Faculty Bibliography

Low-dose oral minoxidil (LDOM) has emerged as a widely used off-label treatment for different types of alopecia, showing a favorable safety profile and effectiveness. Despite its growing use, it is essential to understand the possible associated adverse events (AEs) and their appropriate management to optimize this therapy. The aim of this article was to comprehensively review the AEs of LDOM treatment, describing their frequency, risk factors, affected anatomical sites, and management strategies. A search in the PubMed and EMBASE databases was performed for studies published before 31 December 2024, reporting the treatment of any type of hair loss with oral minoxidil. The most frequent AE is hypertrichosis, occurring in approximately 15% of patients, with a higher incidence in women and patients with higher doses. Fluid retention affects 1.3-10% of patients, particularly women, and typically occurs within 1-3 months of treatment. Other cardiovascular AEs, such as tachycardia or dizziness, occur in fewer than 5% of cases and are usually mild and transient. Severe AEs, including pericardial effusion, are extremely rare and often linked to compounding errors comprising an excessive dose. Management strategies include dose reduction, pharmacological interventions like diuretics for edema, and lifestyle measures such as sodium restriction. In most cases, AEs resolve without the need for treatment discontinuation. The favorable safety profile of LDOM makes it a valuable therapeutic option for alopecia, though careful patient selection, dose titration, and monitoring are essential to minimize risks.

Nager and Rodriguez syndromes are rare craniofacial and limb disorders characterized by midface retrusion, micrognathia, absent thumbs and radial hypoplasia. These disorders result from haploinsufficiency of SF3B4 (splicing factor 3b, subunit 4), a component of the pre-mRNA spliceosomal machinery. Although the spliceosome is present and functions in all cells of the body, most spliceosomopathies - including Nager and Rodriguez syndromes - are cell- or tissue-specific in their pathology. To understand the pathomechanism underlying these conditions, we generated a Xenopus tropicalis sf3b4 mutant line using CRISPR/Cas9 gene-editing technology. Homozygous deletion of sf3b4 is detrimental to the development of cranial neural crest (NC)-derived cartilage progenitors. Temporal RNA-sequencing analyses of mutant embryos identified an increase in exon-skipping events, followed by important transcriptional changes associated with an enrichment for terms consistent with defects in NC cell migration and survival. We propose that disruption of these processes may underly the pathogenesis of Nager and Rodriguez syndromes.

Oral cavity cancer is associated with high morbidity and mortality, particularly with advanced stage diagnosis. Oral cavity cancer, typically squamous cell carcinoma (OSCC), is often preceded by oral potentially malignant disorders (OPMDs), which comprise eleven disorders with variable risks for malignant transformation. While OPMDs are clinical diagnoses, conventional oral exam followed by biopsy and histopathological analysis is the gold standard for diagnosis of OSCC. There is vast heterogeneity in the clinical presentation of OPMDs, with possible visual similarities to early-stage OSCC or even to various benign oral mucosal abnormalities. The diagnostic challenge of OSCC/OPMDs is compounded in the non-specialist or primary care setting. There has been significant research interest in technology to assist in the diagnosis of OSCC/OPMDs. Artificial intelligence (AI), which enables machine performance of human tasks, has already shown promise in several domains of medical diagnostics. Computer vision, the field of AI dedicated to the analysis of visual data, has over the past decade been applied to clinical photographs for the diagnosis of OSCC/OPMDs. Various methodological concerns and limitations may be encountered in the literature on OSCC/OPMD image analysis. This narrative review delineates the current landscape of AI clinical photograph analysis in the diagnosis of OSCC/OPMDs and navigates the limitations, methodological issues, and clinical workflow implications of this field, providing context for future research considerations.

RGS8-associated paraneoplastic neurologic syndrome (PNS) is a recently-described disorder associated with lymphomas and typically presenting with severe, rapidly-progressing cerebellar dysfunction. We describe a patient who presented with mild signs of cerebellar dysfunction, including ocular motor abnormalities and impaired tandem gait. CSF showed elevated protein and a neural-restricted antibody pattern. Mesenteric lymphadenopathy on abdominal CT was biopsied and diagnosed as follicular B-cell lymphoma. After four years, the previously-detected antibody pattern was identified as RGS8 antibodies. This case describes the first RGS8-PNS patient presenting with a subtle and ocular motor predominant cerebellar syndrome with low-grade lymphoma.

Alzheimer's disease (AD) arises from complex multilevel interactions between genetic, epigenetic, and environmental factors. Recent studies suggest that exposure to the environmental and occupational toxicant formaldehyde (FA) may play a significant role in AD development. However, the effects of FA exposure on Aβ and tau pathologies in human neural cell 3D culture systems remain unexplored. To investigate FA's role in AD initiation, we differentiated 3D-cultured immortalized human neural progenitor ReN cells (ReNcell VM) into neurons and glial cells, followed by FA treatment. FA exposure for 12 weeks resulted in a dose-dependent increase in Aβ40, Aβ42, and phosphorylated tau levels. To further examine FA's role in AD progression, we established a 3D human neural cell culture AD model by transfecting ReN cells with AD-related mutant genes, including mutant APP and PSEN1, which recapitulate key AD pathological events. Our findings demonstrate that FA exposure significantly elevated Aβ40, Aβ42, and phosphorylated tau levels in this 3D-cultured AD model. These results suggest that FA exposure contributes to the initiation and progression of AD pathology in 3D-cultured human neural cells.

