Applications and advancements in animal models for antiviral research on mosquito-borne arboviruses.

Vector-borne diseases caused by arthropod-borne viruses (arboviruses) are a considerable challenge to public health globally. Mosquito-borne arboviruses, such as Chikungunya, Dengue, and Zika viruses, cause a range of human illnesses and may be fatal. Currently, efforts to control these diseases still face challenges due to growing vector resistance towards insecticides, urbanization, and limited effective antiviral treatments and vaccines. Animal models are crucial in antiviral research on mosquito-borne arboviruses, playing a role in understanding disease mechanisms, vaccine development, and toxicity testing, but the application of animal models still faces the challenges of ethical considerations and animal-to-human translational success. Genetically engineered mouse models, hamster models and non-human primate (NHP) are currently used in arbovirus research, but new models such as tree shrews and novel humanized mice are emerging. In the context of Malaysian research, the use of long-tailed macaques as potential NHP models for arbovirus research is possible; however, it faces the ethical dilemma of using an endangered species for scientific purposes. Overall, animal models play a crucial role in advancing infectious disease research, but a balance between medical research and species conservation must be upheld.

Standardizing Physical Activity Monitoring in Patients With Degenerative Lumbar Disorders.

BACKGROUND AND OBJECTIVES: Degenerative thoracolumbar disorders (DTDs) typically cause pain and functional impairment. However, little is known regarding the DTD impact on patient's real-life physical activity. The objective of this study is to validate a wearable measure of physical activity monitoring in patients with DTD and to create gender- and sex-specific performance thresholds that are standardized to the mean of a control population. METHODS: A commercially available smartwatch (Apple Watch) was used to monitor preoperative physical activity in patients undergoing surgery for DTD. Mean preoperative physical activity 2 weeks before the scheduled surgery was expressed as raw step count. Standardized z-scores were referenced to age- and sex-specific values of a control population from a large public database. Step counts were assessed for convergent validity with established patient-reported outcome measures, and impairment in activity was stratified into performance groups based on z-score cutoff values. RESULTS: Sixty-five patients (62% female) with a mean (±SD) age of 63.8 (±12.8) years had a mean preoperative daily step count of 5556 (±3978). Physical activity showed significant correlation with patient-reported outcome measures, including Oswestry disability index (r = -0.26, 95% CI: -0.47-0.01), 36-Item Short Form Survey Physical Component Summary score (r = 0.30, 95% CI: 0.06-0.51), and Patient-Reported Outcomes Measurement Information System Physical Function (r = 0.49, 95% CI: 0.27-0.65). "No," "Mild," "moderate," and "severe impairment" in activity performance were defined as corresponding z-scores of >0, 0 to -0.99, -1 to -1.99, and ≤-2, accounting for 22%, 34%, 40%, and 5% of the study population. Each one-step category increase in activity impairment resulted in increased subjective disability as measured by the Oswestry Disability Index, 36-Item Short Form Survey Physical Component Summary, and Patient-Reported Outcomes Measurement Information System Physical Function (all P -values <.05). CONCLUSION: We establish the first wearable objective measure of real-life physical activity for patients with DTD, with the first age- and sex-adjusted standard scores to enable clinicians and researchers to set treatment goals and directly compare activity levels between individual patients with DTD and normal controls.

Socioeconomic disparities in lumbar fusion rates were exacerbated during the COVID-19 pandemic.

Background: The COVID-19 pandemic disrupted healthcare access and utilization throughout the US, with variable impact on patients of different socioeconomic status (SES) and race. We characterize pre-pandemic and pandemic demographic and SES trends of lumbar fusion patients in the US. Methods: Adults undergoing first-time lumbar fusion 1/1/2004-3/31/2021 were assessed in Clinformatics® Data Mart for patient age, geographical location, gender, race, education level, net worth, and Charlson Comorbidity Index (CCI). Multivariable regression models were used to evaluate the significance of trends over time, with a focus on pandemic trends 2020-2021 versus previous trends 2004-2019. Results: The total 217,204 patients underwent lumbar fusions, 1/1/2004-3/31/2021. The numbers and per capita rates of lumbar fusions increased 2004-2019 and decreased in 2020 (first year of COVID-19 pandemic), with large variation in geographic distribution. There was overall a significant decrease in proportion of White patients undergoing lumbar fusion over time (OR=0.997, p<.001), though they were more likely to undergo surgery during the pandemic (OR=1.016, p<.001). From 2004-2021, patients were more likely to be educated beyond high school. Additionally, patients in the highest (>$500k) and lowest (<$25k) net worth categories had significantly more fusions over time (p<.001). During the pandemic (2020-2021), patients in higher net worth groups were more likely to undergo lumbar fusions ($150k-249k & $250k-499k: p<.001) whereas patients in the lowest net worth group had decreased rate of surgeries (p<.001). Lastly, patients' CCI increased significantly from 2004 to 2021 (coefficient=0.124, p<.001), and this trend held true during the pandemic (coefficient=0.179, p<.001). Conclusions: To the best of our knowledge, our work represents the most comprehensive and recent characterization of SES variables in lumbar fusion rates. Unsurprisingly, lumbar fusions decreased overall with the onset of the COVID-19 pandemic. Importantly, disparities in fusion patients across patient race and wealth widened during the pandemic, reversing years of progress, a lesson we can learn for future public health emergencies.

