Ocular Motor and Vestibular Profile in Spinocerebellar Ataxia Type 27B: Toward a Practical Bedside Diagnostic Framework.

Spinocerebellar ataxia type 27B (SCA27B), caused by GAA repeat expansions in FGF14, is an increasingly recognized form of late-onset cerebellar ataxia. However, early diagnosis remains challenging due to mild or absent cerebellar motor signs and often normal brain magnetic resonance imaging (MRI). Oculovestibular abnormalities, although prevalent, are frequently overlooked and not captured by standard clinical scales such as the Scale for the Assessment and Rating of Ataxia (SARA).

The splicing factor kinase SRPK1 is a therapeutic target for peripheral vascular disease.

In peripheral arterial disease (PAD), antiangiogenic VEGF-Ab isoform overexpression in monocytes contributes to impaired collateralization. Serine-arginine protein-kinase-1 (SRPK1) regulates VEGF splicing. To determine whether SRPK1 controlled monocytic VEGF, impairing collateralization, we investigated SRPK1 inhibition and monocyte-specific knockout in mouse models of and in human monocytes from PAD.

Spontaneous Abnormal Vertical Eye Movements of Coma.

Spontaneous vertical eye movements in the critical care setting are often a source of confusion and alarm; while their origin remains at least partly theoretical, understanding their classification and associated clinical implications can inform the diagnostic workup and further clinical management. This case describes a patient who demonstrated ocular dipping: slow conjugate downward eye movements with a quick return to primary gaze. Ocular dipping is a rare phenomenon that was initially described in patients with hypoxic brain injury and has since been described in only a handful of cases.

Pharmacological blocking of microfibrillar-associated protein 4 reduces retinal neoangiogenesis and vascular leakage.

Neovascular age-related macular degeneration and diabetic macular edema are leading causes of vision loss evoked by retinal neovascularization and vascular leakage. The glycoprotein microfibrillar-associated protein 4 (MFAP4) is an integrin αβ ligand present in the extracellular matrix. Single-cell transcriptomics reveal MFAP4 expression in cell types in close proximity to vascular endothelial cells, including choroidal vascular mural cells, retinal astrocytes, and Müller cells.

Virtual practice facilitation as an implementation strategy for launching opioid safety committees for quality improvement in primary care: feasibility, acceptability, and intervention fidelity.

Background: Practice facilitation (PF) is an evidence-based multicomponent in-person implementation strategy. COVID-19-related lockdowns caused many implementation initiatives to rapidly shift to virtual settings, but there is limited evidence on PF deployed exclusively using virtual meeting platforms. Our objective was to assess the feasibility and acceptability of virtual PF used in a primary care setting to implement interdisciplinary opioid safety committees (OSCs) to improve care for patients using opioid medicines for persistent pain and reduce high-dose opioid prescribing.

Cysteamine toxicity presenting with acute encephalopathy and spastic tetraparesis.

Cystinosis is a lysosomal storage disorder usually presenting with renal disease in infancy. As soon as the diagnosis is made, cysteamine (a cystine-depleting medication), is started, significantly improving life expectancy. We describe a young woman taking lifelong cysteamine for nephropathic cystinosis, who became acutely encephalopathic with a spastic tetraparesis secondary to cysteamine toxicity, which was potentially worsened by copper deficiency.

Sustaining connections: feasibility and impact of long-term virtual patient engagement.

Background: Virtual patient engagement has become more common in recent years. Emerging research suggests virtual engagement can increase accessibility for patients managing long-term health conditions and those living in larger geographic areas, but it can also be challenging to establish relationships and maintain engagement over time. Little is known about virtual engagement lasting more than two years, nor about the specific contributions of patients to virtual engagement projects.

Recurrent herpes simplex virus encephalitis with presumptive Human Herpesvirus 6 chromosomal integration.

Viral encephalitis can lead to encephalopathy, epileptic activity, focal neurological deficits, and death. Prompt recognition and a high index of clinical suspicion can lead to early initiation of appropriate management. We describe an interesting case of a 61-year-old presenting with fever and altered mental status, diagnosed with numerous episodes of viral encephalitis caused by divergent and recurrent viruses.

Recurrent Episodes of Transient Global Amnesia: A Rare Clinical Entity.

Transient global amnesia (TGA) is a syndrome characterized by anterograde amnesia with otherwise intact cognitive function, resolving within 24 h of onset, occurring in the absence of neurological changes. Recurrent episodes remain rare. We report an interesting case of recurrent episodes of TGA in a 63-year-old woman presenting with altered mental status.

