Publications by authors named "Nolan N"

Amphibians are among the most threatened vertebrate taxa globally. Their global decline necessitates effective conservation actions to bolster populations across both the larval and adult stages. Constructing man-made ponds is one action proven to enhance reproduction in pond-breeding amphibians.

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Photoreceptors in the retina of a vertebrate's eye are supported by a tissue adjacent to the retina, the retinal pigment epithelium (RPE). The RPE delivers glucose to the outer retina, consumes photoreceptor outer segments discs, and regenerates 11-cis-retinal. Here we address the question of whether photoreceptors also provide metabolic support to the RPE.

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Background: Infectious complications of substance use are increasingly encountered in infectious diseases (ID) clinical care. In this study, we surveyed ID fellows in the United States to assess training experiences, clinical practices, and perspectives in caring for people who use drugs (PWUD).

Methods: An 18-item survey was distributed to ID fellows via email and social media platforms.

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With demographic trends highlighting an inversion of the farming community age pyramid, with those aged 65 years and over constituting the fastest growing subgroup of the farming population globally, this article highlights a social initiative for older farmers called Farmer's Yards, embodying values, and aspirations pertinent to farmers in their later years, that is helping to create an age-friendly environment in farming in line with World Health Organisation (WHO) guidelines. By providing older farmers with a platform for sustained social engagement and inclusion within the farming community, this social initiative aligns with principles promoting active and healthy aging, thereby contributing positively to their mental health and wellbeing in later life. In doing so, Farmer's Yards is helping to address recent calls by the European Commission for an increased emphasis on the delivery of creative mechanisms that enhance the quality of life of older farmers through social policy.

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Due to remarkable advancements in medications, more people are living longer with human immunodeficiency virus (HIV). The HIV workforce has been strained by a supply-demand mismatch, threatening the care of an aging population with multiple comorbidities. Solving the HIV workforce shortage requires multiple novel and creative solutions that recruit new trainees to the field, increase the workforce diversity, and improve disparities in access to care.

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Organic digital education (ODE) includes online medical education content that can take various forms, such as blogs, social media, videos, podcasts, or infographics. Multimedia ODE platforms have unique benefits and have quickly become an essential part of medical education. Modern medical educators with competency in digital teaching modalities can leverage these for teaching as well as career development and dissemination of scientific research.

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Background: Collective decision-making by grading committees has been proposed as a strategy to improve the fairness and consistency of grading and summative assessment compared to individual evaluations. In the 2020-2021 academic year, Washington University School of Medicine in St. Louis (WUSM) instituted grading committees in the assessment of third-year medical students on core clerkships, including the Internal Medicine clerkship.

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Background: Retinitis pigmentosa (RP) is a genetically heterogeneous group of degenerative disorders causing progressive vision loss due to photoreceptor death. RP affects other retinal cells, including the retinal pigment epithelium (RPE). MicroRNAs (miRs) are implicated in RP pathogenesis, and downregulating miR-181a/b has shown therapeutic benefit in RP mouse models by improving mitochondrial function.

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Importance: Despite interest in therapy de-escalation for survivors of human papillomavirus-mediated oropharyngeal squamous cell carcinoma (HPV-positive OPSCC), the association of de-escalated therapy with patient-reported quality of life (QoL) outcomes and burden of depressive symptoms remains unclear.

Objective: To identify associations between clinicopathologic and therapeutic variables with patient-reported QoL outcomes and depression symptom burden in patients with HPV-positive OPSCC, who were enrolled in a therapy de-escalation trial.

Design, Setting, And Participants: In this nonrandomized controlled, open-label, curative-intent therapy de-escalation clinical trial in adults with stage I, II, and III HPV-positive OPSCC, patients were recruited from a high-volume head and neck oncology practice.

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Background And Purpose: Thresholds for abnormal transcranial Doppler cerebrovascular reactivity (CVR) studies are poorly understood, especially for patients with cerebrovascular disease. Using a real-world cohort with cerebral arterial stenosis, we sought to describe a clinically significant threshold for carbon dioxide reactivity (CO2R) and vasomotor range (VMR).

Methods: CVR studies were performed during conditions of breathing room air normally, breathing 8% carbon dioxide air mixture, and hyperventilation.

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Retinitis pigmentosa (RP) is one of the most common forms of hereditary neurodegeneration. It is caused by one or more of at least 3,100 mutations in over 80 genes that are primarily expressed in rod photoreceptors. In RP, the primary rod-death phase is followed by cone death, regardless of the underlying gene mutation that drove the initial rod degeneration.