Neighborhood Deprivation is Associated With Increased Postoperative Complications After Implant-Based Breast Reconstruction.

PURPOSE: The Area Deprivation Index (ADI) ranks neighborhoods by deprivation based on US Census data. This study utilizes ADI scores to investigate the impact of neighborhood deprivation on complication rates following breast reconstruction. PATIENTS AND METHODS: Patients who received implant-based reconstruction from 2019 to 2023 were identified at a single institution in New York. Patients were linked to a state-specific ADI score and categorized into groups: "High ADI" (6-10) and "Low ADI" (1-5). Patient characteristics and complication rates were compared between the ADI groups with Chi-Square analysis and t-tests. The predictive value of ADI scores on complication rates was assessed using logistic regression models. RESULTS: In total, 471 patients were included, of which 16% (n = 73) were in the High ADI group, and 84% (n = 398) were in the Low ADI group. There were no baseline differences between the 2 groups, except that there were more patients of Hispanic descent in the High ADI group (30% vs. 15%, P < .01). The High ADI group had a higher overall complication rate than the Low ADI group (34% vs. 21%, P < .01), as well as higher individual rates of hematoma (12% vs. 3%, P < .01) and unexpected reoperations (18% vs. 7%, P < .01). After adjusting for differences in race, High ADI scores predicted hematoma, reoperations, and any complication (P < .05). CONCLUSION: Patients living in neighborhoods with high ADI had a higher incidence of postoperative complications, independent of comorbidities and race. This measure of disparity should be considered when counselling patients about their risk of complications following procedures like implant-based breast reconstruction.

Standardizing Continuous Physical Activity Monitoring in Patients with Cervical Spondylosis.

STUDY DESIGN/SETTING: Prospective cohort study. OBJECTIVE: To use a commercial wearable device to measure real-life, continuous physical activity in patients with CS and to establish age-adjusted and sex-adjusted standardized scores. SUMMARY OF BACKGROUND DATA: Patients with cervical spondylosis (CS) often present with pain or neurologic deficits that result in functional limitations and inactivity. However, little is known regarding the influence of CS on the patient's real-life physical activity. METHODS: This study included 100 English-speaking adult patients with cervical degenerative diseases undergoing elective spine surgery at Stanford University who owned iPhones. Patients undergoing surgery for spine infections, trauma, tumors, or lumbar degenerative disease were excluded. Activity two weeks before surgery was expressed as raw daily step counts. Standardized z-scores were calculated based on age-specific and sex-specific values of a control population. Responses to patient-reported outcome measures (PROMs) surveys assessed convergent validity. Functional impairment was categorized based on predetermined z-score cut-off values. RESULTS: Thirty CS with a mean (±SD) age of 56.0 (±13.4) y wore an Apple Watch for ≥8 hours/day in 87.1% of the days. The mean watch wear time was 15.7 (±4.2) hours/day, and the mean daily step count was 6400 (±3792). There was no significant difference in activity between 13 patients (43%) with myelopathy and 17 (57%) without myelopathy. Test-retest reliability between wearable step count measurements was excellent (ICC ß=0.95). Physical activity showed a moderate positive correlation with 36-Item Short Form Survey Physical Component Summary, EuroQol-5-dimension visual analog scale, and Patient-Reported Outcomes Measurement Information System Physical Function Subscale. Activity performance was classified into categories of "no impairment" [step count=9640 (±2,412)], "mild impairment" [6054(±816)], "moderate impairment" [3,481 (±752)], and "severe impairment" [1,619 (±240)]. CONCLUSION: CS patients' physical activity is significantly lower than the general population or the frequently stated goals of 7000 to 10,000 steps/day. Standardized, continuous wearable physical activity monitoring in CS is a reliable, valid, and normalized outcome tool that may help characterize functional impairment before and after spinal interventions.

Early-life stress alters chromatin modifications in VTA to prime stress sensitivity.

