Enzymatic transformation of esculetin as a potent class of α-glucosidase inhibitors.

A rapid and simple enzymatic transformation of the representative coumarin esculetin (1) with polyphenol oxidase originating from Agaricus bisporus afforded five new oxidized metabolites, esculetinins A (2), B (3), C (4), D (5), and E (6), together with the known compound isoeuphorbetin (7). The structures of the oligomerized transformation products were established on the basis of spectroscopic interpretations. The esculetin oligomers 2 and 3 revealed highly enhanced inhibitory activities against α-glucosidase, with IC50 values of 0.7 ± 0.1 and 2.3 ± 0.3 µM, respectively, as compared to the original esculetin. Kinetic analysis also exhibited that the two new potent metabolites 2 and 3 have competitive modes of action.

Association between new-onset Parkinson's disease and suicide risk in South Korea: a nationwide cohort study.

BACKGROUND: Parkinson's disease (PD) is an increasingly common neurodegenerative disease in an aging society. Whether PD is associated with an increased suicide risk is unclear. Thus, we investigated the effect of new-onset PD on suicide. METHODS: Using the National Health Insurance Service Senior Sample Cohort of South Korea, 17,143 incident PD patients and 17,143 risk set controls, matched by propensity score, were selected for follow-up. The incidence rate of suicide and 95% confidence interval (CI) were calculated based on a generalized linear model of the Poisson distribution. Effect sizes were expressed as hazard ratios (HRs) using the Cox proportional hazards model with a robust variance estimator that incorporated clustering within matched pairs. RESULTS: The incidence rate of suicide was 206.7 cases per 100,000 person-years (95% CI, 172.8-246.9) among the PD cohort. Compared to the matched controls, patients with PD were 2.64 times (HR, 2.64; 95% CI, 1.31-5.30) more likely to commit suicide during the first 180 days of follow-up and 2.47 times (HR, 2.47; 95% CI, 1.42-4.28) within the first 365 days of follow-up. During the entire follow-up period, patients with PD were 2.26 times more likely to commit suicide than were their matched controls (HR, 2.26; 95% CI, 1.67-3.06). CONCLUSION: Our findings indicated an increased risk of suicide in patients with new-onset PD, regardless of the period after diagnosis. Incorporating mental health care with social and environmental interventions into primary care and PD-specialized care can help reduce suicide risk in people with PD, improving suicide prevention, identification, and risk assessment.

Astigmatism-corrected endoscopic imaging probe for optical coherence tomography using soft lithography.

In endoscopic optical coherence tomography, a transparent protective sheath is used to protect the optics and tissue. However, the sheath causes astigmatism, which degrades transverse resolution and signal-to-noise ratio due to the cylindrical lens effect. Generally used methods for correcting this astigmatism are complex, difficult to control precisely, high-cost, and increase the dimensions of the imaging probe. To overcome these problems, we have developed an astigmatism-corrected imaging probe with an epoxy window. The astigmatism is precisely and cost-effectively adjusted controlling the curvature radius of the epoxy window, which is produced by soft lithography. Using the fiber optic fusion splicing, the fabrication process is simple. The fabricated imaging probe is almost monolithic, so its diameter is similar to that of a standard single-mode fiber. We demonstrate its astigmatism-correcting performance using focal spot analysis, imaging micro-beads and a biological sample.

The natural course of and risk factors for tear progression in conservatively treated full-thickness rotator cuff tears.

