Primary Skin Research Articles

Epidemiology and clinical features ofStreptococcus pyogenesbloodstream infectionsin childrenin Madrid, Spain.

Studies have shown increased invasive Group A Streptococcus (GAS) disease, including bloodstream infections (GAS-BSI). However, the epidemiological data of GAS-BSI are limited in children. We aimed to describe GAS-BSI in children in Madrid, over 13years (2005-2017). Multicenter retrospective cohort study from 16 hospitals from Madrid, Spain. Epidemiology, symptomatology, laboratory, treatment, and outcome of GAS-BSI in children ≤ 16years were analyzed. 109 cases of GAS-BSI were included, with incidence rate of 4.3 episodes/100,000 children attended at the emergency department/year. We compared incidence between two periods (P1:2005-June 2011 vs P2:July 2011-2017) and observed a non-significant increase along the study period (annual percentage change: + 6.0% [95%CI:-2.7, + 15.4]; p = 0.163).Median age was 24.1months (IQR:14.0-53.7), peaking during the first four years of life (89/109 cases;81.6%). Primary BSI (46.8%), skin and soft tissue (21.1%), and osteoarticular infections (18.3%) were the most common syndromes. We compared children with primary BSI with those with a known source and observed that the former had shorter hospital stay (7vs.13days; p = 0.003) and received intravenous antibiotics less frequently (72.5%vs.94.8%; p = 0.001) and for shorter duration of total antibiotic therapy (10vs.21days; p = 0.001). 22% of cases required PICU admission. Factors associated with severity were respiratory distress, pneumonia, thrombocytopenia, and surgery, but in multivariate analysis, only respiratory distress remained significant (adjusted OR:9.23 [95%CI:2.16-29.41]). Two children (1.8%) died. Conclusion: We observed an increasing, although non-significant, trend of GAS-BSI incidence within the study. Younger children were more frequently involved, and primary BSI was the most common and less severe syndrome. PICU admission was frequent, being respiratory distress the main risk factor. What is known: • In recent decades, several reports have shown a worldwide increase in the incidence of invasive Group A streptococcal disease (GAS), including bloodstream infection (BSI). Recently, there have been a few reports showing an increase in severity as well. • There needs to be more information on the epidemiology in children since most studies predominantly include adults. What is new: • This study, carried out in children with GAS-BSI in Madrid, shows that GAS-BSI affects mostly younger children, with a broad spectrum of manifestations, needing PICU admission frequently. Respiratory distress was the leading risk factor for severity, whereas primary BSI seemed to be less severe. • We observed an increasing, although non-significant, trend of GAS-BSI incidence in recent years (2005-2017).

Impact of Canine Amniotic Mesenchymal Stem Cell Conditioned Media on the Wound Healing Process: In Vitro and In Vivo Study.

The aim of this study was to provide a beneficial treatment effect of mesenchymal stem cell products derived from the canine amniotic membrane (AM-MSC) on the complicated wound healing process in dogs. AM-MSCs were characterized in terms of morphology, phenotypic profile, and multilineage differentiation potential. The in vitro study of the effect of canine amniotic mesenchymal stem cell conditioned media (AMMSC-CM) on a primary skin fibroblast cell culture scratch assay showed a decrease in the measured scratch area of about 66.39% against the negative control (Dulbecco's Modified Eagle's Medium-32.55%) and the positive control (Dulbecco's Modified Eagle's Medium supplemented with FGF2, N2, B27, and EGF-82.077%) after 72 h treatment. In the experimental study, seven dogs with complicated nonhealing wounds were treated with a combination of antibiotics, NSAIDs, and local AMMSC-CM application. After 15 days of therapy, we observed a 98.47% reduction in the wound surface area as opposed to 57.135% in the control group treated by conventional therapy based on debridement of necrotic tissue, antibiotic therapy, pain management, and change of wound dressing.

Development of Low-Contact-Impedance Dry Electrodes for Electroencephalogram Signal Acquisition.

