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Abstract Pancreatic islets of Langerhans secrete hormones that are vital to the regulation of blood glucose and are, therefore, a key focus of diabetes research. Purifying viable and functional islets from the pancreas for study is an intricate process. This review highlights the key elements involved with mouse and rat islet isolation, including choices of collagenase, the collagenase digestion process, purification of islets using a density gradient, and islet culture conditions. In addition, this paper reviews commonly used techniques for assessing islet viability and function, including visual assessment, fluorescent markers of cell death, glucose-stimulated insulin secretion, and intracellular calcium measurements. A detailed protocol is also included that describes a common method for rodent islet isolation that our laboratory uses to obtain viable and functional mouse islets for in vitro study of islet function, beta-cell physiology, and in vivo rodent islet transplantation. The purpose of this review is to serve as a resource and foundation for successfully procuring and purifying high-quality islets for research purposes.

Objectives: Transitions to new care environments may have unexpected consequences that threaten patient safety. We undertook a quality improvement project using in situ simulation to learn the new patient care environment and expose latent safety threats before transitioning patients to a newly built adult ICU., Design: Descriptive review of a patient safety initiative., Setting: A newly built 24-bed neurocritical care unit at a tertiary care academic medical center., Subjects: Care providers working in neurocritical care unit., Interventions: We implemented a pragmatic three-stage in situ simulation program to learn a new patient care environment, transitioning patients from an open bay unit to a newly built private room-based ICU. The project tested the safety and efficiency of new workflows created by new patient- and family-centric features of the unit. We used standardized patients and high-fidelity mannequins to simulate patient scenarios, with "test" patients created through all electronic databases. Relevant personnel from clinical and nonclinical services participated in simulations and/or observed scenarios. We held a debriefing after each stage and scenario to identify safety threats and other concerns. Additional feedback was obtained via a written survey sent to all participants. We prospectively surveyed for missed latent safety threats for 2 years following the simulation and fixed issues as they arose., Measurements and Main Results: We identified and addressed 70 latent safety threats, including issues concerning physical environment, infection prevention, patient workflow, and informatics before the move into the new unit. We also developed an orientation manual that highlighted new physical and functional features of the ICU and best practices gleaned from the simulations. All participants agreed or strongly agreed that simulations were beneficial. Two-year follow-up revealed only two missed latent safety threats., Conclusions: In situ simulation effectively identifies latent safety threats surrounding the transition to new ICUs and should be considered before moving into new units., Competing Interests: Dr. Morris’ institution received the Faculty Innovation in Education Award from the American Board of Psychiatry and Neurology. Dr. Johnson disclosed they are a co-inventor with CVRx, Inc., for a cardiac neurostimulation device. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Background: Mesenchymal stromal/stem cells (MSCs) play a critical role in wound healing. Corlicyte ® is an MSC product derived from allogeneic umbilical cord tissue donated under an institutional review board-approved protocol and processed in accordance with section 501(a)(2)(B) of the Federal Food, Drug, and Cosmetic Act. This open-label phase 1 trial was performed under a United States Food and Drug Administration Investigational New Drug Application to establish the safety and tolerability of Corlicyte ® in patients with diabetes and chronic diabetic foot ulcer (DFU)., Methods: Escalating doses were applied topically twice a week for up to 8 weeks after ulcer debridement, wound photography, and measurement. Subjects were followed for 4 weeks after the treatment phase. Adverse events were assessed at every visit., Results: Nine subjects in 2 dosing cohorts completed the trial. No subjects experienced a serious adverse reaction to Corlicyte ® or the development of anti-human leukocyte antigen (HLA) antibodies. Sixty percentage of subjects in the lower dose cohort experienced ulcer closure by Day 70 of follow-up, while the mean ulcer size was reduced by 54-67% in the other subjects., Conclusions: Topical administration of Corlicyte ® , a novel biologic therapy consisting of allogeneic umbilical cord lining MSCs, appeared safe and tolerable and resulted in a significant decrease in ulcer area, demonstrating its potential as a therapy for healing of chronic DFU.

