Electrochemical Analysis of Amyloid Plaques and ApoE4 with Chitosan-Coated Gold Nanostars for Alzheimer's Detection.

Monitoring the progression of Alzheimer's disease (AD) is crucial for mitigating dementia symptoms, alleviating pain, and improving mobility. Traditionally, AD biomarkers like amyloid plaques are predominantly identified in cerebrospinal fluid (CSF) due to their concentrated presence. However, detecting these markers in blood is hindered by the blood-brain barrier (BBB), resulting in lower concentrations. To address this challenge and identify pertinent AD biomarkers-specifically amyloid plaques and apolipoprotein E4 (ApoE4)-in blood plasma, we propose an innovative approach. This involves enhancing a screen-printed carbon electrode (SPCE) with an immobilization matrix comprising gold nanostars (AuNSs) coated with chitosan. Morphological and electrical analyses confirmed superior dispersion and conductivity with 0.5% chitosan, supported by UV-Vis spectroscopy, cyclic voltammetry, and Nyquist plots. Subsequent clinical assays measured electrical responses to quantify amyloid-ß 42 (Aß42) (15.63-1000 pg/mL) and APoE4 levels (0.41 to 40 ng/mL) in human blood plasma samples. Differential pulse voltammetry (DPV) responses exhibited peak currents proportional to biomarker concentrations, demonstrating high linear correlations (0.985 for Aß42 and 0.919 for APoE4) with minimal error bars. Cross-reactivity tests with mixed solutions of amyloid-ß 40 (Aß40), Aß42, and ApoE4 indicated minimal interference between biomarkers (<3% variation), further confirming the high specificity of the developed sensor. Validation studies demonstrated a strong concurrence with the gold-standard enzyme-linked immunosorbent assay (ELISA), while interference tests indicated a minimal variation in peak currents. This improved device presents promising potential as a point-of-care system, offering a less invasive, cost-effective, and simplified approach to detecting and tracking the progression of AD. The substantial surface binding area further supports the efficacy of our method, offering a promising avenue for advancing AD diagnostics.

Transcriptome-wide analysis for glucocorticoid receptor-mediated mRNA decay reveals various classes of target transcripts.

The glucocorticoid receptor (GR) can bind to DNA or RNA, eliciting transcriptional activation/repression or rapid mRNA degradation, respectively. Although GR-mediated transcriptional regulation has been well-characterized, the molecular details of rapid mRNA degradation induced by glucocorticoids (GCs) are not yet fully understood. Here, we demonstrate that GC-induced GR-mediated mRNA decay (GMD) takes place in the nucleus and the cytoplasm, acting on pre-mRNAs and mRNAs. We also performed cross-linking and immunoprecipitation coupled with high-throughput sequencing (CLIP-seq) analysis for GMD factors (GR, YBX1, and HRSP12) and mRNA sequencing (mRNA-seq) analysis to identify endogenous GMD substrates. Our comprehensive CLIP-seq and mRNA sequencing analyses reveal that a range of cellular transcripts containing a common binding site for GR, YBX1, and HRSP12 are preferential targets for GMD, suggesting possible new functions of GMD in various biological events.

Phase 1/2 trials of human bone marrow-derived clonal mesenchymal stem cells for treatment of adults with moderate to severe atopic dermatitis.

BACKGROUND: Mesenchymal stem cells (MSCs) play important roles in therapeutic applications by regulating immune responses. OBJECTIVE: We investigated the safety and efficacy of allogenic human bone marrow-derived clonal MSCs (hcMSCs) in subjects with moderate to severe atopic dermatitis (AD). METHODS: The study included a phase 1 open-label trial followed by a phase 2 randomized, double-blind, placebo-controlled trial that involved 72 subjects with moderate to severe AD. RESULTS: In phase 1, intravenous administration of hcMSCs at 2 doses (1 × 106 and 5 × 105 cells/kg) was safe and well tolerated in 20 subjects. Because there was no difference between the 2 dosage groups (P = .9), it was decided to administer low-dose hcMSCs only for phase 2. In phase 2, subjects receiving 3 weekly intravenous infusions of hcMSCs at 5 × 105 cells/kg showed a higher proportion of an Eczema Area and Severity Index (EASI)-50 response at week 12 compared to the placebo group (P = .038). The differences between groups in the Dermatology Life Quality Index and pruritus numeric rating scale scores were not statistically significant. Most adverse events were mild or moderate and resolved by the end of the study period. CONCLUSIONS: The hcMSC treatment resulted in a significantly higher rate of EASI-50 at 12 weeks compared to the control group in subjects with moderate to severe AD. The safety profile of hcMSC treatment was acceptable. Further larger-scale studies are necessary to confirm these preliminary findings.

