Expanding the empirical study of virtual reality beyond empathy to compassion, moral reasoning, and moral foundations.

This study utilizes a controlled experimental design to investigate the influence of a virtual reality experience on empathy, compassion, moral reasoning, and moral foundations. With continued debate and mixed results from previous studies attempting to show relationships between virtual reality and empathy, this study takes advantage of the technology for its ability to provide a consistent, repeatable experience, broadening the scope of analysis beyond empathy. A systematic literature review identified the most widely used and validated moral psychology assessments for the constructs, and these assessments were administered before and after the virtual reality experience. The study is comprised of two pre-post experiments with student participants from a university in the United States. The first experiment investigated change in empathy and moral foundations among 44 participants, and the second investigated change in compassion and moral reasoning among 69 participants. The results showed no significant change in empathy nor compassion, but significant change in moral reasoning from personal interest to post-conventional stages, and significant increase in the Care/harm factor of moral foundations. By testing four of the primary constructs of moral psychology with the most widely used and validated assessments in controlled experiments, this study attempts to advance our understanding of virtual reality and its potential to influence human morality. It also raises questions about our self-reported assessment tools and provides possible new insights for the constructs examined.

Sustained generation of neurons destined for neocortex with oxidative metabolic upregulation upon filamin abrogation.

Neurons in the neocortex are generated during embryonic development. While the adult ventricular-subventricular zone (V-SVZ) contains cells with neural stem/progenitors' characteristics, it remains unclear whether it has the capacity of producing neocortical neurons. Here, we show that generating neurons with transcriptomic resemblance to upper layer neocortical neurons continues in the V-SVZ of mouse models of a human condition known as periventricular heterotopia by abrogating Flna and Flnb. We found such surplus neurogenesis was associated with V-SVZ's upregulation of oxidative phosphorylation, mitochondrial biogenesis, and vascular abundance. Additionally, spatial transcriptomics analyses showed V-SVZ's neurogenic activation was coupled with transcriptional enrichment of genes in diverse pathways for energy metabolism, angiogenesis, cell signaling, synaptic transmission, and turnovers of nucleic acids and proteins in upper cortical layers. These findings support the potential of generating neocortical neurons in adulthood through boosting brain-wide vascular circulation, aerobic adenosine triphosphate synthesis, metabolic turnover, and neuronal activity.

Fixed-target pump-probe SFX: eliminating the scourge of light contamination.

X-ray free-electron laser (XFEL) light sources have enabled the rapid growth of time-resolved structural experiments, which provide crucial information on the function of macromolecules and their mechanisms. Here, the aim was to commission the SwissMX fixed-target sample-delivery system at the SwissFEL Cristallina experimental station using the PSI-developed micro-structured polymer (MISP) chip for pump-probe time-resolved experiments. To characterize the system, crystals of the light-sensitive protein light-oxygen-voltage domain 1 (LOV1) from Chlamydomonas reinhardtii were used. Using different experimental settings, the accidental illumination, referred to as light contamination, of crystals mounted in wells adjacent to those illuminated by the pump laser was examined. It was crucial to control the light scattering from and through the solid supports otherwise significant contamination occurred. However, the results here show that the opaque MISP chips are suitable for defined pump-probe studies of a light-sensitive protein. The experiment also probed the sub-millisecond structural dynamics of LOV1 and indicated that at Δt = 10 µs a covalent thioether bond is established between reactive Cys57 and its flavin mononucleotide cofactor. This experiment validates the crystals to be suitable for in-depth follow-up studies of this still poorly understood signal-transduction mechanism. Importantly, the fixed-target delivery system also permitted a tenfold reduction in protein sample consumption compared with the more common high-viscosity extrusion-based delivery system. This development creates the prospect of an increase in XFEL project throughput for the field.

Transcriptional synergy in human aortic endothelial cells is vulnerable to combination p300/CBP and BET bromodomain inhibition.

