Complete genome sequence of a Pseudomonas fluorescens bacteriophage UNO-G1W1 isolated from freshwater ice in Nebraska.

We provide the complete genome sequence for a novel Pseudomonas fluorescens bacteriophage named UNO-G1W1. This phage was isolated from a single ice cover sampling. The genome was sequenced on the Nanopore MinION, generated with the direct terminal repeat-phage-pipeline and polished with Illumina short reads. Sequence identity classifies the phage as an otagovirus.

U.S. Army mortality surveillance in active duty soldiers, 2014-2019.

Mortality surveillance is an important activity for capturing information on a population's health. This retrospective surveillance analysis utilizes administrative data sources to describe active duty U.S. Army soldiers who died from 2014 to 2019, and calculate mortality rates, assess trends by category of death, and identify leading causes of death within subpopulations. During the surveillance period, 2,530 soldier deaths were reported. The highest crude mortality rates observed during the 6-year surveillance period were for deaths by suicide, followed by accidental (i.e., unintentional injury) deaths. The crude mortality rates for natural deaths decreased significantly over the 6-year period, by an average of 6% annually. The leading causes of death were suicide by gunshot wound, motor vehicle accidents, suicide by hanging, neoplasms, and cardiovascular events. Significant differences were observed in the leading causes of death in relation to demographic characteristics, which has important implications for the development of focused educational campaigns to improve health behaviors and safe driving habits. Current public health programs to prevent suicide should be evaluated, with new approaches for firearm safety considered.

Multivariate Assessment of Inhibitory Control in Youth: Links With Psychopathology and Brain Function.

Inhibitory control is central to many theories of cognitive and brain development, and impairments in inhibitory control are posited to underlie developmental psychopathology. In this study, we tested the possibility of shared versus unique associations between inhibitory control and three common symptom dimensions in youth psychopathology: attention-deficit/hyperactivity disorder (ADHD), anxiety, and irritability. We quantified inhibitory control using four different experimental tasks to estimate a latent variable in 246 youth (8-18 years old) with varying symptom types and levels. Participants were recruited from the Washington, D.C., metro region. Results of structural equation modeling integrating a bifactor model of psychopathology revealed that inhibitory control predicted a shared or general psychopathology dimension, but not ADHD-specific, anxiety-specific, or irritability-specific dimensions. Inhibitory control also showed a significant, selective association with global efficiency in a frontoparietal control network delineated during resting-state functional magnetic resonance imaging. These results support performance-based inhibitory control linked to resting-state brain function as an important predictor of comorbidity in youth psychopathology.

The Association Between State Minimum Wage and Firearm Homicides, 2000-2020.

INTRODUCTION: Recent research has indicated an association between both poverty and income inequality and firearm homicides. Increased minimum wages may serve as a strategy for reducing firearm violence by increasing economic security among workers earning low wages and reducing the number of families living in poverty. This study aimed to examine the association between state minimum wage and firearm homicides in the U.S. between 2000 and 2020. METHODS: State minimum wage, obtained from Temple's Law Atlas and augmented by legal research, was conceptualized using the Kaitz Index. State-level homicide counts were obtained from 2000 to 2020 multiple-cause-of death mortality data from the National Vital Statistics System. Log-linear regressions were conducted to model the associations between state minimum wage and firearm homicides, stratifying by demographic groups. Analyses were conducted in 2023. RESULTS: A 1% point increase in a state's Kaitz Index was associated with a 1.3% (95% CI: -2.1% to -0.5%) decrease in a state's firearm homicide rate. When interacted with quartile of firearm ownership, the Kaitz Index was associated with decreases in firearm homicide in all except the lowest quartile. These findings were largely consistent across stratifications. CONCLUSIONS: Changing a state's minimum wage, whereby a full-time minimum wage worker's salary is closer to a state's median income, may be an option for reducing firearm homicides.

Glutamate-dependent arginine biosynthesis requires the inactivation of spoVG, sarA, and ahrC in Staphylococcus aureus.

