Non-lesional Areas Research Articles

Microbial imbalance in Darier disease: Dominance of various staphylococcal species and absence of Cutibacteria

Darier disease (DD) is a rare autosomal dominant genodermatosis characterized by erythematous papules and plaques mainly involving sebaceous areas, such as the face, chest and back. Skin microbiome plays an essential role in maintaining skin homeostasis. A disturbed skin microbiome may contribute to the exacerbation of DD. We investigated the bacterial composition of two predilectional sites in DD patients and healthy individuals. We also measured the microbiome composition of deeper skin layers, where diversity was significantly reduced compared to the superficial layer of the skin from the same area. The microbiome of DD patients at lesional sites differed from that of non-lesional skin areas; moreover, non-lesional sites were different from those of the controls. Lesional areas were dominated by Staphylococcus species, such as S. aureus, S. epidermidis, S. hominis, S. sciuri, and S. equorum. However, levels of Cutibacterium acnes (formerly Propionibacterium acnes) and C. acnes subspecies defendens were significantly lower in lesional sites than in non-lesional sites. A significant decrease was measured in the levels of these two bacteria between non-lesional and control samples. Our findings may indicate that alterations in the skin microbiome could contribute to the inflammation of skin lesions in DD.

Evidence of IL-17-secreting mast cells in scalp lesions of folliculitis decalvans points to new therapeutic targets in recalcitrant lesions.

Folliculitis decalvans (FD) is a chronic neutrophilic scarring alopecia which exact pathogenesis remains unknown. The recent report on the successful use of a novel anti-IL17 biologic agent in FD and the presence of IL-17-secreting mast cells in other types of scarring alopecias point to a distinct pathogenic mechanism in this disease. Our aim was to study and correlate the expression of IL-17 and mast cells in lesional and non-lesional FD scalp, using immunohistochemical techniques. Increased expression in IL-17 and mast cells was found in lesional scalp compared to non-lesional scalp areas (p<.05). A significant positive correlation between IL-17 and Mast cell Tryptase immunolabeling in non-lesional scalp (r=.64) highlights the role of IL-17-secreting mast cells in "normal-appearing" sites of FD. These findings suggest that targeting both IL-17 and mast cells may be potentially beneficial to better control the chronic inflammatory status of the disease specially in recalcitrant cases of FD.

Characterization of the forehead skin microbiome in the early phase of acne.

The skin microbiota is known to be imbalanced in acne vulgaris, but the changes occurring during the early stages of acne onset remain poorly described. To characterize the skin microbiome of subclinical stages of acne in adults and adolescents. The composition and diversity of the microbiota from non-lesional skin on the forehead of subjects with mild-to-moderate acne were compared to the ones from non-acne subjects. Analyses of skin swab samples were performed using high-throughput sequencing of the V1-V3 regions of the bacterial 16S ribosomal RNA gene, the tuf gene fragment of Staphylococcus species and the internal transcribed spacer (ITS1) region of the fungal rRNA gene to determine the relative abundance, alpha-diversity and beta-diversity of bacteria and fungi. Compared with non-acne subjects, acne subjects had a higher abundance of Cutibacterium (72.4% vs. 57.8%) and lower abundances of Corynebacterium (2.8% vs. 4.8%) and Streptococcus (1.4% vs. 3.2%). Bacterial alpha- and beta-diversity indices also differed significantly between the two groups, reflecting differences in richness, evenness, abundance and phylogenetic distance between bacterial populations. Differences were also observed at the level of Staphylococcus species: S. capitis was predominant in skin samples from non-acne subjects (46.7%), whereas S. epidermidis was the most abundant Staphylococcus species in non-lesional forehead skin areas of acne subjects (44.2%). Conversely, no significant between-group differences were found for fungi, with Malasseziales being the predominant order in both subject groups. Dysbiosis was observed very early in subclinical acne stages of the forehead skin, with the overall abundance, richness and evenness of the bacterial population being lower in acne than in non-acne skin samples. Dysbiosis was also found at the level of Staphylococcus species. The development of acne lesions could therefore be prevented by using a skin care product that rebalances facial skin microbiota at very early stages.

