Assessing Visual Pathway White Matter Degeneration in Primary Open-Angle Glaucoma Using Multiple MRI Morphology and Diffusion Metrics.

BACKGROUND: Primary open-angle glaucoma (POAG), a leading cause of irreversible blindness, is associated with neurodegeneration in the visual pathway, but the underlying pathophysiology remains incompletely resolved. PURPOSE: To characterize macro- and microstructural white matter abnormalities in optic tract (OT) and optic radiation (OR) of POAG. STUDY TYPE: Prospective. POPULATIONS: A total of 34 POAG patients (21 males, 13 females) and 25 healthy controls (HCs) (16 males, nine females). FIELD STRENGTH/SEQUENCE: 3 T; multiband spin-echo echo planar diffusion spectrum imaging (DSI). ASSESSMENT: We compared multiple morphology metrics, including volume, area, length, and shape metrics, as well as diffusion metrics such as diffusion tensor imaging (fractional anisotropy [FA], mean diffusivity, radial diffusivity, and axial diffusivity), mean apparent propagator (mean squared displacement, q-space inverse variance, return-to-origin probability, return-to-axis probabilities [RTAP] and return-to-plane probabilities, non-Gaussianity, perpendicular non-Gaussianity, parallel non-Gaussianity), and neurite orientation dispersion and density imaging (intracellular volume fraction, orientation dispersion index [ODI], and isotropic volume fraction of the OT and OR). STATISTICAL TESTS: Statistical comparisons and classifications employed linear mixed model and logistic regression. Diagnostic performance was assessed using area under the receiver operating characteristic curve (AUC). P-value <0.05 was statistically significant. RESULTS: Morphology analysis in POAG revealed a lower span in the OR (29.43 ± 2.30 vs. 30.59 ± 2.01, 3.8%) and OT (19.73 ± 2.21 vs. 20.68 ± 1.37, 4.6%), and a higher curl (3.03 ± 0.22 vs. 2.90 ± 0.16, 4.5%) in OT. Diffusion metrics revealed lower mean FA (OR: 0.328 ± 0.03 vs. 0.340 ± 0.018, 3.5%; OT: 0.255 ± 0.022 vs. 0.268 ± 0.018, 4.9%) and lower mean RTAP (OR: 5.919 ± 0.529 vs. 6.216 ± 0.489, 4.8%; OT: 4.089 ± 0.402 vs. 4.280 ± 0.353, 4.5%), with higher mean ODI in the OT (0.448 ± 0.029 vs. 0.433 ± 0.025, 3.5%). Combined models, incorporating these MRI metrics, effectively discriminated POAG from HCs, achieving AUCs of 0.84 for OR and 0.83 for OT. DATA CONCLUSIONS: DSI-derived morphology and diffusion metrics demonstrated macro- and micro abnormalities in the visual pathway, providing insights into POAG-related neurodegeneration. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 3.

Reversible Multimode Luminescence Modulations in Photochromic-Translucent Yb3+/Eu3+ Codoped K0.5Na0.5NbO3 Ceramics.

Luminescent tunable materials have promising application potential in optical switches, optical information storage, and so on. Although europium (Eu) is a good downconversion red luminescent rare earth element, there are few studies on the upconversion luminescence and photochromism of Eu-doped potassium sodium niobate (KNN) ferroelectrics. In this paper, Eu3+ and Yb3+ codoped KNN translucent ferroelectric ceramics were synthesized and the effect of Yb3+ content on the luminescence and photochromism is studied. Both the up- and downconversion luminescence intensity and decay rate before and after photochromism can be well controlled by Yb3+ content. That is, an upconversion luminescent translucent ceramic that can be completely discolored by 405 nm light illumination for 10 s was obtained. The luminescence modulations are closely related to the evolution of oxygen vacancy and crystal field around the luminescence center, which can be verified by the illumination-induced electron paramagnetic resonance (EPR) signal and local piezoresponse switching behavior variation as well as the discovery of energy level splitting and spectral line shift. We believe that this work shows a paradigm for designing high-performance reversible multimode luminescence modulation ferroelectric ceramics.

A progress update on the biological effects of biodegradable microplastics on soil and ocean environment: A perfect substitute or new threat?