Combinatorial signaling by proinflammatory cytokines synergizes to exacerbate toxicity to cells and tissue injury during acute infections. To explore synergism at the gene-regulatory level, we investigated the dynamics of transcription and chromatin signaling in response to dual cytokines by integrating nascent RNA imaging mass spectrometry, RNA sequencing, amplification-independent mRNA quantification, assay for transposase-accessible chromatin using sequencing (ATAC-seq), and transcription factor profiling. Costimulation with interferon-gamma (IFNγ) and tumor necrosis factor alpha (TNFα) synergistically induced a small subset of genes, including the chemokines CXCL9, -10, and -11. Gene induction coincided with increased chromatin accessibility at non-coding regions enriched for p65 and STAT1 binding sites. To discover coactivator dependencies, we conducted a targeted chemogenomic screen of transcriptional inhibitors followed by modeling of inhibitor dose-response curves. These results identified high efficacy of either p300/CREB-binding protein (CBP) or bromodomain and extra-terminal (BET) bromodomain inhibitors to disrupt induction of synergy genes. Combination p300/CBP and BET bromodomain inhibition at half-maximal inhibitory concentrations (subIC50) synergistically abrogated IFNγ/TNFα-induced chemokine gene and protein levels.

Dietary Phosphorus Levels Influence Protein-Derived Uremic Toxin Production in Nephrectomized Male Rats.

Gut microbiota-derived uremic toxins (UT) accumulate in patients with chronic kidney disease (CKD). Dietary phosphorus and protein restriction are common in CKD treatment, but the relationship between dietary phosphorus, a key nutrient for the gut microbiota, and protein-derived UT is poorly studied. Thus, we explored the relationship between dietary phosphorus and serum UT in CKD rats. For this exploratory study, we used serum samples from a larger study on the effects of dietary phosphorus on intestinal phosphorus absorption in nephrectomized (Nx, n = 22) or sham-operated (sham, n = 18) male Sprague Dawley rats. Rats were randomized to diet treatment groups of low or high phosphorus (0.1% or 1.2% w/w, respectively) for 1 week, with serum trimethylamine oxide (TMAO), indoxyl sulfate (IS), and p-cresol sulfate (pCS) analyzed by LC-MS. Nx rats had significantly higher levels of serum TMAO, IS, and pCS compared to sham rats (all p < 0.0001). IS showed a significant interaction between diet and CKD status, where serum IS was higher with the high-phosphorus diet in both Nx and sham rats, but to a greater extent in the Nx rats. Serum TMAO (p = 0.24) and pCS (p = 0.34) were not affected by dietary phosphorus levels. High dietary phosphorus intake for 1 week results in higher serum IS in both Nx and sham rats. The results of this exploratory study indicate that reducing dietary phosphorus intake in CKD may have beneficial effects on UT accumulation.

Associations among drug acquisition and use behaviors, psychosocial attributes, and opioid-involved overdoses.

AIMS: This study sought to develop and assess an exploratory model of how demographic and psychosocial attributes, and drug use or acquisition behaviors interact to affect opioid-involved overdoses. DESIGN: We conducted exploratory and confirmatory factor analysis (EFA/CFA) to identify a factor structure for ten drug acquisition and use behaviors. We then evaluated alternative structural equation models incorporating the identified factors, adding demographic and psychosocial attributes as predictors of past-year opioid overdose. SETTING AND PARTICIPANTS: We used interview data collected for two studies recruiting opioid-misusing participants receiving services from a community-based syringe services program. The first investigated current attitudes toward drug-checking (N = 150). The second was an RCT assessing a telehealth versus in-person medical appointment for opioid use disorder treatment referral (N = 270). MEASUREMENTS: Demographics included gender, age, race/ethnicity, education, and socioeconomic status. Psychosocial measures were homelessness, psychological distress, and trauma. Self-reported drug-related risk behaviors included using alone, having a new supplier, using opioids with benzodiazepines/alcohol, and preferring fentanyl. Past-year opioid-involved overdoses were dichotomized into experiencing none or any. FINDINGS: The EFA/CFA revealed a two-factor structure with one factor reflecting drug acquisition and the second drug use behaviors. The selected model (CFI = .984, TLI = .981, RMSEA = .024) accounted for 13.1% of overdose probability variance. A latent variable representing psychosocial attributes was indirectly associated with an increase in past-year overdose probability (ß = .234, p = .001), as mediated by the EFA/CFA identified latent variables: drug acquisition (ß = .683, p < .001) and drug use (ß = .567, p = .001). Drug use behaviors (ß = .287, p = .04) but not drug acquisition (ß = .105, p = .461) also had a significant, positive direct effect on past-year overdose. No demographic attributes were significant direct or indirect overdose predictors. CONCLUSIONS: Psychosocial attributes, particularly homelessness, increase the probability of an overdose through associations with risky drug acquisition and drug-using behaviors. Further research is needed to replicate these findings with populations at high-risk of an opioid-related overdose to assess generalizability and refine the metrics used to assess psychosocial characteristics.

