Cross-Sectional Survey of Factors Contributing to COVID-19 Testing Hesitancy Among US Adults at Risk of Severe Outcomes from COVID-19.

INTRODUCTION: The United States Centers for Disease Control and Prevention (CDC) advises testing individuals for COVID-19 after exposure or if they display symptoms. However, a deeper understanding of demographic factors associated with testing hesitancy is necessary. METHODS: A US nationwide cross-sectional survey of adults with risk factors for developing severe COVID-19 ("high-risk" individuals) was conducted from August 18-September 5, 2023. Objectives included characterizing demographics and attitudes associated with COVID-19 testing. Inverse propensity weighting was used to weight the data to accurately reflect the high-risk adult US population as reflected in IQVIA medical claims data. We describe here the weighted results modeled to characterize demographic factors driving hesitancy. RESULTS: In the weighted sample of 5019 respondents at high risk for severe COVID-19, 58.2% were female, 37.8% were ≥ 65 years old, 77.1% were White, and 13.9% had a postgraduate degree. Overall, 67% were Non-testers (who indicated that they were unlikely or unsure of their likelihood of being tested within the next 6 months); these respondents were significantly more likely than Testers (who indicated a higher probability of testing within 6 months) to be female (60.2 vs. 54.1%; odds ratio [OR] [95% confidence interval (CI)], 1.3 [1.1‒1.4]), aged ≥ 65 years old (41.5 vs. 30.3%; OR [95% CI] compared with ages 18‒34 years, 0.6 [0.5‒0.7]), White (82.1 vs. 66.8%; OR [95% CI], 1.4 [1.1‒1.8]), and to identify as politically conservative (40.9 vs. 18.1%; OR [95% CI], 2.6 [2.3‒2.9]). In contrast, Testers were significantly more likely than Non-testers to have previous experience with COVID-19 testing, infection, or vaccination; greater knowledge regarding COVID-19 and testing; greater healthcare engagement; and concerns about COVID-19. CONCLUSIONS: Older, female, White, rural-dwelling, and politically conservative high-risk adults are the most likely individuals to experience COVID-19 testing hesitancy. Understanding these demographic factors will help guide strategies to improve US testing rates.

Assessing the stops framework for coping with intraoperative errors: Evidence of efficacy, hints of hubris, and a bridge to abridging burnout.

BACKGROUND: Answering calls in the literature, we developed and introduced an evidence-based tool for surgeons facing errors in the operating room: the STOPS framework (stop, talk to you team, obtain help, plan, succeed). The purpose of this research was to assess the impact of presenting this psychological tool on resident coping in the operating room and the related outcome of burnout while examining sex differences. METHODS: In a natural experiment, general surgery residents were invited to attend 2 separate educational conferences regarding coping with errors in the operating room. Three months later, all residents were asked to fill out a survey assessing their coping in the operating room, level of burnout, and demographics. We assessed the impact of the educational intervention by comparing those who attended the coping conferences with those who did not attend. RESULTS: Thirty-five residents responded to the survey (65% response rate, 54% female respondents, 49% junior residents). Our hypothesized moderated mediation model was supported. Sex was found to moderate the impact of the STOPS framework-female residents who attended the coping educational conference reported higher coping self-efficacy, whereas attendance had no statistically significant impact on male levels of coping self-efficacy. In turn, higher coping self-efficacy was associated with lower levels of burnout. CONCLUSION: Our results suggest that there is evidence of efficacy in this instruction-female residents presented this material report higher levels of coping in the operating room compared to those who did not receive the framework. Further, increase in coping ability was associated with reduced levels of burnout for both genders.

Complete genome sequence of the Streptomyces bacteriophage Amabiko.

Amabiko is a lytic subcluster BE2 bacteriophage that infects Streptomyces scabiei-a bacterium causing common scab in potatoes. Its 131,414 bp genome has a GC content of 49.5% and contains 245 putative protein-coding genes, 45 tRNAs, and one tmRNA. Amabiko is closely related to Streptomyces bacteriophage MindFlayer (gene content similarity: 86.5%).