Conventional plastics are inherently difficult to degrade, causing serious plastic pollution. With the development of society, biodegradable plastics (BPs) are considered as an alternative to traditional plastics. However, current research indicated that BPs do not undergo complete degradation in natural environments. Instead, they may convert into biodegradable microplastics (BMPs) at an accelerated rate, thereby posing a significant threat to environment. In this paper, the definition, application, distribution, degradation behaviors, bioaccumulation and biomagnification of BPs were reviewed. And the impacts of BMPs on soil and marine ecosystems, in terms of physicochemical property, nutrient cycling, microorganisms, plants and animals were comprehensively summarized. The effects of combined exposure of BMPs with other pollutants, and the mechanism of ecotoxicity induced by BMPs were also addressed. It was found that BMPs reduced pH, increased DOC content, and disrupted the nitrification of nitrogen cycle in soil ecosystem. The shoot dry weight, pod number and root growth of soil plants, and reproduction and body length of soil animals were inhibited by BMPs. Furthermore, the growth of marine plants, and locomotion, body length and survival of marine animals were suppressed by BMPs. Additionally, the ecotoxicity of combined exposure of BMPs with other pollutants has not been uniformly concluded. Exposure to BMPs induced several types of toxicity, including neurotoxicity, gastrointestinal toxicity, reproductive toxicity, immunotoxicity and genotoxicity. The future calls for heightened attention towards the regulation of the degradation of BPs in the environment, and pursuit of interventions aimed at mitigating their ecotoxicity and potential health risks to human.

Simultaneous Determination of Rifamycin Antibiotics and Their Active Metabolites in Human Plasma Using UHPLC-MS/MS to Evaluate Their Impact on Target Peak Concentrations: A Short Communication.

BACKGROUND: Standard and proper antituberculosis (anti-TB) treatment is essential for patients with TB, and rifamycin antibiotics are key components of anti-TB therapy. Therapeutic drug monitoring (TDM) of rifamycin antibiotics can shorten the time to response and complete treatment of TB. Notably, antimicrobial activities of the major active metabolites of rifamycin are similar to those of their parent compounds. Thus, a rapid and simple assay was developed for simultaneous determination of rifamycin antibiotics and their major active metabolites in plasma to evaluate their impact on target peak concentrations. Here, the authors have developed and validated a method for simultaneous determination of rifamycin antibiotics and their active metabolites in human plasma using ultrahigh-performance liquid chromatography tandem mass spectrometry. METHODS: Analytical validation of the assay was performed in accordance with the bioanalytical method validation guidance for industry described by the US Food and Drug Administration and the guidelines for bioanalytical method validation described by the European Medicines Agency. RESULTS: The drug concentration quantification method for rifamycin antibiotics, including rifampicin, rifabutin, and rifapentine, and their major active metabolites was validated. Significant differences in the proportions of active metabolites in rifamycin antibiotics may affect the redefinition of their effective concentration ranges in the plasma. The method developed herein is expected to redefine the ranges of "true" effective concentrations of rifamycin antibiotics (including parent compounds and their active metabolites). CONCLUSIONS: The validated method can be successfully applied for high-throughput analysis of rifamycin antibiotics and their active metabolites for TDM in patients receiving anti-TB treatment regimens containing these antibiotics. Proportions of active metabolites in rifamycin antibiotics markedly varied among individuals. Depending on the clinical indications of patients, the therapeutic ranges for rifamycin antibiotics may be redefined.

An Accurate and Individualized Preoperative Estimation Method for the Linear Insertion Depth of Cochlear Implant Electrode Arrays Based on Computed Tomography.