Facial Dermatoses Associated With Mask-Wearing in the COVID-19 Era: A Nationwide, Cross-Sectional, Multicenter, Questionnaire-based Study.

BACKGROUND: Daily usage of facial masks during coronavirus disease 2019 pandemic influenced on facial dermatoses. OBJECTIVE: This study investigated the impact of mask-wearing habits on facial dermatoses. METHODS: A nationwide, observational, questionnaire-based survey was conducted from July through August 2021, involving 20 hospitals in Korea. RESULTS: Among 1,958 facial dermatoses, 75.9% of patients experienced aggravation or development of new-onset facial dermatoses after wearing masks. In aggravated or newly developed acne patients (543 out of 743), associated factors were healthcare provider, female gender, and a long duration of mask-wearing. Irritating symptoms, xerosis, and hyperpigmentation were more frequently observed in this group. Aggravated or newly developed rosacea patients (515 out of 660) were likely to be female, young, and have a long duration of mask-wearing per day. Seborrheic dermatitis patients who experienced aggravation or de novo development (132 out of 184) were younger, and they more frequently involved the chin and jaw in addition to the nasolabial folds and both cheeks. Contact dermatitis patients (132 out of 147) with aggravation or de novo development tended to be female, involve both cheeks, and complain of pruritus. Aggravated or newly developed atopic dermatitis patients (165 out of 224) were more likely to be female, and had a higher baseline investigator global assessment score before mask-wearing. CONCLUSION: Clinical features and factors related to aggravation were different according to the types of facial dermatoses.

Nonsense-mediated mRNA decay of mRNAs encoding a signal peptide occurs primarily after mRNA targeting to the endoplasmic reticulum.

Translation of messenger ribonucleic acids (mRNAs) encoding integral membrane proteins or secreted proteins occurs on the surface of the endoplasmic reticulum (ER). When a nascent signal peptide is synthesized from the mRNAs, the ribosome-nascent chain complex (RNC) is recognized by the signal recognition particle (SRP) and then transported to the surface of the ER. The appropriate targeting of the RNC-SRP complex to the ER is monitored by a quality control pathway, a nuclear cap-binding complex (CBC)-ensured translational repression of RNC-SRP (CENTRE). In this study, using ribosome profiling of CBC-associated and eukaryotic translation initiation factor 4E-associated mRNAs, we reveal that, at the transcriptomic level, CENTRE is in charge of the translational repression of the CBC-RNC-SRP until the complex is specifically transported to the ER. We also find that CENTRE inhibits the nonsense-mediated mRNA decay (NMD) of mRNAs within the CBC-RNC-SRP. The NMD occurs only after the CBC-RNC-SRP is targeted to the ER and after eukaryotic translation initiation factor 4E replaces CBC. Our data indicate dual surveillance for properly targeting mRNAs encoding integral membrane or secretory proteins to the ER. CENTRE blocks gene expression at the translation level before the CBC-RNC-SRP delivery to the ER, and NMD monitors mRNA quality after its delivery to the ER.

Consensus Report on Truncal Acne: The Korean Acne and Rosacea Society Experts Panel.