Genome sequencing has demonstrated that Staphylococcus aureus encodes arginine biosynthetic genes argDCJBFGH synthesizing proteins that mediate arginine biosynthesis using glutamate as a substrate. Paradoxically, however, S. aureus does not grow in a defined, glutamate-replete medium lacking arginine and glucose (CDM-R). Studies from our laboratory have found that specific mutations are selected by S. aureus that facilitate growth in CDM-R. However, these selected mutants synthesize arginine utilizing proline as a substrate rather than glutamate. In this study, we demonstrate that the ectopic expression of the argDCJB operon supports the growth of S. aureus in CDM-R, thus documenting the functionality of this pathway. Furthermore, suppressor mutants of S. aureus JE2 putA::Tn, which is defective in synthesizing arginine from proline, were selected on CDM-R agar. Genome sequencing revealed that these mutants had compensatory mutations within both spoVG, encoding an ortholog of the Bacillus subtilis stage V sporulation protein, and sarA, encoding the staphylococcal accessory regulator. Transcriptional studies document that argD expression is significantly increased when JE2 spoVG sarA was grown in CDM-R. Lastly, we found that a mutation in ahrC was required to induce argD expression in JE2 spoVG sarA when grown in an arginine-replete medium (CDM), suggesting that AhrC also functions to repress argDCJB in an arginine-dependent manner. In conclusion, these data indicate that the argDCJB operon is functional when transcribed in vitro and that SNPs within potential putative regulatory proteins are required to alleviate the repression.IMPORTANCEAlthough Staphylococcus aureus has the capability to synthesize all 20 amino acids, it is phenotypically auxotrophic for several amino acids including arginine. This work identifies putative regulatory proteins, including SpoVG, SarA, and AhrC, that function to inhibit the arginine biosynthetic pathways using glutamate as a substrate. Understanding the ultimate mechanisms of why S. aureus is selected to repress arginine biosynthetic pathways even in the absence of arginine will add to the growing body of work assessing the interactions between metabolism and S. aureus pathogenesis.

Characteristics and spatiotemporal variation of sei whale (Balaenoptera borealis) downsweeps recorded in Atlantic Canada.

The call characteristics and vocal behaviour of sei whales (Balaenoptera borealis) off eastern Canada, including potential spatiotemporal variation, is poorly understood. Such information can improve the performance of automated detector-classifiers, enhancing the accuracy and efficiency of identifying sei whales in large acoustic datasets. Ultimately, these data can be used to understand the occurrence, distribution, and population structure of sei whales in Atlantic Canada. We measured sei whale downsweep characteristics recorded from six locations off Nova Scotia (NS) and Newfoundland and Labrador (NFLD), Canada over a two-year period (2015-2017), and examined variation between call subtypes (singlets, doublets, triplets+), and seasons (Spring, Summer, Fall, Winter). We found that downsweeps had a mean duration of 1.58 s, sweeping from 75.66 to 34.22 Hz, with a peak frequency of 43.89 Hz and an intra-call interval of 2.22 s. Most call characteristics did not vary between location, subtype, or season; however, significantly longer downsweeps occurred off NS, within doublet calls, and in fall months. We also found that NFLD had a higher proportion of doublets (70%) than NS (52%). This variation may be evidence of acoustically diverging sei whale populations, as well as useful for improving detector-classifiers of sei whales in the region.

Acceptability of Personalized Lung Cancer Screening Program Among Primary Care Providers.

