Publications by authors named "McFadden D"

The Test of Basic Auditory Capabilities (TBAC) consists of 19 discrimination and identification tasks selected to study individual differences in audition. In one TBAC study, performance was measured for 340 normal-hearing subjects, but no investigation into possible sex differences was undertaken. That dataset now has been re-analyzed by sex.

View Article and Find Full Text PDF

In the United States, individuals with disabilities and those aged ≥65 can supplement their Medicare with so-called stand-alone Medicare Part D prescription drug plans. Beneficiaries can switch their stand-alone prescription drug plans annually, but most do not. Indirect evidence has raised concerns that non-switchers do not even make plan comparisons (labeled "inattention"), but direct evidence is scarce.

View Article and Find Full Text PDF

Pediatric malignancies frequently harbor chromosomal translocations that induce expression of fusion oncoproteins. The EWSR1-FLI1 fusion oncoprotein acts as a neomorphic transcription factor and is the dominant genetic driver of Ewing's sarcoma. Interrogation of the mechanisms by which EWSR1-FLI1 drives tumorigenesis has been limited by a lack of model systems to precisely and selectively control its expression in patient-derived cell lines and xenografts.

View Article and Find Full Text PDF

Background: Social Support has multiple benefits for health and mental wellbeing. Its existence, and the extent to which it can be beneficial, is dependent upon the context in which it is provided, and the recipients' view of it. Social support has long been established as a 'buffer' to the negative impact of stressful life experiences.

View Article and Find Full Text PDF

Background: Little is known about the real-world use of systemic glucocorticoids to treat patients hospitalized with community-acquired pneumonia (CAP) outside of the intensive care unit (ICU).

Methods: This retrospective cohort study included 11,588 hospitalizations for CAP without chronic pulmonary disease at seven hospitals in Ontario, Canada. We report physician-level variation in the use of glucocorticoids and trends over time.

View Article and Find Full Text PDF

Altered metabolism is a hallmark of cancer; however, it has been difficult to specifically target metabolism in cancer for therapeutic benefit. Cancers with genetically defined defects in metabolic enzymes constitute a subset of cancers where targeting metabolism is potentially accessible. Hürthle cell carcinoma of the thyroid (HTC) tumors frequently harbor deleterious mitochondrial DNA (mtDNA) mutations in subunits of complex I of the mitochondrial electron transport chain (ETC).

View Article and Find Full Text PDF

The ACT Network was funded by NIH to provide investigators from across the Clinical and Translational Science Award (CTSA) Consortium the ability to directly query national federated electronic health record (EHR) data for cohort discovery and feasibility assessment of multi-site studies. NIH refunded the program for expanded research application to become "Evolve to Next-Gen ACT" (ENACT). In parallel, the US Food and Drug Administration has been evaluating the use of real-world data (RWD), including EHR data, as sources of real-world evidence (RWE) for its regulatory decisions involving drug and biological products.

View Article and Find Full Text PDF
Article Synopsis
  • Altered metabolism is a key characteristic of cancer, but specifically targeting it for treatment has been challenging.
  • Hürthle cell carcinoma (HTC) tumors often have harmful mutations in mitochondrial DNA that affect their energy production, which makes them vulnerable to lactate dehydrogenase (LDH) inhibitors.
  • Research identified ways that HTC cells can resist these LDH inhibitors, revealing two mechanisms: an increase in a different LDH isoform and specific mutations that confer resistance; however, the inhibitors still show potential effectiveness against complex I-mutant HTC.
View Article and Find Full Text PDF

Orphan cytotoxins are small molecules for which the mechanism of action (MoA) is either unknown or ambiguous. Unveiling the mechanism of these compounds may lead to useful tools for biological investigation and new therapeutic leads. In selected cases, the DNA mismatch repair-deficient colorectal cancer cell line, HCT116, has been used as a tool in forward genetic screens to identify compound-resistant mutations, which have ultimately led to target identification.

View Article and Find Full Text PDF

Objectives: Intra-abdominal sepsis is commonly diagnosed in the surgical population and remains the second most common cause of sepsis overall. Sepsis-related mortality remains a significant burden in the intensive care unit despite advances in critical care. Nearly a quarter of the deaths in people with heart failure are caused by sepsis.

View Article and Find Full Text PDF
Article Synopsis
  • - The Warburg effect highlights that many cancers, despite having oxygen, consume more glucose and produce lactate, but thyroid Hürthle cell carcinoma (HTC) shows reliance on mitochondrial respiration, especially with complex I defects.
  • - Researchers found that HTC cells with mitochondrial mutations struggle with respiration and rely on glycolysis for survival; CRISPR screening showed key glycolytic enzymes are crucial for these mutant cells.
  • - Targeting lactate production in complex I-deficient HTC cells can trigger an energy crisis leading to cell death, suggesting a potential therapeutic strategy for HTC and other cancers with similar mitochondrial issues.
View Article and Find Full Text PDF

Orphan cytotoxins are small molecules for which the mechanism of action (MoA) is either unknown or ambiguous. Unveiling the mechanism of these compounds may lead to useful tools for biological investigation and in some cases, new therapeutic leads. In select cases, the DNA mismatch repair-deficient colorectal cancer cell line, HCT116, has been used as a tool in forward genetic screens to identify compound-resistant mutations, which have ultimately led to target identification.

View Article and Find Full Text PDF

Mitochondrial electron transport chain (ETC) dysfunction due to mutations in the nuclear or mitochondrial genome is a common cause of metabolic disease in humans and displays striking tissue specificity depending on the affected gene. The mechanisms underlying tissue-specific phenotypes are not understood. Complex I (cI) is classically considered the entry point for electrons into the ETC, and in vitro experiments indicate that cI is required for basal respiration and maintenance of the NAD/NADH ratio, an indicator of cellular redox status.

