Bintrafusp alfa and chemotherapy as first-line treatment in biliary tract cancer: A randomized phase 2/3 trial.

BACKGROUND AND AIMS: We compared the safety and efficacy of bintrafusp alfa (BA) in combination with gemcitabine+cisplatin (GemCis), to those of GemCis alone, in patients with biliary tract cancer (BTC). APPROACH AND RESULTS: This randomized, double-blind, placebo-controlled, adaptive design phase 2/3 trial (NCT04066491) included treatment-naïve adults with locally advanced/metastatic BTC. Patients (N=297) were randomized to receive an intravenous infusion of BA (2400 mg once/3 wk) plus GemCis (gemcitabine 1000 mg/m2+cisplatin 25 mg/m2 on days 1 and 8/3 wk; 8 cycles) (BA group, n=148) or placebo+GemCis (placebo group, n=149). The primary endpoint was overall survival (OS). For adaptation analysis (phase 2-phase 3; data cut-off: May 20, 2021), efficacy was assessed in the first 150 patients who were antibiotic-naïve, when 80 progression-free survival events had occurred and ≥19 weeks of follow-up had been completed (BA, n=73; placebo, n=77). Median OS (95% CI) for the BA (11.5 mo [9.3-not estimable, NE]) and placebo (11.5 mo [10.0-NE]) groups was comparable (hazard ratio 1.23 [95% CI 0.66-2.28]; p=0.7394); OS data maturity was 27.2% (41 events/151 patients). The most common grade ≥3 treatment-related adverse event was anemia (BA, 26.0%; placebo, 22.8%). Bleeding adverse events were reported more frequently in the BA group (28.8%) versus the placebo group (7.4%). Deaths within 60 days of the first dose were reported in 7.5% and 1.3% of patients in the BA and placebo groups, respectively. CONCLUSIONS: BA+GemCis did not provide a clinically meaningful benefit compared to GemCis alone as first-line treatment for BTC and the study was discontinued early (terminated: August 20, 2021).

Phase 2 trial of bintrafusp alfa as second-line therapy for patients with locally advanced/metastatic biliary tract cancers.

BACKGROUND AND AIMS: Biliary tract cancers are rare, heterogeneous cancers with poor prognoses. Bintrafusp alfa, a first-in-class bifunctional fusion protein composed of the extracellular domain of TGF-ßRII (a TGF-ß "trap") fused to a human IgG1 monoclonal antibody blocking programmed death ligand 1, was evaluated in patients with locally advanced/metastatic chemorefractory biliary tract cancers. APPROACH AND RESULTS: This multicenter, single-arm, open-label, phase 2 study (NCT03833661) enrolled adults with locally advanced or metastatic biliary tract cancer that was intolerant to or had failed first-line systemic platinum-based chemotherapy. Patients received 1200 mg bintrafusp alfa intravenously Q2W. The primary endpoint was confirmed objective response according to Response Evaluation Criteria in Solid Tumors 1.1 assessed by IRC. Secondary endpoints included duration of response, durable response rate, safety, progression-free survival, and overall survival.Between March 2019 and January 2020, 159 patients were enrolled. Median follow-up was 16.1 (range, 0.0-19.3) months; 17 patients (10.7%; 95% CI: 6.4%-16.6%) achieved an objective response. Median duration of response was 10.0 (range, 1.9-15.7) months; 10 patients (6.3%; 95% CI: 3.1%-11.3%) had a durable response (≥6 mo). Median progression-free survival was 1.8 months (95% CI: 1.7-1.8 mo); median overall survival was 7.6 months (95% CI: 5.8-9.7 mo). Overall survival rates were 57.9% (6 mo) and 38.8% (12 mo). Grade ≥3 adverse events occurred in 26.4% of patients, including one treatment-related death (hepatic failure). Frequent grade ≥3 adverse events included anemia (3.8%), pruritus (1.9%), and increased alanine aminotransferase (1.9%). CONCLUSIONS: Although this study did not meet its prespecified primary endpoint, bintrafusp alfa demonstrated clinical activity as second-line treatment in this hard-to-treat cancer, with durable responses and a manageable safety profile.