Current lung cancer screening (LCS) guidelines rely on age and smoking history. Despite its benefit, only 5%-15% of eligible patients receive LCS. Personalized screening strategies select individuals based on their lung cancer risk and may increase LCS's effectiveness. We assess current LCS practices and the acceptability of personalized LCS among primary care providers (PCP) in Texas. We surveyed 32,983 Texas-based PCPs on an existing network (Protocol 2019-1257; PI: Dr. Shete) and 300 attendees of the 2022 Texas Academy of Family Physicians (TAFP) conference. We analyzed the responses by subgroups of interest. Using nonparametric bootstrap, we derived an enriched dataset to develop logistic regression models to understand current LCS practices and acceptability of personalized LCS. Response rates were 0.3% (n = 91) and 15% (n = 60) for the 2019-1257 and TAFP surveys, respectively. Most (84%) respondents regularly assess LCS in their practice. Half of the respondents were interested in adopting personalized LCS. The majority (66%) of respondents expressed concerns regarding time availability with the personalized LCS. Most respondents would use biomarkers as an adjunct to assess eligibility (58%), or to help guide indeterminate clinical findings (63%). There is a need to enhance the engagement of Texas-based PCPs in LCS. Most of the respondents expressed interest in personalized LCS. Time availability was the main concern related to personalized LCS. Findings from this project highlight the need for better education of Texas-based PCPs on the benefits of LCS, and the development of efficient decision tools to ensure successful implementation of personalized LCS. PREVENTION RELEVANCE: Personalized LCS facilitated by a risk model and/or a biomarker test is proposed as an alternative to existing programs. Acceptability of personalized approach among PCPs is unknown. The goal of this study is to assess the acceptability of personalized LCS among PCPs.

Phasic Versus Tonic Irritability and Associations with Family Accommodation Among Youth with Selective Mutism: A Latent Profile Analysis.

Clinical presentations of selective mutism (SM) vary widely across affected youth. Although studies have explored general externalizing problems in youth with SM, research has not specifically examined patterns of irritability. Relatedly, research has not considered how affected families differentially accommodate the anxiety of youth with SM as a function of the child's temper outbursts (i.e., phasic irritability) and general angry mood (i.e., tonic irritability). Data were drawn from a sample of treatment-seeking children and adolescents with a primary diagnosis of selective mutism (N = 152; Mean age = 6.12 years; 67.11% female), and their caregivers. Latent profile analysis (LPA) was used to identify distinct profiles in SM youth that were characterized by varying levels of phasic and/or tonic irritability. Analyses further examined whether these different profiles were associated with different levels of family accommodation and global impairment. LPA identified 5 profiles: SM with No irritability, SM with Low Phasic Irritability, SM with High Phasic Irritability, SM with High Phasic and Moderate Tonic Irritability, and SM with High Phasic and High Tonic Irritability. Patterns of family accommodation and global impairment were highest among youth belonging to profiles characterized by high phasic irritability. Findings highlight separable patterns of irritability across youth with SM, with phasic irritability (i.e., temper outbursts) appearing particularly linked with increased family accommodation and overall global impairment. Assessing phasic irritability is critical for optimizing treatment in youth with SM and can be useful for flagging possible patterns of family accommodation contributing to overall impairment.

Costs of Fatal and Nonfatal Firearm Injuries in the U.S., 2019 and 2020.

INTRODUCTION: Firearm-related injuries are among the five leading causes of death for people aged 1-44 years in the U.S. The immediate and long-term harms of firearm injuries pose an economic burden on society. Fatal and nonfatal firearm injury costs in the U.S. were estimated providing up-to-date economic burden estimates. METHODS: Counts of nonfatal firearm injuries were obtained from the 2019-2020 Healthcare Cost and Utilization Project Nationwide Emergency Department Sample. Data on nonfatal injury intent were obtained from the National Electronic Injury Surveillance System - Firearm Injury Surveillance System. Counts of deaths (firearm as underlying cause) were obtained from the 2019-2020 multiple cause-of-death mortality data from the National Vital Statistics System. Analyses were conducted in 2023. RESULTS: The total cost of firearm related injuries and deaths in the U.S. for 2020 was $493.2 billion, a 16 percent increase compared with 2019. There are significant disparities in the cost of firearm deaths in 2019-2020, with non-Hispanic Black people, males, and young and middle-aged groups being the most affected. CONCLUSIONS: Most of the nonfatal firearm injury-related costs are attributed to hospitalization. These findings highlight the racial/ethnic differences in fatal firearm injuries and the disproportionate cost burden to urban areas. Addressing this important public health problem can help ameliorate the costs to our society from the rising rates of firearm injuries.