Dry electroencephalogram (EEG) systems have a short set-up time and require limited skin preparation. However, they tend to require strong electrode-to-skin contact. In this study, dry EEG electrodes with low contact impedance (<150 kΩ) were fabricated by partially embedding a polyimide flexible printed circuit board (FPCB) in polydimethylsiloxane and then casting them in a sensor mold with six symmetrical legs or bumps. Silver-silver chloride paste was used at the exposed tip of each leg or bump that must touch the skin. The use of an FPCB enabled the fabricated electrodes to maintain steady impedance. Two types of dry electrodes were fabricated: flat-disk electrodes for skin with limited hair and multilegged electrodes for common use and for areas with thick hair. Impedance testing was conducted with and without a custom head cap according to the standard 10-20 electrode arrangement. The experimental results indicated that the fabricated electrodes exhibited impedance values between 65 and 120 kΩ. The brain wave patterns acquired with these electrodes were comparable to those acquired using conventional wet electrodes. The fabricated EEG electrodes passed the primary skin irritation tests based on the ISO 10993-10:2010 protocol and the cytotoxicity tests based on the ISO 10993-5:2009 protocol.

Identification of lncRNAs involved in response to ionizing radiation in fibroblasts of long-term survivors of childhood cancer and cancer-free controls.

Long non-coding ribonucleic acids (lncRNAs) are involved in the cellular damage response following exposure to ionizing radiation as applied in radiotherapy. However, the role of lncRNAs in radiation response concerning intrinsic susceptibility to late effects of radiation exposure has not been examined in general or in long-term survivors of childhood cancer with and without potentially radiotherapy-related second primary cancers, in particular. Primary skin fibroblasts (n=52 each) of long-term childhood cancer survivors with a first primary cancer only (N1), at least one second primary neoplasm (N2+), as well as tumor-free controls (N0) from the KiKme case-control study were matched by sex, age, and additionally by year of diagnosis and entity of the first primary cancer. Fibroblasts were exposed to 0.05 and 2 Gray (Gy) X-rays. Differentially expressed lncRNAs were identified with and without interaction terms for donor group and dose. Weighted co-expression networks of lncRNA and mRNA were constructed using WGCNA. Resulting gene sets (modules) were correlated to the radiation doses and analyzed for biological function. After irradiation with 0.05Gy, few lncRNAs were differentially expressed (N0: AC004801.4; N1: PCCA-DT, AF129075.3, LINC00691, AL158206.1; N2+: LINC02315). In reaction to 2 Gy, the number of differentially expressed lncRNAs was higher (N0: 152, N1: 169, N2+: 146). After 2 Gy, AL109976.1 and AL158206.1 were prominently upregulated in all donor groups. The co-expression analysis identified two modules containing lncRNAs that were associated with 2 Gy (module1: 102 mRNAs and 4 lncRNAs: AL158206.1, AL109976.1, AC092171.5, TYMSOS, associated with p53-mediated reaction to DNA damage; module2: 390 mRNAs, 7 lncRNAs: AC004943.2, AC012073.1, AC026401.3, AC092718.4, MIR31HG, STXBP5-AS1, TMPO-AS1, associated with cell cycle regulation). For the first time, we identified the lncRNAs AL158206.1 and AL109976.1 as involved in the radiation response in primary fibroblasts by differential expression analysis. The co-expression analysis revealed a role of these lncRNAs in the DNA damage response and cell cycle regulation post-IR. These transcripts may be targets in cancer therapy against radiosensitivity, as well as provide grounds for the identification of at-risk patients for immediate adverse reactions in healthy tissues. With this work we deliver a broad basis and new leads for the examination of lncRNAs in the radiation response.

