The periodontal ligament, temperature-sensitive ion channels TRPV1-4, and the mechanosensitive ion channels Piezo1 and 2: A Nobel connection.

Teeth are subject to a variety of mechanical forces and vectors. The periodontal ligament (PDL), fibrous tissue that connects the cementum of the tooth to the bony socket, plays a decisive role in transmitting force to alveolar bone via Sharpey fibers, transforming and converting these forces into biological signals. This interaction effects significant osteoblastic and osteoclastic responses via autocrine proliferative and paracrine responses. Recent discoveries of receptors for temperature and touch by the Nobel laureates David Julius and Ardem Patapoutian, respectively have a profound impact on orthodontics. Transient receptor vanilloid channel 1 (TRPV1), initially described as a receptor for temperature, has been proposed to participate in the sensing of force. TRPV4, another ion channel receptor, perceives tensile forces as well as thermal and chemical stimuli. Piezo1 and 2, the classic receptors for touch, in addition to the aforementioned receptors, have similarly been described on PDL-derived cells. In this text, we review the role of the temperature-sensitive ion channels and mechanosensitive ion channels on their biological function and influence in orthodontic treatment.

Infections in Burn Patients: A Retrospective View over Seven Years.

Backgroundand objectives: Burn patients represent a challenging cohort because the injuries entail a vulnerability to colonisation by microorganisms. The ensuing infections can lead to serious complications and, in many cases, to the death of the burn patient. Surgical intervention and wound dressings, as well as antibiotic treatment, are crucial for optimising the treatment of the patient. Materialand Methods: In this retrospective analysis, we analysed the treatment course, antibiotic therapy, and general complications of 252 burn patients with second- or third-degree burns over a time span of 7 years. Results: Patients who developed infections tended to have, on average, a higher total body surface area (TBSA), higher abbreviated burn severity index (ABSI) scores, and longer hospital stays. Patients who were admitted to the burn unit after 2006 had significantly shorter stays in the burn unit. TBSA and ABSI scores were lower in the patient cohort admitted after 2006. Patients exhibiting a TBSA greater than 30% had significantly longer hospital stays and antibiotic treatment periods. TBSA and ABSI scores were significantly higher in patients who died. The results of binary logistic regression indicate that a higher ABSI score increases the odds ratio of developing an infection. Bacteria number had no significant effect on the odds of patient death but positively influenced the odds ratio of developing an infection. TBSA was negatively associated with the risk of developing an infection and was an insignificant predictor of mortality. Conclusions: To gauge the optimal treatment for a burn patient, it is crucial for practitioners to correctly select, dose, and time antibiotics for the patient. Monitoring bacterial colonisation is vital to nip rising infection in the bud and ensure the correct antibiotic selection. This will help prevent the development of multi-resistant bacteria.

Does Increased Patient Load Improve Mortality in Burns?: Identifying Benchmark Parameters Defining Quality of Burn Care.

INTRODUCTION: In burn care, as in other medical fields, there is a tendency to increase the required number of patients for center certifications. Does the increase in patient load automatically improve the quality of burn care? What are the benchmark parameters that have been shown to improve burn care? METHODS: To answer these questions, Medline, Cochrane Library, and Livivo were searched from inception through January 2018 for all studies evaluating the influence of treatment parameters on outcomes in different burn care settings. RESULTS: Fifteen studies were included in this systematic review. In adults, not a single study showed a decreased mortality due to a higher patient load. However, in children, 2 studies demonstrated a further decrease of the already low mortality due to an increase in patient load. In contrast to patient load, benchmark parameters that had a significant influence on the outcome of burn care for adults and children were: single bed isolation, residency programs, American Burn Association certifications of burn centers, speed of wound closure, and standard operating procedures for burn care. CONCLUSIONS: This systematic review demonstrates that a clear correlation between patient load and mortality reduction in adult burn treatment is not supported by the existing literature, requiring future studies. In contrast, all efforts aiming to improve the quality of burn care, such as isolation of burn patients, speed of wound closure, American Burn Association verification and especially standard operating procedures for burn care improve survival and quality of burn care.

Healing Time Correlates With the Quality of Scaring: Results From a Prospective Randomized Control Donor Site Trial.

