Novel structure of secreted small molecular weight antigen Mtb12 from Mycobacterium tuberculosis.

Mtb12, a small protein secreted by Mycobacterium tuberculosis, is known to elicit immune responses in individuals infected with the pathogen. It serves as an antigen recognized by the host's immune system. Due to its immunogenic properties and pivotal role in tuberculosis (TB) pathogenesis, Mtb12 is considered a promising candidate for TB diagnosis and vaccine development. However, the structural and functional properties of Mtb12 are largely unexplored, representing a significant gap in our understanding of M. tuberculosis biology. In this study, we present the first structure of Mtb12, which features a unique tertiary configuration consisting of four beta strands and four alpha helices. Structural analysis reveals that Mtb12 has a surface adorned with a negatively charged pocket adjacent to a central cavity. The features of these structural elements and their potential effects on the function of Mtb12 warrant further exploration. These findings offer valuable insights for vaccine design and the development of diagnostic tools.

Novel structure of the anti-CRISPR protein AcrIE3 and its implication on the CRISPR-Cas inhibition.

As a response to viral infections, bacteria have evolved the CRISPR-Cas system as an adaptive immune mechanism, enabling them to target and eliminate viral genetic material introduced during infection. However, viruses have also evolved mechanisms to counteract this bacterial defense, including anti-CRISPR proteins, which can inactivate the CRISPR-Cas adaptive immune system, thus aiding the viruses in their survival and replication within bacterial hosts. In this study, we establish the high-resolution crystal structure of the Type IE anti-CRISPR protein, AcrIE3. Our structural examination showed that AcrIE3 adopts a helical bundle fold comprising four α-helices, with a notably extended loop at the N-terminus. Additionally, surface analysis of AcrIE3 revealed the presence of three acidic regions, which potentially play a crucial role in the inhibitory function of this protein. The structural information we have elucidated for AcrIE3 will provide crucial insights into fully understanding its inhibitory mechanism. Furthermore, this information is anticipated to be important for the application of the AcrIE family in genetic editing, paving the way for advancements in gene editing technologies.

Risk of autoimmune skin and connective tissue disorders after mRNA-based COVID-19 vaccination.

BACKGROUND: Data on the association between the development of autoimmune diseases and COVID-19 vaccination are limited. OBJECTIVE: To investigate the incidence and risk of autoimmune connective tissue disorders following mRNA-based COVID-19 vaccination. METHODS: This nationwide population-based study was conducted in South Korea. Individuals who received vaccination between September 8, 2020-December 31, 2021, were identified. Historical prepandemic controls were matched for age and sex in 1:1 ratio. The incidence rate and risk of disease outcomes were compared. RESULTS: A total of 3,838,120 vaccinated individuals and 3,834,804 controls without evidence of COVID-19 were included. The risk of alopecia areata, alopecia totalis, primary cicatricial alopecia, psoriasis, vitiligo, anti-neutrophil cytoplasmic antibody-associated vasculitis, sarcoidosis, Behcet disease, Crohn disease, ulcerative colitis, rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, Sjogren syndrome, ankylosing spondylitis, dermato/polymyositis, and bullous pemphigoid was not significantly higher in vaccinated individuals than in controls. The risk was comparable according to age, sex, type of mRNA-based vaccine, and cross-vaccination status. LIMITATIONS: Possible selection bias and residual confounders. CONCLUSION: These findings suggest that most autoimmune connective tissue disorders are not associated with a significant increase in risk. However, caution is necessary when interpreting results for rare outcomes due to limited statistical power.

Psychological Stress in Parents of Children with Atopic Dermatitis: A Cross-sectional Study from the Korea National Health and Nutrition Examination Survey.