Gelatin–chitosan–cellulose nanocrystals as an acellular scaffold for wound healing application: fabrication, characterisation and cytocompatibility towards primary human skin cells

Biopolymers that mimic the extracellular matrix are favourable in tissue engineering. However, the rapid degradation and the lack of mechanical and enzymatic stabilities of these biopolymers prompt researchers to composite different biopolymers. In this study, we aim to develop an acellular gelatin-chitosan-cellulose nanocrystal (GCCNC) scaffold as a potential wound dressing. The GCCNC mixture was homogenised via ultrasonication and the genipin crosslinking was performed by magnetic stirring. The mixture was then frozen at − 80 °C for 6 h and freeze-dried. The effects of different ratios of gelatin and chitosan with cellulose nanocrystals on the physiochemical properties, mechanical properties, and cellular biocompatibility were studied. Our results herein showed that G3C7CNC demonstrated a homogenous interconnected porous structure with a good porosity (67.37 ± 9.09%) and pore size (148.46 ± 48.68 µm), acceptable swelling ratio (1071.11 ± 140.26%), adequate water vapour transmission rate (315.59 ± 25.27 g/m2/day), low contact angle (70.21 ± 6.79°), and sufficient mechanical strength (modulus of 64.67 ± 12.42 MPa). The lower biodegradation rate in the G3C7CNC (0.06 ± 0.01 mg/hr) compared to G10CNC (0.48 ± 0.07 mg/hr) together with the absence of glass transition phenomenon indicated an increase in both enzymatic and thermal stabilities. Furthermore, G3C7CNC was non-cytotoxic and biocompatible with human epidermal keratinocytes (HEKs) and human dermal fibroblasts (HDFs). The presence of collagen type I and α-smooth muscle actin expression in HDFs, together with the expression of cytokeratin-14 in HEKs, demonstrated our scaffold’s ability to maintain normal skin physiological functions. Therefore, this study proposes that the fabricated GCCNC scaffold could serve as a potential acellular skin substitute in managing chronic wounds.

Dynamics of changes in tumor-associated macrophages in patients with primary skin melanoma depending on the method of surgical treatment

Summary: Skin melanoma is one of the deadliest among human skin tumors, and surgery remains the first and main method in its combined treatment. Despite the seemingly radical nature of surgical interventions in patients with primary skin melanoma, the frequency of locoregional recurrence and metastasis remains high. The question of the impact of surgical treatment on the evolution of the melanoma microenvironment remains unclear.Aim: to investigate the dynamics of polarization in tumor-associated macrophages in patients with primary skin melanoma of stage 0-IIa and in subsequent metastatic lesions to assess the impact of postoperative ischemia on survival of patients.Results: it was found that in patients with primary skin melanoma of stage 0-IIa plastic replacement of a tissue defect, compared with conventional suturing, can lead to a decrease in the density in the intrastromal distribution of pro-inflammatory CD68 + macrophages in the surgical focus, as well as less frequent polarization of TAM cells in the M2 direction and migration to the intrastromal component of the tumor, their more frequent mixed content, which, as a result, affects the survival of this category of patients for the better.Conclusions: plastic closing a surgical defect in patients with primary skin melanoma of stage 0-IIa may affect the duration of postoperative ischemia and the polarization of TAM cells. Plastic replacement of a tissue defect after tumor removal improves five-year survival rates (PFS by 22,6 % (p = 0.003) and OS by 13,1% (p = 0.029).

Acenocoumarol, an Anticoagulant Drug, Prevents Melanogenesis in B16F10 Melanoma Cells.

