Type 2 Cytokine-Dependent Skin Barrier Regulation in Personalized 2-Dimensional and 3-Dimensional Skin Models of Atopic Dermatitis: A Pilot Study.

Keratinocytes (KCs) from healthy donors stimulated with type 2 cytokines are often used to experimentally study atopic dermatitis (AD) inflammatory responses. Owing to potential intrinsic alterations, it seems favorable to use KCs from patients with AD. KCs isolated from hair follicles offer a noninvasive approach to investigate AD-derived KCs. To evaluate whether such AD-derived KCs are suitable to mimic AD inflammatory responses, we compared hair follicle-derived KCs from healthy donors with those from patients with AD in a type 2 cytokine environment. Stimulation of AD-derived KCs with IL-4 and IL-13 induced higher expression changes of AD-associated markers than that of healthy KCs. The combination of IL-4 and IL-13 generally induced highest expression changes, but IL-13 alone also induced significant changes of AD-specific markers. Similar to the 2-dimensional cultures, IL-4/IL-13 stimulation of 3-dimensional skin models generated with AD-derived KCs modulated the expression of several AD-relevant factors. Whole-transcriptome analysis revealed that IL-4 and IL-13 acted similarly on these 3-dimensional skin models. Histologically, IL-13 alone and in combination with IL-4 increased epidermal spongiosis, a histological hallmark of AD skin. Taken together, our pilot study suggests that hair follicle-derived KCs from patients with AD represent a useful model system to study AD-related inflammation in a personalized in vitro model.

A Tensioned Human Skin Explant Model Used for Preliminary Assessment of Chemexfoliant-Stimulated Bioeffects.

A tensioned ex vivo full-thickness human skin explant platform was used to assess the bioeffects arising from application of several commercial chemexfoliation agents. Although such treatments are well-established, and improved understanding of the underlying mechanistic processes continues to emerge, research into the optimum treatments for specific skin types/conditions is still needed for enhanced efficacy while minimizing recovery time. The 3 commercial chemexfoliation agents employed all contained trichloroacetic acid at well-defined concentrations (6, 10, and 20%) and were applied to the explants' stratum corneum. Subsequently, measurements of dermal remodeling factors (COL1A1, ELN, HAS2, HAS3, and procollagen type I) and inflammatory marker (IL-1b) were undertaken using qPCR and immunofluorescent analyses. Statistical analysis of these data facilitated the establishment of benchmarking biological responses to these trichloroacetic acid-containing agents against untreated controls. The performance of an innovative trichloroacetic acid-free chemexfoliation agent was then measured and, upon comparison with the previous benchmarking data, indicated that dermal remodeling factors could be upregulated in fashion comparable with that of the trichloroacetic acid-containing agents but with significant suppression of inflammatory response. Our measurements thus underscore the promise of the tensioned explant over prolonged study periods and also that potentially valuable insights to guide preclinical strategies may be forthcoming from the protocol developed.

Tea polyphenols nanoparticles integrated with microneedles multifunctionally boost 5-aminolevulinic acid photodynamic therapy for skin cancer.

