A Review of Natural Fiber-Reinforced Composites for Lower-Limb Prosthetic Designs.

This paper presents a comprehensive review of natural fiber-reinforced composites (NFRCs) for lower-limb prosthetic designs. It covers the characteristics, types, and properties of natural fiber-reinforced composites as well as their advantages and drawbacks in prosthetic designs. This review also discusses successful prosthetic designs that incorporate NFRCs and the factors that make them effective. Additionally, this study explores the use of computational biomechanical models to evaluate the effectiveness of prosthetic devices and the key factors that are considered. Overall, this document provides a valuable resource for anyone interested in using NFRCs for lower-limb prosthetic designs.

Comparison of perioperative outcomes in obese and non-obese patients subjected to open lumbar spine surgery.

OBJECTIVE: Obesity is a global epidemic affecting developing countries. The relationship between obesity and perioperative outcomes during elective lumbar spine surgery remains controversial, especially in those without morbid disease. MATERIALS AND METHODS: We retrospectively revised the medical records of patients with lumbar spine degeneration subjected to elective surgery. The data retrieved included demographic and clinical characteristics, body mass index (BMI), obesity status (BMI ≥ 30), surgical interventions, estimated blood loss (EBL), operative time, length of stay (LOS), and post-operative complications. Perioperative outcomes were compared between Grade I-II obese and non-obese individuals. RESULTS: We enrolled 53 patients, 18 with Grade I-II obesity. Their median age was 51, with no differences in gender, comorbidities, laboratory parameters, and surgical procedures received between groups. No clinically relevant differences were found between grade I-II obese and non-obese participants in EBL (300 mL vs. 250 mL, p = 0.069), operative time (3.2 h vs. 3.0 h, p = 0.037), and LOS (6 days vs. 5 days, p = 0.3). Furthermore, BMI was not associated with the incidence of significant bleeding and long stay but showed a modest correlation with operative time. CONCLUSION: Grade I-II obesity does not increase surgical complexity nor perioperative complications during open lumbar spine surgery.

OBJETIVO: La obesidad es una epidemia mundial que afecta a países subdesarrollados. Su relación con los resultados de la cirugía de columna lumbar electiva sigue siendo controvertida, especialmente en obesos sin enfermedad mórbida. MÉTODOS: Se revisaron los expedientes de pacientes con degeneración de la columna lumbar sometidos a cirugía. Los datos recuperados incluyeron características demográficas y clínicas, índice de masa corporal (IMC), estado de obesidad (IMC > 30), intervenciones quirúrgicas, sangrado estimado, tiempo operatorio, tiempo de estancia y complicaciones. Los resultados se compararon entre individuos obesos grado I-II y controles. RESULTADOS: Se incluyeron 53 pacientes, 18 con obesidad de grado I-II. La edad media fue de 51 años, sin diferencias en el sexo, las comorbilidades, los parámetros de laboratorio y los procedimientos quirúrgicos recibidos entre grupos. No se encontraron diferencias relevantes entre los participantes obesos y los no obesos en sangrado (300 vs. 250 mL, p = 0.069), tiempo operatorio (3.2 vs. 3.0 horas, p = 0.037) y estancia (6 vs. 5 días, p = 0.3). El IMC no se asoció con hemorragia y larga estancia, pero mostró una correlación modesta con el tiempo operatorio. CONCLUSIONES: La obesidad grado I-II no predispone a complicaciones durante la cirugía de columna lumbar.

2-Aminophenanthroline Ligands Enable Mild, Undirected, Iridium-Catalyzed Borylation of Alkyl C-H Bonds.

The catalytic, undirected borylation of alkyl C-H bonds typically occurs at high reaction temperatures or with excess substrate, or both, because of the low reactivity of alkyl C-H bonds. Here we report a new iridium system comprising 2-anilino-1,10-phenanthroline as the ligand that catalyzes the borylation of alkyl C-H bonds with little to no induction period and with high reaction rates. This superior activation and reactivity profile of 2-aminophenanthroline-ligated catalysts leads to broader reaction scope, including reactions of sensitive substrates, such as epoxides and glycosidic acetals, enhanced diastereoselectivity, and higher yields of borylated products. These catalysts also enable the borylation of alkanes, amines, and ethers at room temperature for the first time. Mechanistic studies imply that facile N-borylation occurs under the reaction conditions and that iridium complexes containing N-boryl aminophenanthrolines are competent precatalysts for the reaction.

