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High-grade gliomas present a significant challenge in neuro-oncology because of their aggressive nature and resistance to current therapies. Boron neutron capture therapy (BNCT) is a potential treatment method; however, the boron used by the carrier compounds—such as 4-borono-L-phenylalanine (L-BPA)—have limitations. This study evaluated the use of boron-conjugated 4-iodophenylbutanamide (BC-IP), a novel boron compound in BNCT, for the treatment of glioma. Using in vitro drug exposure experiments and in vivo studies, we compared BC-IP and BPA, with a focus on boron uptake and retention characteristics. The results showed that although BC-IP had a lower boron uptake than BPA, it exhibited superior retention. Furthermore, despite lower boron accumulation in tumors, BNCT mediated by BC-IP showed significant survival improvement in glioma-bearing rats compared to controls (not treated animals and neutrons only). These results suggest that BC-IP, with its unique properties, may be an alternative boron carrier for BNCT. Further research is required to optimize this potential treatment modality, which could significantly contribute to advancing the treatment of high-grade gliomas.

Abstract Radiation therapy is one of standard treatment for malignant glioma after surgery. The microenvironment after irradiation is considered not to be suitable for the survival of tumor cells (tumor bed effect). This study investigated whether the effect of changes in the microenvironment of parenchymal brain tissue caused by radiotherapy affect the recurrence and progression of glioma. 65-Gy irradiation had been applied to the right hemisphere of Fisher rats. After 3 months from irradiation, we extracted RNA and protein from the irradiated rat brain. To study effects of proteins extracted from the brains, we performed WST-8 assay and tube formation assay in vitro. Cytokine production were investigated for qPCR. Additionally, we transplanted glioma cell into the irradiated and sham animals and the median survival time of F98 transplanted rats was also examined in vivo. Immunohistochemical analyses and invasiveness of implanted tumor were evaluated. X-ray irradiation promoted the secretion of cytokines such as CXCL12, VEGF-A, TGF-β1 and TNFα from the irradiated brain. Proteins extracted from the irradiated brain promoted the proliferation and angiogenic activity of F98 glioma cells. Glioma cells implanted in the irradiated brains showed significantly high proliferation, angiogenesis and invasive ability, and the post-irradiation F98 tumor-implanted rats showed a shorter median survival time compared to the Sham-irradiation group. The current study suggests that the microenvironment around the brain tissue in the chronic phase after exposure to X-ray radiation becomes suitable for glioma cell growth and invasion.

Dyslipidemia (DL) is one of the most common lifestyle-related diseases. There are few reports showing the causal relationship between gut microbiota (GM) and DL. In the present study, we used a linear non-Gaussian acyclic model (LiNGAM) to evaluate the causal relationship between GM and DL. A total of 79 men and 82 women aged 40 years or older living in Shika-machi, Ishikawa Prefecture, Japan were included in the analysis, and their clinical information was investigated. DNA extracted from the GM was processed to sequence the 16S rRNA gene using next-generation sequencing. Participants were divided into four groups based on sex and lipid profile information. The results of one-way analysis of covariance, linear discriminant analysis effect size, and least absolute value reduction and selection operator logistic regression model indicated that several bacteria between men and women may be associated with DL. The LiNGAM showed a presumed causal relationship between different bacteria and lipid profiles in men and women. In men, Prevotella 9 and Bacteroides were shown to be potentially associated with changes in low- and high-density lipoprotein cholesterol levels. In women, the LiNGAM results showed two bacteria, Akkermansia and Escherichia/Shigella, had a presumptive causal relationship with lipid profiles. These results may provide a new sex-based strategy to reduce the risk of developing DL and to treat DL through the regulation of the intestinal environment using specific GM.

Fenofibrate (FF), a peroxisome proliferator‐activated receptor‐alpha (PPAR‐α) agonist and a lipid‐lowering agent, can decrease experimental pulmonary fibrosis. However, the mechanisms underlying the antifibrotic effect of FF remain unknown. Hence, this study was conducted to evaluate the effects of FF on transforming growth factor‐beta (TGF‐β)‐induced myofibroblast differentiation and activation in lung fibroblasts. The results showed that FF inhibited alpha‐smooth muscle actin (α‐SMA) and connective tissue growth factor expression, collagen production, cell motility, SMAD3 phosphorylation and nuclear translocation, and metabolic reprogramming in TGF‐β‐exposed cells. The inhibitory effect of FF did not decrease with the addition of a PPAR‐α antagonist. Moreover, the inhibitory effect given by FF could not be reproduced with the addition of an alternative PPAR‐α agonist. FF inhibited mitochondrial respiration. However, rotenone, a complex I inhibitor, did not suppress TGF‐β‐induced myofibroblast differentiation. Furthermore, the TGF‐β‐induced nuclear reduction of protein phosphatase, Mg2+/Mn2+‐dependent 1A (PPM1A), a SMAD phosphatase, was inhibited by FF. These results showed that FF suppressed TGF‐β‐induced myofibroblast differentiation and activation independent of PPAR‐α activation and impaired mitochondrial respiration. In conclusion, this study provides information on the effects of FF on anti‐TGF‐β mechanisms.

Abstract Protein-based materials are considered versatile biomaterials, and their biodegradability is an advantage for sustainable development. Bagworm produces strong silk for use in unique situations throughout its life stages. Rigorous molecular analyses of Eumeta variegata suggested that the particular mechanical properties of its silk are due to the coexistence of poly-A and GA motifs. However, little molecular information on closely related species is available, and it is not understood how these properties were acquired evolutionarily or whether the motif combination is a conserved trait in other bagworms. Here, we performed a transcriptome analysis of two other bagworm species (Canephora pungelerii and Bambalina sp.) belonging to the family Psychidae to elucidate the relationship between the fibroin gene and silk properties. The obtained transcriptome assemblies and tensile tests indicated that the motif combination and silk properties were conserved among the bagworms. Furthermore, our analysis showed that C. pungelerii produces extraordinarily strong silk (breaking strength of 1.4 GPa) and indicated that the cause may be the C. pungelerii -specific balance of crystalline/amorphous regions in the H-fibroin repetitive domain. This particular H-fibroin architecture may have been evolutionarily acquired to produce strong thread to maintain bag stability during the relatively long development period of Canephora species relative to other bagworms.