Standardized Protocols for Clinical and Histopathological Characterization of Hidradenitis Suppurativa Tissue Specimens.

Methods for describing and reporting the clinical and histologic characteristics of cutaneous tissue samples from patients with hidradenitis suppurativa (HS) are not currently standardized, limiting clinicians' and scientists' ability to uniformly record, report, and communicate about the characteristics of tissue used in translational experiments. A recently published consensus statement outlined morphological definitions of typical HS lesions, but no consensus has been reached regarding clinical characterization and examination of HS tissue samples. In this study, we aimed to establish a protocol for reporting histopathologic and clinical characteristics of HS tissue specimens. This study was conducted from May 2023 to August 2023. Experts in clinical care, dermatopathology, and translational research were recruited, and a modified Delphi technique was used to develop a protocol for histologic reporting and clinical characterization of submitted tissue specimens from patients with HS. A total of 27 experts participated (14 dermatologists, 3 fellowship-trained dermatopathologists, 3 plastic surgeons, 3 general surgeons, and 4 research scientists) in creating and reviewing protocols for the clinical and histopathological examination of HS tissue specimens. The protocols were formatted as a synoptic report and will help to consistently classify specimens in biobanks on the basis of histologic features and more accurately report and select samples used in translational research projects.

Subcision with and without suction for acne scars: a split-faced, rater-blinded randomized control trial.

Therapeutic options for acne scars include subcision and suction with microdermabrasion, but these treatment modalities have not been studied in conjunction. To compare effectiveness of subcision alone versus subcision with suction for the treatment of facial acne scars. Randomized, split-faced, evaluator-blinded control trial. Participants underwent one subcision treatment on both sides of the face followed by 10 sessions of suction to one side. Photographs at baseline, 1-month, and 4-months were assessed. Primary outcome measures were the validated Acne Scar Severity Scale (ASSS) (0 = no acne scarring, 4 = severe), Acne Scar Improvement Grading Scale (ASIGS) (-100 to 100%), and modified Quantitative Global Scarring Grades (QGSG) (point-based questionnaire instrument), as well as subject preference. Twenty-eight treatment areas and 154 treatments were analyzed. Dermatologist raters found no differences between subcision alone and subcision-suction at 1-month or 4-months. Mean subject-assessed percent improvement for subcision-suction was higher than that for subcision alone at 1-month (37% versus 24%, p = 0.04) but not at 4-months (p = 0.37). Subjects preferred combination therapy to monotherapy at 1-month (50% vs. 21%) and 4-months (43% vs. 21%). While blinded raters did not detect significant differences, subjects perceived combination treatment as working more quickly than monotherapy, and preferred combination treatment at all time points.Clinical trial registration NCT01696513 on Clinicaltrials.gov.

Integration of a Community Opioid Treatment Program into a Federally Qualified Health Center.

OBJECTIVES: With the increasing rates of opioid overdose deaths in the United States, barriers to treatment access for patients seeking medications for opioid use disorder (OUD), and challenges of initiating buprenorphine in patients who use fentanyl, it is essential to explore novel approaches to expanding access to methadone treatment. An opioid treatment program (OTP) and a federally qualified health center (FQHC) partnered to develop and implement an innovative integrated methadone and primary care treatment model. The process for integrating an OTP and FQHC to provide methadone treatment in the primary care setting will be discussed. METHODS: An OTP methadone dispensing site was co-located in the FQHC, utilizing a staffing matrix built on the expertise of each stakeholder. The OTP managed DEA and state regulatory processes, whereas the FQHC physicians provided medical treatment, including methadone treatment protocols, treatment plans, and primary care. Patient demographics, medical history, and retention data for those who entered the program between January 2021 and February 2023 were collected through chart review and analyzed with descriptive statistics. RESULTS: A total of 288 OTP-FHQC patients were enrolled during the study. Retention rates in methadone treatment at 90 and 180 days were similar to partner clinics. CONCLUSIONS: Collaboration between FQHCs and OTPs is operationally feasible and can be achieved utilizing the current staffing model of the FQHC and OTP. This model can increase access to treatment for OUD and primary care for an urban, underserved patient population.

Conversion of a Validated Melanoma Risk Stratification Tool Into a Tablet-Based Patient Questionnaire for Targeted Melanoma Screening in Primary Care Settings: A Pilot Study.

