Cholesterol Nanofiber Patches with Sustainable Oil Delivery Eliminate Inflammation in Atopic Skin.

Atopic skin is dry and itchy and lacks integrity. Impaired skin barrier results from altered lipid composition of the skin. A crucial skin lipid, cholesterol, provides flexibility and homeostasis of the cell membranes' lipid bilayer. Cholesterol-based creams and natural oils, especially blackcurrant seed oil, are beneficial for skin care as they hydrate the skin and improve its integrity. The major atopic symptom, skin dryness, can be overcome by the application of porous patches enhanced with cholesterol and natural oil. The base of the patches is constructed of polyimide (PI) nanofibers with cholesterol coatings and externally added blackcurrant seed oil. The presence of cholesterol in PI mats hinders the passage of oil through the patches to the skin, resulting in sustained and prolonged skin hydration. The theoretical and numerical investigations of oil dynamics in porous mats confirmed the experimental results, showing a prolonged skin hydration effect up to 6 h. Additionally, as demonstrated by in vivo tests on atopic mice, cholesterol patches lower serum immunoglobulin E levels and expression of proinflammatory cytokines in the skin, thereby accelerating skin healing. Our results hold great promise for the long-term application of the patches in atopic dermatitis treatment.

[Corrigendum] All­trans retinoic acid alters the expression of the tight junction proteins Claudin­1 and ­4 and epidermal barrier function­associated genes in the epidermis.

Following the publication of the above article, the authors contacted the Editorial Office to explain that they had identified a pair of duplicate images in the control (Vehicle) group of mouse images in Fig. 1A on p. 1792. Specifically, the same image (corresponding correctly to the 'Day 5' experiment) was inadvertently chosen to represent the cutaneous manifestations of mice in the Vehicle group on 'Day 3' and 'Day 5' in Fig. 1A. This error arose as a consequence of repetitive application and duplication procedures within the image set, resulting in the inadvertent reuse of the same photo. Additionally, due to minimal alterations observed in the skin condition of mice from the control group following treatment, each mouse exhibited a similar appearance; this similarity further contributed to the delayed identification of this error during the paper revision stage. Consequently, this duplication of the same image was made as a result of insufficient scrutiny. The revised version of Fig. 1, showing the correct image for the 'Day 3' experiment in Fig. 1A, is shown on the next page. The authors can confirm that the error associated with the assembly of this figure did not have any significant impact on either the results or the conclusions reported in this study, and all the authors agree with the publication of this Corrigendum. The authors are grateful to the Editor of International Journal of Molecular Medicine for allowing them the opportunity to publish this; furthermore, they apologize to the readership of the Journal for any inconvenience caused. [International Journal of Molecular Medicine 43: 1789­1805, 2019; DOI: 10.3892/ijmm.2019.4098].

Mendelian randomization analysis reveals higher whole body water mass may increase risk of bacterial infections.

BACKGROUND AND PURPOSE: The association of water loading with several infections remains unclear. Observational studies are hard to investigate definitively due to potential confounders. In this study, we employed Mendelian randomization (MR) analysis to assess the association between genetically predicted whole body water mass (BWM) and several infections. METHODS: BWM levels were predicted among 331,315 Europeans in UK Biobank using 418 SNPs associated with BWM. For outcomes, we used genome-wide association data from the UK Biobank and FinnGen consortium, including sepsis, pneumonia, intestinal infections, urinary tract infections (UTIs) and skin and soft tissue infections (SSTIs). Inverse-variance weighted MR analyses as well as a series of sensitivity analyses were conducted. RESULTS: Genetic prediction of BWM is associated with an increased risk of sepsis (OR 1.34; 95% CI 1.19 to 1.51; P = 1.57 × 10- 6), pneumonia (OR: 1.17; 95% CI 1.08 to 1.29; P = 3.53 × 10- 4), UTIs (OR: 1.26; 95% CI 1.16 to 1.37; P = 6.29 × 10- 8), and SSTIs (OR: 1.57; 95% CI 1.25 to 1.96; P = 7.35 × 10- 5). In the sepsis and pneumonia subgroup analyses, the relationship between BWM and infection was observed in bacterial but not in viral infections. Suggestive evidence suggests that BWM has an effect on viral intestinal infections (OR: 0.86; 95% CI 0.75 to 0.99; P = 0.03). There is limited evidence of an association between BWM levels and bacteria intestinal infections, and genitourinary tract infection (GUI) in pregnancy. In addition, MR analyses supported the risk of BWM for several edematous diseases. However, multivariable MR analysis shows that the associations of BWM with sepsis, pneumonia, UTIs and SSTIs remains unaffected when accounting for these traits. CONCLUSIONS: In this study, the causal relationship between BWM and infectious diseases was systematically investigated. Further prospective studies are necessary to validate these findings.

