Toxic epidermal necrolysis complicated with primary cutaneous aspergillosis: A report of four cases.

Primary cutaneous aspergillosis (PCA) is a rare opportunistic infection caused by Aspergillus that can be life-threatening. PCA is mainly reported in immunocompromised hosts such as patients with AIDS, those with hematologic malignancy, or infants with occlusive dressings. However, no study has previously reported PCA associated with toxic epidermal necrolysis (TEN). This study reports four cases of TEN complicated with PCA, presenting with discrete gray or black spots over newly formed epithelia. Risk factors of PCA in patients with TEN include host factors, iatrogenic factors, indoor environment, and wound care. Two of the four cases eventually died, highlighting the importance of further exploring PCA in patients with TEN.

Case report: Rubella virus-associated cutaneous granuloma in an adult with TAP1 deficiency.

Rubella virus-associated granulomas commonly occur in immunocompromised individuals, exhibiting a diverse range of clinical presentations. These manifestations can vary from predominantly superficial cutaneous plaques or nonulcerative nodules to more severe deep ulcerative lesions, often accompanied by extensive necrosis and significant tissue destruction. TAP1 deficiency, an exceedingly rare primary immune-deficiency disorder, presents with severe chronic sino-pulmonary infection and cutaneous granulomas. This report highlights the occurrence of rubella virus-associated cutaneous granulomas in patients with TAP1 deficiency. Notably, the pathogenic mutation responsible for TAP1 deficiency stems from a novel genetic alteration that has not been previously reported. This novel observation holds potential significance for the field of diagnosis and investigative efforts in the context of immunodeficiency disorders.

Poor clinical outcomes and immunoevasive contexture in CD161+CD8+ T cells barren human pancreatic cancer.

BACKGROUND: The role of CD161 expression on CD8+ T cells in tumor immunology has been explored in a few studies, and the clinical significance of CD161+CD8+ T cells in pancreatic ductal adenocarcinoma (PDAC) remains unclear. This study seeks to clarify the prognostic value and molecular characteristics linked to CD161+CD8+ T cell infiltration in PDAC. METHODS: This study included 186 patients with confirmed PDAC histology after radical resection. CD161+CD8+ T cell infiltration was assessed using immunofluorescence staining on tumor microarrays. Flow cytometry and single-cell RNA sequencing were used to evaluate their functional status. RESULTS: We observed significant associations between tumor-infiltrating CD161+CD8+ T cells and clinicopathological factors, such as tumor differentiation, perineural invasion, and serum CA19-9 levels. Patients with higher tumor-infiltrating CD161+CD8+ T cell levels had longer overall survival (OS) and recurrence-free survival (RFS) than those with lower levels. Multivariable analysis confirmed tumor-infiltrating CD161+CD8+ T cell as an independent prognostic indicator for both OS and RFS. Notably, a combination of tumor-infiltrating CD161+CD8+ T cell and CA19-9 levels showed a superior power for survival prediction, and patients with low tumor-infiltrating CD161+CD8+ T cell and high CA19-9 levels had the worst survival. Furthermore, lower tumor-infiltrating CD161+CD8+ T cells were associated with a better response to adjuvant chemotherapy. Finally, we identified tumor-infiltrating CD161+CD8+ T cells as a unique subtype of responsive CD8+ T cells characterized by increased levels of cytotoxic cytokines and immune checkpoint molecules. CONCLUSION: CD161+CD8+ T cells exhibit elevated levels of both cytotoxic and immune-checkpoint molecules, indicating as a potential and attractive target for immunotherapy. The tumor-infiltrating CD161+CD8+ T cell is a valuable and promising predictor for survival and therapeutic response to adjuvant chemotherapy in PDAC. Further research is warranted to validate its role in the risk stratification and optimization of therapeutic strategies.

Anti-immunoglobulin E provides an additional therapy to conventional steroids for Kimura's disease.

Kimura's disease (KD) is a chronic inflammatory disease characterized by painless subcutaneous head and neck swelling, eosinophilia, and elevated serum immunoglobulin (Ig) E levels. There are various therapies, including surgery, radiation, systemic steroids, and immune suppressants, but their efficacy remains moderate due to the high recurrence rate. Biologics, like monoclonal antibodies, have shown tremendous effectiveness for chronic inflammatory diseases. Omalizumab is a monoclonal antibody against IgE and has not been approved for KD so far. We describe two refractory KD cases that responded to a small dose of steroids plus omalizumab. Additionally, we reviewed another 13 KD cases that were treated with biologics, including omalizumab, rituximab, dupilumab, and mepolizumab. The results indicate that biologics provide an alternative treatment strategy for KD.