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Article Synopsis
  • The 2023 U.S. infectious diseases fellowship match saw many programs left with unfilled positions, prompting a survey of program directors to explore the reasons behind it.
  • Program directors identified factors like geographic location, a limited number of applicants, and low pay as key contributors to these unfilled spots.
  • To improve future match outcomes, suggestions include creating specialized training tracks, boosting funding for ID training programs, advocating for better salaries, and discussing potential changes to fellowship program sizes.
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Background: People who inject drugs (PWID) are at high risk of severe wounds, invasive infections, and overdoses. To date, there are few data on the bacterial and chemical contaminants PWID are exposed to when using illicitly manufactured fentanyls and stimulants.

Methods: Previously used injection drug use equipment was recovered in St Louis, Missouri, by harm reduction organizations over a 12-month period.

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Phages are one of the key ecological drivers of microbial community dynamics, function, and evolution. Despite their importance in bacterial ecology and evolutionary processes, phage genes are poorly characterized, hampering their usage in a variety of biotechnological applications. Methods to characterize such genes, even those critical to the phage life cycle, are labor intensive and are generally phage specific.

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Background: The rise in injection drug use (IDU) has led to an increase in drug-related infections. Harm reduction is an important strategy for preventing infections among people who inject drugs (PWID). We attempted to evaluate the harm reduction counseling that infectious diseases physicians provide to PWID presenting with infections.

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Retinal gene therapies have shown tremendous progress in the past decade, but the sheer number of disease-causing mutations makes their applicability challenging. In this study we test our hypothesis that retinitis pigmentosa-associated retinal degeneration can be prevented through AMP-activated protein kinase (AMPK)-associated metabolic pathway reprogramming using a gene-independent model of degeneration and rescue. We show that recue of photoreceptor structure and function is not achieved through our model of metabolic reprogramming.

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Prime editing (PE) is a novel, double-strand break (DSB)-independent gene editing technology that represents an exciting avenue for the treatment of inherited retinal diseases (IRDs). Given the extensive and heterogenous nature of the 280 genes associated with IRDs, genome editing has presented countless complications. However, recent advances in genome editing technologies have identified PE to have tremendous potential, with the capability to ameliorate small deletions and insertions in addition to all twelve possible transition and transversion mutations.

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Article Synopsis
  • Cones are critical for color vision and sharp sight, and their loss can lead to blindness; thus, understanding how they function is vital for developing treatments for retinal diseases.
  • Researchers created three new mouse models with specific "CreER" sequences to study cone cells in the retina, using a bacterial artificial chromosome method that allows controlled genetic modifications.
  • The Arr3 mouse model, in particular, allows for precise study of cone cell biology without affecting their normal function, and the ability to activate genetic changes early in development opens up new avenues for researching retinal disorders.
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Aims: Patients with haemochromatosis (HFE) are known to have an increased risk of developing hepatocellular carcinoma (HCC). Available data are conflicting on whether such patients have poorer prognosis, and there is lack of data regarding the biology of HFE-HCC. We compared the course of HFE-HCC with a matched non-HFE-HCC control group and examined tumour characteristics using immunohistochemistry.

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The unprecedented rate of global amphibian decline is attributed to The Anthropocene, with human actions triggering the Sixth Mass Extinction Event. Amphibians have suffered some of the most extreme declines, and their lack of response to conservation actions may reflect challenges faced by taxa that exhibit biphasic life histories. There is an urgent need to ensure that conservation measures are cost-effective and yield positive outcomes.

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Objectives: Status epilepticus (SE) is associated with significantly higher morbidity and mortality than isolated seizures. Our objective was to identify clinical diagnoses and rhythmic and periodic electroencephalogram patterns (RPPs) associated with SE and seizures.

Design: Retrospective cohort study.

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Introduction: Outcomes in colorectal cancer treatment are historically worse in Black people and residents of rural areas. Purported reasons include factors such as systemic racism, poverty, lack of access to care, and social determinants of health. We sought to determine whether outcomes worsened when race and rural residence intersected.

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  • Iron accumulation leads to cell death and tissue dysfunction, requiring chelation therapy like deferoxamine (DFO) to reduce excess iron.
  • This study identifies retinal pigment epithelium (RPE) as the primary target for DFO-related damage and explores the underlying mechanisms, including the role of hypoxia inducible factor (HIF) 2α and mitochondrial deficits.
  • The researchers found that using α-ketoglutarate (AKG) can mitigate RPE damage and improve visual function in patients undergoing DFO therapy, indicating a potential therapeutic strategy.
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Article Synopsis
  • * CRISPR technology, particularly the recently approved EDIT-101, shows promise for treating IRDs by targeting genetic mutations, such as those in the CEP290 gene that cause Leber congenital amaurosis.
  • * This study explores prime editing as a cutting-edge method to correct specific mutations, demonstrating its potential through experiments on a mouse model with a mutation that leads to retinitis pigmentosa.
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