OBJECTIVES: Cochlear implantation or auditory brainstem implantation is currently the only accepted method for improving severe or profound sensorineural hearing loss. The length of the electrodes implanted during cochlear implantation is closely related to the degree of hearing improvement of hearing after the surgery. We aimed to explore new methods to accurately estimate the electrode array (EA) linear insertion depth based on computed tomography (CT) images prior surgery, which could help surgeons select the appropriate EA length for each patient. DESIGN: Previous studies estimated the linear insertion depth by measuring the length of the lateral wall of the cochlea rather than the electrode's path in the cochlea duct. Here, we determined the actual position of the EA on the CT image after cochlear surgery in order to predict the path of the EA, and the length of the predicted EA path was measured by the contouring technique (CoT) to estimate the linear insertion depth of the EA. Because CoT can only measure the length of the estimated EA path on a two-dimensional plane, we further modified the measurement by weighting the height of the cochlea and the length of the EA tail (the length of the last stimulating electrode to the end, which cannot be displayed on the CT image), which we termed the modified CoT + height + tail (MCHT) measurement. RESULTS: Based on our established method, MCHT could reduce the error to the submillimeter range (0.67 ± 0.37 mm) when estimating the linear insertion depth of various kinds of EAs compared with the actual implant length. The correlation coefficient between the linear insertion depth as predicted by MCHT and the actual was 0.958. The linear insertion depth estimated by this method was more accurate than that estimated using the classical CoT technique ( R = 0.442) and using the modified Escudé's method ( R = 0.585). CONCLUSIONS: MCHT is a method based on CT images that can accurately predict the linear insertion depth of cochlear implants preoperatively. This is the first report that we are aware of a method for predicting linear insertion depth before cochlear implantation with only submillimeter errors and that is tailored to different types of EAs.

Altered spontaneous neuronal activity and functional connectivity pattern in primary angle-closure glaucoma: a resting-state fMRI study.

PURPOSE: To explore the alterations of spontaneous neuronal activity and functional connectivity pattern using fractional amplitude of low-frequency fluctuation (fALFF) and functional connectivity (FC) in patients with primary angle-closure glaucoma (PACG) and fALFF relationship with the glaucoma clinical indices. MATERIALS AND METHODS: Forty-two PACG patients and 21 normal controls were enrolled in this study. Resting-state functional magnetic resonance imaging was firstly analyzed by fALFF and brain regions with altered fALFF between groups were selected as seeds for the further FC analysis. The relationships between fALFF/FC values of abnormal regions and ophthalmological measures, including mean deviation of visual field (MDVF) and retinal nerve fiber layer (RNFL) thickness, were also analyzed. RESULTS: Compared with NC, PACG had significant lower fALFF values in the left cuneus, left middle temporal gyrus, right middle temporal gyrus, and right precentral gyrus, while higher fALFF values in the bilateral superior frontal gyrus (P < 0.05 after correction). Furthermore, PACG showed increased FC between left cuneus and bilateral superior frontal gyrus/bilateral posterior cingulate gyrus; between left middle temporal gyrus and bilateral superior frontal gyrus; and between right middle temporal gyrus and bilateral insular (P < 0.05 after correction). In addition, in the PACG group, the mean fALFF values of the left cuneus were positively correlated with MDVF (R = 0.419, P = 0.005) and RNFL thickness (R = 0.322, P = 0.038). Meanwhile, the mean fALFF values of bilateral superior frontal gyrus were negatively correlated with MDVF (R = - 0.454, P = 0.003) and RNFL thickness (R = - 0.556, P < 0.001). CONCLUSIONS: PACG exhibited abnormal spontaneous neural activity and connectivity in several brain regions mainly associated with visual and visual-related functions. In addition, the fALFF values of the left cuneus and bilateral superior frontal gyrus may be complementary biomarkers for assessing the disease severity.

Magnetic resonance imaging investigations reveal that PM2.5 exposure triggers visual dysfunction in mice.

