Disproportionate Reduction of Serotonin Transporter May Predict the Response and Adherence to Antidepressants in Patients with Major Depressive Disorder: A Positron Emission Tomography Study with 4-[18F]-ADAM

Background:

Many lines of evidence suggest the role of serotonin transporter (SERT)-mediated reuptake of serotonin in the pathophysiology and treatment of major depressive disorder (MDD). This study aimed to examine whether the pretreatment of SERT binding potential or SERT binding ratio between terminal projection regions relative to the midbrain raphe nuclei was associated with treatment outcomes to SERT-targeted antidepressants.

Methods:

We recruited 39 antidepressant-naïve patients with MDD and 39 heathy controls. Positron emission tomography with N,N-dimethyl-2-(2-amino-4-[¹⁸F]fluorophenylthio)benzylamine (4-[¹⁸F]-ADAM) was used to measure in vivo SERT availability prior to antidepressant treatment. The 21-item Hamilton Depression Rating Scale (HDRS) was use to assess the severity of depression from baseline to week 6. All the patients with MDD had HDRS scores of 18 or more.

Results:

Pretreatment SERT binding in the thalamus and striatum positively correlated with an early reduction in HDRS scores at week 3. Nonresponders and dropout patients showed a proportionate reduction in SERT binding in the terminal projection regions and midbrain compared to healthy controls. In contrast, a disproportionate reduction in SERT binding in the terminal projection regions relative to midbrain was observed in responders.

Conclusions:

The results of this study suggested that a disproportionate reduction in SERT binding between terminal projection regions and midbrain may predict better treatment outcomes in patients with MDD.     

Improved renal function 12 months after bariatric surgery

BackgroundObesity is a risk factor for developing chronic kidney disease (CKD) that may be improved with bariatric surgical weight reduction. The objective of this study was to investigate changes in the glomerular filtration rate (GFR) in severely obese patients 1 year after bariatric surgery.MethodsGFR was measured in 233 severely obese patients before and more than 12 months after bariatric surgery. Patients were separated by baseline GFR: hyperfiltration (GFR>125 mL/min), normal (GFR 125–90 mL/min), CKD stage 2 (GFR 89–60 mL/min), and CKD stage 3 (59–30 mL/min). The groups were reanalyzed 12 months after bariatric surgery.ResultsOf the 233 patients, 61 (26.2%) had hyperfiltration, 127 (54.5%) were normal, 39 (16.7%) had CKD stage 2, and 6 (2.6%) had CKD stage 3. The mean GFR was 146.4±17.1 mL/min in the hyperfiltration group, 105.7±9.6 mL/min in the normal group, 76.8±16.7 mL/min in the CKD stage 2 group, and 49.5±6.6 mL/min in the CKD stage 3 group. The mean GFR 1 year after weight loss surgery decreased to 133.9±25.7 mL/min in the hyperfiltration group, increased to 114.2±22.2 mL/min in the normal group, increased to 93.3±20.4 mL/min in the CKD stage 2 group, and increased to 66.8±19.3 mL/min in the CKD stage 3 group.ConclusionsAbnormal renal function was common in severely obese patients. Bariatric surgery-induced weight loss had positive effects on renal function at 1 year after surgery.     

Mucin 15 is expressed in human placenta and suppresses invasion of trophoblast-like cells in vitro

BACKGROUND: Trophoblast invasion is crucial for the development of normal placentas. Mucins are suggested to be involved in cancer invasion. However, the function of mucins in trophoblast invasion has never been reported. This study was to investigate the expression of mucin (MUC) 15 in human placenta and its role in trophoblast invasion. METHODS: MUC15 mRNA in human tissues was analyzed by Northern blot. MUC15 mRNA and protein in human placenta were detected by real-time RT-PCR and Western blot, respectively. The distribution of MUC15 was revealed by immunohistochemistry. The effects of MUC15 on trophoblast invasion in vitro were analyzed by matrigel invasion assay in human choriocarcinoma JAR and JEG-3 cells. RESULTS: MUC15 was expressed most highly in human placenta. MUC15 mRNA and protein increased with gestational age (P < 0.05, first versus third trimester). Immunohistochemistry showed that MUC15 protein was expressed by both cytotrophoblasts and syncytiotrophoblasts, especially at the apical membrane of syncytiotrophoblasts. In addition, MUC15 was found to be present in the glandular epithelium of the decidua. Overexpression of MUC15 substantially decreased matrigel invasion of JAR and JEG-3 cells by 87.5 +/- 1.1 and 83.8 +/- 5.7%, respectively, versus control, which was closely associated with an increase in mRNA expression of tissue inhibitors of metalloproteinases (TIMP)-1 and TIMP-2. Knockdown of MUC15 with small interfering RNA significantly reversed these effects (P < 0.05). CONCLUSIONS: Differential expression of MUC15 in human placentas may play a critical role in the regulation of trophoblast invasion.     