Abstract Aims/Introduction A low insulin secretion capacity has been implicated in the high prevalence of non‐obese diabetes in East Asians. As alcohol consumption alters insulin and glucose metabolism, we tested the hypothesis that alcohol consumption contributes to impaired insulin secretion and glucose intolerance in lean/normal‐weight non‐diabetic Japanese men. Materials and Methods This cross‐sectional study was undertaken among the residents of Shika town, Japan, between 2011 and 2017. A total of 402 non‐diabetic men, including participants with normal fasting plasma glucose (FPG) and impaired FPG (FPG 5.6–6.9 mmol/L), and aged ≥40 years, were examined. FPG, the homeostasis model assessment of insulin secretion capacity (HOMA‐B) and alcohol consumption were evaluated and compared between the body mass index (BMI)

Abstract Background Food allergy (FA) is a common disease in children, and its prevalence has increased in developed countries. The impact of overweight on children health also becomes an important social problem. However, the relationship between overweight and FA is still unclear. We examined the association between overweight and the prevalence of FA among Japanese children. Methods We analyzed data obtained using a self-administered questionnaire from 1772 Japanese children. Weight groups according to body mass index cutoff points proposed by the International Obesity Task Force were used to create two groups: overweight and non-overweight. Children were separated into four age groups (3–6 years, 6–9 years, 9–12 years, and 12–15 years) to examine age differences. We performed univariate and multivariate logistic models to examine the association between overweight and FA. Results The prevalence of FA was significantly higher in boys (10.6%, p = 0.014) than girls (4.5%) and girls (7.9%, p = 0.012) than boys (2.5%) for 6–9 and 12–15 age groups, respectively. While the prevalence of FA was significantly higher in overweight than non-overweight girls (26.1%, p = 0.005) in the 12–15 age group, no significant difference was found in boys. In girls, overweight was significantly associated with FA after adjustment for age and asthma (odds ratio 1.99, 95% confidence interval 1.01–3.89, p = 0.046). Conclusions Our results showed that being overweight was significantly associated with a higher prevalence of FA in girls, but not in boys. Further prospective studies are necessary to find the causal relationship between overweight and FA.

Abstract Background A striking aspect of evolution is that it often converges on similar trajectories. Evolutionary convergence can occur in deep time or over short time scales, and is associated with the imposition of similar selective pressures. Repeated convergent events provide a framework to infer the genetic basis of adaptive traits. The current study examines the genetic basis of secondary web loss within web-building spiders (Araneoidea). Specifically, we use a lineage of spiders in the genus Tetragnatha (Tetragnathidae) that has diverged into two clades associated with the relatively recent (5 mya) colonization of, and subsequent adaptive radiation within, the Hawaiian Islands. One clade has adopted a cursorial lifestyle, and the other has retained the ancestral behavior of capturing prey with sticky orb webs. We explore how these behavioral phenotypes are reflected in the morphology of the spinning apparatus and internal silk glands, and the expression of silk genes. Several sister families to the Tetragnathidae have undergone similar web loss, so we also ask whether convergent patterns of selection can be detected in these lineages. Results The cursorial clade has lost spigots associated with the sticky spiral of the orb web. This appears to have been accompanied by loss of silk glands themselves. We generated phylogenies of silk proteins (spidroins), which showed that the transcriptomes of cursorial Tetragnatha contain all major spidroins except for flagelliform. We also found an uncharacterized spidroin that has higher expression in cursorial species. We found evidence for convergent selection acting on this spidroin, as well as genes involved in protein metabolism, in the cursorial Tetragnatha and divergent cursorial lineages in the families Malkaridae and Mimetidae. Conclusions Our results provide strong evidence that independent web loss events and the associated adoption of a cursorial lifestyle are based on similar genetic mechanisms. Many genes we identified as having evolved convergently are associated with protein synthesis, degradation, and processing, which are processes that play important roles in silk production. This study demonstrates, in the case of independent evolution of web loss, that similar selective pressures act on many of the same genes to produce the same phenotypes and behaviors.

Trichonephila clavipes (Linnaeus, 1767) is known as a golden silk orb-weaver and belongs to the family Araneidae. T. clavipes is one of the few spider species whose genome has been reported and model organism for a molecular biology. Here, we present the complete mitochondrial genome sequence (mtDNA) of T. clavipes. The sequence was obtained using a long-read Nanopore technology and corrected with an Illumina technology. The circular genome is 14,902 bp in length, and the AT content was 77.21%. The T. clavipes mitochondrial genome contains 13 protein-coding genes (PCGs), 22 tRNA genes, and 2 rRNA genes. The majority of PCGs were found on the heavy strain.

Abstract A key feature of osteoarthritis is the gradual loss of articular cartilage and bone deformation, resulting in the impairment of joint function. The primary cause of cartilage destruction is considered to be the presence of elevated proteases, such as matrix metalloproteinases (MMPs) and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTSs). However, clinically tested global MMP inhibitors have low efficacy that may be due to their lack of selectivity. We previously demonstrated in vitro that a variant of tissue inhibitor of metalloproteinase-3 ([-1A]TIMP3) inhibits ADAMTSs but not MMPs. In this study, we tested whether the selectivity of [-1A]TIMP3 is beneficial compared with that of the wild-type TIMP3 in preventing or delaying the onset of the degenerative effects in a mouse model of osteoarthritis. We generated transgenic mice that overexpressed TIMP3 or [-1A]TIMP3 driven by a chondrocyte-specific type II collagen promoter. TIMP3 transgenic mice showed compromised bone integrity as opposed to [-1A]TIMP3 mice. After surgically induced joint instability, TIMP3 overexpression proved to be less protective in cartilage destruction than [-1A]TIMP3 at late stages of OA. The selective inhibition of ADAMTSs provides the possibility of modifying TIMP3 to specifically target a class of cartilage-degrading proteinases and to minimize adverse effects on bone and possibly other tissues.

Purpose: Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a necrotizing vasculitis syndrome characterized by the destruction of small vessels, leading to various organ disorders. Here, we report a case of posterior scleritis with AAV successfully treated with prednisolone and rituximab (RTX) combination therapy. Observations: A 69-year-old female suffered from ocular pain and redness in her left eye for 2.5 years. She had been diagnosed with idiopathic otitis media before a year. At her initial visit, scleral injection with nodular elevated scleral lesions, vitreous haze, and serous retinal detachment (SRD) in the inferior periphery were observed in the left eye. Enhanced computed tomography revealed the enhancement and thickening of the left sclera. The results of laboratory analysis were positive for myeloperoxidase ANCA. Accordingly, she was diagnosed with AAV. Owing to the exacerbation of vitreous haze and SRD, topical treatment and steroid pulse therapy were initiated. Following therapy, anterior and posterior scleritis improved, and additional RTX was administered to maintain the remission. Following treatment, the patient has maintained remission with 10 mg/day prednisolone to date. Conclusions and importance: We encountered a case of posterior scleritis with AAV in which inflammatory manifestations subsided with RTX and glucocorticoid combination therapy. RTX administration likely contributed to the maintenance of remission.