BACKGROUND: More than half of acne patients have truncal acne on their chest, back, and shoulders. However, since most studies on acne have focused on the face, data on clinical characteristics and proper management for truncal acne are insufficient. OBJECTIVE: To establish a Korean Acne Rosacea Society (KARS) consensus for experts' perception and treatment patterns of truncal acne. METHODS: We conducted two rounds of the Dephi technique to gather expert opinion and reach a consensus on truncal acne. The first round comprised 48 questionnaires focusing on various aspects such as epidemiology, clinical features, diagnosis, treatment, prognosis and more, while second rounds consisted of 26 questionnaires. RESULTS: A total of 36 dermatologists (36/38 KARS members, 94.7%) completed this survey. In the first-round survey, consensus was reached on 20 out of the 48 questions (41.7%). In the second-round questionnaire, consensus was achieved on 9 of the 26 questions (34.6%). The most unresponsive lesion to truncal acne treatment was scars (atrophic/hypertrophic). The most commonly used treatments for each non-inflammatory and inflammatory truncal acne lesions were selected to use topical retinoids (78.1% of the responders) and oral antibiotics (93.8% of the responders). CONCLUSION: Our study has yielded valuable insights into the epidemiology, clinical manifestations, diagnosis, treatment, and quality of life of patients with truncal acne. We anticipate that this study will inspire further comprehensive research for individuals with truncal acne.

Zinc penetration through the skin barrier in atopic dermatitis and rosacea using reflectance confocal microscopy.

Atopic dermatitis (AD) is a chronic, recurrent eczematous disorder with a complex pathophysiology caused by skin barrier abnormalities. Rosacea is a common chronic immune-mediated inflammatory disorder that results in diminished skin barrier function. Reflectance confocal microscopy (RCM) is a non-invasive method for visualizing the dynamic status of epidermal and upper dermal structures. In this study, we compared skin barrier permeability among normal, AD and rosacea groups. To assess skin barrier permeability, zinc was applied to lesional skin and the RCM reflectance intensity of zinc penetration was measured. Reflectance confocal microscopy revealed that the intensity in patients with rosacea and AD was higher than that in the normal group at depths of 8-24 µm in both the face and forearm, which were considered as the stratum corneum (SC) and tight junction (TJ) level (p < 0.0001). When comparing AD and rosacea, the intensity of rosacea was higher than that of AD at a depth of 8 µm in the face (p < 0.0001). The intensity of AD was higher than that of rosacea at a depth of 24 µm (p = 0.009). This suggests that skin barrier permeability is increased in the upper epidermis of patients with AD and rosacea. On the face, patients with rosacea had more SC weakness than did those with AD, whereas patients with AD had more TJ weakness than those with rosacea.

Clinical Characteristics of Lichen Amyloidosis Associated with Atopic Dermatitis: A Single Center, Retrospective Study.

BACKGROUND: Lichen amyloidosis is a chronic pruritic skin disorder associated with atopic dermatitis, however, the pathogenetic link between these two conditions remains to be elucidated. Only limited research has been performed on patients diagnosed with both pruritic dermatological conditions. OBJECTIVE: This study aimed to analyze the clinical features of lichen amyloidosis associated with atopic dermatitis. METHODS: We conducted a matched case-control study of incident lichen amyloidosis with atopic dermatitis between March 2020 and February 2022. Among the 2,481 patients with atopic dermatitis, 20 patients diagnosed with lichen amyloidosis and atopic dermatitis were included as case patients, and 20 patients diagnosed with atopic dermatitis were enrolled as controls. The controls were matched to cases (1:1) by age and sex. We retrospectively reviewed the medical records of the patients. RESULTS: The prevalence of lichen amyloidosis associated with atopic dermatitis was approximately 0.8%, with a male:female sex ratio of 2.33:1. The recorded onset of lichen amyloidosis associated with atopic dermatitis was more common in adult patients, with moderate-to-severe atopic dermatitis. Lichen amyloidosis lesions in patients with atopic dermatitis were most commonly found on the extremities, sparing the head and neck region. The presence of lichen amyloidosis had no significant impact on severity of atopic dermatitis. CONCLUSION: In patients with lichen amyloidosis associated with atopic dermatitis, the clinical manifestations of lesions are similar to those of conventional lichen amyloidosis lesions in terms of morphology and regional distribution. Further research is required to elucidate the link between the pathogenesis of these two pruritic dermatological conditions.