Estimated prevalence of helmet use while bicycling, rollerblading, and skateboarding among middle school students in selected U.S. States- Youth Behavior Risk Survey, 2013-2019.

BACKGROUND: Helmet use helps prevent severe and fatal head and brain injuries from bicycle, rollerblade, and skateboard crashes. This study explores the prevalence of self-reported helmet use among middle school students while bicycling, skateboarding, and rollerblading. METHODS: Data from the Middle School Youth Risk Behavior Survey (YRBS) for selected states were analyzed. Self-reported prevalence (frequency) of helmet use while bicycling, rollerblading, or skateboarding and other variables (sex, grade level, and race/ethnicity) are reported. RESULTS: The overall prevalence of rarely or never wearing a helmet while bicycling among middle school students in selected states was 68.6%; decreasing from 71.7% in 2013 to 67.1% in 2019. The overall prevalence of rarely or never wearing a helmet while rollerblading or skateboarding in middle school students in selected states was 74.6%; decreasing from 76.4% in 2013 to 73.5% in 2019. Students in 7th and 8th grade and students of non-Hispanic race/ethnicity had significantly higher odds of rarely or never wearing a helmet while bicycling or while rollerblading and skateboarding than students in 6th grade and non-Hispanic White students. CONCLUSIONS: While helmet use among middle school students improved over time, overall helmet use during bicycling, rollerblading, and skateboarding remained low. These estimates illustrate the continued call for universal implementation of helmet use efforts among kids using established strategies. PRACTICAL APPLICATIONS: Future research on helmet use among youth who rollerblade and skateboard, as well as multi-pronged efforts to promote helmet use among middle schoolers who bicycle, skateboard, and rollerblade (inclusive of education, helmet distribution, and social marketing techniques, as well as the provision of helmets at no-cost) may be beneficial for addressing perceived risks for injury and other barriers.

S100a9 Protects Against the Effects of Repeated Social Defeat Stress.

Background: Posttraumatic stress disorder, a consequence of psychological trauma, is associated with increased inflammation and an elevated risk of developing comorbid inflammatory diseases. However, the mechanistic link between this mental health disorder and inflammation remains elusive. We previously found that S100a8 and S100a9 messenger RNA, genes that encode the protein calprotectin, were significantly upregulated in T lymphocytes and positively correlated with inflammatory gene expression and the mitochondrial redox environment in these cells. Therefore, we hypothesized that genetic deletion of calprotectin would attenuate the inflammatory and redox phenotype displayed after psychological trauma. Methods: We used a preclinical mouse model of posttraumatic stress disorder known as repeated social defeat stress (RSDS) combined with pharmacological and genetic manipulation of S100a9 (which functionally eliminates calprotectin). A total of 186 animals (93 control, 93 RSDS) were used in these studies. Results: Unexpectedly, we observed worsening of behavioral pathology, inflammation, and the mitochondrial redox environment in mice after RSDS compared with wild-type animals. Furthermore, loss of calprotectin significantly enhanced the metabolic demand on T lymphocytes, suggesting that this protein may play an undescribed role in mitochondrial regulation. This was further supported by single-cell RNA sequencing analysis demonstrating that RSDS and loss of S100a9 primarily altered genes associated with mitochondrial function and oxidative phosphorylation. Conclusions: These data demonstrate that the loss of calprotectin potentiates the RSDS-induced phenotype, which suggests that its observed upregulation after psychological trauma may provide previously unexplored protective functions.

Costs of Implementing Teen Dating Violence and Youth Violence Prevention Strategies: Evidence From 5 CDC-Funded Local Health Departments.

