Pretransplant, Th17 dominant alloreactivity in highly sensitized kidney transplant candidates.

Introduction: Sensitization to donor human leukocyte antigen (HLA) molecules prior to transplantation is a significant risk factor for delayed access to transplantation and to long-term outcomes. Memory T cells and their cytokines play a pivotal role in shaping immune responses, thereby increasing the risk of allograft rejection among highly sensitized patients. This study aims to elucidate the precise contribution of different CD4 memory T cell subsets to alloreactivity in highly sensitized (HS) kidney transplant recipients.

Incidental findings on brain magnetic resonance imaging (MRI) in adults: a review of imaging spectrum, clinical significance, and management.

Utilization of brain MRI has dramatically increased in recent decades due to rapid advancement in imaging technology and improving accessibility. As a result, radiologists increasingly encounter findings incidentally discovered on brain MRIs which are performed for unrelated indications. Some of these findings are clinically significant, necessitating further investigation or treatment and resulting in increased costs to healthcare systems as well as increased patient anxiety.

Idiopathic intracranial hypertension imaging approaches and the implications in patient management.

Idiopathic intracranial hypertension (IIH) represents a clinical disease entity without a clear etiology, that if left untreated, can result in severe outcomes, including permanent vision loss. For this reason, early diagnosis and treatment is necessary. Historically, the role of cross-sectional imaging has been to rule out secondary or emergent causes of increased intracranial pressure, including tumor, infection, hydrocephalus, or venous thrombosis.

Incidental vascular findings on brain magnetic resonance angiography.

Given the ever-increasing utilization of magnetic resonance angiography, incidental vascular findings are increasingly discovered on exams performed for unconnected indications. Some incidental lesions represent pathology and require further intervention and surveillance, such as aneurysm, certain vascular malformations, and arterial stenoses or occlusions. Others are benign or represent normal anatomic variation, and may warrant description, but not further work-up.

Extracellular Vesicles From Kidney Allografts Express miR-218-5p and Alter Th17/Treg Ratios.

Delayed graft function (DGF) in kidney transplantation is associated with ischemic injury and carries long term functional and immunological risks. Extracellular vesicles (EV) released from allografts may signal a degree of ischemic stress, and are thought to play an important role in the development of anti-donor immunity. Here, we show that kidney perfusate-derived extracellular vesicles (KP-EV) express donor-specific human leukocyte antigen.

COVID-19: Extensive epithelial damage and ciliary dyskinesia in hospitalised patients.

Infection with SARS-CoV-2 can cause severe respiratory disease and it is predicted that the COVID-19 pandemic will leave a substantial number of patients with long-term respiratory complications (1).

Amniotic stromal stem cell-loaded hydrogel repairs cardiac tissue in infarcted rat hearts via paracrine mediators.

The use of stem cells to repair the heart after a myocardial infarction (MI) remains promising, yet clinical trials over the past 20 years suggest that cells fail to integrate into the native tissue, resulting in limited improvements in cardiac function. Here, we demonstrate the cardioprotective potential of a composite inserting human amniotic stromal mesenchymal stem cells (ASMCs) in a chitosan and hyaluronic acid (C/HA) based hydrogel in a rat MI model. Mechanical characterization of the C/HA platform indicated a swift elastic conversion at 40°C and a rapid sol-gel transition time at 37°C.

Dysfunctional Bronchial Cilia Are a Feature of Chronic Obstructive Pulmonary Disease (COPD).

Impaired mucociliary clearance may increase COPD exacerbation risk. We aimed to compare bronchial ciliary function and epithelial ultrastructure of COPD patients to healthy controls and explore its relationship to exacerbator phenotypes (frequent [FE] and infrequent [IFE] exacerbator). In this cross-sectional study, 16 COPD patients and 12 controls underwent bronchial brushings.

Higher throughput drug screening for rare respiratory diseases: readthrough therapy in primary ciliary dyskinesia.

Background: Development of therapeutic approaches for rare respiratory diseases is hampered by the lack of systems that allow medium-to-high-throughput screening of fully differentiated respiratory epithelium from affected patients. This is a particular problem for primary ciliary dyskinesia (PCD), a rare genetic disease caused by mutations in genes that adversely affect ciliary movement and consequently mucociliary transport. Primary cell culture of basal epithelial cells from nasal brush biopsies followed by ciliated differentiation at the air-liquid interface (ALI) has proven to be a useful tool in PCD diagnostics but the technique's broader utility, including in pre-clinical PCD research, has been restricted by the limited number of basal cells that can be expanded from such biopsies.