A Case of Eccrine Syringofibroadenoma Related to Senile Gluteal Dermatosis.

Eccrine syringofibroadenoma (ESFA) is a tumor of eccrine ductal differentiation. ESFA is a rare disease, with only approximately 80 cases reported worldwide. ESFA can be classified into five subtypes. Senile gluteal dermatosis (SGD) was first reported in Japan in 1979. It is a relatively common geriatric dermatosis in East Asia, and characterized by hyperkeratotic lichenified skin lesions in the gluteal region. An 86-year-old woman presented with a solitary recurrent dark brown plaque in the sacral area. There was a hyperkeratotic lichenified brownish patch around the plaque, which was clinically considered SGD. Histopathological examination of biopsy specimen revealed thin anastomosing reticulated strands of basaloid cuboidal cells. The tumor extends from the basal layer of the epidermis to the dermis. These findings are consistent with those of ESFA. The patient was treated with total excision of the skin lesion. Reactive ESFA is related to tissue regeneration and remodeling after damage, such as trauma and burns. There is no literature reporting ESFA related to SGD so far, but there have been few reports of cases occurring in soles or buttocks, which are constantly under pressure. This is the first report on reactive ESFA related to SGD, and further research is needed to reveal the pathogenic mechanism.

An interaction between eIF4A3 and eIF3g drives the internal initiation of translation.

An RNA structure or modified RNA sequences can provide a platform for ribosome loading and internal translation initiation. The functional significance of internal translation has recently been highlighted by the discovery that a subset of circular RNAs (circRNAs) is internally translated. However, the molecular mechanisms underlying the internal initiation of translation in circRNAs remain unclear. Here, we identify eIF3g (a subunit of eIF3 complex) as a binding partner of eIF4A3, a core component of the exon-junction complex (EJC) that is deposited onto spliced mRNAs and plays multiple roles in the regulation of gene expression. The direct interaction between eIF4A3-eIF3g serves as a molecular linker between the eIF4A3 and eIF3 complex, thereby facilitating internal ribosomal entry. Protein synthesis from in vitro-synthesized circRNA demonstrates eIF4A3-driven internal translation, which relies on the eIF4A3-eIF3g interaction. Furthermore, our transcriptome-wide analysis shows that efficient polysomal association of endogenous circRNAs requires eIF4A3. Notably, a subset of endogenous circRNAs can express a full-length intact protein, such as ß-catenin, in an eIF4A3-dependent manner. Collectively, our results expand the understanding of the protein-coding potential of the human transcriptome, including circRNAs.

Pigmented contact dermatitis and hair dyes: A retrospective case-control multicentre study in Korea.

BACKGROUND: Pigmented contact dermatitis (PCD), a rare variant of non-eczematous contact dermatitis, is clinically characterized by sudden-onset brown or grey pigmentation on the face and neck. It is hypothesized to be caused by repeated contact with low levels of allergens. OBJECTIVES: This study evaluated the risk of using hair dyes in patients with PCD in Korea. METHODS: A total of 1033 PCD patients and 1366 controls from 31 university hospitals were retrospectively recruited. We collected and analysed the data from the patient group, diagnosed through typical clinical findings of PCD and the control group, which comprised age/sex-matched patients who visited the participating hospitals with pre-existing skin diseases other than current allergic disease or PCD. RESULTS: Melasma and photosensitivity were significantly more common in the control group, and a history of contact dermatitis was more common in the PCD group. There were significantly more Fitzpatrick skin type V participants in the PCD group than in the control group. There was no significant difference in sunscreen use between the groups. Using dermatologic medical history, Fitzpatrick skin type and sunscreen use as covariates, we showed that hair dye use carried a higher PCD risk (odds ratio [OR] before adjustment: 2.06, confidence interval [CI]: 1.60-2.65; OR after adjustment: 2.74, CI: 1.88-4.00). Moreover, henna users had a higher risk of PCD (OR before adjustment: 5.51, CI: 4.07-7.47; OR after adjustment: 7.02, CI: 4.59-10.74), indicating a significant increase in the risk of PCD with henna dye use. Contact dermatitis history was more prevalent in henna users than in those using other hair dyes in the PCD group (17.23% vs. 11.55%). CONCLUSION: Hair dye use is a risk factor for PCD. The risk significantly increased when henna hair dye was used by those with a history of contact dermatitis.

