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Abstract We measured diurnal variations in oxidative stress conditions of cyanobacteria utilizing field observations and laboratory experiments in order to evaluate photoinhibition effects. On clear summer days, transparent bottles filled with surface water were set up at several depths and were collected every three hours together with the measurement of the photosynthetically active radiation (PAR). In the laboratory experiment, two cyanobacterial species were exposed to gradually increasing and then decreasing light intensities. The samples were analyzed with the PAR-induced (H2O2), along with the total hydrogen peroxide concentrations (total H2O2), the catalase activities (CAT), OD730, protein (Protein), and chlorophyll a (Chl a) contents, and so on. Protein was significantly proportionate with OD730 and Chl a, and was used as an indicator of cell biomass. Increasing PAR, H2O2 concentration increased proportionately with the PAR intensity. Then, an oxidative stress indicator in a cell, H2O2/Protein is given by the PAR divided by cell volume, evaluated by Protein. CAT activity in a cell, far largest among antioxidant activities, solely followed total H2O2/Protein. The prediction model for H2O2/Protein was developed with the sufficient agreement with the experimental and field observation results. The model elucidated that the maximum H2O2/Protein in a day was larger with lower cell density even at the water surface, indicating that the higher photoinhibition was imposed at low density, in addition to the lower attenuation of PAR. These results indicate that H2O2/Protein is an effective biomarker to indicate the stress level of cyanobacteria; the observed levels of H2O2 to freshwater may prove useful in designing the criteria for cyanobacteria management.

Abstract To evaluate diagnostic utility of tear meniscus height (TMH) measurement using anterior segment optical coherence tomography (AS-OCT) for lacrimal passage disorder (LPD) in patients scheduled for cataract surgery. Patients with cataracts were enrolled. Lacrimal irrigation test was used to diagnose LPD. TMH measurement was performed using prior to cataract surgery. A receiver operating characteristic curve analysis was performed to calculate the cutoff value of TMH to detect LPD. Correlation between TMH and age, sex, LPD, use of glaucoma eyedrops, and use of dry eye drops in patients with and without LPD was evaluated. Sixty-six patients (127 eyes) were included, of which 12 (9.4%) eyes had LPD. The mean TMH was significantly higher in the LPD group than in the non-LPD group (P = 0.007). Multiple regression analysis revealed a significant association of TMH with LPD (P = 0.000). With an area under the curve of 0.740, the optimal cut-off TMH value was 401.0 μm. The sensitivity and specificity of this cutoff value were 58.3% and 83.0%, respectively. These findings demonstrate the diagnostic utility of TMH, measured using AS-OCT, for LPD. This suggests that AS-OCT is useful for preoperative exclusion of LPD.

Abstract This study investigated whether machine learning (ML) has better predictive accuracy than logistic regression analysis (LR) for gait independence at discharge in subacute stroke patients (n = 843) who could not walk independently at admission. We developed prediction models using LR and five ML algorithms—specifically, the decision tree (DT), support vector machine, artificial neural network, ensemble learning, and k-nearest neighbor methods. Functional Independence Measure sub-items were used to evaluate the ability to walk independently. Model predictive accuracies were evaluated using areas under receiver operating characteristic curves (AUCs) as well as accuracy, precision, recall, F1 score, and specificity. The AUC for DT (0.812) was significantly lower than those for the other algorithms (p

Abstract The incidence of duodenal tumors (DTs) is increasing. However, the mechanisms underlying its development remain unclear. Environmental factors, including the microbiome and bile acids (BAs), are believed to influence tumor development. Therefore, we conducted a single-center, prospective, observational study to investigate the potential differences between patients with DTs and healthy controls (HCs) based on these factors. In addition, the BAs in the duodenal fluid were measured using liquid chromatography-tandem mass spectrometry. We recruited 41 patients and performed 16S rRNA-seq. There was no difference in the observed ASVs or PCoA plot of Bray–Curtis dissimilarity between the DTs and HCs. The lithocholic acid concentration was significantly lower in the DT group than in the control group. The ratio of CDCA to LCA was significantly higher in patients with DTs. No significant differences in microbiota were observed between DTs and HCs. In patients with DTs, the lithocholic acid concentration in duodenal was significantly lower than in HCs.

Abstract The meniscal position within the knee is critical to maintain normal knee function. The joint capsule might dynamically coordinate the medial meniscus (MM) by transmitting a semimembranosus action. However, their interrelationships in vivo are unclear. We aimed to determine relationships among the MM, joint capsule, and semimembranosus during passive tibial external-internal and isometric tibial internal rotation at the medial and posteromedial knees of 10 healthy individuals in vivo using ultrasound. We analyzed images of the MM and joint capsule locations at the medial and posteromedial knee and the velocity waveform similarity of each structure during rotational tasks. Both isometric internal rotation with semimembranosus action and passive tibial external rotation displaced the MM inward at the medial knee. The MM and joint capsule during these MM displacements coordinately moved with more than moderate cross-correlation coefficients (passive external and isometric internal rotations, ≥ 0.54 and ≥ 0.90, respectively). The movements of the MM and joint capsule to the semimembranosus during isometric internal rotation also coordinated with moderate cross-correlation coefficients (≥ 0.62). Therefore, the joint capsule might dynamically coordinate the MM by transmitting semimembranosus action. Whether increased tibial internal rotation or semimembranosus shortening causes MM extrusion awaits further investigation.

Abstract Helicobacter pylori eradication therapy reduces the risk of gastric cancer. However, it is unclear whether the severity of risk factors for gastric cancer such as atrophy and intestinal metaplasia are reduced after eradication in the long term. We aimed to study long-term changes in endoscopic risk factors for gastric cancer up to 20 years post-eradication. The endoscopic severity of gastritis according to the Kyoto Classification of Gastritis in 167 patients was retrospectively evaluated over an average follow-up 15.7 years. A significant improvement in mean total gastric cancer risk score (4.36 ± 1.66 to 2.69 ± 1.07, p

Abstract To investigate the therapeutic potential of photodynamic therapy (PDT) for malignant gliomas arising in unresectable sites, we investigated the effect of tumor tissue damage by interstitial PDT (i-PDT) using talaporfin sodium (TPS) in a mouse glioma model in which C6 glioma cells were implanted subcutaneously. A kinetic study of TPS demonstrated that a dose of 10 mg/kg and 90 min after administration was appropriate dose and timing for i-PDT. Performing i-PDT using a small-diameter plastic optical fiber demonstrated that an irradiation energy density of 100 J/cm2 or higher was required to achieve therapeutic effects over the entire tumor tissue. The tissue damage induced apoptosis in the area close to the light source, whereas vascular effects, such as fibrin thrombus formation occurred in the area slightly distant from the light source. Furthermore, when irradiating at the same energy density, irradiation at a lower power density for a longer period of time was more effective than irradiation at a higher power density for a shorter time. When performing i-PDT, it is important to consider the rate of delivery of the irradiation light into the tumor tissue and to set irradiation conditions that achieve an optimal balance between cytotoxic and vascular effects.