Hydrocephalus and diffuse choroid plexus hyperplasia in primary ciliary dyskinesia-related MCIDAS mutation.

Objective: To report a neuroradiologic phenotype associated with reduced generation of multiple motile cilia (RGMC) and mutations in the gene. We hypothesize that the observed phenotype may reflect the emerging role that ependymal cilia play in regulating CSF production.

Method: Clinical and radiologic records were retrospectively reviewed for 7 consecutive patients diagnosed by the Leicester UK national primary ciliary dyskinesia (PCD) diagnostic laboratory.

Clinical utility of NGS diagnosis and disease stratification in a multiethnic primary ciliary dyskinesia cohort.

Background: Primary ciliary dyskinesia (PCD), a genetically heterogeneous condition enriched in some consanguineous populations, results from recessive mutations affecting cilia biogenesis and motility. Currently, diagnosis requires multiple expert tests.

Methods: The diagnostic utility of multigene panel next-generation sequencing (NGS) was evaluated in 161 unrelated families from multiple population ancestries.

Extracellular Vesicles in Type 1 Diabetes: Messengers and Regulators.

Purpose Of Review: Theories about the pathogenesis of type 1 diabetes (T1D) refer to the potential of primary islet inflammatory signaling as a trigger for the loss of self-tolerance leading to disease onset. Emerging evidence suggests that extracellular vesicles (EV) may represent the missing link between inflammation and autoimmunity. Here, we review the evidence for a role of EV in the pathogenesis of T1D, as well as discuss their potential value in the clinical sphere, as biomarkers and therapeutic agents.

Biallelic Mutations in LRRC56, Encoding a Protein Associated with Intraflagellar Transport, Cause Mucociliary Clearance and Laterality Defects.

Primary defects in motile cilia result in dysfunction of the apparatus responsible for generating fluid flows. Defects in these mechanisms underlie disorders characterized by poor mucus clearance, resulting in susceptibility to chronic recurrent respiratory infections, often associated with infertility; laterality defects occur in about 50% of such individuals. Here we report biallelic variants in LRRC56 (known as oda8 in Chlamydomonas) identified in three unrelated families.

Immune Response to Extracellular Vesicles From Human Islets of Langerhans in Patients With Type 1 Diabetes.

The autoimmune response that characterizes type 1 diabetes (T1D) has no clear cause. Extracellular vesicles (EVs) play an important role in triggering the immune response in other contexts. Here, we propose a model by which EVs isolated from human islets stimulate proinflammatory immune responses and lead to peripheral blood mononuclear cell (PBMC) activation.

Risk factors for situs defects and congenital heart disease in primary ciliary dyskinesia.

Primary ciliary dyskinesia (PCD) is associated with abnormal organ positioning (situs) and congenital heart disease (CHD). This study investigated genotype-phenotype associations in PCD to facilitate risk predictions for cardiac and laterality defects. This retrospective cohort study of 389 UK patients with PCD found 51% had abnormal situs and 25% had CHD and/or laterality defects other than situs inversus totalis.

Ciliated conical epithelial cell protrusions point towards a diagnosis of primary ciliary dyskinesia.

Background: Primary ciliary dyskinesia can result from a number of different ciliary defects that adversely affect ciliary function resulting markedly reduced or absent mucociliary clearance. Improvement in diagnostic testing is an area of current research. During diagnostic evaluation of PCD we observed ciliated conical protrusions from part of the apical surface of ciliated cells in those diagnosed with PCD.

Imaging and Management of Blunt Cerebrovascular Injury.

Blunt cerebrovascular injury (BCVI) is a relatively rare but potentially devastating finding in patients with high-energy blunt force trauma or direct cervical and/or craniofacial injury. The radiologist plays an essential role in identifying and grading the various types of vascular injury, including minimal intimal injury, dissection with raised intimal flap or intraluminal thrombus, intramural hematoma, pseudoaneurysm, occlusion, transection, and arteriovenous fistula. Early identification of BCVI is important, as treatment with antithrombotic therapy has been shown to reduce the incidence of postinjury ischemic stroke.