Concrete incorporating supplementary cementitious materials: Temporal evolution of compressive strength and environmental life cycle assessment.

The use of Supplementary Cementitious Materials (SCMs) or industrial wastes as a partial replacement for cement in the production of concrete is an urgent need in the construction industry due to cement's growing environmental challenges and rising cost. In respect of this, we conducted research work on proportioning binary concrete mixes. Fly ash (FA) replaced 10 %, 20 %, and 30 % of the cement, while silica fume (SF) replaced 5 %, 10 %, and 15 % of the cement. A control concrete mix was also developed with 100 % cement and no SCM. The results showed no increase in compressive strength for FA concrete compared to control at the early age of 3-28 days, but a maximum increase in compressive strength of 4 % was discovered at a later age of 56 days for concrete with 20 % FA. For 5 % SF concrete, a considerable strength increase of 15 % was seen at the early age of 3 days. Like with FA concrete, 2 % improvement in strength was recorded at the later age of 56 days for 10 % SF concrete. This study further focused on the concrete's temporal evolution of compressive strength by developing a strength evolution model (SEM) using nonlinear regression analysis at a 95 % confidence level. Pearson correlation coefficient was used to determine the correlation between the model values and the experimental results. For comparison, the fib Model Code 2010 was applied to the experimental data, and a good agreement was observed among the proposed model, the fib Model values, and the experimental results. The proposed model can be expanded to address further regression-related problems. Finally, environmental life cycle assessment revealed that utilizing 10 %, 20 %, and 30 % of FA lowered Global Warming Potential (GWP) by 9 %, 19 %, and 29 %, respectively. Likewise, using 5 %, 10 %, and 15 % of SF reduced the GWP by 5 %, 9 %, and 14 %.

Neural circuits for the adaptive regulation of fear and extinction memory.

The regulation of fear memories is critical for adaptive behaviors and dysregulation of these processes is implicated in trauma- and stress-related disorders. Treatments for these disorders include pharmacological interventions as well as exposure-based therapies, which rely upon extinction learning. Considerable attention has been directed toward elucidating the neural mechanisms underlying fear and extinction learning. In this review, we will discuss historic discoveries and emerging evidence on the neural mechanisms of the adaptive regulation of fear and extinction memories. We will focus on neural circuits regulating the acquisition and extinction of Pavlovian fear conditioning in rodent models, particularly the role of the medial prefrontal cortex and hippocampus in the contextual control of extinguished fear memories. We will also consider new work revealing an important role for the thalamic nucleus reuniens in the modulation of prefrontal-hippocampal interactions in extinction learning and memory. Finally, we will explore the effects of stress on this circuit and the clinical implications of these findings.

Intrapatient comparison of atopic dermatitis skin transcriptome shows differences between tape-strips and biopsies.

BACKGROUND: Our knowledge of etiopathogenesis of atopic dermatitis (AD) is largely derived from skin biopsies, which are associated with pain, scarring and infection. In contrast, tape-stripping is a minimally invasive, nonscarring technique to collect skin samples. METHODS: To construct a global AD skin transcriptomic profile comparing tape-strips to whole-skin biopsies, we performed RNA-seq on tape-strips and biopsies taken from the lesional skin of 20 moderate-to-severe AD patients and the skin of 20 controls. Differentially expressed genes (DEGs) were defined by fold-change (FCH) ≥2.0 and false discovery rate <0.05. RESULTS: We detected 4104 (2513 Up; 1591 Down) and 1273 (546 Up; 727 Down) DEGs in AD versus controls, in tape-strips and biopsies, respectively. Although both techniques captured dysregulation of key immune genes, tape-strips showed higher FCHs for innate immunity (IL-1B, IL-8), dendritic cell (ITGAX/CD11C, FCER1A), Th2 (IL-13, CCL17, TNFRSF4/OX40), and Th17 (CCL20, CXCL1) products, while biopsies showed higher upregulation of Th22 associated genes (IL-22, S100As) and dermal cytokines (IFN-γ, CCL26). Itch-related genes (IL-31, TRPV3) were preferentially captured by tape-strips. Epidermal barrier abnormalities were detected in both techniques, with terminal differentiation defects (FLG2, PSORS1C2) better represented by tape-strips and epidermal hyperplasia changes (KRT16, MKI67) better detected by biopsies. CONCLUSIONS: Tape-strips and biopsies capture overlapping but distinct features of the AD molecular signature, suggesting their respective utility for monitoring specific AD-related immune, itch, and barrier abnormalities in clinical trials and longitudinal studies.

