A Prospective Study of Sentinel Node Biopsy Omission in Women Age ≥ 65 Years with ER+ Breast Cancer.

BACKGROUND: National guidelines recommend omitting SNB in older patients with favorable invasive breast cancer. However, there is a lack of prospective data specifically addressing this issue. This study evaluates recurrence and survival in estrogen receptor-positive/Her2- (ER+) breast cancer patients, aged ≥ 65 years who have breast-conserving surgery (BCS) without SNB. METHODS: This is a prospective, observational study at a single institution where 125 patients aged ≥ 65 years with clinical T1-2N0 ER+ invasive breast cancer undergoing BCS were enrolled. Patients were treated with BCS without SNB. Primary outcome measure was axillary recurrence. Secondary outcome measures include recurrence-free survival (RFS), disease-free survival (DFS), breast cancer-specific survival (BCSS), and overall survival (OS). RESULTS: From January 2016 to July 2022, 125 patients were enrolled with median follow-up of 36.7 months [95% confidence interval (CI) 35.0-38.0]. Median age was 77.0 years (range 65-93). Median tumor size was 1 cm (range 0.1-5.0). Most tumors were ductal (95/124, 77.0%), intermediate grade (60/116, 51.7%), and PR-positive (117/123, 91.7%). Radiation therapy was performed in 37 of 125 (29.6%). Only 60 of 125 (48.0%) who were recommended hormonal therapy were compliant at 2 years. Chemotherapy was administered to six of 125 (4.8%) patients. There were two of 125 (1.6%) axillary recurrences. Estimated 3-years rates of regional RFS, DFS, and OS were 98.2%, 91.2%, and 94.8%, respectively. Univariate Cox regression identified hormonal therapy noncompliance to be significantly associated with recurrence (p = 0.02). CONCLUSIONS: Axillary recurrence rates were extremely low in this cohort. These results provide prospective data to support omission of SNB in this patient population TRIAL REGISTRATION: ClinicalTrials.gov ID NCT02564848.

Fibromodulin Is Essential for Fetal-Type Scarless Cutaneous Wound Healing.

In contrast to adult and late-gestation fetal skin wounds, which heal with scar, early-gestation fetal skin wounds display a remarkable capacity to heal scarlessly. Although the underlying mechanism of this transition from fetal-type scarless healing to adult-type healing with scar has been actively investigated for decades, in utero restoration of scarless healing in late-gestation fetal wounds has not been reported. In this study, using loss- and gain-of-function rodent fetal wound models, we identified that fibromodulin (Fm) is essential for fetal-type scarless wound healing. In particular, we found that loss of Fm can eliminate the ability of early-gestation fetal rodents to heal without scar. Meanwhile, administration of fibromodulin protein (FM) alone was capable of restoring scarless healing in late-gestation rat fetal wounds, which naturally heal with scar, as characterized by dermal appendage restoration and organized collagen architectures that were virtually indistinguishable from those in age-matched unwounded skin. High Fm levels correlated with decreased transforming growth factor (TGF)-ß1 expression and scarless repair, while low Fm levels correlated with increased TGF-ß1 expression and scar formation. This study represents the first successful in utero attempt to induce scarless repair in late-gestation fetal wounds by using a single protein, Fm, and highlights the crucial role that the FM-TGF-ß1 nexus plays in fetal-type scarless skin repair.

Violence at work: forensic medical examination of police officers assaulted while on duty: comparisons with other groups of workers in two centres of the Paris area, 2010-2012.

PURPOSE: To test for differences in somatic, psychic and functioning outcomes associated with assaults across four groups of workers, of which three are structurally at high risk of occupational violence. To report and compare job characteristics, characteristics of the assault and medical findings in police officers and other workers at the time of a forensic examination performed shortly after they complained for being assaulted while working. METHODS: A two-centre prospective study recruiting adult survivors of workplace violence who lodged a complaint to the judicial authorities and were examined by forensic physicians in the Paris area, between 2010 and 2012 over a 27-month period, was conducted. Victims were administered a dedicated questionnaire and filled in the peritraumatic dissociative experiences questionnaire. Bivariate and multivariate analyses were performed on collected data to account for potential biases. RESULTS: Compared to employees of public transports services, private security guards and other workers, police officers were less likely to report psychic disturbances and peritraumatic dissociative experiences, despite adverse factors such as a worse external working climate or more frequent exposure to workplace assaults. No differences were observed in terms of somatic symptoms or functional impairment across groups. CONCLUSIONS: Although structurally more exposed to adverse factors than other workers, police officers appeared to be more protected from negative outcomes. The reasons for this resilience should be more precisely investigated.

