Understanding the balance and integration of volume and synaptic transmission. Relevance for psychiatry

The major difference of synaptic transmission vs volume transmission (VT) is about the channels which are private in synaptic transmission (axons and terminals) but diffuse in VT represented by the channel plexus of the extracellular space and the CSF. There exist different forms of VT: extrasynatic, long distance, CSF and roamer type VT, the last one mediated via microvesicles (extracellular vesicles). Interleukin-1β (IL-1β) may produce inflammation and sickness behavior via long distance and CSF VT. The balance and integration of VT and synaptic transmission through receptor–receptor interactions in heteroreceptor complexes appears crucial for CNS communication and of high relevance for psychiatric diseases like schizophrenia, depression, cocaine addiction and anxiety. The allosteric receptor–receptor mechanism causes a marked rise of the repertoire of GPCR recognition, pharmacology, trafficking and signaling of the participating receptor protomers. We have introduced the moonlighting concept into the GPCR heteromer field, since GPCR protomers can change their function through the allosteric receptor–receptor interactions. This is achieved through changes in recognition, G protein selectivity, and signaling via other proteins involving, e.g., a switch from G proteins to β-arrestin through conformational changes in single or several strands of amino acids. It is of substantial interest to understand the role of altered receptor–receptor interactions as a mechanism for how neuroinflammatory processes can contribute to mental dysfunctions. It is hypothesized that chemokine and cytokine receptors may directly form heteroreceptor complexes with neuronal receptors known to be dysfunctional in schizophrenia and targets for antipsychotic drugs. Based on the current bioinformatic analysis performed we can postulate that chemokine receptor CXCR4 may directly interact with GABAB2 and NR2A subunits of the NMDAR, chemokine receptor CCR2 with NMDAR, GABAB1 subunit and GABAAR and cytokine receptor IL1R2 with GABAB1 subunit and NMDAR, all known to be involved in schizophrenia. Through the allosteric receptor–receptor interactions in such pathological heteroreceptor complexes the neuronal NMDA, GABAA and GABAB protomers may change their function (moonlighting) in neuronal networks of the brain. This process in neuroinflammation can contribute to positive, negative and/or cognitive symptoms of schizophrenia in line with the mild encephalitis hypothesis of schizophrenia. Neuroinflammation in schizophrenia may also disturb the integrative process of synaptic and volume transmission signals in glutamate synapses by altering kynurenines in the mammalian brain.     

Percutaneous Radiofrequency Ablation of Benign Thyroid Nodules Assisted by a Virtual Needle Tracking System

Our aim was to assess the feasibility and outcome of ultrasound (US)-guided percutaneous radiofrequency (RF) ablation of benign thyroid nodules assisted by a real-time virtual needle tracking (VT) system. Forty-five patients (34 females, mean age ± standard deviation (SD): 44 ± 16 y, range: 29–68 y) with 45 benign non-functioning thyroid nodules (mean volume ± SD: 13.5 ± 6.7 mL, range: 12–22 mL) underwent VT-assisted US-guided RF ablation. Nodule volume was evaluated before treatment and during 6-mo of follow-up. Complication rates and patient satisfaction after treatment were also evaluated. By use of the VT system, the tip of the RF electrode was identified during all ablation procedures. The overall mean volume reduction and complication rate were 72.6 ± 11.3% and 2.5%, respectively. Overall satisfaction at the 6-mo follow-up was rated by patients as positive in 42 cases (93%). The VT system could be useful in thyroid nodule ablation procedures because it is able to track the RF electrode tip even when the tip is obscured by the bubbles produced by the ablative process. VT-assisted RF ablation can be a tolerable, non-surgical treatment for patients with benign non-functioning thyroid nodules.     

应用超高分辨力小动物超声影像系统三维重建技术测量严重联合免疫缺陷小鼠卵巢体积

目的 探讨超高分辨力小动物超声影像系统三维成像技术测量严重联合免疫缺陷（SCID）小鼠卵巢体积的方法及应用价值。方法 选用11只C.B17/SCID纯系雌性小鼠,应用超高分辨力小动物专用超声影像系统及45 MHz探头,以三维成像体积测量技术测量SCID小鼠卵巢的体积,将所得卵巢体积与二维成像进行比较和相关分析。结果 应用超高分辨力小动物超声影像系统获得了清晰的SCID小鼠卵巢的二维平面及三维立体图像。二维超声与三维超声测量的SCID小鼠卵巢体积分别为（5.26±0.51）mm³和（5.47±0.58）mm³（P>0.05）,二者呈高度正相关（r=0.84,P<0.05）。结论 超高分辨力小动物三维超声成像体积测量技术无创,操作简便,能够精确测量小鼠卵巢体积,可作为在体研究卵巢癌小动物模型的重要实验工具。     

Experimental and FE displacement and polymerization stress of bonded restorations as a function of the C-Factor,volume and substrate stiffness

Objectives

To determine the free surface displacement of resin-composite restorations as a function of the C-Factor, volume and substrate stiffness, and to compare the results with interfacial stress values evaluated by finite element analysis (FEA).

