A Phenomenological Exploration of Experiences Related to Learning Styles Among Undergraduate Medical Students in a Barbadian Medical School.

Introduction: Learning style (LS) frameworks have been implemented by educators to promote participatory learning in order to strengthen learner engagement and to enhance learning outcomes. Self-efficacy has been shown to have an association with learning style and is a predictor of clinical performance and other qualities in medical students. This study examined the perspectives of second and final year medical students in a Caribbean-based medical school, relative to their learning approaches, teaching exposures and preparation for assessments. Methods: An interpretivist qualitative approach was used to analyze data from two focus groups, conducted as part of a sequential mixed-methods study (November 2018-February 2019) with medical students in the second and final year of study. Discussions were audio-recorded, transcribed verbatim, and inductively coded with in-depth thematic analysis assisted by NVivo software. Results: Six Year 2 (Female: Male = 5:1) and seven Year 5 (Female: Male = 5:2) participants, ranging between 18 and 34 years and with a range of LS were recruited into the study. Analysis and data reduction produced three organizing themes: "Dynamics of information delivery and acquisition", "Pivoting", and "LS identification, awareness and mutability", and the global construct "Individual and environmental factors modulate the influence of LS preference in triggering self-efficacy". In managing information received in class, students used textbooks, YouTube videos, and collaborative learning to augment perceived gaps in lectures and their personal notes. Learning style self-awareness is useful for facilitating self-efficacy throughout medical school, especially at points of transition within the programme of study. Conclusion: LS theory and testing appear to be useful for student and teacher awareness. In practice, honing students' adaptability to varying learning settings may be more relevant in helping students achieve self-efficacy.

Calreticulin: a multifunctional protein with potential therapeutic applications for chronic wounds.

Calreticulin is recognized as a multifunctional protein that serves an essential role in diverse biological processes that include wound healing, modification and folding of proteins, regulation of the secretory pathway, cell motility, cellular metabolism, protein synthesis, regulation of gene expression, cell cycle regulation and apoptosis. Although the role of calreticulin as an endoplasmic reticulum-chaperone protein has been well described, several studies have demonstrated calreticulin to be a highly versatile protein with an essential role during wound healing. These features make it an ideal molecule for treating a complex, multifactorial diseases that require fine tuning, such as chronic wounds. Indeed, topical application of recombinant calreticulin to wounds in multiple models of wound healing has demonstrated remarkable pro-healing effects. Among them include enhanced keratinocyte and fibroblast migration and proliferation, induction of extracellular matrix proteins, recruitment of macrophages along with increased granulation tissue formation, all of which are important functions in promoting wound healing that are deregulated in chronic wounds. Given the high degree of diverse functions and pro-healing effects, application of exogenous calreticulin warrants further investigation as a potential novel therapeutic option for chronic wound patients. Here, we review and highlight the significant effects of topical application of calreticulin on enhancing wound healing and its potential as a novel therapeutic option to shift chronic wounds into healing, acute-like wounds.

The Protective Effect of Oxitard on Sperm Function and Antioxidant Status in Rats Exposed to Swimming Stress.

BACKGROUND: Infertility is a significant public health issue, but its impact on quality of life and treatment efficacy is limited. Modern medicine lacks safe and effective drugs for male infertility, while traditional medicine has explored herbal extracts like Oxitard, which contains multiple extracts and oils. This study aimed to investigate the effects of Oxitard on male rats exposed to swimming (SW) stress. METHODS: Albino rats weighing 220-250 g were divided into five groups: control, SW stress, and SW treated with Oxitard at low, medium, and high doses of 250, 500, and 750 mg/kg/day, respectively. The rats were subjected to SW stress for 15 days and then assessed for body weight, reproductive organ weight, testosterone, antioxidant status, sperm function, and histological changes in the testes, seminal vesicles, and vas deferens. RESULTS: The results showed that SW stress significantly reduced body weight, seminal vesicle weight, testosterone levels, superoxide dismutase (SOD), catalase (CAT), sperm count, sperm motility, sperm viability, and significantly increased malondialdehyde (MDA) levels. The testes of the SW-stress group rats also showed a significant decrease in spermatogenesis and the number of seminiferous tubules containing sperm. In contrast, treatment with Oxitard, especially at the highest dose, demonstrated potent free radical scavenging activity, recovering antioxidant status, and sperm function. CONCLUSION: SW stress led to decreased sperm function, antioxidant status, and increased lipid peroxidation (LPO) in male rats. Oxitard treatment, particularly in high doses, showed a potential role as a free radical scavenger in treating oxidative stress (OS)-associated male infertility. Further studies are needed to investigate the individual components of Oxitard and conduct clinical trials in human subjects.

