Testing the Reliability of Optical Coherence Tomography to Measure Epidermal Thickness and Distinguish Volar and Nonvolar Skin.

In persons with limb loss, prosthetic devices cause skin breakdown, largely because residual limb skin (nonvolar) is not intended to bear weight such as palmoplantar (volar) skin. Before evaluation of treatment efficacy to improve skin resiliency, efforts are needed to establish normative data and assess outcome metric reliability. The purpose of this study was to use optical coherence tomography to (i) characterize volar and nonvolar skin epidermal thickness and (ii) examine the reliability of optical coherence tomography. Four orientations of optical coherence tomography images were collected on 33 volunteers (6 with limb loss) at 2 time points, and the epidermis was traced to quantify thickness by 3 evaluators. Epidermal thickness was greater (P < .01) for volar skin (palm) (265.1 ± 50.9 µm, n = 33) than for both nonvolar locations: posterior thigh (89.8 ± 18.1 µm, n = 27) or residual limb (93.4 ± 27.4 µm, n = 6). The inter-rater intraclass correlation coefficient was high for volar skin (0.887-0.956) but low for nonvolar skin (thigh: 0.292-0.391, residual limb: 0.211-0.580). Correlation improved when comparing only 2 evaluators who used the same display technique (palm: 0.827-0.940, thigh: 0.633-0.877, residual limb: 0.213-0.952). Despite poor inter-rater agreement for nonvolar skin, perhaps due to challenges in identifying the dermal-epidermal junction, this study helps to support the utility of optical coherence tomography to distinguish volar from nonvolar skin.

Positive correlation of hidradenitis suppurativa and ultra-processed foods consumption.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition whose pathogenesis is not well established. An association between HS and obesity is suggested but few studies explore specific dietary drivers. Non-Hispanic Blacks have the highest HS prevalence and obesity rates as well as the highest UPFs consumption rates, as opposed to Hispanics who have the lowest prevalence of HS despite having the second highest obesity rates in the US. Instead, Hispanics have the lowest UPFs consumption and highest minimally processed foods consumption rates in the US. Since HS appears to correlate more with processed food intake than obesity, we explored this connection more carefully. To identify correlations, we cross referenced 3 sources: (1) relative search volume (RSV) on Google Searches for HS. (2) Published data on prevalence of HS and UPFs consumption by nation, state, race, and age. (3) NHANES data on variation of diet patterns in the US. We identified a strong correlation of RSV and UPFs and HS by country (r = 0.83, p < 0.0001) and state in the US (r = 0.82, p < 0.0001) compared to a negative control (melanoma with UPFs; r = 0.35, p = 0.14 by country and r = 0.22, p = 0.23 by state). The variation in searches for HS from 2004 till 2018 (p < 0.0001) was strongly correlated with the increase in UPFs consumption (r = 0.79, p = 0.019) and inversely correlated with the decrease in minimally-processed foods consumption in the US (r = - 0.941, p = 0.0005). These results suggest an association between UPFs consumption and HS, and the need for future studies to address whether limiting UPFs might ameliorate HS.

Particulate matter 1µm (PM1) dataset collected by low-cost sensors in residential and industrial areas at the neighborhood level.

The incursion of low-cost sensors (LCS) for monitoring particulate matter in different fractions of particles (PM10, PM2.5, and PM1) allows the characterization of the concentration levels of specific sources or events, including the analysis of ultrafine fractions (PM1). Several studies have documented adverse effects on human health due to exposure to PM1, such as morbidity and mortality from respiratory, cardiovascular, and, in some cases, carcinogenic diseases. Hence, studying the concentration levels and the sources that cause PM1 is imperative. LCS is an alternative to understanding contaminant concentration levels by considering spatial and temporal community dynamics by monitoring critical zones. Furthermore, collecting and managing large amounts of data through automatic processing and analysis generates information to support decision-making to reduce exposure and risks to people's health. The dataset presents the concentration level of PM1 (µg/m3) calculated from the particles of size 0.03 µm, 0.05 µm, and 1.0 µm recorded and counted by the sensor in a sample per minute for 24 h for seven continuous days. The values of the meteorological factors of relative humidity, temperature, and heat index complement these attributes. The dataset comprises records collected (in the same period) at four particulate matter monitoring stations, which compose an LCS network supported by Internet of Things (IoT) technologies. The data collection points were located in different areas of Reynosa, Mexico, considering strategic places for monitoring environmental pollution, such as industrial parks, residential areas, avenues with high vehicular traffic and transportation of heavy cargo, and an airport.