5-aminolevulinic acid photodynamic therapy (ALA-PDT) is an emerging therapeutic strategy for skin cancer due to its noninvasiveness and high spatiotemporal selectivity. However, poor skin penetration, poor intratumoral delivery, the instability of aqueous ALA, and the tumor's inherent hypoxia microenvironment are major hurdles hindering the efficacy of ALA-PDT. Herein, we aim to address these challenges by using microneedles (MNs) to assist in delivering nanoparticles based on natural polymeric tea polyphenols (TP NPs) to self-assemble and load ALA (ALA@TP NPs). The TP NPs specifically increase cellular uptake of ALA by A375 and A431 cells and reduce mitochondrial membrane potential. Subsequently, the photosensitizer protoporphyrin IX derived from ALA accumulates in the tumor cells in a dose-dependent manner with TP NPs, generating reactive oxygen species to promote apoptosis and necrosis of A375 and A431 cells. Interestingly, TP NPs can ameliorate the tumor's inherent hypoxia microenvironment and rapid oxygen consumption during PDT by inhibiting hypoxia inducible factor-1α, thereby boosting reactive oxygen species (ROS) generation and enhancing ALA-PDT efficacy through a positive feedback loop. After ALA@TP NPs are loaded into MNs to fabricate ALA@TP NPs@MNs, the MNs enhance skin penetration and storage stability of ALA. Importantly, they exhibit remarkable antitumor efficacy in A375-induced melanoma and A431-induced squamous cell carcinoma with a reduced dose of ALA and reverse hypoxia in vivo. This study provides a facile and novel strategy that integrates MNs and green NPs of TP for addressing the bottlenecks of ALA-PDT and enhancing the ALA-PDT efficacy against skin cancers for future clinical translation.

Silencing of ERRα gene represses cell proliferation and induces apoptosis in human skin fibroblasts.

Estrogen­related receptor (ERR) is an orphan nuclear receptor structurally akin to the estrogen receptor. ERR is expressed in tissues with active energy metabolism and regulates intracellular metabolic functions. Additionally, ERRs are known to be strongly expressed in the epidermis of skin tissue, but their functions are unknown. The present study investigated the function of ERRα in human skin fibroblasts. ERRα expressed in human dermal fibroblast TIG113 was knocked down using small interfering (si)RNA and gene expression was comprehensively analyzed using microarrays 48 h later. Pathway analysis was performed using Wikipathways on genes exhibiting expression changes of ≥1.5­fold. Expression of cell cycle­related and apoptosis­related genes was compared using reverse transcription­quantitative PCR. After treating TIG113 cells with siERRα for 72 h, cell proliferation was assessed using the Cell Counting Kit­8 or a scratch wound healing assay and apoptotic cells were measured using the Poly Caspase Assay Kit. Cell cycle analysis was performed using flow cytometry. The expression of the ERRα gene was suppressed by siRNA. The expression of genes associated with cell cycle­related pathways were decreased while that of those associated with apoptosis­related pathways increased. Furthermore, the expression of cell cycle­related genes such as cell division cycle 25C, cyclin E and cyclin B1 was decreased and the expression of apoptosis­related genes such as caspase3 and Fas cell surface death receptor was increased. Cell proliferation was suppressed and the number of apoptotic cells increased ~2­fold in ERRα­knockdown TIG113 cells. Cell cycle analysis revealed that the number of cells in the Sub­G1 phase increased and that in the S and G2/M phases decreased. The present study suggested that ERRα is an essential for the survival of human skin fibroblasts.

Unilateral acute cataract after facial aesthetic procedure: a case report

ABSTRACT Aging and face sagging have many causes, and various techniques are used for treatment, including noninvasive procedures, such as focused ultrasound, which uses the principle of collagen regeneration by coagulative necrosis of the dermis layers using radiofrequency, but this procedure has complications. We reported a case of a 54-year-old female patient who complained of poor visual acuity in her right eye three days after a focused ultrasound facial aesthetic procedure, with the best visual acuity of 20/60. Biomicroscopy of the right eye revealed an acute cataract with three points of fibrosis extending from the posterior to the anterior capsule. The patient underwent phacoemulsification surgery with visual rehabilitation and improved vision of 20/20. We hypothesized that the occurrence of acute cataract was related to the inappropriate use of focused ultrasound.

Aging, senescence, and cutaneous wound healing-a complex relationship.