Dermoscopic monitoring of pediatric melanocytic nevi regarding pattern and diameter changes.

BACKGROUND: Childhood and adolescence are dynamic period in terms of nevogenesis, and the development and growth of new melanocytic nevus are frequently observed. In this study, the aim was to examine the pattern and diameter changes seen in the follow-up of pediatric melanocytic nevus. OBJECTIVES: To describe the pattern and diameter changes seen in the follow-up of pediatric melanocytic. METHODS: Our study involved the assessment of 301 pediatric melanocytic nevi in 50 patients attended at the Dermatology Clinic of Istanbul Training and Research Hospital between January 2008 and 2022. The pediatric melanocytic nevi were diagnosed clinically and dermoscopically. Subsequently, we conducted video-dermoscopic monitoring of these nevi over a span of 3 months to 3 years. RESULTS: 46% of our patients were female (n = 23), with a mean age of 11.5 years. While the pattern of nevi was globular in 40% patients, the rate of globular pattern decreased to 30% in the follow-up. The basal homogeneous nevus pattern was seen in 10% patients, but was detected in 13.9% in the follow-up. Peripheral globules were observed in 19.3% of the cases, but in the follow-up, 61.1% of the globules regressed completely. Nevus excision was indicated in only 11 of 301 nevi. STUDY LIMITATIONS: Single-center study and a small of studies available on this subject. CONCLUSIONS: Pediatric melanocytic nevi can show dynamic changes compared to nevi in adults. In this study, growth rates, dermoscopic features, and pattern changes seen in the follow-up of melanocytic nevi were evaluated. The globular pattern was observed most frequently. The presence of peripheral globules is frequently observed in pediatric melanocytic nevi with regression during the follow-up period.

The impact of the left inferior frontal gyrus on fear extinction: A transcranial direct current stimulation study.

INTRODUCTION: Fear extinction is a fundamental component of exposure-based therapies for anxiety-related disorders. The renewal of fear in a different context after extinction highlights the importance of contextual factors. In this study, we aimed to investigate the causal role of the left inferior frontal gyrus (LiFG) in the context-dependency of fear extinction learning via administration of transcranial direct current stimulation (tDCS) over this area. METHODS: 180 healthy subjects were assigned to 9 groups: 3 tDCS conditions (anodal, cathodal, and sham) × 3 context combinations (AAA, ABA, and ABB). The fear conditioning/extinction task was conducted over three consecutive days: acquisition, extinction learning, and extinction recall. tDCS (2 mA, 10min) was administered during the extinction learning phase over the LiFG via a 4-electrode montage. Skin conductance response (SCR) data and self-report assessments were collected. RESULTS: During the extinction learning phase, groups with excitability-enhancing anodal tDCS showed a significantly higher fear response to the threat cues compared to cathodal and sham stimulation conditions, irrespective of contextual factors. This effect was stable until the extinction recall phase. Additionally, excitability-reducing cathodal tDCS caused a significant decrease of the response difference between the threat and safety cues during the extinction recall phase. The self-report assessments showed no significant differences between the conditions throughout the experiment. CONCLUSION: Independent of the context, excitability enhancement of the LiFG did impair fear extinction, and led to preservation of fear memory. In contrast, excitability reduction of this area enhanced fear extinction retention. These findings imply that the LiFG plays a role in the fear extinction network, which seems to be however context-independent.

Other Schistosomatoidea and Diplostomoidea.

