Ultrastructural investigation of the posterior hyaloid membrane in posterior vitreous detachment.

Background: Separation of the posterior hyaloid membrane (PHM) from the retina in posterior vitreous detachment (PVD) is a fundamental, but poorly understood, process underlying vitreoretinal disorders including retinal detachment and macular hole. We performed electron microscopy studies of the PHM after PVD to investigate its ultrastructure, associated cellular structures and relationship to the internal limiting membrane (ILM).

Methods: Post-mortem human eyes were collected from recently deceased patients over 70 years of age.

Retinal detachment in Type IX collagen recessive Stickler syndrome.

Objective: Stickler Syndrome (SS) is associated with eye, joint and orofacial abnormalities. Most cases are dominantly inherited through COL2A1/COL11A1 variants encoding type-II/XI collagen, with patients having up to 78% retinal detachment (RD) risk. Rarer cases of recessive SS have also been identified, associated with pathogenic variants of genes including COL9A1, COL9A2 & COL9A3 encoding type-IX collagen, but there is limited published data on patients' phenotype or RD risk.

Pathobiology of the crystalline lens in Stickler syndrome.

Purpose: The Stickler syndromes are a group of connective tissue disorders characterised by congenital myopia, giant retinal tear and retinal detachment, cleft palate, hearing loss and premature arthropathy. Patients with Stickler syndrome are also susceptible to abnormalities of the crystalline lens. Since neither type II or type XI collagen (those typically affected in the vast majority of Stickler patients) are highly expressed in the lens, this observational cohort study explores potential alternative mechanisms to explain why patients frequently exhibit such unusual but characteristic types of cataract.

High-quality lipid suppression and B0 shimming for human brain H MRSI.

Magnetic Resonance Spectroscopic Imaging (MRSI) is a powerful technique that can map the metabolic profile in the brain non-invasively. Extracranial lipid contamination and insufficient B homogeneity however hampers robustness, and as a result has hindered widespread use of MRSI in clinical and research settings. Over the last six years we have developed highly effective extracranial lipid suppression methods with a second order gradient insert (ECLIPSE) utilizing inner volume selection (IVS) and outer volume suppression (OVS) methods.

Peripapillary Hyperreflective Ovoid Mass-Like Structures in Stickler Syndrome.

Purpose: To report a previously undescribed finding of peripapillary hyperreflective ovoid mass-like structures (PHOMS) in Stickler syndrome.

Design: Noncomparative case series.

Subjects: Twenty-two eyes with anomalous optic disc from 11 Stickler syndrome patients were identified and imaged.

Parallel detection of multi-contrast MRI and Deuterium Metabolic Imaging (DMI) for time-efficient characterization of neurological diseases.

Deuterium Metabolic Imaging (DMI) is a novel method that can complement traditional anatomical magnetic resonance imaging (MRI) of the brain. DMI relies on the MR detection of metabolites that become labeled with deuterium (H) after administration of a deuterated substrate and can provide images with highly specific metabolic information. However, clinical adoption of DMI is complicated by its relatively long scan time.

Posterior vitreous detachment and retinal tear - a prospective study of community referrals.

Background: Retinal tears (RT) from posterior vitreous detachment (PVD) are an important and treatable cause of rhegmatogenous retinal detachment (RRD). Better understanding of the risk of RT from PVD will help plan urgent eye care.

Methods: Prospective observational case series over two years.

Repression of TRIM13 by chromatin assembly factor CHAF1B is critical for AML development.

Acute myeloid leukemia (AML) is an aggressive blood cancer that stems from the rapid expansion of immature leukemic blasts in the bone marrow. Mutations in epigenetic factors represent the largest category of genetic drivers of AML. The chromatin assembly factor CHAF1B is a master epigenetic regulator of transcription associated with self-renewal and the undifferentiated state of AML blasts.

Design and realization of a multi-coil array for B field control in a compact 1.5T head-only MRI scanner.

