[Hematologic Diseases and Neurological Complications].

Many hematologic diseases can be complicated by neurological symptoms during the disease course. Hematologic diseases can contribute to strokes and neuropathies; thus, neurologists should be aware of them. Recent reports have increased of neurological side effects associated with new anticancer therapies such as immune checkpoint inhibitors and chimeric antigen receptor-T cell therapy. The relationship between hematologic diseases and neurological complications is expected to become more prevalent.

An Appraisal for Providing Charge Transfer (CT) Through Synthetic Porous Frameworks for their Semiconductor Applications.

In recent years, there has been considerable focus on the development of charge transfer (CT) complex formation as a means to modify the band gaps of organic materials. In particular, CT complexes alternate layers of aromatic molecules with donor (D) and acceptor (A) properties to provide inherent electrical conductivity. In particular, the synthetic porous frameworks as attractive D-A components have been extensively studied in recent years in comparison to existing D-A materials. Therefore, in this work, the synthetic porous frameworks are classified into conjugated microporous polymers (CMPs), covalent organic frameworks (COFs), and metal-organic frameworks (MOFs) and compare high-quality materials for CT in semiconductors. This work updates the overview of the above porous frameworks for CT, starting with their early history regarding their semiconductor applications, and lists CT concepts and selected key developments in their CT complexes and CT composites. In addition, the network formation methods and their functionalization are discussed to provide access to a variety of potential applications. Furthermore, several theoretical investigations, efficiency improvement techniques, and a discussion of the electrical conductivity of the porous frameworks are also highlighted. Finally, a perspective of synthetic porous framework studies on CT performance is provided along with some comparisons.

Effect of high-fat diet on cerebral pathological changes of cerebral small vessel disease in SHR/SP rats.

Cerebral small vessel diseases (CSVD) are neurological disorders associated with microvessels, manifested pathologically as white matter (WM) changes and cortical microbleeds, with hypertension as a risk factor. Additionally, a high-fat diet (HFD) can affect peripheral vessel health. Our study explored how HFD affects cerebral small vessels in normotensive WKY, hypertensive SHR, and SHR/SP rats. The MRI results revealed that HFD specifically increased WM hyperintensity in SHR/SP rats. Pathologically, it increased WM pallor and vacuolation in SHR and SHR/SP rats. Levels of blood-brain barrier (BBB) protein claudin 5 were decreased in SHR and SHR/SP compared to WKY, with HFD having minimal impact on these levels. Conversely, collagen IV levels remained consistent among the rat strains, which were increased by HFD. Consequently, HFD caused vessel leakage in all rat strains, particularly within the corpus callosum of SHR/SP rats. To understand the underlying mechanisms, we assessed the levels of hypoxia-inducible factor-1α (HIF-1α), Gp91-phox, and neuroinflammatory markers astrocytes, and microglia were increased in SHR and SHR/SP compared to WKY and were further elevated by HFD in all rat strains. Gp91-phox was also increased in SHR and SHR/SP compared to WKY, with HFD causing an increase in WKY but little effect in SHR and SHR/SP. In conclusion, our study demonstrates that HFD, in combined with hypertension, intensifies cerebral pathological alterations in CSVD rats. This exacerbation involves increased oxidative stress and HIF-1α in cerebral vessels, triggering neuroinflammation, vascular basement membrane remodeling, IgG leakage, and ultimately WM damage.

The Role of the Vascular System in Degenerative Diseases: Mechanisms and Implications.

