Training of Peer Coaches to Assist Individuals with Knee Osteoarthritis Prepare and Recover From Total Knee Replacement.

OBJECTIVE: The objective of this study is to outline the training of peer coaches in the Moving Well intervention, which was designed to reduce anxiety, depression, and pain catastrophizing in patients before and after total knee replacement (TKR). METHODS: Selected peer coaches had a history of knee osteoarthritis (KOA), a TKR of 12 months or more before training, and were 60 or older. Training was primarily conducted virtually, with a later addition of one in-person session. Training centered on developing skills in motivational interviewing (MoI), encompassing techniques like open-ended questions, affirmations, reflective listening, and summarization. It also covered the MoI processes of engagement, focus, evocation, and planning. Coaches were required to discuss at least 90% of session-specific topics, which were monitored using checklists for each certification, and to complete individual MoI training, which was not graded. The evaluation of peer coach training involved surveys and a focus group. RESULTS: Three women and two men, averaging 75 years in age, completed the peer coach training for the Moving Well intervention. An in-person training session was added to address technology and MoI skill concerns, greatly enhancing their grasp of MoI skills and their ability to guide others through the program effectively. Peer coaches stressed the importance of live feedback, in-person training, and incorporating personal experiences into the program content during their training. CONCLUSION: To effectively train older adults as peer coaches for the Moving Well intervention, flexibility in learning formats, personalized guidance, peer support, and regular evaluations were essential in building the necessary MoI competencies to guide research participants in the program.

State mechanisms of change in eating disorder symptoms and fears during an online imaginal exposure treatment for eating disorders.

Anxiety and fear are key characteristics of eating disorders (EDs). Exposure therapy is a specific type of intervention aimed at reducing fear and anxiety and is efficacious in treating a variety of anxiety and related disorders. A growing body of research suggests that exposure therapy is also efficacious for the treatment of EDs. However, there is currently little research investigating mechanisms of change during exposure therapy for EDs. The current study (N = 143) expanded on an open series trial of imaginal exposure for EDs that found significant reductions in ED symptoms and core ED fears. In the current study we investigated change in state drive for thinness, body dissatisfaction, and anxiety as mechanisms underpinning change in ED symptoms and core ED fears during four sessions of online imaginal exposure treatment for EDs. We found that state body dissatisfaction, but not state drive for thinness or anxiety, was a mechanism of change for ED symptoms and some core ED fears. Our findings suggest that body dissatisfaction may be a mechanism driving change during exposure therapy for EDs. Optimizing exposure treatments to focus on body dissatisfaction may improve treatment outcomes for EDs.

Effect of cognitive behavioural therapy and yoga for generalised anxiety disorder on sleep quality in a randomised controlled trial: the role of worry, mindfulness, and perceived stress as mediators.

Sleep disturbances are present in ~65% of individuals with generalised anxiety disorder (GAD). Although both Kundalini yoga (KY) and cognitive behavioural therapy (CBT) are effective treatment options for GAD, little is known about how these treatments compare in improving sleep for GAD and what drives these changes. Accordingly, we examined the effects of CBT, KY, and stress education (SEdu; an attention control condition) on subjective sleep quality (as measured by the Pittsburgh Sleep Quality Index [PSQI] and Insomnia Severity Index [ISI]) in a randomised controlled trial of 226 adults with GAD (mean age 33.37 years; 70% female; 79% White). We hypothesised that both CBT and KY would outperform SEdu in improving sleep disturbances. Three potential mediators of sleep improvement (worry, mindfulness, perceived stress) were also examined. In line with hypotheses, PSQI and ISI scores significantly improved from pre- to post-treatment for all three treatment groups (all p < 0.001, all d > 0.97). However, contrary to predictions, sleep changes were not significantly greater for CBT or KY compared to SEdu. In mediation analyses, within-person deviations in worry, mindfulness, and stress each significantly mediated the effect of time on sleep outcomes. Degree of change in sleep attributable to worry (CBT > KY > SEdu) and perceived stress (CBT, KY > SEdu) was moderated by treatment group. Personalised medicine as well as combined treatment approaches should be studied to help reduce sleep difficulties for patients with GAD who do not respond.