Cutaneous wound healing is a complex multi-step process that is highly controlled, ensuring efficient repair to damaged tissue and restoring tissue architecture. Multiple cell types play a critical role in wound healing, and perturbations in this can lead to non-healing wounds or scarring and fibrosis. Thus, the process is tightly regulated and controlled. Cellular senescence is defined as irreversible cell cycle arrest and is associated with various phenotypic changes and metabolic alterations and coupled to a secretory program. Its role in wound healing, at least in the acute setting, appears to help promote appropriate mechanisms leading to the complete restoration of tissue architecture. Opposing this is the role of senescence in chronic wounds where it can lead to either chronic non-healing wounds or fibrosis. Given the two opposing outcomes of wound healing in either acute or chronic settings, this has led to disparate views on the role of senescence in wound healing. This review aims to consolidate knowledge on the role of senescence and aging in wound healing, examining the nuances of the roles in the acute or chronic settings, and attempts to evaluate the modulation of this to promote efficient wound healing.

Cross-cultural comparison of the influence of skin-color change on facial impressions.

Skin color is one of the colors we are most frequently exposed to. It contains information, such as ethnic group and health status, and numerous studies have demonstrated the influence of various facial attributes on the formation of impressions. However, no research has specifically explored the repercussions of treating changes in skin color as a singular variable. We cross-culturally examined skin color changes along with the red-yellow axis and how they influence facial impressions across six face shapes from three types of ethnicities. A 7-point scale was used for evaluation, and the observers evaluated the impression of face images according to the following six evaluation items: healthiness, preference, brightness, whiteness, transparency, and skin tone. The observers were divided into the following four groups: Japan, China, Thailand, and the Caucasus. Differences in the evaluation and association of skin color with various traits emerged between cultures. For instance, East Asian cultures associated positive attributes with reddish skin colors, whereas Caucasians often linked positive traits with yellowish skin colors. These cultural disparities emphasize the dynamic interplay between culture and perception in assessing facial impressions.

Study to compare the efficacy of 50% glycolic acid with 65% trichloroacetic acid in the treatment of atrophic acne scar by CROSS technique.

Objectives: Acne scars often become challenging to treat with satisfactory results. The chemical reconstruction of skin scars (CROSS) technique has been used with high concentrations of trichloroacetic acid (TCA) which often produces unacceptable side effects. There is a dearth of data, with 50% glycolic acid (GA) for the same indication in the management of acne scars in the Indian population. This study aimed to assess the clinical response of acne scars after the application of 50% GA with that after the use of 65% TCA in a similar manner. Material and Methods: An institution-based prospective comparative study was performed with patients aged 16-45 years of either sex with acne scars and not been treated within the past 1 year. Subjects were assigned to receive one of the formulations (50% GA [Group A] and 65% TCA [Group B]). Grading of scars was done on day 1 and day 35 based on patients' assessment on a four-point visual scale and physicians' assessment by the Goodman-Baron qualitative global acne scar grading scale. The procedure was repeated every fortnightly for three such. Data were analyzed by Statistica version 6 (Tulsa, Oklahoma: StatSoft Inc. 2001). Results: The visual improvement scale of patients showed 41.38% (n = 12) fair improvement in group A, whereas 58.06% (n = 18) showed good improvement in group B. Grading by the Goodman-Baron scale showed 9.68% (n = 3) showed four grade changes in group B. Conclusion: Improvement is best observed with 65% TCA. Adverse effects were noted more with 65% TCA, especially acneiform eruption which was lacking in the previous studies. GA can be a safer alternative to TCA with acceptable results. Our study opens the scientific window for future research on different concentrations of GA as a CROSS agent.

The relationship of tooth shade and skin tone and its influence on smile attractiveness in native South Indians: A web-based cross sectional survey.