Degenerative diseases, encompassing a wide range of conditions affecting various organ systems, pose significant challenges to global healthcare systems. This comprehensive review explores the intricate interplay between the vascular system and degenerative diseases, shedding light on the underlying mechanisms and profound implications for disease progression and management. The pivotal role of the vascular system in maintaining tissue homeostasis is highlighted, as it serves as the conduit for oxygen, nutrients, and immune cells to vital organs and tissues. Due to the vital role of the vascular system in maintaining homeostasis, its dysfunction, characterized by impaired blood flow, endothelial dysfunction, and vascular inflammation, emerges as a common denominator of degenerative diseases across multiple systems. In the nervous system, we explored the influence of vascular factors on neurodegenerative diseases such as Alzheimer's and Parkinson's, emphasizing the critical role of cerebral blood flow regulation and the blood-brain barrier. Within the kidney system, the intricate relationship between vascular health and chronic kidney disease is scrutinized, unraveling the mechanisms by which hypertension and other vascular factors contribute to renal dysfunction. Throughout this review, we emphasize the clinical significance of understanding vascular involvement in degenerative diseases and potential therapeutic interventions targeting vascular health, highlighting emerging treatments and prevention strategies. In conclusion, a profound appreciation of the role of the vascular system in degenerative diseases is essential for advancing our understanding of degenerative disease pathogenesis and developing innovative approaches for prevention and treatment. This review provides a comprehensive foundation for researchers, clinicians, and policymakers seeking to address the intricate relationship between vascular health and degenerative diseases in pursuit of improved patient outcomes and enhanced public health.

Correction: Shibly et al. Analysis of Cerebral Small Vessel Changes in AD Model Mice. Biomedicines 2023, 11, 50.

In the original publication [...].

α-Pyrrolidinononanophenone derivatives induce differentiated SH-SY5Y neuroblastoma cell apoptosis via reduction of antioxidant capacity: Involvement of NO depletion and inactivation of Nrf2/HO1 signaling pathway.

α-Pyrrolidinononanophenone (α-PNP) derivatives are known to be one of the hazardous new psychoactive substances due to the most extended hydrocarbon chains of any pyrrolidinophenones on the illicit drug market. Our previous report showed that 4'-iodo-α-PNP (I-α-PNP) is the most potent cytotoxic compound among α-PNP derivatives and induces apoptosis due to mitochondrial dysfunction and suppression of nitric oxide (NO) production in differentiated human neuronal SH-SY5Y cells. In this study, to clarify the detailed action mechanisms by I-α-PNP, we investigated the mechanism of reactive oxygen species (ROS) -dependent apoptosis by I-α-PNP in differentiated SH-SY5Y with a focus on the antioxidant activities. Treatment with I-α-PNP elicits overproduction of ROS such as H2O2, hydroxyl radical, and 4-hydroxy-2-nonenal, and pretreatment with antioxidant N-acetyl-L-cysteine is attenuated the SH-SY5Y cells apoptosis by I-α-PNP. These results suggested that the overproduction of ROS is related to SH-SY5Y cell apoptosis by I-α-PNP. In addition, I-α-PNP markedly decreased antioxidant capacity in differentiated cells than in undifferentiated cells and inhibited the upregulation of hemeoxygenase 1 (HO1) and glutathione peroxidase 4 (GPX4) expression caused by induction of differentiation. Furthermore, the treatment with I-α-PNP increased the nuclear expression level of BTB Domain And CNC Homolog 1 (Bach1), a transcriptional repressor of Nrf2, only in differentiated cells, suggesting that the marked decrease in antioxidant capacity in differentiated cells was due to suppression of Nrf2/HO1 signaling by Bach1. Additionally, pretreatment with an NO donor suppresses the I-α-PNP-evoked ROS overproduction, HO1 down-regulation, increased nuclear Bach1 expression and reduced antioxidant activity in the differentiated cells. These findings suggest that the ROS-dependent apoptosis by I-α-PNP in differentiated cells is attributed to the inactivation of the Nrf2/HO1 signaling pathway triggered by NO depletion.

Palmitoyl ascorbic acid glucoside enhanced cell survival with post irradiation treatment.