BACKGROUND: The natural course of and risk factors for tear progression in full-thickness rotator cuff tears (FTRCTs) have not been clarified yet. The study's purpose was to retrospectively evaluate tear progression in FTRCTs by using magnetic resonance imaging (MRI) and to identify risk factors that are relevant to such tear progression. METHODS: Between June 2010 and September 2019, a total of 345 patients with FTRCTs who had been diagnosed via MRI were treated conservatively. Of these, 48 patients who underwent post-treatment follow-up MRI were retrospectively enrolled. Tear progression was defined as significant when the tear size increased by >5 mm. RESULTS: The mean MRI follow-up duration was 22 ± 14 months (range, 12-65 months). Among the 48 patients (mean age, 69 years; range, 53-81), 26 (54%) and 20 (41%) showed medial-lateral (M-L) and anterior-posterior (A-P) tear progression on MRI follow-up. Multivariate analysis revealed that MRI follow-up duration (P = .011), diabetes mellitus (P = .017), and infraspinatus muscle atrophy (P = .011) were independent risk factors for tear progression in the A-P plane. A high critical shoulder angle (P = .011) and supraspinatus (P = .024) and infraspinatus (P = .020) muscle atrophy were risk factors associated with M-L tear progression. CONCLUSION: Among the assessed patients, a considerable number of FTRCTs increased in size during the follow-up period. Severe infraspinatus muscle atrophy was the independent risk factor for exacerbation of A-P and M-L tear progression.

Decrease of serum total ghrelin in extensive atrophic gastritis: comparison with pepsinogens in histological reference.

OBJECTIVE: Ghrelin is mainly secreted by the gastric oxyntic mucosa and its production is impaired in chronic atrophic gastritis. This study aimed at evaluating how serum total ghrelin correlates with the extent of atrophy, and to compare its performance as a serologic marker with that of pepsinogen (PG). MATERIAL AND METHODS: Data were collected from 154 patients with atrophic gastritis. The histological extent of atrophy was assessed by three paired biopsies from the antrum, corpus lesser curvature (CLC), and corpus greater curvature (CGC). Fasting serum concentrations of total ghrelin, pepsinogen I and II were measured. Regression analysis was performed to evaluate the factors associated with serum total ghrelin. The serologic performance was compared with that of pepsinogen using receiver-operating characteristic (ROC) curves. RESULTS: The Helicobacter pylori infection rate was 85%, and extensive atrophic gastritis involving CGC was found in 24%. Serum total ghrelin was significantly decreased in patients with extensive CGC atrophy (median: 170.4 pg/mL, vs 201.1 pg/mL in patients without atrophy; p < 0.001), and its levels correlated with those of pepsinogen I and I/II ratio. The decrease of serum total ghrelin was independent of age, gender, body mass index (BMI), and H. pylori infection status. The sensitivity and specificity of serum total ghrelin in predicting extensive atrophy were 57% and 79%, respectively. The discriminatory ability was similar to that of pepsinogen I/II ratio (p = 0.612), and lower than that of pepsinogen I (p = 0.040). CONCLUSIONS: Serum total ghrelin is decreased during extensive atrophy involving CGC. The serologic performance is lower than that of pepsinogen I.

High Left Ventricular Filling Pressure on Doppler Echocardiography Is Associated With Graft Failure and Overall Mortality Following Kidney Transplantation.

OBJECTIVE: Although E/e´ is prognostic of mortality in patients with end-stage renal disease (ESED), little is known about the prognostic implications of E/e´ following kidney transplant (KT). The objective of this study was to evaluate whether an elevated E/e´ is associated with graft function, postoperative hemodialysis, and overall mortality in end-stage renal disease patients following KT. DESIGN: A retrospective observational study. SETTING: Tertiary teaching hospital. PARTICIPANTS: In total, 1,045 patients underwent KT at the authors' hospital between January 2006 and December 2013. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Patients were divided into groups with an E/e´<15 or≥15, as assessed by preoperative echocardiography (median time from preoperative assessment of echocardiography to surgery: 37 days [IQR: 16-68 days]). Of 1,045 patients, 821 patients (78.6%) had an E/e´<15, and 224 patients (21.4%) had an E/e´≥15. Multivariate analysis indicated that age (odds ratio [OR]: 1.03; 95% confidence interval [CI]: 1.01-1.04, p = 0.001), diabetes mellitus (OR: 2.7; CI: 1.94-3.83, p<0.001), ß-blocker (OR: 1.4; CI: 1.03-1.95, p = 0.034), left atrial dimension (OR: 1.07; CI: 1.04-1.11, p<0.001), and left ventricular mass index (OR: 1.02; CI: 1.01-1.03, p<0.001) are predictive of E/e´≥15. After adjustment using inverse probability of treatment weighting, E/e´≥15 also was associated independently with postoperative hemodialysis (OR: 2.0; 95% CI: 1.5-2.6, p<0.001), graft failure (OR: 1.7; 95% CI: 1.4-2.2; p<0.001), and overall mortality (hazard ratio [HR]: 3.2; 95% CI: 2.1-4.8, p<0.001). CONCLUSIONS: Preoperative E/e´ is a prognostic indicator of overall mortality in ESRD patients undergoing KT.