Abstract We aimed to establish a new method of obtaining femur anteroposterior radiographs from live rats. We used five adult male Sprague–Dawley rats and created a femoral fracture model with an 8 mm segmental fragment. After the surgery, we obtained two femoral anteroposterior radiographs, a novel overhead method, and a traditional craniocaudal view. We obtained the overhead method three times, craniocaudal view once, and anteroposterior radiograph of the isolated femoral bone after euthanasia. We compared the overhead method and craniocaudal view with an isolated femoral anteroposterior view. We used a two-sample t-test and intraclass correlation coefficient (ICC) to estimate the intra-observer reliability. The overhead method had significantly smaller differences than the craniocaudal view for nail length (1.53 ± 1.26 vs. 11.4 ± 3.45, p

Abstract Belt electrode-skeletal muscle electrical stimulation (B-SES) involves the use of belt-shaped electrodes to contract multiple muscle groups simultaneously. Twitch contractions have been demonstrated to protect against denervation-induced muscle atrophy in rats, possibly through mitochondrial biosynthesis. This study examined whether inducing tetanus contractions with B-SES suppresses muscle atrophy and identified the underlying molecular mechanisms. We evaluated the effects of acute (60 Hz, 5 min) and chronic (60 Hz, 5 min, every alternate day for one week) B-SES on the tibialis anterior (TA) and gastrocnemius (GAS) muscles in Sprague–Dawley rats using belt electrodes attached to both ankle joints. After acute stimulation, a significant decrease in the glycogen content was observed in the left and right TA and GAS, suggesting that B-SES causes simultaneous contractions in multiple muscle groups. B-SES enhanced p70S6K phosphorylation, an indicator of the mechanistic target of rapamycin complex 1 activity. During chronic stimulations, rats were divided into control (CONT), denervation-induced atrophy (DEN), and DEN + electrically stimulated with B-SES (DEN + ES) groups. After seven days of treatment, the wet weight (n = 8–11 for each group) and muscle fiber cross-sectional area (CSA, n = 6 for each group) of the TA and GAS muscles were reduced in the DEN and DEN + ES groups compared with that in the CON group. The DEN + ES group showed significantly higher muscle weight and CSA than those in the DEN group. Although RNA-seq and pathway analysis suggested that mitochondrial biogenesis is a critical event in this phenomenon, mitochondrial content showed no difference. In contrast, ribosomal RNA 28S and 18S (n = 6) levels in the DEN + ES group were higher than those in the DEN group, even though RNA-seq showed that the ribosome biogenesis pathway was reduced by electrical stimulation. The mRNA levels of the muscle proteolytic molecules atrogin-1 and MuRF1 were significantly higher in DEN than those in CONT. However, they were more suppressed in DEN + ES than those in DEN. In conclusion, tetanic electrical stimulation of both ankles using belt electrodes effectively reduced denervation-induced atrophy in multiple muscle groups. Furthermore, ribosomal biosynthesis plays a vital role in this phenomenon.

Abstract The preset study tested whether an aphid species can control its reproduction by recognizing the presence and density of a rival species. Acyrthosiphon pisum and Megoura crassicauda often coexist on the same leguminous plant. We established clonal colonies from each species and mixed colonies with one A. pisum and one M. crassicauda adult. There were no significant differences in the population growth patterns of the two species at 20 °C. However, mixed colonies increased faster and attained larger colony sizes than the clonal colonies. Thus, positive interspecific interactions were confirmed. A mixed colony was dominated by the members of a clone that produced a greater number of newborns in the initial stage, irrespective of the species. Thus, we confirmed the priority effect in the interspecific competition. To simulate the priority effect, 15 glass beads coated with the hexane extract of M. crassicauda aphids were attached to a cut leaf, to which one A. pisum adult was transferred. The presence of the hexane extract of M. crassicauda greatly reduced the reproductive rate of A. pisum adults. We conclude that aphids can control their reproduction by evaluating the relative density of rivals to fellow aphids based on the cuticular hydrocarbons.

Abstract The age-related degenerative pathologies of the cervical spinal column that comprise degenerative cervical myelopathy (DCM) cause myelopathy due spinal cord compression. Functional neurological assessment of DCM can potentially reveal the severity and pathological mechanism of DCM. However, functional assessment by conventional MRI remains difficult. This study used resting-state functional MRI (rs-fMRI) to investigate the relationship between functional connectivity (FC) strength and neurophysiological indices and examined the feasibility of functional assessment by FC for DCM. Preoperatively, 34 patients with DCM underwent rs-fMRI scans. Preoperative central motor conduction time (CMCT) reflecting motor functional disability and intraoperative somatosensory evoked potentials (SEP) reflecting sensory functional disability were recorded as electrophysiological indices of severity of the cervical spinal cord impairment. We performed seed-to-voxel FC analysis and correlation analyses between FC strength and the two electrophysiological indices. We found that FC strength between the primary motor cortex and the precuneus correlated significantly positively with CMCT, and that between the lateral part of the sensorimotor cortex and the lateral occipital cortex also showed a significantly positive correlation with SEP amplitudes. These results suggest that we can evaluate neurological and electrophysiological severity in patients with DCM by analyzing FC strengths between certain brain regions.

Abstract Canine primary lung cancer with metastasis has a poor prognosis with no effective treatment. We previously generated a recombinant measles virus (MV) that lost binding affinity to a principal receptor, SLAM, to eliminate its virulence as a new cancer treatment strategy. The virus, rMV-SLAMblind, targets nectin-4, recently listed as a tumor marker, and exerts antitumor activity against nectin-4-positive canine mammary cancer and urinary bladder transitional cell carcinoma cells. However, the effectivity of rMV-SLAMblind for other types of canine cancers is still unknown. Here we evaluated the antitumor effect of rMV-SLAMblind to canine lung cancer. Nectin-4 is expressed on three canine lung cancer cell lines (CLAC, AZACL1, AZACL2) and rMV-SLAMblind was able to infect these cell lines. CLAC cells showed reduced cell viability after virus infection. In the CLAC xenograft nude mouse model, intratumoral administration of rMV-SLAMblind significantly suppressed tumor growth. In rMV-SLAMblind-treated mice, natural killer cells were activated, and Cxcl10 and Il12a levels were significantly increased in comparison with levels in the control group. In addition, the depletion of NK cells reduced the anti-tumor effect. To understand difference in efficacy among canine lung cancer cell lines, we compared virus growth and gene expression pattern after virus treatment in the three canine lung cancer cell lines; virus growth was highest in CLAC cells compared with the other cell lines and the induction of interferon (IFN)-beta and IFN-stimulated genes was at lower levels in CLAC cells. These results suggested that rMV-SLAMblind exhibits oncolytic effect against some canine lung cancer cells and the cellular response after the virus infection may influence its efficacy.

Abstract Nintedanib reduces the decline in forced vital capacity and extends the time to the first acute exacerbation of interstitial lung disease (AE-ILD). However, the effect of additional nintedanib administration after AE-ILD onset is unknown. This study aimed to investigate the efficacy and safety of nintedanib administration after AE-ILD development. We retrospectively collected the data of 33 patients who developed AE-ILD between April 2014 and January 2022. Eleven patients who received nintedanib after AE-ILD development and the remaining who did not were classified into the N and No-N groups, respectively. The survival time in the N group tended to be longer than that in the No-N group. The generalized Wilcoxson test revealed that the cumulative mortality at 90 days from AE-ILD onset was significantly lower in the N group. The time to subsequent AE-ILD development was significantly longer in the N group than that in the No-N group. The incidence of adverse gastrointestinal effects and liver dysfunction in the N group was 9–18%. Treatment without nintedanib after AE-ILD development and the ratio of arterial oxygen partial pressure to fractional inspired oxygen were significant independent prognostic factors in the multivariate analysis. Thus, nintedanib administration may be a treatment option for AE-ILD.