Radiation exposure poses a significant threat to cellular integrity by inducing DNA damage through the generation of free radicals and reactive oxygen species. Ascorbic acid, particularly its derivative Palmitoyl Ascorbic Acid 2-Glucoside (PA2G), has demonstrated remarkable radioprotective properties. While previous research focused on its pre-irradiation application, this study explores the post-irradiation radiomitigation potential of PA2G. Our findings reveal that post-irradiation treatment with PA2G enhances cell survival and accelerates DNA repair processes, particularly the non-homologous end-joining (NHEJ) repair pathway. Notably, PA2G treatment reduces the frequency of lethal chromosomal aberrations and micronuclei formation, indicating its ability to enhance the repair of complex DNA lesions. Furthermore, PA2G is shown to play a role in potentially lethal damage repair (PLDR). These radioprotective effects are specific to NHEJ and ATM pathways, as cells deficient in these mechanisms do not benefit from PA2G treatment. This study highlights PA2G as a versatile radioprotector, both pre- and post-irradiation, with significant potential for applications in radiation therapy and protection, offering new insights into its mechanism of action. Further research is required to elucidate the precise molecular mechanisms underlying PA2G's radiomitigation effects and its potential clinical applications.

Influence of Building Block Symmetry on the Band Structure of Stacked 2D Polyimide Covalent Organic Frameworks.

Covalent organic frameworks (COFs) are a class of crystalline porous materials distinctively built solely from organic elements, carbon, oxygen, hydrogen, and often nitrogen or boron. They form light, mechanically rigid, and chemically stable networks that have many advantages, but their low solubility and poor processability create issues with developing large-scale films or membranes. Two-dimensional (2D) COFs possess periodic porous crystallinity, functionality, modularity, and layered one-dimensional (1D) transport channels. All of these traits, along with the semiconducting properties of selected COFs, make them interesting candidates for integration in optoelectronic devices. Therefore, it is still a challenge to explore computationally and structurally the semiconductivity of COFs and to determine their final potential. Herein, we report on the possible semiconducting properties and results of polyimide-COF materials using density functional theory calculations. Our analysis includes monolayers and multilayers (AA- and AB-stacked modes) of mellitic triimide frameworks designed from mellitic trianhydride (MTA) as the main building knot, including MTI-TAPB-COF, which was previously synthesized from the condensation reaction of MTA and 1,3,5-tris(4-aminophenyl)benzene (TAPB), and other previously unreported structures based on MTA. Respective frameworks have been selected due to the difference in building block symmetry (C3 + C2 and C3 + C3) and different chemical linkages, either by benzene or by pyridine rings. We find the polyimide multilayers to be stable and with varying electronic properties. The finite band gap exhibited by every structure (monolayer and stacked) was sensitive to atomic arrangement. Stacking introduces dispersion to an otherwise flat band structure of the materials, which appeared to be highly sensitive to stacking direction. The effect of stacking was similar for each COF, but the magnitude of band structure change was different and dependent on the symmetry of the building blocks.

Ternary Triazole-Based Organic-Inorganic Proton-Conducting Hybrids Based on Computational Models for HT-PEMFC Application.

We reported a new ternary hybrid anhydrous proton-conducting material based on triazole (Tz), wherein it interacted with TiO2 and cesium hydrogen sulfate (CHS) constructed based on the acid-base interaction. It exhibited high proton conductivity derived by the two acid-base interactions: between CHS and Tz and between Tz and TiO2. As a starting point of discussion, we attempted to theoretically predict the high/low proton conductivity using the push-pull protonated atomic distance (PAD) law, which makes it possible to predict the proton conductivity in the acid-base part based on density functional theory. The calculations indicate the possibility of achieving higher proton conductivity in the ternary composites (CHS·Tz-TiO2) involving two acid-base interactions than in binary hybrids, such as CHS·Tz and TiO2-Tz composites, suggesting the positive effect of two simultaneous acid-base interactions for achieving high proton conductivity. This result is supported by the experimental result with respect to synthesized materials obtained using the mechanochemical method. Adding TiO2 to the CHS·Tz system causes a change in the CHS·Tz interaction and promotes proton dissociation, producing a new and fast proton-conducting layer through the formation of Tz-TiO2 interaction. Applying CHS·Tz-TiO2 to high-temperature proton exchange membrane fuel cells results in improved membrane conductivity and power-generation properties at 150 °C under anhydrous conditions.