Objectives: This study aimed to investigate the influence of tooth shade and skin tone on smile attractiveness among native South Indians. The primary research question was whether there is a significant relationship between these variables and perceived smile attractiveness. Materials and methods: A web-based cross-sectional survey was conducted with approval from the Institutional Review Board of (Thai Moogambigai Dental College and Hospital, Chennai). Standardized smile photographs of two South Indian models (one male and one female) were digitally modified to display four different tooth shades and four different skin tones, resulting in 32 images. These images were incorporated into a Google Form along with a questionnaire and a Visual Analog Scale (VAS) for attractiveness rating. The survey was distributed to 1200 participants, including both dental professionals and the general population, with 1000 valid responses recorded. Statistical analysis was performed using IBM SPSS Statistics, employing parametric tests to evaluate the data. Results: The study found that lighter tooth shades were consistently rated higher in attractiveness for both genders. Lighter tooth shades such as FS1T1 and FS2T1 scored means of 6.88 and 7.27 respectively for females, while darker shades like FS1T4 scored lower with a mean of 4.95. Similarly, males showed a preference for lighter tooth shades with MS1T1 and MS2T1 scoring means of 5.57 and 5.78 respectively compared to darker shades like MS1T4 with a mean of 3.63. Significant differences were noted across age groups and genders, with younger participants and females showing a stronger preference for lighter tooth shades. Conclusions: The study concludes that both tooth shade and skin tone significantly influence smile attractiveness, with a clear preference for lighter tooth shades among the surveyed population. These findings suggest the importance of considering these factors in aesthetic dental treatments to enhance patient satisfaction and achieve optimal results. Clinical relevance: The results underscore the necessity for dental practitioners to take into account both tooth shade and skin tone when planning aesthetic dental treatments. This approach will help in achieving a more harmonious and natural appearance, ultimately improving patient satisfaction with the treatment outcomes. Future research should continue to explore the cultural and individual factors that contribute to these preferences in dental aesthetics.

Can salivary and skin microbiome become a biodetector for aging-associated diseases? Current insights and future perspectives.

Growth and aging are fundamental elements of human development. Aging is defined by a decrease in physiological activities and higher illness vulnerability. Affected by lifestyle, environmental, and hereditary elements, aging results in disorders including cardiovascular, musculoskeletal, and neurological diseases, which accounted for 16.1 million worldwide deaths in 2019. Stress-induced cellular senescence, caused by DNA damage, can reduce tissue regeneration and repair, promoting aging. The root cause of many age-related disorders is inflammation, encouraged by the senescence-associated secretory phenotype (SASP). Aging's metabolic changes and declining immune systems raise illness risk via promoting microbiome diversity. Stable, individual-specific skin and oral microbiomes are essential for both health and disease since dysbiosis is linked with periodontitis and eczema. Present from birth to death, the human microbiome, under the influence of diet and lifestyle, interacts symbiotically with the body. Poor dental health has been linked to Alzheimer's and Parkinson's diseases since oral microorganisms and systemic diseases have important interactions. Emphasizing the importance of microbiome health across the lifetime, this study reviews the understanding of the microbiome's role in aging-related diseases that can direct novel diagnosis and treatment approaches.

Skin conductance response and habituation to emotional facial expressions and words.

Skin conductance response (SCR) serves as a dependable marker of sympathetic activation used to measure emotional arousal. This study investigates the impact of presentation modality (face or word) on the degree of emotional discrimination elicited by SCR. Facial expressions or words associated with six basic emotions-anger, happiness, disgust, fear, sadness, and surprise-were studied among 102 participants. The amplitude of SCR was accurately predicted by subjective arousal ratings of these stimuli, but not by valence ratings. The habituation process to emotional and neutral stimuli across six successive presentations was characterized by an exponential decay function, capturing the rate at which SCR response diminishes in relation to the preceding trial of the same stimulus. Through the subtraction of the response to neutral stimuli from the emotion-evoked SCR, it was demonstrated that the initial presentation of each emotion elicits a substantial response, particularly attributable to the emotional content. Notably, the initial emotional response to faces expressing happiness, disgust, and sadness surpassed that of words conveying the same emotions. The results indicate that different emotional responses can be quantified using a simple electrical instrument.