Staphylococcus aureus proteases trigger eosinophil-mediated skin inflammation.

Staphylococcus aureus skin colonization and eosinophil infiltration are associated with many inflammatory skin disorders, including atopic dermatitis, bullous pemphigoid, Netherton's syndrome, and prurigo nodularis. However, whether there is a relationship between S. aureus and eosinophils and how this interaction influences skin inflammation is largely undefined. We show in a preclinical mouse model that S. aureus epicutaneous exposure induced eosinophil-recruiting chemokines and eosinophil infiltration into the skin. Remarkably, we found that eosinophils had a comparable contribution to the skin inflammation as T cells, in a manner dependent on eosinophil-derived IL-17A and IL-17F production. Importantly, IL-36R signaling induced CCL7-mediated eosinophil recruitment to the inflamed skin. Last, S. aureus proteases induced IL-36α expression in keratinocytes, which promoted infiltration of IL-17-producing eosinophils. Collectively, we uncovered a mechanism for S. aureus proteases to trigger eosinophil-mediated skin inflammation, which has implications in the pathogenesis of inflammatory skin diseases.

Segmented neutrophil-to-monocyte ratio and systemic immune-inflammation index associated with the severity and functional prognosis of acute ischemic stroke.

PURPOSE/AIM OF THE STUDY: To identify the inflammation indexes associated with the severity and functional prognosis in ischemic stroke. MATERIAL AND METHODS: A prospective study was conducted with ischemic stroke cases included in the i-ReNe clinical registry. Patients were divided into groups according to the severity on admission measured by the National Institutes of Health Stroke Scale (NIHSS) and the functional prognosis at 30 and 90 days of discharge measured by the modified Rankin Scale (mRS). RESULTS: We included 145 patients with a mean age of 61.5 ± 12.75, 97 (66.9%) were men. The leukocyte and neutrophil counts, Neutrophil-to-Lymphocyte ratio (NLR), Derived Neutrophil-to-Lymphocyte ratio (dNLR), Platelet-to-Lymphocyte ratio (PLR), Segmented Neutrophil-to-Monocyte ratio (SeMo ratio), and Systemic Immune-inflammation index (SII) were higher in moderate-to-severe stroke (NIHSS ≥6). NLR, PLR, SeMo ratio, and SII were higher in the group with severe disability and death at 30 days (mRS ≥4). In the multiple logistic regression analyses, SeMo ratio >14.966 and SII >623.723 were associated with moderate-to-severe stroke (NIHSS ≥6). In addition, SeMo ratio >7.845 was associated with severe disability and death at 30 days (mRS ≥4). CONCLUSIONS: Systemic inflammation indexes could be rapid and low-cost markers used in the initial evaluation of ischemic stroke, whose values could help to stratify patients according to their severity and functional prognosis. This is the first study to establish a relationship between ischemic stroke and the SeMo ratio.

Implementing a mailed stool sample screening program in clinics providing care for an underserved Hispanic population.