Analysis of facial vascular pattern characteristics in the Korean population.

BACKGROUND: Facial erythema is a common problem among patients visiting dermatologists. However, data on the clinical characteristics of facial erythema in healthy people are lacking. We aimed to compare and analyze the severity and pattern of facial vascularity in healthy subjects based on their age and gender. MATERIALS AND METHODS: This study included 198 Korean volunteers (126 females and 72 males) with Fitzpatrick skin types II, III, or IV. Fourteen different anatomical areas on the face were divided into facial erythema units. Each unit was scored from one (least erythematous) to five (most erythematous) according to the observed level of erythema on the red images implemented as hemoglobin content. We also evaluated the presence of facial telangiectatic macules. RESULTS: On average, the perinasal, nasal, and cheek units were the most hypervascular regions. In contrast, the degree of facial erythema was lowest in the labial (perioral), neck, and temporal regions. The average value of erythema was higher in males than in females. Additionally, the severity of erythema tended to increase with age. In both males and females, the number of telangiectatic macules increased with age. CONCLUSIONS: We analyzed the clinical characteristics of erythema in healthy subjects with Fitzpatrick skin types II, III, or IV in the Korean population. This study is expected to be used to identify the neurovascular pathogenesis of the most common regions of facial dermatosis in the future.

Nine cases of chronic hand and foot eczema treated with baricitinib.

Chronic hand and foot eczema (CHFE) is a common inflammatory disorder that generally lasts for over 3 months. If it is intractable to topical agents, systemic immunomodulators can be considered; however, they are not suitable for long-term management because of their adverse effects. Baricitinib is an oral Janus kinase inhibitor that has been approved for the treatment of moderate-to-severe atopic dermatitis. However, its effect on CHFE has rarely been described. Herein, we report nine cases of recalcitrant CHFE that were treated with baricitinib after an inadequate response to low-dose ciclosporin. All patients had more than moderate improvement within 2-8 weeks without serious adverse effects.

Characterizing the microbiota of cleft lip and palate patients: a comprehensive review.

Orofacial cleft disorders, including cleft lip and/or palate (CL/P), are one of the most frequently-occurring congenital disorders worldwide. The health issues of patients with CL/P encompass far more than just their anatomic anomaly, as patients with CL/P are prone to having a high incidence of infectious diseases. While it has been previously established that the oral microbiome of patients with CL/P differs from that of unaffected patients, the exact nature of this variance, including the relevant bacterial species, has not been fully elucidated; likewise, examination of anatomic locations besides the cleft site has been neglected. Here, we intended to provide a comprehensive review to highlight the significant microbiota differences between CL/P patients and healthy subjects in various anatomic locations, including the teeth inside and adjacent to the cleft, oral cavity, nasal cavity, pharynx, and ear, as well as bodily fluids, secretions, and excretions. A number of bacterial and fungal species that have been proven to be pathogenic were found to be prevalently and/or specifically detected in CL/P patients, which can benefit the development of CL/P-specific microbiota management strategies.

Effect of COVID-19 (SARS-CoV-2) Vaccination on Patients with Atopic Dermatitis Treated with Dupilumab: A Multicenter, Observational Study.