Comparative Whole Metagenome Analysis in Lesional and Nonlesional Scalp Areas of Patients with Psoriasis Capitis and Healthy Individuals

Psoriasis is an immune-mediated inflammatory disorder, where the majority of the patients suffer from psoriasis capitis or scalp psoriasis. Current therapeutics remain ineffective to treat scalp lesions. Here, we present a whole-metagenome characterisation of the scalp microbiome in psoriasis capitis. We investigated how changes in the homeostatic cutaneous microbiome correlate with the condition and identified metagenomic biomarkers (taxonomic, functional, virulence factors, antimicrobial resistance genes) that could partly explain its emergence. Within this study, 83 top and back scalp samples from healthy individuals and 64 lesional and non-lesional scalp samples from untreated psoriasis capitis subjects were analysed. Using qPCR targeting the 16S and 18S rRNA genes, we found a significant decrease in microbial load within scalp regions affected by psoriasis compared to their non-lesional counterparts. Metagenomic analysis revealed that psoriatic lesions displayed significant lower Cutibacterium species (incl. C. modestum, C. namnetense, C. granulosum, C. porci), along with an elevation in Staphylococcus aureus. A heightened relative presence of efflux pump protein-encoding genes was detected, suggesting potential antimicrobial resistance mechanisms. These mechanisms are known to specifically target human antimicrobial peptides (incl. cathelicidin LL-37) which are frequently encountered within psoriasis lesions. These shifts in microbial community dynamics may contribute to psoriasis disease pathogenesis.

Adiponectin Prevents Skin Inflammation in Rosacea by Suppressing S6 Phosphorylation in Keratinocytes

Numerous recent evidence highlights epidemiological connections between rosacea and metabolic disorders. However, the precise path through which metabolic factors impact rosacea risk is still unclear. Therefore, this study aims to investigate the role of adiponectin, a crucial adipokine that regulates metabolic homeostasis, in the pathogenesis of rosacea. We elucidated a detrimental feedback loop between rosacea-like skin inflammation and decreased levels of skin adiponectin. To elaborate, rosacea lesional skin exhibits diminished adiponectin expression compared to non-lesional areas in the same patients. Induction of rosacea-like inflammation reduced adiponectin levels in the skin by generating inflammatory cytokines that suppress adiponectin production from subcutaneous adipocytes. Conversely, complete depletion of adiponectin exacerbated rosacea-like features in the mouse model. Mechanistically, adiponectin deficiency led to heightened S6 phosphorylation, a marker of the mTORC1 signaling pathway, in the epidermis. Adiponectin significantly inhibited S6 phosphorylation in cultured keratinocytes. Notably, replenishing adiponectin whole protein or topically applying an agonist for adiponectin receptor 1 successfully improved rosacea-like features in mice. This study contributes to understanding the role of adiponectin in skin inflammation associated with rosacea pathophysiology, suggesting that restoring adiponectin function in the skin could be a potential therapeutic strategy.

Exploratory multi-omics analysis reveals host-microbe interactions associated with disease severity in psoriatic skin

Psoriasis (Pso) is a chronic inflammatory skin disease that poses both physical and psychological challenges. Dysbiosis of the skin microbiome has been implicated in Pso, yet a comprehensive multi-omics analysis of host-microbe interactions is still lacking. To bridge this gap, we conducted an exploratory study by adopting the integrated approach that combines whole metagenomic shotgun sequencing with skin transcriptomics. This was a cross-sectional study, adult patients with plaque-type Psoriasis (Pso) and healthy volunteers were included. Skin microbiota samples and biopsies were collected from both lesional and non-lesional skin areas on the lower back. Weighted Gene Correlation Network Analysis (WGCNA) was employed for co-expression network analysis, and cell deconvolution was conducted to estimate cell fractions. Taxonomic and functional features of the microbiome were identified using whole metagenomic shotgun sequencing. Association between host genes and microbes was analyzed using Spearman correlation. Host anti-viral responses and interferon-related networks were identified and correlated with the severity of psoriasis. The skin microbiome showed a greater prevalence of Corynebacterium simulans in the PASI severe-moderate groups, which correlated with interferon-induced host genes. Two distinct psoriatic clusters with varying disease severities were identified. Variations in the expression of cell apoptosis-associated antimicrobial peptides (AMPs) and microbial aerobic respiration I pathway may partly account for these differences in disease severity. Our multi-omics analysis revealed for the first time anti-viral responses and the presence of C.simulans associated with psoriasis severity. It also identified two psoriatic subtypes with distinct AMP and metabolic pathway expression. Our study provides new insights into understanding the host-microbe interaction in psoriasis and lays the groundwork for developing subtype-specific strategies for managing this chronic skin disease. The research has received funding from the FP7 (MAARS-Grant 261366) and the Innovative Medicines Initiative 2 Joint Undertaking (JU) under grant agreement No 821511 (BIOMAP). The JU receives support from the European Union's Horizon 2020 research and innovation programme and EFPIA. This publication reflects only the author's view and the JU is not responsible for any use that may be made of the information it contains. GAM was supported by a scholarship provided by CAPES-PRINT, financed by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES (Brazilian Government Agency). The authors thank all patients who participated in our study.