Hyperpigmentation can occur in abnormal skin conditions such as melanomas, as well as in conditions including melasma, freckles, age spots, seborrheic keratosis, and café-au-lait spots (flat brown spots). Thus, there is an increasing need for the development of depigmenting agents. We aimed to repurpose an anticoagulant drug as an effective ingredient against hyperpigmentation and apply cosmeceutical agents. In the present study, the anti-melanogenic effects of two anticoagulant drugs, acenocoumarol and warfarin, were investigated. The results showed that both acenocoumarol and warfarin did not cause any cytotoxicity and resulted in a significant reduction in intracellular tyrosinase activity and melanin content in B16F10 melanoma cells. Additionally, acenocoumarol inhibits the expression of melanogenic enzymes such as tyrosinase, tyrosinase-related protein (TRP)-1, and TRP-2, suppressing melanin synthesis through a cAMP-dependent, protein kinase (PKA)-dependent downregulation of microphthalmia-associated transcription factor (MITF), a master transcription factor in melanogenesis. Furthermore, anti-melanogenic effects were exerted by acenocoumarol through downregulation of the p38 and JNK signaling pathway and upregulation of extracellular signal-regulated kinase (ERK) and phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt)/glycogen synthesis kinase-3β (GSK-3β) cascades. In addition, the β-catenin content in the cell cytoplasm and nucleus was increased by acenocoumarol through a reduction in the phosphorylated β-catenin (p-β-catenin content). Finally, we tested the potential of acenocoumarol for topical applications by conducting primary human skin irritation tests. Acenocoumarol did not induce any adverse reactions during these tests. Based on the results, it can be concluded that acenocoumarol regulates melanogenesis through various signaling pathways such as PKA, MAPKs, PI3K/Akt/GSK-3β, and β-catenin. These findings suggest that acenocoumarol has the potential to be repurposed as a drug for treating hyperpigmentation symptoms and could provide new insights into the development of therapeutic approaches for hyperpigmentation disorders.

493 Triple negative status and progesterone receptor conversion between primary breast cancer and skin metastasis render worst survival among patients with stage 4 breast cancers

493 Triple negative status and progesterone receptor conversion between primary breast cancer and skin metastasis render worst survival among patients with stage 4 breast cancers

1016 Human leukocyte antigen class II alleles, levels of expression of ORAI1 and STIM1 genes in blood in HIV/TB patients with primary skin pathologies and in a control group in Latvia

1016 Human leukocyte antigen class II alleles, levels of expression of ORAI1 and STIM1 genes in blood in HIV/TB patients with primary skin pathologies and in a control group in Latvia

Optimization of Monobenzone-Induced Vitiligo Mouse Model by the Addition of Chronic Stress.

Vitiligo is a common primary, limited or generalized skin depigmentation disorder. Its pathogenesis is complex, multifactorial and unclear. For this reason, few animal models can simulate the onset of vitiligo, and studies of drug interventions are limited. Studies have found that there may be a pathophysiological connection between mental factors and the development of vitiligo. At present, the construction methods of the vitiligo model mainly include chemical induction and autoimmune induction against melanocytes. Mental factors are not taken into account in existing models. Therefore, in this study, mental inducement was added to the monobenzone (MBEH)-induced vitiligo model. We determined that chronic unpredictable mild stress (CUMS) inhibited the melanogenesis of skin. MBEH inhibited melanin production without affecting the behavioral state of mice, but mice in the MBEH combined with CUMS (MC) group were depressed and demonstrated increased depigmentation of the skin. Further analysis of metabolic differences showed that all three models altered the metabolic profile of the skin. In summary, we successfully constructed a vitiligo mouse model induced by MBEH combined with CUMS, which may be better used in the evaluation and study of vitiligo drugs.