BACKGROUND: Risk stratification can identify individuals in primary care settings who are at increased risk of developing melanoma. OBJECTIVE: Converting and implementing a validated risk stratification tool as a patient self-administered tablet-based survey. METHODS: Mackie risk stratification tool was transformed into a patient questionnaire. The questionnaire was completed in academic dermatologist practices by patients and dermatologists and revised to optimize sensitivity and specificity using physician assessment as gold standard. The optimized survey was administered before routine primary care visits during 2019 to 2021. High-risk patients were referred to dermatology. The number needed to screen (NNS), sensitivity, specificity, positive predictive value, and negative predictive value to identify a melanoma were calculated. RESULTS: Of the 7,893 respondents, 5,842 (74%) and 2,051 (26%) patients were categorized as low-risk and high-risk population, respectively. The NNS to identify 1 melanoma was 64 in the high-risk population. CONCLUSION: Incorporating self-administered patient-risk stratification tools in primary care settings can identify high-risk individuals for targeted melanoma screening. Further studies are needed to optimize specificity and sensitivity in more targeted populations.

Incorporating implementation science principles into curricular design.

Implementation science (IS) is an approach focused on increasing the application of evidence-based health interventions into practice, through purposive and thoughtful planning to maximize uptake, scalability, and sustainability. Many of these principles can be readily applied to medical education, to help augment traditional approaches to curriculum design. In this paper, we summarize key components of IS with an emphasis on application to the medical educator.

Current and future applications of artificial intelligence in surgery: implications for clinical practice and research.

Surgeons are skilled at making complex decisions over invasive procedures that can save lives and alleviate pain and avoid complications in patients. The knowledge to make these decisions is accumulated over years of schooling and practice. Their experience is in turn shared with others, also via peer-reviewed articles, which get published in larger and larger amounts every year. In this work, we review the literature related to the use of Artificial Intelligence (AI) in surgery. We focus on what is currently available and what is likely to come in the near future in both clinical care and research. We show that AI has the potential to be a key tool to elevate the effectiveness of training and decision-making in surgery and the discovery of relevant and valid scientific knowledge in the surgical domain. We also address concerns about AI technology, including the inability for users to interpret algorithms as well as incorrect predictions. A better understanding of AI will allow surgeons to use new tools wisely for the benefit of their patients.

The transcription factor ZNF469 regulates collagen production in liver fibrosis.

Non-alcoholic fatty liver disease (NAFLD) - characterized by excess accumulation of fat in the liver - now affects one third of the world's population. As NAFLD progresses, extracellular matrix components including collagen accumulate in the liver causing tissue fibrosis, a major determinant of disease severity and mortality. To identify transcriptional regulators of fibrosis, we computationally inferred the activity of transcription factors (TFs) relevant to fibrosis by profiling the matched transcriptomes and epigenomes of 108 human liver biopsies from a deeply-characterized cohort of patients spanning the full histopathologic spectrum of NAFLD. CRISPR-based genetic knockout of the top 100 TFs identified ZNF469 as a regulator of collagen expression in primary human hepatic stellate cells (HSCs). Gain- and loss-of-function studies established that ZNF469 regulates collagen genes and genes involved in matrix homeostasis through direct binding to gene bodies and regulatory elements. By integrating multiomic large-scale profiling of human biopsies with extensive experimental validation we demonstrate that ZNF469 is a transcriptional regulator of collagen in HSCs. Overall, these data nominate ZNF469 as a previously unrecognized determinant of NAFLD-associated liver fibrosis.

A purified reconstituted bilayer matrix shows improved outcomes in treatment of non-healing diabetic foot ulcers when compared to the standard of care: Final results and analysis of a prospective, randomized, controlled, multi-centre clinical trial.

As the incidence of diabetic foot ulcers (DFU) increases, better treatments that improve healing should reduce complications of these ulcers including infections and amputations. We conducted a randomized controlled trial comparing outcomes between a novel purified reconstituted bilayer membrane (PRBM) to the standard of care (SOC) in the treatment of non-healing DFUs. This study included 105 patients who were randomized to either of two treatment groups (n = 54 PRBM; n = 51 SOC) in the intent to treat (ITT) group and 80 who completed the study per protocol (PP) (n = 47 PRBM; n = 33 SOC). The primary endpoint was the percentage of wounds closed after 12 weeks. Secondary outcomes included percent area reduction, time to healing, quality of life, and cost to closure. The DFUs that had been treated with PRBM healed at a higher rate than those treated with SOC (ITT: 83% vs. 45%, p = 0.00004, PP: 92% vs. 67%, p = 0.005). Wounds treated with PRBM also healed significantly faster than those treated with SOC with a mean of 42 versus 62 days for SOC (p = 0.00074) and achieved a mean wound area reduction within 12 weeks of 94% versus 51% for SOC (p = 0.0023). There were no adverse events or serious adverse events that were related to either the PRBM or the SOC. In comparison to the SOC, DFUs healed faster when treated with PRBM. Thus, the use of this PRBM is an effective option for the treatment of chronic DFUs.