Atopic dermatitis is a chronically relapsing inflammatory skin condition that has profound impacts on quality of life of patients and their family. The aim of this study is to investigate the psychological stress in parents of children with atopic dermatitis in Korea, using data from the Korean National Health and Nutrition Examination Survey (KNHANES). This cross-sectional study included parents of participants under 19 years of age (970 with atopic dermatitis and 5,733 without atopic dermatitis after excluding those who meet the exclusion criteria) from the 2009 to 2012 KNHANES. The psychological stress state was evaluated with the following four questionnaire items: self-perception of stress, depressed mood, suicidal ideation, and diagnosis of depression by a physician. After adjusting for age, gender, education level, occupation, and marital status, logistic regression analyses indicated that mothers of children with atopic dermatitis had a higher frequency of stress perception (adjusted odds ratio (aOR) 1.46 (95% confidence interval (95% CI) 1.22-1.74), p < 0.01) and suicidal ideation (aOR 1.40 (95% CI 1.1-1.79), p < 0.01) than those without atopic dermatitis. In contrast, fathers of children with atopic dermatitis did not show a significant difference in all items compared with those of children without atopic dermatitis. Understanding the psychological stress in parents of children with atopic dermatitis is important for clinicians, since evaluation, management and support for parents, especially mothers, of children with atopic dermatitis are required.

Analysis of Medication Errors Reported by Community Pharmacists in the Republic of Korea: A Cross-Sectional Study.

Background and objectives: We aimed to describe medication-related incidents or medication errors (MEs) reported by community pharmacists and analyze the prevalent medications involved. Materials and Methods: We extracted ME reports from databases comprising patient safety incidents reported to the Korean Pharmaceutical Association between January 2013 and June 2021. Medications were analyzed according to the second (therapeutic subgroup) and fifth (chemical substance) levels of the Anatomical Therapeutic Chemical classification. Results: A total of 9046 MEs were identified, most of which were near miss reports (88.3%). Among the errors that reached the patients (521 cases), harmful incidents accounted for 76.8%. Most MEs occurred during prescription (89.5%), while harmful MEs occurred mainly during dispensing (73.3%). In the prescription step, wrong drugs (44.8%), dosing errors (27.0%), and wrong durations (14.0%) were common. Anti-inflammatory and anti-rheumatic products (M01), drugs for acid-related disorders (A02), and antihistamines for systemic use (R06) were the most frequently reported medication classes involved. Harmful incidents were most common for dosing errors (31.0%) and wrong drugs (26.8%) and were common with warfarin, levothyroxine, and glimepiride. Conclusions: The MEs reported by community pharmacists were mainly prescribing errors, most of which were rectified before reaching patients. The prevalent medications involved in harmful errors include anti-diabetic, anti-thrombotic, and anti-inflammatory agents.

Smoking and Periodontitis Can Play a Synergistic Role in the Development of Psoriasis: A Nationwide Cohort Study.

BACKGROUND: Periodontitis is a chronic inflammatory disorder involving the periodontium. The precise nature of the association between periodontitis and psoriasis has not been determined. OBJECTIVE: This nationwide population-based study investigated the relationship between periodontitis and the risk of psoriasis. METHODS: A health screening database, which is a sub-dataset of the Korean National Health Insurance System database, was used in this study. Subjects with (n = 1,063,004) and without (n = 8,655,587) periodontitis who underwent health examinations from January to December 2009 were followed for 9 years. RESULTS: In multivariable analysis, compared to the non-periodontitis group, periodontitis patients had a significantly higher risk of developing psoriasis (hazard ratio 1.116, 95% confidence interval 1.101-1.13). Non-smokers with periodontitis had an 11% increase in risk of psoriasis and smokers with periodontitis had a 26.5% increase in risk of psoriasis compared to non-smokers without periodontitis. CONCLUSION: Our study highlights periodontitis as a potential independent risk factor for psoriasis, increasing awareness of the synergistic role of smoking and periodontitis in the pathogenesis of psoriasis.

Leukaemia Cutis: Clinical Features and Outcomes of 56 Patients.

Leukaemia is a malignant neoplasm of the haematopoietic system. Cutaneous manifestations of leukaemia are called leukaemia cutis, and are regarded as a sign of poorer prognosis and shorter survival time. A single-institution retrospective review was performed of medical records of patients diagnosed with leukaemia cutis in the dermatology department of Seoul St Mary's Hospital between January 2012 and April 2021. Fifty-six cases with cutaneous leukaemic involvement and underlying haematological malignancy were included (40 acute myelogenous leukaemia, 8 acute lymphoblastic leukaemia, 3 chronic myeloid leukaemia, 2 chronic lymphocytic leukaemia, and 3 myelodysplastic syndrome). Male-female ratio 1.9:1, mean age at diagnosis 45.8 years. Plaques (28%) and papules (27%) were the most common skin lesions, followed by patches (18%) and nodules (16%). Mean time from diagnosis of leukaemia to development of leukaemia cutis was 12.3 months. Forty-six patients (84%) died during the 7-year follow-up; mean time from diagnosis of leukaemia cutis to death was 5.4 months. The results suggest that leukaemia cutis is associated with poor outcomes in patients with leukaemia. Comprehensive skin examination of these patients may help diagnose leukaemia cutis early, enabling prompt treatment.