Perindopril erbumine-entrapped ultradeformable liposomes alleviate sarcopenia via effective skin delivery in muscle atrophy mouse model.

Sarcopenia is a pertinent challenge in the super-aged societies causing reduced functional performance, poor quality of life and increased morbidity. In this study, the potential of perindopril erbumine-loaded ultradeformable liposomes (PE-UDLs) against sarcopenia was investigated. PE-UDLs were prepared by thin-film hydration and extrusion method using egg yolk phosphatidylcholine (EPC) as a lipid bilayer former and Tween 80 or sodium deoxycholate as an edge activator. Owing to the smallest particle size (75.0 nm) and the highest deformability (54.2) and entrapment efficiency (35.7 %), PE-UDLs with EPC to Tween 80 ratio of 8:2 was selected as the optimized formulation. The optimized PE-UDLs showed substantially higher cumulative amount of drug permeated and permeation rate across the rat skin compared to PE solution (485.7 vs. 50.1 µg and 13.4 vs. 2.3 µg/cm2/h, respectively). Topically applied PE-UDLs successfully ameliorated the effects of lipopolysaccharide (LPS)-induced sarcopenia in mice by improving body weight changes, grip strength and muscle weight. Furthermore, PE-UDLs reduced the shrinkage of muscle fibers as demonstrated by higher cross-sectional area than PE solution. PE-UDLs also increased the expression of myosin heavy chain (MHC) protein and reduced the expression of muscle atrophy F-box (Atrogin-1) and muscle ring-finger protein-1 (MuRF1), thereby improving muscles atrophy. In conclusion, these results demonstrate the therapeutic potential of PE-UDLs against sarcopenia.

Boron neutron capture therapy for cutaneous angiosarcoma and malignant melanoma: First in-human phase I clinical trial.

BACKGROUND AND PURPOSE: Definitive radiotherapy for patients with scalp angiosarcoma has a poor prognosis, often resulting in severe skin adverse events. Additionally, malignant melanoma is known for its radioresistant nature. Boron neutron capture therapy (BNCT) may address these challenges due to the high uptake capacity of boron drugs in these cancer types. We aimed to determine the treatment dose for BNCT and evaluate the incidence of acute adverse events AEs following BNCT in patients with primary or recurrent angiosarcoma/malignant melanoma of the skin. MATERIALS AND METHODS: This was a single-center, non-randomized clinical trial with a three-step dose escalation plan, involving maximum skin doses of 12, 15, and 18 Gy-Eq following a 3 + 3 design. The patients underwent BNCT between November 2019 and April 2022. The primary endpoint was to evaluate the incidence of acute adverse events. RESULTS: Ten patients (scalp angiosarcomanine, forefinger malignant melanoma: one) were included. The median target lesion size was 46.5 (range: 20-145) mm. A transient asymptomatic increase in serum amylase level was the only grade 3 adverse event. The best overall response rate within 180 days was 70 % (median tumor shrinkage rate: 77.5 % [4.9-100 %]). CONCLUSIONS: BNCT with a dose of 18 Gy-Eq is a feasible treatment option, demonstrating a favorable safety profile and a high response rate in patients with primary or recurrent angiosarcoma or malignant melanoma of the skin.

Biochemical analysis of soft tissue infectious fluids and its diagnostic value in necrotizing soft tissue infections: a 5-year cohort study.