Purpose: To design and implement a multi-coil (MC) array for B field generation for image encoding and simultaneous advanced shimming in a novel 1.5T head-only MRI scanner.

Methods: A 31-channel MC array was designed following the unique constraints of this scanner design: The vertically oriented magnet is very short, stopping shortly above the shoulders of a sitting subject, and includes a window for the subject to see through.

Use of vitreous phenotype as a key clinical marker to identify Ocular-only Stickler syndrome in a family with Marfan syndrome.

This clinical report describes a family with both Marfan and ocular-only Stickler syndromes. We report 2 cases of ocular-only Stickler syndrome and 2 cases of Marfan syndrome concurrent with ocular-only Stickler syndrome. Type 1 Stickler syndrome and Marfan syndrome share many clinical similarities, and it can be difficult to differentiate them solely based on clinical presentation.

Legg-Calve-Perthes' disease: an opportunity to prevent blindness?

Legg-Calve-Perthes' disease (LCP) is defined as avascular necrosis of the femoral head in a child and may present to a variety of disciplines from general practice to orthopaedics, paediatrics, rheumatology and more. The Stickler syndromes are a group of disorders of type II, IX and XI collagen associated with hip dysplasia, retinal detachment, deafness and cleft palate. The pathogenesis of LCP disease remains an enigma but there have been a small number of cases reporting variants in the gene encoding the α1 chain of type II collagen (COL2A1).

A Human-Centered Design Approach to SOVTE Straw Phonation Instruction.

Objectives: Extensive research has demonstrated that straw/tube phonation exercises produce positive effects on the voice quality of the user. The purpose of this study was to explore pedagogical practices employed by a range of voice professionals when using SOVTEs by applying human-centered design approaches to examine workflow and communication between teachers and students.

Method/design: The researchers conducted a series of five participatory role-playing workshop activities at a multi-disciplinary vocology conference that included speech-language pathologists, voice scientists, physicians, singing teachers, acting voice teachers, choral directors, and singers.

Retinal detachment in Loeys-Dietz syndrome.

Loeys-Dietz syndrome (LDS) is an autosomal-dominant connective-tissue disorder with vascular and musculoskeletal abnormalities similar to Marfan syndrome. However, unlike Marfan, retinal detachment (RD) is rarely reported, and screening protocols do not currently feature ophthalmic assessment or RD counseling. We report a 5-generation family affected by LDS, where RD occurred in six eyes of four individuals.

SARS-CoV-2 Serosurveys: How Antigen, Isotype and Threshold Choices Affect the Outcome.

Background: Evaluating the performance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serological assays and clearly articulating the utility of selected antigens, isotypes, and thresholds is crucial to understanding the prevalence of infection within selected communities.

Methods: This cross-sectional study, implemented in 2020, screened PCRconfirmed coronavirus disease 2019 patients (n 86), banked prepandemic and negative samples (n 96), healthcare workers and family members (n 552), and university employees (n 327) for antiSARS-CoV-2 receptor-binding domain, trimeric spike protein, and nucleocapsid protein immunoglobulin (Ig)G and IgA antibodies with a laboratory-developed enzyme-linked immunosorbent assay and tested how antigen, isotype and threshold choices affected the seroprevalence outcomes. The following threshold methods were evaluated: (i) mean 3 standard deviations of the negative controls; (ii) 100 specificity for each antigen-isotype combination; and (iii) the maximal Youden index.

Autosomal Recessive Stickler Syndrome.

Stickler syndrome (SS) is a genetic disorder with manifestations in the eye, ear, joints, face and palate. Usually inherited in a dominant fashion due to heterozygous pathogenic variants in the collagen genes and , it can rarely be inherited in a recessive fashion from variants in , , and , , as well as the non-collagen genes , and . We review the published cases of recessive SS, which comprise 40 patients from 23 families.