Socioeconomic status and incident depressive symptoms among older adults: A 3-year longitudinal study from the Japan Gerontological Evaluation Study.

OBJECTIVES: The association between socioeconomic status (SES) and the onset of depressive symptoms has attracted considerable attention. However, few studies have simultaneously examined the association of multiple SES indicators, including "assets," with the onset of depressive symptoms. Therefore, this study examined the association of four SES indicators in old age ('years of education' 'equivalent income,' 'equivalent assets,' and 'the longest-held job') with new-onset depressive symptoms in a large Japanese dataset. METHODS: This longitudinal study used panel data of cognitively and physically independent older adults from the Japan Gerontological Evaluation Study (JAGES) conducted in 2013 and 2016. Multivariate logistic regression analysis was conducted to examine the association of each SES indicator with new-onset depressive symptoms, and odds ratios and 95% confidence intervals (CIs) were calculated. RESULTS: We analyzed the data of 40,257 older adults, with a mean age (± standard deviation) of 72.9 (±5.5) years. In the follow-up survey, 4292 older adults had new-onset depression symptoms (10.7%). 39.3% had 10-12 years of education. 36.9% had an equivalent income of up to JPY 1.99 million. 24.4% had equivalent assets of JPY 4-17.99 million. Most had a clerical job for the long time. Furthermore, fewer years of education (males: OR = 1.42, 95% CI = 1.22-1.64, p-value <0.001/females: 1.26, [1.09-1.47], p = 0.002), lower income (males: 1.64, [1.34-2.01], p < 0.001/females: 1.82, [1.49-2.22], p < 0.001), and fewer assets (males: 1.40, [1.16-1.68], p < 0.001/females: 1.21, [1.02-1.42], p = 0.025) resulted in higher odds of having new-onset depressive symptoms, even when other SES indicators were entered simultaneously. CONCLUSIONS: All four SES indicators have an independent association with the development of new-onset depressive symptoms among older adults, reflecting different aspects of SES. The association between the "longest-held job" and new-onset depressive symptoms can be largely explained by other SES indicators. A multifaceted and lifetime approach is required to prevent the onset of depressive symptoms in old age.

Does vacuum phenomenon at non-fused discs affect the postoperative course after transforaminal lumbar interbody fusion in patients showing a positive value of difference in lumbar lordosis?

INTRODUCTION: Preoperative difference in lumbar lordosis (DiLL) was associated with surgical outcomes after single-level transforaminal lumbar interbody fusion (TLIF). Patients with DiLL>0 (DiLL (+)) tended to show worse clinical outcomes and postoperative greater restoration of lumbar lordosis (LL). However, some patients with DiLL (+) showed relatively good outcomes and no postoperative LL restration. This study aimed to elucidate whether the lumbar intervertebral disc vacuum phenomenon (VP) influences clinical course after single-level TLIF in patients with DiLL (+) and DiLL (-). METHODS: Patients with lumbar spinal stenosis and degenerative spondylolisthesis treated with single-level TLIF were included. Pre- and postoperative LL were measured, and postoperative LL improvement was calculated. Preoperative DiLL was calculated as preoperative supine LL minus standing LL. Severity of VP at the non-fused discs (SVP (non-FS)) was evaluated using preoperative reconstructed computed tomography imaging. Clinical outcomes were assessed using the Oswestry disability index, visual analogue scale (VAS; low back pain (LBP), lower-extremity pain, numbness, and the Japanese Orthopaedic Association Back Pain Evaluation Questionnaire. Patients were stratified by the median preoperative SVP (non-FS) score into severe and mild VP groups in patients with DiLL (+) or DiLL (-), and their surgical outcomes were compared. RESULTS: Overall, 89 patients were included. In patients with DiLL (+) (n = 37), patients with severe VP showed worse clinical outcomes, particulary for LBP and DiLL (+) patients with mild VP showed greater LL improvement (6.5° ± 10.0°). In patients with DiLL(-) (n = 52), patients with severe VP showed worse clinical outcomes, particularly for LBP and no differences in preoperative, postoperative, and improvement of LL were observed between two groups. CONCLUSION: Patients with DiLL (+) and DiLL (-) showed different clinical courses depending on VP severity at the non-fused discs after single-level TLIF.