Virtual training of rheumatoid arthritis peer coaches in motivational interviewing skills and concepts of cardiovascular disease.

Background: Peer coaching interventions are effective in helping individuals with chronic conditions understand their disease. Most peer coach training programs occur in person, which has become an obstacle during the COVID pandemic. We describe our experiences with virtual training for future peer coach interventions. Methods: Individuals with rheumatoid arthritis (RA) between 40 and 75 years of age were recruited and interviewed by the research team. We conducted seven virtual training sessions focused on four main points: Listen, Discuss, Practice, and Certify. The peer coaches provided feedback throughout the program, which was used to refine the training and intervention. A post-training focus group assessed satisfaction with the training program and intervention development process. Results: Four peer coaches (3 women, 1 man) were trained, including 2 Black and 2 White individuals with advanced degrees. Their ages ranged from 52 to 57, and their RA duration ranged from 5 to 15 years. An iterative process with the coaches and researchers resulted in a nine-week training program. Peer coaches reported satisfaction, confidence, and a preference for the virtual training format. Conclusion: This virtual peer coach training program was feasible and acceptable for coaches with advanced degrees during the global COVID-19 pandemic. Our approach represents an opportunity to adapt training that has been traditionally done in person. By doing so, our approach facilitates the recruitment and training of a diverse group of coaches and promotes sustainability.

A single-center, open-label, randomized, parallel-group trial to pilot the effectiveness of a peer coach behavioral intervention versus an active control in reducing anxiety and depression in patients scheduled for total knee replacement.

BACKGROUND: Moving Well is a behavioral intervention for patients with knee osteoarthritis (KOA) scheduled for a total knee replacement (TKR). The objective of this intervention is to help patients with KOA mentally and physically prepare for and recover from TKR. METHODS: This is an open-label pilot randomized clinical trial that will test the feasibility and effectiveness of the Moving Well intervention compared to an attention control group, Staying Well, to reduce symptoms of anxiety and depression in patients with KOA undergoing TKR. The Moving Well intervention is guided by Social Cognitive Theory. During this 12-week intervention, participants will receive 7 weekly calls before surgery and 5 weekly calls after surgery from a peer coach. During these calls, participants will be coached to use principles of cognitive behavioral therapy (CBT), stress reduction techniques, and will be assigned an online exercise program, and self-monitoring activities to complete on their own time throughout the program. Staying Well participants will receive weekly calls of similar duration from research staff to discuss a variety of health topics unrelated to TKR, CBT, or exercise. The primary outcome is the difference in levels of anxiety and/or depression between participants in the Moving Well and Staying Well groups 6 months after TKR. DISCUSSION: This study will pilot test the feasibility and effectiveness of Moving Well, a peer coach intervention, alongside principles of CBT and home exercise, to help patients with KOA mentally and physically prepare for and recover from TKR. TRIAL REGISTRATION: Clinicaltrials.gov. NCT05217420; Registered: January 31, 2022.

Personalizing eating disorder treatment using idiographic models: An open series trial.

OBJECTIVE: Treatments for adults with eating disorders (EDs) only work in about 50% of individuals, and for some diagnoses (e.g., anorexia nervosa; atypical anorexia nervosa), there are no existing evidence-based treatments. Part of the reason that treatments may only work in a subset of individuals is because of the high heterogeneity present in the EDs, even within diagnoses. Manualized treatments delivered in a standard format may not always address the most relevant symptoms for a specific individual. METHOD: The current open series trial recruited participants with transdiagnostic ED diagnoses (N = 79) to investigate the feasibility, acceptability, and initial clinical efficacy of a 10-session network-informed personalized treatment for eating disorders. This treatment uses idiographic (i.e., one-person) network models of ecological momentary assessment symptom data to match participants to evidence-based modules of treatment. RESULTS: We found that network-informed personalized treatment was highly feasible with low dropout rates, was rated as highly acceptable, and had strong initial clinical efficacy. ED severity decreased from pre- to posttreatment and at 1-year follow-up with a large effect size. ED cognitions, behaviors, clinical impairment, worry, and depression also decreased from pre- to posttreatment. CONCLUSIONS: These data suggest that network-informed personalized treatment has high acceptability and feasibility and can decrease ED and related pathology, possibly serving as a feasible alternative to existing treatments. Future randomized controlled trials comparing network-informed personalized treatment for ED to existing gold standard treatments are needed. Additionally, more research is needed on this type of personalized treatment both in the EDs, as well as in additional forms of psychopathology, such as depression. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Demography and space-use of Eastern Red-backed Salamanders (Plethodon cinereus) between mature and successional forests.