Abstract Medial meniscal extrusion (MME) is a structural abnormality that leads to early knee osteoarthritis; however, its formation remains debated. For anatomical consideration of the mechanism underlying MME formation, we examined the capsular attachment on the posteromedial tibia and its layered association with the semimembranosus. Fourteen knees of eight body donors were analyzed in this study; six knees were grouped for macroscopic analysis, whereas four knees each were grouped for histological and phosphotungstic acid-enhanced micro-computed tomography analyses. The capsular attachment varied in width according to location and was not distant from the articular cartilage and posterior root. A portion of the posteromedial joint capsule formed the semimembranosus tendinous sheath. The dense fibrous membrane superficial to the semimembranosus, which was continuous from its tendinous sheath, existed as one of the layers of the joint capsule. The aforementioned findings were confirmed in all specimens. Based on the capsular attachment and its layered association with the semimembranosus, the conventional posteromedial knee ligaments may be only a part of the joint capsule divided into two layers by the semimembranosus. If the coordinated action of the joint capsule and semimembranosus partially contributes to the medial meniscus stability, such a structural problem may affect MME formation.

Abstract Although many therapeutic options are available for inflammatory bowel disease (IBD), 5-aminosalicylic acid (5-ASA) is still the key medication, particularly for ulcerative colitis (UC). However, the mechanism of action of 5-ASA remains unclear. The intestinal microbiota plays an important role in the pathophysiology of IBD, and we hypothesized that 5-ASA alters the intestinal microbiota, which promotes the anti-inflammatory effect of 5-ASA. Because intestinal inflammation affects the gut microbiota and 5-ASA can change the severity of inflammation, assessing the impact of inflammation and 5-ASA on the gut microbiota is not feasible in a clinical study of patients with UC. Therefore, we undertook a translational study to demonstrate a causal link between 5-ASA administration and alterations of the intestinal microbiota. Furthermore, by rigorously controlling environmental confounders and excluding the effect of 5-ASA itself with a vertical transmission model, we observed that the gut microbiota altered by 5-ASA affected host mucosal immunity and decreased susceptibility to dextran sulfate sodium-induce colitis. Although the potential intergenerational transmission of epigenetic changes needs to be considered in this study, these findings suggested that alterations in the intestinal microbiota induced by 5-ASA directed the host immune system towards an anti-inflammatory state, which underlies the mechanism of 5-ASA efficacy.

A 58-year-old woman with a history of systemic lupus erythematosus (SLE) who was taking prednisolone and mycophenolate mofetil presented with gait disturbances that progressively worsened over a period of 3 months. Her blood test and cerebrospinal fluid (CSF) examination results did not indicate active SLE. Initial brain magnetic resonance imaging (MRI) revealed a small spotty lesion in the left cerebellar peduncle. The clinical course was consistent with rapidly progressive cerebellar syndrome (RPCS), which sometimes involves neuronal antibodies. The line blot assay detected anti-Yo antibodies, but no malignancy was found. Immunohistological techniques using rat brain sections yielded a negative result for anti-Yo antibodies. The second MRI revealed a focal lesion and surrounding spotty lesion in the left cerebellar peduncle, which was consistent with the punctate pattern observed in progressive multifocal leukoencephalopathy (PML). The CSF JCV-DNA test indicated the presence of cerebellar PML. Immunosuppressants were reduced, and mefloquine and mirtazapine were initiated. After approximately 2 years and 1 month, the CSF JCV-DNA results became negative. Cerebellar PML may exhibit a clinical course that is consistent with RPCS. The punctate pattern should be recognized as an early manifestation of PML. The CSF JCV-DNA copy number may serve as a useful indicator of PML stabilization.

IntroductionBrain positron emission tomography/computed tomography (PET/CT) scans are useful for identifying the cause of dementia by evaluating glucose metabolism in the brain with F-18-fluorodeoxyglucose or Aβ deposition with F-18-florbetaben. However, since imaging time ranges from 10 to 30 minutes, movements during the examination might result in image artifacts, which interfere with diagnosis. To solve this problem, data-driven brain motion correction (DDBMC) techniques are capable of performing motion corrected reconstruction using highly accurate motion estimates with high temporal resolution. In this study, we investigated the effectiveness of DDBMC techniques on PET/CT images using a Hoffman phantom, involving continuous rotational and tilting motion, each expanded up to approximately 20 degrees.Materials and methodsListmode imaging was performed using a Hoffman phantom that reproduced rotational and tilting motions of the head. Brain motion correction processing was performed on the obtained data. Reconstructed images with and without brain motion correction processing were compared. Visual evaluations by a nuclear medicine specialist and quantitative parameters of images with correction and reference still images were compared.ResultsNormalized Mean Squared Error (NMSE) results demonstrated the effectiveness of DDBMC in compensating for rotational and tilting motions during PET imaging. In Cases 1 and 2 involving rotational motion, NMSE decreased from 0.15-0.2 to approximately 0.01 with DDBMC, indicating a substantial reduction in differences from the reference image across various brain regions. In the Structural Similarity Index (SSIM), DDBMC improved it to above 0.96 Contrast assessment revealed notable improvements with DDBMC. In continuous rotational motion, % contrast increased from 42.4% to 73.5%, In tilting motion, % contrast increased from 52.3% to 64.5%, eliminating significant differences from the static reference image. These findings underscore the efficacy of DDBMC in enhancing image contrast and minimizing motion induced variations across different motion scenarios.ConclusionsDDBMC processing can effectively compensate for continuous rotational and tilting motion of the head during PET, with motion angles of approximately 20 degrees. However, a significant limitation of this study is the exclusive validation of the proposed method using a Hoffman phantom; its applicability to the human brain has not been investigated. Further research involving human subjects is necessary to assess the generalizability and reliability of the presented motion correction technique in real clinical scenarios.

Abstract Early detection of cervical myelopathy (CM) is important for a favorable outcome, as its prognosis is poor when left untreated. We developed a screening method for CM using machine learning-based analysis of the drawing behavior of 38 patients with CM and 66 healthy volunteers. Using a stylus pen, the participants traced three different shapes displayed on a tablet device. During the tasks, writing behaviors, such as the coordinates, velocity, and pressure of the stylus tip, along with the drawing time, were recorded. From these data, features related to the drawing pressure, and time to trace each shape and combination of shapes were used as training data for the support vector machine, a machine learning algorithm. To evaluate the accuracy, a receiver operating characteristic curve was generated, and the area under the curve (AUC) was calculated. Models with triangular waveforms tended to be the most accurate. The best triangular wave model identified patients with and without CM with 76% sensitivity and 76% specificity, yielding an AUC of 0.80. Our model was able to classify CM with high accuracy and could be applied to the development of disease screening systems useful outside the hospital setting.