The Impact of Personalized versus Standardized Cardiorespiratory and Muscular Training on Health-Related Outcomes and Rate of Responders.

Recent research has shown more favorable training adaptations for inactive adults when cardiorespiratory fitness (CRF) exercise is prescribed with the use of ventilatory thresholds compared to percentages of heart rate reserve (HRR). However, there is limited research on changes in health-related outcomes with the use of these CRF methods in combination with muscular fitness exercises. The objective of this study was to compare the effectiveness of two training programs for improving CRF, muscular fitness, and cardiometabolic risk factors. Inactive men and women (n=109, aged 49.3±15.5 years) were randomized to a non-exercise control group or one of two exercise training groups. The exercise training groups consisted of 13 weeks of structured exercise with progression using either CRF exercise prescribed with the use of ventilatory thresholds and functional training for muscular fitness (THRESH group) or HRR and traditional muscular fitness training (STND group). After the 13-week protocol, there were significant differences in body weight, body composition, systolic blood pressure, high-density lipoprotein cholesterol (HDL-c), VO2max, 5-repetition maximum (RM) bench press, and 5-RM leg press for both treatment groups compared to the control group after controlling for baseline values. However, the THRESH group had significantly more desirable outcomes for VO2max, 5-RM bench press, 5-RM leg press, body composition, and HDL-c when compared to both the STND and control group. Additionally, the proportion of individuals estimated as likely to respond above 3.5 mL·kg-1·min-1 in VO2max (i.e., the minimal clinically important difference) was 76.4%, 20.8%, and 0.13% for the THRESH, STND, and control groups, respectively. While both exercise programs elicited favorable health-related adaptations after 13 weeks, these results suggest that a personalized program with exercise prescribed based on ventilatory threshold and with the use of functional muscular fitness training may yield greater training adaptations.

Implementation of a Brief Evidence-Based Intraoperative Coping Curriculum.

BACKGROUND AND RATIONALE: Recent research has called for further resident training in coping with errors and adverse events in the operating room. To the best of our knowledge, there currently exists no evidence-based curriculum or training on this topic. MATERIALS AND METHODS: Synthesizing three prior studies on how experienced surgeons react to errors and adverse events, we developed the STOPS framework for handling surgical errors and adverse events (Stop, Talk to your team, Obtain help, Plan, Succeed). This material was presented to residents in two teaching sessions. RESULTS AND CONCLUSION: In this paper, we describe the presentation of, and the uniformly positive resident reaction to, the STOPS framework: an empirically based psychological tool for surgeons who experience operative errors or adverse events.

Exploring associations among morphometric measurements, genetic group of sire, and performance of beef on dairy calves.

Sire selection for beef on dairy crosses plays an important role in livestock systems as it may affect future performance and carcass traits of growing and finishing crossbred cattle. The phenotypic variation found in beef on dairy crosses has raised concerns from meat packers due to animals with dairy-type carcass characteristics. The use of morphometric measurements may help to understand the phenotypic structures of sire progeny for selecting animals with greater performance. In addition, due to the relationship with growth, these measurements could be used to early predict the performance until the transition from dairy farms to sales. The objectives of this study were 1) to evaluate the effect of different beef sires and breeds on the morphometric measurements of crossbred calves including cannon bone (CB), forearm (FA), hip height (HH), face length (FL), face width (FW) and growth performance; and (2) to predict the weight gain from birth to transition from dairy farms to sale (WG) and the body weight at sale (BW) using such morphometric measurements obtained at first days of animals' life. CB, FA, HH, FL, FW, and weight at 7 ±â€…5 d (BW7) (Table 1) were measured on 206 calves, from four different sire breeds [Angus (AN), SimAngus (SA), Simmental (SI), and Limousin (LI)], from five farms. To evaluate the morphometric measurements at the transition from dairy farms to sale and animal performance 91 out of 206 calves sourced from four farms, and offspring of two different sires (AN and SA) were used. To predict the WG and BW, 97 calves, and offspring of three different sires (AN, SA, and LI) were used. The data were analyzed using a mixed model, considering farm and sire as random effects. To predict WG and BW, two linear models (including or not the morphometric measurements) were used, and a leave-one-out cross-validation strategy was used to evaluate their predictive quality. The HH and BW7 were 7.67% and 10.7% higher (P < 0.05) in SA crossbred calves compared to AN, respectively. However, the ADG and adjusted body weight to 120 d were 14.3% and 9.46% greater (P < 0.05) in AN compared to SA. The morphometric measurements improved the model's predictive performance for WG and BW. In conclusion, morphometric measurements at the first days of calves' life can be used to predict animals' performance in beef on dairy. Such a strategy could lead to optimized management decisions and greater profitability in dairy farms.