Space-use and demographic processes are critical to the persistence of populations across space and time. Despite their importance, estimates of these processes are often derived from a limited number of populations spanning broad habitat or environmental gradients. With increasing appreciation of the role fine-scale environmental variation in microgeographic adaptation, there is a need and value to assessing within-site variation in space-use and demographic patterns. In this study, we analyze 3 years of spatial capture-recapture data on the Eastern Red-backed Salamander collected from a mixed-use deciduous forest site in central Ohio, USA. Study plots were situated in both a mature forest stand and successional forest stand separated by <100-m distance. Our results showed that salamander density was reduced on successional plots, which corresponded with greater distance between nearest neighbors, less overlap in core use areas, greater space-use, and greater shifts in activity centers when compared to salamanders occupying the mature habitat. By contrast, individual growth rates of salamanders occupying the successional forest were significantly greater than salamanders in the mature forest. These estimates result in successional plot salamanders reaching maturity more than 1 year earlier than salamanders on the mature forest plots and increasing their estimated lifetime fecundity by as much as 43%. The patterns we observed in space-use and individual growth are likely the result of density-dependent processes, potentially reflecting differences in resource availability or quality. Our study highlights how fine-scale, within-site variation can shape population demographics. As research into the demographic and population consequences of climate change and habitat loss and alteration continue, future research should take care to acknowledge the role that fine-scale variation may play, especially for abiotically sensitive organisms with limited vagility.

A network approach can improve eating disorder conceptualization and treatment.

Eating disorders are severe mental illnesses with the second highest mortality rate of all psychiatric illnesses. Eating disorders are exceedingly deadly because of their complexity. Specifically, eating disorders are highly comorbid with other psychiatric illnesses (up to 95% of individuals with an eating disorder have at least one additional psychiatric illness), have extremely heterogeneous presentations, and individuals often migrate from one specific eating disorder diagnosis to another. In this Perspective, we propose that understanding eating disorder comorbidity and heterogeneity via a network theory approach offers substantial benefits for both conceptualization and treatment. Such a conceptualization, strongly based on theory, can identify specific pathways that maintain psychiatric comorbidity, how diagnoses vary across individuals, and how specific symptoms and comorbidities maintain illness for one individual, thereby paving the way for personalized treatment.

Impact of preference for yoga or cognitive behavioral therapy in patients with generalized anxiety disorder on treatment outcomes and engagement.

There is some, but inconsistent, evidence to suggest that matching patient treatment preference enhances treatment engagement and outcome. The current study examined differential preferences and factors associated with treatment preference for 12-week group cognitive behavioral therapy (CBT), yoga, or stress education in 226 adults with generalized anxiety disorder (GAD; 70% female, Mean age = 33 ± 13.5). In a subsample of 165 patients who reported an intervention preference and were randomized to yoga or CBT, we further examined whether match to preferred intervention improved the primary treatment outcome (responder status on Clinical Global Impressions Scale) and engagement (dropout, homework compliance). Preferences for CBT (44%) and yoga (40%) were similar among patients. Women tended to prefer yoga (OR = 2.75, p = .01) and CBT preference was associated with higher baseline perceived stress (OR = 0.92, p = .04) and self-consciousness meta-cognitions (OR = 0.90, p = .02). Among those not matched to their preference, treatment response was higher for those receiving CBT than yoga (OR = 11.73, p = .013); there were no group differences for those matched to their treatment preference. In yoga, those who received their preference were more likely to drop than those who did not (OR = 3.02, 95% CI = [1.20, 7.58], p = .037). This was not the case for CBT (OR = 0.37, 95% CI = [0.13, 1.03], p = .076). Preference match did not predict homework compliance. Overall, results suggest that treatment preference may be important to consider to optimize outcome and engagement; however, it may vary by treatment modality. Future research incorporating preference, especially with yoga for anxiety, is aligned with personalized medicine. TRIAL REGISTRATION: clinicaltrials.gov: NCT01912287; https://clinicaltrials.gov/ct2/show/NCT01912287.

