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Abstract Background Fluoroquinolone (FQ) antimicrobials have antipyretic effects during the treatment of bacterial infections; however, it is not clear whether these are due to their antimicrobial activities or their hypothermic effects. In this study, we investigated the hypothermic effects of FQ antimicrobials (ciprofloxacin [CPFX], gatifloxacin [GFLX], and levofloxacin [LVFX]) on fever by evaluating rectal body temperature changes in a mouse model of non-bacterial fever. Methods CPFX, GFLX, and LVFX were administered intraperitoneally to non-bacterial fever model mice induced by yeast. Rectal body temperature was measured up to 180 min after administration. Results A decrease in rectal body temperature of up to 1.2 °C for CPFX, 3.4 °C for GFLX, and 1.0 °C for LVFX was observed. The decrease in temperature was induced by an increase in the plasma concentration of FQ antimicrobials, suggesting that they are responsible for the temperature reduction. Focusing on glucocorticoids, one thermoregulation mechanism, we investigated the substances responsible for the reduction in rectal body temperature induced by FQ antimicrobials. Aminoglutethimide (an inhibitor of glucocorticoid production) were premedicated, followed by intraperitoneal administration of GFLX in the yeast-induced fever mouse model, resulting in attenuated GFLX-induced hypothermic effects. Conclusions These results suggest that certain antipyretic effects of CPFX, GFPX, and LVFX during fever may contribute to their hypothermic effects; certain mechanisms are glucocorticoid-mediated.

Abstract Aim This study aimed to identify subgroups of alcohol use disorder (AUD) based on a multidimensional combination of alexithymia, depression, and diverse drinking behavior. Method We recruited 176 patients with AUD, which were initially divided into non‐alexithymic (n = 130) and alexithymic (n = 46) groups using a cutoff score of 61 on the Toronto Alexithymia Scale (TAS‐20). Subsequently, the profiles of the two groups were compared. Thereafter, a two‐stage cluster analysis using hierarchical and K‐means methods was performed with the Z‐scores from the TAS‐20, the Quick Inventory of Depressive Symptomatology Self‐Report Japanese Version, the 12‐item questionnaire for quantitative assessment of depressive mixed state, and the 20‐item questionnaire for drinking behavior pattern. Results In the first analysis, Alexithymic patients with AUD showed greater depressive symptoms and more pathological drinking behavior patterns than those without alexithymia. Cluster analysis featuring alexithymia, depression, and drinking behavior identified three subtypes: Cluster 1 (core AUD type) manifesting pathological drinking behavior highlighting automaticity; Cluster 2 (late‐onset type) showing relatively late‐onset alcohol use and fewer depressive symptoms or pathological drinking behavior; and Cluster 3 (alexithymic type) characterized by alexithymia, depression, and pathological drinking behavior featuring greater coping with negative affect. Conclusion The multidimensional model with alexithymia, depression, and diverse drinking behavior provided possible practical classification of AUD. The alexithymic subtype may require more caution, and additional support for negative affect may be necessary due to accompanying mood problems and various maladaptive drinking behaviors.

Parasitic otitis is an inflammatory process that can affect the external to internal cattle ear, causing discomfort in animals, impairing performance, and even leading to animal death. The infection was initially associated with nematodes of the Rhabditis genus in tropical and subtropical regions. Currently, the nematode species described as associated with bovine otitis are Metarhabditis costai, Metarhabditis freitasi, and, more recently, M. blumi. It is worth highlighting that there is still a lack of robust information regarding the morphological details, ultrastructural aspects, and molecular biology data of these species. The Metarhabditis genus is composed of seven species and two more have recently been added. The objective of this study is to update the morphological data using advanced microscopy techniques to emphasize and clarify the main morphological differences between three species of Metarhabditis currently associated with parasitic otitis. Samples of inflammatory exudate were collected from four adult female Gir cattle (Bos taurus indicus) on a farm in Itabira, Minas Gerais state, Brazil. Specimens were analyzed using light microscopy and scanning electron microscopy. Two species, M. costai and M. freitasi, were morphologically identified, consistent with previous reports. Scanning electron microscopy revealed new structural characteristics of the nematode species involved in parasitic otitis compared with M. blumi obtained from the CGC Center. Significant differences were observed in the male posterior region, bursa, and tail. Molecular analysis was conducted to differentiate these three species, and it was observed that the species first associated with otitis formed distinct clusters compared to M. blumi. However, it is important to note that further studies are needed to genetically characterize species of the Metarhabditis genus.