BACKGROUND: Scar formation remains a potential problem after surgery or trauma. Factors influencing scar tissue have been recognized, most notably healing time and wound depth. OBJECTIVE: To examine the association between healing time and the quality of scar tissue formation. MATERIALS AND METHODS: Scarring was assessed at 3 and 12 months after treatment in an RCT of 219 patients and consecutive 438 split-thickness skin graft donor sites. The primary end point of the study was healing time and the quality of scar tissue, which was scored by a validated scar scale evaluating scar height, surface, and color. RESULTS: The mean time of wound healing was 15.8 days, with a mean scar score of 6.89 at 3 months and 4.66 at 12 months. There was a significant (p < .000001) and linear correlation between healing time and scar quality. Of particular note, at 12 months, all subparameters of the score demonstrated worsening with prolonged time to heal. CONCLUSION: The authors could objectively demonstrate that epithelialization time is an important factor influencing scar quality. In contrast to previous assumptions, this correlation follows linearly. It is reasonable then to assume that treatment strategies expediting healing will also improve scar outcome.

Adipokine concentrations in lipoaspirates may have a role in wound healing.

OBJECTIVES: In addition to its use as a volume filler, fat grafting may have a potential role in wound healing based on the concentration of growth factors in the lipoaspirate. In this study, we compare the quantitative and qualitative concentration of the various growth factors and adipokines using the Shippert or the Coleman techniques to prepare the lipoaspirate. METHODS: We measured leptin, adiponectin and the growth factors, i.e., acidic fibroblast growth factor (aFGF), basic FGF (bFGF), keratinocyte growth factor (KGF), bone morphogenetic protein-2 (BMP-2) and vascular endothelial growth factor (VEGF) by ELISA in solid and liquid fractions obtained with both techniques in human fat obtained with Coleman technique and Shippert technique. RESULTS: All of these peptides, except BMP-2, were detected in relevant quantities in the solid fraction. The Coleman but not the Shippert technique resulted in statistically higher adiponectin concentrations in the solid tissue fraction. The other four growth factors occurred in significantly higher concentrations in the solid fractions compared to the liquid fractions, independent of the processing technique. CONCLUSION: In summary, we demonstrated that KGF, aFGF, bFGF and VEGF, as well as leptin and adiponectin, are contained in fat suspensions obtained by liposuction and in the supernatant. Only the concentration of adiponectin was in the range reported to contribute to wound healing.

Evaporative Water Loss in Superficial to Full Thickness Burns.

INTRODUCTION: Increased evaporative water loss (EWL) in burn patients leads to dehydration and hypothermia. Early clinical studies performed with outdated hygrometers suggested a 17 to 75 times increased EWL in burns with contradicting results for the different burn depths.Our study proposals were: (1) obtain reliable data of the EWL of all burn depths, (2) compare these results with findings from earlier studies, (3) evaluate the usefulness of the EWL in differentiating between superficial and deep partial thickness burns, (4) determine the effect of Biobrane on the EWL of superficial partial thickness burns in vivo, and (5) evaluate the effect of the sterile incision foil Opraflex on the EWL in split skin graft donor sites. METHODS: We measured the EWL of all burn depths in 28 patients under stable and recorded conditions regarding room temperature and humidity with a modern digital evaporimeter (Tewameter TM 300). For the first time in vivo, we also determined the effect of Biobrane on the EWL of burns and evaluated the EWL in split skin graft donor sites covered with Opraflex. RESULTS: The EWL in all burn depths was significantly increased (P < 0.001) compared with unburned skin. There was no significant difference (P > 0.05) in the EWL of superficial compared with deep partial thickness burns, whereas full thickness burns had a significantly lower EWL (P < 0.05) compared with superficial and deep partial thickness burns. Biobrane significantly reduced the EWL (P < 0.05) of superficial partial thickness burns. The EWL of Opraflex covered skin graft donor sites was significantly reduced compared with uncovered donor sites (P < 0.05). CONCLUSIONS: Our data suggest that the actual EWL in burns is approximately 3 times higher in full thickness burns and approximately 4 times higher in superficial and deep partial thickness burns compared with normal skin and therefore much lower than suggested previously.Because there was no significant difference in the EWL of superficial compared with deep partial thickness burns, the EWL cannot be used to differentiate between these burn depths.Biosynthetic wound dressings can significantly reduce the EWL of superficial partial thickness burns and sterile incision foil protects split skin graft donor sites from an increased EWL.

The Effect of Lipoaspirates on Human Keratinocytes.