Background: A phase 3b, open-label, multicenter, expanded-access study (NCT04123548) evaluated safety and clinical outcomes of StrataGraft treatment in adults with deep partial-thickness thermal burns with intact dermal elements., Methods: Adult patients with 3 % to < 50 % total body surface area burns were treated with a single application of ≤ 1:1 meshed StrataGraft and followed for 24 weeks. Primary endpoint was count and percentage of patients with treatment-emergent adverse events (TEAEs). Secondary endpoints included confirmed wound closure (WC) at Week 12, durable WC at Week 24, time to WC, scar evaluation, and wound infection-related events., Results: Fifty-two patients with 96 treatment sites were enrolled. Pruritus was the most common TEAE (22 patients [42.3 %]). Twenty serious TEAEs occurred in 10 patients (19.2 %); none were related to StrataGraft. There were 4 (7.7 %) deaths (aspiration, myocardial infarction, self-injury, Gram-negative rod sepsis); none were related to StrataGraft. Confirmed WC was achieved by Week 12 in 33 patients (63.5 %; 95 % CI: 50.4-76.5 %) and 69 treatment sites (71.9 %; 95 % CI: 62.9-80.9 %). Durable WC was achieved by Week 24 in 29 patients (55.8 %; 95 % CI: 42.3-69.3 %) and 58 treatment sites (60.4 %; 95 % CI: 50.6-70.2 %)., Conclusions: StrataGraft demonstrated clinical benefit. Safety data were consistent with previously reported findings., Competing Interests: Declaration of Competing Interest James H. Holmes IV: Equity positions in Abbott Labs, AbbVie, Change Healthcare Inc, and Imbed Biosciences. Consultant for Avita Medical and has received research support from Avita Medical, Mallinckrodt Pharmaceuticals/Stratatech, SpectralMD, and Keranetics. Jeffrey W. Shupp: Research funding from Mallinckrodt Pharmaceuticals, Avita Medical, Urgo Medical, ACell, and Kerecis. JWS has been a consultant for Integra LifeSciences and Avita Medical. Tracee Short: Participated in the clinical advisory boards for Avita Medical, Mallinckrodt Pharmaceuticals, Synergy Biologics, Polynovo, and KCI. Victor C. Joe: Participated in a Mallinckrodt Pharmaceuticals Advisory Board relating to StrataGraft. Jeffrey Litt: Participated in the speaker bureau for Acelity/3AM (ended) and advisory board for Vericel (ended). Joshua Carson: Received research funding from Mallinckrodt Pharmaceuticals and the Biomedical Research and Development Authority (BARDA) and personal fees from Integra LifeSciences, Avita Medical, and Mallinckrodt Pharmaceuticals. Jeffrey E. Carter: Equity positions in PermeaDerm, Inc and is a consultant for Avita Medical. Research support from Avita Medical, SpectralMD, and Keranetics. Lucy Wibbenmeyer: Received research funding from Mallinckrodt Pharmaceuticals, Mediwound, and Biomedical Research and Development Authority (BARDA) and consultant fees from Vericel, Allosource, and Mallinckrodt Pharmaceuticals. Helen Hahn: Previous employee of Mallinckrodt Pharmaceuticals. Janice M. Smiell: Previous employee of Mallinckrodt Pharmaceuticals. Randi Rutan: Previous employee of Mallinckrodt Pharmaceuticals. Richard Wu: Employee of Mallinckrodt Pharmaceuticals. Angela L. F. Gibson: Received grant/research support from Mallinckrodt Pharmaceuticals., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Demographic histories are frequently a product of the environment, as populations expand or contract in response to major environmental changes, often driven by changes in climate. Meso- and bathy-pelagic fishes inhabit some of the most temporally and spatially stable habitats on the planet. The stability of the deep-pelagic could make deep-pelagic fishes resistant to the demographic instability commonly reported in fish species inhabiting other marine habitats, however the demographic histories of deep-pelagic fishes are unknown. We reconstructed the historical demography of 11 species of deep-pelagic fishes using mitochondrial and nuclear DNA sequence data. We uncovered widespread evidence of population expansions in our study species, a counterintuitive result based on the nature of deep-pelagic ecosystems. Frequency-based methods detected potential demographic changes in nine species of fishes, while extended Bayesian skyline plots identified population expansions in four species. These results suggest that despite the relatively stable nature of the deep-pelagic environment, the fishes that reside here have likely been impacted by past changes in climate. Further investigation is necessary to better understand how deep-pelagic fishes, by far Earth's most abundant vertebrates, will respond to future climatic changes., Competing Interests: The authors declare that they have no conflicts of interest., (© 2024 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)