The in vitro Activity of Echinocandins Against Clinical Trichophyton rubrum Isolates and Review of the Susceptibility of T. rubrum to Echinocandins Worldwide.

Introduction: The emergence of resistance in Trichophyton rubrum to azoles and terbinafine has become increasingly evident in recent years, necessitating the development of novel antifungal drugs and the exploration of new indications for existing agents. Methods: In this study, we retrospectively evaluated the in vitro antifungal activity of 3 echinocandins (anidulafungin, caspofungin, and micafungin) against 73 clinical isolates of T. rubrum collected from a teaching hospital in Shanghai, China, using EUCAST E.DEF 9.3.1 with minor modification. We also reviewed the susceptibility of T. rubrum to echinocandins globally by literature searching. Results: Our findings revealed that micafungin exhibited the lowest modal minimum effective concentration (MEC) value (0.08 mg/L, n = 28) and the lowest geometric mean (GM) MEC value (0.014 mg/L) among the 73 isolates of T. rubrum tested, followed by anidulafungin with a modal MEC value of 0.016 mg/L (n = 67) and a GM of 0.018 mg/L. Caspofungin displayed a higher modal MEC value of 0.5 mg/L (n = 35) and a GM of 0.308 mg/L. Despite variations in methodologies, similar results were obtained from the review of five relevant studies included in our analysis. Discussion: Echinocandins exhibited excellent in vitro activity against T. rubrum isolates, with micafungin and anidulafungin demonstrating greater potency than caspofungin. These findings suggest that echinocandins could be considered as potential treatment options for managing recalcitrant dermatophytoses resulting from the emergence of resistance. However, it is important to note that the clinical efficacy of these in vitro findings has yet to be established and warrants further investigation.

Efficacy and associated neurotransmitters of digital cognitive behavior therapy for atopic dermatitis: A comparative effectiveness research.

BACKGROUND: Negative emotions are a major comorbidity of atopic dermatitis (AD). Evidence that supports the effectiveness of digital cognitive behavioral therapy (dCBT) as an adjuvant therapy for AD remains limited. OBJECTIVE: To investigate the preliminary efficacy of additional dCBT and potential neurotransmitter biomarkers for AD accompanied by negative emotions. METHODS: Thirty-two patients with AD were recruited and examined for clinical severity and negative emotions including insomnia, anxiety, and depression. Patients with mild-to-moderate negative emotions were divided into two groups that received standard care (N = 9) or mobile app-delivered CBT plus standard care (N = 11) for 12 weeks. Plasma levels of 40 neurotransmitters were determined using liquid chromatography tandem mass spectrometry pre- and post-treatment. RESULTS: Skin lesions, itch, and insomnia were significantly improved in both treatment groups. Improvements of itch (P = 0.0449) and insomnia (P = 0.0089) were more robust in the combination treatment group than those in the standard treatment group. Neurotransmitters that involve tryptophan, dopamine, and histidine pathways were markedly altered in patients with AD compared with healthy controls. Taurine levels were selectively increased following dCBT plus standard care (P = 0.0259). Baseline levels of L-tyrosine were negatively correlated with the reduction of skin lesions (r = -0.9073, P = 0.0334) and itch intensity (r = -0.9322, P = 0.0210) in the combination therapy group. CONCLUSIONS: dCBT provides an efficacious supplementary approach for AD accompanied by negative emotions. Emotion-related neurotransmitters may contribute to AD and serve as indicators for treatment effects.

Translation-dependent skin hyperplasia is promoted by type 1/17 inflammation in psoriasis.

BACKGROUND: Psoriasis vulgaris (PV) is a chronic skin inflammatory disease and characterized by aberrant epidermal hyperplasia. The molecule eukaryotic initiation factor (eIF) 4E controls translation initiation of certain protein synthesis and determines cell cycle or differentiation fate. OBJECTIVE: To determine the role of eIF4E in keratinocytes abnormal differentiation in the context of psoriasis. METHODS: The expression of eIF4E in psoriatic skin lesions and normal skin from human subjects was examined by western blot and immunohistochemistry. In a murine model of psoriasis-like dermatitis that is induced by topical imiquimod, 4EGI-1 was used to inhibit eIF4E activities. To measure murine skin eIF4E and keratinocytes differentiation, immunofluorescence and western blot assays were conducted. Normal human epidermal keratinocytes (NHEK) were isolated, cultured, and stimulated with cytokines including TNF-α, IFN-γ, and IL-17A, respectively. Immunofluorescence and western blot were performed to test eIF4E and effect of 4EGI-1 in a co-culture system. RESULTS: Compared with healthy controls, skin lesions from patients with PV exhibited a higher expression of eIF4E, which was positively correlated with the epidermal thickness. This expression pattern of eIF4E was replicated by the imiquimod-induced murine model. Skin hyperplasia and eIF4E activities in the murine model were attenuated by the administration of 4EGI-1. Both IFN-γ and IL-17A, rather than TNF-α, are sufficient to induce NHEK abnormal differentiation. This effect can be disrupted by 4EGI-1. CONCLUSION: eIF4E plays a crucial role in keratinocytes abnormal differentiation driven by type 1/17 inflammation in the context of psoriasis. The initiation of abnormal translation provides an alternative treatment target for psoriasis.