Psychiatric Comorbidity Among Eating Disorders and Obsessive-Compulsive Disorder and Underlying Shared Mechanisms and Features: An Updated Review.

Eating disorders (EDs) are highly comorbid with obsessive-compulsive disorder (OCD), with comorbidity rates as high as 41%. In the current review, we summarize the literature regarding the prevalence of ED-OCD comorbidity. We also identify and review the literature assessing shared features (i.e., shared characteristics or symptoms) and mechanisms (i.e., variables that may explain ED or OCD symptoms) of EDs and OCD. Potential shared features of EDs and OCD include age of onset, course of illness, obsessions, compulsions and ritualistic behaviors, and thought action fusion. Shared mechanisms that may explain ED-OCD comorbidity include genetic and neurobiological mechanisms, anxiety and fear, repetitive negative thinking, perfectionism, intolerance of uncertainty, distress tolerance, and impulsivity. Based on these shared features and mechanisms, a theoretical conceptualization of ED and OCD comorbidity is developed, and outline considerations for assessment, differential diagnosis, treatment, and future research regarding ED-OCD comorbidity are described.

Core eating disorder fears: Prevalence and differences in eating disorder fears across eating disorder diagnoses.

OBJECTIVE: Fear and anxiety are key maintaining factors for eating disorder (ED) pathology. Maladaptive fears lead to ED behaviors and avoidance, which provide temporary relief, but ultimately reinforce the fear and contribute to a cycle that maintains the ED. To date, fears of food and weight gain are the most explored fears underlying ED pathology. However, recently other important ED fears have been identified, including fears of social consequences and personal consequences. METHOD: The current study (N = 229 individuals with an ED) aimed to better characterize ED fears. Specifically, this study examined which ED fears were most endorsed across and within ED diagnoses, and if there were differences in ED fears by diagnosis and by weight status. RESULTS: Overall, fear of gaining weight was the most frequently endorsed fear, followed by fear of food, and fear of judgment. Individuals with anorexia nervosa (AN) most frequently endorsed fear of food, individuals with atypical AN and bulimia nervosa: fear of gaining weight, and those with other specified feeding and eating disorder: fear of judgment. Limited differences were found between diagnoses. When examining by weight category, participants with underweight most frequently endorsed fear of food, participants with normal weight: fear of gaining weight, and participants with overweight and obesity: fear of judgment. DISCUSSION: These findings suggest ED fears are heterogenous. Given such high heterogeneity, this work highlights the importance of assessing for specific ED fears at the beginning of treatment, which could be used to deliver personalized exposure treatment. PUBLIC SIGNIFICANCE STATEMENT: Eating disorders (EDs) are serious mental illnesses with high rates of medical and psychiatric comorbidities. Fear plays an important role in the development and maintenance of EDs. The present study found fear of food, weight gain, and judgment are the most frequently endorsed fears for individuals with EDs and found few differences in fears based on ED diagnosis. These findings highlight the importance of assessing individuals' specific ED fears for treatment.

Protocol for the pilot randomized trial of the CArdiovascular Risk assEssment for Rheumatoid Arthritis (CARE RA) intervention: a peer coach behavioral intervention.