(1) Introduction: Spontaneous spinal epidural hematoma (SSEH) points to hematoma within the epidural space of the spinal cord without traumatic or iatrogenic causes. (2) Case Reports: One patient showed paraplegia, numbness of both legs with acute onset, acute myelopathic signs, subsequent to back pain. Magnetic resonance imaging (MRI) showed hematoma in the posterior part of the thoracic spinal cord. Another patient showed acute numbness in the shoulder, upper part of the back, and the upper extremity on the right side after pain in the back, shoulder, and neck on the right side. Sagittal computed tomography (CT) images of the cervical bone showed a high-density area behind the spinal cord between C4 and C7. MRI analysis showed hematoma in the right diagonally posterior part of the cervical spinal cord. These 2 patients lacked traumatic or iatrogenic events, and their symptoms abated without surgical operation. (3) Conclusions: The location of hematoma correlated with symptoms in each patient. SSEH is rare but should be taken into account in patients with myelopathy or radiculopathy with acute onset subsequent to back pain. The usefulness of emergent CT scans of the spinal cord prior to MRI analysis was shown in the diagnosis of SSEH.

This study aimed to evaluate the clinical characteristics of acute ischemic stroke (AIS) patients who experienced hypoesthesia as the initial symptom. We retrospectively analyzed the medical records of 176 hospitalized AIS patients who met our inclusion and exclusion criteria and evaluated their clinical features and MRI findings. Among this cohort, 20 (11%) patients presented with hypoesthesia as the initial symptom. MRI scans of these 20 patients identified lesions in the thalamus or pontine tegmentum in 14 and brain lesions at other sites in 6. The 20 hypoesthesia patients had higher systolic (p = 0.031) and diastolic blood pressure (p = 0.037) on admission, and a higher rate of small-vessel occlusion (p < 0.001) than patients without hypoesthesia. The patients with hypoesthesia had a significantly shorter average hospital stay (p = 0.007) but did not differ significantly from those without hypoesthesia in National Institutes of Health Stroke Scale scores on admission (p = 0.182) or the modified Rankin Scale scores for neurologic disability on discharge (p = 0.319). In the patients with acute onset hypoesthesia, high blood pressure, and neurological deficits were more likely to be due to AIS than other causes. Since most of the lesions in AIS patients with hypoesthesia as the initial symptom were found to be small, we recommend performing MRI scans with such patients to confirm AIS.

Post-stroke pneumonia (PSP) has an impact on acute ischemic stroke (AIS). Although predictive scores for PSP have been developed, it is occasionally difficult to predict. Clarifying how PSP was treated after its onset in clinical practice is important. Admitted patients with AIS over a 2-year period were retrospectively reviewed. Of 281 patients with AIS, 24 (8.5%) developed PSP. The integer-based pneumonia risk score was higher in patients with PSP. The onset of PSP was frequently seen up to the 4th day of hospitalization. Of patients with PSP, sputum examination yielded Geckler 4 or 5 in only 8.3%. Angiotensin-converting enzyme inhibitor (ACE-I) was more frequently administered to patients with PSP; however, all these cases were started with ACE-I following PSP onset. Nasogastric tubes (NGTs) were inserted in 16 of the patients with PSP, of whom 11 were inserted following PSP onset. Multivariate analysis showed that PSP onset was a poor prognostic factor independent of the female sex, urinary tract infection, and National Institutes of Health Stroke Scale. PSP treatment would benefit from the administration of antimicrobials and ACE-I, as well as NGT insertion. To select effective agents for PSP and evaluate the indications for NGT insertion, further case studies are needed.

Abstract To determine the pathogenesis of trapeziometacarpal (TMC) joint instability, which leads to osteoarthritis, we investigated the anatomical relationships among the surrounding ligaments, muscles (first dorsal interosseous [FDI] and opponens pollicis [OPP]), and joint capsule. We examined the bone morphology and cortical bone thickening in 25 cadaveric thumbs using micro-computed tomography and performed macroscopic and histological analyses. The dorsal trapezium had a tubercle with cortical bone thickening, corresponding to the attachment of the FDI aponeurosis intermingled with the joint capsule. Radially, the thin joint capsule was observed to underlie the muscular part of the OPP. Therefore, the dorsal ligaments, which have been previously considered static stabilizers, could be interpreted as parts of the capsuloaponeurotic complex consisting of the FDI aponeurosis and joint capsule. In the radial aspect, muscular OPP activation may be essential for TMC joint stabilization. Our findings may contribute to the appropriate management of TMC osteoarthritis.

Abstract Belt electrode skeletal muscle electrical stimulation (B-SES) can simultaneously contract multiple muscle groups. Although the beneficial effects of B-SES in clinical situations have been elucidated, its molecular mechanism remains unknown. In this study, we developed a novel rodent B-SES ankle stimulation system to test whether low-frequency stimulation prevents denervation-induced muscle atrophy. Electrical stimulations (7‒8 Hz, 30 min) with ankle belt electrodes were applied to Sprague–Dawley rats daily for one week. All animals were assigned to the control (CONT), denervation-induced atrophy (DEN), and DEN + electrical stimulation (ES) groups. The tibialis anterior (TA) and gastrocnemius (GAS) muscles were used to examine the effect of ES treatment. After seven daily sessions of continuous stimulation, muscle wet weight (n = 8–11), and muscle fiber cross-sectional area (CSA, n = 4–6) of TA and GAS muscles were lower in DEN and DEN + ES than in CON. However, it was significantly higher in DEN than DEN + ES, showing that ES partially prevented muscle atrophy. PGC-1α, COX-IV, and citrate synthase activities (n = 6) were significantly higher in DEN + ES than in DEN. The mRNA levels of muscle proteolytic molecules, Atrogin-1 and Murf1, were significantly higher in DEN than in CONT, while B-SES significantly suppressed their expression (p

Abstract Immunoglobulin A (IgA) is a candidate antibody for oral passive immunization against mucosal pathogens like Shiga toxin-producing Escherichia coli (STEC). We previously established a mouse IgG monoclonal antibody (mAb) neutralizing Shiga toxin 1 (Stx1), a bacterial toxin secreted by STEC. We designed cDNA encoding an anti-Stx1 antibody, in which variable regions were from the IgG mAb and all domains of the heavy chain constant region from a mouse IgA mAb. Considering oral administration, we expressed the cDNA in a plant expression system aiming at the production of enough IgA at low cost. The recombinant-IgA expressed in Arabidopsis thaliana formed the dimeric IgA, bound to the B subunit of Stx1, and neutralized Stx1 toxicity to Vero cells. Colon injury was examined by exposing BALB/c mice to Stx1 via the intrarectal route. Epithelial cell death, loss of crypt and goblet cells from the distal colon were observed by electron microscopy. A loss of secretory granules containing MUC2 mucin and activation of caspase-3 were observed by immunohistochemical methods. Pretreatment of Stx1 with the plant-based recombinant IgA completely suppressed caspase-3 activation and loss of secretory granules. The results indicate that a plant-based recombinant IgA prevented colon damage caused by Stx1 in vivo.