A role for vessel-associated extracellular matrix proteins in multiple sclerosis pathology.

Multiple sclerosis (MS) is unsurpassed for its clinical and pathological hetherogeneity, but the biological determinants of this variability are unknown. HLA-DRB1*15, the main genetic risk factor for MS, influences the severity and distribution of MS pathology. This study set out to unravel the molecular determinants of the heterogeneity of MS pathology in relation to HLA-DRB1*15 status. Shotgun proteomics from a discovery cohort of MS spinal cord samples segregated by HLA-DRB*15 status revealed overexpression of the extracellular matrix (ECM) proteins, biglycan, decorin, and prolargin in HLA-DRB*15-positive cases, adding to established literature on a role of ECM proteins in MS pathology that has heretofore lacked systematic pathological validation. These findings informed a neuropathological characterisation of these proteins in a large autopsy cohort of 41 MS cases (18 HLA-DRB1*15-positive and 23 HLA-DRB1*15-negative), and seven non-neurological controls on motor cortical, cervical and lumbar spinal cord tissue. Biglycan and decorin demonstrate a striking perivascular expression pattern in controls that is reduced in MS (-36.5%, p = 0.036 and - 24.7%, p = 0.039; respectively) in lesional and non-lesional areas. A concomitant increase in diffuse parenchymal accumulation of biglycan and decorin is seen in MS (p = 0.015 and p = 0.001, respectively), particularly in HLA-DRB1*15-positive cases (p = 0.007 and p = 0.046, respectively). Prolargin shows a faint parenchymal pattern in controls that is markedly increased in MS cases where a perivascular deposition pattern is observed (motor cortex +97.5%, p = 0.001; cervical cord +49.1%, p = 0.016). Our findings point to ECM proteins and the vascular interface playing a central role in MS pathology within and outside the plaque area. As ECM proteins are known potent pro-inflammatory molecules, their parenchymal accumulation may contribute to disease severity. This study brings to light novel factors that may contribute to the heterogeneity of the topographical variation of MS pathology.

Regulation of the Immune Cell Repertoire in Psoriasis Patients Upon Blockade of IL-17A or TNFα.

Targeting of the proinflammatory cytokine interleukin 17A (IL-17A) or tumor necrosis factor alpha (TNFα) with the monoclonal antibodies (mAbs) ixekizumab or adalimumab, respectively, is a successful therapy for chronic plaque psoriasis. The effects of these treatments on immune cell populations in the skin are largely unknown. In this study, we compared the composition of cutaneous, lesional and non-lesional immune cells and blood immune cells in ixekizumab- or adalimumab-treated patients with psoriasis. Our data reveal that both treatments efficiently downregulate T cells, macrophages and different subsets of dendritic cells (DCs) in lesional skin towards levels of healthy skin. In contrast to lesional skin, non-lesional areas in patients harbor only few or no detectable DCs compared to the skin of healthy subjects. Treatment with neither ixekizumab nor adalimumab reversed this DC imbalance in non-lesional skin of psoriatic patients. Our study shows that anti-IL-17A and anti-TNFα therapy rebalances the immune cell repertoire of lesional skin in psoriatic patients but fails to restore the disturbed immune cell repertoire in non-lesional skin.