Meningoencephalomyelitis Caused by Brucella Canis: A Case Report and Literature Review.

Human brucellosis, one of the most common zoonoses worldwide, is rare in Japan. Brucella canis is the specific pathogen of human brucellosis carried by dogs. According to an epidemiological study of B. canis infection in Japan, B. canis is the specific pathogen of human brucellosis in dogs. We herein report a rare case of meningoencephalomyelitis caused by B. canis in a 68-year-old Japanese man. Neurobrucellosis was diagnosed based on a serum tube agglutination test and abnormal cerebrospinal fluid findings. The patient was started on targeted treatment with a combination of doxycycline and streptomycin. Although extremely rare, neurobrucellosis should be considered in patients with a fever of unknown origin and unexplained neurological symptoms.

Recent advancements of covalent organic frameworks (COFs) as proton conductors under anhydrous conditions for fuel cell applications.

Recent electrochemical energy conversion devices require more advanced proton conductors for their broad applications, especially, proton exchange membrane fuel cell (PEMFC) construction. Covalent organic frameworks (COFs) are an emerging class of organic porous crystalline materials that are composed of organic linkers and connected by strong covalent bonds. The unique characteristics including well-ordered and tailorable pore channels, permanent porosity, high degree of crystallinity, excellent chemical and thermal stability, enable COFs to be the potential proton conductors in fuel cell devices. Generally, proton conduction of COFs is dependent on the amount of water (extent of humidity). So, the constructed fuel cells accompanied complex water management system which requires large radiators and airflow for their operation at around 80 °C to avoid overheating and efficiency roll-off. To overcome such limitations, heavy-duty fuel cells require robust proton exchange membranes with stable proton conduction at elevated temperatures. Thus, proton conducting COFs under anhydrous conditions are in high demand. This review summarizes the recent progress in emerging COFs that exhibit proton conduction under anhydrous conditions, which may be prospective candidates for solid electrolytes in fuel cells.

Relationship Between Oral Health, Quality of Life, and Comprehensive Health Literacy in Community-Dwelling Older Adults.

Background and purpose: Oral health affects systemic health and the importance of maintaining good oral health is acknowledged. The high prevalence of oral diseases is associated with low health literacy (HL). Therefore, the purpose of this study was to investigate whether comprehensive HL in community-dwelling older adults is associated with objective oral hygiene and oral health-related quality of life (OHRQoL). Methods: Participants aged ≥65 years completed a self-administered questionnaire. On the same day, data collected with the oral health assessment tool were used to assess participants' objective oral status. The questionnaire included the general oral health assessment index to measure OHRQoL and the short version of the European Health Literacy Survey Questionnaire to assess comprehensive HL. Data were analyzed by univariate and multiple logistic regression. Results: In total, 145 people consented to participate in this study, of whom 118 (81.4%) responded effectively. Of the 118 participants, 18% recorded a rating of "unhealthy" for oral cleanliness in objective oral hygiene. Multiple logistic regression analysis identified comprehensive HL as a related factor for both oral cleanliness and OHRQoL (odds ratio = 5.00 and 3.33, p < 0.01 and p < 0.05, respectively). Implications for Practice: These findings indicate that comprehensive HL changes clinical outcomes. Because older adults often have comorbidities as well as oral health problems, it is important for nurses to assess HL during follow-up for comorbidities and take the opportunity to provide personalized oral health guidance and improve OHRQoL.

Development of a stroke risk score with MRI asymptomatic brain lesions attributes to evaluate prognostic vascular events.

