Age-related effects of optineurin deficiency in the mouse eye.

Optineurin (OPTN) is a gene associated with familial normal tension glaucoma (NTG). While NTG involves intraocular pressure (IOP)-independent neurodegeneration of the visual pathway that progresses with age, how OPTN dysfunction leads to NTG remains unclear. Here, we generated an OPTN knockout mouse (Optn-/-) model to test the hypothesis that a loss-of-function mechanism induces structural and functional eye deterioration with aging. Eye anatomy, visual function, IOP, retinal histology, and retinal ganglion cell survival were compared to littermate wild-type (WT) control mice. Consistent with OPTN's role in NTG, loss of OPTN did not increase IOP or alter gross eye anatomy in young (2-3 months) or aged (12 months) mice. When retinal layers were quantitated, young Optn-/- mice had thinner retina in the peripheral regions than young WT mice, primarily due to thinner ganglion cell-inner plexiform layers. Despite this, visual function in Optn-/- mice was not severely impaired, even with aging. We also assessed relative abundance of retinal cell subtypes, including amacrine cells, bipolar cells, cone photoreceptors, microglia, and astrocytes. While many of these cellular subtypes were unaffected by Optn deletion, more dopaminergic amacrine cells were observed in aged Optn-/- mice. Taken together, our findings showed that complete loss of Optn resulted in mild retinal changes and less visual function impairment, supporting the possibility that OPTN-associated glaucoma does not result from a loss-of-function disease mechanism. Further research using these Optn mice will elucidate detailed molecular pathways involved in NTG and identify clinical or environmental risk factors that can be targeted for glaucoma treatment.

Gender Trends in Authorship of Gastroenterology Randomized Controlled Trial Literature.

INTRODUCTION: We describe female authorship trends in gastroenterology (GI) randomized controlled trial literature as a novel focus on gender bias in academic GI. METHODS: Using a systematic PubMed search, we extracted GI randomized controlled trial reports published from 2011 to 2022. We describe time trends in proportions of females among first and last authors overall and within GI subspecialties and high-impact journals. RESULTS: The proportion of females increased from 25.4% to 36.8% and from 14.3% to 24.8% among first and last authors, respectively. Smaller increases in female authorship occurred in most subgroups, although there were proportionately fewer females among authors in high-impact journals and advanced therapeutic endoscopy publications. DISCUSSION: Over the past decade, female authorship in GI RCT reports has increased. However, female representation, particularly among senior authors and in high-impact journals, remains significantly lower. Despite recent improvements, female still constitutes a minority of the authors of original GI RCTs.

Insights into the Evolving Epidemiology of Clostridioides difficile Infection and Treatment: A Global Perspective.

Clostridioides difficile remains an important public health threat, globally. Since the emergence of the hypervirulent strain, ribotype 027, new strains have been reported to cause C. difficile infection (CDI) with poor health outcomes, including ribotypes 014/020, 017, 056, 106, and 078/126. These strains differ in their geographic distribution, genetic makeup, virulence factors, and antimicrobial susceptibility profiles, which can affect their ability to cause disease and respond to treatment. As such, understanding C. difficile epidemiology is increasingly important to allow for effective prevention measures. Despite the heightened epidemiological surveillance of C. difficile over the past two decades, it remains challenging to accurately estimate the burden and international epidemiological trends given the lack of concerted global effort for surveillance, especially in low- and middle-income countries. This review summarizes the changing epidemiology of C. difficile based on available data within the last decade, highlights the pertinent ribotypes from a global perspective, and discusses evolving treatments for CDI.

Glymphatic imaging and modulation of the optic nerve.

Optic nerve health is essential for proper function of the visual system. However, the pathophysiology of certain neurodegenerative disease processes affecting the optic nerve, such as glaucoma, is not fully understood. Recently, it was hypothesized that a lack of proper clearance of neurotoxins contributes to neurodegenerative diseases. The ability to clear metabolic waste is essential for tissue homeostasis in mammals, including humans. While the brain lacks the traditional lymphatic drainage system identified in other anatomical regions, there is growing evidence of a glymphatic system in the central nervous system, which structurally includes the optic nerve. Named to acknowledge the supportive role of astroglial cells, this perivascular fluid drainage system is essential to remove toxic metabolites from the central nervous system. Herein, we review existing literature describing the physiology and dysfunction of the glymphatic system specifically as it relates to the optic nerve. We summarize key imaging studies demonstrating the existence of a glymphatic system in the optic nerves of wild-type rodents, aquaporin 4-null rodents, and humans; glymphatic imaging studies in diseases where the optic nerve is impaired; and current evidence regarding pharmacological and lifestyle interventions that may help promote glymphatic function to improve optic nerve health. We conclude by highlighting future research directions that could be applied to improve imaging detection and guide therapeutic interventions for diseases affecting the optic nerve.