A Critical Approach to Evaluating Clinical Efficacy, Adverse Events and Drug Interactions of Herbal Remedies.

Systematic reviews and meta-analyses represent the uppermost ladders in the hierarchy of evidence. Systematic reviews/meta-analyses suggest preliminary or satisfactory clinical evidence for agnus castus (Vitex agnus castus) for premenstrual complaints, flaxseed (Linum usitatissimum) for hypertension, feverfew (Tanacetum partenium) for migraine prevention, ginger (Zingiber officinalis) for pregnancy-induced nausea, ginseng (Panax ginseng) for improving fasting glucose levels as well as phytoestrogens and St John's wort (Hypericum perforatum) for the relief of some symptoms in menopause. However, firm conclusions of efficacy cannot be generally drawn. On the other hand, inconclusive evidence of efficacy or contradictory results have been reported for Aloe vera in the treatment of psoriasis, cranberry (Vaccinium macrocarpon) in cystitis prevention, ginkgo (Ginkgo biloba) for tinnitus and intermittent claudication, echinacea (Echinacea spp.) for the prevention of common cold and pomegranate (Punica granatum) for the prevention/treatment of cardiovascular diseases. A critical evaluation of the clinical data regarding the adverse effects has shown that herbal remedies are generally better tolerated than synthetic medications. Nevertheless, potentially serious adverse events, including herb-drug interactions, have been described. This suggests the need to be vigilant when using herbal remedies, particularly in specific conditions, such as during pregnancy and in the paediatric population. Copyright © 2016 John Wiley & Sons, Ltd.

Growth Factor Release from Lyophilized Porcine Platelet-Rich Plasma: Quantitative Analysis and Implications for Clinical Applications.

BACKGROUND: Freeze-dried platelet-rich plasma (FD PRP) is of potential value for clinical applications. However, growth factors released from FD PRP have not been well studied. Our study investigates growth factor release from FD PRP preparations, compared with other PRP samples, to further facilitate such clinical use. METHODS: We used four experimental groups: (1) Fresh porcine PRP (PRP), (2) PRP activated by calcium chloride (CaCl2) (Ca PRP), (3) PRP activated by CaCl2, followed by freeze drying (Ca-FD PRP), and (4) PRP freeze-dried first, then activated by CaCl2 (FD-Ca PRP). All FD PRP samples were kept for up to 4 weeks at room temperature (22 °C) and reconstituted prior to analysis. Transforming growth factor-ß1 (TGF-ß1), platelet-derived growth factor AB (PDGF-AB), and vascular endothelial growth factor (VEGF) were quantitated by ELISA at 15 min and 1 h incubation times. RESULTS: The concentrations of all growth factors in Ca PRP, measured at 1 h, were significantly higher than those in PRP (p < 0.05). PDGF-AB concentrations in FD-Ca PRP were not significantly different than in Ca PRP (p > 0.05). Levels of VEGF in Ca-FD PRP were not significantly different than in Ca PRP (p > 0.05). However, TGF-ß1 concentrations in Ca-FD PRP, measured at 15 min, were higher than those in Ca PRP (p < 0.05). CONCLUSIONS: PRP was activated efficiently by calcium chloride. Freeze-dried PRP remained rich in growth factors after storage for 4 weeks at room temperature, indicating its ease of use and wider possibilities for clinical applications. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Defective Mismatch Repair Status was not Associated with DFS and OS in Stage II Colon Cancer Treated with Adjuvant Chemotherapy.