Abstract The outer mucus layer of the colorectal epithelium is easily removable and colonized by commensal microbiota, while the inner mucus layer is firmly attached to the epithelium and devoid of bacteria. Although the specific bacteria penetrating the inner mucus layer can contact epithelial cells and trigger cancer development, most studies ignore the degree of mucus adhesion at sampling. Therefore, we evaluated whether bacteria adhering to tissues could be identified by removing the outer mucus layer. Our 16S rRNA gene sequencing analysis of 18 surgical specimens of human colorectal cancer revealed that Sutterella (P = 0.045) and Enterobacteriaceae (P = 0.045) were significantly enriched in the mucus covering the mucosa relative to the mucosa. Rikenellaceae (P = 0.026) was significantly enriched in the mucus covering cancer tissues compared with those same cancer tissues. Ruminococcaceae (P = 0.015), Enterobacteriaceae (P = 0.030), and Erysipelotrichaceae (P = 0.028) were significantly enriched in the mucus covering the mucosa compared with the mucus covering cancers. Fusobacterium (P = 0.038) was significantly enriched in the mucus covering cancers compared with the mucus covering the mucosa. Comparing the microbiomes of mucus and tissues with mucus removed may facilitate identifying bacteria that genuinely invade tissues and affect tumorigenesis.

Background Since the COVID-19 pandemic started, remote work and education and digital display use have become more prevalent. However, compared with printed material, digital displays cause more eye fatigue and may decrease task performance. For instance, the reflections on the monitor can cause discomfort or distraction, particularly when glare monitors are used with black backgrounds. Methods This study simultaneously uses electroencephalography (EEG) and an eye-tracker to measure the possible negative effects of using a glare monitor on the illegibility of sentences. Results The experiment results showed no difference in reading time and subjective illegibility rating between glare and non-glare monitors. However, with glare monitors, eye fixation when reading lasted longer. Further, EEG beta (15–20 Hz) power variations suggested that the participants were less engaged in the reading task when a glare monitor was used with a black background. Conclusions These results indicate that the negative effects of using a glare monitor are subtle but certainly present. They also show that physiological measures such as EEG and eye tracking can assess the subtle effects in an objective manner, even if behavioral measures such as subjective illegibility ratings or reading time may not show the differences.

Abstract The talocalcaneonavicular joint (TCN-j) is supported by the spring ligament, which has recently been revealed to be part of the joint capsule complex, along with the tendinous sheath of the tibialis posterior and flexor digitorum longus (FDL). Nonetheless, the FDL’s role in TCN-j stability has received limited attention. This study aimed to elucidate the positional relationships between the FDL and sustentaculum tali, which comprises the TCN-j. We hypothesized that the FDL runs medial to the sustentaculum tali, and its course significantly changes from the sitting to the standing position. Six ankles from six body donors were investigated, and seven ankles from seven volunteers were assessed using ultrasonography. The FDL was three-dimensionally located inferomedial to the sustentaculum tali. The FDL tendinous sheath was attached to the sustentaculum tali or connected by the tibialis posterior via the tendinous sheath. Based on the in vivo ultrasound image, the FDL location relative to the sustentaculum tali was maintained; however, the curvature of the FDL course was significantly more prominent in standing than in sitting. The FDL force against the bending moment may prevent the excessive eversion of the foot and aid the conventional spring ligament’s contribution to TCN-j stability for maintaining the longitudinal arch.

Abstract Although the flexion abduction external rotation (FABER) test is a useful hip provocation test, hip soft tissue characteristics in the FABER position remain unclear. This study investigated the in-vivo joint capsule characteristics, including its articular cavity area and relation to the fat pad surrounded by the joint capsule and pericapsular muscles, in the FABER position using magnetic resonance imaging. Thirteen hips from 13 healthy volunteers were analyzed. The images were obtained, with the participant hips at 15°-extension, 45°-flexion, and in the FABER position, to analyze the articular cavity size and fat pad and calculate these ratios to size of the femoral neck. The articular cavity area and its ratio to the femoral neck were significantly greatest in the FABER position, followed by those in the hip flexion and extension. Additionally, the area of the fat pad in the inter-pericapsular muscle space and its ratio to the femoral neck in the FABER position were significantly larger than those in the hip flexion and, as a tendency, larger than those in hip extension. To the best of our knowledge, this is the first in-vivo study to show the interrelationship among the joint capsule, pericapsular muscles, and fat pad in the FABER position.

Abstract The kidney plays a central role in body fluid homeostasis. Cells in the glomeruli and juxtaglomerular apparatus sense mechanical forces and modulate glomerular filtration and renin release. However, details of mechanosensory systems in these cells are unclear. Piezo2 is a recently identified mechanically activated ion channel found in various tissues, especially sensory neurons. Herein, we examined Piezo2 expression and regulation in mouse kidneys. RNAscope in situ hybridization revealed that Piezo2 expression was highly localized in mesangial cells and juxtaglomerular renin-producing cells. Immunofluorescence assays detected GFP signals in mesangial cells and juxtaglomerular renin-producing cells of Piezo2 GFP reporter mice. Piezo2 transcripts were observed in the Foxd1-positive stromal progenitor cells of the metanephric mesenchyme in the developing mouse kidney, which are precursors of mesangial cells and renin-producing cells. In a mouse model of dehydration, Piezo2 expression was downregulated in mesangial cells and upregulated in juxtaglomerular renin-producing cells, along with the overproduction of renin and enlargement of the area of renin-producing cells. Furthermore, the expression of the renin coding gene Ren1 was reduced by Piezo2 knockdown in cultured juxtaglomerular As4.1 cells under static and stretched conditions. These data suggest pivotal roles for Piezo2 in the regulation of glomerular filtration and body fluid balance.

Abstract Type III interferons (IFNs) play an important role in respiratory viral infections, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. This study aimed to determine whether the expression of serum type III IFNs predicted disease severity among patients with the coronavirus disease (COVID-19). A retrospective cohort study was conducted of patients admitted to a single hospital between March 21, 2020, and March 31, 2021. Patients were divided into mild to moderate I (MM) and moderate II to severe (MS) groups based on the COVID-19 severity classification developed by the Japanese Ministry of Health, Labor and Welfare. A total of 257 patients were included in the analysis. Human interleukin-28A (IL-28A/IFN-λ2) expression was significantly lower, and interleukin (IL)-6 expression was significantly higher in the MS group than in the MM group (both p

Abstract The Belousov–Zhabotinsky (BZ) self-oscillation reaction is an important chemical model to elucidate nonequilibrium chemistry in an open system. However, there are only a few studies on the electrical behavior of pH oscillation induced by the BZ reaction, although numerous studies have been carried out to investigate the mechanisms by which the BZ reaction interacts with redox reactions, which results in potential changes. Needless to say, the electrical characteristic of a self-oscillating polymer gel driven by the BZ reaction has not been clarified. On the other hand, a solution-gated ion-sensitive field-effect transistor (ISFET) has a superior ability to detect ionic charges and includes capacitive membranes on the gate electrode. In this study, we carried out the electrical monitoring of self-oscillation behaviors at the chemoelectrical interface based on the BZ reaction using ISFET sensors, focusing on the pH oscillation and the electrical dynamics of the self-oscillating polymer brush. The pH oscillation induced by the BZ reaction is not only electrically observed using the ISFET sensor, the electrical signals of which results from the interfacial potential between the solution and the gate insulator, but also visualized using a large-scale and high-density ISFET sensor. Moreover, the N-isopropylacrylamide (NIPAAm)-based self-oscillating polymer brush with Ru(bpy)3 as a catalyst clearly shows a periodic electrical response based on the swelling–deswelling behavior caused by the BZ reaction on the gate insulator of the ISFET sensor. Thus, the elucidation of the electrical self-oscillation behaviors induced by the BZ reaction using the ISFET sensor provides a solution to the problems of nonequilibrium chemistry.

