Development and preliminary validation of the PC‐SAD5, a screener‐derived short depression severity measure

Background The prevalence of depressive disorders is high among patients with skin disease. The PC‐SAD is a 37‐item self‐administered depression screening questionnaire that has been validated in dermatological patients. Objective The aim of this study was to develop and validate a brief depression severity instrument derived from the PC‐SAD that can be used to assess severity and monitor ongoing clinical course. Methods Two patient samples participated in the study: 72 adult dermatological inpatients and 73 adults attending six primary care practices. Psychiatric assessment included the Structured Clinical Interview for DSM‐IV and an 18‐item version of the PC‐SAD; moreover, dermatological patients completed the Patient Health Questionnaire depression scale (PHQ‐9), while primary care patients were administered the Montgomery‐Asberg Depression Rating Scale (MADRS). A subset of five PC‐SAD items showing the best psychometric properties were selected, and the reliability and validity of the resulting instrument (PC‐SAD5) were examined. Results The PC‐SAD5 showed satisfactory internal consistency in both samples. There was a high correlation between PC‐SAD5 and PHQ‐9 and MADRS scores. Multiple regression analysis revealed a gradient of PC‐SAD5 scores from patients with no mental disorder, those with milder forms of depression, to those with Major Depressive Disorder. Similar results were observed for the 18‐item version of the PC‐SAD. Conclusion The availability of valid and reliable continuous measures of depression severity derived from the PC‐SAD extends its field of application from depression screening to use as a follow‐up measure of depression severity in routine clinical practice. A validated very short instrument such as the PC‐SAD5 may have substantial clinical value.     

Analysis of parametric histogram from dynamic contrast‐enhanced MRI: application in evaluating brain tumor response to radiotherapy

Dynamic contrast‐enhanced MRI (DCE MRI) has been used to study tumor response to treatment for many years. In this study, the modified full width at half‐maximum (mFWHM), calculated from the wash‐in slope histogram, is proposed as a parameter for the evaluation of changes in tumor heterogeneity which respond to radiotherapy. Twenty‐five patients with brain tumors were evaluated and divided into the nonresponder group (n = 11) and the responder group (n = 14) according to the Response Evaluation Criteria in Solid Tumors (RECIST). All selected tumors were evaluated by mFWHM ratios of post‐ to pre‐therapy (the ratio was defined as the therapeutic mFWHM ratio, TMR). The changes in kurtosis of the histograms and the averaged K^trans within a tumor were also calculated for comparison. The receiver operating characteristic analysis and Kaplan–Meier curves were used to examine the diagnosis ability. The TMR values were significantly higher in nonresponders than in responders (p < 0.001). When compared with the other two parameters, the proposed method also demonstrated better sensitivity and specificity. When adopting the TMR for the estimation of prognosis after therapy, there was a significant difference between the population survival curves. In conclusion, the derived mFWHM reflects tumor heterogeneity, and the ability to depict patient survival probability from TMR corresponds well with that from RECIST. The results reveal that, in brain tumors, progression may be exhibited not only by tumor size, but also by tumor heterogeneity. Copyright © 2012 John Wiley & Sons, Ltd.     

Transcranial Focused Ultrasound Enhances Sensory Discrimination Capability through Somatosensory Cortical Excitation

Low-intensity transcranial focused ultrasound (tFUS) has emerged as a non-invasive brain neuromodulation tool with high spatial specificity. Previous studies attributed tFUS-enhanced sensory performance to the ultrasound-induced inhibitory neural effects. However, to date there is no direct evidence validating the neural mechanism underlying ultrasound-mediated somatosensory enhancement. In this study, healthy human subjects (N = 9) were asked to perform tactile vibration frequency discrimination tasks while tFUS was directed onto the primary somatosensory cortex. During this task, we simultaneously recorded 64-channel electroencephalography (EEG) signals and investigated the brain responses at both EEG sensors and source domains by means of electrophysiological source imaging (ESI). The behavioral results indicated that the subjects' discrimination ability was improved by tFUS with an increased percentage of correct responses. EEG and ESI results revealed that tFUS neuromodulation was able to improve sensory discrimination capability through excitatory effects at the targeted sensory cortex.     

Fast volumetric imaging of bound and pore water in cortical bone using three‐dimensional ultrashort‐TE (UTE) and inversion recovery UTE sequences