Colorectal cancer (CRC) is a leading cause of cancer-related deaths in Hispanics in the US. Despite this, Hispanics are being screened for CRC at a much lower rate than their non-Hispanic white counterparts. Implementing mailed fecal immunochemical tests (FITs) is a cost-effective intervention for increasing CRC screening rates in vulnerable populations, such as Hispanic populations in border metroplexes. We aimed to describe the effect of introductory calls coupled with mailed in-home FIT kits on CRC screening completion in two federally qualified health centers (FQHCs) in a US-Mexico border county. This was a prospective, pragmatic, two-arm intervention study with participants allocated to receive a FIT kit with a reminder call (usual care) or usual care preceded by an introductory call. The primary outcome was the percentage of patients who returned the FIT kits. Participants who returned to the FIT were primarily unemployed (54.4%), had less than a high school education (60.2%), lived in the US for at least 20 years (74.4%), and had poor self-reported health (54.4%). In addition, we observed a statistically significant increase in the absolute rate (4.5%, P = 0.003) of FITs returned when a mailed FIT kit was preceded by an introductory call compared with no initial call. This study demonstrated that adding an introductory phone call significantly improved the screening completion rate in a mailed-out CRC screening intervention in the US-Mexico border population.

Factors Associated with Malnutrition Risk in Residents of Long-Term Care Facilities in Mexico.

OBJECTIVE: To investigate factors associated with the nutritional status in institutionalized Mexican older adults. MATERIAL AND METHODS: In this cross-sectional study of residents in three long-term care facilities (LTCFs) in Monterrey, Mexico, a medical history, Mini-Mental State Examination, Barthel index, and geriatric depression scale, and Mini Nutritional Assessment (MNA) were performed. Risk of malnutrition and malnutrition status were defined as MNA 17-23.5 and <17, respectively. RESULTS: Residents (n = 280) had a median age of 85 years and 72.1% were female. A total of 116 (41.4%) were at risk of malnutrition and 35 (12.5%) were malnourished. Having malnutrition or being at risk of malnutrition was associated with age (OR = 1.048), functional dependence (OR = 8.376), body mass index (BMI) <22 (OR = 7.518), cognitive impairment (OR = 2.210), urinary incontinence (OR = 2.397), previous stroke (OR = 2.870), Parkinson's disease (OR = 5.193), use of calcium channel blockers (OR = 3.706), and use of atypical antipsychotics (OR = 2.277). Having benign prostatic hyperplasia (OR = 0.067) or the use of angiotensin II receptor blockers (OR = 0.038) were related to being well-nourished. CONCLUSIONS: In a population of residents of three LTCFs in Mexico, we found a high prevalence of malnutrition or being at risk of malnutrition. This underscores the need to implement guidelines for the prompt identification of this condition and further explanation of the factors identified as possibly related to malnutrition.

Mesenchymal Stem Cell Therapies Approved by Regulatory Agencies around the World.

Cellular therapy has used mesenchymal stem cells (MSCs), which in cell culture are multipotent progenitors capable of producing a variety of cells limited to the mesoderm layer. There are two types of MSC sources: (1) adult MSCs, which are obtained from bone marrow, adipose tissue, peripheral blood, and dental pulp; and (2) neonatal-tissue-derived MSCs, obtained from extra-embryonic tissues such as the placenta, amnion, and umbilical cord. Until April 2023, 1120 registered clinical trials had been using MSC therapies worldwide, but there are only 12 MSC therapies that have been approved by regulatory agencies for commercialization. Nine of the twelve MSC-approved products are from Asia, with Republic of Korea being the country with the most approved therapies. In the future, MSCs will play an important role in the treatment of many diseases. However, there are many issues to deal with before their application and usage in the medical field. Some strategies have been proposed to face these problems with the hope of reaching the objective of applying these MSC therapies at optimal therapeutic levels.

Low-Cost Online Monitoring System for the Etching Process in Fiber Optic Sensors by Computer Vision.