Use of harm reduction strategies by individuals with a history of incarceration: A short report using baseline data collected from the STAMINA clinical trial.

BACKGROUND: Due to the considerably heightened risk of overdose immediately following jail or prison release, expansion of harm reduction interventions for citizens returning to the community after an incarceration episode should be of utmost concern. However, there are no studies examining the adoption and use of harm reduction among this population. This short report examines the use of individual-level harm reduction strategies (HRS) among people who use drugs, comparing those who have lifetime histories of incarceration with those who do not. METHODS: This study included baseline data (N = 274) from a larger clinical trial, which recruited participants at two syringe service programs. Fisher's exact tests examine correlations between HRS and lifetime incarceration. RESULTS: Significant variation in HRS use were observed by demographic characteristics. Those with lifetime incarceration histories were less likely to report ensuring naloxone was available when using, using when others were present, using fentanyl test strips, using a trusted drug supplier, and using some other HRS compared to those without lifetime incarceration histories. Similarly, those with lifetime incarceration histories were also less likely to report using non-prescribed buprenorphine and methadone, which could potentially reduce overdose risk even if not explicitly used as an HRS. CONCLUSION: The results suggest that one of the populations at highest risk of overdose is least likely to use strategies that may reduce overdose risk. Targeted efforts to increase exposure to HRS learning opportunities and access to these resources could help reduce overdose disparities for people returning to the community after incarceration.

Successful Regenerative Therapy of Periodontal Defects Associated With Tongue Piercing: A Clinical Report.

Oral piercing habits are associated with various degrees of complications. Tongue piercing increases the risk of gingival recession and infrabony defects, subsequently leading to localized periodontitis. In the case presented, the patient had persistent swelling and suppuration around her mandibular anterior teeth attributed to tongue piercing jewelry that was placed approximately 12 years prior. Intraoral examinations revealed a localized deep pocket, purulent discharge, swelling, plaque accumulation, bleeding on probing, gingival recession, and teeth mobility. The patient was diagnosed with localized stage III, grade C periodontitis. Following full-mouth debridement and the placement of an extracoronal lingual splint, minimally invasive, papillae-sparing incisions were made, and regenerative therapy with bone allograft and collagen membrane was used to manage the infrabony defects. During the 18-month postoperative follow-up, complete soft-tissue healing was observed along with a significant reduction in pocket depth and the absence of bleeding on probing or suppuration. Radiographic evaluation showed evidence of bone fill. The reported case demonstrates how careful diagnosis and treatment planning are crucial for managing different periodontal defects and emphasizes the importance of proficient periodontal management, which can save teeth that would otherwise be extracted and replaced with implant therapy or fixed bridgework.

Outcomes of Dermal Regeneration Templates in Irradiated and Nonirradiated Scalp Defects.

OBJECTIVES: Dermal regeneration templates (DRTs) are frequently used to treat scalp defects. The aim was to compare the time course of healing for DRTs in scalp defects with and without preoperative radiation. METHODS: The authors conducted a retrospective cohort study of DRT-based scalp reconstruction at 2 academic medical centers between 2013 and 2022. Information was collected on demographic variables, comorbidities, medication use, history of radiation, and DRT outcomes. The primary outcome was DRT loss, defined as exposed calvarium or DRT detachment based on postoperative follow-up documentation. Kaplan-Meier survival analysis and multivariable Cox proportional-hazard regressions were used to compare DRT loss in irradiated and nonirradiated defects. Multivariable logistic regressions were used to compare 30-day postoperative complications (infection, hematoma, or seroma) in irradiated and nonirradiated defects. RESULTS: In total, 158 cases were included. Twenty-eight (18%) patients had a preoperative history of radiation to the scalp. The mean follow-up time after DRT placement was 2.6 months (SD: 4.5 mo). The estimated probability of DRT survival at 2 months was 91% (95% CI: 83%-100%) in nonirradiated patients and 65% (95% CI: 48%-88%) in irradiated patients. In the 55 patients with a bony wound base, preoperative head radiation was associated with a higher likelihood of DRT loss (hazard ratio: 11). Half the irradiated defects experienced uncomplicated total wound closure using Integra Wound Matrix Dressing with or without second-stage reconstruction. CONCLUSIONS: Dermal regeneration template can offer durable coverage in nonirradiated scalp defects. Although DRT loss is more likely in irradiated scalp defects, successful DRT-based reconstruction is possible in select cases.

