Multimodal Evaluation and Management of Wagner Syndrome-Three Patients from an Affected Family.

Wagner syndrome is a rare autosomal dominant vitreoretinopathy caused by mutations in chondroitin sulphate proteoglycan 2 (CSPG2)/Versican (VCAN). Here, we present a retrospective case series of a family pedigree with genetically confirmed Wagner syndrome (heterozygous VCAN exon 8 deletion), as follows: a 34-year-old mother (P1), 12-year-old daughter (P2), and a 2-year-old son (P3). The phenotype included early-onset cataract (P1), optically empty vitreous with avascular membranes (P1, 2), nasal dragging of optic nerve heads associated with foveal hypoplasia (P1, 2), tractional retinoschisis on optical coherence tomography (P2), and peripheral circumferential vitreo-retinal interface abnormality resembling white-without-pressure (P3) progressing to pigmented chorio-retinal atrophy (P1, 2).

Bidirectional Cascaded Superfluorescent Lasing in Air Enabled by Resonant Third Harmonic Photon Exchange from Nitrogen to Argon.

Cavity-free lasing in atmospheric air has stimulated intense research toward a fundamental understanding of underlying physical mechanisms. In this Letter, we identify a new mechanism-a third-harmonic photon mediated resonant energy transfer pathway leading to population inversion in argon via an initial three-photon excitation of nitrogen molecules irradiated by intense 261 nm pulses-that enables bidirectional two-color cascaded lasing in atmospheric air. By making pump-probe measurements, we conclusively show that such cascaded lasing results from superfluorescence rather than amplified spontaneous emission.

Biomolecular Condensation of Trypsin Prevents Autolysis and Promotes Ca-Mediated Activation of Esterase Activity.

The presence of Ca ions is known to facilitate the activity of trypsin-like serine proteases via structural stabilization against thermal denaturation and autolysis. Herein, we report a new and hidden regulatory role of Ca in the catalytic pathways of trypsin and α-chymotrypsin under physiological conditions. We discovered that macromolecular crowding promotes spontaneous homotypic condensation of trypsin via liquid-liquid phase separation to yield membraneless condensates over a broad range of concentrations, pH, and temperature, which are stabilized by multivalent hydrophobic interactions.

Morphological and functional parameters in X-linked retinoschisis patients-A multicentre retrospective cohort study.

Introduction: X-linked retinoschisis (XLRS) is a potential target for gene supplementation approaches. To establish potential structural and functional endpoints for clinical trials, a comprehensive understanding of the inter-eye symmetry, relationship between structural and functional parameters, and disease progression is vital.

Methods: In this retrospective multicentre study, 118 eyes of 59 XLRS patients with mutations were assessed.

Macromolecular Crowding Promotes Re-entrant Liquid-Liquid Phase Separation of Human Serum Transferrin and Prevents Surface-Induced Fibrillation.

Protein aggregation and inactivation upon surface immobilization are major limiting factors for analytical applications in biotechnology-related fields. Protein immobilization on solid surfaces often requires multi-step surface passivation, which is time-consuming and inefficient. Herein, we have discovered that biomolecular condensates of biologically active human serum transferrin (Tf) can effectively prevent surface-induced fibrillation and preserve the native-like conformation of phase-separated Tf over a period of 30 days.

A Carrier Female Manifesting an Unusual X-Linked Retinoschisis Phenotype Associated with the Pathogenic Variant c.266delA, p.(Tyr89LeufsTer37) in , and Skewed X-Inactivation.

X-linked retinoschisis (XLRS) is the most common juvenile macular degeneration in males. Unlike most other X-linked retinal dystrophies, carrier heterozygous females are very rarely reported to show clinical features of the disease. Herein, we describe unusual retinal features in a 2-year-old female infant with family history and genetic testing consistent with XLRS.

PHOTORECEPTOR DAMAGE IN TERSON SYNDROME.

Purpose: To describe photoreceptor damage in patients with Terson syndrome as a potential cause for inconsistent clinical outcomes.

Methods: Clinical evaluation and retinal imaging in six patients.

Results: Four patients were women and two men, with an average age of 46.

RNA-sequencing reveals molecular and regional differences in the esophageal mucosa of achalasia patients.

Achalasia is an esophageal motility disorder characterized by the functional loss of myenteric plexus ganglion cells in the distal esophagus and lower esophageal sphincter. Histological changes have been reported in the esophageal mucosa of achalasia, suggesting its involvement in disease pathogenesis. Despite recent advances in diagnosis, our understanding of achalasia pathogenesis at the molecular level is very limited and gene expression profiling has not been performed.

A Network Meta-Analysis of Retreatment Rates following Bevacizumab, Ranibizumab, Aflibercept, and Laser for Retinopathy of Prematurity.

Topic: To compare bevacizumab, ranibizumab, aflibercept, and laser treatment as primary therapies for retinopathy of prematurity (ROP) in terms of retreatment rate.

Clinical Relevance: Anti-VEGF agents are increasingly used as primary treatment for ROP and may provide superior outcomes compared with laser in posterior disease. Head-to-head comparisons between different anti-VEGFs are lacking.

Variability of retinopathy consequent upon novel mutations in LAMA1.