The present research exposes a novel methodology to manufacture fiber optic sensors following the etching process by Hydrofluoric Acid deposition through a real-time monitoring diameter measurement by computer vision. This is based on virtual instrumentation developed with the National Instruments® technology and a conventional digital microscope. Here, the system has been tested proving its feasibility by the SMS structure diameter reduction from its original diameter of 125 µ until approximately 42.5 µm. The results obtained have allowed us to demonstrate a stable state behavior of the developed system during the etching process through diameter measurement at three different structure sections. Therefore, this proposal will contribute to the etched fiber optic sensor development that requires reaching an enhanced sensitivity. Finally, to demonstrate the previously mentioned SMS without chemical corrosion, and the etched manufactured SMS, both have been applied as glucose concentration sensors.

Neutrophil-intrinsic TNF receptor signaling orchestrates host defense against Staphylococcus aureus.

Staphylococcus aureus is the leading cause of skin and soft tissue infections and is a major health burden due to the emergence of antibiotic-resistant strains. To address the unmet need of alternative treatments to antibiotics, a better understanding of the protective immune mechanisms against S. aureus skin infection is warranted. Here, we report that tumor necrosis factor (TNF) promoted protection against S. aureus in the skin, which was mediated by bone marrow-derived immune cells. Furthermore, neutrophil-intrinsic TNF receptor (TNFR) signaling directed immunity against S. aureus skin infections. Mechanistically, TNFR1 promoted neutrophil recruitment to the skin, whereas TNFR2 prevented systemic bacterial dissemination and directed neutrophil antimicrobial functions. Treatment with a TNFR2 agonist showed therapeutic efficacy against S. aureus and Pseudomonas aeruginosa skin infections, which involved increased neutrophil extracellular trap formation. Our findings revealed nonredundant roles for TNFR1 and TNFR2 in neutrophils for immunity against S. aureus and can be therapeutically targeted for protection against bacterial skin infections.

N6-methyladenosine RNA Methylation Correlates with Immune Microenvironment and Immunotherapy Response of Melanoma.

RNA methylation normally inhibits the self-recognition and immunogenicity of RNA. As such, it is likely an important inhibitor of cancer immune recognition in the tumor microenvironment, but how N6-methyladenosine (m6A) affects prognosis and treatment response remains unknown. In eight independent melanoma cohorts (1,564 patients), the modification patterns of 21 m6A gene signatures were systematically correlated with the immune cell infiltration of melanoma tumor microenvironment. m6A modification patterns for each patient were quantified using the principal component analysis method, yielding an m6Ascore that reflects the abundance of m6A RNA modifications. Two different m6A modification patterns were observed in patients with melanoma, separated into high and low m6Ascores that correlated with survival and treatment response. Low m6Ascores were characterized by an immune-inflamed phenotype, with 61.1% 5-year survival. High m6Ascores were characterized by an immune-excluded phenotype, with 52.2% 5-year survival. Importantly, lower m6Ascores correlated with more sensitive anti-PD-1 and anti-CTLA4 treatment responses, with 90% of patients with low m6Ascore responding, whereas 10% of those with high m6Ascore nonresponding (in cohort GSE63557). At single-cell and spatial transcriptome resolution, m6Ascore reflects melanoma malignant progression, immune exhaustion, and resistance to immune checkpoint blockade therapy. Hence, the m6Ascore correlates to an important facet of tumor immune escape as a tool for personalized medicine to guide immunotherapy in patients with melanoma.

Topical SCD-153, a 4-methyl itaconate prodrug, for the treatment of alopecia areata.