Trematodes of the order Diplostomida are well known as serious pathogens of man, and both farm and wild animals; members of the genus Schistosoma (Schistosomatidae) are responsible for human schistosomosis (schistosomiasis) affecting more than 200 million people in tropical and subtropical countries, and infections of mammals and birds by animal schistosomes are of great veterinary importance. The order Diplostomida is also rich in species parasitizing other major taxa of vertebrates. The "Aporocotylidae" sensu lato are pathogenic in fish, "Spirorchiidae" sensu lato in reptiles. All these flukes have two-host life cycles, with asexually reproducing larvae usually in mollusks and occasionally in annelids, and adults usually live in the blood vessels of their vertebrate hosts. Pathology is frequently associated with inflammatory reactions to eggs trapped in various tissues/organs. On the other hand, the representatives of Diplostomidae and Strigeidae have three- or four-host life cycles in which vertebrates often serve not only as definitive but also as intermediate or paratenic hosts. Pathology is usually associated with migration of metacercariae and mesocercariae within the host tissues. The impact of these trematode infections on both farm and wild animals may be significant.

A BRILLIANT-BRCA study: residual breast tissue after mastectomy and reconstruction.

INTRODUCTION: Different types of mastectomies leave different amounts of residual breast tissue. The significance of the residual breast volume (RBV) is not clear. Therefore, we developed an MRI tool that allows to easily assess the RBV. In this study we evaluated factors associated with RBV after skin or nipple sparing mastectomy (SSM/NSM) in breast cancer BRCA pathogenic variant (PV) carriers who underwent both therapeutic and risk reducing SSM/NSM and its relation to breast cancer outcomes using an innovative MRI-based tool. METHODS: Data of breast cancer BRCA PV who were treated between 2006 and 2020 were retrieved from of the oncogenetics unit databases. Only patients who underwent SSM/NSM and had a postoperative breast MRI available for analysis were included. Data collected included demographics, clinicopathological features, and outcomes. The MRI tool was developed by a breast cancer imaging laboratory. A logistic regression test and 95% confidence interval (CI) were used to assess the associated risk of increased RBV. A forward stepwise linear regression was used to correlate tumour-patient specific factors and RBV, and a Kaplan-Meier curve to show the probability of locoregional relapse. RESULTS: A total of 84 patients undergoing 89 mastectomies were included. At a median follow-up of 98 months, 5 local, 2 regional, and 4 distant recurrences were observed. RBV was not significantly related with breast cancer outcomes (p value = NS). A higher body mass index (BMI) was associated with a higher RBV (p < 0.0001). A larger number of involved axillary nodes was associated with a smaller RBV (p = 0.025). The RBV on the risk-reducing mastectomy side was significantly higher compared to the breast cancer side (p value = 0.007). Local recurrences occurred in the vicinity of the primary tumour.

3D-Bioprinted Skin Tissues for Improving Wound Healing: Current Status and Perspective.

Advancements in tissue engineering enable the fabrication of complex and functional tissues or organs. In particular, bioprinting enables controlled and accurate deposition of cells, biomaterials, and growth factors to create complex 3D skin constructs specific to a particular individual. Despite these advancements, challenges such as vascularization, long-term stability, and regulatory considerations hinder the clinical translation of bioprinted skin constructs. This chapter focuses on such approaches using advanced biomaterials and bioprinting techniques to overcome the current barriers in wound-healing studies. Moreover, it addresses current obstacles in wound-healing studies, highlighting the need for continued research and innovation to overcome these barriers and facilitate the practical utilization of bioprinted skin constructs in clinical settings.

Skin graft surgery and its impact on platelet counts in Iranian burn patients: a non-randomized clinical trial.