OBJECTIVES: To investigate how PM2.5 exposure affects the microstructure, metabolites or functions of the visual system. METHODS: C57BL/6J mice were randomly assigned to groups exposed to the filtered air (the control group) or the concentrated ambient PM2.5 (the PM2.5 group). Visual evoked potentials (VEP), electroretinograms (ERG), diffusion tensor imaging (DTI), proton magnetic resonance spectroscopy (1H-MRS) and resting-state functional MRI (rsfMRI) were performed. Parameters were obtained and compared between the two groups, including latencies and amplitudes of the P1 wave, N1 wave and P2 wave from VEP, latencies and amplitudes of the a wave and b wave from ERG, fractional anisotropy (FA), mean diffusion (MD), axial diffusivity (AD) and radial diffusivity (RD) from DTI, visual cortex (VC) metabolites from 1H-MRS, and regional homogeneity (ReHo) from rsfMRI. RESULTS: Compared with the values of the control group, the PM2.5 group showed a prolonged N1 latency (43.11 ±â€¯7.94 ms vs. 38.75 ±â€¯4.60 ms) and lowered P1 amplitude (5.62 ±â€¯4.38 µV vs. 8.56 ±â€¯5.92 µV) on VEP (all p < 0.05). On ERG, the amplitude of the a wave was lowered (- 91.39 ±â€¯56.29 µV vs. - 138.68 ±â€¯89.05 µV), the amplitude of the b wave was lowered (194.38 ±â€¯126.27 µV vs. 284.72 ±â€¯170.99 µV), and the latency of the b wave was prolonged (37.78 ±â€¯10.72 ms vs. 33.01 ±â€¯4.34 ms) than the values of the control group (all p < 0.05). DTI indicated FA increase in the bilateral piriform cortex (Pir), FA decrease in the bilateral somatosensory cortex (S) and the bilateral striatum (Stri), AD decrease in the bilateral VC, the right S and the bilateral Pir, MD decrease in the bilateral Pir, and RD decrease in the bilateral Pir in the PM2.5 mice (all p < 0.05, Alphasim corrected). 1H-MRS showed Glutamate (Glu) increase and Phosphocholine (PCh) increase in the VC of the PM2.5 group than those of the control group (PCh 1.63 ±â€¯0.25 vs. 1.50 ±â€¯0.25; PCh/total creatine(tCr) 0.19 ±â€¯0.03 vs. 0.18 ±â€¯0.03; Glu 10.46 ±â€¯1.50 vs. 9.60 ±â€¯1.19; Glu/tcr 1.23 ±â€¯0.11 vs. 1.12 ±â€¯0.11) (all p < 0.05). rsfMRI showed higher ReHo in the PM2.5 mice in the left superior colliculus, the left motor cortex, the hippocampus, the periaqueductal gray and the right mesencephalic reticular formation (all p < 0.01, AlphaSim corrected). CONCLUSIONS: This study revealed that PM2.5 exposure triggered visual dysfunction, and altered microstructure, metabolite and function in the retina and visual brain areas along the visual system.

Differentiation of olfactory neuroblastomas from nasal squamous cell carcinomas using MR diffusion kurtosis imaging and dynamic contrast-enhanced MRI.

PURPOSE: To evaluate the use of magnetic resonance (MR) diffusion kurtosis imaging (DKI) and dynamic contrast-enhanced MR imaging (DCE-MRI) in the differentiation of olfactory neuroblastomas (ONBs) from squamous cell carcinomas (SCCs). MATERIALS AND METHODS: DKI and DCE-MRI were performed in 17 patients with ONBs and 23 patients with SCCs on a 3T MR scanner. Parameters derived from DKI and DCE-MRI were measured and compared between ONBs and SCCs using an independent samples t-test. The sensitivity, specificity, accuracy, positive predictive values (PPV), negative predictive values (NPV), and the area under the receiver operating characteristic (ROC) curve were determined. RESULTS: The mean kurtosis (K) value of ONBs was significantly higher than that of SCCs (P < 0.001), and the mean fractional volume in the extravascular extracellular space (Ve ) value of ONBs was lower than that of SCCs (P < 0.001). The ROC curve analyses yielded a cutoff K value of 0.953, with a sensitivity of 94.1%, a specificity of 69.6%, and an accuracy of 80.0%; the cutoff Ve value was 0.493, with a sensitivity of 70.6%, a specificity of 95.7%, and an accuracy of 85.0%. A parallel test with K value >0.953 or Ve value ≤0.493 achieved a sensitivity of 94.1%, a specificity of 100.0%, and an accuracy of 97.5% for differentiating ONBs from SCCs. CONCLUSION: The K value of DKI and Ve value of DCE-MRI have potential use in the differentiation of ONBs and SCCs. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:354-361.

Standard diffusion-weighted, diffusion kurtosis and intravoxel incoherent motion MR imaging of sinonasal malignancies: correlations with Ki-67 proliferation status.