Advancements in non-invasive skin sampling: Clinical conditions characterization via the assessment of skin surface cytokine biomarkers.

The skin is increasingly recognized as a biological active organ interacting with the immune system. Given that the epidermal skin layer actively releases various cytokines, non-invasive skin sampling methods could detect these cytokines, offering insights into clinical conditions. This study aims non-invasively measuring cytokine levels directly from the skin surface to characterize different inflammatory chronic disorders in the adult and elderly population: psoriasis, diabetes type 2, rosacea, chronic kidney disease (CKD) and aging. Cytokines IL-1β, IL-8 and IL-10 were sampled from healthy subjects and patients aged 18-80 using skin surface wash technique. A well with sterile phosphate-buffered saline solution was placed on the skin for 30 min, and the extracted solution was collected from the well for further cytokine levels analysis using ELISA assay. Results show distinct cytokine profiles in different pathological processes, healthy controls, affected and unaffected areas. Aging was associated with increased IL-1β, IL-8, and IL-10 levels in skin. In diabetes, IL-1β and IL-8 levels were elevated in lesional areas, while IL-10 levels were decreased in non-lesional skin. Psoriatic lesions showed elevated levels of IL-1β and IL-8. Rosacea patients had lower IL-10 levels in both lesional and non-lesional areas. CKD patients exhibited significantly lower IL-10 levels compared to healthy individuals. In conclusion, skin surface wash-derived cytokine profiles could serve as "alert biomarkers" for disease prediction, enabling early detection. Additionally, this method's cost-effectiveness allows pre-screening of molecules in clinical studies and holds potential as a tool for biomarkers and omics analysis, enhancing disorder characterization and disease management.

SCF and IL-33 regulate mouse mast cell phenotypic and functional plasticity supporting a pro-inflammatory microenvironment

Mast cells (MCs) are multifaceted innate immune cells often present in the tumor microenvironment (TME). Several recent findings support their contribution to the transition from chronic inflammation to cancer. However, MC-derived mediators can either favor tumor progression, inducing the spread of the tumor, or exert anti-tumorigenic functions, limiting tumor growth. This apparent controversial role likely depends on the plastic nature of MCs that under different microenvironmental stimuli can rapidly change their phenotype and functions. Thus, the exact effect of unique MC subset(s) during tumor progression is far from being understood. Using a murine model of colitis-associated colorectal cancer, we initially characterized the MC population within the TME and in non-lesional colonic areas, by multicolor flow cytometry and confocal microscopy. Our results demonstrated that tumor-associated MCs harbor a main connective tissue phenotype and release high amounts of Interleukin (IL)-6 and Tumor Necrosis Factor (TNF)-α. This MC phenotype correlates with the presence of high levels of Stem Cell Factor (SCF) and IL-33 inside the tumor. Thus, we investigated the effect of SCF and IL-33 on primary MC cultures and underscored their ability to shape MC phenotype eliciting the production of pro-inflammatory cytokines. Our findings support the conclusion that during colonic transformation a sustained stimulation by SCF and IL-33 promotes the accumulation of a prevalent connective tissue-like MC subset that through the secretion of IL-6 and TNF-α maintains a pro-inflammatory microenvironment.

Scratching increases epidermal neuronal branching and alters psychophysical testing responses in atopic dermatitis and brachioradial pruritus.

