HPV16 E7 Genetic Conservation Is Critical to Carcinogenesis.

Although most cervical human papillomavirus type 16 (HPV16) infections become undetectable within 1-2 years, persistent HPV16 causes half of all cervical cancers. We used a novel HPV whole-genome sequencing technique to evaluate an exceptionally large collection of 5,570 HPV16-infected case-control samples to determine whether viral genetic variation influences risk of cervical precancer and cancer. We observed thousands of unique HPV16 genomes; very few women shared the identical HPV16 sequence, which should stimulate a careful re-evaluation of the clinical implications of HPV mutation rates, transmission, clearance, and persistence. In case-control analyses, HPV16 in the controls had significantly more amino acid changing variants throughout the genome. Strikingly, E7 was devoid of variants in precancers/cancers compared to higher levels in the controls; we confirmed this in cancers from around the world. Strict conservation of the 98 amino acids of E7, which disrupts Rb function, is critical for HPV16 carcinogenesis, presenting a highly specific target for etiologic and therapeutic research.

Intravital mucosal imaging of CD8+ resident memory T cells shows tissue-autonomous recall responses that amplify secondary memory.

CD8+ T cell immunosurveillance dynamics influence the outcome of intracellular infections and cancer. Here we used two-photon intravital microscopy to visualize the responses of CD8+ resident memory T cells (TRM cells) within the reproductive tracts of live female mice. We found that mucosal TRM cells were highly motile, but paused and underwent in situ division after local antigen challenge. TRM cell reactivation triggered the recruitment of recirculating memory T cells that underwent antigen-independent TRM cell differentiation in situ. However, the proliferation of pre-existing TRM cells dominated the local mucosal recall response and contributed most substantially to the boosted secondary TRM cell population. We observed similar results in skin. Thus, TRM cells can autonomously regulate the expansion of local immunosurveillance independently of central memory or proliferation in lymphoid tissue.

T Cells in Nonlymphoid Tissues Give Rise to Lymph-Node-Resident Memory T Cells.

Immunosurveillance of secondary lymphoid organs (SLO) is performed by central memory T cells that recirculate through blood. Resident memory T (Trm) cells remain parked in nonlymphoid tissues and often stably express CD69. We recently identified Trm cells within SLO, but the origin and phenotype of these cells remains unclear. Using parabiosis of "dirty" mice, we found that CD69 expression is insufficient to infer stable residence of SLO Trm cells. Restimulation of nonlymphoid memory CD8+ T cells within the skin or mucosa resulted in a substantial increase in bona fide Trm cells specifically within draining lymph nodes. SLO Trm cells derived from emigrants from nonlymphoid tissues and shared some transcriptional and phenotypic signatures associated with nonlymphoid Trm cells. These data indicate that nonlymphoid cells can give rise to SLO Trm cells and suggest vaccination strategies by which memory CD8+ T cell immunosurveillance can be regionalized to specific lymph nodes.

Tropism for ciliated cells is the dominant driver of influenza viral burst size in the human airway.

Influenza viruses pose a significant burden on global human health. Influenza has a broad cellular tropism in the airway, but how infection of different epithelial cell types impacts replication kinetics and burden in the airways is not fully understood. Using primary human airway cultures, which recapitulate the diverse epithelial cell landscape of the human airways, we investigated the impact of cell type composition on virus tropism and replication kinetics. Cultures were highly diverse across multiple donors and 30 independent differentiation conditions and supported a range of influenza replication. Although many cell types were susceptible to influenza, ciliated and secretory cells were predominantly infected. Despite the strong tropism preference for secretory and ciliated cells, which consistently make up 75% or more of infected cells, only ciliated cells were associated with increased virus production. Surprisingly, infected secretory cells were associated with overall reduced virus output. The disparate response and contribution to influenza virus production could be due to different pro- and antiviral interferon-stimulated gene signatures between ciliated and secretory populations, which were interrogated with single-cell RNA sequencing. These data highlight the heterogeneous outcomes of influenza virus infections in the complex cellular environment of the human airway and the disparate impacts of infected cell identity on multiround burst size, even among preferentially infected cell types.

Factors Associated with Planned Future Use of PrEP in the Next 3 Months and Likelihood to Use PrEP Among Black Cisgender HIV-negative Women in Texas.