Abstract Vitamin C plays important roles as a cofactor in many enzymatic reactions and as an antioxidant against oxidative stress. As some mammals including humans cannot synthesize vitamin C de novo from glucose, its uptake from dietary sources is essential, and is mediated by the sodium-dependent vitamin C transporter 1 (SVCT1). Despite its physiological significance in maintaining vitamin C homeostasis, the structural basis of the substrate transport mechanism remained unclear. Here, we report the cryo-EM structures of human SVCT1 in different states at 2.5–3.5 Å resolutions. The binding manner of vitamin C together with two sodium ions reveals the counter ion-dependent substrate recognition mechanism. Furthermore, comparisons of the inward-open and occluded structures support a transport mechanism combining elevator and distinct rotational motions. Our results demonstrate the molecular mechanism of vitamin C transport with its underlying conformational cycle, potentially leading to future industrial and medical applications.

Magnetic fields have been shown to affect sensing, migration, and navigation in living organisms. However, the effects of magnetic fields on microorganisms largely remain to be elucidated. We develop an open-source, 3D-printed magnetic field exposure device to perform experiments on well-mixed and spatially structured microbial populations. This device is designed in AutoCAD, modeled in COMSOL, and validated using a Gaussmeter and experiments on the budding yeast Saccharomyces cerevisiae. We find that static magnetic field exposure slows the spatially structured expansion of yeast mats that expand in two dimensions, but not yeast mats that expand in three dimensions, across the surface of semi-solid yeast extract-peptone-dextrose agar media. We also find that magnetic fields do not affect the growth of planktonic yeast cells in well-mixed liquid yeast extract-peptone-dextrose media. This study provides an adaptable device for performing controlled magnetic field experiments on microbes and advances our understanding of the effects of magnetic fields on fungi.

Abstract Secondary sarcopenia, a risk factor even for young people, has attracted attention because of the deterioration of physical activity and nutritional status due to lifestyle change among university students. However, studies on the factors affecting motor function and their involvement are lacking. This cross-sectional study aimed to examine the influences of muscle mass loss and exercise and sleep habits on lower limb motor function, as well as the involvement of personality traits, in 101 university students. Approximately 6% of the participants had low skeletal muscle mass index, similar to previous reports, and that only exercise habits in high school were responsible for muscle mass loss (direct effect = − 0.493; p

ABSTRACT We aimed to assess the frequency of acute kidney injury (AKI) in different areas under the concentration–time curve (AUC) values of vancomycin (VAN) using a two-point blood collection method, allowing for accurate AUC assessment in critically ill patients. This multicenter retrospective observational study was conducted in eight hospitals. We retrospectively analyzed the data of patients who had received VAN in an intensive care unit (ICU) between January 2020 and December 2022. The primary outcome was the incidence of AKI. Patients were classified into three groups according to the AUC24–48h at the initial therapeutic drug monitoring (TDM) as follows:

Recent studies have highlighted the indispensable role of oxidized lipids in inflammatory responses, cell death, and disease pathogenesis. Consequently, inhibitors targeting oxidized lipids, particularly lipid-derived radicals critical in lipid peroxidation, which are known as radical-trapping antioxidants (RTAs), have been actively pursued. We focused our investigation on nitroxide compounds that have rapid second-order reaction rate constants for reaction with lipid-derived radicals. A novel screening system was developed by employing competitive reactions between library compounds and a newly developed profluorescence nitroxide probe with lipid-derived radicals to identify RTA compounds. A PubMed search of the top hit compounds revealed their wide application as repositioned drugs. Notably, the inhibitory efficacy of methyldopa, selected from these compounds, against retinal damage and bilateral common carotid artery stenosis was confirmed in animal models. These findings underscore the efficacy of our screening system and suggest that it is an effective approach for the discovery of RTA compounds.

Abstract Background Follicular adenomas with papillary architecture are rare tumors of thyroid origin and are composed of completely encapsulated follicular cells with a papillary architecture lacking the nuclear characteristics of papillary carcinoma. Herein, we present a case of follicular adenoma with papillary architecture originating from an ectopic thyroid gland, diagnosed from a mass in the submandibular region. Case Presentation A 70-year-old woman was referred to our hospital with the chief complaint of a painless left submandibular mass that had been present for one year. The patient underwent left submandibular dissection for therapy and diagnosis. Microscopically, papillary lesions with fibrovascular cores were observed in the interior, and the epithelial cells were cylindrical in shape with eosinophilic cytoplasm, round or oval nuclei, with no pathological features, leading to a diagnosis of papillary carcinoma or follicular carcinoma. The mass was diagnosed as a follicular thyroid adenoma with papillary architecture. This is the first report of a follicular adenoma with a papillary architecture originating from an ectopic thyroid gland. Conclusion This experience suggests that follicular adenoma should be included in the differential diagnosis of ectopic thyroid tumors.