Chronic scratching imposes a major stress on the skin and can lead to itch intensity worsening, and consequently, patients may enter an itch-scratch cycle. This repetitive mechanical stress can result in lichenification, worsening of epidermal barrier function, and enhanced cutaneous inflammation. Furthermore, a reduction of intraepidermal nerve fibers was previously described in lichenification. The aim of this study was to investigate the influence of chronic scratching on the epidermal neuroanatomy and on sensory changes, in particular the prevalence of hyperknesis and alloknesis in patients after mechanical, chemical, and electrical stimuli. Analyses were performed on pruritic lichenified (chronically scratched), pruritic non-lichenified (not chronically scratched), and non-pruritic non-lesional (unaffected) skin areas of patients with inflammatory pruritus, i.e., atopic dermatitis (n = 35), and neuropathic pruritus, i.e., brachioradial pruritus (n = 34) vs. healthy matched controls (n = 64). Our fine-grained spatial skin characterization enabled specifically studying the differential effects of chronic scratching in inflammatory and neuropathic itch. Analysis of intraepidermal nerve fiber density showed rarefaction of fibers in all three skin areas of patients compared with healthy controls in both diagnoses. Even more, the two pruritic areas had significantly less nerve fibers than the unaffected skin, whereas electrically induced itch was massively increased. Epidermal branching of the remaining nerve fibers in lichenified/chronically scratched skin was increased, particularly in patients with brachioradial pruritus, which may contribute to the pronounced local neuronal sensitivity. Hyperknesis and alloknesis were found to increase independently of lichenification. Our results indicate that chronic scratching may not affect intraepidermal nerve fiber density but leads to a stronger branching pattern of intraepidermal nerve fibers, which may contribute to local hypersensitivity. The increased sensitivity in the pruritic areas suggests mechanisms of peripheral sensitization, whereas the increased sensation of electrically and chemically induced itch in unaffected skin indicates central sensitization for itch.

Expression and Function of VEGFRs in Normal Epidermis and Psoriatic Lesional Keratinocytes.

The study aimed to explore the expression and function of VEGFRs in normal epidermis and keratinocytes of psoriatic lesions. In this study, the expression and role of VEGFRs in keratinocytes were examined using examples from psoriatic and healthy individuals. The experiment was completed by immunofluorescence analysis, reverse transcription polymerase chain reaction, Western blot, and real-time quantitative RT-PCR after the skin of nonlesional, adjacent, and lesional skin was excised. Observations indicated that in non-lesional psoriatic areas and adjacent lesional areas of the skin of psoriasis patients, the fluorescent signals of VEGFR-1 and VEGFR-2 were strongly labelled with keratinocytes, and in psoriatic lesions, keratinocytes were present throughout the entire thickness of the epidermis, with the exception of the stratum corneum. The distribution of VEGFR-3 in psoriatic nonlesional and adjacent lesional skin was consistent with that in normal epidermis, whereas all layers of the epidermis of psoriatic lesions expressed VEGFR-3. The mRNA expression levels of VEGFR-1,2,3 steadily increased from the normal epidermis to the psoriatic nonlesional, adjacent lesional, and perilesional areas, with the lesional epidermis' keratinocytes exhibiting the greatest levels of mRNA expression. Ca ions upregulate VEGFR-1,2,3 mRNA and protein expression in keratinocytes of nonlesional areas of psoriasis. VEGFRs protein expression and cortical IOD values of psoriatic and normal population cells showed a positive correlation. Hence, in comparison to normal epidermal keratinocytes, psoriatic lesional regions' keratinocytes considerably enhanced their expression of VEGFR-1,2,3 mRNA and protein. The overexpression of VEGFR-1,2,3 in psoriatic lesions may be encouraged by VEGF and Ca þ ions.

Microbiological assessment of the effectiveness of standard therapy in atopic dermatitis

Background. Atopic dermatitis is an inflammatory skin disease characterized by recurrent lesions and intense pruritus. Nowadays there is a stepwise approach to the treatment of atopic dermatitis, which is defined by disease intensity and complications such as secondary skin infections. However, the current management of atopic dermatitis may not always lead to the expected outcome due to not only immune dysregulation of both adaptive and innate immunity but also imbalance of the skin microbiome.&#x0D; Aims. The aim of the study was to evaluate changes in the composition of the skin microbiome in both lesional and non-lesional skin in patients with atopic dermatitis during standard treatment.&#x0D; Materials and methods. Twenty patients with atopic dermatitis and twenty six healthy controls over 18 years old were included into the study. All microbiome samples were obtained from lesional and non-lesional skin sites of atopic dermatitis patients before and after therapy. Whereas samples from healthy controls were taken once from a flexor surface of the elbow. Species identification of clinical isolates were identified using MALDI Biotyper Sirius (Bruker Daltonics).&#x0D; Results. At baseline, the prevalence of S. aureus colonization among patients with atopic dermatitis was 34.20% in lesional skin and 32.50% in non-lesional skin. After treatment, there was a significant decrease in the prevalence of S. aureus carriage in both lesional and non-lesional skin areas (р 0.05). However, no significant difference was observed in the proportion of all other staphylococci (р 0.1). Interestingly, S. aureus was not found in healthy controls.&#x0D; Conclusions. The results of the study demonstrated the effectiveness of standard therapy for managing patients with atopic dermatitis as it had a positive impact on the skin microbial community and showed a decrease in S. aureus proportion after the treatment.