OBJECTIVES: To explore the correlations of parameters derived from standard diffusion-weighted imaging (DWI), diffusion kurtosis imaging (DKI) and intravoxel incoherent motion (IVIM) with the Ki-67 proliferation status. METHODS: Seventy-five patients with histologically proven sinonasal malignancies who underwent standard DWI, DKI and IVIM were retrospectively reviewed. The mean, minimum, maximum and whole standard DWI [apparent diffusion coefficient (ADC)], DKI [diffusion kurtosis (K) and diffusion coefficient (Dk)] and IVIM [pure diffusion coefficient (D), pseudo-diffusion coefficient (D*) and perfusion fraction (f)] parameters were measured and correlated with the Ki-67 labelling index (LI). The Ki-67 LI was categorised as high (> 50%) or low (≤ 50%). RESULTS: The K and f values were positively correlated with the Ki-67 LI (rho = 0.295~0.532), whereas the ADC, Dk and D values were negatively correlated with the Ki-67 LI (rho = -0.443~-0.277). The ADC, Dk and D values were lower, whereas the K value was higher in sinonasal malignancies with a high Ki-67 LI than in those in a low Ki-67 LI (all p < 0.05). A higher maximum K value (Kmax > 0.977) independently predicted a high Ki-67 status [odds ratio (OR) = 7.614; 95% confidence interval (CI) = 2.197-38.674; p = 0.017]. CONCLUSION: ADC, Dk, K, D and f are correlated with Ki-67 LI. Kmax is the strongest independent factor for predicting Ki-67 status. KEY POINTS: • DWI-derived parameters from different models are capable of providing different pathophysiological information. • DWI, DKI and IVIM parameters are associated with Ki-67 proliferation status. • K max derived from DKI is the strongest independent factor for the prediction of Ki-67 proliferation status.

Visual cortex and auditory cortex activation in early binocularly blind macaques: A BOLD-fMRI study using auditory stimuli.

Cross-modal plasticity within the visual and auditory cortices of early binocularly blind macaques is not well studied. In this study, four healthy neonatal macaques were assigned to group A (control group) or group B (binocularly blind group). Sixteen months later, blood oxygenation level-dependent functional imaging (BOLD-fMRI) was conducted to examine the activation in the visual and auditory cortices of each macaque while being tested using pure tones as auditory stimuli. The changes in the BOLD response in the visual and auditory cortices of all macaques were compared with immunofluorescence staining findings. Compared with group A, greater BOLD activity was observed in the bilateral visual cortices of group B, and this effect was particularly obvious in the right visual cortex. In addition, more activated volumes were found in the bilateral auditory cortices of group B than of group A, especially in the right auditory cortex. These findings were consistent with the fact that there were more c-Fos-positive cells in the bilateral visual and auditory cortices of group B compared with group A (p < 0.05). In conclusion, the bilateral visual cortices of binocularly blind macaques can be reorganized to process auditory stimuli after visual deprivation, and this effect is more obvious in the right than the left visual cortex. These results indicate the establishment of cross-modal plasticity within the visual and auditory cortices.

Manganese-enhanced MRI (ME MRI) in evaluation of the auditory pathway in an experimental rat model.

This study aimed to explore the optimal dose and manner of administration for visualization of the auditory pathway on manganese-enhanced MRI (ME MRI). Twenty-four healthy male Sprague-Dawley rats were randomly divided into three experimental groups (n = 8 for Groups A, B and C). The rats in Groups A, B and C were subjected to MnCl2 injection through the tympanum, inner ear endolymph and perilymph, respectively (0.2 M for four rats and 0.4 M for the others in each group) and observed at 1, 2, 3, 4, 7 and 10 days after the operation with 3.0 T MRI. The signal intensity (SI) and dynamic changes of the auditory pathways at various times, and at two doses through three injection routes, were compared by statistical analysis. Administration of MnCl2 through the perilymph best showed the complete auditory pathway (P < 0.01), whereas administration though the tympanum only demonstrated part of the pathway. The SI was highest at 24 h after administration of the tracer and began to decline at 48 h. The SI of the auditory cortex was higher after the injection of 0.4 M MnCl2 than that of 0.2 M MnCl2 . ME MRI best demonstrated the whole auditory pathway at 24 h after the injection of 0.4 M MnCl2 through the perilymph in the rat, which provided an optimal method for the study of ME MRI of the auditory pathway in the animal model.