A novel clinical trial recruitment strategy for women's cancer.

OBJECTIVE: To address a deficiency in clinical trial and research enrollment in gynecologic cancer studies, we launched a paper based patient research registry. To improve registry enrollment, we transitioned to an online registry and trial matching mechanism to aid women in accessing open studies. METHODS: Utilizing a validated verification platform, we designed a web-based registry and trial matching mechanism for women over age 18. Participants completed a questionnaire to provide information for trial matching. A focus group of registry participants was held 9 months after the start of the study to evaluate barriers to participation. RESULTS: A total of 322 women were enrolled in the online registry over a 14 month period which was a 4.3 fold increase over the paper-based registry (p<0.0001). Two hundred and sixty three (82%) women were matched to at least one study. Fifteen percent (39/263) of those eligible for studies went on to enroll. The online enrollment rate to studies was not different from that observed in the paper-based registry (26/172, p=0.934), however, the web-based registry linked participants to subsequent studies 27% more rapidly (68 (+/-98) days vs. 93 (+/-81) days for the paper-based registry, p=0.017). Focus group participants identified areas for improvement. CONCLUSION: Web-based patient driven registry provides dramatic improvement in the number of participants enrolled and the time to trial linkage compared to a paper based registry at a single institution. Further studies of barriers to research participation are necessary to improve on this model.

Detainees in police custody in the Paris, France area: medical data and high-risk situations (a prospective study over 1 year).

BACKGROUND AND OBJECTIVE: The annual number of detainees held in police custody in France is approximately 700,000. Medical data regarding arrestees are scarce across countries. We present the medical characteristics of detainees kept in police custody, including addictive behaviours and high-risk medical situations. METHODS: We conducted a prospective study over 1 year in a suburban area near Paris. RESULTS: A total of 19,098 medical examinations were performed on 13,317 individuals. The examinations mainly concerned male subjects (18,116 of 19,098, 95 %). Median age was 24 years (range 13-83). Medical examination was requested by the detainee in 6,638 of 16,801 cases (40 %). Assaults were reported in 4,052 of 17,312 cases (23 %) and occurred at the time of arrest in most cases (2,243, 13 %). A total of 2,394 of 13,317 detainees (18 %) had at least one chronic somatic disorder including asthma (603, 5 %), diabetes (263, 2 %) and arterial hypertension (205, 2 %). A history of psychiatric disorder was reported by 6 % of individuals (674 of 11,787). Regular alcohol drinking was reported by 58 % of detainees. Illicit drug use mainly involved cannabis (4,021 cases, 30 %). In 14,661 of 19,098 cases (77 %), detainees were considered to be unconditionally fit for detention in custody, and 274 detainees (1 %) were declared unfit to be detained. CONCLUSION: The present study showed a high frequency of alcohol or substance use and reported assaults or traumatic lesions in arrestees. Attending physicians should pay particular attention to addictive behaviours and traumatic injuries in arrestees, both for immediate care and for prevention.

Suspicion of needle pricking/spiking in 2022 in Paris, France, an observational study from the Department of Forensic Medicine.

BACKGROUND: Needle pricking, the act of being intentionally pricked by an assailant, and needle spiking, the covert injection of substances using a needle, have historical precedents and recently resurfaced in Europe in 2022. This resurgence presented a challenge for emergency and forensic medicine departments. METHODS: We conducted a retrospective study in the forensic medicine department of Paris, France, including all patients who consulted for suspected needle pricking/spiking in 2022, following a police report. The study aimed to provide epidemiological data on victims, circumstances, and the results of toxicologic and serological analyses. FINDINGS: Of all assault victims in 2022, patients reporting or suspecting needle pricking/spiking represented 1.2 % of the total (171 cases). Most cases involved women (81.9 %) with a median age of 21.75 years. Incidents often occurred in festive contexts (84.8 %). Over a third of the patients didn't report any symptoms (37.5 %). Amnesia, nausea, and dizziness were common symptoms among those who did. Patients reporting alcohol consumption were more likely to experience symptoms (p < 0.05). Over half of the patients displayed physical examinations consistent with needle pricking, with pricks mostly on their arms. Not all patients underwent toxicologic analyses (30.6 %), but all results were negative. Despite most patients not providing follow-up serology results, all received results were negative. INTERPRETATION: Overall, our data are more suggestive of needle pricking than spiking. Although women were overrepresented, there was no evidence of sexual motivation on the part of the perpetrators. It's possible that the perpetrators wanted to instill fear in the population without a specific goal. This form of violence necessitates preventive measures in festive venues and enhanced efforts to detect psychoactive substance.