Alcohol Use Disorder Polygenic Risk Scores and Trajectories of Early Adolescent Externalizing Behaviors: Examining the Role of Parenting and Family Conflict in the Racially/Ethnically Diverse ABCD Sample.

This study examined the independent and interactive effects of alcohol use disorder genome-wide polygenic scores (AUD-PGS) and parenting and family conflict on early adolescent externalizing behaviors. Data were drawn from White (N = 6181, 46.9% female), Black/African American (N = 1784, 50.1% female), and Hispanic/Latinx (N = 2410, 48.0% female) youth from the adolescent brain cognitive development Study (ABCD). Parents reported on youth externalizing behaviors at baseline (T1, age 9/10), 1-year (T2, age 10/11) and 2-year (T3, age 11/12) assessments. Youth reported on parenting and family environment at T1 and provided saliva or blood samples for genotyping. Results from latent growth models indicated that in general externalizing behaviors decreased from T1 to T3. Across all groups, higher family conflict was associated with more externalizing behaviors at T1, and we did not find significant associations between parental monitoring and early adolescent externalizing behaviors. Parental acceptance was associated with lower externalizing behaviors among White and Hispanic youth, but not among Black youth. Results indicated no significant main effect of AUD-PGS nor interaction effect between AUD-PGS and family variables on early adolescent externalizing behaviors. Post hoc exploratory analysis uncovered an interaction between AUD-PGS and parental acceptance such that AUD-PGS was positively associated with externalizing rule-breaking behaviors among Hispanic youth, but only when parental acceptance was very low. Findings highlight the important role of family conflict and parental acceptance in externalizing behaviors among early adolescents, and emphasize the need to examine other developmental pathways underlying genetic risk for AUD across diverse populations.

Clinical and molecular effects of oral CCR4 antagonist RPT193 in atopic dermatitis: A Phase 1 study.

BACKGROUND: RPT193 is an orally administered small molecule antagonist of the human C-C motif chemokine receptor 4 (CCR4) that inhibits the migration and downstream activation of T-helper Type 2 (Th2) cells. We investigated single- and multiple-ascending doses of RPT193 in healthy subjects, and multiple doses of RPT193 in subjects with moderate-to-severe atopic dermatitis (AD). METHODS: This was a first-in-human randomized, placebo-controlled Phase 1a/1b monotherapy study (NCT04271514) to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and CCR4 surface receptor occupancy in eligible healthy subjects and subjects with moderate-to-severe AD. Clinical efficacy and skin biomarker effects of RPT193 monotherapy were assessed as exploratory endpoints in AD subjects. RESULTS: In healthy (n = 72) and AD subjects (n = 31), once-daily RPT193 treatment was generally well tolerated, with no serious adverse events reported and all treatment-emergent adverse events reported as mild/moderate. In AD subjects, numerically greater improvements in clinical efficacy endpoints were observed with RPT193 monotherapy versus placebo up to the end of the treatment period (Day 29), with statistically significant improvement, compared to Day 29 and placebo, observed 2 weeks after the end of treatment (Day 43) on several endpoints (p < .05). Moreover, significant changes in the transcriptional profile were seen in skin biopsies of RPT193-treated versus placebo-treated subjects at Day 29, which were also significantly correlated with improvements in clinical efficacy measures. CONCLUSIONS: To our knowledge, this is the first clinical study with an oral CCR4 antagonist that showed clinical improvement coupled with modulation of the cutaneous transcriptomic profile in an inflammatory skin disease.

Seasonal Patterns in Tetracycline-Associated Hyperpigmentation Among Patients With Acne Vulgaris.

