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Rickettsia and Coxiella spp. are pathogens transmitted by ticks to humans. However, the developmental stage of the tick carrying the greatest risk of infection is unknown. Detection of pathogen-specific genes proves that ticks carrying Rickettsia or Coxiella spp. constitute a reservoir of infection. However, conventional PCR methods are unable to quantitate the pathogens within ticks. In the present study, we collected ticks in the endemic area of Japanese spotted fever, caused by Rickettsia japonica, and determined the rate of tick-borne pathogens carried by the ticks. As a method of evaluation, next-generation sequencing was used to estimate the proportion of pathogens in 10 adult and 10 larval ticks. Ticks were identified Haemaphysalis longicornis (H.L) from the results of the sequencing of PCR products amplified using tick identification-specific primers. The gene detection rates were 10/10 for Rickettsia sp. and 10/10 for Coxiella sp. among the adult ticks. For the larval ticks, the ratios were 7/10 and 5/10 for Rickettsia sp. and Coxiella sp., respectively. The largest proportion of Coxiella sp.-specific DNA reached 96% in one adult tick. The proportion of Rickettsia sp. genes ranged from 1.76% to 41.81% (mean, 15.56%) in the adult ticks. The proportions of Coxiella and Rickettsia spp. genes in the larvae ranged from 0% to 27.4% (mean 5.86%) and from 0% to 14.6% (mean 3.38%), respectively. When the percentage of Rickettsia sp., out of all pathogens detected via next-generation sequencing, was analyzed between the adult and larval stages of the ticks, a significant difference was observed at p = 0.0254. For Coxiella sp., a highly significant difference (p < 0.0001) was found between the adult and larval stages of the ticks. In conclusion, the detection rates and proportions of Rickettsia and Coxiella spp. genes were highest in adult H.L ticks. The risk of contracting tick-borne infections may increase with bites from adult ticks, especially those harboring Coxiella sp.

An 8-year-old boy developed serpiginous erythema on the soles of his feet and was diagnosed with cutaneous larva migrans (CLM). Following treatment with ivermectin, the erythema improved within 7 days, but it recurred 14 days later, requiring a second dose for complete resolution. Ultrasound and MRI did not reveal any parasites, but fluctuations in eosinophils, IgE and IgA levels were observed during treatment. This case highlights the importance of combining multiple diagnostic methods to evaluate treatment effectiveness., (© 2024 John Wiley & Sons Ltd.)

An 86-year-old woman with residual left hemiplegia from a prior stroke, residing in a nursing facility, presented with swelling of the right side of her neck. Tuberculous lymphadenitis was diagnosed through polymerase chain reaction analysis and sputum culture, leading to treatment with isoniazid, rifampicin, and ethambutol. After 2 months, an abscess and ulcer formed; analysis of the bacterial flora of the ulcer revealed a Pseudomonas infection. Treatment with a topical iodine-containing ointment eradicated the Pseudomonas and led to increased diversity with the emergence of species from the Eukaryota and Archaea kingdoms. Subsequently, a loss of diversity occurred, ultimately resulting in a dominance of Escherichia-Shigella. We suggest that the bacterial flora of early ulcers may be dominated by multidrug-resistant Pseudomonas. Escherichia-Shigella may emerge during the ulcer healing process. We, therefore, strongly encourage recognition of the fact that individuals with tuberculosis are immunocompromised and emphasize the critical importance of early intervention in such infections., (© 2024 The Author(s). The Journal of Dermatology published by John Wiley & Sons Australia, Ltd on behalf of Japanese Dermatological Association.)

Music education often struggles to sustain students' long-term commitment, with many perceiving lessons as frustrating or unengaging, leading to discontinuation. To address this gap, our study aimed to elucidate the primary reasons for dropout from the perspectives of various stakeholders, including students, parents, teachers, and principals. Drawing upon the self-determination theory, our research comprehensively investigated external and internal factors contributing to dropout. Among external factors, competing extracurricular commitments, music theory and solfége lessons, and teacher's approach emerge as the most prominent. Among internal factors, our findings highlighted the critical role of autonomy, competency, and relatedness in shaping students' decisions to continue or discontinue music education. Inadequate teacher-student relationships, limited peer interactions, and uninspiring classroom atmospheres significantly impacted dropout. Moreover, challenges in the music school curriculum, such as difficulties with music theory and solfège, resource limitations, and excessive workloads, emerged as prominent barriers to student engagement. By addressing these multifaceted issues, our study underscores the importance of fostering supportive environments that cater to individual needs and interests, ultimately enhancing the overall music education experience and reducing dropout rates. This research represents the first systematic empirical study in Slovenian music education, laying the groundwork for future quantitative investigations to advance education practices in Slovenia., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Kavčič Pucihar, Habe, Rotar Pance and Laure.)