Kinetics of Metastable Argon Optical Excitation and Gain in Ar/He Microplasmas.

The optically pumped rare-gas metastable laser is capable of high-intensity lasing on a broad range of near-infrared transitions for excited-state rare gas atoms (Ar*, Kr*, Ne*, Xe*) diluted in flowing He. The lasing action is generated by photoexcitation of the metastable atom to an upper state, followed by collisional energy transfer with He to a neighboring state and lasing back to the metastable state. The metastables are generated in a high-efficiency electric discharge at pressures of ∼0.4 to 1 atm. The diode-pumped rare-gas laser (DPRGL) is a chemically inert analogue to diode-pumped alkali laser (DPAL) systems, with similar optical and power scaling characteristics for high-energy laser applications. We used a continuous-wave linear microplasma array in Ar/He mixtures to produce Ar(1s5) (Paschen notation) metastables at number densities exceeding 1013 cm-3. The gain medium was optically pumped by both a narrow-line 1 W titanium-sapphire laser and a 30 W diode laser. Tunable diode laser absorption and gain spectroscopy determined Ar(1s5) number densities and small-signal gains up to ∼2.5 cm-1. Continuous-wave lasing was observed using the diode pump laser. The results were analyzed with a steady-state kinetics model relating the gain and the Ar(1s5) number density.

HIF1-α upregulation induces proinflammatory factors to boost host killing capacity after Aspergillus fumigatus exposure.

Aims: HIF1-α is an important transcription factor in the regulation of the immune response. The protective function of HIF1-α in the host epithelial immune response to Aspergillus fumigatus requires further clarification. Methods: In this study we demonstrated the effect of upregulation of HIF1-α expression in A549 cells and mouse airway cells exposed to A. fumigatus in vivo. Results: The killing capacity was enhanced by boosting proinflammatory factors both in vitro and in vivo. Moreover, airway inflammation was reduced in the HIF1-α-upregulated mice. Conclusion: We identified a protective role for HIF1-α in anti-A. fumigatus immunity. Modulation of HIF1-α might be a target for the development of aspergillosis therapy.

Development and Validation of a Combined Ferroptosis and Immune Prognostic Model for Melanoma.

Background: Melanoma development and progression are significantly influenced by ferroptosis and the immune microenvironment. However, there are no reliable biomarkers for melanoma prognosis prediction based on ferroptosis and immunological response. Methods: Ferroptosis-related genes (FRGs) were retrieved from the FerrDb website. Immune-related genes (IRGs) were collected in the ImmPort dataset. The TCGA (The Cancer Genome Atlas) and GSE65904 datasets both contained prognostic FRGs and IRGs. The model was created using multivariate Cox regression, the least absolute shrinkage and selection operator (LASSO) Cox regression analysis, and the analysis and comparison between the expression patterns of ferroptosis and immune cell infiltration were done. Last but not least, research was conducted to assess the expression and involvement of the genes in the comprehensive index of ferroptosis and immune (CIFI). Results: Two prognostic ferroptosis- and immune-related markers (PDGFRB and FOXM1) were utilized to develop a CIFI. In various datasets and patient subgroups, CIFI exhibits consistent predictive performance. The fact that CIFI is an independent prognostic factor for melanoma patients was revealed. Patients in the CIFI-high group further exhibited immune-suppressive characteristics and had elevated ferroptosis gene expression levels. The results of in vitro research point to the possibility that the PDGFRB and FOXM1 genes function as oncogenes in melanoma. Conclusion: In this study, a novel prognostic classifier for melanoma patients was developed and validated using ferroptosis and immune expression profiles.

Electronic Configuration Assignments for UO from Electric Dipole Moment Measurements.