OBJECTIVES: In 2016, the Centers for Disease Control and Prevention supported 5 local health departments (LHDs) to implement teen dating violence and youth violence primary prevention strategies across multiple levels of the social-ecological model and build capacity for the expansion of such prevention efforts at the local level. The objective of this study was to estimate the total cost of implementing primary prevention strategies for all LHDs across 3 years of program implementation. METHODS: We used a microcosting analytic approach to identify resources and compute costs for all prevention strategies implemented by LHDs. We computed the total program cost, total and average cost per strategy by social-ecological model level, and average cost of implementation per participant served by the program. All costs were inflated via the monthly Consumer Price Index and reported in August 2020 dollars. RESULTS: For 3 years of program implementation, the total estimated cost of implementing teen dating violence and youth violence primary prevention strategies was >$7.1 million across all 5 LHDs. The largest shares of program-related costs were program staff (55.9%-57.0%) and contracts (22.4%-25.5%). Among prevention strategies, the largest share of total costs was for strategies implemented at the community level of the social-ecological model (42.8%). CONCLUSIONS: The findings from this analysis provide a first look at the total costs of implementing comprehensive teen dating violence and youth violence primary prevention strategies and serve as a foundation for investments in local violence prevention funding for young people.

Distinct neural representations during a brain-machine interface and manual reaching task in motor cortex, prefrontal cortex, and striatum.

Although brain-machine interfaces (BMIs) are directly controlled by the modulation of a select local population of neurons, distributed networks consisting of cortical and subcortical areas have been implicated in learning and maintaining control. Previous work in rodents has demonstrated the involvement of the striatum in BMI learning. However, the prefrontal cortex has been largely ignored when studying motor BMI control despite its role in action planning, action selection, and learning abstract tasks. Here, we compare local field potentials simultaneously recorded from primary motor cortex (M1), dorsolateral prefrontal cortex (DLPFC), and the caudate nucleus of the striatum (Cd) while nonhuman primates perform a two-dimensional, self-initiated, center-out task under BMI control and manual control. Our results demonstrate the presence of distinct neural representations for BMI and manual control in M1, DLPFC, and Cd. We find that neural activity from DLPFC and M1 best distinguishes control types at the go cue and target acquisition, respectively, while M1 best predicts target-direction at both task events. We also find effective connectivity from DLPFC → M1 throughout both control types and Cd → M1 during BMI control. These results suggest distributed network activity between M1, DLPFC, and Cd during BMI control that is similar yet distinct from manual control.

Association between social vulnerability factors and unintentional fatal injury rates - United States, 2015-2019.

BACKGROUND: Differences in social and environmental factors can contribute to disparities in fatal injury rates. The purpose of this study was to examine the relationship between social and environmental factors and unintentional fatal injury across counties in the United States and how this relationship varies by geography. METHODS: County-level vital statistics on age-adjusted unintentional fatal injury rates for 2015-2019 were linked with county-level data from the 2018 Social Vulnerability Index (SVI), a dataset identifying socially vulnerable communities. We conducted linear regression to examine the association between SVI and unintentional fatal injury, overall and by Census region/division. We mapped county-level data for SVI and unintentional fatal injury rates in bivariate choropleth maps using quartiles. RESULTS: SVI was positively associated with unintentional fatal injury (ß = 18.29, p < 0.001) across U.S. counties. The geographic distribution of SVI and unintentional fatal injury rates varied spatially and substantially for U.S. counties, with counties in the South and West regions having the greatest levels of SVI and rates of unintentional fatal injury. CONCLUSIONS: Our findings demonstrate that the social vulnerability of counties is associated with unintentional fatal injury rates. Modification of the SVI for injury research could include additional social determinants and exclude variables not applicable to injuries. A modified SVI could inform unintentional injury prevention strategies by prioritizing efforts in areas with high levels of social vulnerability. PRACTICAL APPLICATIONS: This study is the first step in combining the SVI and injury mortality data to provide researchers with an index to investigate upstream factors related to injury.