BACKGROUND: Necrotizing soft tissue infections (NSTI) are rapidly progressing and life-threatening conditions that require prompt diagnosis. However, differentiating NSTI from other non-necrotizing skin and soft tissue infections (SSTIs) remains challenging. We aimed to evaluate the diagnostic value of the biochemical analysis of soft tissue infectious fluid in distinguishing NSTIs from non-necrotizing SSTIs. METHODS: This cohort study prospectively enrolled adult patients between May 2023 and April 2024, and retrospectively included patients from April 2019 to April 2023. Patients with a clinical suspicion of NSTI in the limbs who underwent successful ultrasound-guided aspiration to obtain soft tissue infectious fluid for biochemical analysis were evaluated and classified into the NSTI and non-necrotizing SSTI groups based on their final discharge diagnosis. Common extravascular body fluid (EBF) criteria were applied. RESULTS: Of the 72 patients who met the inclusion criteria, 10 patients with abscesses identified via ultrasound-guided aspiration were excluded. Based on discharge diagnoses, 39 and 23 patients were classified into the NSTI and non-necrotizing SSTI groups, respectively. Biochemical analysis revealed significantly higher albumin, lactate, lactate dehydrogenase (LDH), and total protein levels in the NSTI group than in the non-necrotizing SSTI group, and the NSTI group had significantly lower glucose levels and pH in soft tissue fluids. In the biochemical analysis, LDH demonstrated outstanding discrimination (area under the curve (AUC) = 0.955; p < 0.001) among the biochemical markers. Albumin (AUC = 0.884; p < 0.001), lactate (AUC = 0.891; p < 0.001), and total protein (AUC = 0.883; p < 0.001) levels also showed excellent discrimination. Glucose level (AUC = 0.774; p < 0.001) and pH (AUC = 0.780; p < 0.001) showed acceptable discrimination. When the EBF criteria were evaluated, the total scores of Light's criteria (AUC = 0.925; p < 0.001), fluid-to-serum LDH ratio (AUC = 0.929; p < 0.001), and fluid-to-serum total protein ratio (AUC = 0.927; p < 0.001) demonstrated outstanding discrimination. CONCLUSION: Biochemical analysis and EBF criteria demonstrated diagnostic performances ranging from acceptable to outstanding for NSTI when analyzing soft tissue infectious fluid. These findings provide valuable diagnostic insights into the recognition of NSTI. Further research is required to validate these findings.

Primary cutaneous infections with non-tuberculous mycobacteria: a report of 6 cases.

BACKGROUND: The incidence of non-tuberculous mycobacterium infection has shown a gradual increasing trend in recent years, among which cutaneous manifestations as an important aspect. This study aimed to describe the clinical features and microbiological findings in 6 cases of primary cutaneous nontuberculous mycobacterium infection. METHODS: In this retrospective study from June 2021 to June 2022, the clinical data and microbiological results of six cases diagnosed with primary cutaneous non-tuberculous mycobacterium infection in department of dermatology, Hangzhou Third People's Hospital were analyzed. RESULTS: All six cases were primary cutaneous non-tuberculous mycobacterium infections, four of which had a history of trauma or exposure, and two had an underlying disease that could lead to compromised immunity. All patients presented with erythema nodular skin lesions, four on the upper or lower extremities, one on the face, and one on the right hip. The histopathological findings of five patients who underwent biopsy were granulomatous inflammatory changes with mixed infiltration. Laboratory cultures using tissue or tissue fluid were all successful, including four Mycobacterium marinum, one Mycobacterium abscessus, and one Mycobacterium avium. Metagenomics next-generation sequencing detected results consistent with culture colonies in only two cases. With the exception of case 4, all patients responded well to oral medication, with a course of treatment ranging from 4 months to 1 year, and the prognosis was good. CONCLUSIONS: The clinical features of primary cutaneous non-tuberculous mycobacterium infection are often lacking in specificity, and the identification of related strains is difficult for a variety of reasons. Although the results of metagenomics next-generation sequencing are useful for pathogen spectrum identification, its diagnostic value should be carefully reevaluated under certain circumstances. Patients with suspected triggers who do not respond well to conventional treatments should be suspected as atypical infection and potential immunosuppression. If diagnosed and treated promptly, the prognosis of primary cutaneous non-tuberculous mycobacterium infection is generally good.

Determining the Mean Dermatology Life Quality Index of Skin of Color (SOC) Patients With Vitiligo: A South Asian Perspective.