BMP6 is a central cytokine in the induction of Sjögren’s syndrome–associated (SS-associated) secretory hypofunction. However, the upstream initiation leading to the production of this cytokine in SS is unknown. In this study, RNA ISH on salivary gland sections taken from patients with SS indicated monocytic lineage cells as a cellular source of BMP6. RNA-Seq data on human salivary glands suggested that TLR4 signaling was an upstream regulator of BMP6, which was confirmed by in vitro cell assays and single-cell transcriptomics of human PBMCs. Further investigation showed that HSP70 was an endogenous natural TLR4 ligand that stimulated BMP6 expression in SS. Release of HSP70 from epithelial cells could be triggered by overexpression of lysosome-associated membrane protein 3 (LAMP3), a protein also associated with SS in several transcriptome studies. In vitro studies supported the idea that HSP70 was released as a result of lysosomal exocytosis initiated by LAMP3 expression, and reverse transcription PCR on RNA from minor salivary glands of patients with SS confirmed a positive correlation between BMP6 and LAMP3 expression. BMP6 expression could be experimentally induced in mice by overexpression of LAMP3, which developed an SS-like phenotype. The newly identified LAMP3/HSP70/BMP6 axis provided an etiological model for SS gland dysfunction and autoimmunity.

Empyema necessitans is a rare empyema complication characterized by an extension of empyema out of the pleural space into the subcutaneous tissues of the chest wall. We herein report a case of empyema necessitans that presented as a subcutaneous chest wall abscess caused by Porphyromonas gingivalis (P. gingivalis), an important anaerobic periodontal pathogen, in a 74-year-old woman with periodontitis. The patient was admitted to our hospital with a painful soft tissue mass in the chest wall extending from a subpleural lung abscess associated with empyema. Exploratory percutaneous puncture and aspiration of the chest wall mass yielded foul-smelling chocolate-colored pus, which was found to be caused due to infection with P. gingivalis. Treatment with antibacterials resulted in a relapse of empyema necessitans requiring a second admission 1 month later. An additive treatment with surgical open drainage and decortication of the subcutaneous abscess successfully cured the abscess. Physicians must be aware of emphysema necessitans as an etiology of a chest wall mass and should consider periodontitis as a source of infection.

This study aimed to elucidate the 12-month durability of neutralizing antibodies (NAbs) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in patients infected during the 2020 workplace outbreaks of coronavirus disease 2019 (COVID-19) in Japan. We followed 33 Japanese patients infected with SARS-CoV-2 in April 2020 for 12 months (12M). Patients were tested for NAbs and for antibodies against the SARS-CoV-2 nucleocapsid (anti-NC-Ab) and antibodies against the spike receptor-binding domain (anti-RBD-Ab). Tests were performed at 2M, 6M, and 12M after the primary infection (api) with commercially available test kits. In 90.9% (30/33) of patients, NAbs persisted for 12M api, though the median titers significantly declined from 78.7% (interquartile range [IQR]: 73.0-85.0%) at 2M, to 59.8% (IQR: 51.2-77.9) at 6M (P = 0.008), and to 56.2% (IQR: 39.6-74.4) at 12M (P

Although chronic pain (CP) is classified as inflammatory or non-inflammatory, the involvement of fatty acid intake in this process has not yet been examined in detail. Therefore, the present study investigated whether the relationship between CP and fatty acid intake differs between high and low C-reactive protein (CRP) levels in middle-aged and elderly individuals in the Shika study. One-thousand and seven males and 1216 females with mean ages of 68⋅78 and 69⋅65 years, respectively, participated in the present study. CRP was quantified by blood sampling from participants who responded to a CP questionnaire. The brief-type self-administered diet history questionnaire (BDHQ) was used to assess fatty acid intake. Interactions were observed between CP and CRP on monounsaturated fatty acids (MUFA) and eicosadienoic acid in a two-way analysis of covariance adjusted for sex, age, lack of exercise, lack of sleep, current smoking and drinking status, and BMI. MUFA (OR 1⋅359) and eicosadienoic acid (OR 1⋅072) were identified as significant independent variables for CP in a multiple logistic regression analysis, but only in the low CRP group. Only a high intake of MUFA and eicosadienoic acid was associated with chronic neck/shoulder/upper limb pain without elevated CRP. In psychogenic and neuropathic pain without elevated CRP, an increased intake of MUFA and eicosadienoic acid, a family member of n-6 fatty acids, appears to affect CP. Further longitudinal studies are needed to elucidate this relationship.

Abstract Autoimmune disorders are an important cause of acute respiratory distress syndrome (ARDS). We report a case of a patient with steroid‐responsive ARDS that relapsed in 10 months with an initial manifestation of seronegative polymyositis. ARDS associated with polymyositis may develop earlier than myopathy and may relapse later.

Spider silk is a protein-based material whose toughness suggests possible novel applications. A particularly fascinating example of silk toughness is provided by Darwin's bark spider (Caerostris darwini) found in Madagascar. This spider produces extraordinarily tough silk, with an average toughness of 350 MJ m−1 and over 50% extensibility, and can build river-bridging webs with a size of 2.8 m2. Recent studies have suggested that specific spidroins expressed in C. darwini are responsible for the mechanical properties of its silk. Therefore, a more comprehensive investigation of spidroin sequences, silk thread protein contents and phylogenetic conservation among closely related species is required. Here, we conducted genomic, transcriptomic and proteomic analyses of C. darwini and its close relative Caerostris extrusa. A variety of spidroins and low-molecular-weight proteins were found in the dragline silk of these species; all of the genes encoding these proteins were conserved in both genomes, but their genes were more expressed in C. darwini. The potential to produce very tough silk is common in the genus Caerostris, and our results may suggest the existence of plasticity allowing silk mechanical properties to be changed by optimizing related gene expression in response to the environment.