Quantitative evaluation of the lumbar ligamentum flavum using MRI T2-mapping: Efficacy of its clinical application in patients with lumbar spinal stenosis.

OBEJECTIVE: To perform a magnetic resonance imaging T2-mapping of the ligamentum flavum in healthy individuals and patients with lumbar spinal stenosis scheduled for surgery and compare the T2 relaxation times. SUBJECTS AND METHODS: The T2 relaxation time of the ligamentum flavum was compared among 3 groups, healthy young individuals (H group (age< 50)), healthy middle-aged and older individuals (H group (age≥50)), and patients with lumbar spinal stenosis (L group). Additionally, the thickness of the ligament was measured in the axial image plane, and the occupied area ratio of each fiber was measured by staining the surgically obtained ligament, and each was correlated with the T2 relaxation time. We also evaluated the adhesion of the ligamentum flavum with the dura mater during the surgery. RESULTS: The T2 relaxation times were significantly prolonged in H group (age ≥50) and L group (P < 0.001) compared to H group (age<50). The relationship between collagen fiber and T2 relaxation times was significantly positive (r = 0.720, P < 0.001). Moreover, the relaxation times were significantly prolonged in those with adhesion of the ligamentum flavum with the dura mater (P < 0.05). The cut-off for the relaxation time was 50 ms (sensitivity: 62.50%, false positive rate: 10.8%). CONCLUSION: Healthy middle-aged and older individuals and patients with lumbar spinal stenosis and adhesion of the ligamentum flavum with the dura mater have prolonged T2 relaxation times. Hence, the adhesion between the ligamentum flavum and dura mater should be considered in cases with a relaxation time ≥50 ms.

Fibrocyte Phenotype of ENTPD1+CD55+ Cells and Its Association with Pain in Osteoarthritic Synovium.

Osteoarthritis (OA) is a prevalent degenerative joint disorder characterized by cartilage erosion, structural changes, and inflammation. Synovial fibroblasts play a crucial role in OA pathophysiology, with abnormal fibroblastic cells contributing significantly to joint pathology. Fibrocytes, expressing markers of both hematopoietic and stromal cells, are implicated in inflammation and fibrosis, yet their marker and role in OA remain unclear. ENTPD1, an ectonucleotidase involved in purinergic signaling and expressed in specific fibroblasts in fibrotic conditions, led us to speculate that ENTPD1 plays a role in OA pathology by being expressed in fibrocytes. This study aimed to investigate the phenotype of ENTPD1+CD55+ and ENTPD1-CD55+ synovial fibroblasts in OA patients. Proteomic analysis revealed a distinct molecular profile in ENTPD1+CD55+ cells, including the upregulation of fibrocyte markers and extracellular matrix-related proteins. Pathway analysis suggested shared mechanisms between OA and rheumatoid arthritis. Correlation analysis revealed an association between ENTPD1+CD55+ fibrocytes and resting pain in OA. These findings highlight the potential involvement of ENTPD1 in OA pain and suggest avenues for targeted therapeutic strategies. Further research is needed to elucidate the underlying molecular mechanisms and validate potential therapeutic targets.

IL24 Expression in Synovial Myofibroblasts: Implications for Female Osteoarthritis Pain through Propensity Score Matching Analysis.