Diagnostic accuracy of SPECT/CT arthrography in patients with suspected aseptic joint prostheses loosening.

PURPOSE: To evaluate the diagnostic accuracy of SPECT/CT arthrography in patients with suspected aseptic prosthesis loosening following hip and knee arthroplasty. METHODS: A retrospective review of 63 SPECT/CT arthrogram studies (36 knees and 27 hips) between February 1, 2013, and July 1, 2018, was conducted. All patients underwent clinical and radiologic evaluation as part of their assessment for persistent pain following hip and knee arthroplasty. The detection of tracer activity along the bone-prosthetic interface on SPECT/CT suggests aseptic loosening. Operative assessment as well as clinical/radiologic follow-up at a minimum of 1 year was used as the reference standard. RESULTS: The sensitivity and specificity of SPECT/CT for detection of aseptic loosening was 6/7 (86%) and 55/56 (98%), respectively. This gives a positive predictive value (PPV) of 6/7 (86%), a negative predictive value (NPV) of 55/56 (98%), and a diagnostic accuracy of 61/63 (97%). CONCLUSION: SPECT/CT arthrography has a high diagnostic accuracy (97%) in the evaluation of loosening of both hip and knee arthroplasties in patients with persistent post-procedural pain.

Human serum mast cell tryptase levels in elbow fractures or dislocations and its association with injury severity.

Mast cells contain an abundance of tryptase, and preclinical models have shown elevated serum mast cell tryptase (SMCT) in the setting of posttraumatic joint contractures. Therefore, SMCT emerged as a potential biomarker to help recognize patients with more severe injuries and a higher likelihood of developing contractures. The objective of this study is to assess SMCT levels in participants with varying severity of elbow fractures and/or dislocations. A prospective cohort including 13 participants with more severe injuries that required an operation and 28 participants with less severe injuries managed nonoperatively were evaluated. A control group of eight individuals without elbow injuries was also evaluated. The SMCT levels were measured using an enzyme-linked immunosorbent assay kit specific for human mast cell tryptase. A one-way analysis of variance and Tukey's Honest Significance test was used to assess for statistical significance among and between the three groups. The average time from injury to the collection of the blood samples was 4 ± 2 days. Highly significant differences were identified between the operative, nonoperative, and control groups (P = .0005). In the operative group, SMCT levels were significantly higher than the nonoperative group (P = .0005) and the control group (P = .009), suggesting a correlation between SMCT levels and injury severity. There was no statistically significant difference in SMCT levels between the nonoperative and control groups. The SMCT levels were elevated in participants with acute elbow injuries requiring operative intervention, suggesting that SMCT levels were higher in injuries regarded as more severe.

Applications of Manganese-Enhanced Magnetic Resonance Imaging in Ophthalmology and Visual Neuroscience.

Understanding the mechanisms of vision in health and disease requires knowledge of the anatomy and physiology of the eye and the neural pathways relevant to visual perception. As such, development of imaging techniques for the visual system is crucial for unveiling the neural basis of visual function or impairment. Magnetic resonance imaging (MRI) offers non-invasive probing of the structure and function of the neural circuits without depth limitation, and can help identify abnormalities in brain tissues in vivo. Among the advanced MRI techniques, manganese-enhanced MRI (MEMRI) involves the use of active manganese contrast agents that positively enhance brain tissue signals in T1-weighted imaging with respect to the levels of connectivity and activity. Depending on the routes of administration, accumulation of manganese ions in the eye and the visual pathways can be attributed to systemic distribution or their local transport across axons in an anterograde fashion, entering the neurons through voltage-gated calcium channels. The use of the paramagnetic manganese contrast in MRI has a wide range of applications in the visual system from imaging neurodevelopment to assessing and monitoring neurodegeneration, neuroplasticity, neuroprotection, and neuroregeneration. In this review, we present four major domains of scientific inquiry where MEMRI can be put to imperative use - deciphering neuroarchitecture, tracing neuronal tracts, detecting neuronal activity, and identifying or differentiating glial activity. We deliberate upon each category studies that have successfully employed MEMRI to examine the visual system, including the delivery protocols, spatiotemporal characteristics, and biophysical interpretation. Based on this literature, we have identified some critical challenges in the field in terms of toxicity, and sensitivity and specificity of manganese enhancement. We also discuss the pitfalls and alternatives of MEMRI which will provide new avenues to explore in the future.