Community-based HIV Self-testing for Persons Who Use Drugs Can Contribute to Reaching Ending the HIV Epidemic in the US (EHE) Goals.

In a pilot study providing HIV self-testing to persons who use drugs (N = 40), we identified 3 new HIV cases when partnering with a community-based organization. Most (82%) participants were interested in preexposure prophylaxis. HIV self-testing could contribute to efforts to Ending the HIV Epidemic in the United States. ClinicalTrials.gov registration: NCT05528562.

Neural Sensitivity to Peer Feedback and Depressive Symptoms: Moderation by Executive Function.

Theories of adolescent development suggest that elevated neural sensitivity to social evaluation confers tradeoffs for adolescents' wellbeing, promoting adaptation to changing social contexts but increasing risk for emotional distress and depression. This study investigated whether the association between neural processing of peer feedback and depressive symptoms depends on teacher-reported executive function (EF) ability in adolescent girls. Girls showed activation to negative and positive peer feedback in regions implicated in social-emotional processing that interacted with EF to predict depressive symptoms. Specifically, activation predicted more depression in youth with poorer EF but less depression in youth with better EF, suggesting that the impact of increased social sensitivity may depend on youths' ability to regulate this sensitivity in adaptive ways.

A Communications Campaign to Build Confidence in Covid-19 Vaccines: The Boston Medical Center Experience.

Health systems could play an important role in efforts to build vaccine confidence in communities that have been hardest hit by Covid-19. Boston Medical Center (BMC) health system, New England's largest safety-net hospital, along with its community partners, implemented a Covid Response Program aimed at building vaccine confidence. The program was supported by a multifaceted and multilingual communications campaign including: 1) traditional and social media channels with trusted messengers, 2) consistent and accessible core messaging, 3) transparent dialogue, and 4) partnership with state and local health government officials. Between December 2020 and June 2022, BMC disseminated 650 social media posts leading to 12 million impressions and more than 1.8 million post engagements. The campaign included a TikTok video later featured during the presidential inauguration, resulting in more than 3.7 million views. BMC's HealthCity digital publication released 20 articles gaining more than 73,000 views while the FAQ/vaccine scheduling site, translated into seven languages, reached 844,000 page visits. At six months into the vaccination program, 70% of BMC primary care patients 18 years or older had received at least one shot and 60% were fully vaccinated, having received either two mRNA doses or one adenovirus vaccine. The proportions rose to 82% with one dose and 75% fully vaccinated at 12 months. By 24 months into the program, 83% of BMC primary care patients had received at least one shot and 77% were fully vaccinated; however, notable differences existed by race/ethnicity. Seventy six percent of Black patients and 75% of Latino patients were fully vaccinated, compared with 85% of Asian and 81% White patients. Key lessons learned include the importance of a multilingual, multimedia campaign and the need for bidirectional communication that could quickly shift to address evolving issues.

Intrafamily heterooligomerization as an emerging mechanism of methyltransferase regulation.

Protein and nucleic acid methylation are important biochemical modifications. In addition to their well-established roles in gene regulation, they also regulate cell signaling, metabolism, and translation. Despite this high biological relevance, little is known about the general regulation of methyltransferase function. Methyltransferases are divided into superfamilies based on structural similarities and further classified into smaller families based on sequence/domain/target similarity. While members within superfamilies differ in substrate specificity, their structurally similar active sites indicate a potential for shared modes of regulation. Growing evidence from one superfamily suggests a common regulatory mode may be through heterooligomerization with other family members. Here, we describe examples of methyltransferase regulation through intrafamily heterooligomerization and discuss how this can be exploited for therapeutic use.

Rapid and Quantitative Detection of Lung Cancer Biomarker ENOX2 Using a Novel Aptamer in an Electrochemical DNA-Based (E-DNA) Biosensor.

To overcome early cancer detection challenges, diagnostic tools enabling more sensitive, rapid, and noninvasive detection are necessary. An attractive cancer target for diagnostic blood tests is human Ecto-NOX disulfide-thiol exchanger 2 (ENOX2), expressed in most human cancer types and regularly shed into blood sera. Here, we developed an electrochemical DNA-based (E-DNA) biosensor that rapidly detects physiologically relevant levels of ENOX2. To identify ENOX2-binding aptamers that could potentially be used in a biosensor, recombinantly expressed ENOX2 was used as a binding target in an oligonucleotide library pull-down that generated a highly enriched ENOX2-binding aptamer. This candidate aptamer sensitively bound ENOX2 via gel mobility shift assays. To enable this aptamer to function in an ENOX2 E-DNA biosensor, the aptamer sequence was modified to adopt two conformations, one capable of ENOX2 binding, and one with disrupted ENOX2 binding. Upon ENOX2 introduction, a conformational shift to the ENOX2 binding state resulted in changed dynamics of a redox reporter molecule, which generated a rapid, significant, and target-specific electrical current readout change. ENOX2 biosensor sensitivity was at or below the diagnostic range. The ENOX2 E-DNA biosensor design presented here may enable the development of more sensitive, rapid, diagnostic tools for early cancer detection.