PD12-08 A NOVEL THERAPEUTIC STRATEGY FOR THE MANAGEMENT OF PENOSCROTAL PAGET'S DISEASE

You have accessJournal of UrologyCME1 Apr 2023PD12-08 A NOVEL THERAPEUTIC STRATEGY FOR THE MANAGEMENT OF PENOSCROTAL PAGET'S DISEASE Xiang Wan, Zhong Wang, Bin Xu, and Haijun Yao Xiang WanXiang Wan More articles by this author , Zhong WangZhong Wang More articles by this author , Bin XuBin Xu More articles by this author , and Haijun YaoHaijun Yao More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003259.08AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Penoscrotal Paget’s disease is a rare type of intraepithelial adenocarcinoma. Postsurgical reconstruction is a major challenge for surgeons. In this study, we evaluated the surgical outcomes after reconstruction surgery in patients with penoscrotal Paget's disease and proposed a novel strategy. METHODS: In this study, patients with penoscrotal Paget's disease who were referred to Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine between May 2004 and February 2021, were included. We proposed a three-step Perineal Reconstruction (PR) strategy to describe the location and extent of the defect and provide a reconstructive surgical method. Accordingly, all the postsurgical defects were reconstructed based on our strategy. The clinical data and outcomes during the follow-up were recorded and analyzed. RESULTS: Patients were 42–91 years old with a diagnostic delay of 2–201 months. Further, most patients had large defects, thin tumors, and erythematous plaques. All patients underwent frozen biopsy-guided wide local excision and lymph node biopsy or dissection. Further, 16 patients underwent re-excision with positive margins. According to the PR strategy, 54, 41, 58, and 80 of the patients underwent primary closure, skin grafting, flap coverage, or skin grafting combined with flap coverage, respectively. Three patients underwent multimodal treatment. The results showed no obvious difference between preoperative and postoperative sexual satisfaction. The follow-up time ranged from 9 to 210 months. Further, 3 patients died from metastasis and 10 patients died from other cancers, natural death, or other reasons. CONCLUSIONS: Wide local excision achieves a relatively low recurrence rate and preserves sexual function in patients with penoscrotal Paget's disease. The PR strategy is a promising method to assess defects and guide reconstruction. Source of Funding: The manuscript was supported by the Project of Biobank of Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine (YBKB202119); Medical Research Foundation of Shanghai Science and Technology Commission (20Y11904300); Clinical Research Foundation of Shanghai Municipal Health Commission (202040437); Cross Research Fund of Medicine and Engineering of Shanghai 9th People's Hospital, Shanghai Jiao Tong University, School of Medicine (JYJC201912). © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e403 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Xiang Wan More articles by this author Zhong Wang More articles by this author Bin Xu More articles by this author Haijun Yao More articles by this author Expand All Advertisement PDF downloadLoading ...

A Disease, a Syndrome, or Both?

Journal of Gynecologic SurgeryVol. 39, No. 2 EditorialFree AccessA Disease, a Syndrome, or Both?Mitchel S. HoffmanMitchel S. Hoffman—Mitchel S. Hoffman, MD, Editor-in-Chief Department of Obstetrics and Gynecology, University of South Florida Morsani College of Medicine, Tampa, Florida, USA.MCC GYN Program, Moffitt Cancer Center, Tampa, Florida, USA.Search for more papers by this authorPublished Online:12 Apr 2023https://doi.org/10.1089/gyn.2023.0025AboutSectionsPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail As a gynecologist and oncologist, I have long been interested in Paget's disease of the vulva, so the article on this condition (pp. 66–69) was particularly interesting to me.The condition, termed extramammary Paget's disease (EMPD), falls under a deceptively simple heading for what is a spectrum of potential abnormalities that characterize the syndrome. The study in this issue by Dr. Sánchez-Prieto and associates touches on several of the many interesting aspects of EMPD.Sir James Paget, 1st baronet, FRS HFRSE, a prominent professor of surgery and anatomy at St. Bartholomew's Hospital, in London, United Kingdom, in the nineteenth century, described both the bone and breast diseases that bear his name. EMPD was first described toward the end of the nineteenth century.While the disease is rare, the gynecologic surgeon will occasionally encounter EMPD—especially as the population continues to age. This disease is not only difficult to recognize but has challenging complexity.The most-distinguishing aspect of EMPD is its symptomatic skin disease that most commonly involves the external genitalia of postmenopausal Caucasian females. However, there are many manifestations of EMPD beyond the skin. Some of the other clinical characteristics of EMPD include its potential to become invasive, the phenomenon of “heralding” an underlying carcinoma (apocrine gland, urothelial, rectal), the association with cancers at remote sites (such as the breast), and the marked incongruity of clinical and microscopic extents of the skin disease—the clinical significance of which is unclear.There are a variety of therapeutic options for treating EMPD, some of which are under investigation. Wide local excision continues to be the treatment of choice for the primary skin disease. However, the importance of achieving negative margins and the methods of accomplishing this goal are still being investigated. Some recent therapeutic options include Mohs surgery and the use of fluorescein dye mapping. Management of recurrent skin disease is highly individualized and such disease may be symptomatic only in elderly women.The journal's editorial staff and editorial board are working hard to provide a combination of the best educational and research content for you, our readers. Please let us know how we are doing and feel free to provide suggestions for improvement in content.FiguresReferencesRelatedDetails Volume 39Issue 2Apr 2023 InformationCopyright 2023, Mary Ann Liebert, Inc., publishersTo cite this article:Mitchel S. Hoffman.A Disease, a Syndrome, or Both?.Journal of Gynecologic Surgery.Apr 2023.59-59.http://doi.org/10.1089/gyn.2023.0025Published in Volume: 39 Issue 2: April 12, 2023PDF download