Ultrasmall polymer-coated cerium oxide nanoparticles as a traumatic brain injury therapy.

No medication has been approved for secondary injuries after traumatic brain injury (TBI). While free radicals are considered a major mediator of secondary injury, conventional antioxidants only have modest clinical efficacy. Here, we synthesized CX201 consisting of core cerium oxide nanoparticles coated with 6-aminocaproic acid and polyvinylpyrrolidone in aqueous phase. CX201 with 3.49 ± 1.11 nm of core and 6.49 ± 0.56 nm of hydrodynamic diameter showed multi-enzymatic antioxidant function. Owing to its excellent physiological stability and cell viability, CX201 had a neuroprotective effect in vitro. In a TBI animal model, an investigator-blinded randomized experiment showed a single intravenously injected CX201 significantly improved functional recovery compared to the control. CX201 reduced lipid peroxidation and inflammatory cell recruitment at the damaged brain. These suggest ultrasmall CX201 can efficiently reduce secondary brain injuries after TBI. Given the absence of current therapies, CX201 may be proposed as a novel therapeutic strategy for TBI.

The long-term risk of lymphoma and skin cancer did not increase after topical calcineurin inhibitor use and phototherapy in a cohort of 25,694 patients with vitiligo.

BACKGROUND: Topical calcineurin inhibitors have been used to treat vitiligo, either alone or in combination with phototherapy; however, the long-term safety of these agents remains controversial. OBJECTIVE: To investigate the risk of lymphoma and skin cancer in vitiligo patients who received topical calcineurin inhibitors or phototherapy. METHODS: A multicenter retrospective cohort study of 25,694 vitiligo patients who received topical calcineurin inhibitors or phototherapy for 6 weeks or more between 2001 and 2019 was performed. Cumulative doses of topical calcineurin inhibitors and total phototherapy sessions were determined. Outcomes were the development of lymphoma or skin cancer after enrollment, confirmed through chart review and pathology reports. RESULTS: During 95,203 person-years, 13 cases of lymphoma, 22 of actinic keratosis, 15 of nonmelanoma skin cancer, and 5 of melanoma were observed. The risk of lymphoma and skin cancer was not significantly increased by topical calcineurin inhibitor dose or phototherapy sessions. The interaction between the topical calcineurin inhibitors and phototherapy was not associated with an increased risk of skin cancer. LIMITATIONS: Retrospective study, individual follow-up duration less than 4 years, and no adjustment for comorbidities and medication history. Not generalizable to other races. CONCLUSION: The long-term risk of skin cancer or lymphoma was not associated with the use of topical calcineurin inhibitors, phototherapy, and both treatments in combination in patients with vitiligo.

Epigallocatechin-3-gallate Can Prevent Type 2 Human Papillomavirus E7 from Suppressing Interferon-Stimulated Genes.

Human papillomavirus (HPV) in high-risk groups is known to suppress the type I interferon (IFN) signaling pathway leading to the transcription of interferon-stimulated genes (ISGs), which have many antiviral functions. However, the effects of HPV on the action of various ISGs in low-risk groups are not fully understood. We aimed to investigate whether antiviral ISGs are expressed in transfected keratinocytes with type 2 HPV (HPV-2) E7. The mRNA and protein expressions of ISGs and type I IFN signaling pathway components were evaluated by quantitative real-time polymerase chain reaction, western blot, immunofluorescence, and/or immunohistochemistry. Compared with normal skin, mRNA expression of all ISGs in HPV-2 positive cutaneous warts was significantly decreased (p < 0.05). In comparison with empty vector transfection, E7 transfection significantly down-regulated the mRNA and protein expressions of ISGs and type I IFN signaling pathway components, which were significantly up-regulated by E7 siRNA transfection (p < 0.05). Interestingly, epigallocatechin-3-gallate (EGCG) pretreatment up-regulated the mRNA and protein expressions of ISGs and type I IFN signaling pathway components, which were significantly down-regulated by E7 transfection (p < 0.05). Our results demonstrate that EGCG is a potential candidate for cutaneous wart prevention.