Common Components of General Surgery Robotic Educational Programs.

OBJECTIVE: Robotically assisted surgery has become more common in general surgery, but there is limited guidance from the Accreditation Council for Graduate Medical Education (ACGME) regarding this type of training. We sought to determine common elements and differences in the robotic educational curricula developed by general surgery residency programs. DESIGN: Robotic educational curricula were obtained from the 7 individuals who presented at the workshop, "Robotic Education in General Surgery" at the 2023 Association of Program Directors in Surgery annual meeting. RESULTS: All 7 general surgery programs had training beginning intern year, required online robotic modules, had at least 1 dedicated simulation training console not used for clinical purposes, and ran dry and wet (tissue) robotic labs at least annually. All programs had bedside and console surgeon case minimums and had administrative support to run the educational programs. Differences existed regarding how training intern year was executed, the simulations required, clinical practice minimum requirements, how progress was monitored over time, and how case numbers were tracked. Some programs had salary support for a director of robotic education. CONCLUSIONS: There are several common elements to robotic educational curricula in general surgery, however significant variation does exist between programs. Given the frequency of robotic use in general surgery and current lack of standardization, formal guidance from the ACGME specifically regarding robotic education in general surgery residency is warranted.

Operationalizing risk-appropriate perinatal care in a rural US State: directions for policy and practice.

BACKGROUND: Risk-appropriate care improves outcomes by ensuring birthing people and infants receive care at a facility prepared to meet their needs. Perinatal regionalization has particular importance in rural areas where pregnant people might not live in a community with a birthing facility or specialty care. Limited research focuses on operationalizing risk-appropriate care in rural and remote settings. Through the implementation of the Centers for Disease Control and Prevention (CDC) Levels of Care Assessment Tool (LOCATe), this study assessed the system of risk-appropriate perinatal care in Montana. METHODS: Primary data was collected from Montana birthing facilities that participated in the CDC LOCATe version 9.2 (collected July 2021 - October 2021). Secondary data included 2021 Montana birth records. All birthing facilities in Montana received an invitation to complete LOCATe. LOCATe collects information on facility staffing, service delivery, drills, and facility-level statistics. We added additional questions on transport. RESULTS: Nearly all (96%) birthing facilities in Montana completed LOCATe (N = 25). The CDC applied its LOCATe algorithm to assign each facility with a level of care that aligns directly with guidelines published by the American Academy of Pediatrics (AAP) and the American College of Obstetricians and Gynecologists (ACOG), and Society for Maternal-Fetal Medicine (SMFM). LOCATe-assessed levels for neonatal care ranged from Level I to Level III. Most (68%) facilities LOCATe-assessed at Level I or lower for maternal care. Close to half (40%) self-reported a higher-level of maternal care than their LOCATe-assessed level, indicating that many facilities believe they have greater capacity than outlined in their LOCATe-assessed level. The most common ACOG/SMFM requirements contributing to the maternal care discrepancies were the lack of obstetric ultrasound services and a physician anesthesiologist. CONCLUSIONS: The Montana LOCATe results can drive broader conversations on the staffing and service requirements necessary to provide high-quality obstetric care in low-volume rural hospitals. Montana hospitals often rely on Certified Registered Nurse Anesthetists (CRNA) for anesthesia services and telemedicine to access specialty providers. Integrating a rural health perspective into the national guidelines could enhance the utility of LOCATe to support state strategies to improve the provision of risk-appropriate care.