(1) Introduction: Despite documented clinical and pain discrepancies between male and female osteoarthritis (OA) patients, the underlying mechanisms remain unclear. Synovial myofibroblasts, implicated in synovial fibrosis and OA-related pain, offer a potential explanation for these sex differences. Additionally, interleukin-24 (IL24), known for its role in autoimmune disorders and potential myofibroblast production, adds complexity to understanding sex-specific variations in OA. We investigate its role in OA and its contribution to observed sex differences. (2) Methods: To assess gender-specific variations, we analyzed myofibroblast marker expression and IL24 levels in synovial tissue samples from propensity-matched male and female OA patients (each n = 34). Gene expression was quantified using quantitative polymerase chain reaction (qPCR). The association between IL24 expression levels and pain severity, measured by a visual analog scale (VAS), was examined to understand the link between IL24 and OA pain. Synovial fibroblast subsets, including CD45-CD31-CD39- (fibroblast) and CD45-CD31-CD39+ (myofibroblast), were magnetically isolated from female patients (n = 5), and IL24 expression was compared between these subsets. (3) Results: Females exhibited significantly higher expression of myofibroblast markers (MYH11, ET1, ENTPD2) and IL24 compared to males. IL24 expression positively correlated with pain severity in females, while no correlation was observed in males. Further exploration revealed that the myofibroblast fraction highly expressed IL24 compared to the fibroblast fraction in both male and female samples. There was no difference in the myofibroblast fraction between males and females. (4) Conclusions: Our study highlights the gender-specific role of myofibroblasts and IL24 in OA pathogenesis. Elevated IL24 levels in females, correlating with pain severity, suggest its involvement in OA pain experiences. The potential therapeutic implications of IL24, demonstrated in autoimmune disorders, open avenues for targeted interventions. Notwithstanding the limitations of the study, our findings contribute to understanding OA's multifaceted nature and advocate for future research exploring mechanistic underpinnings and clinical applications of IL24 in synovial myofibroblasts. Additionally, future research directions should focus on elucidating the precise mechanisms by which IL24 contributes to OA pathology and exploring its potential as a therapeutic target for personalized medicine approaches.

(E)-7-phenyl-2-heptene-4,6-diyn-1-ol from Bidens pilosa as a repellent against isopods.

The development of repellents as alternatives to insecticides has expanded in recent years. However, their use in isopod pest control is limited. To develop an isopod repellent, a plant extract library from wild plants native to the Kochi Prefecture was screened for repellent activity against pillbugs, and 82 samples (87%) exhibited repellent activity. Among them, (E)-7-phenyl-2-heptene-4,6-diyn-1-ol was isolated and identified as a repellent from the root of Bidens pilosa. It had a half-maximal effective concentration of 0.20 µm, with a strong repellency. A study of the structure-activity relationship to (E)-7-phenyl-2-heptene-4,6-diyn-1-ol revealed that the presence of a hydroxyl group and an aromatic at both ends of the length of the seven-carbon chain is important for the expression of repellency. These results can potentially lead to a new repellent of phenylalkyl alcohol.

Postoperative change in lumbopelvic alignment after short-segment transforaminal lumbar interbody fusion is related to preoperative postural difference in lumbar lordosis.