BACKGROUND: One increasingly important trend in plastic, reconstructive, and aesthetic surgery is the use of fat grafts to improve cutaneous wound healing. In clinical practice, lipoaspirates (adipose tissue harvested by liposuction) are re-injected in a procedure called lipofilling. Previous studies, however, mainly evaluated the regenerative effect of isolated adipocytes, adipose-derived stem cells, and excised en bloc adipose tissue on keratinocytes, whereas no study to date has examined the effect of lipoaspirates. OBJECTIVES: The authors aimed to investigate differences in the regenerative property of en bloc adipose tissue and lipoaspirates on keratinocytes. METHODS: Human keratinocytes, lipoaspirates, and en bloc adipose tissue from 36 healthy donors were isolated. In vitro proliferation, differentiation, migration, stratification, and wound healing of keratinocyte monolayers were measured. Furthermore, secreted levels of VEGF, bFGF, IGF-1, MMP-9, and MIF were detected by ELISA. RESULTS: Migration, proliferation, and wound healing of keratinocytes were increased by lipoaspirates. Interestingly, the effect of lipoaspirates on keratinocyte proliferation was significantly higher than by en bloc adipose tissue after 5 days. The differentiation of keratinocytes was equally attenuated by lipoaspirates and en bloc adipose tissue. Stratification of keratinocyte layers was enhanced by lipoaspirates and en bloc fat when compared to controls. Lipoaspirates secrete higher levels of bFGF, whereas higher levels of VEGF and IGF-1 are released by en bloc adipose tissue. CONCLUSION: We show that lipoaspirates and en bloc adipose tissue have a regenerative effect on keratinocytes. One reason for the higher effect of lipoaspirates on keratinocyte proliferation may be the secretion of different cytokines.

Intraoperative use of enriched collagen and elastin matrices with freshly isolated adipose-derived stem/stromal cells: a potential clinical approach for soft tissue reconstruction.

BACKGROUND: Adipose tissue contains a large number of multipotent cells, which are essential for stem cell-based therapies. The combination of this therapy with suitable commercial clinically used matrices, such as collagen and elastin matrices (i.e. dermal matrices), is a promising approach for soft tissue reconstruction. We previously demonstrated that the liposuction method affects the adherence behaviour of freshly isolated adipose-derived stem/stromal cells (ASCs) on collagen and elastin matrices. However, it remains unclear whether freshly isolated and uncultured ASCs could be directly transferred to matrices during a single transplantation operation without additional cell culture steps. METHODS: After each fat harvesting procedure, ASCs were isolated and directly seeded onto collagen and elastin matrices. Different time intervals (i.e. 1, 3 and 24 h) were investigated to determine the time interval needed for cellular attachment to the collagen and elastin matrices. Resazurin-based vitality assays were performed after seeding the cells onto the collagen and elastin matrices. In addition, the adhesion and migration of ASCs on the collagen and elastin matrices were visualised using histology and two-photon microscopy. RESULTS: A time-dependent increase in the number of viable ASCs attached to the collagen and elastin matrices was observed. This finding was supported by mitochondrial activity and histology results. Importantly, the ASCs attached and adhered to the collagen and elastin matrices after only 1 h of ex vivo enrichment. This finding was also supported by two-photon microscopy, which revealed the presence and attachment of viable cells on the upper layer of the construct. CONCLUSION: Freshly isolated uncultured ASCs can be safely seeded onto collagen and elastin matrices for ex vivo cellular enrichment of these constructs after liposuction. Although we observed a significant number of seeded cells on the matrices after a 3-h enrichment time, we also observed an adequate number of isolated cells after a 1-h enrichment time. However, this approach must be optimised for clinical use. Thus, in vivo studies and clinical trials are needed to investigate the feasibility of this approach.

[Surgical management of burn injury patients : Comments on the guidelines on treatment of thermal injuries in adults]. / Chirurgisches Management des brandverletzten Patienten : Kommentar zur Leitlinie Behandlung thermischer Verletzungen des Erwachsenen.