Accurate analysis of injuries is paramount when allocating resources for prevention, research, education, and legislation. As burn mortality has improved over recent decades, the societal burden of burn injuries has grown ambiguous to the public while a scarcity of investigational funding for survivors has led to a gap in understanding lifelong sequela. We aim to compare national references reporting the incidence of burn injuries in the United States. The American Burn Association Burn Injury Summary Report (ABA-BISR), American Burn Association Fact Sheet, Centers for Disease Control and Prevention (CDC) Web-based Injury Statistics Query and Reporting (WISQARS) database, the CDC National Center for Health Statistics' National Hospital Ambulatory Medical Care Survey (NHAMCS), National Inpatient Sample (NIS), National Emergency Department Sample (NEDS), and commercially available claims databases were queried for 2020 or the most recent data available. The BISR estimated 30,135 burn admissions in 2022. The 2016 ABA Fact Sheet reported 486,000 burns presented to US emergency departments (ED). In 2020, CDC's WISQARS database reported 3,529 fatal, and 287,926 non-fatal, burn injuries. The 2020 NEDS reported 438,185 ED visits while the 2020 NIS estimated 103,235 inpatients. The NHAMCS reported 359,000 ED visits for burn injuries in the same period, and an analysis of ICD-10 burn codes demonstrated over 698,555 claims. Our study demonstrates a large variability in the reported incidence of burn injury by the ABA, CDC, national samples, and claims databases. Per our analyses, we estimate that 600,000 individuals annually suffer a burn injury which merits emergent care in the United States., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Burn Association. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Despite differing etiologies, acute thermal burn injuries and full-thickness (FT) skin defects are associated with similar therapeutic challenges. When not amenable to primary or secondary closure, the conventional standard of care (SoC) treatment for these wound types is split-thickness skin grafting (STSG). This invasive procedure requires adequate availability of donor skin and is associated with donor site morbidity, high healthcare resource use (HCRU), and costs related to prolonged hospitalization. As such, treatment options that can facilitate effective healing and donor skin sparing have been highly anticipated. The RECELL ® Autologous Cell Harvesting Device facilitates preparation of an autologous skin cell suspension (ASCS) for the treatment of acute thermal burns and FT skin defects. In initial clinical trials, the approach showed superior donor skin-sparing benefits and comparable wound healing to SoC STSG among patients with acute thermal burn injuries. These findings led to approval of RECELL for this indication by the US Food and Drug Administration (FDA) in 2018. Subsequent clinical evaluation in non-thermal FT skin wounds showed that RECELL, when used in combination with widely meshed STSG, provides donor skin-sparing advantages and comparable healing outcomes compared with SoC STSG. As a result, the device received FDA approval in June of 2023 for treatment of FT skin defects caused by traumatic avulsion or surgical excision or resection. Given that health economic advantages have been demonstrated for RECELL ± STSG versus STSG alone when used for burn therapy, it is prudent to examine similarities in the burn and FT skin defect treatment pathways to forecast the potential health economic advantages for RECELL when used in FT skin defects. This article discusses the parallels between the two indications, the clinical outcomes reported for RECELL, and the HCRU and cost benefits that may be anticipated with use of the device for non-thermal FT skin defects., (© 2024. The Author(s).)

Introduction: Lack of an accurate, publicly available database of burn/trauma resources creates challenges in providing burn care. In response to this gap, our group developed the National Injury Resource Database (NIRD), a comprehensive database of all US burn centers (BC) and trauma centers (TC) and their capabilities., Methods: Lists of all national BC and TC were obtained from the American Burn Association (ABA), the American College of Surgeons, and every state department of health. Data was cross-checked and included BC/TC were linked with a 7-digit identification number using the American Hospital Association Quick Search guide. Each center's resources and verification status were validated with electronic or telephonic communications., Results: The final database includes 135 BC and 617 TC, of which 18 are BC-only, 500 are TC-only, and 117 are combined BC/TC. ABA-verified BC (n = 76) are only found in Washington DC and 31 states, and 8 states have no BC. In the last 10 years, a net increase of 7 burn centers was found nationally. The ABA's online BC directory is outdated., Conclusions: NIRD represents the only up-to-date, comprehensive listing of BC and TC in existence. It categorizes all currently operating BC and TC across myriad classifications of designation and capabilities., Competing Interests: Declaration of Competing Interest Mr. Phillips is the CEO of BData, Inc. Dr. Phelan serves as a consultant with Avita Medical and SpectralMD. Dr. Carter is a stockholder for Permeaderm, Inc. and SpectralMD, and serves as Chief Medical Consultant for SpectralMD. He also serves as a consultant for Avita Medical and Polynovo Ltd. where, in lieu of compensation, all proceeds are donated to a local burn charity to support burn education, survivor programs, outreach, and research. Dr. Hickerson serves as the Medical Monitor for SpectralMD, the Chief Medical Officer for Access Pro Medical, the Chief Medical Officer for SiOxMed, a consultant for Avita, and a consultant for PolyNovo., (Copyright © 2023. Published by Elsevier Ltd.)