Abstract Comprehensive data are needed to prevent substandard and falsified (SF) medicines as they pose a major risk to human health. To assess the quality of selected medicines, samples were collected from random private drug outlets of Dhaka North and South City Corporation, Bangladesh. Sample analysis included visual observation of the packaging, authenticity of the samples, legitimacy and registration verification of the manufacturer, physicochemical analysis, and price. Chemical analysis of the samples was performed using a portable Raman spectroscopy and high-performance liquid chromatography according to the pharmacopoeia. Several discrepancies were noted in the visual observation of samples. Among the 189 collected samples of esomeprazole (ESM), cefixime (CFIX), and amoxicillin-clavulanic acid (CVA-AMPC), 21.2% were confirmed to be authentic, 91.3% manufacturers were confirmed legitimate, and 2.1% of all samples were unregistered. Chemical analysis of the samples revealed that 9.5% (95% CI 5.7–14.6) of samples were SFs. Falsified samples and quality variation in the same generic branded samples were both detected by Raman spectroscopic analysis. Overall, sample prices were satisfactory relative to the international reference price. This study documents the availability of poor-quality medicines, demonstrating the need for immediate attention by the national medicine regulatory authority.

Objective To investigate the effectiveness of joint mobilization (JM) combined with acupuncture (AC) for the treatment of pain, physical function and depression in poststroke patients. Methods A total of 69 poststroke patients were randomly assigned to the JM+AC group (n = 23), the JM group (n = 23), and the control group (n = 23). Patients in the JM+AC group and the JM group received JM for 30 minutes, twice a week for 12 weeks, and the JM+AC group received AC for 30 minutes separately once a week. The control group did not receive JM or AC. Pain (visual analog scale, shoulder pain and disability index, Western Ontario and McMaster universities osteoarthritis index), physical function (range of motion, 10-m walking speed test, functional gait assessment, manual function test, activities of daily living scale, instrumental activities of daily living scale), and depression (center for epidemiologic studies depression scale, Beck depression inventory) were assessed for each patient before and after the 12 weeks of intervention. Results Pain and physical function were improved significantly in the JM+AC group compared with the JM and control groups. Physical function and depression were improved significantly in the JM+AC and JM groups compared with the control group. Conclusion The treatment of JM combined with AC improved pain, depression, and physical function of poststroke patients with chronic neuropathic pain in this study. This valuable finding provides empirical evidence for the designing therapeutic interventions and identifying potential therapeutic targets.

Abstract Genome editing techniques such as CRISPR/Cas9 have both become common gene engineering technologies and have been applied to gene therapy. However, the problems of increasing the efficiency of genome editing and reducing off-target effects that induce double-stranded breaks at unexpected sites in the genome remain. In this study, we developed a novel Cas9 transduction system, Exci-Cas9, using an adenovirus vector (AdV). Cas9 was expressed on a circular molecule excised by the site-specific recombinase Cre and succeeded in shortening the expression period compared to AdV, which expresses the gene of interest for at least 6 months. As an example, we chose hepatitis B, which currently has more than 200 million carriers in the world and frequently progresses to liver cirrhosis or hepatocellular carcinoma. The efficiencies of hepatitis B virus genome disruption by Exci-Cas9 and Cas9 expression by AdV directly (Avec) were the same, about 80–90%. Furthermore, Exci-Cas9 enabled cell- or tissue-specific genome editing by expressing Cre from a cell- or tissue-specific promoter. We believe that Exci-Cas9 developed in this study is useful not only for resolving the persistent expression of Cas9, which has been a problem in genome editing, but also for eliminating long-term DNA viruses such as human papilloma virus.

Abstract Prevention of postoperative anastomotic leakage in rectal surgery is still required. This study investigated the feasibility of endoscopic hand suturing (EHS) on rectal anastomosis ex vivo. By using isolated porcine colon, we prepared ten anastomoses 6–10 cm from the virtual anus. Then, we sutured anastomoses intraluminally by EHS, which involved a continuous suturing method in 5 cases and a nodule suturing method with extra corporeal ligation in 5 cases. Completeness of suturing, number of stitches, procedure time and presence of stenosis were investigated. Furthermore, the degree of stenosis was compared between the two suturing methods. In all cases, EHS were successfully completed. The median number of stitches and procedure time was 8 and 5.8 min, respectively. Stenosis was created in all continuous suturing cases whereas none was seen in nodule suturing cases. The shortening rate was significantly greater in the continuous suturing method than in the nodule suturing method. Intraluminal reinforcement of rectal anastomosis by EHS using nodule suturing with extra corporeal ligation is feasible without stenosis, which may be helpful as a countermeasure against possible postoperative anastomotic leakage in rectal surgery.

Abstract Recently, pathological changes in the fat pad on the anterior inferior iliac spine (AIIS), between the proximal rectus femoris and joint capsule, have been highlighted as a cause of anterior hip pain. However, precise fat pad features, such as the spatial distribution distal to the AIIS, histological features, and in vivo tissue elasticity, remain unclear. This study aimed to investigate the morphological characteristics of the fat pad on the AIIS. Four hips from four cadaveric donors were both macroscopically and histologically investigated, and eight hips from four volunteers were assessed using ultrasonography. The fat pad on the AIIS was also surrounded by the iliopsoas and gluteus minimus, extending distally to the superficial portion of the vastus lateralis, and the anterior portion of the gluteus maximus tendon. Histological analysis revealed that the fat pad was composed of loose connective tissue. Based on the ultrasonography, the shear wave velocity in the fat pad was significantly lower than that in the joint capsule. Conclusively, the pathological adhesion between the joint capsule and pericapsular muscles, if caused by fat pad fibrosis, may occur following the abovementioned fat pad spatial distribution.

Abstract Muscle atrophy occurs in a variety of physiological and pathological conditions. Specific molecular networks that govern protein synthesis and degradation play important roles in controlling muscle mass under diverse catabolic states. MicroRNAs (miRNAs) were previously found to be regulators of protein synthesis and degradation, and their expressions in skeletal muscle were altered in muscle wasting conditions. However, functional roles of miRNAs in muscle atrophy are poorly understood. In this study, we generated tamoxifen-inducible Dicer knockout (iDicer KO) mice and subjected them to 2 weeks of single hindlimb denervation. The expression of Dicer mRNA was significantly reduced in muscle of the iDicer KO mice compared to that of WT mice. The loss of Dicer moderately reduced levels of muscle-enriched miRNAs, miR-1, miR-133a and miR-206 in both innervated and denervated muscles of the iDicer KO mice. We also found that the extent of denervation-induced muscle atrophy as well as changes of signaling molecules related to protein synthesis/degradation pathways in the iDicer KO mice were comparable to these in WT mice. Taken together, Dicer knockout in adult skeletal muscle did not affect denervation-induced muscle atrophy.