Metabolic Changes in the Bilateral Visual Cortex of the Monocular Blind Macaque: A Multi-Voxel Proton Magnetic Resonance Spectroscopy Study.

The metabolic changes accompanied with adaptive plasticity in the visual cortex after early monocular visual loss were unclear. In this study, we detected the metabolic changes in bilateral visual cortex of normal (group A) and monocular blind macaque (group B) for studying the adaptive plasticity using multi-voxel proton magnetic resonance spectroscopy (1H-MRS) at 32 months after right optic nerve transection. Then, we compared the N-Acetyl aspartate (NAA)/Creatine (Cr), myoinositol (Ins)/Cr, choline (Cho)/Cr and Glx (Glutamate + glutamine)/Cr ratios in the visual cortex between two groups, as well as between the left and right visual cortex of group A and B. Compared with group A, in the bilateral visual cortex, a decreased NAA/Cr and Glx/Cr ratios in group B were found, which was more clearly in the right visual cortex; whereas the Ins/Cr and Cho/Cr ratios of group B were increased. All of these findings were further confirmed by immunohistochemical staining. In conclusion, the difference of metabolic ratios can be detected by multi-voxel 1H-MRS in the visual cortex between groups A and B, which was valuable for investigating the adaptive plasticity of monocular blind macaque.

Nanocluster of superparamagnetic iron oxide nanoparticles coated with poly (dopamine) for magnetic field-targeting, highly sensitive MRI and photothermal cancer therapy.

In this paper, a core­shell nanocomposite of clusters of superparamagnetic iron oxide nanoparticles coated with poly(dopamine) (SPION clusters@PDA) is fabricated as a magnetic field-directed theranostic agent that combines the capabilities of highly sensitive magnetic resonance imaging (MRI) and photothermal cancer therapy. The highly concentrated SPION cluster core is suitable for sensitive MRI due to its superparamagnetic properties, and the poly(dopamine) coating layer can induce cancer cell death under near-infrared (NIR) laser irradiation because of the photothermal conversion ability of PDA. MRI scanning reveals that the nanocomposite has relatively high r2 and r2(*) relaxivities, and the r2(*) values are nearly threefold higher than the r2 values because of the clustering of the SPIONs in the nanocomposite core. Due to the rapid response to magnetic field gradients, enhanced cellular uptake of our nanocomposite mediated by an external magnetic field can be achieved, thus producing significantly enhanced local photothermal killing efficiency against cancer cells under NIR irritation.

Multifunctional PEG modified DOX loaded mesoporous silica nanoparticle@CuS nanohybrids as photo-thermal agent and thermal-triggered drug release vehicle for hepatocellular carcinoma treatment.

The combination of a multi-therapeutic mode with a controlled fashion is a key improvement in nanomedicine. Here, we synthesized polyethylene glycol (PEG)-modified doxorubicin (DOX)-loaded mesoporous silica nanoparticle (MSN) @CuS nanohybrids as efficient drug delivery carriers, combined with photothermal therapy and chemotherapy to enhance the therapeutic efficacy on hepatocellular carcinoma (HCC). The physical properties of the nanohybrids were characterized by transmission electron microscopy (TEM), N2 adsorption and desorption experiments and by the Vis-NIR absorption spectra. The results showed that the doxorubicin could be stored in the inner pores of mesoporous silica nanoparticles; the CuS nanoparticles, which are coated on the surface of a mesoporous silica nanoparticle, could serve as efficient photothermal therapy (PTT) agents; the loaded drug release could be easily triggered by NIR irradiation. The combination of the PTT treatment with controlled chemotherapy could further enhance the cancer ablation ability compared to any of the single approaches alone. Hence, the reported PEG-modified DOX-loaded mesoporous silica nanoparticle@CuS nanohybrids might be very promising therapeutic agents for HCC treatment.