BACKGROUND: Mismatch repair (MMR) status has been proposed, with some controversy, as a prognostic and predictive marker in stage II colon cancer. The aim of this study was to evaluate the association between MMR and survival in stage II colon cancer. METHODS: A total of 860 patients with curatively resected stage II colon cancer were selected for inclusion between January 2003 and December 2008. Tumors lacking expression of MLH1 and/or MSH2, as determined by immunohistochemistry, were classified as having deficient MMR (dMMR), whereas other tumors were classified as having proficient MMR (pMMR). Clinical risk (CR) factors were used to divide patients into high or standard CR groups. RESULTS: Of 860 patients, 14.7 % were dMMR, 42.4 % had ≥1 CR factors, and 85.8 % patients received adjuvant chemotherapy. MMR status did not affect disease-free survival (DFS; hazard ratio [HR] 1.191, p = 0.415) or overall survival (OS; HR 1.300, p = 0.344). Among CR factors, only pathologic T4 disease tended to associate with poor OS (HR 1.979, p = 0.071). Adjuvant chemotherapy was associated with better DFS (HR 0.393, p < 0.0001) in patients with pMMR tumors. However, in patients with dMMR tumors, adjuvant chemotherapy was not associated with DFS. CONCLUSIONS: MMR status did not affect DFS or OS in patients with stage II colon cancer. In patients treated with adjuvant chemotherapy, dMMR was not associated with DFS and OS. However, adjuvant chemotherapy was associated with improved DFS in pMMR patients.

Meta-atom loaded circularly polarized triple band patch antenna for Wi-Fi, ISM and X-band communications.

Microstrip antennas usually suffer from high losses, gain, and efficiency degradation. It is a challenging task to miniaturize the patch antenna without degrading the performance parameters. To mitigate the above problems, a microstrip patch antenna loaded with stubs and printed on the ground plane loaded with dumbbell meta-atom is presented in this paper. The proposed double dumbbell meta-atom consists of two complementary split ring resonator (CSRR) cells loaded with rectangular rings. This exhibits the Double Negative (DNG) characteristic at 2.45 GHz. The devised meta-atom possesses dimensions of 0.05λ x 0.03λ at lower giga-hertz range. The meta-atom is further analyzed in CST-Microwave Studio and the corresponding S-parameters are extracted in MATLAB using the Nicolson Ross Weir (NRW) method. The electrical model of the meta-atom is also analyzed using Agilent ADS simulator. Further, two models of the proposed antenna with FR-4 and RT/Duroid-5880 are designed and compared. The proposed patch antenna resonates at three different frequency bands i.e. 2.445 GHz with a 3-dB bandwidth of 110 MHz (2.4 GHz-2.51 GHz), at 5.85 GHz with a 3-dB bandwidth of 730 MHz (5.13 GHz-5.86 GHz), and at 8.83 GHz with a 3-dB bandwidth of 1.83 GHz (7.7 GHz-9.53 GHz). This exhibit peak gains of 2.75dBi, 3.53dBc and 4.36dBi with low cross polarization levels at the said frequencies of operation. Further, the antenna possesses circular polarization in the frequency band (5.15 GHz-5.63 GHz). This antenna is used for Wi-Fi, ISM and X-band communications. The designed prototype is fabricated and tested and bears resemblance to the simulated results.

Spatio-temporal structures of satellite-derived water quality indicators along the Korean South Coast.

The structure of 9-year time series data for Sea Surface Temperature (SST), Chlorophyll a (Chl-a) and Total Suspended Solids (TSS), derived from the Visible Infrared Imaging Radiometer Suite (VIIRS), was examined in this study. Authors found that there exists strong seasonality among the three variables with spatial heterogeneity along the Korean South Coast (KSC). In specific, SST was in phase with Chl-a, but out of phase with TSS by six months. A strong inversed spectral power with six-month phase-lag was found between Chl-a and TSS. This could be attributed to different dynamics and environmental settings. For example, Chl-a concentration seemed to have strong positive correlation with SST indicating typical seasonality of marine biogeochemical processes such as primary production; while a strong negative correlation between TSS and SST might have been influenced by changes in physical oceanographic processes, such as stratification and monsoonal wind-driven vertical mixing. In addition, the strong east-west heterogeneity of Chl-a suggests that the marine coastal environments are predominantly governed by distinct local hydrological conditions and human activities associated with land cover and land use, while the east-west spatial pattern revealed in TSS timeseries was associated with the gradient of tidal forcings and topographical changes keeping tidally induced resuspension low eastward.