Integrin αvβ3 is more highly expressed in high-grade glioma cells than in normal tissues. In this study, a novel boron-10 carrier containing maleimide-functionalized closo-dodecaborate (MID), serum albumin as a drug delivery system, and cyclic arginine-glycine-aspartate (cRGD) that can target integrin αvβ3 was developed. The efficacy of boron neutron capture therapy (BNCT) targeting integrin αvβ3 in glioma cells in the brain of rats using a cRGD-functionalized MID-albumin conjugate (cRGD-MID-AC) was evaluated. F98 glioma cells exposed to boronophenylalanine (BPA), cRGD-MID-AC, and cRGD + MID were used for cellular uptake and neutron-irradiation experiments. An F98 glioma-bearing rat brain tumor model was used for biodistribution and neutron-irradiation experiments after BPA or cRGD-MID-AC administration. BNCT using cRGD-MID-AC had a sufficient cell-killing effect in vitro, similar to that with BNCT using BPA. In biodistribution experiments, cRGD-MID-AC accumulated in the brain tumor, with the highest boron concentration observed 8 h after administration. Significant differences were observed between the untreated group and BNCT using cRGD-MID-AC groups in the in vivo neutron-irradiation experiments through the log-rank test. Long-term survivors were observed only in BNCT using cRGD-MID-AC groups 8 h after intravenous administration. These findings suggest that BNCT with cRGD-MID-AC is highly selective against gliomas through a mechanism that is different from that of BNCT with BPA.

Although depression and body weight have individually been associated with chronic pain (CP), it currently remains unclear whether the combination of depressive symptoms (DS) and being underweight/overweight is related to CP. Therefore, we herein investigated the relationships among depression, body mass index (BMI), and CP in community-dwelling middle-aged and elderly individuals. Participants comprised 2216 inhabitants of Shika town in Ishikawa prefecture, Japan, including 1003 males (mean age of 68.72 years, standard deviation (SD) of 8.36) and 1213 females (mean age of 69.65 years, SD of 9.36). CP and DS were assessed using a CP questionnaire and Geriatric Depression Scale-15, respectively. The Breslow–Day test indicated that DS positively correlated with lumbar/knee pain in the BMI < 25 group, but not in the BMI ≥ 25 group. Furthermore, lumber/knee pain was related to a higher BMI. These results were confirmed by a logistic analysis with age, sex, BMI, solitary living, the duration of education, no exercise/hobbies, smoking history, alcohol intake, and medical treatment for diabetes, hyperlipidemia, or hypertension as confounding factors. The present study indicates the importance of considering DS and BMI in the prevention of CP. Further studies are needed to clarify the causal relationships among depression, BMI, and CP.

Ambient polycyclic aromatic hydrocarbons’ (PAHs) specific components are likely involved in respiratory disease development and exacerbation in children and adults. Airborne PAH exposure’s effects on cough symptoms in children and adults with chronic coughs in Kanazawa and Fukuoka, Japan, were investigated in this longitudinal study. A total of 98 patients with chronic coughs were enrolled and followed up between 1 April and 31 May 2020. The enrolled patients were non-smoking adults and children aged 3–83 years. Cough diaries were used to record and collect daily cough symptoms. High-performance liquid chromatography coupled with a fluorescence detector was used to determine the particulate PAH content in daily total suspended particles collected on quartz fiber filters. Ambient concentrations of fine particulate matter, nitrogen dioxide, and sulfur dioxide were obtained from local monitoring sites. Generalized estimated equations were used to estimate the association between daily PAHs and cough symptoms. Among nine PAHs measured, benz[a]anthracene (BaA) was significantly associated with cough symptoms for both lag4 and lag5 PAH exposure. These findings suggest that airborne specific PAHs, especially BaA, affect cough symptoms in children and adults with chronic cough. Further studies are needed to develop effective measures to prevent respiratory diseases against specific PAHs.

The relationship between exposure to polycyclic aromatic hydrocarbons and nasal symptoms currently remains unclear. Therefore, we herein examine this relationship in 51 adults living in Ishikawa prefecture, Japan, and conducted a 2 month follow-up survey on these participants. All participants were asked to record daily nasal symptoms in an allergy diary during the study period between 1 April to 31 May 2020. We collected air pollutant samples during the study period and determined the concentrations of PAHs and total suspended particulates by high-performance liquid chromatography. Sulfur dioxide and nitrogen dioxide concentrations were obtained through the Atmospheric Environmental Regional Observation System. We used generalized estimating equations to analyze the association between pollutant and nasal symptoms. After adjustment for confounding factors, the B values of fluoranthene, pyrene, and Benzo[k]fluoranthene were 2.389 (p = 0.026), 3.744 (p = 0.022) and 9.604 (p = 0.041), respectively, with a one-day lag. In contrast, the B value of indeno[1,2,3-cd]pyrene was −6.664 (p = 0.013) with no lag. Collectively, these results suggest ambient PAHs such as Flt, Pyr, and BkF were associated with nasal symptoms in adults. Further studies are needed to elucidate the mechanisms contributing to the relationships between specific PAHs and nasal symptoms.

Abstract Nonislet tumor hypoglycemia (NICTH) is a rare paraneoplastic syndrome characterized by refractory hypoglycemia, which often requires multifaceted therapy. We reported a case of a patient with pleural malignant mesothelioma and developed NICTH, for which chemotherapy, glucocorticoids, and nutrition were given to achieve optimal glycemic control.

The two-spotted cricket Gryllus bimaculatus is a popular food for reptiles and other insectivorous animals, for the ease of breeding and rich nutrients. It goes through eight moulting cycles until it grows into an adult of size around 30–40 mm, but different larval instars are also used for their sizes matching the fed animals. We therefore provide a transcriptomic resource on different developmental stages of G. bimaculatus to understand the inner molecular workings of these stages contributing to varying nutrients. The raw RNA sequence data is available at NCBI Sequence Read Archive (SRA) under the BioProject PRJNA716138 and the assembled contigs are available as a supplementary data of this report.

Mask wearing can protect health care workers. However, its efficacy in avoiding the health effects of air pollution is not well studied. Recently, we evaluated the relationship between air pollution and health status or peak expiratory flow rate (PEFR). At the beginning of that study, about 20% of people were wearing masks. However, in the same period one year later, most people were wearing masks because of the COVID-19 pandemic. Therefore, in this study, we examined the relationship between mask wearing, concentration of ionic components of PM2.5, respiratory symptoms, and PEFR. Seventy-two patients in Fukuoka City with asthma and allergic diseases measured PEFR daily and recorded respiratory symptoms and mask wearing in a diary. We measured the ionic components of PM2.5 in Fukuoka City and examined the relationships between patient measurements, mask wearing, and air pollution. Univariate analysis showed that, in 2020, but not in 2021, some ionic components of PM2.5, i.e., Cl−, NO3−, Na+, and Mg2+, were significantly correlated with the frequency of cough and nasal symptoms and a decrease in PEFR. Some ionic components of PM2.5 may increase the frequency of respiratory symptoms and decrease PEFR in patients with allergic diseases; however, this tendency is not seen when masks are used. The use of masks may be one of the factors that attenuate the effects of PM2.5 ionic components.