The Interplay between Bioactive Sphingolipids in the Psoriatic Skin and the Severity of the Disease.

Psoriasis is a complex chronic immunologically mediated disease that may involve skin, nails, and joints. It is characterized by hyperproliferation, deregulated differentiation, and impaired apoptosis of keratinocytes. Sphingolipids, namely ceramide, sphingosine-1-phosphate, sphingosine, sphingomyelin, and sphinganine-1-phosphate, are signal molecules that may regulate cell growth, immune reactions, and apoptosis. Fifteen patients with psoriasis and seventeen healthy persons were enrolled in the study. Skin samples were taken from psoriatic lesions and non-lesional areas. Tissue concentration of ceramides, sphingosine-1-phosphate, sphingosine, sphingomyelin, and sphinganine-1-phosphate was measured by liquid chromatography. We assessed that all levels of ceramides, sphingosine-1-phosphate, sphingosine, sphingomyelin, and sphinganine-1-phosphate were higher in lesioned psoriatic skin than in non-affected skin. The profile of bioactive lipids in the lesional skin of patients with psoriasis differed significantly from non-involved psoriatic skin and skin in healthy subjects.

Selenium disulfide: a key ingredient to rebalance the scalp microbiome and sebum quality in the management of dandruff

Dandruff is a chronic and relapsing scalp condition characterized by flaky scalp. Environmental and host factors (exposome) may alter the sebaceous gland activity, sebum composition, epidermal barrier function, and scalp microbiome balance, resulting in dandruff. Selenium disulfide (SeS2) improves the clinical signs of dandruff. To investigate the mode of action of SeS2 shampoo during treatment and relapse phases. Two single-center studies assessed dandruff severity, subjective efficacy perception, microbial balance, microbiota diversity and sebum lipids. SeS2 significantly (p≤0.01) reduced scaling and led to a significant decrease of Malassezia and Staphylococcus spp. counts in both lesional and non-lesional areas, compared to the vehicle at D28 returning to baseline levels at D56. Cutibacterium spp. levels were not different between the SeS2 and the vehicle treatment groups but had significantly increased with SeS2 (p<0.001) in the lesional zone at D56. The ratio Malassezia spp./Cutibacterium spp. decreased significantly in lesional zones compared to baseline levels, at both D28 and D35 (p<0.001). The total squalene content significantly increased (p<0.05), whereas peroxided squalene had significantly decreased by almost 50% at D31. The ratio triglycerides/free fatty acids significantly (p<0.0001) increased, almost 5-fold, between D0 and D31. SeS2 shampoo was very well tolerated. SeS2 is beneficial in scalp dandruff, even after treatment interruption. It is well tolerated, rebalances the equilibrium between the main bacterial and fungal populations, and improves sebum quality.

Intra– and inter–hemispheric network dynamics supporting object recognition and speech production

We built normative brain atlases that animate millisecond-scale intra- and inter-hemispheric white matter-level connectivity dynamics supporting object recognition and speech production. We quantified electrocorticographic modulations during three naming tasks using event-related high-gamma activity from 1,114 nonepileptogenic intracranial electrodes (i.e., non-lesional areas unaffected by epileptiform discharges). Using this electrocorticography data, we visualized functional connectivity modulations defined as significant naming-related high-gamma modulations occurring simultaneously at two sites connected by direct white matter streamlines on diffusion-weighted imaging tractography. Immediately after stimulus onset, intra- and inter-hemispheric functional connectivity enhancements were confined mainly across modality-specific perceptual regions. During response preparation, left intra-hemispheric connectivity enhancements propagated in a posterior-to-anterior direction, involving the left precentral and prefrontal areas. After overt response onset, inter- and intra-hemispheric connectivity enhancements mainly encompassed precentral, postcentral, and superior-temporal (STG) gyri. We found task-specific connectivity enhancements during response preparation as follows. Picture naming enhanced activity along the left arcuate fasciculus between the inferior-temporal and precentral/posterior inferior-frontal (pIFG) gyri. Nonspeech environmental sound naming augmented functional connectivity via the left inferior longitudinal and fronto-occipital fasciculi between the medial-occipital and STG/pIFG. Auditory descriptive naming task enhanced usage of the left frontal U-fibers, involving the middle-frontal gyrus. Taken together, the commonly observed network enhancements include inter-hemispheric connectivity optimizing perceptual processing exerted in each hemisphere, left intra-hemispheric connectivity supporting semantic and lexical processing, and inter-hemispheric connectivity for symmetric oral movements during overt speech. Our atlases improve the currently available models of object recognition and speech production by adding neural dynamics via direct intra- and inter-hemispheric white matter tracts.