Augmented Decision-Making in wound Care: Evaluating the clinical utility of a Deep-Learning model for pressure injury staging.

BACKGROUND: Precise categorization of pressure injury (PI) stages is critical in determining the appropriate treatment for wound care. However, the expertise necessary for PI staging is frequently unavailable in residential care settings. OBJECTIVE: This study aimed to develop a convolutional neural network (CNN) model for classifying PIs and investigate whether its implementation can allow physicians to make better decisions for PI staging. METHODS: Using 3,098 clinical images (2,614 and 484 from internal and external datasets, respectively), a CNN was trained and validated to classify PIs and other related dermatoses. A two-part survey was conducted with 24 dermatology residents, ward nurses, and medical students to determine whether the implementation of the CNN improved initial PI classification decisions. RESULTS: The top-1 accuracy of the model was 0.793 (95% confidence interval [CI], 0.778-0.808) and 0.717 (95% CI, 0.676-0.758) over the internal and external testing sets, respectively. The accuracy of PI staging among participants was 0.501 (95% CI, 0.487-0.515) in Part I, improving by 17.1% to 0.672 (95% CI, 0.660-0.684) in Part II. Furthermore, the concordance between participants increased significantly with the use of the CNN model, with Fleiss' κ of 0.414 (95% CI, 0.410-0.417) and 0.641 (95% CI, 0.638-0.644) in Parts I and II, respectively. CONCLUSIONS: The proposed CNN model can help classify PIs and relevant dermatoses. In addition, augmented decision-making can improve consultation accuracy while ensuring concordance between the clinical decisions made by a diverse group of health professionals.

Antigen-independent IL-17A production by bystander-activated CD4+IL-1R1+ cells in patients with multiple sclerosis.

Multiple sclerosis (MS) is a demyelinating disease caused by auto-antigen recognizing CD4+ T cells. However, IL-17A-producing CD4+ T cells that are bystander-activated by IL-1ß and IL-23, and T cell receptors independently, could contribute to experimental autoimmune encephalomyelitis. Here, we studied the differences in the frequency and function of bystander-activated CD4+ T cells in patients with MS. A significantly higher frequency of CD4 + IL-1Rl + T cells was found in memory than in naïve CD4+ T cells and in Th17/Th17.1 than in Th1/Th2 subtypes in both MS and healthy controls (HC). Following IL-1ß and IL-23 stimulation, IL-1Rl expression was markedly increased in both memory and Th17/Th17.1 cells, and their IL-17A-production was increased after bystander-activation, which was significantly higher in MS compared with HC. Our study suggests a potential role of IL-17A-producing bystander-activated CD4+IL-1Rl+ T cells in MS.

Inhibition of STAT3 signaling and induction of SHP1 mediate antiangiogenic and antitumor activities of ergosterol peroxide in U266 multiple myeloma cells.

BACKGROUND: Ergosterol peroxide (EP) derived from edible mushroom has been shown to exert anti-tumor activity in several cancer cells. In the present study, anti-angiogenic activity of EP was investigated with the underlying molecular mechanisms in human multiple myeloma U266 cells. RESULTS: Despite weak cytotoxicity against U266 cells, EP suppressed phosphorylation, DNA binding activity and nuclear translocalization of signal transducer and activator of transcription 3 (STAT3) in U266 cells at nontoxic concentrations. Also, EP inhibited phosphorylation of the upstream kinases Janus kinase 2 (JAK2) and Src in a time-dependent manner. Furthermore, EP increased the expression of protein tyrosine phosphatase SHP-1 at protein and mRNA levels, and conversely silencing of the SHP-1 gene clearly blocked EP-mediated STAT3 inactivation. In addition, EP significantly decreased vascular endothelial growth factor (VEGF), one of STAT3 target genes at cellular and protein levels as well as disrupted in vitro tube formation assay. Moreover, EP significantly suppressed the growth of U266 cells inoculated in female BALB/c athymic nude mice and immunohistochemistry revealed that EP effectively reduced the expression of STAT3 and CD34 in tumor sections compared to untreated control. CONCLUSION: These findings suggest that EP can exert antitumor activity in multiple myeloma U266 cells partly with antiangiogenic activity targeting JAK2/STAT3 signaling pathway as a potent cancer preventive agent for treatment of multiple myeloma cells.