Optimizing purification and activity assays of N-terminal methyltransferase complexes.

In vitro methyltransferase assays have traditionally been carried out with tritiated S-adenosyl-methionine (SAM) as the methyl donor, as site-specific methylation antibodies are not always available for Western or dot blots and structural requirements of many methyltransferases prohibit the use of peptide substrates in luminescent or colorimetric assays. The discovery of the first N-terminal methyltransferase, METTL11A, has allowed for a second look at non-radioactive in vitro methyltransferase assays, as N-terminal methylation is amenable to antibody production and the limited structural requirements of METTL11A allow for its methylation of peptide substrates. We have used a combination of Western blots and luminescent assays to verify substrates of METTL11A and the two other known N-terminal methyltransferases, METTL11B and METTL13. We have also developed these assays for use beyond substrate identification, showing that METTL11A activity is opposingly regulated by METTL11B and METTL13. Here we provide two methods for non-radioactive characterization of N-terminal methylation, Western blots with full-length recombinant protein substrates and luminescent assays with peptide substrates, and describe how each can be additionally adapted to look at regulatory complexes. We will review the advantages and disadvantages of each method in context with the other types of in vitro methyltransferase assays and discuss why these types of assays could be of general use to the N-terminal modification field.

Does comorbid depression impact executive functioning (EF) in adults diagnosed with ADHD?: a comparison of EF across diagnoses in clinically-referred individuals.

INTRODUCTION: Executive functioning (EF) is a salient factor in both ADHD as well as depressive disorders. However, sparse literature has examined whether depression severity impacts EF concurrently among adults with ADHD. The goal of this study was to examine differences in EF between adult patients diagnosed with ADHD and those diagnosed with a non-ADHD primary psychopathological condition, as a function of both ADHD presentation and depression severity in a diverse clinical sample. METHOD: This crosssectional study included 404 adult patients clinically referred for neuropsychological evaluation to assist with differential diagnosis and/or treatment planning related to known or suspected ADHD. Various EF tasks and a measure of depression severity were administered. One-way MANOVA analyses were conducted to compare EF performance between individuals diagnosed with ADHD or a non-ADHD primary psychopathological condition, with additional analyses examining group differences based on ADHD presentation and depression severity. Regression analyses also examined the potential contribution of depression severity to each EF measure within each group. RESULTS: No significant EF performance differences were found when comparing individuals diagnosed with ADHD and those with a non-ADHD primary psychopathological condition, nor based on ADHD presentation. When comparing across groups using cut-offs for high or low depression, only one EF measure showed significant differences between groups. Further, depression severity generally did not predict reduced EF performances with the exception of verbal fluency and working memory performances in select groups. CONCLUSIONS: This study demonstrated that individuals with ADHD generally perform comparably on EF measures regardless of the presence or absence of comorbid depression. These results suggest further examination of EF deficits when they emerge for adults with ADHD, especially beyond comorbid depression severity.

Opposing regulation of the Nα-trimethylase METTL11A by its family members METTL11B and METTL13.

N-terminal protein methylation (Nα-methylation) is a posttranslational modification that influences numerous biological processes by regulating protein stability, protein-DNA interactions, and protein-protein interactions. Although significant progress has been made in understanding the biological roles of Nα-methylation, we still do not completely understand how the modifying methyltransferases are regulated. A common mode of methyltransferase regulation is through complex formation with close family members, and we have previously shown that the Nα-trimethylase METTL11A (NRMT1/NTMT1) is activated through binding of its close homolog METTL11B (NRMT2/NTMT2). Other recent reports indicate that METTL11A co-fractionates with a third METTL family member METTL13, which methylates both the N-terminus and lysine 55 (K55) of eukaryotic elongation factor 1 alpha. Here, using co-immunoprecipitations, mass spectrometry, and in vitro methylation assays, we confirm a regulatory interaction between METTL11A and METTL13 and show that while METTL11B is an activator of METTL11A, METTL13 inhibits METTL11A activity. This is the first example of a methyltransferase being opposingly regulated by different family members. Similarly, we find that METTL11A promotes the K55 methylation activity of METTL13 but inhibits its Nα-methylation activity. We also find that catalytic activity is not needed for these regulatory effects, demonstrating new, noncatalytic functions for METTL11A and METTL13. Finally, we show METTL11A, METTL11B, and METTL13 can complex together, and when all three are present, the regulatory effects of METTL13 take precedence over those of METTL11B. These findings provide a better understanding of Nα-methylation regulation and suggest a model where these methyltransferases can serve in both catalytic and noncatalytic roles.

