Self-Trephination in Cranial Excoriation Disorder.

BACKGROUND AND IMPORTANCE: Trephination is a procedure in which a small hole is made in the skull. Rare cases of self-trephination by individuals seeking medical benefit have been reported. Excoriation disorder is a compulsive skin-picking condition in which an individual self-inflicts cutaneous lesions. Left untreated, severe excoriation disorder can pose significant health risks. CLINICAL PRESENTATION: Here, we describe 5 patients who presented with self-trephination due to a severe form of compulsive cranial excoriation at 2 neighboring academic medical centers over a 4-year period. We review the clinical presentation of self-trephination in cranial excoriation disorder and associated risk factors, surgical and nonsurgical interventions, complications of the disease, treatments, and mortality. Defining clinical characteristics include repetitive self-induced destruction of the scalp and skull with entry into the intracranial compartment, frequent psychiatric comorbidities, infection or injury of the brain with consequent neurological morbidity or mortality, and frequent treatment failures because of poor adherence. CONCLUSION: Self-trephination in cranial excoriation disorder is a severe neuropsychological disorder and neurosurgical emergency that exposes the brain and is often life-threatening. Appropriate therapy requires antibiotics, surgical debridement and repair of the wound, and concomitant effective psychiatric management of the underlying compulsion, including the use of antidepressants and behavioral therapy.

Parental Education for the Prevention of Plagiocephaly.

INTRODUCTION: The American Academy of Pediatrics Back-to-Sleep Campaign significantly reduced infant mortality from sudden infant death syndrome. As a result of prolonged supine positioning, the incidence of deformational plagiocephaly has also risen 5-fold since its adoption. We aimed to improve the current educational paradigm for new parents with the goal of reducing the incidence of plagiocephaly within the confines of the Back-to-Sleep Campaign. We hypothesized that the early addition of plagiocephaly focused education for parents would reduce cephalic index, the ratio of head width to length, used as an easily measured objective proxy for positional plagiocephaly. METHODS: Children were screened at their newborn visit. Premature newborns and those diagnosed with craniofacial disorders were excluded. For those enrolled, biparietal and anteroposterior measurements of the head were obtained using manual calipers to obtain cephalic index. Subjects randomly assigned to the intervention group were shown a 2-minute video and given an educational pamphlet on methods to prevent plagiocephaly. Unpaired 2-sample t tests comparing mean differences in intervention and control were performed. RESULTS: Thirty-nine subjects were enrolled as of November 2023 with variable lengths of follow-up completed. The average baseline cephalic index for subjects in the control group was 82.7 and 83.8 for intervention group. Unpaired 2-sample t tests were performed at 2-, 4-, and 6-month time points to analyze the difference between groups. At 4 months, average cephalic index for subjects in the control and treatment group, respectively, was 90.6 and 83.4 (P = 0.02). SIGNIFICANCE: Parental education at the newborn visit led to decreases in cephalic index, a proxy for positional plagiocephaly, compared with control patients. This simple intervention has the potential to reduce parental stress and healthcare costs associated with the evaluation and treatment of plagiocephaly.

Chronic Glucocorticoid Exposure Induced an S1PR2-RORγ Axis to Enhance Hepatic Gluconeogenesis in Male Mice.