Cutaneous Disorders Associated with Castleman's Disease.

Castleman's disease is a rare disease of the lymph nodes and related tissues, presenting as angiofollicular or giant lymph node hyperplasia. Although various skin manifestations have been reported to occur in Castleman's disease, a comprehensive study of cutaneous disorders in Castleman's disease is lacking. Therefore, the aim of this study was to investigate Castleman's disease-associated cutaneous disorders. The medical records of 57 patients with Castleman's disease who visited our hospitals from January 2007 to May 2018 were analysed retrospectively. Patients were classified according to the presence of skin involvement. Plasma variant-type Castleman's disease and multicentric Castleman's disease were more commonly found in patients with Castleman's disease with a cutaneous disorder than in those without a cutaneous disorder. In addition, the skin disorders were classified according to pathomechanisms: immune complex-related (paraneoplastic pemphigus, xanthogranulomas), cytokine-related (vasculitis-like lesion, cherry angioma, hyperpigmentation), and non-specific (pruritus). This study builds on previous case reports of cutaneous disorders in Castleman's disease and proposes a new classification system.

Ceria Nanoparticles Synthesized With Aminocaproic Acid for the Treatment of Subarachnoid Hemorrhage.

Background and Purpose- Despite early aneurysm repair and aggressive management for complications, subarachnoid hemorrhage (SAH) results in at least 25% mortality rate and 50% persistent neurological deficit. We investigated whether ceria nanoparticles which have potent antioxidative activities can protect against subarachnoid hemorrhage via attenuating fatal brain injuries. Methods- Uniform, 3 nm, water-dispersed ceria nanoparticles were prepared from short sol-gel reaction of cerium (III) ions with aminocaproic acid in aqueous phase. SAH was induced by endovascular perforation of middle cerebral artery of rats. A single dose of ceria nanoparticles (0.5 mg Ce/kg) or saline control was randomly administered intravenously at an hour post-SAH. Neuronal death, macrophage infiltration, SAH grade, and brain edema were evaluated at 72 hours. Mortality and neurological function were assessed for 14 days. Results- The obtained ceria nanoparticles with high Ce3+ to Ce4+ ratio demonstrated potent antioxidative, cytoprotective, and anti-inflammatory activities in vitro. In rodent SAH models, the severity of hemorrhage was comparable between the ceria nanoparticles- and saline-treated groups. However, ceria nanoparticles significantly reduced neuronal death, macrophage infiltration, and brain edema after SAH. Ceria nanoparticles successfully improved survival rates (88.2% in the ceria nanoparticles group versus 21.1% in the control group; P<0.001) and neurological outcomes (modified Garcia score: 12.1±0.5 in the ceria nanoparticles group versus 4.4±0.5 in the control group; P<0.001) of the animals with SAH. Conclusions- Ceria nanoparticles, totally synthesized in aqueous phase using aminocaproic acid, demonstrated promising results against SAH via potent antioxidative, neuroprotective and anti-inflammatory activities. Given the obvious limitations of current therapies for SAH, ceria nanoparticles can be a potential therapeutic agent which might result in a paradigm shift in SAH treatment.

Epidemiology and Medication Trends in Patients with Psoriasis: A Nationwide Population-based Cohort Study from Korea.

This study investigated the prevalence of psoriasis and trends in prescription of medications for patients with psoriasis using the Korean National Health Insurance Claims Database from 2006 to 2015. The prevalence of psoriasis and psoriatic arthritis per 10,000 people increased from 47.4 to 61.5 and from 0.04 to 0.23 respectively. The prescription of topical agents was a mean of 73.3%. For systemic agents, prescription of acitretin decreased from 74.8 to 44.5%, methotrexate showed a fluctuation, with a mean of 14.9% and cyclosporine increased from 9.0 to 41.2%. The prescription of biological agents increased sharply from 18 to 1,127 patients. Use of ustekinumab increased from 4.1 to 82.4%; use of infliximab decreased from 20.7 to 6.7% and etanercept decreased from 100 to 6.1%. This study showed an increasing trend in the prevalence of psoriasis. We also reported a rapid increase in the use of biologics in recent years.