Preliminary study of diffusion-weighted imaging and magnetic resonance spectroscopy imaging in Kimura disease.

In this study, we evaluated the value of diffusion-weighted imaging (DWI) and magnetic resonance (MR) spectroscopy imaging (MRSI) combined with computed tomography (CT) and conventional MR imaging (MRI) in the diagnosis of Kimura disease (KD). The clinical data and CT and MRI findings of 5 patients with KD proven by histopathologic examination were retrospectively reviewed. Diffusion-weighted imaging and MRSI were performed at 1.5 T in 3 patients with KD. Apparent diffusion coefficient (ADC) values and the choline/creatine ratio of the lesions were compared with those of the contralateral normal parotid glands. All imaging results were compared with histopathologic findings. The typical features of KD were subcutaneous lesions, continuously infiltrative parotid lesions with or without intraparotid lymphadenopathies, and reactive cervical lymphadenopathies on CT and conventional MRI. On DWI, the ADC values of all subcutaneous and infiltrative parotid lesions were higher compared to those of normal parotid glands, and the ADC values of reactive lymphadenopathies were lower compared to both. The choline/creatine levels of subcutaneous and infiltrative parotid lesions were slightly higher than those of normal parotid glands. In conclusion, DWI and MRSI offer valuable information that may be characteristic of KD, which can highly suggest the diagnosis of KD when combined with morphological imaging.

Development of a Prognostic Nomogram for Modified Tinnitus Relieving Sound Therapy for Subjective Tinnitus.

OBJECTIVE: We aimed to develop a modified tinnitus-relieving sound system and establish a model for predicting its treatment effects. STUDY DESIGN: Retrospective study. SETTING: Tinnitus Specialist Clinic of Eye & ENT Hospital, Fudan University. METHODS: We recruited 107 patients undergoing modified tinnitus-relieving sounds between August 2020 and May 2021. Patients were divided into training (n = 75) and validation (n = 32) cohorts in a 7:3 ratio. The treatment outcome was Tinnitus Handicapped Inventory scores. Features were established using a least absolute shrinkage and selection operator-derived logistic regression model, where the selected clinical risk factors were included in the multivariate logistic regression, and a nomogram was established based on the model. The discrimination and calibration abilities of the nomogram were evaluated using the Hosmer-Lemeshow test and calibration curves. Decision curve analysis (DCA) was used to evaluate the net benefit of predictive efficacy. RESULTS: Multivariate logistic analysis indicated that the initial Tinnitus Handicapped Inventory score (odds ratio [OR]: 1.13 [1.07-1.19], P < .001) and treatment duration (OR: 3.4 [1.34-8.62], P < .001) were positive factors for improved tinnitus. The nomogram model that included baseline Tinnitus Handicapped Inventory score and treatment duration achieved a better concordance index of 0.880. DCA revealed that the nomogram model could lead to net benefits and exhibited a wider range of threshold probabilities for the prediction of therapeutic effects. CONCLUSION: Our study suggests that the nomogram model, including baseline Tinnitus Handicapped Inventory score and treatment duration, could achieve optimal performance in the preoperative prediction of the therapeutic effect of modified tinnitus-relieving sound.

A validated UPLC-MS/MS method for the quantification of immunosuppressive drugs in peripheral blood mononuclear cells using liquid-liquid extraction with low temperature purification without complex pretreatment steps.