Personal protective equipment (PPE) related adverse skin reactions among healthcare workers at the main COVID-19 isolation center in Barbados.

Background: The use of personal protective equipment (PPE) reduces the risk of transmission of infectious agents significantly among healthcare workers (HCWs). The study aimed to investigate the prevalence and characteristics of PPE-related adverse skin reactions among HCWs working at the main COVID-19 isolation center in Barbados. Methods: A cross-sectional web-based online survey was conducted during April to June 2021 which recorded demographic information, details of PPE use and adverse skin reactions including severity and duration of onset of symptoms. Results: Most of the respondents used PPE for consecutive days (77.9%), 1-6 h/day (59.2%), and more than a year (62.5%). Fewer than half of the participants (45.6%) experienced adverse skin reactions from the use of PPE. The reactions were mostly observed in the cheeks (40.4%) and nose bridges (35.6%). Females had more reactions than their male counterparts (p = 0.003). The use of N95 masks and a combination of surgical and N95 masks produced adverse effects predominantly in the ears (60%) and cheeks (56.4%). Binary logistic regression showed that female HCWs (OR = 5.720 95% CI: 1.631, 20.063), doctors (OR = 5.215 95% CI: 0.877, 31.002), and longer duration of PPE use (>1 year) (OR = 2.902 95% CI: 0.958, 8.787) caused a significantly higher prevalence of adverse skin reactions. Conclusion: The PPE-related skin reactions were common among HCWs which mainly occurred due to prolonged use. Preventive measures inclusive of appropriate training of HCWs on the use of PPE are recommended to minimize these adverse events.

Dichotomous role of miR193b-3p in diabetic foot ulcers maintains inhibition of healing and suppression of tumor formation.

Despite the hyperproliferative environment marked by activation of ß-catenin and overexpression of c-myc, the epidermis surrounding chronic diabetic foot ulcers (DFUs) is clinically hypertrophic and nonmigratory yet does not undergo malignant transformation. We identified miR193b-3p as a master regulator that contributes to this unique cellular phenotype. We determined that induction of tumor suppressor miR193b-3p is a unique feature of DFUs that is not found in venous leg ulcers, acute wounds, or cutaneous squamous cell carcinoma (SCC). Genomic analyses of DFUs identified suppression of the miR193b-3p target gene network that orchestrates cell motility. Inhibition of migration and wound closure was further confirmed by overexpression of miR193b-3p in human organotypic and murine in vivo wound models, whereas miR193b-3p knockdown accelerated wound reepithelialization in human ex vivo and diabetic murine wounds in vivo. The dominant negative effect of miR193b-3p on keratinocyte migration was maintained in the presence of promigratory miR31-5p and miR15b-5p, which were also overexpressed in DFUs. miR193b-3p mediated antimigratory activity by disrupting stress fiber formation and by decreasing activity of GTPase RhoA. Conversely, miR193b-3p targets that typically participate in malignant transformation were found to be differentially regulated between DFUs and SCC, including the proto-oncogenes KRAS (Kirsten rat sarcoma viral proto-oncogene) and KIT (KIT proto-oncogene). Although miR193b-3p acts as a tumor suppressor contributing to low tumor incidence in DFUs, it also acts as a master inhibitor of cellular migration and epithelialization in DFUs. Thus, miR193b-3p may represent a target for wound healing induction, cancer therapeutics, and diagnostics.

COVID-19 Vaccine Intent Among Health Care Professionals of Queen Elizabeth Hospital, Barbados.