Change in Cutibacterium acnes phylotype abundance and improvement of clinical parameters using a new dermocosmetic product containing Myrtus communis and Celastrol enriched plant cell culture extracts in patients with acne vulgaris.

Acne is a multifactorial chronic inflammatory disease of the pilosebaceous unit, where Cutibacterium acnes plays a main role. Recent papers demonstrated that specific C.acnes phylotypes were correlated with the severity of inflammatory acne and reported a specific loss of C.acnes phylotype diversity in this context. The aim of this exploratory study was to evaluate the efficacy of a new dermocosmetic product containing Myrtus communis and Celastrol-enriched plant cell culture extracts on C.acnes phylotype abundance and clinical parameters in subjects with mild to moderate acne vulgaris. Cutibacterium acnes phylotype diversity was evaluated by single-locus sequence typing sequencing on the nonlesional areas of the forehead, that is, areas excluding inflammatory lesions (papules and pustules) on day 1 (D1) and after 56 days (D57) of twice daily application of the dermocosmetic product on the whole face. Clinical efficacy on acne was also assessed by acne lesion counting and Global Evaluation Acne (GEA) score on D1 and D57. Our study confirmed the link between the presence of some C.acnes phylotypes and acne severity. The dermocosmetic cream was linked to a positive impact on C.acnes phylotypes: a significant decrease in pro-pathogen phylotype IC and increase in nonpathogen phylotype IB were observed in the nonlesional areas of acne on D57 compared to D1. In parallel, the clinical results showed a significant decrease in inflammatory and comedonal acne lesions and a significant improvement in the acne severity according to the GEA score. This study showed that the application of a new dermocosmetic product containing M.communis and Celastrol-enriched plant cell culture extracts was linked to a change in the C.acnes phylotype abundance and an improvement in acne severity.

Improvement of Nonlesional Skin Tone and Skin Barrier in Severe Atopic Dermatitis after Dupilumab Treatment

Dupilumab, approved for the treatment of moderate‐to‐severe atopic dermatitis (AD), has been proven to improve skin barrier and postinflammatory hyperpigmentation on nonlesional areas. Previous studies, however, are only based on subjective visual assessments rather than objective biophysical measurements. We aimed to objectively measure transepidermal water loss (TEWL) and skin tone improvements after dupilumab treatment through bioengineering devices. Nineteen patients with severe AD were enrolled. Biophysical measurements were conducted in three nonlesional skin areas, the cheek, forearm, and lower abdomen, on a monthly basis for 5 months since the first dupilumab injection. TEWL was measured using a Tewameter®. Skin tones represented by L∗ (lightness), a∗ (redness), and b∗ (yellowness) parameters were measured by the spectrophotometer®; the erythema and melanin index measured by the narrow‐band reflectance spectrophotometer® were additionally assessed. Improvement from baseline was evaluated by the Wilcoxon’s rank‐sum test and Bonferroni correction. Correlation among biophysical parameters was evaluated by Pearson’s correlation. p &lt; 0.05 was considered statistically significant. TEWL and skin tone parameters in all anatomical regions showed significant improvement. The L∗ and a∗ values of the arm and trunk significantly improved after 2 months of dupilumab therapy and the face 3 months after. Similarly, b∗ value of all anatomical regions significantly decreased after 1 month of treatment, and the TEWL did so after 2 months. When compared between anatomic regions, the trunk demonstrated higher improvement in L∗ value, the arm in erythema index, and the face in melanin index. TEWL positively correlated with erythema index (r = 0.51, p &lt; 0.05), melanin index (r = 0.45, p &lt; 0.05), and a∗ (r = 0.50, p &lt; 0.05); negative correlation was observed with L∗ (r = −0.48, p &lt; 0.05). On top of AD symptom relief, dupilumab objectively improves the skin barrier and skin tone of nonlesional areas.