Extranasal T/NK lymphoma with a fatal outcome: A case report

Extranodal T/NK lymphoma (LTNKEN) is a rare and aggressive form of non-Hodgkin lymphoma of high-grade malignancy. A distinction is made between the nasal forms, characterized by primary involvement of the nasal cavity, and the extranasal forms. Primary skin involvement is highly rare. Diagnosis is based on immunohistochemical studies. Treatment includes chemotherapy and radiotherapy. This type of lymphoma has a poor prognosis even with treatment. Herein, we report a Moroccan case of cutaneous T/NK lymphoma in a young patient with a primary cutaneous localization of fatal evolution. Key words: Lymphoma; Extranodal lymphoma; T/NK lymphoma; Non-hodgkin lymphoma

Skin eruptions and infectious rash diseases in children in the practice of a primary care physician

Skin eruptions sometimes appear as the first signs of disease in children, allowing for early diagnosis and treatment. Examination of the child’s skin is a routine element of the physical examination, which provides valuable information facilitating the correct diagnosis. Distinguishing individual skin eruptions that make up the overall picture of the disease often causes diagnostic difficulties in the context of rash diseases in children in the practice of a primary care physician. These diseases include viral, bacterial, and parasitic infections as well as those of ambiguous aetiology, such as Kawasaki disease. In this paper, individual primary and secondary skin eruptions are characterised. Primary eruptions are typically a direct result of the development of the disease process in the skin; secondary eruptions, in turn, usually develop from primary eruptions, as consequences thereof. A rash is a lesion that affects the appearance and texture of the skin surface. This paper discusses the most common infectious diseases with a rash in the clinical picture. In addition, when differentiating infectious rash diseases in children, attention was paid to other – non-infectious – skin diseases, such as atopic dermatitis, seborrhoeic dermatitis, and psoriasis. These are disease entities characterised by a diverse clinical picture depending on the stage of the disease and the age of the child. When diagnosing a high-fever child, life-threatening conditions such as meningococcal sepsis, with petechiae that do not disappear under pressure, should always be considered. Prolonged fever, especially lasting more than 5 days, should prompt the physician to conduct diagnostics towards Kawasaki syndrome – a disease of ambiguous aetiology.