INTRODUCTION: Due to increased exposure risk and the potential impact of COVID-19 infection, health care professionals (HCP) are a target group for COVID-19 vaccination. This study aimed to examine the acceptability of COVID-19 vaccines among HCP at the Queen Elizabeth Hospital, Barbados. DESIGN AND METHODS: A cross-sectional survey of HCP was conducted between February 14 and 27, 2021 using an online questionnaire. The questionnaire included demographic information, knowledge of novel coronavirus, intention to accept the COVID-19 vaccination, vaccine literacy (VL), and perceptions and attitudes regarding COVID-19 vaccines. Mean VL scores were calculated. The relationship between socio-demographic variables and vaccine intent was assessed using a multivariable logistic regression model. RESULTS: Of 343 HCPs, 55.1% indicated they would accept the COVID-19 vaccine if it were available; 44.9% expressed hesitancy towards the COVID-19 vaccine. We assessed the impact of socio-demographic factors and previous vaccine behavior on vaccine intent; after adjustment of the multivariable logistic regression model, non-Barbadian nationality and previous flu vaccine uptake were statistically significant predictors of reported intent to take the COVID-19 vaccine. Persons who indicated that they would take the vaccine had a higher mean vaccine literacy score [3.46 95% CI (3.40, 3.52)] than those who were not ready to take the vaccine immediately [3.23 95% CI (3.15, 3.30)]. VL scores were higher among the 29.5% of HCPs who believed vaccines should be mandatory. CONCLUSION: This study highlighted vaccine hesitancy among HCPs in the sole public tertiary hospital of Barbados. As HCP perceptions may help or hinder the campaign to promote vaccine uptake in Barbados, vaccine promotion programs targeting HCPs are needed to ensure the success of the country's COVID-19 vaccination drive.

Anthropometric cut-offs to identify hyperglycemia in an Afro-Caribbean population: a cross-sectional population-based study from Barbados.

INTRODUCTION: Body mass index (BMI) and waist circumference (WC) cut-offs associated with hyperglycemia may differ by ethnicity. We investigated the optimal BMI and WC cut-offs for identifying hyperglycemia in the predominantly Afro-Caribbean population of Barbados. RESEARCH DESIGN AND METHODS: A cross-sectional study of 865 individuals aged ≥25 years without known diabetes or cardiovascular disease was conducted. Hyperglycemia was defined as fasting plasma glucose ≥5.6 mmol/L or hemoglobin A1c ≥5.7% (39 mmol/mol). The Youden index was used to identify the optimal cut-offs from the receiver operating characteristic (ROC) curves. Further ROC analysis and multivariable log binomial regression were used to compare standard and data-derived cut-offs. RESULTS: The prevalence of hyperglycemia was 58.9% (95% CI 54.7% to 63.0%). In women, optimal BMI and WC cut-offs (27 kg/m2 and 87 cm, respectively) performed similarly to standard cut-offs. In men, sensitivities of the optimal cut-offs of BMI ≥24 kg/m2 (72.0%) and WC ≥86 cm (74.0%) were higher than those for standard BMI and WC obesity cut-offs (30.0% and 25%-46%, respectively), although with lower specificity. Hyperglycemia was 70% higher in men above the data-derived WC cut-off (prevalence ratio 95% CI 1.2 to 2.3). CONCLUSIONS: While BMI and WC cut-offs in Afro-Caribbean women approximate international standards, our findings, consistent with other studies, suggest lowering cut-offs in men may be warranted to improve detection of hyperglycemia. Our findings do, however, require replication in a new data set.

Use of an Adaptive e-Learning Platform as a Formative Assessment Tool in the Cardiovascular System Course Component of an MBBS Programme.

BACKGROUND: Technology-enhanced learning includes the adaptive e-learning platform, a data-driven method with computer algorithms, providing customised learning enhancing critical thinking of individual learners. "Firecracker" - an online adaptive e-learning platform, and assessment software, promotes critical thinking, helps prepare students for courses and high-stakes examinations, and evaluates progress relative to co-learners. The objectives of this study were to determine the usage rates of Firecracker, examine the performance of Firecracker formative quizzes, identify the correlation between Firecracker use and performance with that of performance at summative course assessments, and assess students' satisfaction with Firecracker usage. METHODS: Study participants were Year-2 MBBS (Bachelor of Medicine, Bachelor of Surgery) students (n=91) of the Faculty of Medical Sciences, The University of the West Indies, Cave Hill Campus, Barbados. The Firecracker Administrator uploaded quizzes covering basic science content in the Cardiovascular System course. Access, usage, and performance on Firecracker formative quizzes were retrieved from the Firecracker dashboard. A questionnaire sought the views of study participants. RESULTS: Seven sets of quizzes were administered over nine weeks, with weekly student completion rates ranging from 53% to 73%. Mean quiz scores ranged from 52% to 72%. Students completing >4 quiz sessions compared to those completing ≤4 demonstrated significantly better performance in Firecracker quizzes (P<0.01), final examinations (P<0.01) and in-course assessment plus final examination (P<0.05) scores. Correlations between overall Firecracker performance and in-course assessment marks (P<0.05); between total overall Firecracker performance and final examination (P<0.01); and overall Firecracker performance and total course marks (P<0.01) were all significant. Most students (70%) were happy using Firecracker and felt it complemented coursework (78%) and prepared them for course exams (58%) (P<0.01). CONCLUSION: Overall, Firecracker was perceived very positively and welcomed by the students. Students were satisfied with the Firecracker as a formative assessment tool, and its use correlated with improved performance in the course examinations.