Identifying and then addressing barriers and leveraging facilitators is important to help increase pre-exposure prophylaxis (PrEP) use among Black women vulnerable to HIV acquisition. The present cross-sectional study examined what factors were associated with future plans to use PrEP, and general likelihood to use it among a convenience sample of 152 adult, Black cisgender women from three metropolitan areas in Texas. The final multivariable logistic regression model revealed that relationship status (aOR = 0.20, 95% CI: 0.05-0.73, p < 0.05), PrEP anticipated stigma (aOR = 0.29, 95% CI: 0.10-0.78, p < 0.05), perceived discrimination (aOR = 0.40, 95% CI: 0.21-0.78, p < 0.01) and interest in learning more about PrEP (aOR = 5.32, 95% CI: 2.60-10.9, p < 0.001) were associated with future plans to use PrEP. The final multivariable linear regression model with maximum likelihood estimation identified that perceived discrimination (ß=-0.24, SE: -0.38 - -0.10, p < 0.01), perceived HIV risk (ß = 0.33, SE: 0.18-0.49, p < 0.001), willingness to use PrEP with condoms (ß = 1.26, SE: 0.94-1.60, p < 0.001), and comfort communicating about PrEP with a provider (ß = 0.23, SE: 0.06-0.41, p < 0.01) were associated with general likelihood to use PrEP. Findings reveal key factors that warrant further attention and examination toward improving PrEP use within this population.

Use of Stated Preference Methods in HIV Treatment and Prevention Research in the United States: A Systematic Review.

Stated preference (SP) methods are increasingly being applied to HIV-related research and continuously provide researchers with health utility scores of select healthcare products or services that populations consider important. Following PRISMA guidelines, we sought to understand how SP methods have been applied in HIV-related research. We conducted a systematic review to identify studies meeting the following criteria: SP method is clearly stated, conducted in the United States, was published between 01/01/2012 and 02/12/2022, and included adults aged 18 and over. Study design and SP method application were also examined. We identified six SP methods (e.g., Conjoint Analysis, Discrete Choice Experiment) across 18 studies, which were categorized into one of two groups: HIV prevention and HIV treatment-care. Categories of attributes used in SP methods largely focused on: administration, physical/health effects, financial, location, access, and external influences. SP methods are innovative tools capable of informing researchers on what populations consider most beneficial when deciding on treatment, care, or prevention options for HIV.

Dyadic Influences on Pre-exposure Prophylaxis (PrEP) Use and Attitudes Among Male Couples.

Pre-exposure prophylaxis (PrEP) affords an opportunity to significantly reduce the risk of HIV infection among male couples. We used cross-sectional dyadic data from 382 concordant-negative male couples to examine demographic and relationship characteristics associated with current PrEP use, willingness to use PrEP in the future, and perceived ability to adhere to PrEP using Actor-Partner Independence Models. Few partnered men reported currently using PrEP (16.4%) and 57.7% of non-users reported being unlikely to use PrEP in the future. Actor and partner perceptions of PrEP stigma significantly reduced PrEP use and perceptions of willingness to use PrEP or the ability to adhere to PrEP, while perceiving a higher prevalence of HIV among men was associated with significant increases in PrEP use, willingness and perceived ability to adhere. Perceptions that more friends would support PrEP use were also significantly associated with increases in willingness and perceived ability to adhere to PrEP. Dyadic interventions are needed to provide couples the skills to communicate about HIV risk and prevention, and address myths around the protective effect of relationships against HIV acquisition.

Efficacy of a Telehealth Delivered Couples' HIV Counseling and Testing (CHTC) Intervention to Improve Formation and Adherence to Safer Sexual Agreements Among Male Couples in the US: Results from a Randomized Control Trial.