BACKGROUND: Atopic dermatitis (AD) patients usually wonder if their condition will worsen after vaccination or if they should continue with the treatment they are receiving. Considering that many patients treated with dupilumab had previously experienced severe AD symptoms and flares, the concerns are more understandable. OBJECTIVE: This study aimed to investigate the safety of the coronavirus disease 2019 (COVID-19) vaccination in patients with AD treated with dupilumab. METHODS: We enrolled 133 patients (101 dupilumab-treated and 32 systemic oral agents-treated as control group) with AD from six hospitals. Patients were asked about worsening pruritus and AD (5-point Likert scale) after vaccination. AD variables (eczema area and severity index [EASI], investigator's global assessment [IGA], itch numerical rating scale [NRS], sleep NRS, and patient-oriented eczema measure [POEM]) were compared pre- and post-vaccination. Adverse reactions to the COVID-19 vaccination were observed. RESULTS: The incidence of adverse reactions to COVID-19 vaccines and worsening AD symptoms in dupilumab-treated patients were not significantly different compared with that in the control group. The itch NRS score increased significantly after vaccination (p<0.001). However, there were no statistically significant differences between the pre-and post-EASI, IGA, and POEM scores. Eight patients (7.9%) had worse EASI scores and required rescue therapy; however, most were easily managed with low-dose steroids or topical agents. None of the patients discontinued dupilumab treatment. CONCLUSION: No serious adverse reactions were observed in patients with AD after COVID-19 vaccination. Exacerbation of pruritus and AD symptoms was observed but was mostly mild and transient.

Erratum: Assessment of Disease Severity and Quality of Life in Patients with Atopic Dermatitis from South Korea.

This corrects the article on p. 419 in vol. 34, PMID: 36478424.

An analysis of shapes and location of anterior hairline in Asian men.

An individual's first impression can be influenced by a number of esthetic factors, one of which is a natural hairline. The anterior hairline can be affected by various factors, such as race, age, forehead shape, and hair loss progression, similar to androgenetic alopecia. Information on the shape, hairline location on the forehead, and race are required to classify the anterior hairline. According to previous studies, the shape of the anterior hairline can be classified as round, M-shaped, rectangular, bell-shaped, or triangular. This study aimed to analyze the type of anterior hairline in Asian males without androgenetic alopecia. The subjects consisted of 461 males in China, Japan, Kazakhstan, Mongolia, the Philippines, South Korea, and Taiwan. We classified the shape of the anterior hairline into four types: M-shaped (M), rectangular (R), round (O), and wave-shaped (W). We classified the location of the anterior hairline into three types: high (H), middle (M) and low (L), according to the subjects' forehead ratio. Finally, we combined the shape and location types to devise a novel classification system for the anterior hairline type. The most common hairline types in our newly developed classification were MM (23.94%), RM (18.00%) and ML (11.04%). The least common types were OL (0.58%), OH (2.34%) and WH (2.74%). Our results will set standards for hairline shapes and locations, which will be helpful for evaluating hair loss treatment, establishing criteria and designs for reconstructive surgery, and developing camouflage makeups for the forehead hairline.

Proposal of facial pigmentary unit and facial hyperpigmentation type for Fitzpatrick skin types II-IV.

BACKGROUND: Studies on facial hyperpigmentation across different facial units are limiting. We aimed to analyze melanin pigmentation images to observe facial pigmentary demarcation lines (FPDLs) and suggest facial hyperpigmentation types for normal individuals. MATERIALS AND METHODS: 3D facial melanin pigmentation images of 173 volunteers were obtained and analyzed for the presence of FPDLs. Pigmentation severity was assessed for each of the thirteen facial pigment units. The images were then grouped according to a pattern of hyperpigmentation to suggest three facial hyperpigmentation types-dark spot, photoaging and post-inflammatory hyperpigmentation. RESULTS: Four groups of FPDLs including a novel group I were observed. Nasal, frontal, auricular were the darkest pigmented facial pigment unit, and the anterior neck was the least pigmented. The dark spot type was the most common facial hyperpigmentation type. The photoaging type and the PIH type showed age-dependent distribution, as the photoaging type was more common among the subjects over 40s, and the PIH type was more common in younger subjects. CONCLUSION: Facial hyperpigmentation among healthy individuals with Fitzpatrick skin types II-IV is often accompanied by FPDLs and categorized into three types. Each type is modeled after the pattern of pigmentation associated with certain dermatological disorders. The practical implications of facial hyperpigmentation types can be resourceful in various fields including prevention and treatment of pigmentary disorders.