BACKGROUND: Postoperative changes in lumbar lordosis (LL) after transforaminal lumbar interbody fusion (TLIF) and the related factors are not well-understood. Recently, the preoperative difference in LL between standing and supine positions (DiLL) was proposed as a factor for predicting postoperative radiologic outcomes after short-segment TLIF. This study investigated the influence of DiLL on mid-term radiological outcomes after short-segment TLIF. METHODS: Sixty-six patients with lumbar degenerative disease treated with short-segment TLIF (1-2 levels) who underwent lumbar spine standing radiographs at 3 months, 6 months, 1 year, 2 years, 3 years, 4 years, and 5 years postoperatively were divided into DiLL (+) and DiLL (-) groups (preoperative DiLL ≥0° and <0°, respectively). Associations between the postoperative change in LL and DiLL and clinical outcomes (Oswestry disability index (ODI) and Nakai score) were evaluated. RESULTS: Temporary restoration of LL (+4.5°) until 1 year postoperatively and a subsequent decrease in LL from 1 to 5 years postoperatively (-5.3°) was observed in the DiLL (+) group. No postoperative change in LL was observed in the DiLL (-) group. Postoperative changes in LL were mainly observed in non-fused segments. The postoperative change in LL (ΔLL) until 1 year postoperatively had a significant positive association with DiLL (p = 0.00028), whereas ΔLL from 1 to 5 years postoperatively showed a significant negative association with DiLL (p = 0.010) and a positive association with Nakai score (p = 0.028). ΔLL until 5 years postoperatively showed a significant positive association with postoperative ODI improvement (p = 0.011). CONCLUSIONS: DiLL (+) patients showed a specific time course with temporary LL restoration until 1 year postoperatively and a subsequent decrease in LL from 1 to 5 years postoperatively. Patients with larger postoperative increase in LL until 5 years postoperatively and lesser decrease in LL from 1 to 5 years postoperatively tended to show better mid-term clinical outcomes.

Discovery of IL-5-binding unnatural cyclic peptides from multiple libraries by directed evolution.

Interleukin-5 (IL-5) is a type 2 cytokine involved in various allergic diseases, including severe eosinophilic asthma. In this study, we performed directed evolution against human IL-5 using systematic evolution of ligands by exponential enrichment (SELEX) from multiple mRNA-displayed peptide libraries. Peptide libraries were prepared with Escherichia coli-based reconstituted cell-free transcription and translation coupling system (PURE system) and spontaneously cyclized using multiple intramolecularly thiol-reactive benzoic acid-derived linkers, which were ribosomally incorporated through genetic code expansion. We successfully identified multiple novel IL-5-binding unnatural cyclic peptides with different cyclization linkers from multiple highly diverse mRNA-displayed libraries. Chemical dimerization was also performed to increase the avidity of unnatural cyclic IL-5-binding peptides. The novel IL-5-binding unnatural cyclic peptides discovered in this study could be used in various research, therapeutic, and diagnostic applications involving IL-5 signaling.

Artificial aptamer that inhibits interleukin-23/interleukin-23 receptor interaction discovered via SELEX.

Interaction between the pro-inflammatory cytokine interleukin-23 (IL-23) and IL-23 receptor (IL-23R) is related to the development of inflammatory autoimmune diseases such as psoriasis, inflammatory bowel disease, and Crohn's disease. In this study, we conducted systematic evolution of ligands by exponential enrichment (SELEX) for in vitro selection against human IL-23 and observed RNA sequence enrichment in the final SELEX round. IL-23-pull-down assay by chemiluminescence detection and fluorescence imaging demonstrated that SELEX-enriched RNA clone bound to IL-23. Quantitative polymerase chain reaction-based pull-down assay using the IL-23 alpha (IL-23A) subunit, a component of the IL-23 heterodimer, indicated that the RNA clone bound to IL-23A, which is favorable for autoimmune disease treatment. We also observed that the novel IL-23-binding RNA aptamer inhibited interaction between IL-23 and IL-23R. Thus, the novel IL-23-binding RNA aptamer can be used for IL-23 studies and has potential to be used for IL-23 diagnosis and IL-23-related inflammatory autoimmune disease treatment.

12-O-Tetradecanoylphorbol 13-acetate promotes proliferation and epithelial-mesenchymal transition in HHUA cells cultured on collagen type I gel: A feasible model to find new therapies for endometrial diseases.

HHUA endometrial adenocarcinoma cells aggregated into spheroids when cultured on collagen type I gels. 12-O-Tetradecanoylphorbol 13-acetate, a PKC activator, disassembled the spheroids through epithelial-mesenchymal transition and increased their proliferation rate, while inducing cell death under monolayer culture conditions. These unusual behaviors of endometrial epithelial cells with collagen fibers could be a target for the treatment of some endometrial diseases.