This paper reports the results of a randomized controlled trial (RCT) to assess the efficacy of Nexus, a telehealth delivered intervention that combines Couples' HIV counseling and testing (CHTC) with home-based HIV-testing, examining the impact of the intervention on the couples' formation and adherence to safer sexual agreements. Between 2016 and 2018, 424 couples were recruited online from the U.S and randomized to the intervention arm (a telehealth delivered CHTC session with two home HIV-testing kits) or a control arm (two home HIV-testing kits), with study assessments at baseline, 3 and 6 months. Outcomes were the formation and adherence to safer sexual agreements, dyadic discordance in sexual agreements, breakage of sexual agreements, and perceptions of PrEP. Couples in the intervention arm had significantly greater odds of reporting a safer sexual agreement (3 months OR 1.87, p-value 0.005, and 6 months OR 1.84, p-value 0.007), lower odds of reporting discordant sexual agreements at 6 months (OR 0.62, p-value 0.048), and a significantly lower odds of reporting breaking their sexual agreement (3 months OR 0.51, p-value 0.035, and 6 months OR 0.23, p-value 0.000). By 6 months, couples in the intervention arm were less likely to say PrEP was beneficial to one (RRR 0.33, P = 0.000) or both of them (RRR 0.29, P = 0.000) than being beneficial to neither of the partners. The high levels of acceptability and efficacy of the intervention demonstrate strong potential for the scale-up of this efficacious intervention that is delivered through a low-cost telehealth platform.

Adoptive T Cell Therapy with IL-12-Preconditioned Low-Avidity T Cells Prevents Exhaustion and Results in Enhanced T Cell Activation, Enhanced Tumor Clearance, and Decreased Risk for Autoimmunity.

Optimal ex vivo expansion protocols of tumor-specific T cells followed by adoptive cell therapy must yield T cells able to home to tumors and effectively kill them. Our previous study demonstrated ex vivo activation in the presence of IL-12-induced optimal CD8+ T cell expansion and melanoma regression; however, adverse side effects, including autoimmunity, can occur. This may be due to transfer of high-avidity self-specific T cells. In this study, we compared mouse low- and high-avidity T cells targeting the tumor Ag tyrosinase-related protein 2 (TRP2). Not surprisingly, high-avidity T cells provide superior tumor control, yet low-avidity T cells can promote tumor regression. The addition of IL-12 during in vitro expansion boosts low-avidity T cell responsiveness, tumor regression, and prevents T cell exhaustion. In this study, we demonstrate that IL-12-primed T cells are resistant to PD-1/PD-L1-mediated suppression and retain effector function. Importantly, IL-12 preconditioning prevented exhaustion as LAG-3, PD-1, and TOX were decreased while simultaneously increasing KLRG1. Using intravital imaging, we also determined that high-avidity T cells have sustained contacts with intratumoral dendritic cells and tumor targets compared with low-avidity T cells. However, with Ag overexpression, this defect is overcome, and low-avidity T cells control tumor growth. Taken together, these data illustrate that low-avidity T cells can be therapeutically beneficial if cocultured with IL-12 cytokine during in vitro expansion and highly effective in vivo if Ag is not limiting. Clinically, low-avidity T cells provide a safer alternative to high-avidity, TCR-engineered T cells, as IL-12-primed, low-avidity T cells cause less autoimmune vitiligo.

Partner Support and Communication for Pre-exposure Prophylaxis (PrEP) Use Among Male Couples.

Between one to two-thirds of HIV infections among gay, bisexual, and other men who have sex with men are from primary partners, and there has been increased research attention focused on strategies to increase PrEP adoption among male couples. While there is evidence that partner support is a strong correlate of pre-exposure prophylaxis (PrEP) adoption, there has been a lack of attention on PrEP communication dynamics among male couples. In this paper, we build upon this literature through analysis of dyadic data from a large cross-sectional survey of 543 concordant sero-negative and serodiscordant male couples to examine individual and relationship factors associated with reports of partner communication around PrEP, comfort in discussing PrEP, and perceived partner-level support for PrEP use. PrEP use was relatively low (16.2%), and although 87.5% of men reported their partners would support their PrEP use, only 26.3% had talked to their partner recently about PrEP. PrEP communication and perceived support for PrEP were significantly negatively associated with PrEP stigma and stigma based on sexuality (i.e., internalized homophobia and enacted external stigma based on sexuality), while men with sexual agreements were more comfortable talking about PrEP with their partner. There is a need to adapt current interventions, or develop new dyadic interventions, that provide opportunities for male couples to talk and learn about PrEP together, as a potential pathway to engage them toward PrEP use.

Perspectives on a Couples-Based, e-Health HIV Prevention Toolkit Intervention: A Qualitative Dyadic Study with Black, Heterosexual Couples in New York State.