Single-cell and spatial profiling identify three response trajectories to pembrolizumab and radiation therapy in triple negative breast cancer.

Strategies are needed to better identify patients that will benefit from immunotherapy alone or who may require additional therapies like chemotherapy or radiotherapy to overcome resistance. Here we employ single-cell transcriptomics and spatial proteomics to profile triple negative breast cancer biopsies taken at baseline, after one cycle of pembrolizumab, and after a second cycle of pembrolizumab given with radiotherapy. Non-responders lack immune infiltrate before and after therapy and exhibit minimal therapy-induced immune changes. Responding tumors form two groups that are distinguishable by a classifier prior to therapy, with one showing high major histocompatibility complex expression, evidence of tertiary lymphoid structures, and displaying anti-tumor immunity before treatment. The other responder group resembles non-responders at baseline and mounts a maximal immune response, characterized by cytotoxic T cell and antigen presenting myeloid cell interactions, only after combination therapy, which is mirrored in a murine model of triple negative breast cancer.

Effects of paravertebral blocks versus liposomal bupivacaine on hospital utilization after mastectomy with reconstruction.

INTRODUCTION: Inadequate pain control frequently extends length of stay (LOS) and costs for patients undergoing mastectomy with implant-based reconstruction (IBR). We sought to examine the effects of Paravertebral blocks (PVB) and liposomal bupivacaine (LB) and compare LOS, pain scores and costs of hospitalization. METHODS: Prospective database review of patients undergoing mastectomy with IBR was performed. RESULTS: 541 patients were identified. 51/491 (9.4%) received PVB and 50 (9.2%) received LB. LOS in the PVB group was significantly less than that of the no block (NB) group (1 [1-2] days PVB vs 3 [2-4] days NB (p < 0.0001), but was not different from the LB group (1 [1-2] days LB, p = 0.23). PVB patients had lower PACU pain scores compared to NB patients (3.2 ± 2.9 PVB vs 5.7 ± 2.6 NB, p < 0.0001), but similar PACU pain scores to LB patients (4.1 ± 2.3). Patients who received PVB had higher total costs compared to NB patients ($27148±$7053 PVB vs $23113 ± 6860 NB, p = 0.003) but similar to LB patients ($26183 ± $3761). CONCLUSION: PVB and LB are associated with shorter LOS and lower pain scores compared to NB.

Breast MRI after bilateral mastectomy: is it indicated?

Little is known about the use of breast MRI as a diagnostic or surveillance tool in patients after bilateral mastectomy. The objective of this study was to evaluate breast MRI after bilateral mastectomy. Participants consisted of 48 women with prior bilateral mastectomy who underwent breast MRI between 2003 and 2009. Seventy-nine breast MRIs were obtained. The median time between mastectomy and first MRI was 36 months. MRI was ordered most often by a medical oncologist (71%). Median age at bilateral mastectomy was 49 years (range, 33 to 72 years). Reasons for obtaining MRI included surveillance in 60 (76%), mass in eight (10%), lymph nodes in four (5%), pain in three (4%), and abscess in one (1%). Overall, 68 (86%) MRIs showed benign imaging findings only. Within the surveillance group, six patients had MRIs with findings that changed management; four patients had some residual breast tissue, and two patients had findings outside the breast that were better evaluated by CT or bone scan and were ultimately benign. MRI confirmed locoregional recurrence in two patients with highly suspicious physical findings. Overall, postmastectomy breast MRI had limited use, finding no unsuspected recurrences within our study group. Although MRI can be helpful to establish the presence of residual breast tissue after bilateral mastectomy, subsequent routine screening breast MRI should be questioned if no residual breast tissue is identified.

A roadmap to the safe practice of forensic medicine in the COVID-19 pandemic.