The double-pipe heat exchanger is one of the most popular heat exchanger devices. In this study, the concentric tube heat exchanger as the double pipe heat exchanger device was simulated with ANSYS code FLUENT. The simulation was done by based on the Reynolds number variation from 400010.000 using the method of co-current and counter flow. The hydrodynamic and thermal simulation results agree with the empirical correlation of the Pethukov and Dittus-Bolter equations, respectively. The friction factors of the water base fluid and nanofluid f TiO2/water f (0.1 vol.%) do not result in a significant difference in the turbulent flow regime for both co-current and counter flow. The thermal performance of TiO2/water (0.1% vol) nanofluid as indicated by the value of the heat transfer coefficient results in an increase of 6.9% for counter low flow and 6.0% for co-current flow. Meanwhile, the direction of fluid flow in the heat exchanger does not have a significant effect on its thermal performance.

Abstract Anti-vascular endothelial growth factor (VEGF) therapy is the first-line treatment for diabetic macular edema (DME), but is less effective in some patients. We conducted a prospective study to determine whether laser combination therapy with anti-VEGF was more effective than Ranibizumab monotherapy in anti-VEGF-resistant DME patients. There was no significant difference in the improvement of the best-corrected visual acuity (BCVA) between the laser combination therapy and Ranibizumab monotherapy groups (3.2 letters and -7.5 letters, p = 0.165). BCVA did not significantly change between visits 1 and 7 (the laser combination group, 64.3 letters 70.3 letters, respectively, p = 0.537; the Ranibizumab monotherapy group, 72.3 letters and 64.8 letters, respectively, p = 0.554), with no significant improvements in central foveal retinal thickness (the laser combination therapy group, 9.3%: the Ranibizumab monotherapy groups, − 7.3%; p = 0.926). There was no significant difference in the number of Ranibizumab intravitreal therapy (IVT) sessions between the groups (laser combination therapy, 5.2; ranibizumab monotherapy, 6.0; p = 0.237). This study did not show that laser combination therapy was significantly more effective for anti-VEGF-resistant DME than anti-VEGF monotherapy alone. Therefore, for anti-VEGF-resistant DME, alternative therapeutic approaches beyond combined laser therapy may be considered.

Polyethylene oxide (PEO) has become a highly sought−after polymer electrolyte for lithium−ion batteries (LIBs) due to its high ionic conductivity, strong mechanical properties, and broad electrochemical stability range. However, its usefulness is hindered by its limited ionic conductivity at typical temperatures (

In parallel with advances in microscale imaging techniques, the fields of biology and materials science have focused on precisely extracting particle properties based on their diffusion behavior. Although the majority of real-world particles exhibit anisotropy, their behavior has been studied less than that of isotropic particles. In this study, we introduce a method for estimating the diffusion coefficients of individual anisotropic particles using short-trajectory data on the basis of a maximum likelihood framework. Traditional estimation techniques often use mean-squared displacement (MSD) values or other statistical measures that inherently remove angular information. Instead, we treated the angle as a latent variable and used belief propagation to estimate it while maximizing the likelihood using the expectation-maximization algorithm. Compared to conventional methods, this approach facilitates better estimation of shorter trajectories and faster rotations, as confirmed by numerical simulations and experimental data involving bacteria and quantum rods. Additionally, we performed an analytical investigation of the limits of detectability of anisotropy and provided guidelines for the experimental design. In addition to serving as a powerful tool for analyzing complex systems, the proposed method will pave the way for applying maximum likelihood methods to more complex diffusion phenomena.

Abstract Chronic kidney disease (CKD) involves progressive renal fibrosis, which gradually reduces kidney function and often causes various complications in extrarenal tissues. Therefore, we investigated fibrogenesis in extrarenal tissues (heart, liver, and lungs) in different experimental CKD models, such as the 5/6‐nephrectomy (5/6 Nx), unilateral ureteral obstruction (UUO), and a combination (2/3 Nx + UUO). We evaluated the degree of fibrogenesis in kidneys and extrarenal tissues by histological analysis and quantification of fibrosis‐related gene and protein expression. To elucidate the fibrosis mechanisms observed in 2/3 Nx + UUO mice, we evaluated the effect of indoxyl sulfate (IS), a typical uremic toxin accumulated in CKD, and transforming growth factor‐β (TGF‐β), a fibrosis‐related factor, on fibrosis using human hepatoma (HepG2) and RAW264.7 cells. A significant decline in renal function was observed in the 5/6 Nx and 2/3 Nx + UUO models, whereas a significant increase in renal fibrosis was observed only in the obstructed kidneys. Notable amount of fibrosis was induced in the liver and heart in the 2/3 Nx + UUO model, with the induction of macrophage infiltration and increased tissue IS and TGF‐β levels. In agreement with the results of in vivo experiments, co‐stimulation with IS, TGF‐β, and macrophage‐conditioned medium increased the expression of fibrogenic genes in HepG2 cells. We demonstrated that the 2/3 Nx + UUO model induced both loss of renal function and renal fibrosis in the earlier stages, providing a novel CKD model that induces remote organ fibrosis in a shorter time.