The treatment of burn injury patients is a unique challenge for clinicians. The extent of thermal injuries ranges from very small burns to life-threatening burn injuries. Insufficient treatment can result in a substantial impairment in the quality of life. In order to avoid such sequelae a targeted treatment must be carried out. A precise diagnosis determines the necessary treatment. Superficial second-degree burns (2a) not involving the face, hand or joints with a total body surface area smaller than 10% can usually be treated with modern wound dressings in an outpatient setting. Deep second-degree burns (2b) are an indication for debridement. In addition to the classical surgical procedures with tangential excision, enzymatic debridement can also be employed. Similarly, indeterminate burns (2a/2b) are also considered to be an indication for enzymatic debridement. Third-degree burns are treated with early debridement and skin grafting. These patients can also benefit from special dermal replacement procedures for an improvement of the functional and esthetic results. Due to the long-term visible sequelae of burns, aftercare of these patients is indicated.

Roles of Mechanosensitive Channel Piezo1 in Wound Healing and Scar Formation.

The ability to heal one's wounds is perhaps one of the most fundamental and critical of physiologic processes. This coordinated and closely regulated sequential biological process involves a variety of migratory and resident cells. The activation, modulation, balance, and control of these functions depend upon soluble mediators that activate cells and modulate their diverse functions. Recent advances have identified mechanotransduction as functionally integral in many different cell types and physiologic processes. The mechanically sensitive ion channel Pieoz1 is expressed on platelets, neutrophils, macrophages, endothelial cells, keratinocytes, and fibroblasts, all of which are principally involved in wound healing. On a cellular level, there have been great advances in our understanding of the functional role of Piezo1 mechanotransduction in cutaneous wounding. The blocking of Piezo1 has recently been shown to reduce scarring in vivo and yet, thus far, a comprehensive understanding of the roles that Piezo1 plays in in vivo wound healing remains lacking. Recognizing the ever-present and critical importance of optimal and reparative wound healing, and with the availability of new physical mechanomodulating devices, the time is ripe for gaining deeper insights into optimizing wound healing. In this review, we describe the current knowledge of Piezo1 related to wound healing.

Paracrine loop of keratinocyte proliferation and directed neuritic outgrowth in a neuroepithelial coculture.

In the absence of skin innervation, wound healing is delayed and chronic nonhealing wounds may occur. Keratinocytes produce neurotrophic factors, such as nerve growth factor (NGF), which has been suggested to attract primary cutaneous afferent axons and exert mitogenic effects on keratinocytes. The present study was performed to examine the interaction of primary human keratinocytes (hKTs) and rat cutaneous primary afferent dorsal root ganglion (DRG) neurons with regard to neuritic outgrowth and keratinocyte proliferation. Neuritic outgrowth was assessed with neurofilament immunostaining where cell bodies and fine neuritic processes were identified. Neuritic outgrowth of neurons alone in culture is spatially random and radial. Neurites in cocultures of DRG neurons insinuated between the hKTs and grew to "clumps" of hKTs within the cultures. Immunostaining with anti-NGF antibody indicates that hKTs expressed the neurotrophin NGF. Proliferation of keratinocytes was significantly enhanced in coculture with DRG and hKT, and NGF levels were increased as compared to DRG or hKT culture alone. These results indicate a dynamic interaction between DRG neurons and hKTs whereby the DRG neurons issue neurites in association with hKTs and the hKTs up-regulate NGF and increase their proliferation rate. These findings support the hypothesis that nerve-skin interactions play a significant role in wound healing.

[Psychiatric co-morbidity, body image problems and psychotherapeutic interventions for burn survivors: a review]. / Psychische Komorbidität, Körperbildprobleme und psychotherapeutische Interventionen bei Brandopfern: ein Überblick.

Due to progress in burn treatment, more patients even with severe burn injuries survive. Despite this positive development, however, there are still negative somatic and mental consequences. These include the life-long care of scars and pain. In addition, posttraumatic-stress disorder and depression are common consequences. Also distress due to disfigurement and body image problems have to be considered, since this is likely to result in social withdrawal, low self-esteem, and reduction of quality of life. Overall, the impact of mental strain on burn victims is quite high. Therefore, psychotherapeutic treatment approaches should be integrated into the care of patients with burns. This might be helpful for both coping and compliance with long-term treatment. This paper provides a review of the mental co-morbidity of burn victims and of psychotherapeutic treatment approaches focusing on changes in body image and the respective social consequences.

[Surgical management of burn injury patients : Comments on the guidelines on treatment of thermal injuries in adults]. / Chirurgisches Management des brandverletzten Patienten : Kommentar zur Leitlinie Behandlung thermischer Verletzungen des Erwachsenen.