View Article and Find Full Text PDF

Ewing sarcoma (EWS) is a pediatric malignancy driven by the EWSR1-FLI1 fusion protein formed by the chromosomal translocation t(11; 22). The small molecule TK216 was developed as a first-in-class direct EWSR1-FLI1 inhibitor and is in phase II clinical trials in combination with vincristine for patients with EWS. However, TK216 exhibits anti-cancer activity against cancer cell lines and xenografts that do not express EWSR1-FLI1, and the mechanism underlying cytotoxicity remains unresolved.

View Article and Find Full Text PDF

Muscle stem cells (MuSCs) experience age-associated declines in number and function, accompanied by mitochondrial electron transport chain (ETC) dysfunction and increased reactive oxygen species (ROS). The source of these changes, and how MuSCs respond to mitochondrial dysfunction, is unknown. We report here that in response to mitochondrial ROS, murine MuSCs directly fuse with neighboring myofibers; this phenomenon removes ETC-dysfunctional MuSCs from the stem cell compartment.

View Article and Find Full Text PDF

Background: Novel therapies are needed to improve outcomes for women diagnosed with ovarian cancer. Oncolytic viruses are multifunctional immunotherapeutic biologics that preferentially infect cancer cells and stimulate inflammation with the potential to generate antitumor immunity. Herein we describe (Orf virus (OrfV)), an oncolytic poxvirus, as a viral immunotherapy for ovarian cancer.

View Article and Find Full Text PDF

We propose a practical method for radiometrically calibrating cameras using widely available gaseous tritium light sources (). Along with the gain (conversion factor) and read noise level, the predictable photon flux of the source allows us to gauge the quantum efficiency. The design is easily reproducible with a 3D printer (three-dimensional printer) and three inexpensive parts.

View Article and Find Full Text PDF

Purpose: The purpose of this quality improvement project was to examine the feasibility of rapidly converting a Tai Chi program for older Veterans from face-to-face to virtual classes.

Methods: Eighteen Veterans attending our face-to-face Tai Chi course were invited to transition to virtual classes. Feasibility was defined as the ability of program staff and participants to successfully connect and complete the initial and subsequent classes by VA Video Connect (VVC) with little to no technical difficulties, participant ability to participate in the course without safety concerns, and favorable feedback from participants and program staff.

View Article and Find Full Text PDF

Objectives: The purpose of the present study was to assess and describe the severity of symptoms reported by Covid-19 positive patients who vaped (smoked e-cigarettes) when compared to those who did not vape or smoke at the time of the diagnosis of Covid-19.

Methods: Patients from this study are from a well-characterized patient cohort collected at Mayo Clinic between March 1, 2020 and February 28, 2021; with confirmed COVID-19 diagnosis defined as a positive result on reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assays from nasopharyngeal swab specimens. Among the 1734 eligible patients, 289 patients reported current vaping.

View Article and Find Full Text PDF

Earwitnesses to the 1963 assassination of President John F. Kennedy (JFK) did not agree about the location of the gunman even though their judgments about the number and timing of the gunshots were reasonably consistent. Even earwitnesses at the same general location disagreed.

View Article and Find Full Text PDF

Abdominal ultrasonography is increasingly used as a standard diagnostic test in veterinary practices, however, there is little published information regarding the effects of operator experience on image quality. In this prospective observer agreement study, image quality was assessed for abdominal ultrasound examinations performed by nine sonographers (three general practitioners, three credentialed veterinary technicians, and three board-certified specialists). Each sonographer independently performed abdominal ultrasound examinations on the same group of 4 sedated clinically healthy animals (3 dogs, 1 cat) using the same model machine and standardized presets.

View Article and Find Full Text PDF

Background: Post-mortem examination of the nervous system is a complex task that culminates in "brain cutting". It relies on expertise in neuroanatomy, clinical neurosciences, neuroimaging and experience in order to recognise the most subtle abnormalities. Like any specialist examination in medicine, it warrants formal training, a standardised approach and optimal conditions.

View Article and Find Full Text PDF

Hürthle cell lesions have been a diagnostic conundrum in pathology since they were first recognized over a century ago. Controversy as to the name of the cell, the origin of the cell, and even which cells in particular may be designated as such still challenge pathologists and confound those treating patients with a diagnosis of "Hürthle cell" anything within the diagnosis, especially if that anything is a sizable mass lesion. The diagnosis of Hürthle cell adenoma (HCA) or Hürthle cell carcinoma (HCC) has typically relied on a judgement call by pathologists as to the presence or absence of capsular and/or vascular invasion of the adjacent thyroid parenchyma, easy to note in widely invasive disease and a somewhat subjective diagnosis for minimally invasive or borderline invasive disease.

View Article and Find Full Text PDF

Substance use disorders are highly prevalent among forensic patients. They are associated with many challenges for patients with these problems, including their ability to rehabilitate and successfully move through secure forensic mental health services, as well as increasing risk for recidivism. Traditionally, forensic services have been more adept at focusing on and treating the primary mental health diagnosis alone and have been less likely to prioritise this co-occurring patient need.

View Article and Find Full Text PDF

As the COVID-19 pandemic continues to evolve around the world, it is important to examine its effect on societies and individuals, including health and social care (HSC) professionals. The aim of this study was to compare cross-sectional data collected from HSC staff in the UK at two time points during the COVID-19 pandemic: Phase 1 (May-July 2020) and Phase 2 (November 2020-January 2021). The HSC staff surveyed consisted of nurses, midwives, allied health professionals, social care workers and social workers from across the UK (England, Wales, Scotland, Northern Ireland).

View Article and Find Full Text PDF