Patterns and correlates of sedentary behavior among university students.

Objective: To characterize the context, patterns, and correlates of sedentary behavior (SB) in university students. Participants: A total of 95 adults (41% men) enrolled in 34 different undergraduate majors. Methods: SB was assessed by questionnaire and accelerometer. Results: Objective SB and moderate-to-vigorous physical activity (MVPA) accounted for 8.4 ± 1.5 and 1.2 ± 0.5 h·day-1, respectively. Most SB was spent in occupational, leisure, and screen time behaviors, and was accumulated in short bouts of 10 min or longer. Women were more sedentary than men (522.0 ± 80.3 vs. 486.1 ± 91.3 min·day-1, p = 0.03) and engaged in more prolonged bouts of SB. Correlates of SB included female sex, smoking, light activity, MVPA, and markers of obesity, with higher levels of light activity and current smoking the strongest and most consistent correlates of reduced SB. Conclusions: University students engage in high amounts of SB and accumulate most of their SB in short bouts, with differences in patterns of SB between men and women.

Assessment of complementary white matter microstructural changes and grey matter atrophy in a preclinical model of Alzheimer's disease.

Alzheimer's disease (AD) has been associated with amyloid and tau pathology, as well as neurodegeneration. Beyond these hallmark features, white matter microstructural abnormalities have been observed using MRI. The objective of this study was to assess grey matter atrophy and white matter microstructural changes in a preclinical mouse model of AD (3xTg-AD) using voxel-based morphometry (VBM) and free-water (FW) diffusion tensor imaging (FW-DTI). Compared to controls, lower grey matter density was observed in the 3xTg-AD model, corresponding to the small clusters in the caudate-putamen, hypothalamus, and cortex. DTI-based fractional anisotropy (FA) was decreased in the 3xTg model, while the FW index was increased. Notably, the largest clusters for both FW-FA and FW index were in the fimbria, with other regions including the anterior commissure, corpus callosum, forebrain septum, and internal capsule. Additionally, the presence of amyloid and tau in the 3xTg model was confirmed with histopathology, with significantly higher levels observed across many regions of the brain. Taken together, these results are consistent with subtle neurodegenerative and white matter microstructural changes in the 3xTg-AD model that manifest as increased FW, decreased FW-FA, and decreased grey matter density.

Identification of in vivo roles of ErbB4-JMa and its direct nuclear signaling using a novel isoform-specific knock out mouse.

Like all receptor tyrosine kinases (RTKs), ErbB4 signals through a canonical signaling involving phosphorylation cascades. However, ErbB4 can also signal through a non-canonical mechanism whereby the intracellular domain is released into the cytoplasm by regulated intramembrane proteolysis (RIP) and translocates to the nucleus where it regulates transcription. These different signaling mechanisms depend on the generation of alternative spliced isoforms, a RIP cleavable ErbB4-JMa and an uncleavable ErbB4-JMb. Non-canonical signaling by ErbB4-JMa has been implicated in the regulation of brain, heart, mammary gland, lung, and immune cell development. However, most studies on non-canonical ErbB4 signaling have been performed in vitro due to the lack of an adequate mouse model. We created an ErbB4-JMa specific knock out mouse and demonstrate that RIP-dependent, non-canonical signaling by ErbB4-JMa is required for the regulation of GFAP expression during cortical development. We also show that ErbB4-JMa signaling is not required for the development of the heart, mammary glands, sensory ganglia. Furthermore, we identify genes whose expression during cortical development is regulated by ErbB4, and show that the expression of three of them, CRYM and DBi, depend on ErbB4-JMa whereas WDFY1 relies on ErbB4-JMb. Thus, we provide the first animal model to directly study the roles of ErbB4-JMa and non-canonical ErbB4 signaling in vivo.