Strategies for implementing the interRAI home care frailty scale with home-delivered meal clients.

Introduction: Frailty is a complex condition that is highly associated with health decline and the loss of independence. Home-delivered meal programs are designed to provide older adults with health and nutritional support that can attenuate the risk of frailty. However, home-delivered meal agencies do not routinely assess frailty using standardized instruments, leading to uncertainty over the longitudinal impact of home-delivered meals on frailty levels. Considering this knowledge gap, this study aimed to facilitate home-delivered meal staff's implementation of a standardized frailty instrument with meal clients as part of routine programming. This article (a) describes the use of Implementation Mapping principles to develop strategies supporting frailty instrument implementation in one home-delivered meal agency and (b) examines the degree to which a combination of strategies influenced the feasibility of frailty instrument use by home-delivered meal staff at multiple time points. Methods and materials: This retrospective observational study evaluated staff's implementation of the interRAI Home Care Frailty Scale (HCFS) with newly enrolled home-delivered meal clients at baseline-, 3-months, and 6-months. The process of implementing the HCFS was supported by five implementation strategies that were developed based on tenets of Implementation Mapping. Rates of implementation and reasons clients were lost to 3- and 6-month follow-up were evaluated using univariate analyses. Client-level data were also examined to identify demographic factors associated with attrition at both follow-up time points. Results: Staff implemented the HCFS with 94.8% (n = 561) of eligible home-delivered meal clients at baseline. Of those clients with baseline HCFS data, staff implemented the follow-up HCFS with 43% of clients (n = 241) at 3-months and 18.0% of clients (n = 101) at 6-months. Insufficient client tracking and documentation procedures complicated staff's ability to complete the HCFS at follow-up time points. Discussion: While the HCFS assesses important frailty domains that are relevant to home-delivered meal clients, its longitudinal implementation was complicated by several agency- and client-level factors that limited the extent to which the HCFS could be feasibly implemented over multiple time points. Future empirical studies are needed to design and test theoretically derived implementation strategies to support frailty instrument use in the home- and community-based service setting.

Effect of Technology-Enhanced Screening in Addition to Standard Targeted Clinician Education on the Duration of Untreated Psychosis: A Cluster Randomized Clinical Trial.

Importance: Reducing the duration of untreated psychosis (DUP) is essential to improving outcomes for people with first-episode psychosis (FEP). Current US approaches are insufficient to reduce DUP to international standards of less than 90 days. Objective: To determine whether population-based electronic screening in addition to standard targeted clinician education increases early detection of psychosis and decreases DUP, compared with clinician education alone. Design, Setting, and Participants: This cluster randomized clinical trial included individuals aged 12 to 30 years presenting for services between March 2015 and September 2017 at participating sites that included community mental health clinics and school support and special education services. Eligible participants were referred to the Early Diagnosis and Preventative Treatment (EDAPT) Clinic. Data analyses were performed in September and October 2019 for the primary and secondary analyses, with the exploratory subgroup analyses completed in May 2021. Interventions: All sites in both groups received targeted education about early psychosis for health care professionals. In the active screening group, clients also completed the Prodromal Questionnaire-Brief using tablets at intake; referrals were based on those scores and clinical judgment. In the group receiving treatment as usual (TAU), referrals were based on clinical judgment alone. Main Outcomes and Measures: Primary outcomes included DUP, defined as the period from full psychosis onset to the date of the EDAPT diagnostic telephone interview, and the number of individuals identified with FEP or a psychosis spectrum disorder. Exploratory analyses examined differences by site type, completion rates between conditions, and days from service entry to telephone interview. Results: Twenty-four sites agreed to participate, and 12 sites were randomized to either the active screening or TAU group. However, only 10 community clinics and 4 school sites were able to fully implement population screening and were included in the final analysis. The total potentially eligible population size within each study group was similar, with 2432 individuals entering at active screening group sites and 2455 at TAU group sites. A total of 303 diagnostic telephone interviews were completed (178 [58.7%] female individuals; mean [SD] age, 17.09 years [4.57]). Active screening sites reported a significantly higher detection rate of psychosis spectrum disorders (136 cases [5.6%], relative to 65 [2.6%]; P < .001) and referred a higher proportion of individuals with FEP and DUP less than 90 days (13 cases, relative to 4; odds ratio, 0.30; 95% CI, 0.10-0.93; P = .03). There was no difference in mean (SD) DUP between groups (active screening group, 239.0 days [207.4]; TAU group 262.3 days [170.2]). Conclusions and Relevance: In this cluster trial, population-based technology-enhanced screening across community settings detected more than twice as many individuals with psychosis spectrum disorders compared with clinical judgment alone but did not reduce DUP. Screening could identify people undetected in US mental health services. Significant DUP reduction may require interventions to reduce time to the first mental health contact. Trial Registration: ClinicalTrials.gov Identifier: NCT02841956.