Assessment of locomotive syndrome in patients with visceral cancer, the comparison with non-cancer patients using propensity score matching.

BACKGROUND: When treating cancer patients, the progression of symptoms is accompanied by the deterioration of systemic conditions and motor function. From a risk-benefit perspective, a certain level of physical function must be maintained to continue cancer treatment. Recently, outpatient cancer treatment has become more common. Motor function is important to determine the feasibility of continuing cancer treatment. The study aimed to evaluate the motor function of patients with visceral cancer using locomo tests established by Japanese Orthopaedic Association. METHODS: Locomo tests were performed, and the results were compared with data from non-cancer individuals. Background data were matched by propensity score matching. Data from 53 cancer patients (group C) were compared with that of 75 non-cancer patients (group N). RESULTS: The average score in the two-step test of group C was lower than that of group N (1.27: 1.37, p = 0.004). The average function in the stand-up test of group C was worse than that of group N (p = 0.001). The average score in the 25-question geriatric locomotive function scale (GLFS) of group C was significantly higher than that of group N (19.92: 5.29, SE 2.21, p < 0.001). Higher 25-question GLFS scores indicate reduced mobility. The proportion of the locomo stage 2 in group C was significantly higher than in group N (51%: 13%, p < 0.001). The results of the two field tests revealed a clinically minimal difference between the two groups, but a statistically significant difference. Locomo tests may be detect potential motor dysfunction in outpatient cancer patients with apparently maintained motor function. CONCLUSIONS: Even in cancer patients who attend outpatient clinics, their motor functions could be potentially impaired. Therapeutic interventions to maintain and enhance motor function for cancer patients could be useful for continuing cancer treatment, and furthermore, improving prognosis.

Selective association of desmin intermediate filaments with a phospholipid layer in droplets.

Desmin, an intermediate filament protein expressed in muscle cells, plays a key role in the integrity and regulation of the contractile system. Furthermore, the distribution of desmin in cells and its interplay with plasma and organelle membranes are crucial for cell functions; however, the fundamental properties of lipid-desmin interactions remain unknown. Using a water-in-oil method for a limited space system in vitro, we examined the distribution of desmin in three types of phospholipid droplets: 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE), and 1,2-dioleoyl-sn-glycero-3-phosphoserine (DOPS). When fluorescent-labeled desmin was observed for 60 min after desmin assembly was initiated by adding 25 mM KCl, desmin accumulated on both the DOPE and DOPS layers; however, it did not accumulate on the DOPC layer of droplets. An increase in salt concentration did not moderate the accumulation. The initial form of either oligomer or mature filament affected the accumulation on each lipid layer. When liposomes were included in the droplets, desmin was associated with DOPE but not on DOPC liposomes. These results suggest that desmin has the potential for association with phospholipids concerning desmin form and lipid shape. The behavior and composition of living membranes may affect the distribution of desmin networks.

Verbascoside from Verbena incompta is a plant root growth inhibitor.

The use of biopesticides has expanded rapidly in recent years; however, their use in weed control is less advanced. Herein, we describe the development of a weed control agent by screening 208 plant extracts (104 species) for their plant growth-inhibition activities, which resulted in 142 active samples (from 89 plant species). Verbascoside, isolated from the shoots of Verbena incompta, was identified as a growth inhibitor against rice root (EC50, 1.75 m m), and its root growth-inhibition activity was also confirmed in radish, tomato, and Lotus japonicus. Verbascoside is composed of hydroxytyrosol (EC50,12.51 m m) and caffeic acid (EC50, 4.08 m m), 2 poorly water-soluble phenolic components with weak growth-inhibition activities, and 2 sugars, which are more soluble but inactive. The plant apparently developed a more active and highly soluble compound by condensing these 4 components. We conclude that a biopesticide containing verbascoside may be useful for weed-control purposes.

Crescentic IgA nephropathy in children.