Alopecia areata is a chronic hair loss disorder that involves autoimmune disruption of hair follicles by CD8+  T cells. Most patients present with patchy hair loss on the scalp that improves spontaneously or with topical and intralesional steroids, topical minoxidil, or topical immunotherapy. However, recurrence of hair loss is common, and patients with extensive disease may require treatment with oral corticosteroids or oral Janus kinase (JAK) inhibitors, both of which may cause systemic toxicities with long-term use. Itaconate is an endogenous molecule synthesized in macrophages that exerts anti-inflammatory effects. To investigate the use of itaconate derivatives for treating alopecia areata, we designed a prodrug of 4-methyl itaconate (4-MI), termed SCD-153, with increased lipophilicity compared to 4-MI (CLogP 1.159 vs. 0.1442) to enhance skin and cell penetration. Topical SCD-153 formed 4-MI upon penetrating the stratum corneum in C57BL/6 mice and showed low systemic absorption. When added to human epidermal keratinocytes stimulated with polyinosinic-polycytidylic acid (poly I:C) or interferon (IFN)γ, SCD-153 significantly attenuated poly I:C-induced interleukin (IL)-6, Toll-like receptor 3, IL-1ß, and IFNß expression, as well as IFNγ-induced IL-6 expression. Topical application of SCD-153 to C57BL/6 mice in the resting (telogen) phase of the hair cycle induced significant hair growth that was statistically superior to vehicle (dimethyl sulfoxide), the less cell-permeable itaconate analogues 4-MI and dimethyl itaconate, and the JAK inhibitor tofacitinib. Our results suggest that SCD-153 is a promising topical candidate for treating alopecia areata.

Commensal microbiome promotes hair follicle regeneration by inducing keratinocyte HIF-1α signaling and glutamine metabolism.

Tissue injury induces metabolic changes in stem cells, which likely modulate regeneration. Using a model of organ regeneration called wound-induced hair follicle neogenesis (WIHN), we identified skin-resident bacteria as key modulators of keratinocyte metabolism, demonstrating a positive correlation between bacterial load, glutamine metabolism, and regeneration. Specifically, through comprehensive multiomic analysis and single-cell RNA sequencing in murine skin, we show that bacterially induced hypoxia drives increased glutamine metabolism in keratinocytes with attendant enhancement of skin and hair follicle regeneration. In human skin wounds, topical broad-spectrum antibiotics inhibit glutamine production and are partially responsible for reduced healing. These findings reveal a conserved and coherent physiologic context in which bacterially induced metabolic changes improve the tolerance of stem cells to damage and enhance regenerative capacity. This unexpected proregenerative modulation of metabolism by the skin microbiome in both mice and humans suggests important methods for enhancing regeneration after injury.

Clinical and molecular change induced by repeated low-dose visible light exposure in both light-skinned and dark-skinned individuals.

BACKGROUND: Visible light (VL) is known to induce pigmentation in dark-skinned individuals and immediate erythema in light-skinned individuals. However, the effects of accumulated low-dose VL exposure across skin types are not well established. METHODS: Thirty-one healthy subjects with light (Fitzpatrick skin types [FST] I-II, n = 13) and dark (FST V-VI, n = 18) skin types were enrolled. Subjects' buttocks were exposed daily to VL, wavelength 400-700 nm, with a dose of 120 J/cm2 at 50 mW/cm2 , for four consecutive days. Microarray using Affymetrix GeneChip (49,395 genes) was performed followed by qRT-PCR on skin samples. RESULTS: Repeated low-dose VL irradiation induced immediate pigment darkening and delayed tanning in dark-skinned individuals while no discernable pigmentation and erythema were observed in light-skinned individuals. Top ten upregulated genes by repeated VL exposure in microarray included melanogenic genes such as tyrosinase (TYR), tyrosinase-related protein-1 (TYRP1), dopachrome tautomerase (DCT), premelanosome protein (PMEL), melan-A (MLANA), and solute carrier family 24, member 5 (SLC24A5) and genes involved in inflammation/matrix remodeling/cell signaling including chemokine (C-C motif) ligand 18 (CCL18), BCL2-related protein A1 (BCL2A1), and cartilage oligomeric matrix protein (COMP). In qRT-PCR CCL18 was upregulated in light skin with a greater extent (mean fold change ± SD; 4.03 ± 3.28, p = .04) than in dark-skinned individuals (1.91 ± 1.32, p = .07) while TYR was not significantly upregulated in both skin types. CONCLUSION: This study highlights the genes upregulated by cumulative VL exposure involved in pigmentation, immune response, oxidation/reduction, and matrix remodeling across skin types providing relevant information on daily solar exposure.