Keloids: Current and emerging therapies.

Keloids are pathological scars that grow over time and extend beyond the initial site of injury after impaired wound healing. These scars frequently recur and rarely regress. They are aesthetically disfiguring, can cause pain, itching, discomfort as well as psychological stress, often affecting quality of life. Many treatment modalities, including surgical and non-surgical, have been explored and have been reported to be beneficial; however, none have been absolutely satisfactory or optimal for the treatment of all keloid subtypes to date. This poses a major challenge to clinicians. Often, a combinational therapeutic approach appears to offer the best results with higher patient satisfaction compared to monotherapy. The aetiopathogenesis of keloids is not fully elucidated; however, with recent advances in molecular biology and genetics, insight is being gained on the complex process of scar formation and hence new therapeutic and management options for keloids. In this paper, we explore the literature and summarise the general concepts surrounding keloid development and review both current (corticosteroids, surgical excision, silicone-based products, pressure therapy, radiotherapy, cryotherapy, laser therapy, imiquimod and 5-fluorouracil) and emerging (stem cell therapy, mitomycin C, verapamil, interferons, bleomycin, botulinum toxin type A and angiotensin-converting enzyme inhibitors) treatments. Increased knowledge and understanding in this area may potentially lead to the discovery and development of novel therapeutic options that are more efficacious for all keloid types. LAY SUMMARY: Keloids are problematic scars that are difficult to treat and manage. The aetiopathogenesis of keloids is not clear; however, recent advances in molecular biology and genetics are beginning to shed light on the underlying mechanisms implicated in keloid scar formation which will hopefully lead to the development of treatment options for all keloid types. This review summarises current and emerging therapies.

Zinc Adequacy Is Essential for the Maintenance of Optimal Oral Health.

Zinc, a metal found in the Earth's crust, is indispensable for human health. In the human body, around 60% of zinc is present in muscles, 30% in bones, and the remaining 10% in skin, hair, pancreas, kidneys and plasma. An adequate zinc balance is essential for the maintenance of skeletal growth, development and function. It is also necessary for basic cellular functions including enzyme activation, cell signaling and energy metabolism. Inadequate zinc status is associated with a wide variety of systemic disorders including cardiovascular impairment, musculoskeletal dysfunctions and oromaxillary diseases. In this article, we briefly discuss the role of zinc deficiency in the genesis of various oromaxillary diseases, and explain why adequate zinc homeostasis is vital for the maintenance of oral and general health.

Is hypertension in African-descent populations contributed to by an imbalance in the activities of the ACE2/Ang-(1-7)/Mas and the ACE/Ang II/AT1 axes?

INTRODUCTION: Low plasma renin activity hypertension is prevalent in Afro-Caribbean persons. Reduced angiotensin converting enzyme 2 activity from the counter angiotensin converting enzyme 2 /angiotensin-(1-7)/Mas receptor axis of the renin angiotensin aldosterone system has been reported in people with pre-hypertension, type 2 diabetes mellitus and chronic renal disease. This study investigates whether an imbalance in the regulatory mechanisms between the pressor arm of the renin angiotensin aldosterone system (angiotensin converting enzyme/angiotensin II/AT1 receptor) and the depressor axis (angiotensin converting enzyme 2/angiotensin-(1-7)/Mas receptor) predisposes persons of African descent to hypertension. METHODS: In total, 30 normotensives and 30 recently diagnosed hypertensives aged 18-55 of Afro-Caribbean origin who are naïve to antihypertensive treatment will be recruited from public sector polyclinics in Barbados. Demographic and anthropometric data, clinical blood pressure readings, 24-hour urine collections and venous blood samples will be collected. Biological samples will be analysed for renin angiotensin aldosterone system peptide markers using radioimmunoassay. CONCLUSION: We describe the design, methods and rationale for the characterization of renin angiotensin aldosterone system mechanisms that may contribute to hypertension predisposition in persons of African descent. Our findings will characterize any imbalance in the counter axes of the renin angiotensin aldosterone system in hypertensive Afro-Caribbeans with a potential view of identifying novel approaches with the use of renin angiotensin aldosterone system and mineralocorticoid blockers to manage the condition.