Focusing on the components of fine particulate matter, i.e., PM2.5, we have analyzed the factors that led to the high concentrations of each chemical component in PM2.5 during our observations in Fukuoka, Japan in spring 2020. The backward trajectory showed that air masses reached Fukuoka via the Yellow Sea and the southern part of South Korea when PM2.5 and each chemical component were high in concentrations. On the other hand, diurnal variations in ozone were also observed, suggesting that both transboundary and local air pollution are involved. Air masses reached the southern part of the Kyushu region when only sulfate concentrations were high. A volcano eruption led the high sulfate concentration. When only polycyclic aromatic hydrocarbons (PAHs) concentrations were high, air masses often reached the northern part of Kyushu, indicating that there may be a specific local source for PAHs.

(1) Background: Few studies have evaluated the association between the ionic components of PM2.5 and respiratory symptoms or peak expiratory flow rate (PEFR). The aim of this study was to clarify these associations. (2) Methods: Patients with allergic diseases treated at Fukuoka Hospital recorded their morning and evening PEFR and respiratory symptoms in a diary. We measured PM2.5 and its ionic components in Fukuoka City and examined the relationship with PEFR and respiratory symptoms by univariate and multivariate analysis. (3) Results: Among the ionic components of PM2.5, Cl−, NO3−, Na+, K+, and Mg2+ were significantly correlated with the frequency of coughing and nasal symptoms. In univariate analysis, the concentrations of each of the above ions was significantly associated with a decrease in PEFR and the concentrations of each was associated with at least one respiratory symptom or PEFR. Multivariate analysis of items significantly correlated with PEFR indicated that the concentration of ionic components may predict changes in PEFR. (4) Conclusions: In patients with allergic diseases, some ionic components of PM2.5 may increase the frequency of respiratory symptoms and decrease PEFR, so further study and caution are required in daily clinical practice.

Although the relationship between hypertension and depression is influenced by several physiological factors, including body weight and other lifestyle factors, such as eating behavior, the specific involvement of depression in hypertension remains unclear. Therefore, this epidemiological study examined the role of body weight in the relationship between hypertension and depressive symptoms among the middle-aged and elderly living in the community of Shika town. In total, 1141 males and 1142 females with mean ages of 69.09 and 70.61 years, respectively, participated this study. Physiological factors, including blood pressure, body mass index (BMI), and lifestyle, were investigated in a medical check-up in Shika town. Depressive symptoms were evaluated using the Geriatric Depression Scale 15 (GDS-15). A two-way analysis of covariance exhibited a significant interaction between the two hypertensive groups and body size groups on GDS in females. The post hoc Bonferroni method showed that in the hypertensive groups, GDS was significantly higher in the underweight group (BMI < 18.5) than in the standard/overweight group; however, this relationship was not observed in the no-hypertensive groups. Multiple regression analysis also verified this relationship. Therefore, it is suggested that the combination of hypertension and being underweight is associated with depressive symptoms only in females.

Polycyclic aromatic hydrocarbons (PAHs) and hydroxylated PAHs (OH-PAHs) are ubiquitous atmospheric pollutants that are a concern because of their endocrine disrupting activities. In this study, seasonal air sampling was conducted in 2017 and 2018 in Kanazawa, Ishikawa Prefecture, Japan. The concentrations and seasonal variations of PAHs and OH-PAHs were analyzed, and health risks of individual congeners were evaluated based on their relative endocrine activity. The atmospheric concentrations of PAHs and OH-PAHs showed seasonal trends with higher concentrations in the winter (daily average ± standard deviation: 1.00 ± 0.26 ng/m3 for PAHs and 75.06 ± 23.38 pg/m3 for OH-PAHs) and lower concentrations in the summer (0.30 ± 0.09 ng/m3 for PAHs and 17.08 ± 4.83 pg/m3 for OH-PAHs). There were significant positive correlations between the concentrations of atmospheric PAHs and OH-PAHs. Additionally, the health risk from the endocrine disrupting potential of each OH-PAH was evaluated using relative estrogenic and antiestrogenic activities. OH-PAHs with four rings, such as OH-chrysenes and OH-benz[a]anthracene, had particularly high health risks. These results suggest that atmospheric OH-PAHs are a potential health risk for organisms and thus warrant further research.

Introduction Changes in albuminuria or estimated glomerular filtration rate (eGFR) can be used as a surrogate endpoint of end-stage kidney disease (ESKD) in people with type 2 diabetes. We investigated whether the combined changes in albuminuria and eGFR are more strongly associated with future risk of ESKD.Research design and methods Using data from a multicenter observational cohort study of people with type 2 diabetes, we evaluated the association of percentage change in urine albumin to creatinine ratio (UACR) and/or annual change in eGFR over 2 years with subsequent ESKD risk.Results Among 1417 patients with repeated albuminuria and eGFR over 2 years, 129 (9.1%) developed ESKD. Patients with >30% UACR decline had lower ESKD risk (HR 0.47; 95% CI 0.29 to 0.77), whereas those with >30% UACR increase had higher ESKD risk (HR 2.31; 95% CI 1.52 to 3.51), compared with those with minor UACR change. Patients with greater eGFR decline had an increased ESKD risk than those with minor eGFR change (a decline of 5 and 2.5–5 mL/min/1.73 m2/year, respectively. When the combined changes in UACR and eGFR were used, the highest ESKD risk (HR 5.60; 95% CI 2.08 to 15.09) was observed among patients with >30% UACR increase and an eGFR decline of >5 mL/min/1.73 m2/year compared with those with a minor change in UACR and eGFR.Conclusions Combined changes in albuminuria and eGFR over 2 years were strongly associated with future risk of kidney failure in patients with type 2 diabetes.