BACKGROUND: Platelets are critical in maintaining homeostasis and immune response in burn patients. The concentration of platelets decreases in burn patients, and any intervention that increases serum platelet concentration can prevent serious consequences and patient death. The present study aimed to assess the impact of skin graft surgery on burn patients' platelet counts. METHODS: In this non-randomized clinical trial, 200 burn patients were investigated. The patients were recruited from the surgical ward of Imam Khomeini Teaching Hospital during the first six months of 2021. After completing the checklist, patients underwent skin graft surgery. Blood was taken from the patients during surgery in the operating room and on the third and fifth day after the surgery to check platelets. Data analysis was conducted using SPSS software (ver. 22.0). RESULTS: Most patients (63.5%) were male, and 73 (36.5%) were female. One hundred eighty-one patients (90.5%) had deep burns, and 19 (9.5%) had superficial burns. The mean burns percentage in the patients was 19.3 ± 15.4%, the lowest was 2%, and the highest was 90%. The most common burns were caused by flame (42%) and boiling water (30.5%). The patients' outcomes revealed that 6% gained complete recovery, 86.5% partial recovery, 2.5% showed transplant rejection, and 5% died. Mean platelet levels in deceased patients had an upward trend. The mean platelet counts of patients were elevated during surgery (289,855 ± 165,378), decreased three days after surgery (282,778 ± 317,310), and elevated again five days after surgery (330,375 ± 208,571). However, no significant difference was found between the mean platelet counts during surgery, the third and fifth days after surgery in patients undergoing skin grafts (P = 0.057). CONCLUSIONS: This study suggests that skin graft positively increases the patient's platelets. Further studies are needed to confirm the findings and elucidate the mechanism. Iranian Registry of Clinical Trial approval code (IRCT# IRCT20131112015390N8 & 06/01/2024).

Long-term culture of patient-derived mammary organoids in non-biogenic electrospun scaffolds for identifying metalloprotein and motor protein activities in aging and senescence.

We recently identified TMEM230 as a master regulator of the endomembrane system of cells. TMEM230 expression is necessary for promoting motor protein dependent intracellular trafficking of metalloproteins for cellular energy production in mitochondria. TMEM230 is also required for transport and secretion of metalloproteinases for autophagy and phagosome dependent clearance of misfolded proteins, defective RNAs and damaged cells, activities that decline with aging. This suggests that aberrant levels of TMEM230 may contribute to aging and regain of proper levels may have therapeutic applications. The components of the endomembrane system include the Golgi complex, other membrane bound organelles, and secreted vesicles and factors. Secreted cellular components modulate immune response and tissue regeneration in aging. Upregulation of intracellular packaging, trafficking and secretion of endosome components while necessary for tissue homeostasis and normal wound healing, also promote secretion of pro-inflammatory and pro-senescence factors. We recently determined that TMEM230 is co-regulated with trafficked cargo of the endomembrane system, including lysosome factors such as RNASET2. Normal tissue regeneration (in aging), repair (following injury) and aberrant destructive tissue remodeling (in cancer or autoimmunity) likely are regulated by TMEM230 activities of the endomembrane system, mitochondria and autophagosomes. The role of TMEM230 in aging is supported by its ability to regulate the pro-inflammatory secretome and senescence-associated secretory phenotype in tissue cells of patients with advanced age and chronic disease. Identifying secreted factors regulated by TMEM230 in young patients and patients of advanced age will facilitate identification of aging associated targets that aberrantly promote, inhibit or reverse aging. Ex situ culture of patient derived cells for identifying secreted factors in tissue regeneration and aging provides opportunities in developing therapeutic and personalized medicine strategies. Identification and validation of human secreted factors in tissue regeneration requires long-term stabile scaffold culture conditions that are different from those previously reported for cell lines used as cell models for aging. We describe a 3 dimensional (3D) platform utilizing non-biogenic and non-labile poly ε-caprolactone scaffolds that supports maintenance of long-term continuous cultures of human stem cells, in vitro generated 3D organoids and patient derived tissue. Combined with animal component free culture media, non-biogenic scaffolds are suitable for proteomic and glycobiological analyses to identify human factors in aging. Applications of electrospun nanofiber technologies in 3D cell culture allow for ex situ screening and the development of patient personalized therapeutic strategies and predicting their effectiveness in mitigating or promoting aging.

The Challenge of Chronic Wounds in Older Adults.

Care for the older patient living with a chronic wound comes with challenges not seen in younger patients. The aging skin, impacted by the environment and intrinsic physiologic changes, makes it susceptible to injury and poor healing. Likewise, older adults' goals with regards to wound healing may vary depending on their functional abilities and quality of life. The clinician must pay attention to these nuances and collaborate with the older patient in developing a treatment plan. Careful systematic description, documentation, and communication with the patient/caregiver aids the clinician in tracking the treatment goals and potentially reducing medical liability risk.

Surgical Aspects of Wound Care in Older Adults.