Effects of bihemispheric transcranial direct current stimulation on motor recovery in subacute stroke patients: a double-blind,randomized sham-controlled trial

Persons with Parkinson’s disease (PD) often exhibit difficulties with dexterity during the performance of activities of daily living (ADL), inter alia due to dysfunctional supplementary motor area (SMA). Combined intermittent theta-burst stimulation (iTBS) over the SMA followed by video game-based training (VBT) may therefore improve dexterity related ADL. The VBT may induce high flow levels related to high performance during the training. The aim of this study is to evaluate the feasibility of a combined iTBS-VBT intervention in persons with PD. A total of nine persons with PD (mean age 63.3?±?8.76 years) with self-reported difficulties with dexterity related ADL were included in this pilot iTBS-VBT study. All participants received either iTBS or sham stimulation over the SMA followed by a 45-min VBT, three times a week for a total of three weeks. Feasibility was measured by means of the adherence rate and the system usability (System Usability Scale). Moreover, flow was measured after the last VBT session. Adherence rate was excellent with 100%. High system usability scores (i.e., mean 80%, range 55–97.5) and a significant Spearman’s correlation with the Flow State Scale (r?=?.762, p?=?.017) further point to the high feasibility of the VBT. Neither demographic variables nor difficulties in dexterity related ADL affected the usability of the VBT. This study demonstrates the high feasibility of a combined iTBS-VBT intervention. Moreover, the level of self-reported usability was related to flow experience. Whether this kind of combined iTBS-VBT intervention improves dexterity will be evaluated in a randomized controlled trial. Trial registration clincaltrials.gov NCT04699149, date of registration 1. June 2021     

Structured reporting in radiologic education – Potential of different PI-RADS versions in prostate MRI controlled by in-bore MR-guided biopsies

Objectives:To evaluate the efficiency of structured reporting in radiologic education – based on the example of different PI-RADS score versions for multiparametric MRI (mpMRI) of the prostate.Methods:MpMRI of 688 prostate lesions in 180 patients were retrospectively reviewed by an experienced radiologist and by a student using PI-RADS V1 and V2. Data sets were reviewed for changes according to PI-RADS V2.1. The results were correlated with results obtained by MR-guided biopsy. Diagnostic potency was evaluated by ROC analysis. Sensitivity, specificity and correct-graded samples were evaluated for different cutpoints. The agreement between radiologist and student was determined for the aggregation of the PI-RADS score in three categories. The student’s time needed for evaluation was measured.Results:The area under curve of the ROC analysis was 0.782/0.788 (V1/V2) for the student and 0.841/0.833 (V1/V2) for the radiologist. The agreement between student and radiologist showed a Cohen‘s weighted κ coefficient of 0.495 for V1 and 0.518 for V2. Median student’s time needed for score assessment was 4:34 min for PI-RADSv1 and 2:00 min for PI-RADSv2 (p < 0.001). Re-evaluation for V2.1 changed the category in 1.4% of all ratings.Conclusion:The capacity of prostate cancer detection using PI-RADS V1 and V2 is dependent on the reader‘s experience. The results from the two observers indicate that structured reporting using PI-RADS and, controlled by histopathology, can be a valuable and quantifiable tool in students‘ or residents’ education. Herein, V2 was superior to V1 in terms of inter-observer agreement and time efficacy.Advances in knowledge:Structured reporting can be a valuable and quantifiable tool in radiologic education. Structured reporting using PI-RADS can be used by a student with good performance. PI-RADS V2 is superior to V1 in terms of inter-observer agreement and time efficacy.     

Sensitivity and specificity of four assays to detect human T− lymphotropic virus type I or type I/II antibodies

BACKGROUND: Assays that detect human T-lymphotropic virus type I and type II antibody (HTLV-I/II) are widely used in the routine screening of blood donors. STUDY DESIGN AND METHODS: Four commercially available anti-HTLV-I (Fujirebio and Organon Teknika) or -HTLV-I/II assays (Murex and Ortho) were evaluated in various serum panels: A) HTLV-I-positive specimens (n = 41), confirmed by Western blot and polymerase chain reaction; B) a commercially available anti-HTLV-I/II panel; C) serial dilutions of sera from HTLV-I-positive individuals (n = 30), confirmed by immunofluorescence assay and Western blot: D) serial dilutions of HTLV-II-positive blood donors (n = 20), confirmed by Western blot and polymerase chain reaction, and E) sera from first-time blood donors (n = 1055). RESULTS: All four assays elicited reactions in all 82 HTLV-I- positive samples in Panels A, B, and C. Of 32 HTLV-II-positive specimens in Panels B and D, 31 (96.9%) reacted in the Organon Teknika assay and all 32 reacted in the remaining tests. Probit analysis of test results in Panels C and D indicated that the Fujirebio test was the most sensitive assay, followed by Organon Teknika, Ortho, and Murex. The specificities of Fujirebio, Murex, Organon Teknika, and Ortho tests in 1055 first-time blood donors were 99.9, 100, 99.6, and 99.9 percent, respectively. CONCLUSION: All four studied assays for detecting HTLV-I or HTLV-I/II antibodies are appropriate as screening tests.     

股方肌肌骨瓣植入治疗成人股骨头缺血性坏死

目的:目前成人股骨头缺血性坏死的手术方法较多,但远期疗效大多不肯定。股方肌肌骨瓣植入术可以治疗成人股骨头缺血性坏死,但需验证其近远期疗效。方法:选择2001-01/2007-01铜川市矿务局中心医院骨科收治的股方肌肌骨瓣植入治疗股骨头坏死患者15例(18髋),均知情同意。术中暴露股方肌及其在股骨近端的附着点,于附着点处凿取骨瓣,骨瓣为4cm×1.5cm×1.0cm的长方形,将骨瓣插入股骨头内,远端用可吸收骨钉固定。术后3,6,12,24个月门诊复查拍患髋正位和蛙式位X射线片,根据临床查体和X射线片表现将手术效果分为优、良、差3级。结果:全部患者均获随访,随访时间4～36个月。近期疗效满意,出院时疼痛症状均缓解,未见手术相关并发症。中远期随访结果优10髋,良6髋,差2髋,优良率88.9%。结论:股方肌肌骨瓣植入术治疗成人股骨头缺血性坏死近远期疗效确切,手术操作相对简单。