BACKGROUND: Oral tetracyclines (TCNs) are commonly prescribed for acne, but they have been shown to increase the risk of hyperpigmentation, particularly in the setting of sun exposure. OBJECTIVE: We evaluated seasonal trends in TCN-associated hyperpigmentation incidence in addition to Google search trends for hyperpigmentation-related terms. METHODS: We performed a retrospective review of acne patients seen at Massachusetts General Brigham and Women’s Hospital between 1992 and 2022. We calculated the incidence of new hyperpigmentation diagnoses for each drug cohort. We also analyzed search volume of hyperpigmentation-related terms extracted from Google Trends. RESULTS: Seasonal differences in new hyperpigmentation diagnoses were identified among acne patients prescribed doxycycline (P=0.016), with peak incidence in April. In the control group of patients who had never received a TCN, diagnoses peaked in May. There were no significant seasonal differences among patients prescribed minocycline (P=0.885). There was greater search volume for hyperpigmentation-related terms in spring and summer compared to fall and winter (P<0.001). Limitations of this study include its retrospective nature and reliance on prescription and diagnosis coding data. CONCLUSIONS: Our findings support the seasonal periodicity of acne-related hyperpigmentation, underscoring the importance of photoprotection counseling for patients with acne. Additionally, doxycycline may be associated with an earlier onset of hyperpigmentation, suggesting a potential benefit of considering minocycline or other alternatives to doxycycline. J Drugs Dermatol. 2023;22(11):e9-e11    doi:10.36849/JDD.7409e.

Laser-Assisted Prostaglandin Analogs in the Treatment of Hypopigmented Scars: A Systematic Review.

Background: Hypopigmented scars are challenging to treat due to a lack of effective treatments and often transient results. Recent reports suggest that prostaglandin analog-induced hyperpigmentation may have favorable dermatological applications. Objective: Analyze previous studies involving the use of prostaglandin analogs in the treatment of hypopigmented scars. Methods: PubMed/Medline was queried through 10/01/2022 with the following search terms: (bimatoprost AND scar), (latanoprost AND scar), (travoprost AND scar), (prostaglandin analogs AND hypopigmented scars), (PGF2alpha AND hyperpigmentation), (prostaglandin analogs AND hyperpigmentation). Results: In total, 88 unique studies were reviewed for eligibility. Five studies met inclusion criteria including two prospective, double-blinded, randomized (only one was placebo-controlled), one prospective case series, one retrospective chart review, and one case report; comprising a total of 87 patients. All five studies utilized topical prostaglandin analogs as an adjunctive treatment via laser-assisted delivery. While both, the placebo-controlled and non-placebo-controlled, trials reported more than 75 percent of patients experienced at least 50 percent or more (Grade 3 or higher) improvement, the retrospective study reported 100 percent of patients experienced at least 75 percent or more (Grade 4 or higher) improvement, measured as scar repigmentation. The prospective case series and the reported single case showed overall qualitative improvement in all patients measured as repigmentation of hypopigmented and depigmented scars. Limitations: Different laser devices, parameters, treatment frequency, and follow-up timepoints. Conclusion: All studies evaluated demonstrated favorable treatment outcomes with no reported adverse events. Additional, large randomized controlled trials are needed to fully assess the effectiveness and long-term safety of PGF2α agonists for hypopigmented scars.

Applications of Laser Speckle Contrast Imaging Technology in Dermatology.

Laser speckle contrast imaging or laser speckle imaging (LSI) is a noninvasive imaging technology that can detect areas of dynamic perfusion or vascular flow. Thus, LSI has shown increasing diagnostic utility in various pathologies and has been employed for intraoperative, postoperative, and long-term monitoring in many medical specialties. Recently, LSI has gained traction in clinical dermatology because it can be effective in the assessment of pathologies that are associated with increased perfusion and hypervascularity compared with that of normal tissue. To date, LSI has been found to be highly accurate in monitoring skin graft reperfusion, determining the severity of burns, evaluating neurosurgical revascularization, assessing persistent perfusion in capillary malformations after laser therapy, and differentiating malignant and benign skin lesions. LSI affords the advantage of noninvasively assessing lesions before more invasive methods of diagnosis, such as tissue biopsy, while remaining inexpensive and exhibiting no adverse events to date. However, potential obstacles to its clinical use include tissue movement artifact, primarily qualitative data, and unclear impact on clinical practice given the lack of superiority data compared with the current standard-of-care diagnostic methods. In this review, we discuss the clinical applications of LSI in dermatology for use in the diagnosis and monitoring of vascular, neoplastic, and inflammatory skin conditions.

[Transcultural adaptation and validation of the DASH questionnaire in Mexican healthy volunteers and patients with neurogenic disorders of the upper extremity]. / Adaptación transcultural y validación de la versión mexicana del cuestionario DASH en individuos sanos y pacientes con trastornos neurogénicos del miembro superior.