The treatment of burn injury patients is a unique challenge for clinicians. The extent of thermal injuries ranges from very small burns to life-threatening burn injuries. Insufficient treatment can result in a substantial impairment in the quality of life. In order to avoid such sequelae a targeted treatment must be carried out. A precise diagnosis determines the necessary treatment. Superficial second-degree burns (2a) not involving the face, hand or joints with a total body surface area smaller than 10% can usually be treated with modern wound dressings in an outpatient setting. Deep second-degree burns (2b) are an indication for debridement. In addition to the classical surgical procedures with tangential excision, enzymatic debridement can also be employed. Similarly, indeterminate burns (2a/2b) are also considered to be an indication for enzymatic debridement. Third-degree burns are treated with early debridement and skin grafting. These patients can also benefit from special dermal replacement procedures for an improvement of the functional and esthetic results. Due to the long-term visible sequelae of burns, aftercare of these patients is indicated.

Autologous Fat Transfer for Thumb Carpometacarpal Joint Osteoarthritis: Long Term Results. / Eigenfettinjektion bei Rhizarthrose: 5 Jahresergebnisse bei 42 Patienten.

BACKGROUND: Initial results after autologous fat transfer for treatment of thumb carpometacarpal joint osteoarthritis have been promising. But long-term results have not yet been available. METHODS: In a prospective study, 42 patients with thumb carpometacarpal joint osteoarthritis were observed for a mean time of 5 years after autologous fat transfer. Manual liposuction and centrifugation were performed. Pain rating according to numerous analogue pain scale; objective force of pinch grip and fist closure; and Disabilities of the Arm, Shoulder, and Hand questionnaire score (DASH score) before and after treatment were analysed. RESULTS: The average pain preoperatively was 8.0 ± 1.6 and 4.0 ± 3.0 after 5 years overall. Force and pinch force of the treated hand improved from 71% and 60% preoperative in comparison to the non-treated hand to 100% and 96%, respectively, 5 years after fat transplantation. There were similar improvements for the parameters strength and DASH score. All improvements were statistically significant. No serious adverse events were observed. CONCLUSIONS: Autologous fat transplantation is a real alternative to trapeziectomy even in the long term in basal joint osteoarthritis of the thumb. The low invasiveness of the procedure and early recovery of patients compared with classical procedures such as trapeziectomy, and the superior long-term results compared with classical injection therapy, make this approach feasible as a first-line therapy in basal joint osteoarthritis of the thumb as it offers stable results and warrants a high patient satisfaction rate.

Preparation of human amniotic membrane for transplantation in different application areas.

The human amniotic membrane (hAM) is the inner layer of the placenta and plays protective and nutritional roles for the fetus during pregnancy. It contains multiple growth factors and proteins that mediate unique regenerative properties and enhance wound healing in tissue regeneration. Due to these characteristics hAM has been successfully utilized in ophthalmology for many decades. This material has also found application in a variety of additional therapeutic areas. Particularly noteworthy are the extraordinary effects in the healing of chronic wounds and in the treatment of burns. But hAM has also been used successfully in gynecology, oral medicine, and plastic surgery and as a scaffold for in vitro cell culture approaches. This review aims to summarize the different graft preparation, preservation and storage techniques that are used and to present advantages and disadvantages of these methods. It shows the characteristics of the hAM according to the processing and storage methods used. The paper provides an overview of the currently mainly used application areas and raises new application possibilities. In addition, further preparation types like extracts, homogenates, and the resulting treatment alternatives are described.

Reconstruction of Upper and Lower Limb Defects with Medial Sural Artery Perforator Flaps: Is Aesthetics Worth the Effort? A Retrospective Analysis.