Thumbs up or thumbs down: neural processing of social feedback and links to social motivation in adolescent girls.

Adolescence is a period of rapid biological and psychological development, characterized by increasing emotional reactivity and risk-taking, especially in peer contexts. Theories of adolescent neural development suggest that the balance in sensitivity across neural threat, reward and regulatory systems contributes to these changes. Building on previous research, this study used a novel social feedback task to explore activation and functional connectivity in the context of social threat and reward in a sample of mid-adolescent girls (n = 86, Mage = 16.32). When receiving negative peer feedback, adolescents showed elevated activation in, and amygdala connectivity with, social processing regions [e.g. medial prefrontal cortex (mPFC) and temporoparietal junction (TPJ)]. When receiving positive feedback, adolescents showed elevated activation in social and reward (e.g. mPFC and ventromedial prefrontal cortex) processing regions and less striatum-cerebellum connectivity. To understand the psychological implications of neural activation and co-activation, we examined associations between neural processing of threat and reward and self-reported social goals. Avoidance goals predicted elevated amygdala and striatum connectivity with social processing regions [e.g. medial temporal gyrus (MTG)], whereas approach goals predicted deactivation in social processing regions (e.g. MTG/TPJ and precuneus), highlighting the importance of considering individual differences in sensitivity to social threat and reward in adolescence.

Novel regulation of the transcription factor ZHX2 by N-terminal methylation.

N-terminal methylation (Nα-methylation) by the methyltransferase NRMT1 is an important post-translational modification that regulates protein-DNA interactions. Accordingly, its loss impairs functions that are reliant on such interactions, including DNA repair and transcriptional regulation. The global loss of Nα-methylation results in severe developmental and premature aging phenotypes, but given over 300 predicted substrates, it is hard to discern which physiological substrates contribute to each phenotype. One of the most striking phenotypes in NRMT1 knockout (Nrmt1-/-) mice is early liver degeneration. To identify the disrupted signaling pathways leading to this phenotype and the NRMT1 substrates involved, we performed RNA-sequencing analysis of control and Nrmt1-/- adult mouse livers. We found both a significant upregulation of transcripts in the cytochrome P450 (CYP) family and downregulation of transcripts in the major urinary protein (MUP) family. Interestingly, transcription of both families is inversely regulated by the transcription factor zinc fingers and homeoboxes 2 (ZHX2). ZHX2 contains a non-canonical NRMT1 consensus sequence, indicating that its function could be directly regulated by Nα-methylation. We confirmed misregulation of CYP and MUP mRNA and protein levels in Nrmt1-/- livers and verified NRMT1 can methylate ZHX2 in vitro. In addition, we used a mutant of ZHX2 that cannot be methylated to directly demonstrate Nα-methylation promotes ZHX2 transcription factor activity and target promoter occupancy. Finally, we show Nrmt1-/- mice also exhibit early postnatal de-repression of ZHX2 targets involved in fetal liver development. Taken together, these data implicate ZHX2 misregulation as a driving force behind the liver phenotype seen in Nrmt1-/- mice.

"Doctor" Badge Promotes Accurate Role Identification and Reduces Gender-Based Aggressions in Female Resident Physicians.