Is intraoperative MRI use in malignant brain tumor surgery a health care burden? A matched analysis of MarketScan Database.

BACKGROUND: Intraoperative magnetic resonance imaging (iMRI) is a useful adjunct for resection of primary malignant brain tumors (MBTs). The aim of our study is to investigate the impact of iMRI on health care utilization in patients who underwent craniotomy for resection of MBTs. MATERIALS AND METHODS: MarketScan database were queried using the ICD-9/10 and CPT 4th edition, from 2008 to 2020. We included patients ≥ 18 years of age who underwent a craniotomy with at-least one year follow-up. Outcomes were length of stay (LOS), discharge disposition, hospital/emergency room (ER) re-admissions, outpatient services, medication refills and corresponding payments. RESULTS: Of 6,640 patients who underwent craniotomy for MBTs, 465 patients (7%) had iMRI used during the procedure with 0.7% per year increase in iMRI use during the study period. Patients without iMRI use had higher complications at index hospitalization compared to those with iMRI use (19% vs. 14%, p = 0.04). There was no difference in the ER admission rates among the patients who underwent surgery with and without iMRI use at 6-months and 1-year after the index procedure. In terms of post-discharge payments, no significant differences were noted among the patients without and with iMRI use at 6-months ($81,107 vs. $ 81,458, p = 0.26) and 1-year ($132,657 vs. $ 118,113, p = 0.12). CONCLUSION: iMRI use during craniotomy for MBT gradually increased during the study period. iMRI did not result in higher payments at index hospitalization, 6-months, and 1-year after the index procedure.

Evaluation of an opioid and addiction treatment tele-education program for healthcare providers in a rural and frontier state.

OBJECTIVE: To develop and evaluate a relevant and readily accessible post-professional opioid use disorder (OUD) education program for a rural and frontier state. DESIGN: Observational study. SETTING/PARTICIPANTS: Healthcare providers enrolled in Extension for Community Healthcare Outcomes (ECHO) Idaho Opioid, a tele-mentoring education program. MAIN OUTCOME MEASURE: Participant-level demographics of those that attended the ECHO Idaho Opioid program and post-session and program evaluation -surveys. RESULTS: A total of 273 individuals attended at least one ECHO Idaho Opioid session (per session average = 22.8); 183 post-session evaluations (per session average = 6.3) and 42 program evaluations were completed. The program was well received by providers in a rural and frontier state and may be a viable option to enhance patient care for OUD patients in these communities. CONCLUSION: The Project ECHO model is successful at reaching providers across diverse geographic regions, overcoming barriers associated with attending advanced trainings or developing peer networks to improve patient care. The model can be used to develop educational content and delivery that participants believe is satisfactory, valuable, and applicable to their profession and practice.

Microbial phytase reduces basal endogenous loss of calcium in pigs fed diets containing phytate phosphorus at commercial levels.