Longitudinal MRI brain studies in live adult zebrafish.

Zebrafish (Danio rerio) has been successfully used for decades in developmental studies and disease modelling. The remarkable uptake of zebrafish as a model system is partly due to its transparency during the early weeks of its development, allowing in vivo imaging of cellular and molecular processes. However, this key advantage wears off when tissues become opaque as the animal reaches juvenile and adult stages, rendering access to tissues for live imaging and longitudinal studies difficult.

Ancient marine sediment DNA reveals diatom transition in Antarctica.

Antarctica is one of the most vulnerable regions to climate change on Earth and studying the past and present responses of this polar marine ecosystem to environmental change is a matter of urgency. Sedimentary ancient DNA (sedaDNA) analysis can provide such insights into past ecosystem-wide changes. Here we present authenticated (through extensive contamination control and sedaDNA damage analysis) metagenomic marine eukaryote sedaDNA from the Scotia Sea region acquired during IODP Expedition 382.

Serine-arginine-rich protein kinase-1 inhibition for the treatment of diabetic retinopathy.

Angiogenic VEGF isoforms are upregulated in diabetic retinopathy (DR), driving pathological growth and fluid leakage. Serine-arginine-rich protein kinase-1 (SRPK1) regulates VEGF splicing, and its inhibition blocks angiogenesis. We tested the hypothesis that SRPK1 is activated in diabetes, and an SRPK1 inhibitor (SPHINX31) switches VEGF splicing in DR and prevents increased vascular permeability into the retina.

Dorsal arachnoid web: A rare clinical entity.

A dorsal arachnoid web is a rare entity involving abnormal formation of arachnoid mater into a dense web which may result in ventral herniation of the spinal cord and significant neurologic symptoms. Back pain or a compressive myelopathy are two of the most common presenting symptoms. CT myelogram or MRI can aid in the diagnosis of arachnoid web, and management of includes surgical and conservative approaches.

Quantification of Angiogenesis in Laser Choroidal Neovascularization.

Murine laser-induced laser choroidal neovascularization is a widely used and robust model of wet (exudative) age-related macular degeneration (wAMD). wAMD is one of the leading causes of blindness in the Western world. In brief, a focused laser beam is used to penetrate Bruch's membrane, which separates the choriocapillaris (well-vascularized choroid layer) from the pigmented layers of the retina.

Noninvasive Measurement of Retinal Microvascular Permeability During Loss of Endothelial Quiescence.

In the retina EC dysfunction and angiogenesis are driven by an altered microenvironment e.g., diabetes, leading to hypoxia and inflammation in the retinal layers, resulting in excessive vascular leakage and growth.

Transmission Electron Microscopy of Endothelium.

Transmission electron microscopy using resin sections still remains an exceptionally useful tool in evaluating cellular ultrastucture within tissue. For the endothelium the best method for maintaining such structure is perfusion fixation: fixing the tissue under physiological pressure. Here the focus is on a method of maintaining the vascular wall structure including the endothelial glycocalyx and extending this with tilt series tomography.

Preventing persistent postsurgical pain: A systematic review and component network meta-analysis.

Background And Objectives: Evidence for perioperative methods to prevent persistent postsurgical pain (PPP) is uncertain, in part because few treatments have been directly compared. Here we have used component network meta-analysis (cNMA) to incorporate both direct and indirect evidence in the evaluation of the efficacy and tolerability of pharmacological and neural block treatments.

Databases And Data Treatment: We searched the Cochrane Central Registry of Controlled Trials, Embase, MEDLINE, ClinicalTrials.

A roadmap to operationalize and evaluate impact in a learning health system.

Background: Many health systems invest in initiatives to accelerate translation of knowledge into practice. However, organizations lack guidance on how to develop and operationalize such Learning Health System (LHS) programs and evaluate their impact. Kaiser Permanente Washington (KPWA) launched our LHS program in June 2017 and developed a logic model as a foundation to evaluate the program's impact.

Hydrogen Sulfide Is a Novel Protector of the Retinal Glycocalyx and Endothelial Permeability Barrier.

Significantly reduced levels of the anti-inflammatory gaseous transmitter hydrogen sulfide (HS) are observed in diabetic patients and correlate with microvascular dysfunction. HS may protect the microvasculature by preventing loss of the endothelial glycocalyx. We tested the hypothesis that HS could prevent or treat retinal microvascular endothelial dysfunction in diabetes.