OBJECTIVE: Role misidentification among hospital staff is common. Female resident physicians are more likely to be misidentified as non-physicians. This study utilized a pre-post examination to determine if the usage of a "doctor" badge by resident physicians at a Veterans Affairs Medical Center influences role identification, gender-based aggressions, and workplace experience. METHODS: Twenty-six psychiatry residents at the Veterans Affairs Boston Healthcare System participated in a voluntary, anonymous electronic pre-survey in December 2020 and post-survey in March 2021 to report their experiences with role identification and gender-based aggressions before and after the implementation of a "doctor" badge. RESULTS: Females were significantly more likely than males to report role misidentification (x2(1)=10.8, p=0.001). Females were significantly more likely to experience gender-based aggressions compared to males (x2(1)=19.5, p<0.001). Compared to pre-intervention, females who wore the badge were significantly less likely to be misidentified (x2(1)=9.6, p=0.002). There was no significance when comparing males who were misidentified pre- to post-intervention (x2(1)=1.1, p=0.294). Compared to pre-intervention, females who wore the badge were significantly less likely to experience gender-based aggressions (x2(1)=17.3, p=<0.001). Compared to pre-intervention, there was no significant change in gender-based aggressions for males who wore the badge (x2(1)=1.05, p=0.306). CONCLUSIONS: Female residents were more likely than male residents to report role misidentification. Usage of the "doctor" badge resulted in improved role identification and a reduction in gender-based aggressions for females, but not males. "Doctor" badges can improve role identification, gender-based aggressions, workplace experience, patient communication, and care.

Peer Adversity Predicts Interpersonal Needs in Adolescent Girls.

The need to belong (NTB) and need for approval (NFA) are fundamental interpersonal needs vital to social development. Although these needs are universal, individual differences in the strength of these needs likely emerge from critical social experiences. In particular, given the growing salience of peer social evaluation and belonging across adolescence, interpersonal needs during this stage may be strongly tied to both early and recent experiences in the peer group. The aim of the present study was to examine the contribution of lifetime and recent peer adversity to both general and situation-specific interpersonal needs in a sample of adolescent girls (N = 89, Mage = 15.85). Results revealed that recent peer adversity predicted avoidance-oriented NFA, whereas a significant interaction between lifetime and recent peer adversity predicted approach-oriented NFA. Although neither lifetime nor recent peer adversity predicted individual differences in NTB, both predicted threats to interpersonal needs in the context of a laboratory manipulation of social exclusion. Specifically, both lifetime and recent peer adversity predicted greater need-threat prior to the exclusion, but only individuals who had experienced lifetime peer adversity continued to display ongoing high levels of threatened interpersonal needs.

The Validity of Perceived Recovery Status as a Marker of Daily Recovery Following a High-Volume Back-Squat Protocol.

Although a variety of tools to monitor recovery have been developed, many are impractical for daily use due to cost, time, and challenges with interpretation. The Perceived Recovery Status (PRS) scale was recently developed as an expeditious, noninvasive tool to assess recovery status. While PRS has been strongly associated with repeated sprinting performance, a paucity of research exists relating PRS and performance recovery following resistance exercise. PURPOSE: The purpose of this study was to evaluate the sensitivity of PRS as a subjective marker of recovery up to 72 hours after a high-volume back-squat protocol. METHODS: Eleven resistance-trained men reported to the laboratory on 5 separate occasions (1 familiarization session and 4 testing sessions). The first testing session was considered the baseline session and consisted of a nonfatiguing performance assessment (ie, countermovement jumps and back squats) and a fatiguing back-squat protocol of 8 sets of 10 at 70% 1-repetition maximum separated by 2 minutes of recovery. Participants returned 24, 48, and 72 hours following baseline to provide a PRS rating and complete the performance assessment. RESULTS: Repeated-measures correlations revealed strong associations between PRS countermovement jump (r = .84) and mean bar velocity (r = .80) (both P < .001). CONCLUSIONS: The current findings suggest that PRS can be used as a method to effectively assess daily recovery following a fatiguing bout of resistance exercise. Practitioners are cautioned that the relationship between PRS and performance recovery is individualized, and equivalent PRS scores between individuals are not indicative of similar recovery.

Emotion mindsets and depressive symptoms in adolescence: The role of emotion regulation competence.