BACKGROUND: Cardiovascular disease (CVD) is the most common cause of death among people with rheumatoid arthritis (RA), with an estimated increased risk of 50-60% compared to the general population. Lipid-lowering strategies have been shown to lower CVD risk significantly in people with RA and hyperlipidemia. Thus, CVD risk assessment has an important role to play in reducing CVD among people with RA. Yet currently only 37 to 45% of this population are receiving primary lipids screening. This paper describes the CArdiovascular Risk assEssment for RA (CARE RA) intervention, which is designed to address this issue. CARE RA is a peer coach intervention, that is, an intervention in which a person with RA coaches another person with RA, which is designed to educate people with RA about the relation between RA and CVD risk and to help them obtain evidence-based CVD risk assessment and treatment. METHODS: This is an open-label pilot study that will test if the participants assigned to complete the CARE RA curriculum with a peer coach will receive a cardiovascular risk assessment more frequently compared to those that complete the CARE RA curriculum by themselves. The CARE RA intervention is guided by Social Cognitive Theory. Participants in the peer coach intervention arm will receive the assistance of a peer coach who will call the participants once a week for 5 weeks to go over the CARE RA curriculum and train them on how to obtain CVD risk assessment. The control arm will complete the CARE RA curriculum without any assistance. Participants will be randomized 1:1 either to the control arm or to the peer coach intervention arm. The primary outcome is a participant's having a CVD risk assessment or initiating a statin, if indicated. Secondary outcomes include patient activation and RA medication adherence. The RE-AIM implementation framework guides the implementation and evaluation of the intervention. DISCUSSION: This pilot study will test the feasibility of the peer coach intervention in anticipation of a larger trial. CARE RA pioneers the use of peer coaches to facilitate the implementation of evidence-based treatment guidelines among people with RA. TRIAL REGISTRATION: ClinicalTrials.gov NCT04488497 . Registered on July 28, 2020.

Using individual networks to identify treatment targets for eating disorder treatment: a proof-of-concept study and initial data.

BACKGROUND: Eating disorders (EDs) are severe mental illnesses, with high morbidity, mortality, and societal burden. EDs are extremely heterogenous, and only 50% of patients currently respond to first-line treatments. Personalized and effective treatments for EDs are drastically needed. METHODS: The current study (N = 34 participants with an ED diagnosis collected throughout the United States) aimed to investigate best methods informing how to select personalized treatment targets utilizing idiographic network analysis, which could then be used for evidence based personalized treatment development. We present initial data collected via experience sampling (i.e., ecological momentary assessment) over the course of 15 days, 5 times a day (75 total measurement points) that were used to select treatment targets for a personalized treatment for EDs. RESULTS: Overall, we found that treatment targets were highly variable, with less than 50% of individuals endorsing central symptoms related to weight and shape, consistent with current treatment response rates for treatments designed to target those symptoms. We also found that different aspects of selection methods (e.g., number of items, type of centrality measure) impacted treatment target selection. CONCLUSIONS: We discuss implications of these data, how to use idiographic network analysis to personalize treatment, and identify areas that need future research. TRIAL REGISTRATION: Clinicaltrials.gov, NCT04183894. Registered 3 December 2019-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04183894 . NCT04183894 (ClinicalTrials.gov identifier).

Eating disorders are severe psychiatric illnesses that carry high mortality, morbidity, and societal and personal burden. Treatments for eating disorders only work in 50% of patients, signifying a great need to improve treatments. One reason that treatments may not work, is because eating disorders vary substantially from one individual to the next, which existing treatments do not fully consider. The current study (N = 34 participants with an eating disorder diagnosis) uses a new modeling technique to identify which symptoms should be targeted in treatment in a personalized manner. As expected, we found that, using this modeling technique, symptoms that should be targeted in treatment vary considerably. We discuss how to use this modeling technique to identify individual treatment targets and ways in which the field can use this strategy to improve existing and create new treatments.

A pilot randomized control trial of online exposure for eating disorders and mechanisms of change delivered after discharge from intensive eating disorder care: A registered report.