Late adolescences, as a developmentally challenging transitional period between childhood and adulthood, provides a number of pressures that impact well-being of youth. Among approaches for facilitating well-being, music is reported to be one of the most effective ones, which was especially proven during Covid-19 pandemic. Given the significance of music and music listening in late adolescence, our study sought to examine the relationship between psychological well-being and music listening among university students ( N  = 603; N female = 356, N male = 247) with a focus on the social, intrapersonal, and sociocultural context of music listening. The RESPECT music scale, the SPWB, and the PANAS were used to measure positive and negative affect as well as the six components of psychological well-being. The findings revealed that, while there were no gender differences in the sociocultural setting, females reported to listen to music more frequently than males in intrapersonal and social contexts. In two areas, female students rated their psychological well-being higher than male students: personal growth and positive relationships with others. They also reported experiencing positive and negative affect more frequently than men. Regression analyses revealed that the functions of music explained only a small amount of the variance in psychological well-being. Specifically, music listening in a social and sociocultural context significantly explained two aspects of psychological well-being: personal growth and positive relations with others. The intrapersonal context of music listening predicted a positive affect, while the social context predicted a negative affect. Our study highlights several implications of music listening in youth regarding gender either in everyday activities or in educational and clinical setting., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Habe, Dobrota and Reić Ercegovac.)

Intense itching significantly reduces the quality of life, and atopic dermatitis is associated with psychiatric conditions, such as anxiety and depression. Psoriasis, another inflammatory skin disease, is often complicated by psychiatric symptoms, including depression; however, the pathogenesis of these mediating factors is poorly understood. This study used a spontaneous dermatitis mouse model (KCASP1Tg) and evaluated the psychiatric symptoms. We also used Janus kinase (JAK) inhibitors to manage the behaviors. Gene expression analysis and RT-PCR of the cerebral cortex of KCASP1Tg and wild-type (WT) mice were performed to examine differences in mRNA expression. KCASP1Tg mice had lower activity, higher anxiety-like behavior, and abnormal behavior. The mRNA expression of S100a8 and Lipocalin 2 (Lcn2) in the brain regions was higher in KCASP1Tg mice. Furthermore, IL-1β stimulation increased Lcn2 mRNA expression in astrocyte cultures. KCASP1Tg mice had predominantly elevated plasma Lcn2 compared to WT mice, which improved with JAK inhibition, but behavioral abnormalities in KCASP1Tg mice did not improve, despite JAK inhibition. In summary, our data revealed that Lcn2 is closely associated with anxiety symptoms, but the anxiety and depression symptoms caused by chronic skin inflammation may be irreversible. This study demonstrated that active control of skin inflammation is essential for preventing anxiety.

The skin is one of the major immune organs producing large amounts of proinflammatory and inflammatory cytokines in response to internal or exogenous stimuli, inducing systemic inflammation in various internal organs. In recent years, organ damage associated with inflammatory skin diseases such as psoriasis and atopic dermatitis has received increasing attention, and vascular disorder such as arteriosclerosis is one of the serious complications of chronic inflammatory skin diseases. However, the detailed mechanism of arteriosclerosis in dermatitis and the role of cytokines have not been clarified so far. In the current study, using a spontaneous dermatitis model, we investigated the pathophysiology of arteriosclerosis and the treatment option for inflammatory skin conditions. We employed spontaneous dermatitis model mice overexpressing human caspase-1 in the epidermal keratinocyte (Kcasp1Tg). The thoracic and abdominal aorta was investigated histologically. GeneChip and RT-PCR analysis were performed to measure the changes in mRNA levels in the aorta. To elucidate the direct effect on the artery by major inflammatory cytokines, endothelial cells, vascular smooth muscle cells, and fibroblast cells were co-cultured with several cytokines, and mRNA expression levels were measured. In order to observe the efficacy of IL-17A/F in arteriosclerosis, cross-mating with IL-17A, IL-17F, and IL-17A/F deficient mice was performed. Finally, we also measured snap tension in the abdominal aorta in WT, Kcasp1Tg, and IL17A/F-deficient mice. Kcasp1Tg showed a decrease in the diameter of the abdominal aorta compared to wild-type mice. mRNA levels for six genes including Apol11b , Camp , Chil3 , S100a8 , S100a9 , and Spta1 were increased in the abdominal aorta of Kcasp1Tg. Some of the above mRNA levels were also increased in the co-culture with major inflammatory cytokines, IL-17A/F, IL-1β, and TNF-α. Dermatitis improved and mRNA levels were partially ameliorated in Kcasp1Tg with IL-17A/F deletion. Arterial fragility was also evidenced in the inflammatory model, but arterial flexibility was revealed in the IL-17A/F deletion model. Severe dermatitis is closely related to secondary arteriosclerosis caused by the persistent release of inflammatory cytokines. The results also proved that treatment against IL-17A and F may ameliorate arteriosclerosis.