Oral manifestations of magnesium and vitamin D inadequacy.

Adequate nutrition is essential for maintaining good oral health. Minerals such as magnesium, calcium, and phosphorus found in the diet constitute the main structural components of the tooth. Their inadequacy leads to absorption impairment, increased bleeding tendency, bone resorption, looseness, and premature tooth loss. Inadequacy of those essential minerals is associated with delayed tooth eruption and with enamel or dentin hypoplasia. Taking calcium without magnesium results in soft dental enamel, which cannot resist the acids causing tooth decay. In addition to magnesium, calcium, and phosphorus, adequate vitamin D is needed to maintain optimal oral health. Vitamin D exerts anti-inflammatory effects and helps in calcium absorption and bone remodeling. Moreover, adequate vitamin D status could reduce formation of dental caries by delaying its onset and progression. Here we summarize the oral manifestations of vitamin D and magnesium inadequacy.

An evaluative study of objective structured clinical examination (OSCE): students and examiners perspectives.

Background: The objective structured clinical examination (OSCE) is the gold standard and universal format to assess the clinical competence of medical students in a comprehensive, reliable and valid manner. The clinical competence is assessed by a team of many examiners on various stations of the examination. Therefore, it is found to be a more complex, resource- and time-intensive assessment exercise compared to the traditional examinations. Purpose: The objective of this study was to determine the final year MBBS students' and OSCE examiners' perception on the attributes, quality, validity, reliability and organization of the Medicine and Therapeutics exit OSCE held at the University of the West Indies (Cave Hill) in June 2017. Methods: At the end of the OSCE, students and examiners were provided with a questionnaire to obtain their views and comments about the OSCE. Due to the ordinal level of data produced by the Likert scale survey, statistical analysis was performed using the median, IQR and chi-square. Results: A total of 52 students and 22 examiners completed the questionnaire. The majority of the students provided positive views regarding the attributes (eg, fairness, administration, structure, sequence, and coverage of knowledge/clinical skills), quality (eg, awareness, instructions, tasks, and sequence of stations), validity and reliability (eg, true measure of essential clinical skills, standardized, practical and useful experiences), and organization (eg, orientation, timetable, announcements and quality of examination rooms) of the OSCE. Similarly, majority of the examiners expressed their satisfaction with organization, administration and process of OSCE. However, students expressed certain concerns such as stressful environment and difficulty level of OSCE. Conclusion: Overall, the OSCE was perceived very positively and welcomed by both the students and examiners. The concerns and challenges regarding OSCE can be overcome through better orientation of the faculty and preparation of the students for the OSCE.

The Relationship Between Self-Esteem, Emotional Intelligence, and Empathy Among Students From Six Health Professional Programs.

Theory: Psychosocial skills such as communication, empathy, and emotional intelligence are now considered key attributes of health professionals. Self-esteem is another important construct that is less well studied. Self-esteem is important because low levels have been linked to depression, suicide, and eating disorders. Given that health professional students experience high levels of stress and are at increased risk for similar psychopathology, self-esteem may be an important variable in student well-being and performance after graduation. Hypotheses: This study sought to explore self-esteem during students' 1st year of training hypothesizing that several would demonstrate low self-esteem. It is also hypothesized that emotional intelligence and empathy would be associated with self-esteem. Method: A cross-sectional survey was conducted, and data were gathered from dental, medical, nursing, optometry, pharmacy and veterinary students. Self-report questionnaires assessing self-esteem, emotional intelligence, and empathy were completed and demographic information was collected. Scores were calculated and differences between groups analyzed with analysis of variance and chi-square testing. Pearson's correlation was used to assess associations between the constructs. Results: The mean self-esteem score was 26.2 ± 2.3 but 21% of the sample evidenced low self-esteem. There was no difference in the proportion of students demonstrating low self-esteem among programs. Gender did not have a significant effect on self-esteem scores, though ethnicity did. Emotional intelligence scores were higher among male individuals than among female. Emotional intelligence and empathy showed a small association with self-esteem. Conclusions: A significant proportion of health professional students suffer from low self-esteem during their 1st year of study. Such students may be more susceptible to the stresses associated with study and the development of psychopathology. More research needs to be conducted to explore the relationships between self-esteem, emotional intelligence, and empathy with a view to strengthening training in these areas and managing the challenges faced by health professional students.