Purpose: Bi-allelic mutations in LAMA1 (laminin 1) (OMIM # 150320) cause Poretti-Boltshauser Syndrome (PTBHS), a rare non-progressive cerebellar dysplasia disorder with ophthalmic manifestations including oculomotor apraxia, high myopia, and retinal dystrophy. Only 38 variants, nearly all loss of function have been reported. Here, we describe novel LAMA1 variants and detailed retinal manifestations in two unrelated families.

Macromolecular Crowding-Induced Unusual Liquid-Liquid Phase Separation of Human Serum Albumin via Soft Protein-Protein Interactions.

Macromolecular crowding has a profound impact on the conformational dynamics and intermolecular interactions of biological macromolecules. In this context, the role of inert synthetic crowders in the protein-protein interactions of globular proteins is poorly understood. Here, using native human serum albumin (HSA) under physiological conditions, we show that macromolecular crowding induces liquid-liquid phase separation (LLPS) via liquid-like membrane-less droplet formation in a concentration- and time-dependent manner.

Whole genome sequencing in a Knobloch syndrome family confirms the molecular diagnosis.

Background: To establish the molecular diagnosis in two brothers presenting with the ocular features of Knobloch Syndrome using whole genome sequencing (WGS).

Methods: Clinical examination and ophthalmological phenotyping were completed under general anaesthesia. DNA samples were tested on a targeted retinal dystrophy next-generation sequencing panel.

Ectopic vortex veins and varices in Donnai Barrow syndrome.

Background: Donnai Barrow Syndrome (DBS) is a rare, multi-system autosomal recessively inherited disorder of relevance to ophthalmologists. To aim to describe the ocular phenotype using multimodal imaging for two cases of genetically confirmed DBS and compare against the published phenotype.

Materials And Methods: Retrospective case series of two unrelated patients with DBS and review of the literature.

Evolving outcomes of surgery for retinal detachment in retinopathy of prematurity: the need for a national service in the United Kingdom : An audit of surgery for acute tractional retinal detachment complicating ROP in the UK.

Objectives: To audit the structural and functional outcomes of surgery for acute tractional retinal detachment due to retinopathy or prematurity between 2004 and 2014 in Oxford UK.

Methods: Consecutive operations were identified from a surgical log. Clinical data including demography, perioperative data, and retinal outcomes were extracted into a spreadsheet and compared against two international data sets referenced in the method section.

Retinal imaging in infants.

Digital retinal imaging is at the core of a revolution that is continually improving the screening, diagnosis, documentation, monitoring, and treatment of infant retinal diseases. Historically, imaging the retina of infants had been limited and difficult to obtain. Recent advances in photographic instrumentation have significantly improved the ability to obtain high quality multimodal images of the infant retina.

Intraosseous Regional Administration of Vancomycin in Primary Total Knee Arthroplasty Does Not Increase the Risk of Vancomycin-Associated Complications.

Background: Periprosthetic joint infection (PJI) after total knee arthroplasty (TKA) is a rare but major complication. Owing to an increasing antibiotic resistance in bacteria causing PJI, vancomycin has been investigated as a prophylactic agent. Intraosseous regional administration (IORA) of vancomycin achieves significantly higher local tissue concentrations than systemic administration.

Towards improved outcome in children treated surgically for spontaneous intracranial suppuration in South Wales.

Introduction: Spontaneous central nervous system (CNS) infections in children are rare. Treatment involves surgical intervention and antibiotic therapy. We describe a single centre experience of managing this condition in South Wales.

Flying baby optical coherence tomography alters the staging and management of advanced retinopathy of prematurity.

Purpose: To report the use of flying baby spectral domain optical coherence tomography (SD-OCT) on infants with advanced retinopathy of prematurity (ROP), where clinical findings alone failed to differentiate between retinoschisis and retinal detachment.

Methods: Prospective, non-interventional case-series study of three premature infants with advanced ROP of clinically uncertain stage, after examination by indirect ophthalmoscopy. To confirm the diagnosis, table-mounted SD-OCT retinal imaging was performed with the infant held in the flying baby position under topical ocular anaesthesia only.

Railway anaesthesiologists and Indian railway COVID-19 management system.

Ever since the outbreak of novel Corona Virus 2019 pandemic, Anaesthesiologists are among the frontline leaders in not only the prevention of and control over the spread of the pandemic but also planning, organizing and coordinating the deployment and utilization of the medical and all other resources effectively and efficiently in order to minimize the losses and sufferings of human lives and recouping the global wellbeing at large. This article briefly highlights the prompt, optimal and effective contributions of the Indian Railways, Indian Railway Health Services and the Railway Association of ISA (RAISA) towards the provision of safe and scientific health services to maximum number of our fellow citizens.

The Other Side of Medical Student Mistreatment: Teaching Cultural Competency Across the Generational Divide.

Introduction: Medical student mistreatment continues to be a significant problem despite increased awareness and longitudinal efforts to address the issue. Through audience discussions of a previously published film depicting learner mistreatment, we identified challenges created by student behaviors that negatively impact the learning environment. In addition, the need to address cultural competency in a multigenerational clinical environment became apparent.

Improved Diagnosis of Retinal Laser Injuries Using Near-Infrared Autofluorescence.

Purpose: To assess whether near infrared autofluorescence (NIR-AF) imaging is a useful imaging modality in the diagnosis of handheld laser retinal injuries.

Design: Retrospective observational case series.

Methods: Twelve patients identified to have handheld laser retinal injuries were included at 2 academic centers.