The COVID-19 pandemic has forced forensic practitioners to consider how we perform our normal duties, especially when those duties involve humans. The potential for contracting the virus from working in close contact with living sufferers is high, and we have yet to fully determine the risk of infection from the deceased. In an attempt to support the community, the Journal of Forensic & Legal Medicine has drawn together three articles which underline the importance of continued forensic medical practice during the pandemic and highlight some factors to consider in a Roadmap towards safe practice. Our Roadmap has intentionally taken an international perspective and supports other work we have published in the Journal on our collective response to the COVID-19 crisis.

Increased use of MRI for breast cancer surveillance and staging is not associated with increased rate of mastectomy.

The use of MRI in preoperative staging of breast cancer has escalated recently. Breast MRI has greater sensitivity than mammography, ultrasound, and clinical examination in cancer detection. Because of its variable specificity, however, there has been concern that increased MRI use will result in increased rates of mastectomy for early-stage breast cancer. We postulated that mastectomy rates are not affected by trends in MRI use. We performed a retrospective analysis of imaging tests ordered by surgeons at our breast center from 2003 to 2007. We also reviewed all breast cancer cases reported to the National Cancer Database from our institution during the same time period and categorized them as having been treated with mastectomy or breast-conserving surgery. From 2003 to 2007, the number of breast MRIs ordered annually by surgeons increased from 68 to 358. The rate of MRI use increased from 4.1 per every 100 patients seen to 5.7 and from 1.6 per every 100 new patients seen to 2.9. The percentage of women undergoing mastectomy for breast cancer remained unchanged during this 5-year interval. Therefore, although MRI use in breast cancer staging and surveillance has increased, mastectomy rates have not.

A data model for clinical legal medicine practice and the development of a dedicated software for both practitioners and researchers.

OBJECTIVE: To present a data model for clinical legal medicine and the software based on that data model for both practitioners and researchers. The main functionalities of the presented software are computer-assisted production of medical certificates and data capture, storage and retrieval. METHODS: The data model and the software were jointly developed by the department of forensic medicine of the Jean Verdier Hospital (Bondy, France) and an bioinformatics laboratory (LIMICS, Paris universities 6-13) between November 2015 and May 2016. The data model was built based on four sources: i) a template used in our department for producing standardised medical certificates; ii) a random sample of medical certificates produced by the forensic department; iii) anterior consensus between four healthcare professionals (two forensic practitioners, a psychologist and a forensic psychiatrist) and iv) anatomical dictionaries. The trial version of the open source software was first designed for examination of physical assault survivors. RESULTS: An UML-like data model dedicated to clinical legal practice was built. The data model describes the terminology for examinations of sexual assault survivors, physical assault survivors, individuals kept in police custody and undocumented migrants for age estimation. A trial version of a software relying on the data model was developed and tested by three physicians. DISCUSSION: The software allows files archiving, standardised data collection, extraction and assistance for certificate generation. It can be used for research purpose, by data exchange and analysis. Despite some current limitations of use, it is a tool which can be shared and used by other departments of forensic medicine and other specialties, improving data management and exploitation. Full integration with external sources, analytics software and use of a semantic interoperability framework are planned for the next months.

Characterization of primary human mammary epithelial cells isolated and propagated by conditional reprogrammed cell culture.

PURPOSE: Conditional reprogramming methods allow for the inexhaustible in vitro proliferation of primary epithelial cells from human tissue specimens. This methodology has the potential to enhance the utility of primary cell culture as a model for mammary gland research. However, few studies have systematically characterized this method in generating in vitro normal human mammary epithelial cell models. RESULTS: We show that cells derived from fresh normal breast tissues can be propagated and exhibit heterogeneous morphologic features. The cultures are composed of CK18, desmoglein 3, and CK19-positive luminal cells and vimentin, p63, and CK14-positive myoepithelial cells, suggesting the maintenance of in vivo heterogeneity. In addition, the cultures contain subpopulations with different CD49f and EpCAM expression profiles. When grown in 3D conditions, cells self-organize into distinct structures that express either luminal or basal cell markers. Among these structures, CK8-positive cells enclosing a lumen are capable of differentiation into milk-producing cells in the presence of lactogenic stimulus. Furthermore, our short-term cultures retain the expression of ERα, as well as its ability to respond to estrogen stimulation. MATERIALS AND METHODS: We have investigated conditionally reprogrammed normal epithelial cells in terms of cell type heterogeneity, cellular marker expression, and structural arrangement in two-dimensional (2D) and three-dimensional (3D) systems. CONCLUSIONS: The conditional reprogramming methodology allows generation of a heterogeneous culture from normal human mammary tissue in vitro. We believe that this cell culture model will provide a valuable tool to study mammary cell function and malignant transformation.