Web-based technology provides an unparalleled opportunity to increase access and uptake of couples-based HIV prevention interventions. e-Health HIV prevention interventions for US Black heterosexual couples have largely been understudied. To address this gap, we applied the Assessment Phase of the ADAPT-ITT Framework to investigate Black heterosexual couples' perspectives on an existing e-Health, couples-based HIV prevention intervention. Applying a qualitative descriptive approach, joint dyadic interviews were conducted with 28 Black heterosexual couples from three jurisdictions in New York State. Content dyadic analysis revealed three descriptive categories: perspectives of the toolkit intervention (sub-codes: perceived relevance, reactions to core components), recommendations to enhance intervention relevancy (sub-codes: tailoring to relationship type, adding new content), and lasting intervention considerations (sub-codes: toolkit usability and language use). Overall, couples found the toolkit intervention content and usability acceptable and reflected on its potential to build sexual and relationship health. Couples recommended to enhance toolkit adaptability for varied couple's motivation and types re-consider terms like sexual agreements, and include content to facilitate communication regarding sensitive topics (e.g., childhood sexual trauma, co-parenting, family planning) and other issues that may have more relevance to the experience of US Black persons (i.e., wealth building).

Evidence and implication of interventions across various socioecological levels to address pre-exposure prophylaxis uptake and adherence among men who have sex with men in the United States: a systematic review.

BACKGROUND: Pre-exposure prophylaxis (PrEP) represents a proven biomedical strategy to prevent HIV transmissions among men who have sex with men (MSM) in the United States (US). Despite the design and implementation of various PrEP-focus interventions in the US, aggregated evidence for enhancing PrEP uptake and adherence is lacking. The objective of this systematic review is to synthesize and evaluate interventions aimed to improve PrEP uptake and adherence among MSM in the US, and identify gaps with opportunities to inform the design and implementation of future PrEP interventions for these priority populations. METHODS: We followed the PRISMA guidelines and conducted a systematic review of articles (published by November 28, 2021) with a focus on PrEP-related interventions by searching multiple databases (PubMed, MEDLINE, Web of Science and PsycINFO). Details of PrEP interventions were characterized based on their socioecological level(s), implementation modalities, and stage(s) of PrEP cascade continuum. RESULTS: Among the 1363 articles retrieved from multiple databases, 42 interventions identified from 47 publications met the inclusion criteria for this review. Most individual-level interventions were delivered via text messages and/or apps and incorporated personalized elements to tailor the intervention content on participants' demographic characteristics or HIV risk behaviors. Interpersonal-level interventions often employed peer mentors or social network strategies to enhance PrEP adoption among MSM of minority race. However, few interventions were implemented at the community-, healthcare/institution- or multiple levels. CONCLUSIONS: Interventions that incorporate multiple socioecological levels hold promise to facilitate PrEP adoption and adherence among MSM in the US given their acceptability, feasibility, efficacy and effectiveness. Future PrEP interventions that simultaneously address PrEP-related barriers/facilitators across multiple socioecological levels should be enhanced with a focus to tackle contextual and structural barriers (e.g., social determinants of health, stigma or medical mistrust) at the community- and healthcare/institution-level to effectively promote PrEP use for MSM of color.

Dyadic effects of enacted stigma, internalized homophobia, and communal coping on depressive symptoms among cisgender sexual minority male couples.

The present study investigated the dyadic direct and indirect effects of enacted stigma on depressive symptoms via internalized homophobia and whether communal coping moderated the effects of enacted stigma on internalized homophobia and depressive symptoms. Hypotheses were tested using actor-partner interdependence models with a sample of 543 cisgender sexual minority male couples. Results showed both partners' enacted stigma experiences were associated with elevated levels of internalized homophobia via actor and partner effects. Internalized homophobia was only associated with elevated depressive symptoms via actor effects. Indirect effects analysis suggested that internalized homophobia mediated the actor and partner influence of enacted stigma on depressive symptoms. Communal coping moderated the direct effects of enacted stigma on internalized homophobia and attenuated the conditional indirect actor and partner effects of enacted stigma on depressive symptoms. Findings underscore the role of intimate relationship processes in understanding the impacts of enacted stigma on depressive symptoms.