Diffusion Tensor Imaging of the Spinal Cord: Clinical Value, Investigational Applications, and Technical Limitations.

Although diffusion-weighted imaging (DWI) has become a mainstay in modern brain imaging, it remains less utilized in the evaluation of the spinal cord. Many studies have shown promise in using DWI and diffusion-tensor imaging (DTI) for evaluation of the spinal cord; however, application has been stalled by technical obstacles and artifacts, and questions remain regarding its clinical utility on an individual examination level. This review discusses the background, concepts, and technical aspects of DWI and DTI, specifically for imaging of the spinal cord.

Test-Retest and Interreader Reproducibility of Semiautomated Atlas-Based Analysis of Diffusion Tensor Imaging Data in Acute Cervical Spine Trauma in Adult Patients.

Background And Purpose: DTI is a tool for microstructural spinal cord injury evaluation. This study evaluated the reproducibility of a semiautomated segmentation algorithm of spinal cord DTI.

Materials And Methods: Forty-two consecutive patients undergoing acute trauma cervical spine MR imaging underwent 2 axial DTI scans in addition to their clinical scan.

High prevalence of p.His154Pro mutation causing primary ciliary dyskinesia disrupts protein oligomerisation and is associated with normal diagnostic investigations.

Rationale: Primary ciliary dyskinesia is a genetically heterogeneous inherited condition characterised by progressive lung disease arising from abnormal cilia function. Approximately half of patients have situs inversus. The estimated prevalence of primary ciliary dyskinesia in the UK South Asian population is 1:2265.

T2*-Weighted and Diffusion Magnetic Resonance Imaging Differentiation of Cerebral Fat Embolism From Diffuse Axonal Injury.

Objective: This study differentiates cerebral fat embolism (CFE) and diffuse axonal injury (DAI) on diffusion-weighted magnetic resonance imaging (DWI) and T2*-weighted magnetic resonance imaging.

Methods: Consecutive CFE and DAI cases were retrospectively selected. Hemorrhages were characterized by number, size/shape, and distribution, whereas DWI lesions by pattern.

Presence of diabetes autoantigens in extracellular vesicles derived from human islets.

Beta-cell (β-cell) injury is the hallmark of autoimmune diabetes. However, the mechanisms by which autoreactive responses are generated in susceptible individuals are not well understood. Extracellular vesicles (EV) are produced by mammalian cells under normal and stressed physiological states.

A missense mutation in Katnal1 underlies behavioural, neurological and ciliary anomalies.

Microtubule severing enzymes implement a diverse range of tissue-specific molecular functions throughout development and into adulthood. Although microtubule severing is fundamental to many dynamic neural processes, little is known regarding the role of the family member Katanin p60 subunit A-like 1, KATNAL1, in central nervous system (CNS) function. Recent studies reporting that microdeletions incorporating the KATNAL1 locus in humans result in intellectual disability and microcephaly suggest that KATNAL1 may play a prominent role in the CNS; however, such associations lack the functional data required to highlight potential mechanisms which link the gene to disease symptoms.

High-resolution intracranial vessel wall imaging: imaging beyond the lumen.

Accurate and timely diagnosis of intracranial vasculopathies is important due to significant risk of morbidity with delayed and/or incorrect diagnosis both from the disease process as well as inappropriate therapies. Conventional vascular imaging techniques for analysis of intracranial vascular disease provide limited information since they only identify changes to the vessel lumen. New advanced MR intracranial vessel wall imaging (IVW) techniques can allow direct characterisation of the vessel wall.

A computed tomography radiogenomic biomarker predicts microvascular invasion and clinical outcomes in hepatocellular carcinoma.

Unlabelled: Microvascular invasion (MVI) in hepatocellular carcinoma (HCC) is an independent predictor of poor outcomes subsequent to surgical resection or liver transplantation (LT); however, MVI currently cannot be adequately determined preoperatively. Radiogenomic venous invasion (RVI) is a contrast-enhanced computed tomography (CECT) biomarker of MVI derived from a 91-gene HCC "venous invasion" gene expression signature. Preoperative CECTs of 157 HCC patients who underwent surgical resection (N = 72) or LT (N = 85) between 2000 and 2009 at three institutions were evaluated for the presence or absence of RVI.