Craniosynostosis in transgenic mice overexpressing Nell-1.

Previously, we reported NELL-1 as a novel molecule overexpressed during premature cranial suture closure in patients with craniosynostosis (CS), one of the most common congenital craniofacial deformities. Here we describe the creation and analysis of transgenic mice overexpressing Nell-1. Nell-1 transgenic animals exhibited CS-like phenotypes that ranged from simple to compound synostoses. Histologically, the osteogenic fronts of abnormally closing/closed sutures in these animals revealed calvarial overgrowth and overlap along with increased osteoblast differentiation and reduced cell proliferation. Furthermore, anomalies were restricted to calvarial bone, despite generalized, non-tissue-specific overexpression of Nell-1. In vitro, Nell-1 overexpression accelerated calvarial osteoblast differentiation and mineralization under normal culture conditions. Moreover, Nell-1 overexpression in osteoblasts was sufficient to promote alkaline phosphatase expression and micronodule formation. Conversely, downregulation of Nell-1 inhibited osteoblast differentiation in vitro. In summary, Nell-1 overexpression induced calvarial overgrowth resulting in premature suture closure in a rodent model. Nell-1, therefore, has a novel role in CS development, perhaps as part of a complex chain of events resulting in premature suture closure. On a cellular level, Nell-1 expression may modulate and be both sufficient and required for osteoblast differentiation.

Willingness of Rhode Island Dentists to Provide Limited Preventive Primary Care.

In response to the shortage of primary care physicians and the need for greater intercollaboration among health professionals, dentists with sufficient medical and surgical training are an untapped resource to provide limited preventive primary care (LPPC), such as chairside screening for chronic diseases. The objective of this study was to determine attitudes of Rhode Island dentists toward becoming more involved in the overall health of their patients. Using a 5-point scale (1 being highest), a pretested survey was administered to 92 respondent RI dentists who were asked to indicate their willingness to become more involved in patients' overall health, and undergo additional training to provide LPPC. Their moderate level of willingness was offset by great concern for liability, with older dentists being significantly more willing to assume these additional responsibilities than younger dentists (p< .05). Rank order of designation of oral health providers among dentist, dental physician, oral physician, odontologist, stomatologist, and stomiatrist was still dentist first, but with no significant difference between the mean ranks of dentist and oral physician.[Full article available at http://rimed.org/rimedicaljournal-2016-07.asp, free with no login].

Intimate Partner Sexual Assault: Traumatic Injuries, Psychological Symptoms, and Perceived Social Reactions.

OBJECTIVE: To compare the consequences of sexual assault based on the relationship of the woman to her named assailant. METHODS: From January 2008 to March 2011, we conducted an observational and prospective study of females older than age 15 years who were examined at a sexual assault referral center. Data were collected and comparisons made between groups based on the victim's relationship to her named assailant: a current or former intimate partner (grouped as intimate partner), stranger, or acquaintance. Data were collected regarding the patients, assailants, and type of assault. At a 1-month follow-up examination, we evaluated clinical findings and reported reactions by the victim's friends, family, and acquaintances. We conducted descriptive analyses and searched for overall and pairwise differences among groups. RESULTS: There were 797 individuals seen during this time period. Thirty of the victims were male and were excluded from the study, leaving 767 females older than 15 years of age, 294 (38%) of whom attended the follow-up consultation. Simultaneous physical and sexual assaults were more frequent in intimate partner assaults than in assaults by unknown individuals or acquaintances: 55% (95% confidence interval [CI] 49-61) compared with 31% (95% CI 26-36) and 32% (95% CI 26-38; P<.001). One month after the initial examination, psychological trauma was noted in 92% of the patients and was evenly distributed among the three groups. Reactions from family members were similar for victims assaulted by intimate partners and other victims. CONCLUSION: Sexual assault by an intimate partner is associated with higher rates of extragenital trauma and similar rates of psychologic trauma and disrupted other relationships as that associated with assaults by strangers or acquaintances. Sexual assaults by intimate partners should be viewed as serious as assault by other assailants by law enforcement, the judiciary, and the public.

Skin repair and scar formation: the central role of TGF-beta.