Mo and Zn-Dual doped CuxO nanocrystals confined High-Conductive Cu arrays as novel sensitive sensor for neurotransmitter detection.

The development of sensitive and selective sensors using facile and low-cost methods for detecting neurotransmitter molecules is a critical factor in the health care system in regard to early diagnosis. In this research, an electrocatalyst derived from Mo,Zn dual-doped CuxO nanocrystals-based layer coating over one-dimensional copper nanowire arrays (Mo,Zn-CuxO/CuNWs) was successfully designed using a facile electrodeposition approach and used as an electrochemical sensor for non-enzymatic dopamine (DA) neurotransmitter detection. The synergistic effect caused by the dual-doping effect along with its excellent conductivity produced a large electroactive surface area and an improved hetero-charge transfer, thereby boosting DA sensing ability with a low limit detection of 0.32 µM, wide-range of detection (0.5 µM - 3.9 mM), long-term stability (5 weeks), and high selectivity in phosphate buffer solution (pH 7.4). Also, the sensor accurately determined DA in real blood serum-spiked solutions. The achieved results evidenced that the Mo,Zn-CuxO/CuNWs derived sensor is highly suitable for DA detection. Therefore, it also opens new windows for the development of low-cost, accurate, high-performance, and stable sensors for other neurotransmitter sensing for the purposes of better health care and early diagnosis.

Expression of c-Jun and KROX-20 Following Facial Nerve Injury and Recovery in Rats.

BACKGROUND: This study evaluated whether recovery from facial paralysis was associated with the expression of Krox-20 and c-Jun genes that are shown to be related to facial nerve regeneration after facial nerve compression and cutting. METHODS: The left facial nerves of 24 male Sprague-Dawley rats aged 6 weeks were subjected to crushing or cutting injury. Whisker movements of the vibrissae muscle and blink reflexes of the eyelids were measured on days 4 and 14 after facial nerve injury. The facial nerves on both sides were removed, and the expression of c-Jun and Krox-20 proteins was evaluated by Western blotting. RESULTS: The level of expression of Krox-20 on day 4 was lower in the crushing group, especially in the cutting group than in the control group (P < .05), but there was no statistically significant difference on day 14 (P > .05). The expression of c-Jun expression was significantly higher in the crushing and cutting groups than in the control group on days 4 and 14 (P < .05). CONCLUSION: The degree of facial paralysis was more severe and the recovery rate was lower in the cutting group than in the crushing group. The levels of expression of Krox-20 and c-Jun were associated with facial nerve regeneration after facial nerve injury.

Landmarks and techniques to perform minimally invasive liver surgery: A systematic review with a focus on hepatic outflow.

PURPOSE: In this systematic review, we aimed to clarify the useful anatomic structures and assess available surgical techniques and strategies required to safely perform minimally invasive anatomic liver resection (MIALR), with a particular focus on the hepatic veins (HVs). METHODS: A systematic review was conducted using MEDLINE/PubMed for English articles and Ichushi databases for Japanese articles through September 2020. The quality assessment of the articles was performed in accordance with the Scottish Intercollegiate Guidelines Network (SIGN). RESULTS: A total of 3372 studies were obtained, and 59 were selected and reviewed. Due to the limited number of published comparative studies and case series, the degree of evidence from our review was low. Thirty-two articles examined the anatomic landmarks and crucial structures for approaching HVs. Regarding the direction of HV exposure, 32 articles focused on the techniques and advantages of exposing HVs from either the root or the periphery. Ten articles focused on the techniques to perform a segmentectomy 8 in particularly difficult cases of MIALR. In seven articles, bleeding control from HVs was also discussed. CONCLUSIONS: This review may help experts reach a consensus regarding the best approach to the management of hepatic veins during MIALR.