More than 50% of individuals with an eating disorder (ED) will readmit to treatment within 6 months of treatment discharge and often due to persistent cognitive ED pathology. Interventions addressing unremitted cognitive ED pathology following discharge from intensive treatment are crucial to prevent readmission. Imaginal exposure therapy facilitates the approach of feared stimuli not accessible in everyday life (e.g., rapidly gaining weight). In the current pilot randomized control trial (RCT), participants will be randomly assigned to a five-session online imaginal exposure condition (n = 65) or a control online writing and thinking intervention (n = 65) within a month of discharge from intensive treatment. Exposure participants write about and imagine an ED fear and control participants will write about their ED generally. We will examine the feasibility and acceptability of the treatment conditions and whether imaginal exposure is more effective in preventing readmission than the control condition. We will test the efficacy of the imaginal exposure treatment in reducing ED symptoms and fears of food and weight gain, and whether fear learning is a mechanism of change related to ED pathology. Ultimately, this research will lead to the development of an easily deployable readmission prevention treatment based on fear conditioning targets.

Anhedonia is central for the association between quality of life, metacognition, sleep, and affective symptoms in generalized anxiety disorder: A complex network analysis.

BACKGROUND: Poor quality of life, sleep problems, anhedonia, and negative metacognitions are common in anxiety and depression. To examine the nature of the relationship between these features and the role of metacognitions, anhedonia, and quality of life in anxiety and depression, we conducted a complex network analysis with items of self-report measures assessing quality of life, sleep, negative thinking styles, anxiety, and depression. METHODS: Participants were 226 treatment seeking individuals with a primary DSM-5 diagnosis of generalized anxiety disorder. Node centrality, strength, expected influence, community, and bridge estimation were calculated using partial correlation coefficients and glasso regularization. RESULTS: Results revealed that anhedonia was the most central node followed by quality of life nodes. Moreover, anhedonia exhibited the highest strength and expected influence, which were both stable, reliable metrics within the network. Metacognitions were not central nodes in the network, but were strong bridge symptoms between communities. LIMITATIONS: The results are limited by the cross-sectional nature of the data and the administration of self-report scales at one time-point, despite different rating anchors. CONCLUSION: These findings suggest that anhedonia is a crucial element for the association between quality of life, sleep problems, and negative cognitions.

A Perfect Ten-Decoy Maps Uncover Polymerase Complexes within Reoviridae Virion.

In this issue of Structure, Kaelber et al. (2020) use cryo-EM and synthetic decoy maps to reveal the patterning of 10 polymerase complexes within FAKV, a Reoviridae family member containing 9 genome segments. Their findings support a model for FAKV assembly that has implications for the entire Reoviridae family.

Towards a precision psychiatry approach to anxiety disorders with ecological momentary assessment: the example of panic disorder.

BACKGROUND: Treatments for anxiety disorders are among the most effective in psychiatry. Yet, there is considerable room for improvement. AIM: In this paper, we discuss the value of ecological momentary assessment as a research method and clinical tool. METHODS: We begin by describing ecological momentary assessment and its advantages, including the ability to collect ecologically valid information about mental disorders, in real time, in individual patients. We then illustrate the value of this approach for anxiety disorder treatment using two patients with panic disorder who completed ecological momentary assessments for 2 weeks before and after a cognitive-behavioural therapy intervention. We focus especially on two key pieces of information provided by ecological momentary assessment data: information about symptom dynamics and information about the relationships among symptoms as they unfold over time within individual patients. PERSPECTIVE: Although considerable work is needed to further develop this methodology in the context of anxiety disorder treatment, we believe that these pieces of information may ultimately inform our understanding of how anxiety disorder treatments have their effect and how those treatments can be tailored to individual patients.

A multi-disciplinary clinic for SCN8A-related epilepsy.