Abstract Pathogenic mitochondrial NADH dehydrogenase (ND) gene mutations enhance the invasion and metastasis of various cancer cells, and they are associated with metastasis in human non-small cell lung cancer (NSCLC). Moreover, monocarboxylate transporter 4 (MCT4) is overexpressed in solid cancers and plays a role in cancer cell proliferation and survival. Here, we report that MCT4 is exclusively expressed in mouse transmitochondrial cybrids with metastasis-enhancing pathogenic ND6 mutations. A high level of MCT4 is also detected in human NSCLC cell lines and tissues predicted to carry pathogenic ND mutations and is associated with poor prognosis in NSCLC patients. MCT4 expression in the cell lines is suppressed by N-acetyl-L-cysteine. Phosphatidylinositol-3 kinase (PI3K), AMP-activated protein kinase (AMPK) and mechanistic target of rapamycin (mTOR) are involved in the regulation of MCT4 expression in the transmitochondrial cybrid cells. An MCT1/4 inhibitor effectively kills NSCLC cells with predicted pathogenic ND mutations, but an MCT1/2 inhibitor does not have the same effect. Thus, MCT4 expression is augmented by pathogenic ND mutations and could be a biomarker and a therapeutic target in pathogenic ND mutation-harbouring metastatic tumours.

Abstract The purpose of this study was to design a convenient, small-scale dissolution test for extracting potential substandard and falsified (SF) medicines that require full pharmacopoeial analysis. The probability of metronidazole samples complying with the US Pharmacopoeia (USP) dissolution test for immediate-release tablet formulations was predicted from small-scale dissolution test results using the following criteria: (1) 95% confidence interval lower limit (95% CIlow) of the average dissolution rate of any n = 3 of n = 24 units of each sample, and (2) average and minimum dissolution rates for any n = 3 of n = 24 units. Criteria values were optimized via bootstrap sampling with Thinkeye data-mining software. Compliant metronidazole samples in the USP first-stage and second-stage dissolution test showed complying probabilities of 99.7% and 81.0%, respectively, if the average dissolution rate of n = 3 units is equal to or greater than the monograph-specified amount of dissolved drug (Q; 85% of labeled content for metronidazole). The complying probabilities were 100.0% and 79.0%, respectively, if the average dissolution rate of n = 3 units is 91% or higher and the minimum dissolution rate is 87% or higher. Suitable compliance criteria for the small-scale dissolution test are: average dissolution rate of n = 3 units is Q + 6% or more and minimum dissolution rate is Q + 2% or more.

Abstract Cesarean section (C/S) is one way of delivering babies, and is chosen when mothers or babies are facing problems or life-threatening conditions during pregnancy. Many meta-analyses have suggested an etiological relationship between C/S delivery and autism spectrum disorders (ASDs). However, as a risk factor for ASDs, C/S delivery has not yet been well studied. Because C/S deliveries have been increasing, it is very important to investigate the causal association between C/S and ASDs. Here, using three approaches, we showed experimentally that C/S delivery induced ASD-like traits in offspring mice, and that some of these changes were ameliorated by one-time oxytocin (OXT) treatment. Treatment with OXT receptor antagonists before natural delivery also induced ASD-related behaviors. Moreover, wild-type mice born to OXT-KO dams showed similar changes. Thus, insufficient OXT exposure from dams to offspring during delivery may be a trigger for ASD-related behaviors.

Cyclic GMP-dependent protein kinases (PKGs) are key mediators of the nitric oxide/cyclic guanosine monophosphate (cGMP) signaling pathway that regulates biological functions as diverse as smooth muscle contraction, cardiac function, and axon guidance. Understanding how cGMP differentially triggers mammalian PKG isoforms could lead to new therapeutics that inhibit or activate PKGs, complementing drugs that target nitric oxide synthases and cyclic nucleotide phosphodiesterases in this signaling axis. Alternate splicing of PRKG1 transcripts confers distinct leucine zippers, linkers, and auto-inhibitory (AI) pseudo-substrate sequences to PKG Iα and Iβ that result in isoform-specific activation properties, but the mechanism of enzyme auto-inhibition and its alleviation by cGMP is not well understood. Here, we present a crystal structure of PKG Iβ in which the AI sequence and the cyclic nucleotide-binding (CNB) domains are bound to the catalytic domain, providing a snapshot of the auto-inhibited state. Specific contacts between the PKG Iβ AI sequence and the enzyme active site help explain isoform-specific activation constants and the effects of phosphorylation in the linker. We also present a crystal structure of a PKG I CNB domain with an activating mutation linked to Thoracic Aortic Aneurysms and Dissections. Similarity of this structure to wildtype cGMP-bound domains and differences with the auto-inhibited enzyme provide a mechanistic basis for constitutive activation. We show that PKG Iβ auto-inhibition is mediated by contacts within each monomer of the native full-length dimeric protein, and using the available structural and biochemical data we develop a model for the regulation and cooperative activation of PKGs.

Objective To elucidate the diagnostic accuracy of pretest probability of influenza (%) by physicians and the factors affecting the clinical diagnosis.Design Retrospective, single-centre observational study.Setting A community primary care clinic in Japan.Participants The participants were recruited from a database of studies conducted during the influenza season from December 2017 to April 2019.Primary outcome measure Sensitivity and specificity of the physician’s clinical diagnosis of influenza recorded in the medical record as pretest probability.Results A total of 335 patients (median age, 31 years; male, 66.6%) were analysed in this study. The area under the curve (AUC) of the physician’s pretest probability was 0.77. At a cut-off value of 30%, the sensitivity and negative likelihood ratio were 92.0% (95% CI 86.7 to 95.7) and 0.19 (95% CI 0.11 to 0.33), respectively. At a cut-off value of 80%, the specificity and positive likelihood ratio were 90.8% (95% CI 85.4 to 94.6) and 4.01 (95% CI 2.41 to 6.66), respectively. The AUCs of patients who had and had not taken any medications before visiting the clinic were 0.77 (95% CI 0.69 to 0.85) and 0.78 (95% CI 0.71 to 0.84), respectively. The AUCs of patients with type A and B influenza were 0.78 (95% CI 0.72 to 0.84) and 0.76 (95% CI 0.70 to 0.82), respectively. The AUCs of vaccinated and unvaccinated patients were 0.80 (95% CI 0.72 to 0.88) and 0.76 (95% CI 0.63 to 0.89), respectively. The AUC for patients less than 12 hours after onset was 0.69 (95% CI 0.51 to 0.88), and that for patients aged younger than 6 years was 0.69 (95% CI 0.49 to 0.88).Conclusions The physician’s pretest probability of influenza (%) may be useful for both definitive and exclusionary diagnoses within the limits of our study.