OBJECTIVES: Crescentic IgA nephropathy (C-IgAN) is defined as IgAN with more than 50% of glomeruli showing crescents. C-IgAN in children is rare; we investigate in detail for the first time. METHODS: We retrospectively analyzed the 515 consecutive children who were newly diagnosed with biopsy-proven IgAN between June 1976 and May 2010. We compared clinical and pathological findings between C-IgAN and non-C-IgAN. RESULTS: Among 515 cases of childhood IgAN, 25 children (4.9%) had C-IgAN. Of these 25, 16 children (64%) were referred to hospitals by annual school screening. Clinical findings showed significant differences in gross hematuria (76 vs. 50%, p = .03), excretion of proteinuria (1.9 vs. 0.5 g/day/m2, p < .0001), eGFR (102 vs. 108 ml/min/1.73 m2, p = .03), and duration from onset to renal biopsy (4.0 vs. 8.0 months, p = .04) between groups. Pathological findings showed significant differences in M1 (88 vs. 55%, p = .02), E1 (83 vs. 53%, p = .008), and presence of tubular atrophy/interstitial fibrosis (88 vs. 53%, p < .0001) between groups. The 16 children with C-IgAN were treated with prednisolone and immunosuppressant. Four cases (16%) reached chronic renal failure (eGFR < 60) at the latest observation (mean observation period: 6.0 ± 3.6 years). Patients with C-IgAN had significantly lower renal survival curve than non-C-IgAN patients according to Kaplan-Meier analysis (77.1% vs. 92.6% at 13 years, p < .0001). Compared with previous reports, however, they had better renal outcome. CONCLUSIONS: We confirmed the importance of school screening to find C-IgAN. Although most crescents (mean: 98.1%) of C-IgAN were cellular/fibrocellular, and acute lesions were well modified with combination therapy, the presence of tubular atrophy in C-IgAN may be the reason for poorer prognosis.

Induction of 2-cyanoethyl-isoxazolin-5-one as an antifeedant against the tobacco cutworm (Spodoptera litura) by jasmonic acid in sweet pea leaf.

Although sweet pea (Lathyrus odoratus) beans contain toxic ß-aminopropionitrile, the plant itself is readily attacked by insects and is, therefore, protected through the use of pesticides. Consequently, the induction of L. odoratus resistance to insect attack via exogenous treatment is promising for pest control development. Screening of inducible elicitor effects showed that treatment of sweet pea foliage with jasmonic acid (JA) can induce antifeeding-based resistance to tobacco cutworm (Spodoptera litura) larvae. Spectroscopic analysis identified 2-cyanoethyl-isoxazolin-5-one (2-CEIX) as the antifeedant with a half-maximal effective concentration of 33.6 µmol/g fr. wt., i.e., exogenous JA treatment induced antifeeding activity due to the accumulation of 2-CEIX. Moreover, 2-CEIX-induced mortality of S. litura larvae was evaluated by a dipping test and the half-maximal lethal dose was determined to be 5.9 mg/mL. Therefore, 2-CEIX was concluded to be a suitable induced resistance target for elicitors or a lead compound for insecticide development.

Does the increased motion probing gradient directional diffusion tensor imaging of lumbar nerves using multi-band SENSE improve the visualization and accuracy of FA values?