Open abdomen: a comprehensive review

When the abdominal viscera are visible due to a defect in the abdominal wall, which is usually caused intentionally or as a result of abdominal compartment syndrome, it is referred to as an open abdomen. As a protracted open abdomen can result in problems including fluid and protein losses, intestinal fistulization, and loss of abdominal dominance, the main goals of temporal abdominal closure techniques are to prevent fluid losses and loss of dominance. There are several techniques for short-term abdominal closure, each having advantages and disadvantages. These techniques include patch closure, silo closure, and negative pressure systems based on towels and sponges. After temporary abdominal closure, the patient is monitored in the critical care unit while any required adjustments are made to the abdominal dressings. Observational studies have shown that the Wittmann Patch has the highest average rate of primary fascial closure when compared to other operations. Yet, a temporary closure of this sort might not be adequate to stop fluid loss on its own. To monitor fluid loss, a negative pressure device (sponge- or towel-based) is advised. It can be used either on its own or in combination with other techniques for closing the temporal abdominal cavity. When the sign of an open abdomen has been removed, the abdomen is closed, ideally using a major fascial closure. If primary fascial closure cannot be achieved, functional closure may be accomplished using a biological mesh inlay method. While there is a good probability of developing a posterior hernia, this treatment adds new fascial tissue where the natural fascial limits are located. The fascia defect may be filled in with primary skin closure or skin grafts once a layer of granulation tissue has developed over the consolidated visceral mass if the space between the fascia's borders is too large for functional closure. Effective abdominal closure and the prevention of issues ultimately depend on proper management and supervision of temporary abdominal closure.

A 7-Hydroxy 4-Methylcoumarin Enhances Melanogenesis in B16-F10 Melanoma Cells.

The objectives of this study were to investigate the melanogenetic potentials of the naturally occurring 7-hydroxy coumarin derivatives 7-hydroxy 5,6-dimethoxycoumarin (7H-5,6DM), 7-hydroxy 6,8-dimethoxycoumarin (7H-6,8DM), 7-hydroxy 6-methoxycoumarin (7H-6M), and 7-hydroxy 4-methylcoumarin (7H-4M) in the melanogenic cells model for murine B16F10 melanoma cells. The initial results indicated that melanin production and intracellular tyrosinase activity were significantly stimulated by 7H-4M but not by 7H-5,6DM, 7H-6,8DM, or 7H-6M. Therefore, our present study further investigated the melanogenic effects of 7H-4M in B16-F10 cells, as well as its mechanisms of action. In a concentration-dependent manner, 7H-4M increased intracellular tyrosinase activity, leading to the accumulation of melanin without affecting the viability of B16-F10 cells. Our study further investigated the effects of 7H-4M on melanogenesis, including its ability to promote tyrosinase activity, increase melanin content, and activate molecular signaling pathways. The results indicate that 7H-4M effectively stimulated tyrosinase activity and significantly increased the expression of melanin synthesis-associated proteins, such as microphthalmia-associated transcription factor (MITF), tyrosinase, tyrosinase-related protein-1 (TRP1), and TRP2. Based on our findings, we can conclude that 7H-4M has the ability to activate the melanogenesis process through the upregulation of cAMP-dependent protein kinase (PKA) and the cAMP response element-binding protein (CREB). Additionally, our study showed that 7H-4M induced melanogenic effects by downregulating the extracellular signal-regulated kinase (ERK) and the phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt)/glycogen synthesis kinase-3β (GSK-3β) cascades, while upregulating the JNK and p38 signaling pathways. Finally, the potential of using 7H-4M in topical applications was tested through primary human skin irritation tests. During these tests, no adverse reactions were induced by 7H-4M. In summary, our results indicate that 7H-4M regulates melanogenesis through various signaling pathways such as GSK3β/β-catenin, AKT, PKA/CREB, and MAPK. These findings suggest that 7H-4M has the potential to prevent the development of pigmentation diseases.

Generation of two induced pluripotent stem cell lines and the corresponding isogenic controls from Parkinson’s disease patients carrying the heterozygous mutations c.1290A > G (p.T351A) or c.2067A > G (p.T610A) in the RHOT1 gene encoding Miro1

Primary skin fibroblasts from two Parkinson’s disease (PD) patients carrying distinct heterozygous mutations in the RHOT1 gene encoding Miro1, namely c.1290A > G (Miro1 p.T351A) and c.2067A > G (Miro1 p.T610A), were converted into induced pluripotent stem cells (iPSCs) by episomal reprogramming. The corresponding isogenic gene-corrected lines have been generated using CRISPR/Cas9 technology. Here, we provide a comprehensive characterization and quality assurance of both isogenic pairs, which will be used to study Miro1-related molecular mechanisms underlying neurodegeneration in iPSC-derived neuronal models (e.g., midbrain dopaminergic neurons and astrocytes).