Cross-Sectional Examination of Physical Abuse Victimization Differences Between Lesbian, Gay, Bisexual, and Heterosexual Service Members in the U.S. Military, 2018.

Purpose: The primary objective was to analyze the association between sexual orientation and physical abuse victimization using a representative sample from the U.S. active-duty military population. The secondary objective was to determine if differences exist by sexual orientation in perceived barriers (e.g., stigma) to mental health care utilization among physical abuse victimization survivors. Methods: The 2018 Department of Defense Health Related Behaviors Survey (HRBS) (n = 17,166 active-duty respondents) was used for analysis. Weighted logistic regressions and Poisson regressions were used for multivariable analyses, controlling for demographic and military variables. Results: Approximately 93.7% of respondents identified as heterosexual or straight, 2.3% identified as gay or lesbian, and 4% as bisexual. Bisexual active-duty service members had 1.5-fold greater odds of reporting any form of physical abuse victimization (adjusted odds ratio: 1.50 and 95% confidence interval: 1.07-2.10). However, there was no difference observed between gay/lesbian and heterosexual service members for physical abuse victimization. Among survivors of physical abuse victimization, bisexual (p = 0.0038) and gay (p < 0.0001) service members were more likely to report more than one mental health care barrier compared to their heterosexual counterparts. Conclusions: Bisexual service members were more likely to experience physical abuse victimization when compared to their heterosexual counterparts. In addition, gay and bisexual survivors of physical abuse were more likely to experience barriers to mental health care. Tailored interventions should explore strategies to prevent victimization and disparities in mental health care utilization by sexual orientation.

Learning Needs of Patients with Cancer and a Pre-Existing Autoimmune Disease Who Are Candidates to Receive Immune Checkpoint Inhibitors.

Patients with pre-existing autoimmune disorders and cancer considering immune checkpoint inhibitors (ICIs) need to receive balanced information about the benefits and risk of developing immune-related adverse events (irAEs) and flare-ups of their autoimmune disease. To assess the learning needs of patients with cancer and pre-existing autoimmune disease regarding ICI treatment, we interviewed 29 patients with autoimmune disease and cancer from a comprehensive cancer center, of whom 20 had received ICI and 9 were candidates to receive ICI at a US Cancer Center. In-depth semi-structured interviews were conducted from August 2021 and January 2022. Interviewee's opinions and preferences about content and information delivery methods were collected. We recorded and transcribed interviews and analyzed them using thematic analysis. Half of the participants were female, and their median (SD) age was 62.9 (±10.9) years. The identified health information needs included the following: (1) information on irAEs and autoimmune disease flare-ups; (2) benefits of ICI; (3) ICI mechanism in the context of autoimmune disease; (4) management of flare-ups; (5) reasons for stopping or modifying cancer or autoimmune disease treatment; (6) likelihood of autoimmune disease progression or organ damage; and (7) lifestyle changes that could help avoid irAEs. Patients who had received ICI and those who had not yet received treatment reported similar needs, although patients who had received ICI had more questions about cancer treatment modifications. Patients also expressed the need to better understand when to contact their provider and how to share information with multiple providers. Most patients wanted to receive information in visual formats for review at home and at their own pace. Patients expressed interest in having educational tools to facilitate shared decision-making with their physicians, and they identified several areas of health information concerning therapy with ICI. They also highlighted the importance of communication among their various providers.

Distinct neural representations during a brain-machine interface and manual reaching task in motor cortex, prefrontal cortex, and striatum.