Background: BNCT (Boron Neutron Capture Therapy) is a tumor-selective particle radiotherapy that combines preferential boron accumulation in tumors and neutron irradiation. Although p-boronophenylalanine (BPA) has been clinically used, new boron compounds are needed for the advancement of BNCT. Based on previous studies in colon tumor-bearing mice, in this study, we evaluated MID:BSA (maleimide-functionalized closo-dodecaborate conjugated to bovine serum albumin) biodistribution and MID:BSA/BNCT therapeutic effect on tumors and associated radiotoxicity in the hamster cheek pouch oral cancer model. Methods: Biodistribution studies were performed at 30 mg B/kg and 15 mg B/kg (12 h and 19 h post-administration). MID:BSA/BNCT (15 mg B/kg, 19 h) was performed at three different absorbed doses to precancerous tissue. Results: MID:BSA 30 mg B/kg protocol induced high BSA toxicity. MID:BSA 15 mg B/kg injected at a slow rate was well-tolerated and reached therapeutically useful boron concentration values in the tumor and tumor/normal tissue ratios. The 19 h protocol exhibited significantly lower boron concentration values in blood. MID:BSA/BNCT exhibited a significant tumor response vs. the control group with no significant radiotoxicity. Conclusions: MID:BSA/BNCT would be therapeutically useful to treat oral cancer. BSA toxicity is a consideration when injecting a compound conjugated to BSA and depends on the animal model studied.

Polypyrrole-based polyamides are used as sequence-specific DNA probes. However, their cellular uptake and distribution are affected by several factors and have not been extensively studied in vivo. Here, we generated a series of fluorescence-conjugated polypyrrole compounds and examined their cellular distribution using live zebrafish and cultured human cells. Among the evaluated compounds, Py3-FITC was able to visualize collagen-rich tissues, such as the jaw cartilage, opercle and bulbus arteriosus, in early-stage living zebrafish embryos. Then, we stained cultured human cells with Py3-FITC and found that the staining became more intense as the amount of collagen was increased. In addition, Py3-FITC-stained HR cells, which represent a type of ionocyte on the body surface of living zebrafish embryos. Py3-FITC has low toxicity, and collagen-rich tissues and ionocytes can be visualized when soaked in Py3-FITC solution. Therefore, Py3-FITC may be a useful live imaging tool for detecting changes in collagen-rich tissue and ionocytes, including their mammalian analogues, during both normal development and disease progression.

Selenoprotein P is a hepatokine with antioxidative properties that eliminate a physiologic burst of reactive oxygen species required for intracellular signal transduction. Serum levels of selenoprotein P are elevated during aging and in people with type 2 diabetes, non-alcoholic fatty liver disease, and hepatitis C. However, how serum levels of full-length selenoprotein P are regulated largely remains unknown, especially in the general population. To understand the significance of serum selenoprotein P levels in the general population, we evaluated intrinsic and environmental factors associated with serum levels of full-length selenoprotein P in 1,183 subjects participating in the Shika-health checkup cohort. Serum levels of selenium were positively correlated with liver enzymes and alcohol intake and negatively correlated with body mass index. Serum levels of selenoprotein P were positively correlated with age, liver enzymes, and alcohol intake. In multiple regression analyses, alcohol intake was positively correlated with serum levels of both selenium and selenoprotein P independently of age, gender, liver enzymes, and fatty liver on ultrasonography. In conclusion, alcohol intake is associated with elevated serum levels of selenium and selenoprotein P independently of liver enzyme levels and liver fat in the general population. Moderate alcohol intake may exert beneficial or harmful effects on health, at least partly by upregulating selenoprotein P. These findings increase our understanding of alcohol-mediated redox regulation and form the basis for the adoption of appropriate drinking guidelines.

A polymorphism in the ADRB3 gene (Trp64Arg) has been associated with obesity, insulin resistance, and hypertension. This cross-sectional study investigated the relationships among this polymorphism, hypertension, and insulin resistance values (HOMA-IR) in 719 Japanese subjects aged 40 years and older. The genotype frequencies of Trp64Trp (homozygous, wild), Trp64Arg (heterozygous, variant), and Arg64Arg (homozygous, variant) were 466 (65%), 233 (32%), and 20 (3%), respectively. Insulin resistance was associated with an increased risk of hypertension in a Japanese population. This relationship was dependent on the presence or absence of the Trp64Arg polymorphism (odds ratio, 2.054; confidence interval, 1.191 to 3.541; P value, 0.010). Therefore, the Trp64Arg polymorphism of ADRB3 was associated with hypertension and insulin resistance in a healthy Japanese population. This relationship, which was dependent on the polymorphism, may predict the development of hypertension and diabetes.

Our daily activities require vigilance. Therefore, it is useful to externally monitor and predict our vigilance level using a straightforward method. It is known that the vigilance level is linked to pupillary fluctuations via Locus Coeruleus and Norepinephrine (LC-NE) system. However, previous methods of estimating long-term vigilance require monitoring pupillary fluctuations at rest over a long period. We developed a method of predicting the short-term vigilance level by monitoring pupillary fluctuation for a shorter period consisting of several seconds. The LC activity also fluctuates at a timescale of seconds. Therefore, we hypothesized that the short-term vigilance level could be estimated using pupillary fluctuations in a short period and quantified their amplitude as the Micro-Pupillary Unrest Index (M-PUI). We found an intra-individual trial-by-trial positive correlation between Reaction Time (RT) reflecting the short-term vigilance level and M-PUI in the period immediately before the target onset in a Psychomotor Vigilance Task (PVT). This relationship was most evident when the fluctuation was smoothed by a Hanning window of approximately 50 to 100 ms (including cases of down-sampled data at 100 and 50 Hz), and M-PUI was calculated in the period up to one or two seconds before the target onset. These results suggest that M-PUI can monitor and predict fluctuating levels of vigilance. M-PUI is also useful for examining pupillary fluctuations in a short period for elucidating the psychophysiological mechanisms of short-term vigilance.

Apolipoprotein E E4 (APOE4) is a risk factor for cognitive decline. A high blood vitamin C (VC) level reduces APOE4-associated risk of developing cognitive decline in women. In the present study, we aimed to examine the effects of functional variants of VC transporter genes expressed in the brain (SLC2A1, SLC2A3, and SLC23A2) on APOE4-associated risk of developing cognitive decline. This case–control study involved 393 Japanese subjects: 252 cognitively normal and 141 cognitively impaired individuals (87 mild cognitive impairment and 54 dementia). Database searches revealed that rs1279683 of SLC23A2, and rs710218 and rs841851 of SLC2A1 are functional variants that are significantly associated with the altered expression of the respective genes and genotyped as three single nucleotide variants (SNVs). When stratified by SNV genotype, we found a significant association between APOE4 and cognitive decline in minor allele carriers of rs1279683 (odds ratio [OR] 2.02, 95% CI, 1.05–3.87, p = 0.035) but not in the homozygote carriers of the major allele. Significant associations between APOE4 and cognitive decline were also observed in participants with major allele homozygotes of rs710218 (OR 2.35, 95% CI, 1.05–5.23, p = 0.037) and rs841851 (OR 3.2, 95% CI, 1.58–6.46, p = 0.0012), but not in minor allele carriers of the respective SNVs. In contrast, the three functional SNVs showed no significant effect on cognitive decline. Our results imply that functional SNVs of VC transporter genes can affect APOE4-associated risk of developing cognitive decline via altered VC levels in the brain.