Pancreatic cancer has the worst prognosis among all cancers, underscoring the need for improved management strategies. Dysregulated mitochondrial function is a common feature in several malignancies, including pancreatic cancer. Although mitochondria have their own genome, most mitochondrial proteins are nuclear-encoded and imported by a multi-subunit translocase of the outer mitochondrial membrane (TOMM). TOMM22 is the central receptor of the TOMM complex and plays a role in complex assembly. Pathobiologic roles of TOMM subunits remain largely unexplored. Here we report that TOMM22 protein/mRNA is overexpressed in pancreatic cancer and inversely correlated with disease outcomes. TOMM22 silencing decreased, while its forced overexpression promoted the growth and malignant potential of the pancreatic cancer cells. Increased import of several mitochondrial proteins, including those associated with mitochondrial respiration, was observed upon TOMM22 overexpression which was associated with increased RCI activity, NAD+/NADH ratio, oxygen consumption rate, membrane potential, and ATP production. Inhibition of RCI activity decreased ATP levels and suppressed pancreatic cancer cell growth and malignant behavior confirming that increased TOMM22 expression mediated the phenotypic changes via its modulation of mitochondrial protein import and functions. Altogether, these results suggest that TOMM22 overexpression plays a significant role in pancreatic cancer pathobiology by altering mitochondrial protein import and functions., Implications: TOMM22 bears potential for early diagnostic/prognostic biomarker development and therapeutic targeting for better management of patients with pancreatic cancer., (©2023 American Association for Cancer Research.)

Introduction: Our group previously reported a burn biopsy algorithm (BBA-V1) for categorizing burn wound depth. Here, we sought to promulgate a newer, simpler version of the BBA (BBA-V2)., Methods: Burn wounds undergoing excision underwent 4 mm biopsies procured every 25 cm 2 . Serial still photos were obtained at enrollment and at excision intraoperatively. Burn wounds assessed as likely to heal by 21 days were imaged within 72 h of injury and at 21 days. A sample of 798 burn wound biopsies were classified by both BBAV1 and BBAV2 algorithms. For nonoperative burn wounds, the proportion of healing versus nonhealing pixels at 21 days after injury were compared., Results: The 798 biopsies were classified by BBAV1 as 24% SPT, 47% DPT, 28% FT and by BBAV2 as 3% SPT, 67% DPT, and 30% FT (p < 0.0001). Overall, the proportion of biopsies whose wound reclassification changed from a nonoperative to operative pathway was 21% (95% CI: 18-24%). Nonoperative wounds judged at injury as being SPT contained 12.8 million pixels. Repeat 21-day imaging revealed 11.3 million healed pixels (accuracy = 89.6% (95% CI: 89.59-89.62))., Conclusions: BBA-V2 was associated with a significantly higher concordance with visual assessment for burn wounds clinically judged as deep partial and full thickness., Competing Interests: Declaration of Competing Interest Dr. Phelan serves as a consultant with Avita Medical and SpectralMD. Dr. Holmes has equity positions in Abbott Labs, AbbVie, Change Healthcare Inc, & Imbed Biosciences, and is a consultant for Avita Medical & Stratatech/Mallinckrodt. Dr. Hickerson serves as a consultant for Avita Medical, Vericel, and Stedical. Dr. Cockerell has no disclosures. Dr. Shupp states that he has no competing disclosures relevant to imaging or burn depth determination. Dr. Carter is a stockholder for Permeaderm, Inc. and SpectralMD, and serves as Chief Medical Consultant for SpectralMD. He also serves as a consultant for Avita Medical and Polynovo Ltd. where, in lieu of compensation, all proceeds are donated to a local burn charity to support burn education, survivor programs, outreach, and research., (Copyright © 2023. Published by Elsevier Ltd.)