BACKGROUND: The use of a combination of stroke predictors, such as clinical factors and asymptomatic lesions on brain magnetic resonance imaging (MRI), may improve the accuracy of stroke risk prediction. Therefore, we attempted to develop a stroke risk score for healthy individuals. METHODS: We investigated the presence of cerebral stroke in 2365 healthy individuals who underwent brain dock screening at the Health Science Center in Shimane. We examined the factors that contributed to stroke and attempted to determine the risk of stroke by comparing background factors and MRI findings. RESULTS: The following items were found to be significant risk factors for stroke: age (≥60 years), hypertension, subclinical cerebral infarction, deep white matter lesion, and microbleeds. Each item was scored with 1 point, and the hazard ratios for the risk of developing stroke based on the group with 0 points were 17.2 (95% confidence interval [CI] 2.31-128) for 3 points, 18.1 (95% CI 2.03-162) for 4 points, and 102 (95% CI 12.6-836) for 5 points. CONCLUSIONS: A precise stroke prediction score biomarker can be obtained by combining MRI findings and clinical factors.

Alzheimer's Amyloid ß Peptide Induces Angiogenesis in an Alzheimer's Disease Model Mouse through Placental Growth Factor and Angiopoietin 2 Expressions.

Increased angiogenesis, especially the pathological type, has been documented in Alzheimer's disease (AD) brains, and it is considered to be activated due to a vascular dysfunction-mediated hypoxic condition. To understand the role of the amyloid ß (Aß) peptide in angiogenesis, we analyzed its effects on the brains of young APP transgenic AD model mice. Immunostaining results revealed that Aß was mainly localized intracellularly, with very few immunopositive vessels, and there was no extracellular deposition at this age. Solanum tuberosum lectin staining demonstrated that compared to their wild-type littermates, the vessel number was only increased in the cortex of J20 mice. CD105 staining also showed an increased number of new vessels in the cortex, some of which were partially positive for collagen4. Real-time PCR results demonstrated that placental growth factor (PlGF) and angiopoietin 2 (AngII) mRNA were increased in both the cortex and hippocampus of J20 mice compared to their wild-type littermates. However, vascular endothelial growth factor (VEGF) mRNA did not change. Immunofluorescence staining confirmed the increased expression of PlGF and AngII in the cortex of the J20 mice. Neuronal cells were positive for PlGF and AngII. Treatment of a neural stem cell line (NMW7) with synthetic Aß1-42 directly increased the expression of PlGF and AngII, at mRNA levels, and AngII at protein levels. Thus, these pilot data indicate that pathological angiogenesis exists in AD brains due to the direct effects of early Aß accumulation, suggesting that the Aß peptide regulates angiogenesis through PlGF and AngII expression.

Neither Trimethylamine-N-Oxide nor Trimethyllysine Is Associated with Atherosclerosis: A Cross-Sectional Study in Older Japanese Adults.

Recent evidence suggests that trimethylamine-N-oxide (TMAO), a metabolite of L-carnitine and choline, is linked to atherosclerosis and cardiovascular diseases. As TMAO content is very high in fish, we raised the following question: why do Japanese people, who consume lots of fish, show a low risk of atherosclerosis? To address this question, we investigated the effects of TMAO and other L-carnitine-related metabolites on carotid intima-media thickness (IMT). Participants were recruited from a small island and a mountainous region. Plasma L-carnitine, γ-butyrobetaine (γBB), TMAO, trimethyllysine (TML), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) levels were measured using liquid or gas chromatography-mass spectrometry. Plasma L-carnitine concentration was higher in men than in women. TMAO and TML were significantly higher in the residents of the island than in the mountainous people. In multiple linear regression analyses in all participants, TML showed a significant inverse association with max-IMT and plaque score (PS), whereas TMAO did not show any associations. In women, L-carnitine was positively associated with max-IMT and PS. TMAO was correlated with both EPA and DHA levels, implying that fish is a major dietary source of TMAO in Japanese people. Our study found that plasma TMAO was not an apparent risk factor for atherosclerosis in elderly Japanese people, whereas a low level of TML might be a potential risk. L-carnitine may be a marker for atherosclerosis in women.

Increase in cerebral microbleeds and cognitive decline.