Short symmetric and highly selective asymmetric first and second order gradient modulated offset independent adiabaticity (GOIA) pulses for applications in clinical MRS and MRSI.

Gradient modulated RF pulses, especially gradient offset independent adiabaticity (GOIA) pulses, are increasingly gaining attention for high field clinical magnetic resonance spectroscopy and spectroscopic imaging (MRS/MRSI) due to the lower peak B amplitude and associated power demands achievable relative to its non-modulated adiabatic full passage counterparts. In this work we describe the development of two GOIA RF pulses: 1) A power efficient, 3.0 ms wideband uniform rate with smooth truncation (WURST) modulated RF pulse with 15 kHz bandwidth compatible with a clinically feasible peak B amplitude of 0.

Interleaved fluid-attenuated inversion recovery (FLAIR) MRI and deuterium metabolic imaging (DMI) on human brain in vivo.

Purpose: To integrate deuterium metabolic imaging (DMI) with clinical MRI through an interleaved MRI and DMI acquisition workflow. Interleaved MRI-DMI was enabled with hardware and pulse sequence modifications, and the performance was demonstrated using fluid-attenuated inversion recovery (FLAIR) MRI as an example.

Methods: Interleaved FLAIR-DMI was developed by interleaving the H excitation and acquisition time windows into the intrinsic delay periods presented in the FLAIR method.

Modulating immune responses to AAV by expanded polyclonal T-regs and capsid specific chimeric antigen receptor T-regulatory cells.

Immune responses to adeno-associated virus (AAV) capsids limit the therapeutic potential of AAV gene therapy. Herein, we model clinical immune responses by generating AAV capsid-specific chimeric antigen receptor (AAV-CAR) T cells. We then modulate immune responses to AAV capsid with AAV-CAR regulatory T cells (Tregs).

Stickler syndrome - lessons from a national cohort.

In 2011 NHS England commissioned a new national specialist MDT service for patients and families affected by Stickler syndrome. The Stickler syndromes form part of the spectrum of inherited vitreoretinopathies and are the most common cause of retinal detachment in childhood and the most common cause of familial retinal detachment. Now in its 10th year, the Stickler Highly Specialised Service (HSS) has assessed 1673 patients from 785 families.

Contemporary Outcomes After Partial Resection of Infected Aortic Grafts.

Introduction: Aortic graft infection remains a considerable clinical challenge, and it is unclear which variables are associated with adverse outcomes among patients undergoing partial resection.

Methods: A retrospective, multi-institutional study of patients who underwent partial resection of infected aortic grafts from 2002 to 2014 was performed using a standard database. Baseline demographics, comorbidities, operative, and postoperative variables were recorded.

Novel Combinatorial MicroRNA-Binding Sites in AAV Vectors Synergistically Diminish Antigen Presentation and Transgene Immunity for Efficient and Stable Transduction.

Recombinant adeno-associated virus (rAAV) platforms hold promise for gene therapy but are undermined by the undesirable transduction of antigen presenting cells (APCs), which in turn can trigger host immunity towards rAAV-expressed transgene products. In light of recent adverse events in patients receiving high systemic AAV vector doses that were speculated to be related to host immune responses, development of strategies to mute innate and adaptive immunity is imperative. The use of miRNA binding sites (miR-BSs) to confer endogenous miRNA-mediated regulation to detarget transgene expression from APCs has shown promise for reducing transgene immunity.

Comparison of 30 Day Stroke and Death in Hybrid Intervention and Open Surgical Reconstruction for the Treatment of Tandem Carotid Bifurcation and Supra-aortic Trunk Disease.

Objective: The optimal approach for the treatment of tandem carotid bifurcation and supra-aortic trunk (SAT) disease remains controversial. The hybrid technique of carotid endarterectomy (CEA) with ipsilateral proximal endovascular intervention (IPE) has provided an attractive alternative to CEA with open SAT reconstruction (SATr). However, no studies have compared cohorts treated by these two approaches.