Body CT and PET/CT detection of extracranial lymphoma in patients with newly diagnosed central nervous system lymphoma.

BACKGROUND: We aimed to investigate the detection rate of body CT or PET/CT for sites of extracranial disease in patients with a new pathological diagnosis of CNS DLBCL and to identify factors associated with sites of extracranial disease. METHODS: An international multicenter cohort study of consecutive immunocompetent patients with a new diagnosis of CNS DLBCL confirmed by brain biopsy who underwent CT and/or PET/CT to evaluate for sites of extracranial disease between 1998 and 2019. The primary outcome was the detection rate of extracranial lymphoma by CT or PET/CT. Subgroup analyses according to age and EBV status were also performed. Logistic regression analyses were performed to determine factors related to sites of extracranial disease. Detection rates of CT and PET/CT were compared. RESULTS: One thousand and forty-three patients were included. The overall detection rate of CT or PET/CT was 2.6% (27/1043). The treatment approach was adjusted in 74% of these patients. Multivariable analysis demonstrated that age >61 years (OR, 3.10; P = .016) and EBV positivity (OR, 3.78; P = .045) were associated with greater odds of extracranial lymphoma. There was no statistically significant difference in detection rate between CT and PET/CT (P = .802). In patients ≤61 years old, the false-referral rates were significantly higher than the detection rates (P < .001). CONCLUSION: Our results showed increased odds of extracranial lymphoma in patients with older age or EBV-positive lymphoma. Treatment was adjusted in a majority of patients diagnosed with extracranial lymphoma, thereby supporting the current guidelines for the use of contrast-enhanced body CT or PET/CT in patients with newly diagnosed CNS DLBCL.

Association Between Visit-to-Visit Fasting Plasma Glucose Variability and Osteoporotic Fractures in Nondiabetic Subjects.

CONTEXT: Although long-term glucose variability has been reported to be a risk factor associated with osteoporosis, there have been no previous studies between the relationship of glucose variability and fractures in people without diabetes. OBJECTIVE: We assessed visit-to-visit variations in fasting plasma glucose (FPG) as a prognostic factor in predicting osteoporotic fractures in individuals without diabetes. METHODS: Using a nationwide cohort database, we examined the impact of FPG on the development of osteoporotic fractures in men and women (aged ≥50 years). The primary outcomes were the number of total fractures and vertebral fractures. FPG variability was measured using standard deviation (FPG-SD), coefficient of variation (FPG-CV), and variability independent of the mean (FPG-VIM). RESULTS: Of the 92 929 participants, 5262 (5.7%) developed osteoporotic fractures during the mean follow-up of 8.4 years. Individuals in the highest quartile of FPG-SD showed an 11% and 16% increase in risk of total and vertebral fractures, respectively, compared with those in the lowest quartile after adjustment for mean FPG and other risk factors. Analyses using FPG-CV and FPG-VIM demonstrated similar results. Subgroup analyses and sensitivity analyses to explore potential heterogeneity showed consistent results. CONCLUSION: FPG variability may be a novel risk factor for osteoporotic fractures independent of risk factors in the general population without diabetes.

Rational Design, Synthesis and Evaluation of Oxazolo[4,5-c]-quinolinone Analogs as Novel Interleukin-33 Inhibitors.

Interleukin-33 (IL-33) is an epithelial-derived cytokine that plays an important role in immune-mediated diseases such as asthma, atopic dermatitis, and rheumatoid arthritis. Although IL-33 is considered a potential target for the treatment of allergy-related diseases, no small molecule that inhibits IL-33 has been reported. Based on the structure-activity relationship and in vitro 2D NMR studies employing 15 N-labeled IL-33, we identified that the oxazolo[4,5-c]-quinolinone analog 7 c binds to the interface region of IL-33 and IL-33 receptor (ST2), an orphan receptor of the IL-1 receptor family. Compound 7 c effectively inhibited the production of IL-6 in human mast cells in a dose-dependent manner. Compound 7 c is the first low molecular weight IL-33 inhibitor and may be used as a prototype molecule for structural optimization and investigation of the IL-33/ST2 signaling pathway.