The objective of this experiment was to test the hypothesis that increasing dietary phytase reduces basal endogenous loss of Ca and increases P balance in pigs. Seventy barrows (initial body weight: 17.66 ± 1.69 kg) were allotted to seven Ca-free diets using a randomized complete block design with two blocks and five pigs per diet in each block. All diets were based on corn, potato protein concentrate, and full-fat rice bran. A positive control (PC) diet was formulated to contain P at the requirement for standardized total tract digestible (STTD) P by 11 to 25 kg pigs. Six negative control (NC) diets were formulated by reducing the provision of digestible P by 0.15% and adding 0, 250, 500, 1,000, 2,000, or 4,000 phytase units/kg diet. Pigs were housed individually in metabolism crates that allowed for total, but separate, collection of urine and feces. Daily feed allowance was 3.0 times the maintenance requirement for metabolizable energy and was divided into two equal meals. Diets were fed for 12 d with the first 5 d considered the adaptation period. Urine collections started on day 6 in the morning and ceased on day 10 in the morning. Fecal markers were also included in the morning meals on day 6 and day 10 and feces were collected according to the marker-to-marker procedure. Results indicated that the apparent total tract digestibility of dry matter was not affected by dietary P or phytase levels. The basal endogenous loss of Ca was not affected by dietary P, but exponentially decreased (P = 0.030) as phytase level increased in the diets. Phosphorus retention (g/d) and standardized total tract digestibility of phosphorus were greater (P < 0.05) in pigs fed the PC diet compared with pigs fed the NC diet with no phytase. The STTD of P exponentially (P < 0.001) increased as phytase level increased in the diets, but because of the lack of Ca, retention of P (% of absorbed) linearly decreased (P = 0.006) as phytase increased. In conclusion, basal endogenous loss of Ca decreased as dietary phytase increased demonstrating that endogenous Ca can be bound to phytate in the intestinal tract of pigs. However, STTD of P increased as phytase level in the diets increased.

Phytate in plant-based ingredients limits the amount of phosphorus available for absorption and can form indigestible complexes with endogenous calcium. However, breakdown of the phytate molecule by phytase increases digestibility of phosphorus and may also reduce endogenous loss of calcium. Therefore, the objective of this experiment was to test the hypothesis that level of phytase influences the utilization of phosphorus and basal endogenous loss of calcium in growing pigs fed calcium-free diets. Results demonstrated that total tract digestibility of phosphorus increased as phytase increased in the diets, but not all of the absorbed P was retained in the pigs due to a lack of calcium. Dietary concentration of phosphorus did not affect basal endogenous loss of calcium, but increasing concentrations of microbial phytase reduced basal endogenous loss of calcium. These results demonstrate that some endogenous calcium is bound to phytate, but including microbial phytase in diets helps release this calcium and therefore reduce endogenous loss of calcium.

Video feedback with error-focused or correct-focused examples in surgical skills distance learning: A randomized trial.

BACKGROUND: Although it seems natural that surgical trainees would learn from demonstrations of a correct performance, evidence outside of surgical education has suggested that error-focused examples may promote error detection and improved procedural task performance. We hypothesized that feedback through error-focused videos would improve procedural learning more than correct-focused videos. METHODS: We conducted a randomized controlled trial of video feedback comparing error-focused versus correct-focused examples. The participants were interviewees at our general surgery residency program in December 2020. All of the interviewees performed suturing and knot tying tasks on their interview day (baseline), with 70 common errors identified. For each error, we created an instructional feedback video in two formats: one video demonstrating the error and another demonstrating correct performance. The study participants received feedback videos based on baseline performance errors, with the format randomly assigned. Two blinded raters assessed the baseline and postintervention performances. RESULTS: Thirty-seven interviewees enrolled and 17 submitted postintervention videos. The postintervention mean performance scores were significantly higher (P = .02) in the error-focused than the correct-focused example group (suturing [maximum score 18]: 16.9 vs 13.9 [difference 2.9; 95% CI 0.7, 5.1]; knot-tying [maximum score 24]: 21.6 vs 17.8 [difference 3.8; 95% CI 0.5, 7.0]). We found no between-group differences in performance time ([error-focused versus correct-focused] suturing: 246 vs 256 s; knot-tying: 170 vs 138 s; P = .08). Mean satisfaction with feedback was similar between groups (error-focused: mean = 5.3 versus correct-focused: mean = 5.2, out of 7; P = .95). CONCLUSION: Feedback that highlights errors is associated with better learning of surgical skills than feedback demonstrating correct performance, confirming our hypothesis.

Conditioning Dogs for an Active Lifestyle.