California's 2023 snow deluge: Contextualizing an extreme snow year against future climate change.

The increasing prevalence of low snow conditions in a warming climate has attracted substantial attention in recent years, but a focus exclusively on low snow leaves high snow years relatively underexplored. However, these large snow years are hydrologically and economically important in regions where snow is critical for water resources. Here, we introduce the term "snow deluge" and use anomalously high snowpack in California's Sierra Nevada during the 2023 water year as a case study. Snow monitoring sites across the state had a median 41 y return interval for April 1 snow water equivalent (SWE). Similarly, a process-based snow model showed a 54 y return interval for statewide April 1 SWE (90% CI: 38 to 109 y). While snow droughts can result from either warm or dry conditions, snow deluges require both cool and wet conditions. Relative to the last century, cool-season temperature and precipitation during California's 2023 snow deluge were both moderately anomalous, while temperature was highly anomalous relative to recent climatology. Downscaled climate models in the Shared Socioeconomic Pathway-370 scenario indicate that California snow deluges-which we define as the 20 y April 1 SWE event-are projected to decline with climate change (58% decline by late century), although less so than median snow years (73% decline by late century). This pattern occurs across the western United States. Changes to snow deluge, and discrepancies between snow deluge and median snow year changes, could impact water resources and ecosystems. Understanding these changes is therefore critical to appropriate climate adaptation.

The long-term intercorrelation between post-burn pain, anxiety, and depression: a post hoc analysis of the "RE-ENERGIZE" double-blind, randomized, multicenter placebo-controlled trial.

BACKGROUND: Despite the growing prevalence of burn survivors, a gap persists in our understanding of the correlation between acute burn trauma and the long-term impact on psychosocial health. This study set out to investigate the prevalence of long-term pain and symptoms of anxiety and depression in survivors of extensive burns, comparing this to the general population, and identify injury and demographic-related factors predisposing individuals to psychosocial compromise. METHODS: RE-ENERGIZE was an international, double-blinded, randomized-controlled trial that enrolled 1200 patients with partial- or full-thickness burns that required surgical treatment. For the post hoc analysis, we excluded participants who did not complete the Short Form Health Survey (SF-36) questionnaire. Normative data were taken from the 2021 National Health Interview Survey dataset. Propensity score matching was performed using the nearest-neighbor 1-to-1 method, and the two cohorts were compared in terms of chronic pain, and symptoms of anxiety and depression. A multivariable analysis was performed on the burns cohort to identify factors predicting post-discharge pain and symptoms of anxiety and depression. RESULTS: A total of 600 burn patients and 26,666 general population adults were included in this study. Following propensity score matching, both groups comprised 478 participants each, who were predominately male, white, overweight and between 20 and 60 years old. Compared to the general population, burn patients were significantly more likely to report the presence of moderate and a lot of pain (p = 0.002). Symptoms of anxiety were significantly higher in the burn population in two of four levels (most of the time; some of the time; p < 0.0001 for both). Responders in the burn population were significantly less likely to report the absence of depressive symptoms (p < 0.0001). Burn patients were also significantly more likely to report that their mental health affects their social life. TBSA, history of depression, and female sex were identified as independently associated factors for pain, anxiety, and depressive symptoms. The presence of chronic pain and anxiety symptoms independently predicted for symptoms of depression. CONCLUSIONS: Analyzing the largest multicenter cohort of patients with extensive burns, we find that burn injury is associated with chronic pain, and symptoms of anxiety and depression. In addition, TBSA-burned and history of depression directly correlate with the prevalence of chronic pain, and symptoms of anxiety and depression. Finally, pain, and symptoms of anxiety and depression are interrelated and may have interactive effects on the process of recovery following burn injury. Burn patients would, therefore, benefit from a multidisciplinary team approach with early mobilization of pain and mental health experts, in order to promptly prevent the development of psychosocial challenges and their consequences.