Association of Early Clinical Response to Laser Rejuvenation of Photoaged Skin with Increased Lipid Metabolism and Restoration of Skin Barrier Function.

Laser resurfacing treatments for photoaged skin have improved dramatically over the past decades, but few studies have examined the molecular mechanisms underlying differences in clinical response. Seventeen white female participants with moderate-to-severe photoaging received nonablative fractional laser treatment on the face and forearm once monthly for 6 months. Biopsies for microarray analysis were performed at baseline and 7 days after facial treatment and at baseline and 1, 7, 14, and 29 days after forearm treatment in each participant, resulting in 119 total samples. Participants were stratified into fast (n = 11) and slow (n = 6) responders on the basis of the presence of clinical improvement after the first treatment. Microarray analysis revealed the upregulation of genes associated with matrix metalloproteinases, collagen and extracellular components, TGF-ß signaling, double-stranded RNA signaling, and retinoic acid synthesis after treatment that did not differ significantly between fast and slow responders. Cluster and enrichment analyses suggested significantly greater activation of lipid metabolism and keratinocyte differentiation in fast responders, who showed greater upregulation of acyltransferases, fatty acid elongases, fatty acid 2-hydroxylase, fatty acid desaturases, and specific keratins that may contribute to epidermal barrier function. These results create, to our knowledge, a previously unreported atlas of molecular changes that correlate with improvements in photoaging after laser therapy.

Wound-Induced Hair Neogenesis Model.

Skin wounds in adult mammals typically heal with a fibrotic scar and fail to restore ectodermal appendages, such as hair follicles or adipose tissue. Intriguingly, new hair follicles regenerate in the center of large full-thickness wounds of mice in a process called wound-induced hair neogenesis (WIHN). WIHN is followed by neogenesis of dermal adipose tissue. Both neogenic events reactivate embryonic-like cellular and molecular programs. The WIHN model provides a platform for studying mammalian regeneration, and findings from this model could instruct future regenerative medicine interventions for treating wounds and alopecia. Since Ito et al. rediscovered WIHN 15 years ago, numerous investigators have worked on the WIHN model using varying wounding protocols and model interpretations. Because a variety of factors, including environmental variables and choice of mouse strains, can affect the outcomes of a WIHN study, the purpose of this article is to provide an overview of the experimental variables that impact WIHN so that experiments between laboratories can be compared in a meaningful manner.

Keratinocyte-derived defensins activate neutrophil-specific receptors Mrgpra2a/b to prevent skin dysbiosis and bacterial infection.

Healthy skin maintains a diverse microbiome and a potent immune system to fight off infections. Here, we discovered that the epithelial-cell-derived antimicrobial peptides defensins activated orphan G-protein-coupled receptors (GPCRs) Mrgpra2a/b on neutrophils. This signaling axis was required for effective neutrophil-mediated skin immunity and microbiome homeostasis. We generated mutant mouse lines lacking the entire Defensin (Def) gene cluster in keratinocytes or Mrgpra2a/b. Def and Mrgpra2 mutant animals both exhibited skin dysbiosis, with reduced microbial diversity and expansion of Staphylococcus species. Defensins and Mrgpra2 were critical for combating S. aureus infections and the formation of neutrophil abscesses, a hallmark of antibacterial immunity. Activation of Mrgpra2 by defensin triggered neutrophil release of IL-1ß and CXCL2 which are vital for proper amplification and propagation of the antibacterial immune response. This study demonstrated the importance of epithelial-neutrophil signaling via the defensin-Mrgpra2 axis in maintaining healthy skin ecology and promoting antibacterial host defense.