Methods

Surface displacement was determined by an extensometer using restorations with 4 or 6 mm diameter and 1 or 2 mm depth, prepared in either bovine teeth or glass. The maximum displacement of the free surface was monitored for 5 min from the start of photoactivation, at an acquisition rate of 1 s⁻¹. Axisymmetric cavity models were performed by FEA. Structural stiffness and maximum stresses were investigated.

Results

For glass, displacement showed a stronger correlation with volume (r = 0.771) than with C-Factor (r = 0.395, p < 0.001 for both). For teeth, a stronger correlation was found with C-Factor (r = 0.709; p < 0.001) than with volume (r = 0.546, p < 0.001). For similar dimensions, stress and displacement were defined by stiffness. Simultaneous increases in volume and C-Factor led to increases in stress and surface displacement. Maximum stresses were located at the cavosurface angle, internal angle (glass) and at the dentine–enamel junction (teeth). The displacement of the restoration's free surface was related to interfacial stress development.

Conclusions

Structural stiffness seems to affect the shrinkage stress at the tooth/resin-composite interface in bonded restorations. Deep restorations are always problematic because they showed high shear stress, regardless of their width. FEA is the only tool capable of detecting shear stress due to polymerization as there is still no reliable experimental alternative.     

Donor milk volume and characteristics of donors and their children

Background

Little is known regarding the effect of the characteristics of donors and their children on the volume of donor milk delivered to a human milk bank (HMB).

Aims

Our study aimed to determine the relationship between different social and demographic variables of donors and their infants with the volume of human milk delivered.

Methods

We included donors accepted at the Hospital Doce de Octubre HMB from January 1st, 2009 until April 31st, 2013, and who had finished their donation. Data of social and demographic characteristics of the donors and their children, and the total volume of DHM given were obtained from our HMB database. Included variables were previous donors, donor age, number of children, place of residence, gestational age of the infant at birth, child's age at the start of the donation, hospital admission, and death of the infant.A linear regression model was used to study the relationship between independent variables that were significant in bivariate analysis and the volume of donated milk.

Results

A total of 415 donations from 391 women were included. The median volume of milk delivered was 3.1 l (IQR—interquartile range—1.3–8.3 l). In the linear regression model, previous donors, smaller gestational age of children, and the start of donation at earlier stages of lactation were associated with a larger quantity of HMB donated (p ≤ 0.001).

Conclusion

Previous donors, smaller gestational age of children, and the start of donation at earlier stages of lactation are associated with a larger quantity of milk donated to the HMB.     

Validation of Simple Quantification Methods for 18F-FP-CIT PET Using Automatic Delineation of Volumes of Interest Based on Statistical Probabilistic Anatomical Mapping and Isocontour Margin Setting

Purpose

¹⁸F-FP-CIT positron emission tomography (PET) is an effective imaging for dopamine transporters. In usual clinical practice, ¹⁸F-FP-CIT PET is analyzed visually or quantified using manual delineation of a volume of interest (VOI) for the striatum. In this study, we suggested and validated two simple quantitative methods based on automatic VOI delineation using statistical probabilistic anatomical mapping (SPAM) and isocontour margin setting.

Methods

Seventy-five ¹⁸F-FP-CIT PET images acquired in routine clinical practice were used for this study. A study-specific image template was made and the subject images were normalized to the template. Afterwards, uptakes in the striatal regions and cerebellum were quantified using probabilistic VOI based on SPAM. A quantitative parameter, Q_SPAM, was calculated to simulate binding potential. Additionally, the functional volume of each striatal region and its uptake were measured in automatically delineated VOI using isocontour margin setting. Uptake-volume product (Q_UVP) was calculated for each striatal region. Q_SPAM and Q_UVP were compared with visual grading and the influence of cerebral atrophy on the measurements was tested.

Results

Image analyses were successful in all the cases. Both the Q_SPAM and Q_UVP were significantly different according to visual grading (P < 0.001). The agreements of Q_UVP or Q_SPAM with visual grading were slight to fair for the caudate nucleus (κ = 0.421 and 0.291, respectively) and good to perfect to the putamen (κ = 0.663 and 0.607, respectively). Also, Q_SPAM and Q_UVP had a significant correlation with each other (P < 0.001). Cerebral atrophy made a significant difference in Q_SPAM and Q_UVP of the caudate nuclei regions with decreased ¹⁸F-FP-CIT uptake.