BACKGROUND: Vitiligo has a special significance to the skin of colour (SOC) population because depigmentation is more obvious in the SOC population. As a result, vitiligo exerts a huge stigma on the affected individuals. The literature so far has reported on the health-related quality of life (QOL), including the dermatology life quality index (DLQI), and has demonstrated the profound effect of vitiligo on a patient's QOL. Those affected by vitiligo are found to have lower self-esteem when compared to the non-affected individuals. The impact on the SOC population is even graver and underrepresented. Thus, the objective of this study was to report the mean DLQI in vitiligo in SOC individuals. MATERIALS AND METHODS: This descriptive, cross-sectional study was performed in the dermatology outpatient department of a tertiary healthcare setup in Rawalpindi Pakistan. A total of 113 patients suffering from vitiligo, aged 15 to 65 years, both male and female, were included in the study. In all the cases, the DLQI score was noted. RESULTS:  With the age ranging from 15 to 65 years and a mean age of 34.96 ± 9.59 years, 70% (n=77) of the patients were between 15 to 40 years of age. The male-to-female ratio was 1:1.3, with male patients comprising 38.21% (n=47) and females being 61.79% (n=66). The mean DLQI score of the vitiligo patients in our cohort was 9.39 ± 6.35. CONCLUSION: This study concluded that the mean DLQI score was higher in female patients and in vitiligo universalis patients, compared to other variants of vitiligo. The SOC population affected with vitiligo is at a higher risk of having a decreased QOL and hence may need special attention with regard to quality health delivery services.

The Nasolabial Flap in Nose Reconstruction: Tips and Tricks Towards Expanded Usage and Optimized Cosmesis.

Background: The nose is the most critical aesthetic element of the face and even the smallest loss of substance can create a deformity of concern. The forehead flap has been the workhorse for nasal reconstruction for centuries but requires multiple surgical steps and leads to prominent donor-site scarring. The nasolabial flap allows a single-step reconstruction with a donor-site scar concealed in the nasolabial crease but is conventionally designated for small defects involving the ala. Methods: The authors analysed all surgical records of patients undergone nasal reconstruction by nasolabial flap between May 2005 and December 2021 by the Plastic Surgery Unit of a major regional hospital in Lombardy. Defects were classified according to Burget's subunit principle and the 3-component approach. Reconstruction features and finesses were reported and analysed. Results: In the 16-year period under analysis, 378 patients with nasal defects of various aetiologies received nose reconstruction by nasolabial flap. All nasal subunits were involved; 20 patients had multisubunit defects. In all the cases the reconstruction with nasolabial flap, alone or combined with other solutions, was intended to be one-stage. Conclusions: The authors present several tips and tricks about preoperative planning and design, choice of the pedicle, flap harvesting and sculpting with preservation/restoration of grooves and convexities, conjoining multiple flaps, downsizing extensive defects by a rhinoplasty-like framework reduction. With a careful planning and refined technique, the range of application of the nasolabial flap can include defects involving any nasal subunit and larger and/or multisubunit defects.