Minimally invasive surgery is becoming the standard of care across surgical subspecialties. Several new "minimally invasive" options for burn debridement and autografting exist. Enzymatic bromelain-based debridement (BBD) and autologous skin cell spray (ASCS) have independently proven to reduce the rate of split-thickness skin grafting (STSG) and decrease donor site size when grafting is performed. There is a paucity in the literature regarding the combination of these two therapies. The purpose of this study is to characterize a cohort of patients treated with both BBD and ASCS and qualitatively compare data to expected outcomes without these therapies. This retrospective study of a single academic burn center's experience using BBD and ASCS together included 13 patients with a total burn surface area (TBSA) from 1-30% and all had >50% deep partial thickness. All patients received BBD and ASCS. Deeper burns additionally received STSG with ASCS overspray. Median burn size was 14% TBSA (IQR:5.45,20), donor site size was 225 sq cm (IQR:28.5,556.5), and ratio of donor site area to total treatment area of 0.082 (IQR: 0.039, 0.241) was observed. Median observed length of stay (LOS) was 19 days (IQR:10,27), expected LOS was 15.4 days, and O/E ratio 1.06. Donor sites in both groups of patients were much smaller than expected versus treatment with conventional meshed STSG alone and length of stay is lower than expected based on burn size. An emphasis on expenses and scar development will guide future studies into the patient subset and wound features that are best for this combination treatment., (© 2023 Euro-Mediterranean Council for Burns and Fire Disasters.)

As some of the smallest vertebrates, yet largest producers of consumed reef biomass, cryptobenthic reef fishes serve a disproportionate role in reef ecosystems and are one of the most poorly understood groups of fish. The blenny genera Hypleurochilus and Parablennius are currently considered paraphyletic and the interrelationships of Parablennius have been the focus of recent phylogenetic studies. However, the interrelationships of Hypleurochilus remain understudied. This genus is transatlantically distributed and comprises 11 species with a convoluted taxonomic history. In this study, relationships for ten Hypleurochilus species are resolved using multi-locus nuclear and mtDNA sequence data, morphological data, and mined COI barcode data.  Mitochondrial and nuclear sequence data from 61 individuals collected from the western Atlantic and northern Gulf of Mexico (N. GoM) delimit seven species into a temperate clade, a tropical clade, and a third distinct lineage. This lineage, herein referred to as H. cf. aequipinnis, may represent a species of Hypleurochilus whose range has expanded into the N. GoM. Inclusion of publicly available COI sequence for an additional three species provides further phylogenetic resolution. H. bananensis forms a new eastern Atlantic clade with H. cf. aequipinnis, providing further evidence for a western Atlantic range expansion. Single marker COI delimitation was unable to elucidate the relationships between H. springeri/H. pseudoaequipinnis and between H. multifilis/H. caudovittatus due to incomplete lineage sorting. Mitochondrial data are also unable to accurately resolve the placement of H. bermudensis. However, a comprehensive approach using multi-locus phylogenetic and species delimitation methods was able to resolve these relationships. While mining publicly available sequence data allowed for the inclusion of an increased number of species in the analysis and a more comprehensive phylogeny, it was not without drawbacks, as a handful of sequences are potentially mis-identified. Overall, we find that the recent divergence of some species within this genus and potential introgression events confound the results of single locus delimitation methods, yet a combination of single and multi-locus analyses has allowed for insights into the biogeography of this genus and uncovered a potential transatlantic range expansion., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

MYB acts as a potentiator of aggressiveness and castration resistance in prostate cancer (PCa) through aberrant activation of androgen receptor (AR) signaling. Since Black men experience higher PCa incidence and mortality than White men, we examined if MYB was differentially expressed in prostate tumors from patients of these racial backgrounds. The data reveal that aberrant MYB expression starts early in precancerous high-grade prostate intraepithelial neoplastic lesions and increases progressively in malignant cells. PCa tissues from Black patients exhibit higher MYB expression than White patients in overall and grade-wise comparisons. MYB also exhibits a positive correlation with AR expression and both display higher expression in advanced tumor stages. Notably, we find that MYB is a better predictor of biochemical recurrence than AR, pre-treatment PSA, or Gleason's grades. These findings establish MYB as a promising molecular target in PCa that could be used for improved risk prediction and therapeutic planning., Competing Interests: A.P.S. and S.S. hold a patent (US9458456B2), which is partly related to this work., (© 2023 The Authors.)