The physical, emotional, and financial toll of acute and chronic nonhealing wounds on older adults and their caregivers is immense. Surgical treatment of wounds in older adults can facilitate healing but must consider the medical complexity of the patient, the patient's desires for treatment and the likelihood of healing. Innovative approaches and devices can promote rapid healing. By using a team approach, from preoperative planning to postoperative care, with a focus on the needs and desires of the patient, successful outcomes with improved patient satisfaction are possible even in medically complex patients.

Pressure Injuries and Skin Failure.

Pressure injuries are a common chronic wound in the older adult. Care of pressure injuries is an interprofessional effort and involves physicians, nurses, registered dieticians, rehabilitation therapists, and surgical subspecialties. Numerous treatment modalities exist but have varying evidence to substantiate their efficacy. All primary and other care providers, particularly geriatricians, need to be aware of current evidence-based prevention and treatment standards. When healing is not expected, palliative care should be considered to avoid futile procedures and preserve dignity and quality of life.

Infectious Aspects of Chronic Wounds.

The treatment, maintenance, and suppression of infection in chronic wounds remain a challenge to all practitioners. From an infectious disease standpoint, knowing when a chronic wound has progressed from colonized to infected, when to use systemic antimicrobial therapy and when and how to culture such wounds can be daunting. With few standardized clinical guidelines for infections in chronic wounds, caring for them is an art form. However, there have been notable advances in the diagnosis, treatment, and management of infected wounds. This article will discuss the pathophysiology of infection in older adults, including specific infections such as cutaneous candidiasis, necrotizing soft tissue infection, osteomyelitis, and infections involving hardware.

Deodorant pad for ulcerated breast cancer: safety and efficacy.

OBJECTIVES: APOLLO study, 'efficacy and safety of the deodorAnt Pad against Odour and uLceration for LOcally advanced breast cancer', aimed to assess the safety and efficacy of wearing a deodorant pad in patients with locally advanced breast cancer (LABC) with an ulceration. METHODS: Komagome Pads were previously developed by Juntendo University and Kao Corporation. In test A, a conventional pad consisting of gauze, a commercially available diaper, pad, etc and the Komagome Pad were compared over 3 days to assess their efficacy and possible improvements for short-term use. In test B, the Komagome Pad was used continuously for 1 month to evaluate its safety during long-term use. RESULTS: This study included 14 patients in test A and nine in test B. In odour evaluation using sensory testing in test A, nine patients reported more significant efficacy in odour suppression with the Komagome Pad. The odour intensity of the Komagome Pad was lower on the gas chromatography-mass spectrometry. The group with a high level of exudation reported significantly higher satisfaction with the Komagome Pad. In test B, no adverse events were observed. CONCLUSIONS: A new deodorant pad for LABC demonstrated high safety and deodorant efficacy.

Let­7f­5p Regulated by Hsa_circ_0000437 Ameliorates Bleomycin-Induced Skin Fibrosis.

The current treatment of skin fibrosis is limited in its effectiveness due to a lack of understanding of the underlying mechanisms. Previous research has shown a connection between microRNAs (miRNAs) and the development of skin fibrosis. Therefore, investigating miRNA for the treatment of skin fibrotic diseases is highly important and merits further exploration. In this study, we have discovered that let-7f-5p could suppress the proliferation, migration, and expression of collagen type I alpha 1 (COL1A1) in human dermal fibroblasts (HDFs). It was further determined that let-7f-5p could target thrombospondin-1 (THBS1), thereby inhibiting the TGF-ß2/Smad3 signaling pathway and exerting its biological effects. Additionally, let-7f-5p is regulated by Hsa_circ_0000437, which acts as a sponge molecule for let-7f-5p and consequently regulates the biological function of HDFs. Furthermore, our findings indicate that in vivo overexpression of let-7f-5p leads to a reduction in dermal thickness and COL1A1 expression, effectively inhibiting the progression of bleomycin (BLM)-induced skin fibrosis in mice. Hence, our research enhances the comprehension of the Hsa_circ_0000437/let-7f-5p/THBS1/TGF-ß2/Smad3 regulatory network, highlighting the potential of let-7f-5p as a therapeutic approach for the treatment of skin fibrosis.

How to undertake a pain assessment for -patients with acute post-operative pain.