A 91-year-old woman visited our department with scattered small nodule lesions and multiple pules or plaques with a stuck-on appearance. The lesions were intractable and resistant to several treatments. Immunodeficiency was excluded by examinations including a CT scan, white blood cell (WBC) counts, natural killer and neutrophil function assays, and IgG titers against human papillomavirus (HPV) 20. HPV20 was identified using the PCR method. The finding of the skin biopsy showed an irritated type of feature of seborrheic keratosis. Additionally, immunohistochemical staining of the lesion revealed that both TNF-α and IFN-ɤ were produced at the skin lesions. The patient's serum zinc level was slightly low. We noticed that zinc deficiency has been reported to decrease the cytotoxic activity of natural killer cells, which play an important role in eliminating virus-infected cells and tumor cells. Finally, zinc oxide ointment was found to improve the lesions dramatically. HPV20 causes tumors only in immunodeficient patients or in patients with epidermodysplasia verruciformis (EV). In EV, EVER1- or EVER2-encoding membrane proteins, of which are related to zinc transport protein-1 expressed on the membrane of the endoplasmic reticulum, were mutated, leading to increased susceptibility to various viral and bacterial infections due to the decreased intracellular zinc concentration. We speculated that the reduction in local zinc concentration was ameliorated by using zinc oxide ointment, resulting in the recovery from HPV20 infection.

Atopic dermatitis (AD) is classified as a type 2 disease owing to the majority of type 2 lymphocytes that constitute the skin-infiltrating leukocytes. However, all of the type 1-3 lymphocytes intermingle in inflamed skin lesions. Here, using an AD mouse model where caspase-1 was specifically amplified under keratin-14 induction, we analyzed the sequential changes in type 1-3 inflammatory cytokines in lymphocytes purified from the cervical lymph nodes. Cells were cultured and stained for CD4, CD8, and γδTCR, followed by intracellular cytokines. Cytokine production in innate lymphocyte cells (ILCs) and the protein expression of type 2 cytokine IL-17E (IL-25) were investigated. We observed that, as inflammation progresses, the cytokine-producing T cells increased and abundant IL-13 but low levels of IL-4 are produced in CD4-positive T cells and ILCs. TNF-α and IFN-γ levels increased continuously. The total number of T cells and ILCs peaked at 4 months and decreased in the chronic phase. In addition, IL-25 may be simultaneously produced by IL-17F-producing cells. IL-25-producing cells increased in a time-dependent manner during the chronic phase and may work specifically for the prolongation of type 2 inflammation. Altogether, these findings suggest that inhibition of IL-25 may be a potential target in the treatment of inflammation.

Objectives: Aeromonas spp. often cause life-threatening diseases, including necrotizing fasciitis, which may lead to septic shock and ultimately death. Aeromonas infections are believed to be transmitted via minor wounds or the consumption of fresh fish. However, after the detection of Aeromonas hydrophila in ticks in areas endemic to Japanese-spotted fever (JSF), a novel transmission route of A. hydrophila (i.e., via tick bites) has been proposed. We investigated the prevalence of A. hydrophila in ticks in areas endemic and not endemic to JSF in the Mie Prefecture, Japan., Methods: We collected ticks from endemic and nonendemic areas in summer and winter and assessed them for presence of A. hydrophila using polymerase chain reaction., Results: Six A. hydrophila isolates were obtained from 95 ticks in endemic areas, whereas one A. hydrophila isolate was obtained from 142 ticks in non-endemic areas, in summer. All ticks that harboured A. hydrophila were Haemaphysalis longicornis (H.L); these ticks were almost at the larval stage and also carried Rickettsia spp. in the endemic area. In contrast, 51 and 41 ticks in the endemic and non-endemic areas were captured in winter, respectively; A. hydrophila was not detected in these., Conclusions: This study revealed the prevalence of tick-borne A. hydrophila. Therefore, the risk of transmission of A. hydrophila via a tick bite should be considered in the following conditions: areas abundant in H. L. harbouring Rickettsia spp., in areas endemic for JSF, presence of ticks in the larval stage and during the summer season., (© 2022 John Wiley & Sons Ltd.)