It is well established that chronic glucocorticoid exposure causes hyperglycemia. While glucocorticoid receptor (GR) stimulates hepatic gluconeogenic gene transcription, additional mechanisms are activated by chronic glucocorticoid exposure to enhance gluconeogenesis. We found that chronic glucocorticoid treatment activated sphingosine-1-phosphate (S1P)-mediated signaling. Hepatic knockdown of hepatic S1P receptor 1 (S1PR1) had no effect on chronic glucocorticoid-induced glucose intolerance but elevated fasting plasma insulin levels. In contrast, hepatic S1PR3 knockdown exacerbated chronic glucocorticoid-induced glucose intolerance without affecting fasting plasma insulin levels. Finally, hepatic S1PR2 knockdown attenuated chronic glucocorticoid-induced glucose intolerance and reduced fasting plasma insulin levels. Here, we focused on dissecting the role of S1PR2 signaling in chronic glucocorticoid response on glucose homeostasis. We found that chronic glucocorticoid-induced hepatic gluconeogenesis, gluconeogenic gene expression, and GR recruitment to the glucocorticoid response elements (GREs) of gluconeogenic genes were all reduced in hepatic S1PR2 knockdown male mice. Hepatic S1PR2 knockdown also enhanced glucocorticoid suppression of RAR-related orphan receptor γ (RORγ) expression. Hepatic RORγ overexpression in hepatic S1PR2 knockdown mice restored glucocorticoid-induced glucose intolerance, gluconeogenic gene expression, and GR recruitment to their GREs. Conversely, RORγ antagonist and the reduction of hepatic RORγ expression attenuated such glucocorticoid effects. Thus, chronic glucocorticoid exposure induces an S1PR2-RORγ axis to cooperate with GR to enhance hepatic gluconeogenesis. Overall, this work provides novel mechanisms of and pharmaceutical targets against steroid-induced hyperglycemia.

Heterozygous FOXJ1 Mutations Cause Incomplete Ependymal Cell Differentiation and Communicating Hydrocephalus.

Heterozygous mutations affecting FOXJ1, a transcription factor governing multiciliated cell development, have been associated with obstructive hydrocephalus in humans. However, factors that disrupt multiciliated ependymal cell function often cause communicating hydrocephalus, raising questions about whether FOXJ1 mutations cause hydrocephalus primarily by blocking cerebrospinal fluid (CSF) flow or by different mechanisms. Here, we show that heterozygous FOXJ1 mutations are also associated with communicating hydrocephalus in humans and cause communicating hydrocephalus in mice. Disruption of one Foxj1 allele in mice leads to incomplete ependymal cell differentiation and communicating hydrocephalus. Mature ependymal cell number and motile cilia number are decreased, and 12% of motile cilia display abnormal axonemes. We observed decreased microtubule attachment to basal bodies, random localization and orientation of basal body patches, loss of planar cell polarity, and a disruption of unidirectional CSF flow. Thus, heterozygous FOXJ1 mutations impair ventricular multiciliated cell differentiation, thereby causing communicating hydrocephalus. CSF flow obstruction may develop secondarily in some patients harboring FOXJ1 mutations. Heterozygous FOXJ1 mutations impair motile cilia structure and basal body alignment, thereby disrupting CSF flow dynamics and causing communicating hydrocephalus.

Transcriptional coactivation by EHMT2 restricts glucocorticoid-induced insulin resistance in a study with male mice.

The classical dogma of glucocorticoid-induced insulin resistance is that it is caused by the transcriptional activation of hepatic gluconeogenic and insulin resistance genes by the glucocorticoid receptor (GR). Here, we find that glucocorticoids also stimulate the expression of insulin-sensitizing genes, such as Irs2. The transcriptional coregulator EHMT2 can serve as a transcriptional coactivator or a corepressor. Using male mice that have a defective EHMT2 coactivation function specifically, we show that glucocorticoid-induced Irs2 transcription is dependent on liver EHMT2's coactivation function and that IRS2 play a key role in mediating the limitation of glucocorticoid-induced insulin resistance by EHMT2's coactivation. Overall, we propose a model in which glucocorticoid-regulated insulin sensitivity is determined by the balance between glucocorticoid-modulated insulin resistance and insulin sensitizing genes, in which EHMT2 coactivation is specifically involved in the latter process.

Distance Learning and Spaced Review to Complement Dermoscopy Training for Primary Care.