Background: The Disability of the Arm, Shoulder and Hand (DASH) questionnaire assesses the impact of upper extremity disorders on quality of life. However, its use in the Mexican population has not been formally validated. Objective: To conduct a cultural adaptation and validation of the DASH questionnaire to evaluate the perspective of patients with neurogenic disorders of the upper extremity regarding the impact on their quality of life. Method: We performed an adaptation of the Spanish version of the DASH questionnaire to the Mexican vocabulary and applied it to 478 volunteers. Ceiling effect, floor effect, item-total correlation, descriptive statistics of items and total score, internal consistency, precision, cross-sectional and longitudinal validity were estimated by comparing healthy controls and affected individuals with different disability levels. Results: Our DASH questionnaire version was equivalent to those previously approved and showed homogeneity of the items with respect to the total value of the questionnaire (Cronbach's alpha > 0.96). In addition, it showed an accuracy of 7.25 points and the crosssectional and longitudinal validity was documented with significant differences between groups and subgroups with distinct disability levels. Conclusions: The DASH questionnaire can be used with a high level of confidence in the Mexican population.

Antecedentes: El cuestionario de discapacidad de brazo, hombro y mano (DASH, Disabilities of the Arm, Shoulder and Hand) mide el impacto de patologías del miembro superior en la calidad de vida. Sin embargo, su uso en la población mexicana no ha sido formalmente validado. Objetivo: Realizar la adaptación cultural y validación del cuestionario DASH para conocer la perspectiva de pacientes con trastornos neurogénicos del miembro superior respecto al impacto en su calidad de vida. Método: Se realizó una adaptación al vocabulario mexicano de la versión española del cuestionario DASH y se aplicó en 478 voluntarios. Se estimaron el efecto techo, el efecto suelo, la correlación ítem-total, las medidas de tendencia central de ítems y el puntaje total, la consistencia interna, la precisión y la validez transversal y longitudinal mediante la comparación de individuos sanos y enfermos con diferente nivel de discapacidad. Resultados: Nuestra versión del cuestionario DASH resultó equivalente a las previamente aprobadas y mostró homogeneidad de los ítems respecto al valor total del cuestionario (alfa de Cronbach > 0.96). Además, tuvo una precisión de 7.25 puntos y se documentó la validez transversal y longitudinal con diferencias significativas entre grupos y subgrupos con diferente nivel de discapacidad. Conclusiones: El cuestionario DASH puede ser empleado con un nivel de confianza alto en la población mexicana.

Neurochemical plasticity of the carotid body in hypertension.

The carotid body (CB), a main peripheral arterial chemoreceptor, has lately been implicated in the pathophysiology of various cardiovascular disorders. Emerging experimental evidence supports a causal relationship between CB dysfunction and augmented sympathetic outflow which is the common hallmark of human sympathetic-related diseases, including essential hypertension. To gain insight into the neurotransmitter profile of chemosensory cells in the hypertensive CB, we examined the expression and cellular localization of some classical neurotransmitters, neuropeptides, and gaseous signaling molecules as well as neurotrophic factors and their receptors in the CB of spontaneously hypertensive rats, a common animal model of hypertension. Our immunohistochemical experiments revealed an elevated catecholamine and serotonin content in the hypertensive CB compared to normotensive controls. GABA immunostaining was seen in some peripherally located glomus cells in the CB of SHR and it was significantly lower than in control animals. The density of substance P and vasoactive intestinal peptide-immunoreactive fibers was diminished whereas that of neuropeptide Y-immunostained nerve fibers was increased and that of calcitonin gene-related peptide-containing fibers remained almost unchanged in the hypertensive CB. We have further demonstrated that in the hypertensive state the production of nitric oxide is impaired and that the components of the neurotrophin signaling system display an abnormal enhanced expression. Our results provide immunohistochemical evidence that the altered transmitter phenotype of CB chemoreceptor cells and the elevated production of neurotrophic factors modulate the chemosensory processing in hypertensive animals which contributes to autonomic dysfunction and elicits sympathetic hyperactivity, consequently leading to elevated blood pressure.

Cross-Sectional Study of Psoriasis, Atopic Dermatitis, Rosacea, and Alopecia Areata Suggests Association With Cardiovascular Diseases.