Measuring the quality of skin cancer management in primary care: A scoping review.

Skin cancer is a growing global problem and a significant health and economic burden. Despite the practical necessity for skin cancer to be managed in primary care settings, little is known about how quality of care is or should be measured in this setting. This scoping review aimed to capture the breadth and range of contemporary evidence related to the measurement of quality in skin cancer management in primary care settings. Six databases were searched for relevant texts reporting on quality measurement in primary care skin cancer management. Data from 46 texts published since 2011 were extracted, and quality measures were catalogued according to the three domains of the Donabedian model of healthcare quality (structure, process and outcome). Quality measures within each domain were inductively analysed into 13 key emergent groups. These represented what were deemed to be the most relevant components of skin cancer management as related to structure, process or outcomes measurement. Four groups related to the structural elements of care provision (e.g. diagnostic tools and equipment), five related to the process of care delivery (e.g. diagnostic processes) and four related to the outcomes of care (e.g. poor treatment outcomes). A broad range of quality measures have been documented, based predominantly on articles using retrospective cohort designs; systematic reviews and randomised controlled trials were limited.

Selective whole-genome amplification reveals population genetics of Leishmania braziliensis directly from patient skin biopsies.

In Brazil, Leishmania braziliensis is the main causative agent of the neglected tropical disease, cutaneous leishmaniasis (CL). CL presents on a spectrum of disease severity with a high rate of treatment failure. Yet the parasite factors that contribute to disease presentation and treatment outcome are not well understood, in part because successfully isolating and culturing parasites from patient lesions remains a major technical challenge. Here we describe the development of selective whole genome amplification (SWGA) for Leishmania and show that this method enables culture-independent analysis of parasite genomes obtained directly from primary patient skin samples, allowing us to circumvent artifacts associated with adaptation to culture. We show that SWGA can be applied to multiple Leishmania species residing in different host species, suggesting that this method is broadly useful in both experimental infection models and clinical studies. SWGA carried out directly on skin biopsies collected from patients in Corte de Pedra, Bahia, Brazil, showed extensive genomic diversity. Finally, as a proof-of-concept, we demonstrated that SWGA data can be integrated with published whole genome data from cultured parasite isolates to identify variants unique to specific geographic regions in Brazil where treatment failure rates are known to be high. SWGA provides a relatively simple method to generate Leishmania genomes directly from patient samples, unlocking the potential to link parasite genetics with host clinical phenotypes.

Primary skin abscess microbiota a systematic review.

An abscess is a collection of pus forming a cavity in the tissue, for example, the skin. They are generally perceived as the result of infection but infection is not mandatory for the diagnosis. Skin abscesses may occur independently (primary) or be part of other diseases such as the recurrent inflammatory skin disease hidradenitis suppurativa (HS). HS is noninfectious but nevertheless abscesses are a common differential diagnosis. The purpose of this study is to review the microbiome of bacteria positive primary skin abscesses in order to explore the reported microbiota. EMBASE, MEDLINER, and COCHRANE LIBRABRY were searched on 9th of October 2021 for microbiome, skin, and abscesses. Studies with more than 10 patients reporting the microbiome in human skin-abscesses were included and studies with abscess microbiota sampled from HS patients, microbiota not sampled from skin-abscesses, missing information on microbiome data, sampling bias, studies in other language than English or Danish, reviews and meta-analyses were excluded. In total 11 studies were included for further analysis. S.aureus is likely to dominate the microbiome of bacteria positive primary skin abscesses in contrast to the polymicrobial microbiome of HS.