Wound healing is a complex process that we have only recently begun to understand. Central to wound repair is transforming growth factor beta (TGF-beta), a cytokine secreted by several different cell types involved in healing. TGF-beta has diverse effects, depending upon the tissue studied. This review focuses on healing in skin, particularly the phases of cutaneous wound repair and the role of TGF-beta in normal and impaired wound-healing models. It also explores TGF-beta activity in scarless foetal wound healing. Knowledge of TGF-beta function in scarless repair is critical to improving healing in clinical scenarios, such as diabetic wounds and hypertrophic scars.

Fetal wound healing current perspectives.

Early in gestation, fetal wounds are capable of healing scarlessly. Scarless healing in the fetus is characterized by regeneration of an organized dermis with normal appendages and by a relative lack of inflammation. Although there is a transition period between scarless and scar-forming repair, scarless healing also depends on wound size and the organ involved. The ability to heal scarlessly, furthermore, appears to be intrinsic to fetal skin. Unique characteristics of fetal fibroblasts, inflammatory cells, extra-cellular matrix, cytokine profile, and developmental gene regulation may be responsible for the scarless phenotype of early gestation fetal wounds. With the current knowledge, only minimal success has been achieved with the topical application of neutralizing antibodies, antisense oligonucleotides, and growth factors to improve wound-healing outcomes. Thus, further investigation into the mechanisms underlying scarless repair is crucial in order to devise more effective therapies for scar reduction and the treatment of cirrhosis, scleroderma, and other diseases of excessive fibrosis.

Scarless fetal wounds are associated with an increased matrix metalloproteinase-to-tissue-derived inhibitor of metalloproteinase ratio.

In contrast to adult cutaneous wounds, early fetal wounds heal scarlessly. Fetal rat skin transitions from scarless repair to healing, with scar formation between days 16.5 (E16) and 18.5 (E18) of gestation. Term gestation is 21.5 days. The composition of the extracellular matrix in fetal skin and wounds differs from that of the adult. Matrix metalloproteinases (MMPs) and their tissue-derived inhibitors (TIMPs) determine the architecture of the extracellular matrix. The authors hypothesized that differential expression of MMPs and TIMPs occurs during the ontogenetic transition to scar-forming repair in fetal skin and wounds. Full-thickness, excisional wounds (2 mm) were created on the dorsum of E16 (n = 42 fetuses) and E19 fetal rats (n = 42 fetuses). Wounds were harvested at 24, 48, and 72 hours. Nonwounded skin from littermates was also harvested as controls. Six E16 and E19 wounds were fixed 72 hours after injury, stained with hematoxylin and eosin, and examined by light microscopy. RNA was isolated from the remaining wounds and skin, and a reduced-cycle, primer-specific, reverse-transcriptase polymerase chain reaction was performed to semiquantitatively determine relative gene expression of MMP-1, MMP-2, MMP-7, MMP-9, and MMP-14 and of TIMP-1, TIMP-2, and TIMP-3. Significance was determined by unpaired two-tailed t test (p < 0.05) and analysis of variance. In both E16 and E19 wounds, reepithelialization was complete by 72 hours. E16 wounds healed scarlessly, whereas E19 wounds healed with scar. During late gestation, skin expression of MMP-1 and MMP-14 (membrane type-1 MMP) doubled, whereas MMP-2 expression increased nearly 50-fold. Levels of MMP-7 and MMP-9 were unchanged in developing skin. As for the TIMPs, skin expression of TIMP-2 increased more than four-fold, whereas TIMP-1 and TIMP-3 expression was unchanged. In both scarless and scarring wounds, up-regulation of MMP-1 and MMP-9 occurred. However, the maximal increase in MMP-1 and MMP-9 expression occurred much more rapidly and was much greater in the scarless E16 wounds (28-fold versus 23-fold for MMP-1 and 18-fold versus nine-fold for MMP-9). Unchanged in scarless wounds, MMP-2 levels decreased more than three-fold in scarring wounds. MMP-14 (membrane type-1 MMP) expression increased three-fold in scarless wounds but was unchanged in scarring wounds. In contrast, TIMP-1 and TIMP-3 expression in E19 scarring wounds increased six-fold and four-fold, respectively. MMP-7 and TIMP-2 expression did not change in response to injury. E16 scarless wounds have greater MMP relative to TIMP expression than E19 scarring wounds. This favors extracellular matrix turnover, facilitates migration of fetal cells, and promotes scarless repair.