Study objectivesAlthough associations between sleep quality and environmental factors and nutrient intake have been reported, interactions between these factors have not been elucidated in detail. Therefore, this cross-sectional study examined the effects of regular exercise and nutrient intake on sleep quality using the Pittsburgh Sleep Quality Index (PSQI), which is the most frequently used index for sleep evaluation.MethodsThe participants included 378 individuals aged 40 years or older living in Shika Town, Ishikawa Prefecture. Of these individuals, 185 met the inclusion criteria. The participants completed a self-administered questionnaire assessing lifestyle habits and frequency and duration of exercise, the PSQI, and the brief-type self-administered diet history questionnaire (BDHQ) on nutrient intake.ResultsA two-way analysis of covariance on regular exercise and PSQI scores indicated that protein intake (17.13% of energy) was significantly higher in the regular exercise and PSQI ≤10 groups than in the non-regular exercise or PSQI ≥11 groups (p = 0.002). In a multiple logistic regression analysis with PSQI scores (≤10 and ≥11), protein intake was a significant independent variable in any of the models adjusted for confounding factors such as age, sex, body mass index, current smoker, and current drinker (OR: 1.357, 95% CI: 1.081, 1.704, p = 0.009) in the regular exercise group but not in the non-regular exercise group.Conclusions We identified a positive relationship between sleep quality and protein intake in the regular exercise group. These findings suggest that regular exercise at least twice a week for 30 minutes or longer combined with high protein intake contributes to good sleep quality.

Dietary intake modification is important for the treatment of chronic kidney disease (CKD); however, little is known about the association between dietary intake of antioxidant vitamins and kidney function based on gender difference. We examined the relationship of dietary intake of antioxidant vitamins with decreased kidney function according to gender in Japanese subjects. This population-based, cross-sectional study included 936 Japanese participants with the age of 40 years or older. A validated brief self-administered diet history questionnaire was used to measure dietary intakes of vitamin E and its four isoforms, vitamin A and vitamin C. Decreased kidney function was defined as estimated glomerular filtration rate

Intraoperative massive bleeding is associated with high rates of mortality and anesthetic management of massive bleeding is challenging because it is necessary to achieve volume resuscitation and electrolyte correction simultaneously during massive transfusion. We report a case of life-threatening bleeding of more than 80,000 mL during liver transplantation in which real-time QTc monitoring was useful for an extremely large amount of calcium administration for treatment of hypocalcemia. A 47-year-old female with a giant liver due to polycystic liver disease was scheduled to undergo liver transplantation. During surgery, life-threatening massive bleeding occurred. The maximum rate of blood loss was approximately 15,000 mL/hr and the total amount of estimated blood loss was 81,600 mL. It was extremely difficult to maintain blood pressure and a risk of cardiac arrest continued due to hypotension. In addition, even though administration of insulin and calcium was performed, electrolyte disturbances of hyperkalemia and hypocalcemia with prolongation of QTc interval occurred. At that time, we visually noticed that the QT interval was shortened in response to bolus calcium administration, and we used the change of real-time QTc interval as a supportive indicator for calcium correction. This monitoring allowed for us to administer calcium at an unusually high rate, by which progression of hypocalcemia was prevented. Levels of hemoglobin and coagulation factors were preserved both by restriction of crystalloid infusion and by a massive transfusion protocol. The patient was extubated without pulmonary edema or cardiac overload and was finally discharged without any sequelae. Intensive and cooperative management for massive transfusion and electrolyte correction using QTc monitoring was considered to be a key for successful management.

Objective: Tumor cells experience hypoxia, acidosis, and hypoglycemia. Metabolic adaptation to glucose shortage is essential to maintain tumor cells’ survival because of their high glucose requirement. This study evaluated the hypothesis that acidosis might promote tumor survival during glucose shortage and if so, explored a novel drug targeting metabolic vulnerability to glucose shortage. Methods: Cell survival and bioenergetics metabolism were assessed in lung cancer cell lines. Our in-house small-molecule compounds were screened to identify those that kill cancer cells under low-glucose conditions. Cytotoxicity against non-cancerous cells was also assessed. Tumor growth was evaluated in vivo using a mouse engraft model. Results: Acidosis limited the cellular consumption of glucose and ATP, causing tumor cells to enter a metabolically dormant but energetically economic state, which promoted tumor cell survival during glucose deficiency. We identified ESI-09, a previously known exchange protein directly activated by cAMP (EAPC) inhibitor, as an anti-cancer compound that inhibited cancer cells under low-glucose conditions even when associated with acidosis. Bioenergetic studies showed that independent of EPAC inhibition, ESI-09 was a safer mitochondrial uncoupler than a classical uncoupler and created a futile cycle of mitochondrial respiration, leading to decreased ATP production, increased ATP dissipation, and fuel scavenging. Accordingly, ESI-09 exhibited more cytotoxic effects under low-glucose conditions than under normal glucose conditions. ESI-09 was also more effective than actively proliferating cells on quiescent glucose-restricted cells. Cisplatin showed opposite effects. ESI-09 inhibited tumor growth in lung cancer engraft mice. Conclusions: This study highlights the acidosis-induced promotion of tumor survival during glucose shortage and demonstrates that ESI-09 is a novel potent anti-cancer mitochondrial uncoupler that targets a metabolic vulnerability to glucose shortage even when associated with acidosis. The higher cytotoxicity under lower-than-normal glucose conditions suggests that ESI-09 is safer than conventional chemotherapy, can target the metabolic vulnerability of tumor cells to low-glucose stress, and is applicable to many cancer cell types.