Diatomic UO has more than 48 bound states within 10000 cm-1 of the ground state. This electronic state congestion has been attributed to interleaved states from the electronic configurations U2+(5f37s)O2- and U2+(5f27s2)O2-, respectively. Ligand field theory predicts that each electronic configuration will exhibit states with distinguishable, characteristic vibrational and rotational constants. However, vibronic state mixing modifies the observed vibration-rotation constants, leading to uncertainty in the configurational assignments. The permanent electric dipole moment (µe) of an electronic state should also manifest a value that is characteristic of the parent electronic configuration. µe and other electrostatic and magnetostatic properties should be less influenced by the vibronic state mixing, providing more robust indicators for configurational assignments. In the present study, we have measured the µe values for four electronic states of UO. The results clearly demonstrate that the ground state (X(1)4) and the first electronically excited state ((2)4) are derived from the U2+(5f37s)O2- and U2+(5f27s2)O2- configurations, respectively.

Integrating lncRNAs and mRNAs Expression Profiles in Penicillin-Induced Persistent Chlamydial Infection in HeLa Cells.

Chlamydia trachomatis (C. trachomatis) is a major etiological agent of sexually transmitted infection. Some stressing conditions can result in persistent chlamydial infection, which is thought to be associated with severe complications including ectopic pregnancy and tubal factor infertility. Long noncoding RNAs (lncRNAs) have been identified as key modulators in many biological processes. Nevertheless, the role of lncRNAs in persistent chlamydial infection is still unclear. In this study, we used lncRNA and mRNA microarray to identify the global lncRNAs and mRNAs expression in penicillin-induced persistent chlamydial infection in HeLa cells as well as the control group (HeLa cells without C. trachomatis infection). Among 1005 differentially expressed lncRNAs, 585 lncRNAs were upregulated and 420 downregulated in persistent chlamydial infection, while 410 mRNAs were identified to express differentially, of which 113 mRNAs were upregulated and 297 downregulated. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis with differentially expressed genes were performed. We then constructed the lncRNA-miRNA-mRNA competing endogenous RNAs (ceRNAs) network. Four mRNAs were validated to be changed by quantitative real-time PCR which were correlated with the microarray result. Integration of protein-protein interaction network was constructed and hub genes were identified. These findings provide a new perspective on the molecular mechanisms of penicillin-induced persistent chlamydial infection.

Case Report: Pemphigus in Young Patients With Thymic Anomalies.

Pemphigus is an autoimmune disease that occurs mainly in elderly individuals. Young patients with pemphigus are rare, and the risk factors are unclear. The thymus is associated with a variety of autoimmune diseases, and there have been reports of pemphigus complicated with thymic diseases. Here, we report three cases of young patients with pemphigus that were associated with thymic anomalies. We suggest that thymic anomalies may be a risk factor for the early onset of pemphigus and may be associated with increased severity of the disease. Interventions for thymic diseases have certain benefits for improving the effect of treatments and prognosis of these patients.

Inhibition of tumor necrosis factor improves conventional steroid therapy for Stevens-Johnson syndrome/toxic epidermal necrolysis in a cohort of patients.

BACKGROUND: Systemic steroid therapies for Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) have been challenged because of their limited benefits. Whether additional tumor necrosis factor (TNF) α inhibition provides an optimized approach remains unexplored. OBJECTIVE: To investigate the efficacy of TNF-α inhibition combined with a steroid to treat SJS/TEN and to identify potential biomarkers. METHODS: Twenty-five patients with SJS/TEN were recruited and divided into 2 groups: 10 patients received methylprednisolone and 15 patients received etanercept plus methylprednisolone. Serum levels of granzyme B, perforin, interferon-γ, interleukin (IL) 6, IL-15, IL-18, macrophage inflammatory protein 1α, macrophage inflammatory protein 1ß, and TNF-α were measured by multiplex cytokine analysis kits during the acute and resolution phases. RESULTS: Compared with the steroid monotherapy, the combination therapy significantly shortened the course of the initial steroid treatment and the duration of the acute stage, hospitalization stay, and skin re-epithelialization. Although both therapies significantly reduced IL-15 levels; the combination therapy also decreased IL-6 and IL-18 levels. While the level of IL-15 was positively correlated with skin re-epithelialization time in both groups, the level of IL-6 served as an additional marker for the course of the disease in the combination therapy group. LIMITATIONS: The cohort size is relatively small. CONCLUSION: Additional TNF-α inhibition to steroid treatment appeared to improve outcomes for SJS/TEN.

Primary Eccrine Porocarcinoma of the Thumb With Metastasis: A Rare Case Report and Literature Review.