BACKGROUND: In spite of increasing evidence of the clinical importance of cerebral microbleeds (CMBs), the relationship between CMBs and cognitive impairment is still controversial. In addition, there are very limited prior data regarding the prospective association of additional CMBs over time with a decline in cognitive function. This study thus aimed to investigate the effects of newly detected CMBs on cognitive decline in a Japanese health examination cohort. PATIENTS AND METHODS: We performed a prospective cohort study involving 769 Japanese participants (mean age, 61.6 years) with a mean follow-up of 7.3 ± 3.5 years. CMBs were classified according to their locations. Cognitive functions were evaluated using Okabe's Intelligence Scale, Koh's block design test, and the Wisconsin Card Sorting Test. Multiple linear regression analyses were performed to examine the relationship between the newly detected CMBs and cognitive decline. RESULTS: Fifty-six (7.3%) participants (16 had new strictly lobar cerebral microbleeds and 40 had new deep or infratentorial cerebral microbleeds) developed new CMBs during the follow-up period. In multivariable analysis, newly detected strictly lobar CMBs were associated with a greater decline in the Wisconsin Card Sorting Test in the categories achieved (ß: - 0.862 [95% CI: - 1.325, - 0.399]; P < 0.0001), greater increase in perseverative errors of Nelson (ß: 0.603 [95% CI: 0.023, 1.183]; P = 0.04), and greater increase in the difficulty with maintaining set (ß: 1.321 [95% CI: 0.801, 1.842]; P < 0.0001). CONCLUSIONS: Strictly lobar CMBs over time were associated with a decline in executive function.

Altered Feedback-Related Negativity in Mild Cognitive Impairment.

INTRODUCTION: Feedback-related negativity (FRN) is electrical brain activity related to the function of monitoring behavior and its outcome. FRN is generated by negative feedback input, such as punishment or monetary loss, and its potential is distributed maximally over the frontal-central part of the skull. Our previous study demonstrated that FRN latency was delayed and that the amplitude was increased in patients with mild Alzheimer's disease (AD). As mild cognitive impairment (MCI) is considered to be a prodromal stage of AD, we speculated that FRN would also be altered in MCI, as in AD. The aim of this study is to examine whether MCI patients showed changes in FRN during a gambling task. METHODS: Thirteen MCI patients and thirteen age-matched healthy elderly individuals participated in a simple gambling task and underwent neuro-psychological assessments. The participants were asked to choose one out of two options and randomly received positive or negative feedback to their response. An EEG was recorded during the task, and FRN was obtained by subtracting the positive feedback-related activity from the negative feedback-related activity. RESULTS: The reaction time to probe stimuli was comparable in the two groups. The group comparisons revealed that the FRN amplitude was significantly larger for the MCI group than for the healthy elderly (F(1,24) = 6.4, ηp2 = 0.22, p = 0.019), but there was no group difference in the FRN latency. The FRN amplitude at the frontocentral electrode positively correlated with the mini-mental state examination score (Spearman's rhopartial = 0.41, p = 0.043). The finding of increased FRN amplitude in MCI was consistent with the previous finding in AD. CONCLUSION: Our findings indicate that monitoring dysfunction might also be involved in the prodromal stage of dementia.

Analysis of the time-dependent changes of phospholipids in the brain regions of a mouse model of Alzheimer's disease.