En el presente estudio se investigaron los efectos diádicos directos e indirectos del estigma externo en los síntomas depresivos mediante la homofobia internalizada, y si el afrontamiento comunitario moderó los efectos del estigma externo en la homofobia internalizada y los síntomas depresivos. Se comprobaron hipótesis utilizando modelos de interdependencia actor-pareja con una muestra de 543 parejas masculinas cisgénero pertenecientes a minorías sexuales. Los resultaros indicaron que las experiencias de estigma externo de ambos integrantes de la pareja estuvieron asociadas con niveles elevados de homofobia internalizada mediante efectos en el actor y la pareja. La homofobia internalizada solo estuvo asociada con síntomas depresivos elevados mediante efectos en el actor. El análisis de efectos indirectos indicó que la homofobia internalizada medió la influencia del estigma externo del actor y la pareja en los síntomas depresivos. El afrontamiento comunitario moderó los efectos directos del estigma externo en la homofobia internalizada y atenuó los efectos condicionales indirectos del estigma externo en los síntomas depresivos del actor y la pareja. Los resultados subrayan el papel que desempeñan los procesos relacionales íntimos a la hora de comprender los efectos del estigma externo en los síntomas depresivos.

Reducing HIV Risk Behaviors Among Black Women Living With and Without HIV/AIDS in the U.S.: A Systematic Review.

This systematic review provides an examination of the status of HIV/AIDS prevention interventions for Black, heterosexual women in the U.S. from 2012 to 2019. Using PRISMA guidelines, 28 interventions were identified. Over half of the interventions were: conducted in the southern region of the U.S.; evaluated using a randomized controlled trial; focused on adults; used a group-based intervention delivery; were behaviorally focused and theoretically driven. None included biomedical strategies of PrEP, nPEP, and TasP. Few interventions included adolescent or aging Black women; none included their sex/romantic partners. Future studies dedicated to addressing the specific needs of subpopulations of Black, heterosexual women may provide opportunities to expand and/or tailor current and future HIV/AIDS prevention interventions, including offering participants with options to choose which, and the level of involvement, of their sex/romantic partner(s) in their sexual health decision-making. While strides to improve HIV prevention efforts with Black, heterosexual women have occurred, more is needed.

Perceived facilitators of decision-making and usage of biomedical HIV prevention strategies: findings from an online, qualitative study with same-gender male couples in the United States.

The early stages of gay and bisexual men's relationships are a critical period for communicating about HIV prevention strategies. This study sought to: (1) explore facilitators to decision-making to use prevention strategies and (2) describe the prevention strategies being used by same-gender male couples in new relationships. Individual interviews were conducted with 76 partnered men, representing 37 couples and 2 individuals. Couples had been together for one year or less, and varied by U.S. geographical region of residence and HIV serostatus: 8 seroconcordant positive, 17 seroconcordant negative, and 13 serodiscordant couples. Two overarching qualitative themes emerged: (1) communication and (2) information and resources. Notably, few couples had both partners mention the same facilitator. The most commonly used HIV prevention strategies were treatment as prevention for partners in seroconcordant positive and serodiscordant couple relationships, and HIV/STI testing for partners of seroconcordant negative couples. Compared to the other two couple groups, fewer seroconcrdant negative couples were aware of each other's use of strategies. Study findings suggest these facilitators are important to include in future interventions. Efforts are also needed to improve within-dyad awareness about which strategies partners are using and how they may best support one another toward their sexual health goals.

Chrysalis: A New Method for High-Throughput Histo-Cytometry Analysis of Images and Movies.

Advances in imaging have led to the development of powerful multispectral, quantitative imaging techniques, like histo-cytometry. The utility of this approach is limited, however, by the need for time consuming manual image analysis. We therefore developed the software Chrysalis and a group of Imaris Xtensions to automate this process. The resulting automation allowed for high-throughput histo-cytometry analysis of three-dimensional confocal microscopy and two-photon time-lapse images of T cell-dendritic cell interactions in mouse spleens. It was also applied to epi-fluorescence images to quantify T cell localization within splenic tissue by using a "signal absorption" strategy that avoids computationally intensive distance measurements. In summary, this image processing and analysis software makes histo-cytometry more useful for immunology applications by automating image analysis.

TCR Affinity Biases Th Cell Differentiation by Regulating CD25, Eef1e1, and Gbp2.