We report the three‐dimensional ultrashort‐TE (3D UTE) and adiabatic inversion recovery UTE (IR‐UTE) sequences employing a radial trajectory with conical view ordering for bi‐component T₂* analysis of bound water (T₂*^BW) and pore water (T₂*^PW) in cortical bone. An interleaved dual‐echo 3D UTE acquisition scheme was developed for fast bi‐component analysis of bound and pore water in cortical bone. A 3D IR‐UTE acquisition scheme employing multiple spokes per IR was developed for bound water imaging. Two‐dimensional UTE (2D UTE) and IR‐UTE sequences were employed for comparison. The sequences were applied to bovine bone samples (n = 6) and volunteers (n = 6) using a 3‐T scanner. Bi‐component fitting of 3D UTE images of bovine samples showed a mean T₂*^BW of 0.26 ± 0.04 ms and T₂*^PW of 4.16 ± 0.35 ms, with fractions of 21.5 ± 3.6% and 78.5 ± 3.6%, respectively. The 3D IR‐UTE signal showed a single‐component decay with a mean T₂*^BW of 0.29 ± 0.05 ms, suggesting selective imaging of bound water. Similar results were achieved with the 2D UTE and IR‐UTE sequences. Bi‐component fitting of 3D UTE images of the tibial midshafts of healthy volunteers showed a mean T₂*^BW of 0.32 ± 0.08 ms and T₂*^PW of 5.78 ± 1.24 ms, with fractions of 34.2 ± 7.4% and 65.8 ± 7.4%, respectively. Single‐component fitting of 3D IR‐UTE images showed a mean T₂*^BW of 0.35 ± 0.09 ms. The 3D UTE and 3D IR‐UTE techniques allow fast volumetric mapping of bound and pore water in cortical bone. Copyright © 2016 John Wiley & Sons, Ltd.     

Open-top axially swept light-sheet microscopy

Open-top light-sheet microscopy (OT-LSM) is a specialized microscopic technique for high throughput cellular imaging of large tissue specimens including optically cleared tissues by having the entire optical setup below the sample stage. Current OT-LSM systems had relatively low axial resolutions by using weakly focused light sheets to cover the imaging field of view (FOV). In this report, open-top axially swept LSM (OTAS-LSM) was developed for high-throughput cellular imaging with improved axial resolution. OTAS-LSM swept a tightly focused excitation light sheet across the imaging FOV using an electro tunable lens (ETL) and collected emission light at the focus of the light sheet with a camera in the rolling shutter mode. OTAS-LSM was developed by using air objective lenses and a liquid prism and it had on-axis optical aberration associated with the mismatch of refractive indices between air and immersion medium. The effects of optical aberration were analyzed by both simulation and experiment, and the image resolutions were under 1.6µm in all directions. The newly developed OTAS-LSM was applied to the imaging of optically cleared mouse brain and small intestine, and it demonstrated the single-cell resolution imaging of neuronal networks. OTAS-LSM might be useful for the high-throughput cellular examination of optically cleared large tissues.     

Compensated active noise cancellation earphone for audiometric screening tests in noisy environments

Abstract

Objective: This study investigated hearing screening tests by using a custom-designed compensated hybrid active noise cancellation (ANC) earphone and compared it with TDH39 and Audiocups audiometric earphones under conditions of quiet, 45?dB HL masking narrowband, wideband speech-shaped, and white noise.

Design: The hearing screening tests were conducted to characterise the shifts of screening results under noisy conditions, and real-ear attenuations at thresholds were assessed to quantify real-ear noise reduction performance.

Study sample: Twenty-four normal-hearing adults, aged 20–25?years, participated in this study.

Results: The ANC earphone exhibited significantly lower/better mean screening results than those of the TDH39 earphone at 250 and 500?Hz and those of the Audiocups earphone at 250?Hz under conditions of narrowband, speech-shaped, and white noise. Compared with the TDH39 earphone at 250 and 500?Hz, applying a hybrid ANC earphone reduced the shifts in screening results by 14.2 and 12.3?dB, respectively, under the narrowband noise condition.

Conclusion: This study demonstrated that the compensated hybrid ANC earphone provided lower shifts of screening results than the TDH39 and Audiocups earphones and that it was capable of screening at 250 and 500?Hz from 20?dB HL under 45?dB HL masking narrowband and wideband noise.     

Gab1 is essential for membrane translocation,activity and integrity of mTORCs after EGF stimulation in urothelial cell carcinoma

Urothelial carcinoma is the most common type of malignancy in long-term dialysis patients and kidney transplant recipients in Taiwan. mTORCs (mammalian target of rapamycin complexes) and EGF are important in urothelial carcinoma. To identify the regulation of mTORCs upon EGF stimulation is necessary. mTOR integrates signals from growth factors via mTOR Complex 1 (mTORC1) and mTOR Complex 2 (mTORC2). The mechanism of mTORC1 action has been widely studied; however, the regulation of mTORC2 has not been well studied. Here, we demonstrate that Gab1 is an important upstream regulator in EGF-mediated activation of mTORCs. In our study, we confirm that mTORCs translocate from the cytoplasm to the plasma membrane via the PH domain of Gab1 upon EGF stimulation. Moreover, Gab1 associates with mTORCs. This association stabilizes the integrity of mTORCs and induces mTORC activity. Compared to normal bladder tissue, the expression of Gab1 and activity of mTORCs are elevated in urothelial carcinoma. Collectively, our results suggest that Gab1 is an essential regulator of the EGF-mediated mTORC pathways and may potentially be used as a biomarker for urothelial carcinoma to predict diagnosis and drug response.