Conclusion

Simple quantitative measurements of Q_SPAM and Q_UVP showed acceptable agreement with visual grading. Although Q_SPAM in some group may be influenced by cerebral atrophy, these simple methods are expected to be effective in the quantitative analysis of ¹⁸F-FP-CIT PET in usual clinical practice.     

PICCO监测在重症感染患者CRRT容量管理中的应用与护理措施

目的探讨脉波轮廓温度稀释连续心排量测量技术(PICCO)在重症感染患者连续性肾脏替代治疗(CRRT)容量管理中的应用价值及护理措施。方法行CRRT治疗的重症感染患者25例,应用PICCO技术,监测全心舒张末期容积(GEDV)、胸腔内血容积(ITBV)、中心静脉压(CVP)、系统血管阻力指数(SVRI)等各参数,于CRRT治疗前、治疗12、24、72h采集数据;观察治疗前后乳酸、碱剩余、APACHEⅡ评分的变化。结果 25例患者均顺利完成CRRT治疗,未发现相关不良耐受反应;治疗12h时,严重感染患者的GEDV、ITBV和SVRI分别为(626.12±61.42)ml/m2、(649.64±87.18)ml/m2、(1957.28±139.69)dyne.s.cm-5/m2,与治疗前比较差异均有统计学意义(P<0.01),在随后的治疗过程中均出现稳定的升高;治疗前后各时点CVP差异无统计学意义;治疗后72h,乳酸水平、碱剩余、APACHEⅡ评分分别为(3.65±1.02)mmol/L、(5.35±0.96)mmol/L、(25.00±3.00)分,较治疗前差异有统计学意义(P<0.05)。结论 PICCO的容量指标可以准确、可靠地评估患者的容量状况,指导重症感染患者的CRRT容量管理。     

Patient specific tumor growth prediction using multimodal images

Personalized tumor growth model is valuable in tumor staging and therapy planning. In this paper, we present a patient specific tumor growth model based on longitudinal multimodal imaging data including dual-phase CT and FDG-PET. The proposed Reaction–Advection–Diffusion model is capable of integrating cancerous cell proliferation, infiltration, metabolic rate and extracellular matrix biomechanical response. To bridge the model with multimodal imaging data, we introduce Intracellular Volume Fraction (ICVF) measured from dual-phase CT and Standardized Uptake Value (SUV) measured from FDG-PET into the model. The patient specific model parameters are estimated by fitting the model to the observation, which leads to an inverse problem formalized as a coupled Partial Differential Equations (PDE)-constrained optimization problem. The optimality system is derived and solved by the Finite Difference Method. The model was evaluated by comparing the predicted tumors with the observed tumors in terms of average surface distance (ASD), root mean square difference (RMSD) of the ICVF map, average ICVF difference (AICVFD) of tumor surface and tumor relative volume difference (RVD) on six patients with pathologically confirmed pancreatic neuroendocrine tumors. The ASD between the predicted tumor and the reference tumor was 2.4 ± 0.5 mm, the RMSD was 4.3 ± 0.4%, the AICVFD was 2.6 ± 0.6%, and the RVD was 7.7 ± 1.3%.     

Albumin Leakage in Online Hemodiafiltration,More Convective Transport,More Losses?

Online hemodiafiltration (OL‐HDF) has now demonstrated some benefits in reducing mortality. It seems that rising convective volumes improve the outcomes, but the risks of it, such as albumin leakage, are not well defined yet. The aim of the present study was to evaluate the albumin leakage using two different filters with 20 and 30 L of post‐dilution OL‐HDF. In this cross‐sectional study, 20 prevalent patients receiving post‐dilution OL‐HDL were included. We analyzed two dialyzers: FX1000, FMC and Polyflux 210H, Gambro. During four consecutive dialysis sessions, monitors were programmed using control‐volume to obtain 20 or 30 L with both dialyzers. We collected albumin samples of the effluent at 5, 15, 30, 45 and 60 min and performed area under the curve (AUC) determinations for evaluating the losses. Mean patient age was 60 ± 9 years, and 70% were men. Albumin leakage was significant higher with Polyflux 210H when compared to FX 1000 FMC. A convective volume of 30 L produced greater albumin leakage than 20 L with both filters, though only with the FX 1000 FMC was it significant (minimum albumin leakage during first hour with FX 1000 FMC 20 L: 79.2 [0.0–175.7] mg; 30 liters: 403.3 [63.5–960.7] mg; with PF 210 Gambro 20 L: 869.1 [420.0–3214.7] mg; 30 L: 1841.7 [443.8–3417.5] mg). During OL‐HDF, convective transport causes albumin leakage at least during the first hour. The albumin concentration in the effluent differs according to the type of filter used and the convective volume.