PURPOSE: Diffusion tensor imaging (DTI) is useful to evaluate lumbar nerves visually and quantitatively. Multi-band sensitivity encoding (MB-SENSE) is a technique to reduce the scan time. This study aimed to investigate if super-multi-gradient DTI with multi-band sensitivity encoding (MB-SENSE) is better in evaluating lumbar nerves than the conventional method. METHODS: The participants were 12 healthy volunteers (mean age 33.6 years). In all subjects, DTI was performed using echo planar imaging with different motion probing gradient (MPG) directions (15 without MB, and 15, 32, 64, and 128 with MB) and the lumbar nerve roots were visualized with tractography. In the five groups, we evaluated the resultant DTI both visually and quantitatively. For visual measures, we counted the number of fluffs and disruptions of the nerve fibers. For quantitative measures, the fractional anisotropy (FA) and standard deviation of the fractional anisotropy (FA-SD) values at two regions (proximal and distal) of the lumbar nerve roots were quantified and compared. RESULTS: Among the five groups, the number of fluffs decreased as the number of MPG directions increased. However, the number of disruptions showed no significant differences. The FA-SD values decreased as the number of MPG directions increased, indicating that the signal variation was reduced with multi-gradient directional DTI. CONCLUSION: High-resolution multi-directional DTI with MB-SENSE may be useful to visualize nerve entrapments and may allow for more accurate DTI parameter quantification with opportunities for clinical diagnostic applications.

Objective evaluation of postoperative changes in real-life activity levels in the postoperative course of lumbar spinal surgery using wearable trackers.

BACKGROUND: Lumbar spinal disease causes disabilities in performing daily activities. Operative treatments are aimed at pain relief and rapid return to routine activity. Patient-based outcome measures are used to evaluate pathologies and therapeutic effects associated with lumbar spinal disease. Nevertheless, it remains unknown as to how much such treatment improves activity levels. The purpose of the current study was to measure changes in activity levels before and after lumbar spinal surgery using a wearable activity tracker and to analyze the differences between results and patient-based outcomes. METHODS: Sixty patients who underwent lumbar surgery were studied. The physical activity of participants was objectively evaluated using a wearable Micro-Motion logger system (Actigraph). We measured the amount of activity before and at 1, 3, 6, and 12 months after the surgery to evaluate postoperative changes. The Japanese Orthopaedic Association Back Pain Evaluation Questionnaire, Oswestry Disability Index, Roland-Morris Disability Questionnaire and visual analog scale were used to assess patient-based outcomes of pain and activities of daily living-related scores; we analyzed the relationships between scores and actual activity levels. RESULTS: The amount of actual activity decreased significantly 1 month after the surgery compared to that during the preoperative period, which then improved after 3 months postoperatively (p < 0.01). Furthermore, there was a significant improvement 6 months after the surgery compared to that during the preoperative period (p < 0.05). The changes in activity for each period were strongly correlated, regardless of the period. In contrast, a significant improvement was observed at 1 month after the surgery in almost all items of the patient-based questionnaires (p < 0.05). CONCLUSIONS: The objective activity tracker demonstrated that lumbar surgery results in the amount of activity decreasing 1 month just after surgery followed by gradual postoperative recovery within 3 months. By contrast, patient-based outcomes showed improvement in 1 month that was significantly different from the change in actual activity, indicating a gap between patient-oriented clinical scores and their actual activities.

Growth inhibition by 1-deoxy-d-allulose, a novel bioactive deoxy sugar, screened using Caenorhabditis elegans assay.

The biological activities of deoxy sugars (deoxy monosaccharides) have remained largely unstudied until recently. We compared the growth inhibition by all 1-deoxyketohexoses using the animal model Caenorhabditis elegans. Among the eight stereoisomers, 1-deoxy-d-allulose (1d-d-Alu) showed particularly strong growth inhibition. The 50% inhibition of growth (GI50) concentration by 1d-d-Alu was estimated to be 5.4 mM, which is approximately 10 times lower than that of d-allulose (52.7 mM), and even lower than that of the potent glycolytic inhibitor, 2-deoxy-d-glucose (19.5 mM), implying that 1d-d-Alu has a strong growth inhibition. In contrast, 5-deoxy- and 6-deoxy-d-allulose showed no growth inhibition of C. elegans. The inhibition by 1d-d-Alu was alleviated by the addition of d-ribose or d-fructose. Our findings suggest that 1d-d-Alu-mediated growth inhibition could be induced by the imbalance in d-ribose metabolism. To our knowledge, this is the first report of biological activity of 1d-d-Alu which may be considered as an antimetabolite drug candidate.