Correlation Between the Warrior/Worrier Gene on Post Burn Pruritus and Scarring: A Prospective Cohort Study.

INTRODUCTION: Associations between genetic variation and clinical conditions suggest that single nucleotide polymorphisms (SNPs) might correlate with postburn outcomes. COMT modulates catecholamine metabolism, and polymorphisms within the rs4680 allele result in variable enzyme activity. Catechol-amines are known to modulate the inflammatory process and may affect scar formation. The aim of this study was to determine whether variants in the rs4680 SNP of the COMT gene are associated with post-burn pruritus and scarring. METHODS: Adult burn patients, admitted between 2007 and 2017, with deep partial-thickness burns or delayed healing provided blood samples for genotyp-ing and self-reported itch scores within 1 year of injury. Scarring was measured using the Vancouver Scar Scale (VSS). Itch scores ≥ 4 and VSS scores >7 were considered severe. Genomic deoxyribonucleic acid was genotyped for the rs4680 SNP using realtime polymerase chain reaction (PCR). RESULTS: Median itch and VSS scores were highest for GG homozygotes and lowest for AA homozygotes. This difference was statistically significant for VSS score (P < 0.0001) and approached significance for itch (P = 0.052). After accounting for confounding variables, including race/ethnicity, age, sex, and burn size, the GG homozygotes demonstrated worse scarring (odds ratio 1.88, P = 0.005) compared to AG heterozygotes whereas the AA homozygotes trended towards a protective effect against scarring (odds ratio 0.71, P = 0.10). itch did not demonstrate a statistically significant difference between rs4680 genotype. CONCLUSIONS: Our analysis identifies a trend between COMT genotype with scarring, with rs4680 genetic variation constituting an independent risk factor for VSS score.

Impact of genetic predisposition to late-onset neurodegenerative diseases on early life outcomes and brain structure.

Most patients with late-onset neurodegenerative diseases such as Alzheimer's and Parkinson's have a complex aetiology resulting from numerous genetic risk variants of small effects located across the genome, environmental factors, and the interaction between genes and environment. Over the last decade, genome-wide association studies (GWAS) and post-GWAS analyses have shed light on the polygenic architecture of these diseases, enabling polygenic risk scores (PRS) to estimate an individual's relative genetic liability for presenting with the disease. PRS can screen and stratify individuals based on their genetic risk, potentially years or even decades before the onset of clinical symptoms. An emerging body of evidence from various research studies suggests that genetic susceptibility to late-onset neurodegenerative diseases might impact early life outcomes, including cognitive function, brain structure and function, and behaviour. This article summarises recent findings exploring the potential impact of genetic susceptibility to neurodegenerative diseases on early life outcomes. A better understanding of the impact of genetic susceptibility to neurodegenerative diseases early in life could be valuable in disease screening, detection, and prevention and in informing treatment strategies before significant neural damage has occurred. However, ongoing studies have limitations. Overall, our review found several studies focused on APOE haplotypes and Alzheimer's risk, but a limited number of studies leveraging polygenic risk scores or focused on genetic susceptibility to other late-onset conditions.

The genetic identity of the Vedda: A language isolate of South Asia.

Linguistic data from South Asia identified several language isolates in the subcontinent. The Vedda, an indigenous population of Sri Lanka, are the least studied amongst them. Therefore, to understand the initial peopling of Sri Lanka and the genetic affinity of the Vedda with other populations in Eurasia, we extensively studied the high-resolution autosomal and mitogenomes from the Vedda population of Sri Lanka. Our autosomal analyses suggest a close genetic link of Vedda with the tribal populations of India despite no evidence of close linguistic affinity, thus suggesting a deep genetic link of the Vedda with these populations. The mitogenomic analysis supports this association by pointing to an ancient link with Indian populations. We suggest that the Vedda population is a genetically drifted group with limited gene flow from neighbouring Sinhalese and Sri Lankan Tamil populations. Interestingly, the genetic ancestry sharing of Vedda neglects the isolation-by-distance model. Collectively, the demography of Sri Lanka is unique, where Sinhalese and Sri Lankan Tamil populations excessively admixed, whilst Vedda largely preserved their isolation and deep genetic association with India.

Impact of the affordable care act's medicaid expansion on burn outcomes and disposition.

BACKGROUND: We aimed to analyze the impact of the Affordable Care Act's Medicaid Expansion on clinical outcomes and patient disposition after burn injury. We hypothesized that increased insurance coverage results in improved outcomes and higher rates of discharge to inpatient rehabilitation. METHODS: We reviewed the University of Washington Regional Burn Center registry data for patients admitted from 2011 to 2018. Patients were grouped into two categories: before (2011-2013) and after (2015-2018) Medicaid expansion; we excluded 2014 data to serve as a washout period. Outcomes assessed included length of hospital stay, patient disposition, and mortality. Multivariable logistic and linear regression models with covariates for sex, age, burn size, ethnicity ethnicity, distance from burn center, etiology of burn, and presence of inhalation injury were used to determine the impact of Medicaid expansion on outcomes. RESULTS: Rates of uninsured patients decreased while Medicaid coverage increased. Despite increased median burn size after Medicaid expansion, inpatient mortality rates did not change, but average acute care length of stay increased. More patients were discharged to rehabilitation centers. CONCLUSIONS: Our study corroborates prior findings of increased insurance coverage since Medicaid expansion. Increased insurance coverage is associated with higher rates of discharge to inpatient rehabilitation programs after burn injury.

Ephrin-A3 is required for tonotopic map precision and auditory functions in the mouse auditory brainstem.

Tonotopy is a prominent feature of the vertebrate auditory system and forms the basis for sound discrimination, but the molecular mechanism that underlies its formation remains largely elusive. Ephrin/Eph signaling is known to play important roles in axon guidance during topographic mapping in other sensory systems, so we investigated its possible role in the establishment of tonotopy in the mouse cochlear nucleus. We found that ephrin-A3 molecules are differentially expressed along the tonotopic axis in the cochlear nucleus during innervation. Ephrin-A3 forward signaling is sufficient to repel auditory nerve fibers in a developmental stage-dependent manner. In mice lacking ephrin-A3, the tonotopic map is degraded and isofrequency bands of neuronal activation upon pure tone exposure become imprecise in the anteroventral cochlear nucleus. Ephrin-A3 mutant mice also exhibit a delayed second wave in auditory brainstem responses upon sound stimuli and impaired detection of sound frequency changes. Our findings establish an essential role for ephrin-A3 in forming precise tonotopy in the auditory brainstem to ensure accurate sound discrimination.

A New Source of Nonprofit Neurosurgical Funding.

The purpose of this paper is to propose and qualify a novel funding mechanism for international neurosurgical nonprofits. The article first identifies and explains neurosurgeons' means for practicing in the developing world through a literature review. After this examination of the current funding methods for surgical care in low-income regions, the work transitions to an explanation of the applications and limitations of a new resource: the internal wealth of a developing country. This wealth may be leveraged by way of a for-profit hospital to create sustainable and domestic funding for nonprofit neurosurgical training. The applicability of the proposed mechanism extends beyond the field of neurosurgery to nonprofits in any health-related discipline. Factors influencing the viability of this mechanism (including local disease burden, economic trajectory, and political stability) are examined to create a baseline set of conditions for success.