Immunosuppressive drugs (ISDs) are given to avoid the allograft rejection after transplantation. The concentrations of ISDs should be closely monitored owing to their wide inter-individual variability in its pharmacokinetics and narrow therapeutic window. Currently, the whole blood concentration measurement is the major approach of therapeutic drug monitoring of clinical ISDs in organ transplantation. Its correlation with the efficacy of ISDs remains elusive. While the acute rejection after transplantation may occur even when whole-blood ISDs concentrations are within the target range. Since the site of action of ISDs are within the lymphocyte, direct measurement of drug exposure in target cells may more accurately reflect the clinical efficacy of ISDs. Although several methods have been developed for the peripheral blood mononuclear cells (PBMCs) extraction and drug concentration measurement, the complex pre-processing has limited the study of the relationship between intracellular ISDs concentrations and the occurrence of rejection. In this study, the extraction of ISDs in PBMCs was carried out by the liquid-liquid extraction with low temperature purification, without centrifugation. The lower limit of quantitation were 0.2 ng/mL for cyclosporine A, tacrolimus and sirolimus, 1.0 ng/mL for mycophenolic acid, and the within-run and between-run coefficient of variations were both less than 12.4 %. The calibration curves of mycophenolic acid had a linear range (ng/mL): 1.0-128.0 (r2 = 0.9992). The calibration curves of other three ISDs had a linear range (ng/mL): 0.2-20.48 (r2 > 0.9956). A total of 157 clinical samples were analyzed by the UPLC-MS/MS for ISDs concentration in blood or plasma ([ISD]blood or plasma) and the concentration within PBMCs ([ISD]PBMC). Although there was strong association between [ISD]PBMC and [ISD]blood or plasma, the large discrepancies between concentration within [ISD]blood or plasma and [ISD]PBMC were observed in a small proportion of clinical samples. The developed method with short analysis time and little amounts of blood sample can be successfully applied to therapeutic drug monitoring of ISDs in PBMCs for analysis of large numbers of clinical samples and is helpful to explore the clinical value of ISDs concentration in PBMCs.

Enhancing Concrete Mechanical Properties through Basalt Fibers and Calcium Sulfate Whiskers: Optimizing Compressive Strength, Elasticity, and Pore Structure.

To study the effects of basalt fibers (BFs), calcium sulfate whiskers (CSWs), and modified calcium sulfate whiskers (MCSWs) on the compressive strength and dynamic modulus of elasticity of concrete, this paper utilizes Mercury Intrusion Porosimetry (MIP) to measure the microstructure of concrete and calculate the fractal dimension of pore surface area. The results indicate that both CSWs and BFs can increase the compressive strength of concrete. CSWs can enhance the dynamic modulus of elasticity of concrete, while the effect of BFs on the dynamic modulus of elasticity is not significant. The improvement in compressive strength and dynamic modulus of elasticity provided by MCSWs is significantly greater than that provided by CSWs. Both CSWs and BFs can effectively improve the pore structure of concrete and have a significant impact on the surface fractal dimension. CSWs inhibit the formation of ink-bottle pores, while BFs increase the number of ink-bottle pores. Due to the ink-bottle pore effect, the fractal dimension of the capillary pore surface is generally greater than three, lacking fractal characteristics. The compressive strength and dynamic modulus of elasticity of concrete have a good correlation with the fractal dimensions of large pores and transition pores.

Molecular Characterization of Plant Volatile Compound Interactions with Cnaphalocrocis medinalis Odorant-Binding Proteins.

Odorant-binding proteins (OBPs) play important roles in the insect olfactory system since they bind external odor molecules to trigger insect olfactory responses. Previous studies have identified some plant-derived volatiles that attract the pervasive insect pest Cnaphalocrocis medinalis (Lepidoptera: Pyralidae), such as phenylacetaldehyde, benzyl acetate, 1-heptanol, and hexanal. To characterize the roles of CmedOBPs in the recognition of these four volatiles, we analyzed the binding abilities of selected CmedOBPs to each of the four compounds, as well as the expression patterns of CmedOBPs in different developmental stages of C. medinalis adult. Antennaes of C. medinalis adults were sensitive to the studied plant volatile combinations. Expression levels of multiple CmedOBPs were significantly increased in the antennae of 2-day-old adults after exposure to volatiles. CmedOBP1, CmedOBP6, CmedPBP1, CmedPBP2, and CmedGOBP2 were significantly up-regulated in the antennae of volatile-stimulated female and male adults when compared to untreated controls. Fluorescence competition assays confirmed that CmedOBP1 could strongly bind 1-heptanol, hexanal, and phenylacetaldehyde; CmedOBP15 strongly bound benzyl acetate and phenylacetaldehyde; and CmedOBP26 could weakly bind 1-heptanol. This study lays a theoretical foundation for further analysis of the mechanisms by which plant volatiles can attract C. medinalis. It also provides a technical basis for the future development of efficient plant volatile attractants of C. medinalis.