Although brain-machine interfaces (BMIs) are directly controlled by the modulation of a select local population of neurons, distributed networks consisting of cortical and subcortical areas have been implicated in learning and maintaining control. Previous work in rodent BMI has demonstrated the involvement of the striatum in BMI learning. However, the prefrontal cortex has been largely ignored when studying motor BMI control despite its role in action planning, action selection, and learning abstract tasks. Here, we compare local field potentials simultaneously recorded from the primary motor cortex (M1), dorsolateral prefrontal cortex (DLPFC), and the caudate nucleus of the striatum (Cd) while nonhuman primates perform a two-dimensional, self-initiated, center-out task under BMI control and manual control. Our results demonstrate the presence of distinct neural representations for BMI and manual control in M1, DLPFC, and Cd. We find that neural activity from DLPFC and M1 best distinguish between control types at the go cue and target acquisition, respectively. We also found effective connectivity from DLPFC→M1 throughout trials across both control types and Cd→M1 during BMI control. These results suggest distributed network activity between M1, DLPFC, and Cd during BMI control that is similar yet distinct from manual control.

Physician Views on the Provision of Information on Immune Checkpoint Inhibitor Therapy to Patients with Cancer and Pre-Existing Autoimmune Disease: A Qualitative Study.

Immune checkpoint inhibitors (ICIs) have improved cancer outcomes but can cause severe immune-related adverse events (irAEs) and flares of autoimmune conditions in cancer patients with pre-existing autoimmune disease. The objective of this study was to identify the information physicians perceived as most useful for these patients when discussing treatment initiation with ICIs. Twenty physicians at a cancer institution with experience in the treatment of irAEs were interviewed. Qualitative thematic analysis was performed to organize and interpret data. The physicians were 11 medical oncologists and 9 non-oncology specialists. The following themes were identified: (1) current methods used by physicians to provide information to patients and delivery options; (2) factors to make decisions about whether or not to start ICIs in patients who have cancer and pre-existing autoimmune conditions; (3) learning points for patients to understand; (4) preferences for the delivery of ICI information; and (5) barriers to the implementation of ICI information in clinics. Regarding points to discuss with patients, physicians agreed that the benefits of ICIs, the probability of irAEs, and risks of underlying autoimmune condition flares with the use of ICIs were most important. Non-oncologists were additionally concerned about how ICIs affect the autoimmune disease (e.g., impact on disease activity, need for changes in medications for the autoimmune disease, and monitoring of autoimmune conditions).

Implementation of genomic medicine for rare disease in a tertiary healthcare system: Mayo Clinic Program for Rare and Undiagnosed Diseases (PRaUD).

BACKGROUND: In the United States, rare disease (RD) is defined as a condition that affects fewer than 200,000 individuals. Collectively, RD affects an estimated 30 million Americans. A significant portion of RD has an underlying genetic cause; however, this may go undiagnosed. To better serve these patients, the Mayo Clinic Program for Rare and Undiagnosed Diseases (PRaUD) was created under the auspices of the Center for Individualized Medicine (CIM) aiming to integrate genomics into subspecialty practice including targeted genetic testing, research, and education. METHODS: Patients were identified by subspecialty healthcare providers from 11 clinical divisions/departments. Targeted multi-gene panels or custom exome/genome-based panels were utilized. To support the goals of PRaUD, a new clinical service model, the Genetic Testing and Counseling (GTAC) unit, was established to improve access and increase efficiency for genetic test facilitation. The GTAC unit includes genetic counselors, genetic counseling assistants, genetic nurses, and a medical geneticist. Patients receive abbreviated point-of-care genetic counseling and testing through a partnership with subspecialty providers. RESULTS: Implementation of PRaUD began in 2018 and GTAC unit launched in 2020 to support program expansion. Currently, 29 RD clinical indications are included in 11 specialty divisions/departments with over 142 referring providers. To date, 1152 patients have been evaluated with an overall solved or likely solved rate of 17.5% and as high as 66.7% depending on the phenotype. Noteworthy, 42.7% of the solved or likely solved patients underwent changes in medical management and outcome based on genetic test results. CONCLUSION: Implementation of PRaUD and GTAC have enabled subspecialty practices advance expertise in RD where genetic counselors have not historically been embedded in practice. Democratizing access to genetic testing and counseling can broaden the reach of patients with RD and increase the diagnostic yield of such indications leading to better medical management as well as expanding research opportunities.