricuspid Valve; Atrial Fibrillation; Vena Cava, Superior; Vena Cava, Inferior; Thrombosis
PubMed: 38374097
DOI: 10.1186/s13019-024-02571-8 -
BMC Ophthalmology Feb 2024To determine the efficacy and safety of intravitreally injected conbercept, a vascular endothelial growth factor receptor fusion protein, for the treatment of idiopathic...
BACKGROUND
To determine the efficacy and safety of intravitreally injected conbercept, a vascular endothelial growth factor receptor fusion protein, for the treatment of idiopathic choroidal neovascularization (ICNV).
METHODS
This retrospective study analyzed outcomes in 40 patients (40 eyes) with ICNV who received intravitreal injections of conbercept 0.5 mg (0.05 ml) and were followed up for at least 12 months. All patients underwent full ophthalmic examinations, including best-corrected vision acuity (BCVA), intraocular pressure (IOP), slit-lamp examination, color fundus photography, optical coherence tomography angiography, multifocal electroretinogram, and fundus fluorescence angiography, if necessary, at baseline and after 1, 3, 6, and 12 months. BCVA, macular central retinal thickness (CRT), IOP, CNV blood flow area, thickness of the CNV-pigment epithelial detachment complex, thickness of the retinal nerve fiber layer (RNFL), and the first positive peak (P1) amplitude density in ring 1 before and after treatment were compared.
RESULTS
Mean baseline BCVA (logMAR), CRT, CNV blood flow area, and CNV-pigment epithelial detachment complex thickness were significantly lower 1, 3, 6, and 12 months after than before conbercept treatment (P < 0.05 each). IOP and baseline RNFL thickness were unaffected by conbercept treatment. P1 amplitude density was significantly higher 1, 3, 6, and 12 months after than before conbercept treatment (P < 0.05 each). None of the 40 eyes showed obvious ocular adverse reactions, such as endophthalmitis, glaucoma, cataract progression, and retinal detachment, and none of the patients experienced systemic adverse events, such as cardiovascular and cerebrovascular accidents.
CONCLUSIONS
Intravitreal injection of conbercept is beneficial to eyes with ICNV, inducing the recovery of macular structure and function and improving BCVA, while not damaging the neuroretina. Intravitreal conbercept is safe and effective for the treatment of ICNV.
Topics: Humans; Intravitreal Injections; Vascular Endothelial Growth Factor A; Retrospective Studies; Choroidal Neovascularization; Retina; Tomography, Optical Coherence; Retinal Detachment; Angiogenesis Inhibitors; Treatment Outcome; Fluorescein Angiography; Recombinant Fusion Proteins
PubMed: 38373901
DOI: 10.1186/s12886-024-03344-6 -
Blood Pressure Monitoring Jun 2024Local vibration can cause microcirculatory abnormalities such as blood stasis and symmetrical intermittent digital artery vasospasm. Finger SBP (FSBP) measurement is a...
OBJECTIVE
Local vibration can cause microcirculatory abnormalities such as blood stasis and symmetrical intermittent digital artery vasospasm. Finger SBP (FSBP) measurement is a potential way of assessing vascular components. This study aims to comprehensively investigate the relationship between the occurrence of the vibration-induced white finger (VWF) and changes in FSBP and then set the application value of FSBP measurements in the early diagnosis of VWF.
METHODS
All samples were judgmental sampling from one factory. Totally 50 patients with VWF were the case group, while 50 without occupational hand-transmitted vibration exposure were the control group. FSBP measurements and epidemiological feature investigations were taken.
RESULTS
There were significant reductions in FSBP level and %FSBP index at both 10 °C and 30 °C in fingers reported VWF ( P < 0.05). The %FSBP abnormal rate of the index, ring and little finger in the VWF group was higher than the control (44.00% vs. 18.00%, 78.00% vs. 26.00%, 64.00% vs. 8.00%). The %FSBP of the ring and little finger had a relatively high application value (area under curve = 0.902, 0.737), while their standard regression coefficients were -0.23 and -0.412. The diagnostic cutoff value of the ring finger was 77.60%, while the sensitivity and specificity were 86.67%.
CONCLUSION
FSBP measurements were proven helpful in monitoring and diagnosing VWF prospectively and proved to have great application value in our study. %FSBP of the ring finger was the appropriate diagnostic index in FSBP measurements, while its abnormal value could be set as 80.00%.
Topics: Humans; Fingers; Male; Female; Cross-Sectional Studies; Adult; China; Vibration; Blood Pressure; Middle Aged; Microcirculation
PubMed: 38349343
DOI: 10.1097/MBP.0000000000000695 -
Diagnostics (Basel, Switzerland) Jan 2024We aimed to evaluate retrospectively associated anomalies and outcome in prenatal aortic arch anomalies (AAAs). We included ninety patients with aberrant right...