Psoriasis and atopic dermatitis are inflammatory skin diseases, and these patients have an increased risk of cardiovascular events and other medical complications. It has been clarified that skin inflammation affects internal organs. Additionally, dental caries tends to occur more frequently in patients with psoriasis and atopic dermatitis. In this study, we aim to investigate the effects of dermatitis on the salivary glands using an inflammation model mouse. Salivary secretion stimulated with pilocarpine was reduced in dermatitis mice. Histologically, dermatitis mice showed amyloid deposition, glandular atrophy, and fibrosis in the salivary glands. Expression of inflammatory cytokines in the salivary glands was higher in dermatitis mice; however, secretion of cytokines in saliva was not significantly different. Dermatitis mice showed decreased salivary secretion and histological changes, which may cause periodontal disease. Therefore, appropriate control of skin inflammation is essential., (© 2022 Japanese Dermatological Association.)

Systemic amyloidosis is recognized as a serious complication of rheumatoid arthritis or inflammatory bowel disease, but also of inflammatory skin disease. However, the detailed molecular mechanism of amyloidosis associated with cutaneous inflammation remains unclear, and therapeutic approaches are limited. Here, we investigated the pathophysiology of amyloidosis secondary to cutaneous inflammation and the therapeutic effects of Janus kinase (JAK) inhibitors by examining a mouse model of spontaneous dermatitis (KCASP1Tg mice). Moreover, KCASP1Tg mice were crossed with interleukin-17A (IL-17A) knockout mice to generate IL-17A-/KCASP1Tg and examine the role of IL-17A in amyloidosis under cutaneous inflammation. KCASP1Tg mice showed severe amyloid deposition in the liver and spleen. Increased serum-neutral fat levels and decreased lymphocyte production were observed in the spleen. Overproduction of amyloidosis was partially ameliorated by the administration of JAK inhibitors and was further improved in IL-17A-/KCASP1Tg mice. IL-17A-producing cells included CD4, gamma delta, and CD8 T cells. In summary, our results from the analysis of a mouse model of dermatitis revealed that skin-derived inflammatory cytokines can induce amyloid deposition in the liver and spleen, and that the administration of JAK inhibitors and, even more, IL-17A ablation, reduced amyloidosis. This study demonstrates that active control of skin inflammation is essential to prevent internal organ amyloidosis.

We report a case of eosinophilic fasciitis triggered by strenuous physical activity, which did not relapse during the follow-up period. We ascertained that interleukin-33 (IL-33) was released from the vascular endothelial cells after intense exercise, inducing type 2 innate lymphocytes (ILC2) and causing fasciitis. A healthy woman experienced itching on both limbs a few hours after a game of drumming. Her hand, knee joints, and legs gradually swelled up with groove signs along the superficial veins. White blood cell and eosinophil counts were significantly elevated. Magnetic resonance imaging revealed a high signal at the fascia on both lower limbs. Histopathological findings of the left lower limb tissue specimen showed edematous fascia with eosinophils. No relapse of eosinophilic fasciitis was observed after finishing treatment with prednisolone. Immunological staining for IL-4, IL-5, IL-33, tumor necrosis factor-α, and interferon-γ was performed on the fascial tissue. Both IL-4 and IL-5 were stained on the lymphocytes at the muscle and fascia levels; however, CD3 and CD4 were unstained in these cells, suggesting that those cells were ILC2. Tumor necrosis factor-α and interferon-γ were unstained. Vascular endothelial cells in the fascia strongly expressed IL-33. Eosinophilic fasciitis may be associated with type 2 immunity triggered by IL-33 in the current case., (© 2022 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)