Naive CD4+ T lymphocytes differentiate into various Th cell subsets following TCR binding to microbial peptide:MHC class II (p:MHCII) complexes on dendritic cells (DCs). The affinity of the TCR interaction with p:MHCII plays a role in Th differentiation by mechanisms that are not completely understood. We found that low-affinity TCRs biased mouse naive T cells to become T follicular helper (Tfh) cells, whereas higher-affinity TCRs promoted the formation of Th1 or Th17 cells. We explored the basis for this phenomenon by focusing on IL-2R signaling, which is known to promote Th1 and suppress Tfh cell differentiation. SIRP⍺+ DCs produce abundant p:MHCII complexes and consume IL-2, whereas XCR1+ DCs weakly produce p:MHCII but do not consume IL-2. We found no evidence, however, of preferential interactions between Th1 cell-prone, high-affinity T cells and XCR1+ DCs or Tfh cell-prone, low-affinity T cells and SIRP⍺+ DCs postinfection with bacteria expressing the peptide of interest. Rather, high-affinity T cells sustained IL-2R expression longer and expressed two novel Th cell differentiation regulators, Eef1e1 and Gbp2, to a higher level than low-affinity T cells. These results suggest that TCR affinity does not influence Th cell differentiation by biasing T cell interactions with IL-2-consuming DCs, but instead, directly regulates genes in naive T cells that control the differentiation process.

Programmed Death-1 Restrains the Germinal Center in Type 1 Diabetes.

Programmed death-1 (PD-1) inhibits T and B cell function upon ligand binding. PD-1 blockade revolutionized cancer treatment, and although numerous patients respond, some develop autoimmune-like symptoms or overt autoimmunity characterized by autoantibody production. PD-1 inhibition accelerates autoimmunity in mice, but its role in regulating germinal centers (GC) is controversial. To address the role of PD-1 in the GC reaction in type 1 diabetes, we used tetramers to phenotype insulin-specific CD4+ T and B cells in NOD mice. PD-1 or PD-L1 deficiency, and PD-1 but not PD-L2 blockade, unleashed insulin-specific T follicular helper CD4+ T cells and enhanced their survival. This was concomitant with an increase in GC B cells and augmented insulin autoantibody production. The effect of PD-1 blockade on the GC was reduced when mice were treated with a mAb targeting the insulin peptide:MHC class II complex. This work provides an explanation for autoimmune side effects following PD-1 pathway inhibition and suggests that targeting the self-peptide:MHC class II complex might limit autoimmunity arising from checkpoint blockade.

Percutaneous CT-Guided Cryoablation of the Celiac Plexus: A Retrospective Cohort Comparison with Ethanol.

PURPOSE: To retrospectively analyze and compare the incidence of diarrhea in patients who underwent cryoablation of the celiac plexus for intractable abdominal pain versus ethanol therapy over a 5-year period. MATERIALS AND METHODS: From June 2014 to August 2019, 83 patients were identified who underwent neurolysis of the celiac plexus for management of intractable abdominal pain by using either cryoablation (n = 39 [59% female; age range, 36-79 years old [average, 60 ± 11 years old]) or alcohol (n = 44 [48% female; age range, 29-76 years old [average, 60 ± 12 years old]). Pain scores and reports of procedure-related complications or side effects, with special attention to diarrhea and/or other gastrointestinal symptoms, were collected from follow-up visits at 1 week, 1 month, and 3 months post-intervention and were compared between groups. RESULTS: The mean time of follow-up was 17.7 days. Four patients who underwent cryoablation developed gastrointestinal symptoms consisting of 2 cases of nausea and vomiting and 2 cases of diarrhea (5.1%). Twelve patients who underwent ethanol ablation developed gastrointestinal symptoms, including 1 case of nausea, 3 cases of vomiting, and 9 cases of diarrhea (20.5%). There was a significantly higher incidence of both diarrhea (chi-squared likelihood ratio, P = .03) and overall gastrointestinal symptoms (chi-squared likelihood ratio, P = .04) in the ethanol group than in the cryoablation group. CONCLUSIONS: Cryoablation of the celiac plexus may provide a new treatment option for intractable abdominal pain, and it appears to have a lower incidence of diarrhea and fewer gastrointestinal side effects than ablation using ethanol.

Natural History of Mixed and Motor Nerve Cryoablation in Humans-A Cohort Analysis.

Eight patients who underwent percutaneous cryoablation of mixed and/or motor nerves over a period of 5 years were identified. Distances from the ablation sites to origins of distal musculature were measured, and times to initial clinical recovery were collected. Strength progression over time following muscle activation was also collected and analyzed. All patients demonstrated activation of all muscles distal to the ablation, and the calculated mean rate of nerve regeneration based on distance to the origin of the assessed musculature and time to muscle activation for the group was 1.5 mm/day ± 1.1.