RATIONALE AND KEY POINTS: Acute post-operative pain is common among patients in secondary care settings, and the alleviation of this pain is a principal responsibility for all healthcare professionals, including nurses. To achieve this, it is essential to regularly undertake comprehensive pain assessments, using validated pain assessment tools, for all patients who have undergone a surgical procedure. Inadequate pain assessment may lead to ineffective or inappropriate pain management, which can adversely affect the patient's recovery and increase their risk of developing chronic pain. •  Pain is a subjective experience and therefore requires individualised, comprehensive assessment and management interventions. •  The assessment process for patients with acute pain is fundamental to understanding the patient's current status, informing differential diagnoses regarding the underlying cause of the pain, providing appropriate treatment and monitoring, and evaluating the effectiveness of treatment. •  Pain assessment should not be undertaken as a one-off care activity; it should be completed whenever a patient reports pain and repeated following pharmacological and/or non-pharmacological interventions. REFLECTIVE ACTIVITY: 'How to' articles can help you to update your practice and ensure it remains evidence-based. Apply this article to your practice. Reflect on and write a short account of: •  How this article might improve your practice when undertaking a comprehensive pain assessment with patients experiencing acute post-operative pain. •  How you could use this information to educate nursing students or colleagues on the appropriate actions to take when undertaking a comprehensive pain assessment with patients experiencing acute post-operative pain.

Dermatomyositis-like skin eruptions under hydroxyurea therapy conceal TP53-mutated atypical keratinocytes: A histopathologic and molecular pathologic case series.

Hydroxyurea is an antimetabolite that inhibits DNA synthesis and is used as a treatment option in chronic myeloproliferative disorders. Rarely, "dermatomyositis (DM)-like" skin lesions are observed after long-term therapy. In this case series, five skin biopsies of four patients were evaluated by histology, immunohistochemistry, and next-generation sequencing of the TP53 gene locus. All biopsies showed focal basal pleomorphic keratinocytes and suprabasal aberrant p53 expression as well as sparse to severe vacuolar interface dermatitis. Histopathologically, "DM-like" skin lesions can be clearly distinguished from DM by marked subepidermal fibrosis, vascular proliferation, and the absence of dermal mucin deposits. In 75% of the specimens multiple, partly inactivating and/or pathogenic point mutations of TP53 were found in low frequencies. "DM-like" skin eruptions as a long-term consequence of hydroxyurea therapy are possibly not chemotherapy-associated benign toxic changes, but rather inflammatory reactions to complex keratinocyte alterations that clinically mimic the picture of DM. Synergistic mutagenic effects of hydroxyurea and sunlight might be responsible for this unique drug side effect and could provide a pathogenic link to the known increased risk of skin cancer in these patients.

Core-Shell Gel Nanofiber Scaffolds Constructed by Microfluidic Spinning toward Wound Repair and Tissue Regeneration.

Growing demand for wound care resulting from the increasing chronic diseases and trauma brings intense pressure to global medical health service system. Artificial skin provides mechanical and microenvironmental support for wound, which is crucial in wound healing and tissue regeneration. However, challenges still remain in the clinical application of artificial skin since the lack of the synergy effect of necessary performance. In this study, a multi-functional artificial skin is fabricated through microfluidic spinning technology by using core-shell gel nanofiber scaffolds (NFSs). This strategy can precisely manipulate the microstructure of artificial skin under microscale. The as-prepared artificial skin demonstrates superior characteristics including surface wettability, breathability, high mechanical strength, strain sensitivity, biocompatibility and biodegradability. Notably, this artificial skin has the capability to deliver medications in a controlled and sustained manner, thereby accelerating the wound healing process. This innovative approach paves the way for the development of a new generation of artificial skin and introduces a novel concept for the structural design of the unique core-shell gel NFSs.

Case Report: Could topical epidermal growth factor be considered a new therapy for skin injuries in premature infants?

In this case report, we present the experience of a premature neonate born at 28 weeks of gestation who, following prolonged respiratory support, developed a pressure injury on the columella despite the implementation of all appropriate preventive techniques. This injury did not improve with standard therapies; therefore, it was necessary to apply a topical galenic therapy containing epidermal growth factor, resulting in complete healing of the lesion.