Case Report: ISG15 deficiency caused by novel variants in two families and effective treatment with Janus kinase inhibition.

ISG15 deficiency is a rare disease caused by autosomal recessive variants in the gene, which encodes the ISG15 protein. The ISG15 protein plays a dual role in both the type I and II interferon (IFN) immune pathways. Extracellularly, the ISG15 protein is essential for IFN-γ-dependent anti-mycobacterial immunity, while intracellularly, ISG15 is necessary for USP18-mediated downregulation of IFN-α/β signalling.

Combined novel homozygous variants in both and STAT presenting with severe combined immune deficiency: case report and literature review.

Background: Sphingosine phosphate lyase insufficiency syndrome (SPLIS) is associated with biallelic variants in , comprising a multisystemic disease characterized by steroid resistant nephrotic syndrome, primary adrenal insufficiency, neurological problems, skin abnormalities and immunodeficiency in described cases. Signal transducer and activator of transcription 1 (STAT1) plays an important role in orchestrating an appropriate immune response through JAK-STAT pathway. Biallelic loss of function (LOF) variants lead to STAT1 deficiency with a severe phenotype of immunodeficiency with increased frequency of infections and poor outcome if untreated.

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.

Inter-subject correlations during natural viewing: A filter-bank approach.

A central question in neuroscience is how the brain processes real-world sensory input. For decades most classical studies focus on carefully controlled artificial stimuli. More recently researchers started to investigate brain activity under more realistic conditions.

Feasibility of high-flow nasal oxygen therapy and two-stage sedation during endoscopic hypopharyngeal therapy.

Background: Structural disorders of the hypopharynx can lead to dysphagia-related morbidity. Endoscopic therapy in this area, for example, myotomy for Zenker's diverticulum (ZD), has traditionally been performed under general anesthesia (GA). We have developed a two-stage sedation process, which is used along with high-flow nasal oxygen therapy (HFNOT) to facilitate endoscopic hypopharyngeal procedures.

Real-time cortical simulation on neuromorphic hardware.

Real-time simulation of a large-scale biologically representative spiking neural network is presented, through the use of a heterogeneous parallelization scheme and SpiNNaker neuromorphic hardware. A published cortical microcircuit model is used as a benchmark test case, representing ≈1 mm of early sensory cortex, containing 77 k neurons and 0.3 billion synapses.

SpiNNTools: The Execution Engine for the SpiNNaker Platform.

SpiNNaker is a massively parallel distributed architecture primarily focused on real time simulation of spiking neural networks. The largest realization of the architecture consists of one million general purpose processors, making it the largest neuromorphic computing platform in the world at the present time. Utilizing these processors efficiently requires expert knowledge of the architecture to generate executable code and to harness the potential of the unique inter-processor communications infra-structure that lies at the heart of the SpiNNaker architecture.

Measurement of synovial tissue volume in knee osteoarthritis using a semiautomated MRI-based quantitative approach.

Purpose: Synovitis is common in knee osteoarthritis and is associated with both knee pain and progression of disease. Semiautomated methods have been developed for quantitative assessment of structure in knee osteoarthritis. Our aims were to apply a novel semiautomated assessment method using 3D active appearance modeling for the quantification of synovial tissue volume (STV) and to compare its performance with conventional manual segmentation.

sPyNNaker: A Software Package for Running PyNN Simulations on SpiNNaker.

This work presents sPyNNaker 4.0.0, the latest version of the software package for simulating PyNN-defined spiking neural networks (SNNs) on the SpiNNaker neuromorphic platform.

With a biomechanical treatment in knee osteoarthritis, less knee pain did not correlate with synovitis reduction.

Background: Braces are used to treat pain in patellofemoral joint osteoarthritis (PFJOA). In a trial, we previously reported pain improvement after 6-weeks brace use. The pain reduction did not correlate with changes in Magnetic Resonance Imaging (MRI) assessed Bone Marrow Lesion volume or static synovial volume.

Structural predictors of response to intra-articular steroid injection in symptomatic knee osteoarthritis.

Background: The aim was to examine if structural factors could affect response to intra-articular steroid injections (IASI) in knee osteoarthritis (OA).

Method: Persons with painful knee OA participated in an open-label trial of IASI where radiographic joint space narrowing (JSN) and Kellgren-Lawrence (KL) grade, whole-organ magnetic resonance imaging (MRI) scores (WORMS) and quantitative assessment of synovial tissue volume (STV) were assessed on baseline images. Participants completed the Knee Injury and Osteoarthritis Outcome Score (KOOS) and a question about knee pain with a visual analogue scale for pain during nominated activity (VAS), and Outcome Measures in Rheumatology (OMERACT)-Osteoarthritis Research Society International (OARSI) criteria were used to assess responder status within 2 weeks (short term) and 6 months (longer term).

Synovial volume vs synovial measurements from dynamic contrast enhanced MRI as measures of response in osteoarthritis.

Objective: Synovium is increasingly a target of osteoarthritis (OA) treatment, yet its optimal measurement is unclear. Using dynamic contrast enhanced (DCE) MRI in knee OA patients before and after intraarticular steroid injection, we compared the responsiveness of static synovial volume measures to measures of dynamic changes in synovial enhancement, changes that are strongly related to synovial vascularity.

Methods: Ninety three patients underwent DCE-MRI before and 1-2 weeks after intra-articular injection of 80 mg methylprednisolone.

Synovial tissue volume: a treatment target in knee osteoarthritis (OA).

Background: Synovitis occurring frequently in osteoarthritis (OA) may be a targeted outcome. There are no data examining whether synovitis changes following intra-articular intervention.

Methods: Persons aged 40 years and older with painful knee OA participated in an open label trial of intra-articular steroid therapy.

A randomised trial of a brace for patellofemoral osteoarthritis targeting knee pain and bone marrow lesions.

Objective: Braces used to treat (PF) osteoarthritis (OA) may reduce contact stress across the PF joint. We hypothesised that in PF OA, braces would decrease knee pain and shrink PF bone marrow lesions (BMLs).

Methods: Eligible subjects had painful PF OA.

Bone marrow lesions in knee osteoarthritis change in 6-12 weeks.

Objectives: Knee osteoarthritis (OA) is thought to be a slowly evolving disease with glacial changes in cartilage morphology necessitating trials of potential treatments lasting 1-2 years with evidence that over 6 months change in cartilage is not detectable. In contrast to cartilage, bone has the capacity to adapt rapidly, such as after fracture. We tested whether bone marrow lesions (BMLs) change in volume in 6 and 12 weeks, suggesting they may provide evidence of short term fluctuations of joint damage.

Airway management at floor level: a comparison of tracheal intubation using the Macintosh and Airtraq laryngoscopes.

Practitioners providing pre-hospital care during civilian practice and on military operations may be required to perform airway management and tracheal intubation at floor level. It has been shown that intubation using the Airtraq laryngoscope is easier to learn than standard Macintosh laryngoscopy. We hypothesised that the Airtraq would be easier to use and have shorter intubation times than Macintosh intubation.