Associated Anomalies and Outcome in Patients with Prenatal Diagnosis of Aortic Arch Anomalies as Aberrant Right Subclavian Artery, Right Aortic Arch and Double Aortic Arch.
We aimed to evaluate retrospectively associated anomalies and outcome in prenatal aortic arch anomalies (AAAs). We included ninety patients with aberrant right subclavian artery (ARSA), right aortic arch (RAA) with mirror image branching (RAA-mirror) or aberrant left subclavian artery (RAA-ALSA) and double aortic arch (DAA) between 2011 and 2020. In total, 19/90 (21.1%) had chromosomal anomalies, the highest rate being within the ARSA subgroup (17/46, 37%). All (13/13) of the RAA-mirror subgroup, 10/27 (37.0%) of RAA-ALSA, 13/46 (28.3%) of ARSA and 0/4 within the DAA subgroup had additional intracardiac anomaly. The rate of extracardiac anomalies was 30.7% in RAA-mirror, 28.3% in ARSA, 25.0% in DAA and 22.2% in the RAA-ALSA subgroup. A total of 42/90 (46.7%) had isolated AAAs: three (7.1%) with chromosomal anomalies, all trisomy 21 (3/26, 11.5%) within the ARSA subgroup. Out of 90, 19 (21.1%) were lost to follow-up (FU). Two (2.2%) intrauterine deaths occurred, and six (6.7%) with chromosomal anomalies terminated their pregnancy. In total, 63 (70.0%) were liveborn, 3/63 (4.8%) with severe comorbidity had compassionate care and 3/60 (5.0%) were lost to FU. The survival rate in the intention-to-treat cohort was 53/57 (93%). Forty-one (77.4%) presented with vascular ring/sling, two (4.9%) with RAA-ALSA developed symptoms and one (2.4%) needed an operation. We conclude that intervention due to vascular ring is rarely necessary. NIPT could be useful in isolated ARSA cases without higher a priori risk for trisomy 21 and after exclusion of other anomalies.
PubMed: 38337754
DOI: 10.3390/diagnostics14030238 -
Cells Jan 2024Heart development is a spatiotemporally regulated process that extends from the embryonic phase to postnatal stages. Disruption of this highly orchestrated process can... (Review)
Review
Heart development is a spatiotemporally regulated process that extends from the embryonic phase to postnatal stages. Disruption of this highly orchestrated process can lead to congenital heart disease or predispose the heart to cardiomyopathy or heart failure. Consequently, gaining an in-depth understanding of the molecular mechanisms governing cardiac development holds considerable promise for the development of innovative therapies for various cardiac ailments. While significant progress in uncovering novel transcriptional and epigenetic regulators of heart development has been made, the exploration of post-translational mechanisms that influence this process has lagged. Culling-RING E3 ubiquitin ligases (CRLs), the largest family of ubiquitin ligases, control the ubiquitination and degradation of ~20% of intracellular proteins. Emerging evidence has uncovered the critical roles of CRLs in the regulation of a wide range of cellular, physiological, and pathological processes. In this review, we summarize current findings on the versatile regulation of cardiac morphogenesis and maturation by CRLs and present future perspectives to advance our comprehensive understanding of how CRLs govern cardiac developmental processes.
Topics: Ubiquitin; Cullin Proteins; Ubiquitination; Ubiquitin-Protein Ligases
PubMed: 38334627
DOI: 10.3390/cells13030235 -
Acta Cirurgica Brasileira 2024The current study aimed at evaluating the repair of a partial defect of the trachea with a muscle flap, an advanced technique that employs combined suture patterns.
PURPOSE
The current study aimed at evaluating the repair of a partial defect of the trachea with a muscle flap, an advanced technique that employs combined suture patterns.
METHODS
Sixteen healthy male New Zealand white rabbits were used as an experimental model. A partial defect in the trachea within the ventral region of the fourth to eighth tracheal ring was created. Subsequently, repair was initiated with a flap of the sternocephalicus muscle. The animals were divided into four groups for postoperative evaluation using clinical, tracheoscopic, and histopathological analyses. Each group was separated according to the time of euthanasia, programmed at interval of seven (G7), 15 (G15), 30 (G30), and 60 days (G60).
RESULTS
One animal from the G60 group died, whereas the other animals had good surgical recovery without serious changes in the breathing pattern. The major clinical signs observed were stridor and coughing. Tracheoscopy revealed secretions in the tracheal lumen, exuberant granulation, and stenosis. Histopathological analysis showed growth of the ciliary respiratory epithelium at the flap site 30 days after implantation.
CONCLUSIONS
Partial repair showed satisfactory results owing to the anatomical location of the muscle, adequate vascular support, and structural and physiological maintenance without serious changes in the respiratory system.
Topics: Rabbits; Male; Animals; Trachea; Plastic Surgery Procedures; Surgical Flaps; Muscles
PubMed: 38324799
DOI: 10.1590/acb390324