Salt intake is one of the most important environmental factors impacting hypertension onset. Meanwhile, the potential roles of the gut microbiome (GM) in altering the health status of hosts have drawn considerable attention. Here, we aimed to perform an observational study to investigate the impact of intestinal bacterial flora in hypertensive patients with low-salt or high-salt intake. A total of 239 participants were enrolled, and their gut microbiomes, clinical and demographic details, as well as physiological parameters pertaining to the renin-angiotensin-aldosterone system and inflammatory cytokine profiles, were examined. The participants were classified into four groups based on the presence of different enterotype bacteria, as determined via cluster analysis, and salt intake: low salt/GM enterotype 1, low salt/GM enterotype 2, high salt/GM enterotype 1, and high salt/GM enterotype 2. Results show that the prevalence of hypertension was significantly lower in the low-salt/GM enterotype 2 group (27%) compared to the low salt/GM enterotype 1 group (47%; p = 0.04). Alternatively, no significant differences were observed in hypertension prevalence between the two high-salt intake groups (GM enterotype 1 = 50%, GM enterotype 2 = 47%; p = 0.83). Furthermore, The low-salt/GM enterotype 2 was higher in the relative abundances of Blautia, Bifidobacterium, Escherichia-Shigella, Lachnoclostridium, and Clostridium sensu stricto than the low-salt/GM enterotype 1. differed significantly between the GM enterotypes. These results suggested that consumption of a low-salt diet was ineffective in regulating hypertension in individuals with a specific gut bacteria composition. Our findings support the restoration of GM homeostasis as a new strategy for controlling blood pressure and preventing the development of hypertension.

Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease of unknown etiopathogenesis. The activation of extracellular matrix (ECM)-producing myofibroblasts plays a key role in fibrotic tissue remodeling. The dedifferentiation of myofibroblasts has attracted considerable attention as a promising target for the development of effective therapeutic interventions against IPF. Here, we screened a small library of epigenetics-related inhibitors using dedifferentiation assay of lung myofibroblasts prepared from a patient at the terminal stages of IPF and chose UNC0379. The inhibition of SET8, a histone H4 lysine 20 (H4K20) monomethyltransferase, by UNC0379 markedly suppressed the expression of α-smooth muscle actin (SMA) and ED-A-fibronectin in myofibroblasts. In IPF myofibroblasts, SET8 expression and H4K20 monomethylation (H4K20me1) levels, which were significantly higher than those in normal human lung fibroblasts, were reduced upon treatment with UNC0379. Hence, the changes in the expression of the two fibrotic markers clearly correlated with those in SET8 expression and H4K20me1 level. Furthermore, in a mouse model of bleomycin (BLM)-induced lung fibrosis, the intratracheal administration of UNC0379 at an early fibrotic stage markedly ameliorated the histopathological changes associated with collagen deposition in the lungs. However, treatment with UNC0379 did not significantly affect the number of proinflammatory cells or cytokine production in the bronchoalveolar lavage fluids from mice treated with BLM. In the BLM-injured lung, SET8 was predominantly localized to the nuclei of α-SMA-positive cells, which colocalized with H4K20me1. Taken together, our results indicate that the inhibition of SET8 resulting in myofibroblast dedifferentiation may partly mitigate lung fibrosis without affecting the inflammatory responses.

Background: Heavy metal contamination and related risks for the environment and human health are matters of increasing concern. Methods: The levels of 4 heavy metals (Cr, Cd, Pb, and As) were evaluated in 2 water types (surface and well), 4 types of seafood (tiger shrimp, stuffed snail, snake-head fish, and catfish), and 27 types of vegetables (12 leafy vegetables, 4 pea plants, 4 tuber vegetables, and 7 herbs) that are commonly consumed in northern coastal communes located in Vietnam. Atomic absorption spectrometry was employed for quantification. Results: The mean concentrations of heavy metals detected in water, seafood, and vegetable samples exceeded the national permitted standards and World Health Organization (WHO) recommendation values by at least 2-fold, 2.5-fold, and 5-fold for surface water, vegetables, and well water, respectively. The concentrations of all 4 heavy metals detected in seafood samples were higher than the standards. The levels of heavy metals decreased with increasing distance between the sample collection point and the pollution source. Conclusions: This is the first report of heavy metal contamination of common sources of food and water in the northern coastal area of Vietnam. Significantly, the concentrations of heavy metals detected in study samples exceeded the regulatory limits. These results underscore the importance of continued monitoring and the development of intervention measures to ensure that the quality of food and water meets established standards and protects the health of the local population.

To clarify different effects of Asian dust (AD), long-range transported from Asian continent, on total suspended particles (TSP) and polycyclic aromatic hydrocarbons (PAHs) in Japan, TSP were simultaneously collected during AD periods (from 1 March to 31 May 2020 and 2021) in Fukuoka and Kanazawa. During AD days, decided by Light Detection and Ranging and Japan Meteorological Agency, TSP concentrations increased significantly (p < 0.001) at two sampling sites. PAH concentrations increased in Kanazawa (p < 0.001) but not in Fukuoka on AD days. Correlation coefficients (r) between daily TSP and total PAHs concentrations were weak in Kanazawa: 0.521 (non-AD) and 0.526 (AD) (p < 0.01), and in Fukuoka: 0.321 (non-AD) and 0.059 (AD). However, correlation between seasonal (average monthly) TSP and total PAH concentrations were stronger: 0.680 (Kanazawa) and 0.751 (Fukuoka). The reasons might be that seasonal variations of TSP and total PAHs in two cities depend equally on planetary scale westerly, while daily TSP and total PAHs variations in each city varied by different transportation distances from AD and PAHs sources in the Asian continent to Japan. Different local sources and meteorological conditions were considered. These results are important for elucidating the causes of chronic and acute respiratory diseases.

Abstract Background We aimed to determine the presepsin concentration in pleural fluid from patients with pleural effusions of different aetiologies and to compare its diagnostic value with that of pleural fluid C-reactive protein (CRP) and procalcitonin (PCT). Methods We enrolled 132 patients with pleural effusion who underwent diagnostic evaluation, and we classified them into six categories: empyema, parapneumonic effusion, tuberculous effusion, malignant effusion, paramalignant effusion, and transudate effusion. Additionally, all pleural effusions were categorised as infectious or non-infectious effusions. Results Receiver operating characteristic analysis was used to evaluate diagnostic performance. When diagnosing empyema, the marker with the highest sensitivity was pleural fluid presepsin (cut-off: 754 pg/mL; sensitivity: 90.9%, specificity: 74.4%) and that with the highest specificity was pleural fluid CRP (cut-off: 4.91 mg/dL; sensitivity: 63.6%, specificity: 89.3%). Pleural fluid PCT tended to be lower in patients with empyema than in those with parapneumonic effusion, but this was not useful for the diagnosis of empyema. When diagnosing infectious pleural effusion, a combination of pleural fluid CRP (cut-off: 2.59 mg/dL) and presepsin (cut-off: 680 pg/mL) produced the highest diagnostic accuracy (83.3%). Conclusions Pleural fluid presepsin was found at high levels in patients with empyema and parapneumonic effusion. This pattern closely resembles the previously reported pattern of pleural fluid CRP. Some combinations of pleural fluid inflammatory markers may be more clinically useful than these markers in isolation.