Phospholipid levels are reported to be decreased in Alzheimer's disease (AD). For a better understanding, we investigated the time-dependent changes of phospholipids species in a mouse model of AD. The levels of phospholipids in the hippocampus and prefrontal cortex of wild-type and APP-Tg (J20) mice were measured by LC-ESI-MS/MS. Compared to wild-type, total phosphatidylcholine (PC), phosphatidylethanolamine (PE), and lysophosphatidylcholine (LPC) were Increased at 3 months but decreased at 6 months in the cortex of J20 mice. Total lysophosphatidylethanolamine (LPE) was decreased both at 3 and 6 months. PC was decreased and LPC was increased at 6 months, resulting in an increased LPC/PC ratio in the hippocampus of J20 mice. At species levels, PCA analysis could discriminate wild-type and J20 based on PC and LPC distribution at 6 months. At 6 months, several highly abundant PC including PC (16:0/16:0), PC (16:0/18:0), PC (16:0/18:1), and PC (18:0/18:1) were decreased in the cortex and hippocampus of J20. Conversely, LPC species including LPC 16:0, LPC 18:1, and LPC 20:4 were increased especially in the hippocampal area. Increased activation of phospholipid-metabolizing enzyme cPLA2 was seen in the hippocampus and cortex of J20 mice at 9 months. On the other hand, ROS levels started to increase as early as 3 months. Compared to 3 months, ROS levels were higher at 6 months in J20 mice. Thus, we demonstrated here a time- and area-dependent alteration of phospholipid composition during the early stage of AD, which could be important in understanding the pathological process.

[A CASE OF ALLERGIC BRONCHOPULMONARY MYCOSIS WITH NONTUBERCULOUS MYCOBACTERIOSIS SUCCESSFULLY TREATED WITH BENRALIZUMAB FOR STEROID WITHDRAWAL].

A 56-year-old woman who had allergic bronchopulmonary mycosis (ABPM) with nontuberculous mycobacteriosis (NTM) was treated with prednisone. After treatment, her respiratory symptoms, eosinophil count, and infiltrative shadow diminished. However, when the dosage of prednisone was tapered and finally stopped, the eosinophil count increased and the infiltrative shadow returned. Since there was a risk of exacerbation of NTM, benralizumab without prednisone was administrated, which improved the patient's respiratory symptoms and eosinophil count, while the infiltrative shadow remained. When the dosage of prednisone was restarted, the shadow disappeared. After prednisone discontinuation, no exacerbation of the shadows nor relapse were observed. In recent years, clinical usefulness of biologics like benralizumab for ABPM has been reported, but evidence to support their use is insufficient. Furthermore, it is expected that the number of the combined cases of NTM and ABPM will increase with the increase in NTM; however, reports of biologics for the management of both cases are extremely rare. The risk of complications of infectious diseases, interaction with antifungal drugs, and steroid sparing effects should be considered when deciding the treatment strategy. Accumulation of more cases in the future may lead to the establishment of a treatment method for the combined cases of NTM and ABPM.

The Urinary Bladder is Rich in Glycosphingolipids Composed of Phytoceramides.

Glycosphingolipids (GSLs) are composed of a polar glycan chain and a hydrophobic tail known as ceramide. Together with variation in the glycan chain, ceramides exhibit tissue-specific structural variation in the long-chain base (LCB) and N-acyl chain moieties in terms of carbon chain length, degree of desaturation, and hydroxylation. Here, we report the structural variation in GSLs in the urinary bladders of mice and humans. Using TLC, we showed that the major GSLs are hexosylceramide, lactosylceramide, globotriaosylceramide, globotetraosylceramide, Neu5Ac-Gal-Glc-Ceramide, and Neu5Ac-Neu5Ac-Gal-Glc-Ceramide. Our LC-MS analysis indicated that phytoceramide structures with a 20-carbon LCB (4-hydroxyeicosasphinganine) and 2-hydroxy fatty acids are abundant in hexosylceramide and Neu5Ac-Gal-Glc-Ceramide in mice and humans. In addition, quantitative PCR demonstrated that DES2 and FA2H, which are responsible for the generation of 4-hydroxysphinganine and 2-hydroxy fatty acid, respectively, and SPTLC3 and SPTSSB, which are responsible for the generation of 20-carbon LCBs, showed significant expressions in the epithelial layer than in the subepithelial layer. Immunohistochemically, dihydroceramide:sphinganine C4-hydroxylase (DES2) was expressed exclusively in urothelial cells of the urinary bladder. Our findings suggest that these ceramide structures have an impact on membrane properties of the stretching and shrinking in transitional urothelial cells.