Background One of the most essential goals in managing complex limb defects is obtaining adequate soft tissue coverage with excellent functional and aesthetic outcomes. Free perforator skin flaps represent an optimal option for such defects. Therefore, our intention was to reconstruct these kinds of defects with thin fasciocutaneous flaps without the need for debulking. Herein, we define the legitimate use of the medial sural artery perforator (MSAP) flaps for small-moderate size defect coverage of the hand and foot. Patients and Methods Seven patients received MSAP flaps for reconstruction of different hand and foot defects, of which the majority were males (4/7). Age, sex, flap size, location, number of perforators, recipient vessel, type of anastomosis, technique of donor site closure, and postoperative morbidity were recorded. Patients' age ranged from 48 to 84 years. Results Single-stage debridement followed by reconstruction was performed. Flap sizes ranged from 6 to 18 cm in length and 4 to 10 cm in width. The pedicles of 6 flaps were anastomosed to the tibial artery system (three posterior tibial artery, three dorsalis pedis artery) and one to the ulnar artery. Conclusion MSAP flap can be a versatile option for single-stage reconstruction of small-moderate size defects of the extremities, where thin, soft tissue envelope is required. This flap has lower donor site morbidity, more tedious elevation process, and has a good reconstructive and aesthetic result without the need for debulking in the future.

Too little appreciation for great expenditure? Workload and resources in ICUs.

PURPOSE: The aim of this study was providing descriptive information and the comparative examination of job strain and mental health of nurses and physicians in different intensive care units (ICU). METHODS: The Effort-Reward Imbalance Questionnaire by Siegrist and standardized psychometric questionnaires, like Hospital Anxiety and Depression Scale, Impact of Event Scale, Brief Symptom Inventory, Social Support Questionnaire, and Life Satisfaction Questionnaire were used. Five ICUs of the same German medical school were included (N = 142). RESULTS: For all ICUs investigated, a significantly lower mental health and a high effort-reward imbalance were found when compared with other samples. Only a few differences between the wards or both professional groups (nurses vs. physicians) were noted. The values for social support were comparable with those of healthy controls but differed between the wards. The life satisfaction in our cohort was lower compared to a population-based sample but was significant different between the wards. CONCLUSIONS: Our study demonstrates the high job strain in an ICU, largely independent of the professional group. Noteworthy, a high effort-reward imbalance was found that stands in positive relation to adverse health effects (anxiety, depression, and general mental health). As a consequence, necessary interventions like stress management, supervision, and communication trainings should consider ward-specific conditions of employment rather than professional affiliation. After these interventions, a follow-up study will be performed to examine beneficial effects on job strain and health.

Evaluation of prophylactic anticoagulation, deep venous thrombosis, and heparin-induced thrombocytopenia in 21 burn centers in Germany, Austria, and Switzerland.

Heparin-induced thrombocytopenia (HIT) is a life-threatening complication in intensive care settings. The timely diagnosis and management of HIT are challenging, and the incidences of HIT and deep venous thrombosis (DVT) may be related to prophylactic anticoagulation standards in burn units. We therefore evaluated, using a questionnaire, prophylactic anticoagulation, HIT management, and incidences of DVT and HIT in burn centers located in the German-speaking part of Europe. In the 21 responding burn centers, 1611 patients were treated and the overall incidences for clinically overt DVT and HIT in 2008 were 1.1% and 1.4%, respectively. Burn centers using low molecular weight heparin (LMWH) subcutaneous for all patients had a low rate of DVT (0.9%) and significantly lower rates of HIT (0.2%) relative to all other centers (P < 0.05). The highest rates of HIT (2.7%) and DVT (3.8%) were found in burn centers administering unfractionated heparin intravenous. While current HIT guidelines do not specify the administration of unfractionated heparin or LMWH for burn patients, these data warrant controlled prospective studies to confirm the advantage of LMWH administration in burn patients.

Burn Injury: Mechanisms of Keratinocyte Cell Death.

Cutaneous burn injury is associated with epidermal loss in the zone of coagulation zone and delayed tissue loss in the zone of stasis. Thus, thermal stress can trigger both necrosis and regulated cell death (RCD) or apoptosis. Experimental in vitro and in vivo work has clearly demonstrated apoptotic events of thermally injured keratinocytes that are accompanied by morphological and biochemical markers of regulated cell death. However, in vivo data for the different pathways of regulated cell death are sparse. In vitro experiments with heat-stressed human keratinocytes have demonstrated death receptor involvement (extrinsic apoptosis), calcium influx, and disruption of mitochondrial membrane potential (intrinsic apoptosis) in regulated cell death. In addition, caspase-independent pathways have been suggested in regulated cell death. Keratinocyte heat stress leads to reduced proliferation, possibly as a result of reduced keratinocyte adhesion (anoikis) or oncogene involvement. Understanding the underlying mechanisms of RCD and the skin's responses to thermal stress may lead to improved strategies for treating cutaneous burn trauma.