Staphylococcus aureus Triggers Induction of miR-15B-5P to Diminish DNA Repair and Deregulate Inflammatory Response in Diabetic Foot Ulcers.

Diabetic foot ulcers (DFUs) are a debilitating complication of diabetes in which bacterial presence, including the frequent colonizer Staphylococcus aureus, contributes to inhibition of healing. MicroRNAs (miRs) play a role in healing and host response to bacterial pathogens. However, the mechanisms by which miR response to cutaneous S. aureus contributes to DFU pathophysiology are unknown. Here, we show that S. aureus inhibits wound closure and induces miR-15b-5p in acute human and porcine wound models and in chronic DFUs. Transcriptome analyses of DFU tissue showed induction of miR-15b-5p to be critical, regulating many cellular processes, including DNA repair and inflammatory response, by suppressing downstream targets IKBKB, WEE1, FGF2, RAD50, MSH2, and KIT. Using a human wound model, we confirmed that S. aureus-triggered miR-15b-5p induction results in suppression of the inflammatory- and DNA repair-related genes IKBKB and WEE1. Inhibition of DNA repair and accumulation of DNA breaks was functionally confirmed by the presence of the pH2AX within colonized DFUs. We conclude that S. aureus induces miR-15b-5p, subsequently repressing DNA repair and inflammatory response, showing a mechanism of inhibition of healing in DFUs previously unreported, to our knowledge. This underscores a previously unknown role of DNA damage repair in the pathophysiology of DFUs colonized with S. aureus.

Learning style preferences: A study of pre-clinical medical students in Barbados.

INTRODUCTION: Educators need to be aware of different learning styles to effectively tailor instructional strategies and methods to cater to the students' learning needs and support a conductive learning environment. The VARK [an acronym for visual (V), aural (A), read/write (R) and kinesthetic (K)] instrument is a useful model to assess learning styles. The aim of this study was to use the VARK questionnaire to determine the learning styles of pre-clinical medical students in order to compare the perceived and assessed learning style preferences, assess gender differences in learning style preferences, and determine whether any relationships exists between awareness of learning styles and academic grades, age, gender and learning modality. METHODS: The VARK questionnaire was administered to pre-clinical students taking a variety of courses in the first three years of the undergraduate MB BS degree programme at the Faculty of Medical Sciences, The University of the West Indies, Cave Hill Campus, Barbados in 2014. RESULTS: The majority of the students were multimodal learners with no differences observed between males (59.5%) and females (60.0%), with tetramodal being the most common. Read/write (33.8%) followed by kinesthetic (32.5%) were the most common learning style preferences. The sensory modality preference for females was read/write (34.2%) and for males it was kinesthetic (40.5%). Significant differences were observed between the perceived and assessed learning style preferences with a majority of visual and read/write learners correctly matching their perceived to their actual learning styles. Awareness of learning styles was associated with learning modality but not with academic performance, age or gender. Overall, 60.7% of high achievers used multimodal learning compared to 56.9% low achievers. CONCLUSION: The findings from this study indicated that the VARK tool was useful in gathering information about different learning styles, and might assist educators in designing blended teaching strategies to cater to the students' needs as well as help the students in becoming aware of their learning style preferences to enhance learning.

In vitro skin models to study epithelial regeneration from the hair follicle.