ABSTRACT: Eccrine porocarcinoma (EPC) is a rare malignant sweat gland tumor that accounts for approximately 0.005% of all cutaneous carcinomas. It favors the lower extremities. Only 3% of EPCs are on the hand, and only 6 cases occurring specifically on fingers have been previously documented. However, we met a patient with EPC presenting the primary lesion on the left thumb and an extensive cutaneous metastasis on the left forearm. Pathologic findings of axillary lymph nodes confirmed lymphatic metastasis.

Association Between Daily Dietary Eicosatetraenoic Acid Intake and the Lower Risk of Psoriasis in American Adults.

PURPOSE: Unlike eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), the relationship between eicosatetraenoic acid (ETA) and psoriasis remains unclear. Therefore, We performed a cross-sectional study in the general American population to investigate the association between daily dietary ETA, EPA, and DHA intake and the risk of psoriasis. PARTICIPANTS AND METHODS: This study applied data from the National Health and Nutrition Examination Survey (NHANES) 2003-2006 and 2009-2014. Dietary n3 polyunsaturated fatty acids (PUFA) were calculated based on two 24-hour dietary recall interviews. We defined psoriasis by responding to the question "Have you ever been told by a doctor or other health care professional that you had psoriasis?". Multivariable logistic regression analysis, trend tests, subgroup analysis, and interaction tests were used to evaluate the associations of ETA, EPA, and DHA intake with the risk of psoriasis, respectively. RESULTS: A total of 15,733 participants were included in this study. In our optimal multivariate-adjusted model, the odds ratio (OR) with 95% confidence interval (CI) of psoriasis were 0.30 (0.12, 0.88), 1.92 (0.78, 4.74), 1.28 (0.72, 2.27) for daily dietary ETA, EPA, and DHA intake, respectively. Trend tests showed a dose-effect relationship between daily dietary ETA intake and the lower risk of psoriasis. Subgroup analysis and tests for interaction showed that the association was stable in different subgroups. CONCLUSION: Our study revealed that there might be a dose-effect association of daily dietary ETA intake with the lower risk of psoriasis in American adults.

Electronic Spectroscopy and Photoionization of LiBe.

LiBe has been the subject of several theoretical investigations and one spectroscopic study. Initially, these efforts were motivated by interest in the intermetallic bond. More recent work has explored the potential for producing LiBe and LiBe+ at ultracold temperatures. In the present study, we have advanced the spectroscopic characterization of several electronic states of LiBe and the ground state of LiBe+. For the neutral molecule, the 12Π, 22Σ+, 32Σ+, and 42Π(3d) states were observed for the first time. Data for the 22Σ+-X2Σ+ transition support a theoretical prediction that this band system is suitable for direct laser cooling. Photoelectron spectroscopy has been used to determine the ionization energy of LiBe and map the low-energy vibrational levels of LiBe+ X1Σ+. Overall, the results validate the predictions of high-level quantum chemistry calculations for both LiBe and LiBe+.

Vacuum-Assisted Closure and Skin Grafting Combined with Amphotericin B for Successful Treatment of an Immunocompromised Patient with Cutaneous Mucormycosis Caused by Mucor irregularis: A Case Report and Literature Review.

Cutaneous mucormycosis caused by Mucor irregularis (M. irregularis) is a rare condition that typically occurs in immunocompetent patients. Herein, we describe an immunocompromised patient with cutaneous M. irregularis infection who was successfully treated with debridement combined with vacuum assisted closure (VAC) negative pressure technique and split-thickness skin grafting. We present this case owing to its complexity and rarity and the successful treatment with surgical therapy. A 58-year-old man presented to our hospital with a history of skin ulcers and eschar on the right lower leg since two months. He had been receiving methylprednisolone therapy for bullous pemphigoid that occurred five months prior to the present lesions. Histopathological examination of a right leg lesion showed broad, branching hyphae in the dermis. Fungal culture and subsequent molecular cytogenetic analysis identified the pathogen as M. irregularis. After admission, methylprednisolone was gradually tapered and systemic treatment with amphotericin B (total dose 615 mg) initiated along with others supportive therapies. However, the ulcers showed no improvement, and amphotericin B had to be discontinued owing to development of renal dysfunction. After extensive surgical debridement combined with VAC and skin grafting, his skin ulcers were healed; subsequent fungal cultures of the lesions were negative. The patient exhibited no signs of recurrence at 36-month follow-up. Twenty-six cases with M. irregularis-associated cutaneous mucormycosis in literature were reviewed.