Abstract Shrimp is a causative food that elicits food-dependent exercise-induced anaphylaxis (FDEIA). In this study, we sought to identify IgE-binding allergens in patients with shrimp-FDEIA. Sera were obtained from eight patients with shrimp-FDEIA and two healthy control subjects. Proteins were extracted from four shrimp species by homogenization in Tris buffer. Immunoblot analysis revealed that IgE from patient sera bound strongly to a 70-kDa and a 43-kDa protein in a preparation of Tris-soluble extracts from Litopenaeus vannamei. Mass spectrometry identified the 70-kDa and 43-kDa proteins as a P75 homologue and fructose 1,6-bisphosphate aldolase (FBPA), respectively. To confirm that the putative shrimp allergens were specifically recognized by serum IgE from shrimp-FDEIA patients, the two proteins were purified by ammonium sulfate precipitation followed by reversed-phase HPLC and/or anion-exchange hydrophobic interaction chromatography and then subjected to immunoblot analysis. Purified P75 homologue and FBPA were positively bound by serum IgE from one and three, respectively, of the eight patients with shrimp-FDEIA, but not by sera from control subjects. Thus, P75 homologue and FBPA are identified as IgE-binding allergens for shrimp-FDEIA. These findings could be useful for the development of diagnostic tools and desensitization therapy for shrimp-FDEIA patients.

Abstract Background Poor quality medicines have serious implications for public health. The aim of this study was to explore the quality of the antidiabetic pioglitazone, using samples collected in China and Myanmar, and samples purchased online. Methods In this cross-sectional study, we examined samples (n = 163) collected from hospitals in Shanghai, China in 2012 (n = 44), products purchased via the internet and imported into Japan in 2013 (n = 59), and samples purchased in shops in Yangon, Myanmar in 2015 (n = 60). Collected samples were subjected to visual inspection, authenticity investigation and quality testing (potency, content uniformity and dissolution test) by high-performance liquid chromatography. Samples were rated as compliant or non-compliant based on the relevant pharmacopoeial acceptance criteria. Results Visual inspection of all samples revealed compliant products. However, responses from manufacturers during authenticity investigation were poor. Among the n = 44 samples from China, one was non-compliant in the potency test. Among the n = 59 samples personally imported into Japan, 38% of generic samples were found to be non-compliant. In Myanmar, 13.3% of samples were non-compliant. Non-compliant samples predominantly failed in the dissolution test. All non-compliant samples were generic. Conclusions Despite the apparent satisfactory outcome on the samples from China, pioglitazone samples collected in Myanmar and purchased online for personal import into Japan included many substandard products, which failed quality assessment predominantly because of poor dissolution. Internet providers did not comply with Japanese regulations in various respects.

Abstract Burkholderia glumae is a causal agent of bacterial grain and seedling rot in rice, and is a threat to stable global food supply. The virulence of B. glumae was suppressed when it was inoculated on budding seed rather than on non-budding seed. To clarify the phenomena, pathogen titer inside the rice plant was measured by serial dilution plating of lysates from budding rice seedlings. Surprisingly, morphologically different types of colonies were observed on the plates. These ‘contaminated’ rice seed-born bacteria (RSB) were identified by sequencing 16S rRNA genes as three strains of Pseudomonas putida (RSB1, RSB10, RSB15) and Stenotrophomonas maltophilia (RSB2). All bacteria and B. glumae were simultaneously inoculated onto rice seeds, and all three P. putida RSBs suppressed the growth disruption caused by B. glumae, whereas RSB2 had no effect. Thus, the virulence was synergistically suppressed when co-treated with RSBs. The effect could be dependent on the high biofilm formation ability of RSB2. By comprehensive microbiota analysis, endogenous rice flora were changed by RSBs treatment. These results suggest the possibility of novel pathogen control through pre-treatment with endogenous beneficial microorganisms. The method would contribute substantially to the implementation of sustainable agriculture stated in Sustainable Development Goals of United Nations.

Abstract The antidiabetic adiponectin receptor agonist AdipoRon has been shown to suppress the tumour growth of human pancreatic cancer cells. Because obesity and diabetes affect pancreatic cancer progression and chemoresistance, we investigated the effect of AdipoRon on orthotopic tumour growth of Panc02 pancreatic cancer cells in DIO (diet-induced obese) prediabetic mice. Administration of AdipoRon into DIO mice fed high-fat diets, in which prediabetic conditions were alleviated to some extent, did not reduce either body weight or tumour growth. However, when the DIO mice were fed low-fat diets, body weight and the blood leptin level gradually decreased, and importantly, AdipoRon became effective in suppressing tumour growth, which was accompanied by increases in necrotic areas and decreases in Ki67-positive cells and tumour microvessels. AdipoRon inhibited cell growth and induced necrotic cell death of Panc02 cells and suppressed angiogenesis of endothelial MSS31 cells. Insulin and IGF-1 only slightly reversed the AdipoRon-induced suppression of Panc02 cell survival but had no effect on the AdipoRon-induced suppression of MSS31 cell angiogenesis. Leptin significantly ameliorated AdipoRon-induced suppression of angiogenesis through inhibition of ERK1/2 activation. These results suggest that obesity-associated factors weaken the anticancer effect of AdipoRon, which indicates the importance of weight loss in combating pancreatic cancer.

Abstract The impact of birth weight (BW) on adult health has been studied, related to the autonomic nervous system, and implicated in cardiovascular risk. We investigated cardiorespiratory and heart rate (HR) autonomic recovery after moderate effort in healthy term-born adults with different BWs. We studied 28 healthy physically active women aged between 18 to 30 years split equally into two groups according to BW: G1 (n = 14), BW between 2500 g and 3200 g and G2 (n = 14), BW > 3200 g. The groups remained seated at rest for 15 min, followed by aerobic exercise on a treadmill (five minutes at 50–55% of maximum HR and 25 min 60–65% of maximum HR) and then remained seated for 60 min during recovery from the exercise. Cardiorespiratory parameters and HR variability (HRV) [RMSSD, HF (ms2)] were assessed before and during recovery from exercise. In G1, HR was increased from 0 to 20 min after exercise whilst in G2 HR was higher from 0 to 7 min following exercise. In G1, short-term HRV was increased from 5 to 10 min after exercise but in G2 it recovered prior to 5 min following effort. In conclusion, healthy term-born women with low normal BW present slower HR autonomic recovery after exercise.

Abstract Autosomal dominant hypoparathyroidism, deafness, and renal dysplasia (HDR) syndrome are typically diagnosed by manifestations of the three features with a positive family history. Our case carried a de novo variant in causative gene, GATA3, but presenting no renal dysplasia or family history. The phenotypic heterogeneity raises a caution for diagnosis.

Abstract The diagnosis of gastrointestinal stromal tumor (GIST) using conventional endoscopy is difficult because submucosal tumor (SMT) lesions like GIST are covered by a mucosal layer. Near-infrared hyperspectral imaging (NIR-HSI) can obtain optical information from deep inside tissues. However, far less progress has been made in the development of techniques for distinguishing deep lesions like GIST. This study aimed to investigate whether NIR-HSI is suitable for distinguishing deep SMT lesions. In this study, 12 gastric GIST lesions were surgically resected and imaged with an NIR hyperspectral camera from the aspect of the mucosal surface. Thus, the images were obtained ex-vivo. The site of the GIST was defined by a pathologist using the NIR image to prepare training data for normal and GIST regions. A machine learning algorithm, support vector machine, was then used to predict normal and GIST regions. Results were displayed using color-coded regions. Although 7 specimens had a mucosal layer (thickness 0.4–2.5 mm) covering the GIST lesion, NIR-HSI analysis by machine learning showed normal and GIST regions as color-coded areas. The specificity, sensitivity, and accuracy of the results were 73.0%, 91.3%, and 86.1%, respectively. The study suggests that NIR-HSI analysis may potentially help distinguish deep lesions.