BACKGROUND: A growing body of evidence suggests that several inflammatory skin diseases (ISDs) are associated with systemic inflammation and cardiovascular disease (CVDs). METHODS: We used the TriNetX analytics platform to conduct a retrospective, cross-sectional, single-center study in the Mount Sinai Health System network. Cases (all patients ≥18 years of age with a diagnosis of 1 of the 4 ISDs studied) were compared with matched controls (no history of any of these ISDs) to evaluate odds ratios for being diagnosed with CVD. RESULTS: We identified a total of 70,090 patients with ISDs, including 35,160 patients with atopic dermatitis, 19,490 with psoriasis, 12,470 with rosacea, and 2,970 with alopecia areata, and 70,090 propensity score-matched controls without any of these ISDs. Patients with atopic dermatitis and psoriasis had significantly increased odds of all CVD diagnoses analyzed compared to controls (P<0.001 for all comparisons). Patients with rosacea had significantly increased odds of being diagnosed with all diseases of the circulatory system (P<0.001), hypertensive diseases (P<0.001), cerebrovascular diseases (P=0.037), and arterial disease (P<0.001) compared to controls. Patients with alopecia areata had increased odds for all diseases of the circulatory system (P<0.001), hypertensive diseases (P<0.001), and arterial disease (P<0.001). The prevalence of patients with elevated C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) levels was significantly greater in all ISD groups compared to controls. CONCLUSION: This study identified significant associations between ISDs and several CVD diagnoses. Furthermore, CRP and ESR were elevated in all ISD groups compared to controls. Pagan AD, Jung S, Caldas S, et al. Cross-sectional study of psoriasis, atopic dermatitis, rosacea, and alopecia areata suggests association with cardiovascular diseases. J Drugs Dermatol. 2023;22(6):576-581. doi:10.36849/JDD.7424.

Molecular Modeling of Double Retrograde Vaporization Using Monte Carlo Simulations and Equations of State.

Vapor-liquid equilibria of binary systems consisting of a low-boiling (i.e., more volatile) and a high-boiling compound may exhibit unexpected behavior near the critical point of the low-boiling compound. Near the critical temperature of the low-boiling compound and for compositions rich in the low-boiling compound, increasing the pressure may result in multiple crossings of the dew- and bubble-point curves. This phenomenon is often called double retrograde vaporization (or condensation) and may play a role in oil field operations and gas transport through pipelines, but the microscopic driving forces for the unusual shape of the dew-point curve are not well understood. Monte Carlo simulations in the constant-pressure, constant-temperature Gibbs ensemble using the united-atom version of the TraPPE force field were carried out for the methane/n-butane mixture at temperatures ranging from 0.95 to 1.05 of the reduced (T/Tc) temperature of methane. The simulations predict a wealth of additional thermodynamic data (densities and free energies of transfer) and structural data that are used to provide much needed molecular-level insights into the fluid properties associated with double retrograde vaporization. Simulated thermodynamic data are also compared with calculations using the Peng-Robinson and PC-SAFT equations of state.

Age of onset defines two distinct profiles of atopic dermatitis in adults.

BACKGROUND: The incidence of adult-onset atopic dermatitis (AOAD) is increasing. However, the unique characteristics of AOAD compared to pediatric-onset AD persisting into adulthood (POAD) are underexplored, hampering the development of targeted-therapeutics for this growing population. We thus assessed the profile of AOAD in skin and blood compared to that of POAD. METHODS: We collected skin biopsies and blood from adults with AOAD, POAD, and healthy controls (n = 15 in each group). Skin samples were analyzed by RNA sequencing, qRT-PCR, and immunohistochemistry, and Olink Proseek multiplex assay was used to identify the serum proteomic profile. RESULTS: Compared to healthy controls, both AOAD and POAD showed cutaneous immune and barrier dysregulations with a shared Th2/Th22 hyperactivation. Overall, POAD showed greater inflammation in lesional skin, with more prominent expression of Th2/Th17/Th22 markers (CCL17/22, S100A8/9, IL-36A, PI3/Elafin, DEFB4) in POAD compared to AOAD (p-value < .05). In contrast, higher Th1-(IFN-γ, IL-2, IL-15, CCL5) upregulation and Th1-skewing were seen in AOAD. The epidermal barrier was also more compromised in POAD, with greater epidermal hyperplasia and lower expression of markers related to terminal differentiation, lipids, and cell adhesion. In parallel with increased rates of cardiovascular comorbidities, AOAD demonstrated many more significantly dysregulated proteins in serum (n = 148) compared to POAD (n = 86), including pro-inflammatory and cardiovascular-risk markers. Th1-related products showed significant correlations between their skin and blood expressions only in AOAD subjects. CONCLUSION: Age-of-onset delineates two distinct endophenotypes in adult AD potentially suggesting the need for broader (beyond Th2) therapeutic targeting in AOAD.