The aim of conditioning is to remodel body tissues in preparation for the physical demands of activity. Body tissues need strength to produce and withstand the forces generated during movement. Body tissues remodel in response to load, for example, training can remodel and increase the size of tendons, but this takes time. Training does more than just strengthening tissues; it also improves tissue response to exercise and recovery time. The National Sports Medicine Institute in the United Kingdom states "regular exercise increases muscle tone, facilitates good circulation, improves strength, agility and flexibility and improves the rate of waste product disposal."

Disablement in the Physically Active Scale Short Form-8: psychometric evaluation.

BACKGROUND: Patient-centered care and evidence-based practice (EBP) are core competencies for health care professionals. The importance of EBP has led to an increase in research involving clinical outcomes; current recommendations emphasize collecting patient focused measures, thus increasing the need for psychometrically sound patient reported outcome measures (PROMs) of health. Disablement has been identified as a valuable multi-dimensional construct for patient care. The Disablement in the Physically Active Scale Short Form-8 (DPA SF-8) has been proposed as a tool to be used in the physically active population that assesses a physical summary component of health and a quality of life component however, further analysis is necessary to ensure the instrument is psychometrically sound. METHODS: Confirmatory factor analyses (CFAs) were conducted on the DPA SF-8 at each time point to ensure factor structure. Reliability of the scale and internal consistency of the subscales were assessed, and a minimal detectable change (MDC) calculated. Additionally, a minimal clinically important difference (MCID) was also established, and invariance testing across three time points and groups was conducted. RESULTS: The CFAs at all three visits exceeded recommended model fit indices. The interclass correlation coefficient value (.924) calculated indicated excellent scale reliability and Cronbach's alpha for subscales PHY and QOL were within recommend values. The MDC value calculated was 5.83 and the MCID for persistent injuries were 2 points and for acute injuries, 3 points. The DPA SF-8 was invariant across time and across subgroups. CONCLUSIONS: The DPA SF-8 met CFA recommendations and criteria for multi-group and longitudinal invariance testing, which indicates the scale may be used to assess for differences between the groups or across time. Our overall analysis indicates the DPA SF-8 is a valid, reliable, and responsive instrument to assess patient improvement in the physically active population.

Poly (ADP-Ribose) Polymerase 1 Regulates Cajal-Retzius Cell Development and Neural Precursor Cell Adhesion.

Poly (ADP-ribose) polymerase 1 (PARP1) is a ubiquitously expressed enzyme that regulates DNA damage repair, cell death, inflammation, and transcription. PARP1 functions by adding ADP-ribose polymers (PAR) to proteins including itself, using NAD+ as a donor. This post-translational modification known as PARylation results in changes in the activity of PARP1 and its substrate proteins and has been linked to the pathogenesis of various neurological diseases. PARP1 KO mice display schizophrenia-like behaviors, have impaired memory formation, and have defects in neuronal proliferation and survival, while mutations in genes that affect PARylation have been associated with intellectual disability, psychosis, neurodegeneration, and stroke in humans. Yet, the roles of PARP1 in brain development have not been extensively studied. We now find that loss of PARP1 leads to defects in brain development and increased neuronal density at birth. We further demonstrate that PARP1 loss increases the expression levels of genes associated with neuronal migration and adhesion in the E15.5 cerebral cortex, including Reln. This correlates with an increased number of Cajal-Retzius (CR) cells in vivo and in cultures of embryonic neural progenitor cells (NPCs) derived from the PARP1 KO cortex. Furthermore, PARP1 loss leads to increased NPC adhesion to N-cadherin, like that induced by experimental exposure to Reelin. Taken together, these results uncover a novel role for PARP1 in brain development, i.e., regulation of CR cells, neuronal density, and cell adhesion.

Physical Medicine and Rehabilitation.

Cancer patients have unique symptoms from tumor burden and cancer treatments, which affect functional status and quality of life. Reports have shown approximately 65% of cancer patients have at least one functional/rehabilitation need, yet fewer than 10% of these needs get addressed during their cancer journey.