OBJECTIVE: We endeavored to evaluate a cohort of patients diagnosed with SCN8A-related epilepsy in a multi-disciplinary clinic and to create a bio-repository. METHODS: We recruited patients with epilepsy due to SCN8A variants at Children's National Medical Center, through family organizations, or SCN8A.net. Study procedures included medical record review, review of EEG and MRI data, clinical evaluation, the Vineland Adaptive Behavior Scales, Third Edition (VABS-3), DNA extraction, and preparation of peripheral blood mononuclear cells. RESULTS: Seventeen patients (9 months - 19 years) completed the study. Age at seizure onset was 1 day to 4 years old (median age 4 months). Epilepsy phenotype ranged from mild epilepsy to severe developmental and epileptic encephalopathy. Medications targeting the voltage-gated sodium channel were most often effective, while levetiracetam resulted in worsening seizures and/or developmental regression in 7/16 (p < 0.05). VABS-3 scores were below age expectations for most children; older children had lower scores. Neurological examination revealed hypotonia (13), spastic quadriparesis (1), ataxia (9), dyskinesia (2)/ dystonia (7), and four non-ambulatory. CONCLUSIONS: This is the first report of a large series of patients with epilepsy due to SCN8A variants evaluated in a single multi-disciplinary clinic. By utilizing a more comprehensive and consistent evaluation, we clarify specific seizure and epilepsy types, describe a distinct epilepsy phenotype in a patient with a nonsense variant, delineate patterns of developmental delay, language, and swallow function (specifically anomic aphasia and flaccid dysarthria), identify and characterize movement disorders, report common findings on physical exam, and demonstrate clinical worsening with levetiracetam.

In Vitro Double-Stranded RNA Synthesis by Rotavirus Polymerase Mutants with Lesions at Core Shell Contact Sites.

The rotavirus polymerase VP1 mediates all stages of viral RNA synthesis within the confines of subviral particles and while associated with the core shell protein VP2. Transcription (positive-strand RNA [+RNA] synthesis) by VP1 occurs within double-layered particles (DLPs), while genome replication (double-stranded RNA [dsRNA] synthesis) by VP1 occurs within assembly intermediates. VP2 is critical for VP1 enzymatic activity; yet, the mechanism by which the core shell protein triggers polymerase function remains poorly understood. Structural analyses of transcriptionally competent DLPs show that VP1 is located beneath the VP2 core shell and sits slightly off-center from each of the icosahedral 5-fold axes. In this position, the polymerase is contacted by the core shell at 5 distinct surface-exposed sites, comprising VP1 residues 264 to 267, 547 to 550, 614 to 620, 968 to 980, and 1022 to 1025. Here, we sought to test the functional significance of these VP2 contact sites on VP1 with regard to polymerase activity. We engineered 19 recombinant VP1 (rVP1) proteins that contained single- or multipoint alanine mutations within each individual contact site and assayed them for the capacity to synthesize dsRNA in vitro in the presence of rVP2. Three rVP1 mutants (E265A/L267A, R614A, and D971A/S978A/I980A) exhibited diminished in vitro dsRNA synthesis. Despite their loss-of-function phenotypes, the mutants did not show major structural changes in silico, and they maintained their overall capacity to bind rVP2 in vitro via their nonmutated contact sites. These results move us toward a mechanistic understanding of rotavirus replication and identify precise VP2-binding sites on the polymerase surface that are critical for its enzymatic activation.IMPORTANCE Rotaviruses are important pathogens that cause severe gastroenteritis in the young of many animals. The viral polymerase VP1 mediates all stages of viral RNA synthesis, and it requires the core shell protein VP2 for its enzymatic activity. Yet, there are several gaps in knowledge about how VP2 engages and activates VP1. Here, we probed the functional significance of 5 distinct VP2 contact sites on VP1 that were revealed through previous structural studies. Specifically, we engineered alanine amino acid substitutions within each of the 5 VP1 regions and assayed the mutant polymerases for the capacity to synthesize RNA in the presence of VP2 in a test tube. Our results identified residues within 3 of the VP2 contact sites that are critical for robust polymerase activity. These results are important because they enhance the understanding of a key step of the rotavirus replication cycle.