Understanding the "fit" of models designed to predict binary outcomes has been a long-standing problem across the social sciences. We propose a flexible, portable, and intuitive metric for quantifying the change in accuracy between two predictive systems in the case of a binary outcome: the InterModel Vigorish (IMV). The IMV is based on an analogy to weighted coins, well-characterized physical systems with tractable probabilities. The IMV is always a statement about the change in fit relative to some baseline model-which can be as simple as the prevalence-whereas other metrics are stand-alone measures that need to be further manipulated to yield indices related to differences in fit across models. Moreover, the IMV is consistently interpretable independent of baseline prevalence. We contrast this metric with alternatives in numerous simulations. The IMV is more sensitive to estimation error than many alternatives and also shows distinctive sensitivity to prevalence. We consider its performance using examples spanning the social and natural sciences. The IMV allows for precise answers to questions about changes in model fit in a variety of settings in a manner that will be useful for furthering research and the understanding of social outcomes.

Up to half of individuals with depression do not respond to first-line treatments, possibly due to a lack of treatment interventions informed by neurobiology. A novel therapeutic approach for depression has recently emerged from translational work targeting aberrant activity of ventral tegmental area (VTA) dopamine neurons via modulation of the KCNQ voltage-gated potassium channels. In this study, individuals with major depressive disorder (MDD) with elevated anhedonia were randomized to five weeks of the KCNQ channel opener, ezogabine (up to 900 mg/day) or placebo. Participants completed functional MRI during a monetary anticipation task and resting-state at baseline and at end-of-treatment. The clinical results were reported previously. Here, we examined VTA activity during monetary anticipation and resting-state functional connectivity between the VTA and the ventromedial prefrontal cortex (mesocortical pathway) and ventral striatum (mesolimbic pathway) at baseline and end-of-treatment. Results indicated a significant drug-by-time interaction in VTA activation during anticipation (F_(1,34) = 4.36, p = 0.044), where VTA activation was reduced from pre-to-post ezogabine, compared to placebo. Mesocortical functional connectivity was also higher in depressed participants at baseline compared to a healthy control group (t₍₅₆₎ = 2.68, p = 0.01) and associated with VTA hyper-activity during task-based functional MRI at baseline (R = 0.352, p = 0.033). Mesocortical connectivity was also reduced from pre-to-post ezogabine, compared to placebo (significant drug-by-time interaction, F_(1,33) = 4.317, p = 0.046). Together this translational work is consistent with preclinical findings highlighting VTA hyper-activity in depression, and suggesting a mechanism of action for KCNQ channel openers in normalizing this hyper-activity in individuals with both depression and anhedonia.

This document is an update to the 2014 recommendations for optimizing the adequacy of bowel cleansing for colonoscopy from the US Multi-Society Task Force on Colorectal Cancer, which represents the American College of Gastroenterology and the American Society for Gastrointestinal Endoscopy. The US Multi-Society Task Force developed consensus statements and key clinical concepts addressing important aspects of bowel preparation for colonoscopy. The majority of consensus statements focus on individuals at average risk for inadequate bowel preparation. However, statements addressing individuals at risk for inadequate bowel preparation quality are also provided. The quality of a bowel preparation is defined as adequate when standard screening or surveillance intervals can be assigned based on the findings of the colonoscopy. We recommend the use of a split-dose bowel preparation regimen and suggest that a 2 L regimen may be sufficient. A same-day regimen is recommended as an acceptable alternative for individuals undergoing afternoon colonoscopy, but we suggest that a same-day regimen is an inferior alternative for individuals undergoing morning colonoscopy. We recommend limiting dietary restrictions to the day before a colonoscopy, relying on either clear liquids or low-fiber/low-residue diets for the early and midday meals. We suggest the adjunctive use of oral simethicone for bowel preparation before colonoscopy. Routine tracking of the rate of adequate bowel preparations at the level of individual endoscopists and at the level of the endoscopy unit is also recommended, with a target of >90% for both rates.

Extended reality (XR) modalities in health care are quickly evolving. There is a lack of systematically described developmental process and the "how to" execute a business-case guidance. This article formulates a systematic approach on the technical developmental steps and generation of business-case to guide the iterative development of an XR tool. An international expert group was established and several available frameworks related to entrepreneurship and business-case development were used to generate recommendations. Our ongoing experience with the development life cycle of an XR tool for cardiopulmonary resuscitation training is provided as a real-life case illustration. Market demand, value proposition, stakeholder analyses, and profitability scenarios are captured with a business model canvas. Developmental process is divided into 4 aspects: Desirability, Feasibility, Viability, and Scalability. Technical- and Investment Readiness Level models are used in defining the technical feasibility and the business viability and scalability, respectively. Best practice recommendations including examples are provided. Health care professionals, health care financers, and health care policymakers are urged to consider the provided systematic approach and recommendations prior to starting a venture with XR.

Rogers' teaching of changes in her science is briefly presented. Selective ideas of teaching Rogers' science are discussed. The question "Who is Martha Rogers?" provides the bases to understand Rogers' pattern manifestations as a person. Changing scientific theoretical ideas support Rogers' perspective of the paranormal. A call to continue the birthing of Rogers' science is made.