Early-life stress increases sensitivity to subsequent stress, which has been observed among humans, other animals, at the level of cellular activity, and at the level of gene expression. However, the molecular mechanisms underlying such long-lasting sensitivity are poorly understood. We tested the hypothesis that persistent changes in transcription and transcriptional potential were maintained at the level of the epigenome, through changes in chromatin. We used a combination of bottom-up mass spectrometry, viral-mediated epigenome-editing, behavioral quantification, and RNA-sequencing in a mouse model of early-life stress, focusing on the ventral tegmental area (VTA), a brain region critically implicated in motivation, reward learning, stress response, and mood and drug disorders. We find that early-life stress in mice alters histone dynamics in VTA and that a majority of these modifications are associated with an open chromatin state that would predict active, primed, or poised gene expression, including enriched histone-3 lysine-4 methylation and the H3K4 monomethylase Setd7. Mimicking ELS through over-expression of Setd7 and enrichment of H3K4me1 in VTA recapitulates ELS-induced behavioral and transcriptional hypersensitivity to future stress. These findings enrich our understanding of the epigenetic mechanisms linking early-life environmental experiences to long-term alterations in stress reactivity within the brain's reward circuitry, with implications for understanding and potentially treating mood and anxiety disorders in humans.

Evaluation of an individual examination remediation policy in a professional pharmacy course.

INTRODUCTION: Maintaining institutional remediation policies is required for pharmacy education accreditation, but specific policies and students' perceptions of remediation are not well described in the literature. The purpose of this research was to determine whether the individual examination remediation policy utilized in a biomedical literature evaluation course was a viable approach to ensuring positive student experiences and success. METHODS: This study utilized a pre-/post-quantitative survey design. An 11-item pre-remediation questionnaire was offered to all students enrolled in the course in 2022. A matched post-survey was administered to students eligible to remediate individual examinations. Survey items were assessed using a five-point Likert rating. Remediation examination grades were analyzed in aggregate. Descriptive statistics were utilized as appropriate. RESULTS: One hundred of the 108 (92.5%) enrolled students completed the pre-remediation survey. Students strongly agreed they would prefer to remediate individual examinations instead of taking one cumulative course remediation examination (median 5) and that remediating would improve their understanding of course material (median 5). Nineteen (44%) of 43 students eligible for individual examination remediation chose to remediate, and 16 (37%) responded to the post-remediation survey. Among those eligible, the most common reason for remediating was desire to receive a better score. Significantly more students improved their examination scores through remediation. CONCLUSIONS: Students in the course preferred to remediate individual examinations, but only 44% of students eligible to remediate chose to do so. Future studies with larger sample sizes and course outcome data are warranted to further explore examination remediation in professional pharmacy courses.

A Metagenomic Survey of Wood Decay Fungi in the Urban Trees of Singapore.

Mature tropical urban trees are susceptible to root and trunk rot caused by pathogenic fungi. A metagenomic survey of such fungi was carried out on 210 soil and tissue samples collected from 134 trees of 14 common species in Singapore. Furthermore, 121 fruiting bodies were collected and barcoded. Out of the 22,067 OTUs (operational taxonomic units) identified, 10,646 OTUs had annotation information, and most were either ascomycetes (63.4%) or basidiomycetes (22.5%). Based on their detection in the diseased tissues and surrounding soils and/or the presence of fruiting bodies, fourteen basidiomycetes (nine Polyporales, four Hymenochaetales, one Boletales) and three ascomycetes (three species of Scytalidium) were strongly associated with the diseased trees. Fulvifomes siamensis affected the largest number of tree species surveyed. The association of three fungi was further supported by in vitro wood decay studies. Genetic heterogeneity was common in the diseased tissues and fruiting bodies (Ganoderma species especially). This survey identified the common pathogenic fungi of tropical urban trees and laid the foundation for early diagnosis and targeted mitigation efforts. It also illustrated the complexity of fungal ecology and pathogenicity.

High prevalence of cranial asymmetry exists in infants with neonatal brachial plexus palsy.

PURPOSE: This study aimed to: 1) evaluate the prevalence of cranial asymmetry (positional plagiocephaly) in infants with neonatal brachial plexus palsy (NBPP); 2) examine the association of patient demographics, arm function, and NBPP-related factors to positional plagiocephaly; and 3) determine percentage of spontaneous recovery from positional plagiocephaly and its association with arm function. METHODS: Infants < 1 year of age with NBPP and no previous exposure to plagiocephaly cranial remolding therapy or surgical intervention were recruited for this prospective cross-sectional study. Positional plagiocephaly (diagonal difference) measurements were captured using a fiberglass circumferential mold of the cranium. Included infants were divided into 2 groups: 1) those with positional plagiocephaly at most recent evaluation (plagio group), including infants with resolved positional plagiocephaly (plagio-resolved subgroup); and 2) those who never had positional plagiocephaly (non-plagio group). Standard statistics were applied. RESULTS: Eighteen of 28 infants (64%) had positional plagiocephaly. Delivery type might be predictive for plagiocephaly. Infants in the non-plagio group exhibited more active range of motion than infants in the plagio group. All other factors had no significant correlations. CONCLUSIONS: A high prevalence of positional plagiocephaly exists among the NBPP population examined. Parents and physicians should encourage infants to use their upper extremities to change position and reduce chance of cranial asymmetry.