Recent theories posit that emotion mindsets (i.e., the extent to which individuals believe emotions are malleable or fixed) play a crucial role in experiences of emotion and influence emotion regulation (ER) processes. Drawing from mindset theory, this study examined the hypothesis that fixed emotion mindsets (FEMs) would predict depressive symptoms via compromised ER competence in adolescence, a period when many first episodes of depression occur. Results supported these hypotheses across two studies assessing participants in midadolescence (ages 14-18; M age = 16.17) and late adolescence (ages 18-21; M age = 18.52). Using a comprehensive approach to assessing ER, results demonstrated that FEMs were associated with less voluntary engagement and more disengagement and emotion dysregulation. In turn, higher voluntary engagement was associated with lower depressive symptoms, whereas higher disengagement and emotion dysregulation were associated with higher depressive symptoms. These findings highlight that one understudied pathway from FEMs to depressive symptoms may be the manner in which individuals respond to their emotions, implicating emotion mindsets as one target for efforts to improve clinical outcomes during adolescence. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Treatment of Electroconvulsive Therapy-Emergent Hypomania and Mania: A Systematic Review of the Literature.

Objective: Electroconvulsive therapy (ECT)-emergent hypomania/mania is a clinically significant problem that has lacked evidence-based guidelines for effective management. The aim of this systematic literature review is to compile the current published literature on treating ECT-emergent hypomania/mania to help guide treatment course in patients with unipolar and bipolar depression.Data Sources: MEDLINE/PubMed was searched for studies published from 1980 through August 2020 that evaluated the treatment of ECT-emergent hypomania/mania. Search terms included Boolean combinations of the following: mania, hypomania, ECT, ECT induced mania, and ECT induced hypomania.Study Selection: There were 1,662 articles reviewed, and all published studies detailing the treatment of ECT-emergent hypomania/mania written in English that met inclusion criteria were included. Due to the limited number of articles, there were no restrictions.Data Extraction: Two reviewers extracted relevant articles and assessed each study based on inclusion criteria.Results: The literature review identified 12 articles that described the treatment course of ECT-emergent hypomania/mania in 17 patients. There were 9 patients who had no known history of manic or hypomanic episodes and were diagnosed with unipolar depression and 8 patients diagnosed with bipolar disorder. There were 4 primary treatment courses identified: continuing ECT alone, continuing ECT in conjunction with lithium, discontinuing ECT with no medication treatment, or discontinuing ECT and starting a medication.Conclusions: The available data are insufficient to support definitive conclusions; however, potential treatment guidelines are suggested within the review to providers based on the limited data available.

Translating Knowledge to Optimize Value-Based Occupational Therapy: Strategies for Educators, Practitioners, and Researchers.

With the continued evolution of health care reform and payment models, it is imperative that the occupational therapy profession consistently and clearly articulate its distinct value. As payment models shift from paying for the volume of services provided to paying for the value of services, the field of occupational therapy must be sure to implement high-quality care by translating evidence into practice and facilitating improvements in client outcomes. Yet the process of translating evidence-based interventions and programs to real-world settings can be quite complex, and successful implementation often requires active collaboration across occupational therapy stakeholders. In this Health Policy Perspectives article, we provide occupational therapy educators, practitioners, and researchers with key recommendations for how the profession can translate evidence into practice, ultimately leading to the improvement of client outcomes and the provision of value-based care.

Advancing the management of upper extremity musculoskeletal conditions: Insights from the field of implementation science.

INTRODUCTION: The development of effective interventions in hand and upper extremity rehabilitation is critically important; yet even the most promising interventions may not successfully be implemented in practice. Occupational and physical therapists who provide specialized hand and upper extremity rehabilitation services ("hand therapists") can face extensive, multi-level barriers when attempting to use research findings in real-world settings, widening the long-standing research-to-practice gap. Concepts from the field of implementation science can be leveraged to address this gap and expedite the application of research discoveries that can maximize treatment outcomes of the musculoskeletal upper extremity client. As the intersection of hand and upper extremity rehabilitation and implementation science draws growing attention, there is a great need for researchers and clinicians to infuse implementation science into the hand and upper extremity rehabilitation research and practice contexts. PURPOSE: The purpose of this article is to define implementation science and synthesize several studies from the hand and upper extremity rehabilitation field that have examined the effect of implementation strategies (eg, chart audit and feedback techniques; implementation teams) on implementation outcomes (eg, acceptability, fidelity). We also present recommendations for how (1) hand and upper extremity rehabilitation researchers can design studies to examine both patient outcomes and implementation outcomes relative to interventions for the musculoskeletal upper extremity and (2) hand and upper extremity rehabilitation specialists and administrators can develop implementation teams to facilitate the use of evidence in practice. CONCLUSION: Collaboration between researchers and clinicians has great potential to advance the entirety of the hand and upper extremity rehabilitation profession, especially when such collaborations are guided by the implementation science field.