BACKGROUND: Dermoscopy aids in skin cancer identification. For family physicians who use dermoscopy, there is higher sensitivity for melanoma detection than naked-eye examination. There is a shortage of dermoscopy training for primary care providers. The triage amalgamated dermoscopic algorithm (TADA) is designed for novice dermoscopists. While TADA can be taught in a short dermoscopy workshop, spaced review and blended learning strategies improve knowledge retention. OBJECTIVES: This study determined the impact that the addition of a distance learning platform has on clinical dermoscopy use. Moreover, it evaluated dermoscopic image identification (knowledge retention) following the addition of distance learning via Extension for Community Health Outcomes (ECHO) to a traditional TADA dermoscopy workshop. METHODS: Primary care providers voluntarily attended a 120-minute TADA dermoscopy workshop. Participants completed pre-intervention, post-TADA, and post-ECHO tests of 30 dermoscopic images of benign and malignant skin lesions. A survey was also administered to analyze clinical dermoscopy use and prior dermoscopy training. RESULTS: Twenty-seven residents, faculty, and advanced practice providers participated in this longitudinal observational cohort study. Mean test scores (out of 30) for images of benign and malignant lesions improved from 20.29 pre-intervention to 24.62 post-TADA and 27.63 post-ECHO (P < .001). On average, participants attended 4 ECHO sessions (out of 7 total) and there was a positive correlation (r = 0.77) between the number of ECHOs attended and post-ECHO scores. Dermoscope use increased from 37.0% to 96.3% (P < .001). CONCLUSION: Distance learning and spaced review complement dermoscopy workshop training for primary care.

Public R&D Investments and Private-sector Patenting: Evidence from NIH Funding Rules.

We quantify the impact of scientific grant funding at the National Institutes of Health (NIH) on patenting by pharmaceutical and biotechnology firms. Our paper makes two contributions. First, we use newly constructed bibliometric data to develop a method for flexibly linking specific grant expenditures to private-sector innovations. Second, we take advantage of idiosyncratic rigidities in the rules governing NIH peer review to generate exogenous variation in funding across research areas. Our results show that NIH funding spurs the development of private-sector patents: a $10 million boost in NIH funding leads to a net increase of 2.3 patents. Though valuing patents is difficult, we report a range of estimates for the private value of these patents using different approaches.

The applied value of public investments in biomedical research.

Scientists and policy-makers have long argued that public investments in science have practical applications. Using data on patents linked to U.S. National Institutes of Health (NIH) grants over a 27-year period, we provide a large-scale accounting of linkages between public research investments and subsequent patenting. We find that about 10% of NIH grants generate a patent directly but 30% generate articles that are subsequently cited by patents. Although policy-makers often focus on direct patenting by academic scientists, the bulk of the effect of NIH research on patenting appears to be indirect. We also find no systematic relationship between the "basic" versus "applied" research focus of a grant and its propensity to be cited by a patent.

The Forensic Lens: Bringing Elder Neglect Into Focus in the Emergency Department.

We present 2 case studies of older patients who were brought to the emergency department (ED) in severely debilitated states. Both presented with severe malnutrition, contractures, and decubitus ulcers, and were nonverbal, with histories of dementia and end-stage disease. Their primary caregivers, adult children, were uncooperative with Adult Protective Services and disregarded treatment recommendations. Although both elders had signs suspicious for neglect, a comprehensive review revealed many layers of complexity. We use these cases to illustrate an approach to the assessment of possible elder neglect in ED settings and how to intervene to ensure patient safety. We begin with a discussion of the differences between willful, unintentional, and unsubstantiated neglect by a caregiver and then describe when to suspect neglect by evaluating the elder, interviewing the caregiver and first responders, assessing the caregiver's ability to meet the elder's needs, and, if possible, obtaining medical history and information about the home care environment. These cases illustrate the importance of careful documentation in cases of suspected neglect to assist investigative agencies, reduce the risk of further harm, and improve patient outcomes.

Research funding. Big names or big ideas: do peer-review panels select the best science proposals?

This paper examines the success of peer-review panels in predicting the future quality of proposed research. We construct new data to track publication, citation, and patenting outcomes associated with more than 130,000 research project (R01) grants funded by the U.S. National Institutes of Health from 1980 to 2008. We find that better peer-review scores are consistently associated with better research outcomes and that this relationship persists even when we include detailed controls for an investigator's publication history, grant history, institutional affiliations, career stage, and degree types. A one-standard deviation worse peer-review score among awarded grants is associated with 15% fewer citations, 7% fewer publications, 19% fewer high-impact publications, and 14% fewer follow-on patents.