Can angiographic Flat Detector Computed Tomography blood volume measurement be used to predict final infarct size in acute ischemic stroke?

Introduction and purposeFlat detector computed tomography (FD-CT) technology is becoming more widely available in the angiography suites of comprehensive stroke centers. In patients with acute ischemic stroke (AIS), who are referred for endovascular therapy (EVT), FD-CT generates cerebral pooled blood volume (PBV) maps, which might help in predicting the final infarct area. We retrospectively analyzed pre- and post-recanalization therapy quantitative PBV measurements in both the infarcted and hypoperfused brain areas of AIS patients referred for EVT. Materials and methodsWe included AIS patients with large vessel occlusion in the anterior circulation referred for EVT from primary stroke centers to our comprehensive stroke center. The pre- and post-recanalization FD-CT regional relative PBV (rPBV) values were measured between ipsilateral lesional and contralateral non-lesional areas based on final infarct area on post EVT follow-up cross-sectional imaging. Statistical analysis was performed to identify differences in PBV values between infarcted and non-infarcted, recanalized brain areas. ResultsWe included 20 AIS patients. Mean age was 63 years (ranging from 36 to 86 years). The mean pre- EVT rPBV value was 0.57 (±0.40) for infarcted areas and 0.75 (±0.43) for hypoperfusion areas. The mean differences (Δ) between pre- and post-EVT rPBV values for infarcted and hypoperfused areas were respectively 0.69 (±0.59) and 0.69 (±0.90). We found no significant differences (p > 0.05) between pre-EVT rPBV and ΔrPBV values of infarct areas and hypoperfusion areas. ConclusionAngiographic PBV mapping is useful for the detection of cerebral perfusion deficits, especially in combination with the fill run images. However, we were not able to distinguish irreversibly infarcted tissue from potentially salvageable, hypoperfused brain tissue based on quantitative PBV measurement in AIS patients.

A Single Center, Prospective, Randomized, Blinded Study to Evaluate the Efficacy and Safety of a Topical Tripeptide/Hexapeptide Anhydrous Gel When Used Pre- and Post- Hybrid Fractional Laser for the Treatment of Acne Scars.

Acne scarring remains a significant problem. Laser therapy has produced varying results with deeper ablative therapies occasionally associated with side effects including delayed healing, infection, scarring, erythema, acne, milia, edema and dyspigmentation. Can adjuvant topical therapy impact the healing process and outcome of patients treated with fractional laser for acne scarring? Ten patients were randomized to receive either Regenerating Skin Nectar with TriHex Technology®- RSN or a bland moisturizer. Patients underwent two laser procedures one month apart with Hybrid Fractional Laser. The topical was applied twice daily for 2 weeks prior to the first laser procedure, and through completion of the study. Seven study visits occurred over a 90-day period. Measurements were conducted in lesional and non-lesional areas - transepidermal water loss (TEWL), erythema, photography, Goodman and Baron qualitative scale, Global Aesthetic Improvement Scale and patient questionnaires - to assess functional recovery and aesthetic outcomes in the scarred areas. One patient from each cohort consented to biopsy before the procedures and 90 days after the first procedure. Reduced TEWL scores in the RSN group were evident at all time points with statistically significant reductions occurring 4 days after first and second procedures indicating more efficient fluid conservation at a critical point in the healing trajectory. Erythema index demonstrated a consistent decrease in the RSN cohort over the control from day 4 through day 90 on lesional and non-lesional skin. Acne scar assessment scores improved in the RSN cohort compared with the control at all time points. Biopsy results showed early elastin regeneration in the RSN biopsy with controlled non-hypertrophic collagen formation evident. The use of RSN pre- and post- laser resurfacing significantly decreased postprocedural TEWL and erythema, and increased aesthetic improvement in acne scars and patient satisfaction, when compared with bland moisturizer.