Historique: Le nez est l'élément esthétique primordial du visage, et même la plus petite perte de substance peut créer une malformation préoccupante. Le lambeau du front est utilisé pour la reconstruction nasale depuis des siècles, mais il est associé à de multiples étapes chirurgicales et entraîne des cicatrices importantes au foyer du donneur. Le lambeau nasolabial (ou nasogénien) favorise une reconstruction en une seule étape dissimulée dans le pli nasolabial, mais est habituellement conçu pour corriger de petites malformations de l'aile du nez. Méthodologie: Les auteurs ont analysé tous les dossiers chirurgicaux des patients qui avaient subi une reconstruction nasale par lambeau nasolabial entre mai 2005 et décembre 2021 à l'unité de chirurgie plastique d'un important hôpital régional de la Lombardie. Ils ont classé les malformations d'après le principe des sous-unités de Burget et l'approche en trois éléments. Ils ont également rendu compte des caractéristiques et des subtilités de la reconstruction et les ont analysées. Résultats: Au cours des 16 années analysées, 378 patients ayant des malformations nasales de diverses étiologies ont subi une reconstruction nasale par lambeau nasolabial. Toutes les sous-unités nasales étaient touchées. Ainsi, 20 patients présentaient de multiples malformations sous-unitaires. Dans tous les cas, la reconstruction à l'aide d'un lambeau nasolabial, seule ou combinée à d'autres solutions, était prévue en une étape. Conclusions: Les auteurs proposent plusieurs trucs et conseils au sujet de la planification et de la méthodologie préopératoires, du choix du pédicule, du prélèvement du lambeau et de la sculpture pour préserver ou restaurer les plis et les convexités, de la combinaison de multiples lambeaux, afin d'atténuer les malformations importantes par une réduction selon une structure similaire à celle de la rhinoplastie. Grâce à une planification attentive et une technique raffinée, l'éventail d'applications du lambeau nasolabial peut inclure les malformations touchant toutes les sous-unités nasales et les malformations sous-unitaires plus importantes ou multiples.

Case report of disseminated borrelial lymphocytoma with isolation of Borrelia burgdorferi sensu stricto in chronic lymphatic leukemia stage Binet A-an 11 year follow up.

We report a rare manifestation of cutaneous borreliosis in a patient with pre-existing malignant lymphoproliferative disease, in particular chronic lymphocytic B cell leukemia (B-CLL). The patient's cutaneous lesions were initially diagnosed histologically as leukemia cutis. Distribution pattern of the skin lesions were in typical localizations for borrelial lymphocytoma. Borrelia burgdorferi sensu stricto was isolated and cultured from two sites (ear, mammilla). Antibiotic therapy improved the cutaneous lesions and the general condition of the patient. However, a second round of antibiotic therapy was required to resolve the lesions. At eleven years of follow-up the patient's skin was clear and she still had a stable condition of B-CLL without chemotherapy. In conclusion, the patient suffered from Lyme borreliosis (Borrelia lymphocytoma) and the cutaneous symptoms were aggravated by the underlying condition of chronic B-CLL condition.

Skin senescence-from basic research to clinical practice.

The most recognizable implications of tissue aging manifest themselves on the skin. Skin laxity, roughness, pigmentation disorders, age spots, wrinkles, telangiectasia or hair graying are symptoms of physiological aging. Development of the senescent phenotype depends on the interaction between aging cells and remodeling of the skin's extracellular matrix (ECM) that contains collagen and elastic fiber. Aging changes occur due to the combination of both endogenous (gene mutation, cellular metabolism or hormonal agents) and exogenous factors (ultraviolet light, environmental pollutants, and unsuitable diet). However, overproduction of mitochondrial reactive oxygen species (ROS) is a key factor driving cellular senescence. Aging theories have disclosed a range of diverse molecular mechanisms that are associated with cellular senescence of the body. Theories best supported by evidence include protein glycation, oxidative stress, telomere shortening, cell cycle arrest, and a limited number of cell divisions. Accumulation of the ECM damage is suggested to be a key factor in skin aging. Every cell indicates a functional and morphological change that may be used as a biomarker of senescence. Senescence-associated ß-galactosidase (SA-ß-gal), cell cycle inhibitors (p16INK4a, p21CIP1, p27, p53), DNA segments with chromatin alterations reinforcing senescence (DNA-SCARS), senescence-associated heterochromatin foci (SAHF), shortening of telomeres or downregulation of lamina B1 constitute just an example of aging biomarkers known so far. Aging may also be assessed non-invasively through measuring the skin fluorescence of advanced glycation end-products (AGEs). This review summarizes the recent knowledge on the pathogenesis and clinical conditions of skin aging as well as biomarkers of skin senescence.