The development of dermal equivalents (DEs) for the treatment of burns has contributed toward efficient wound closure. A collagen-glycosaminoglycan DE (C-GAG) grafted with hair follicles converted a full-thickness wound to partial-thickness resulting in complete wound closure and restored hair. In this study we compared the ability of both intact pilosebaceous units (PSU) or truncated hair follicles (THF) to regenerate a multilayered epidermis in vitro when implanted into de-epidermalized dermis (DED) or C-GAG with the epidermis generated in vivo using C-CAG. Keratinocytes explanted from the outer root sheath of PSU and THF in both DED and C-GAG but only formed a multilayered epidermis with PSU in DED. PSU were more effective at forming multilayered epidermis in DED than THF. Both DED and C-GAG skin expressed proliferation (PCNA), differentiation (K1, K10), hyperproliferation (K6, K16), basal (K14), putative stem cell (p63), extracellular matrix protein (Collagen IV), mesenchymal (vimentin) and adherens junction (ß-catenin) markers. These data suggest DEs supported initial maintenance of the implanted hair follicles, in particular PSU, and provide an excellent model with which to investigate the regulation of hair follicle progenitor epithelial cells during epidermal regeneration. Although neither PSU nor THF formed multilayered epidermis in C-CAG in vitro, hair follicles implanted into engrafted C-GAG on a burns patient resulted in epithelial regeneration and expression of proliferation and differentiation markers in a similar manner to that seen in vitro. However, the failure of C-GAG to support epidermal regeneration in vitro suggests in vivo factors are essential for full epidermal regeneration using C-GAG.

Epithelial-mesenchymal transition in tissue repair and fibrosis.

The epithelial-mesenchymal transition (EMT) describes the global process by which stationary epithelial cells undergo phenotypic changes, including the loss of cell-cell adhesion and apical-basal polarity, and acquire mesenchymal characteristics that confer migratory capacity. EMT and its converse, MET (mesenchymal-epithelial transition), are integral stages of many physiologic processes and, as such, are tightly coordinated by a host of molecular regulators. Converging lines of evidence have identified EMT as a component of cutaneous wound healing, during which otherwise stationary keratinocytes (the resident skin epithelial cells) migrate across the wound bed to restore the epidermal barrier. Moreover, EMT plays a role in the development of scarring and fibrosis, as the matrix-producing myofibroblasts arise from cells of the epithelial lineage in response to injury but are pathologically sustained instead of undergoing MET or apoptosis. In this review, we summarize the role of EMT in physiologic repair and pathologic fibrosis of tissues and organs. We conclude that further investigation into the contribution of EMT to the faulty repair of fibrotic wounds might identify components of EMT signaling as common therapeutic targets for impaired healing in many tissues. Graphical Abstract Model for injury-triggered EMT activation in physiologic wound repair (left) and fibrotic wound healing (right).

Skin Metabolite, Farnesyl Pyrophosphate, Regulates Epidermal Response to Inflammation, Oxidative Stress, and Migration.

Skin produces cholesterol and a wide array of sterols and non-sterol mevalonate metabolites, including isoprenoid derivative farnesyl pyrophosphate (FPP). To characterize FPP action in epidermis, we generated transcriptional profiles of primary human keratinocytes treated with zaragozic acid (ZGA), a squalene synthase inhibitor that blocks conversion of FPP to squalene resulting in endogenous accumulation of FPP. The elevated levels of intracellular FPP resulted in regulation of epidermal differentiation and adherens junction signaling, insulin growth factor (IGF) signaling, oxidative stress response and interferon (IFN) signaling. Immunosuppressive properties of FPP were evidenced by STAT-1 downregulation and prominent suppression of its nuclear translocation by IFNγ. Furthermore, FPP profoundly downregulated genes involved in epidermal differentiation of keratinocytes in vitro and in human skin ex vivo. Elevated levels of FPP resulted in induction of cytoprotective transcriptional factor Nrf2 and its target genes. We have previously shown that FPP functions as ligand for the glucocorticoid receptor (GR), one of the major regulator of epidermal homeostasis. Comparative microarray analyses show significant but not complete overlap between FPP and glucocorticoid regulated genes, suggesting that FPP may have wider transcriptional impact. This was further supported by co-transfection and chromatin immunoprecipitation experiments where we show that upon binding to GR, FPP recruits ß-catenin and, unlike glucocorticoids, recruits co-repressor GRIP1 to suppress keratin 6 gene. These findings have many clinical implications related to epidermal lipid metabolism, response to glucocorticoid therapy as well as pleiotropic effects of cholesterol lowering therapeutics, statins. J. Cell. Physiol. 231: 2452-2463, 2016. © 2016 Wiley Periodicals, Inc.