Psychiatric disorders have long and dominantly been regarded to be induced by disturbances of neuronal networks including synapses and neurotransmitters. Thus, the effects of psychotropic drugs such ...as antipsychotics and antidepressants have been understood to modulate synaptic regulation via receptors and transporters of neurotransmitters such as dopamine and serotonin. Recently, microglia, immunological/inflammatory cells in the brain, have been indicated to have positive links to psychiatric disorders. Positron emission tomography (PET) imaging and postmortem studies have revealed microglial activation in the brain of neuropsychiatric disorders such as schizophrenia, depression and autism. Animal models of neuropsychiatric disorders have revealed the underlying microglial pathologies. In addition, various psychotropic drugs have been suggested to have direct effects on microglia. Until now, the relationship between microglia, neurotransmitters and psychiatric disorders has not been well understood. Therefore, in this review, at first, we summarize recent findings of interaction between microglia and neurotransmitters such as dopamine, serotonin, norepinephrine, acetylcholine and glutamate. Next, we introduce up-to-date knowledge of the effects of psychotropic drugs such as antipsychotics, antidepressants and antiepileptics on microglial modulation. Finally, we propose the possibility that modulating microglia may be a key target in the treatment of various psychiatric disorders. Further investigations and clinical trials should be conducted to clarify this perspective, using animal in vivo studies and imaging studies with human subjects.
Circulating tumor nucleic acids (ctNAs) are promising biomarkers for minimally invasive cancer assessment. The FGFR2 : FAM76A fusion gene is one of the highly promising ovarian cancer biomarkers ...detectable in ctNAs. Herein, we introduce a new amplification‐free electrochemical assay for the detection of FGFR2 : FAM76A fusion gene in ctNAs extracted from ovarian cancer patients. The assay relies on the electrocatalytic activity of a new class of superparamagnetic graphene‐loaded iron oxide nanoparticles (GO‐NPFe2O3). After isolation and purification, the target RNA was directly adsorbed onto the GO‐NPFe2O3 surface through graphene‐RNA affinity interaction. The electrocatalytic signal was achieved by the reduction of surface‐attached ruthenium hexaammine(III) chloride which was further amplified by using the ferricyanide redox system. Our assay depicted an excellent detection sensitivity down to 1.0 fM, high specificity and excellent reproducibility (% RSD=<5 %, for n=3). The analytical performance of our method was validated with standard qRT‐PCR analysis. We believe that this newly developed assay would be practically applicable in clinical research.
Single crystalline W (tungsten) samples irradiated at 633, 963 and 1073 K by neutrons to a damage level of 0.1 dpa were exposed to a high-flux D (deuterium) plasma at 673, 873 and 973 K, ...respectively, in TPE (Tritium Plasma Experiment) at INL (Idaho National Laboratory). Deuterium desorption was analyzed by TDS (Thermal Desorption Spectroscopy), and D depth profiles were determined by NRA (Nuclear Reaction Analysis) at SNL (Sandia National Laboratories). HIDT (Hydrogen Isotope Diffusion and Trapping) simulation code was applied to evaluate D behavior for neutron-damaged W at higher temperature.
The D retention at depths up to 3 μm for the neutron-damaged sample at 673 K was two orders of magnitude larger than that for undamaged tungsten, and its D desorption spectrum had a single broad stage at around 900 K. As the neutron irradiation/plasma exposure temperature increased, D retention was largely reduced, and the desorption temperature was shifted to higher temperatures above 1100 K. The D depth profiles by NRA also showed D migration toward bulk by higher temperature irradiation, compared to undamaged W.
The HIDT simulation indicated that the major binding energy of D was changed from 1.43 eV to 2.07 eV at higher neutron irradiation and plasma exposure temperatures, suggesting that some vacancies and small vacancy clusters would aggregate to form larger voids, or depopulation of weak traps at high D plasma exposure temperatures. It can be said that more stable trapping sites played dominant roles in the D retention at higher neutron irradiation and plasma exposure temperature. The binding energy by HIDT simulation was almost consistent with the reported value by TMAP, but the consideration of not only total D retention measured by TDS but also D depth profile by NRA led to the more accurate D behavior in neutron-damaged W.
DT+ ion irradiation with energy of 0.5 and 1.0keV was performed on helium pre-irradiated tungsten and the amount of retained tritium and the long-term release of retained tritium in vacuum was ...investigated using an IP technique and BIXS. Tritium retention and long-term tritium release were significantly influenced by helium pre-irradiation. The amount of retained tritium increased until it reached 1×1017He/cm2, and at 1×1018He/cm2 it became smaller compared to 1×1017He/cm2. The amount of retained tritium in tungsten without helium pre-irradiation largely decreased after several weeks preservation in vacuum, and the long-term release rate during vacuum preservation was retarded by helium pre-irradiation. The results indicate that the long-term tritium release and the helium irradiation effect on it should be taken into account for more precise estimation of tritium retention in the long-term use of tungsten in fusion devices.
Objectives Acceptable limb salvage rates underlie the widespread use of endovascular therapy (EVT) for patients with critical limb ischemia (CLI) secondary to isolated infrapopliteal lesions; ...however, post-EVT delayed wound healing remains a challenge. Predictors of delayed wound healing and their use in risk stratification of EVT in patients with CLI due to isolated infrapopliteal lesions are explored. Methods This was a retrospective multicenter study. 871 consecutive critically ischemic limbs were studied. There was tissue loss in 734 patients (age: 71 ± 10 years old; 71% male) who had undergone EVT between April 2004 and December 2012. The wound healing rate after EVT was estimated by the Kaplan–Meier method. The association between baseline characteristics and delayed wound healing was assessed by the Cox proportional hazard model. Results Diabetes mellitus and regular dialysis were present in 75% (553/734) and 64% (476/734) of patients, respectively; 67% of limbs (585/871) had Rutherford class 5 CLI; 8% (67/871) of wounds were located in the heel only; 25% (219/871) of limbs had Rutherford 6 (involving not only the heel); and 42% (354/871) of wounds were complicated by infection. The rate of freedom from major amputation at 1 year reached 88%, whereas the wound healing rate was 67%. Median time to wound healing was 146 days. By multivariate analysis, non-ambulatory status (hazard ratio HR, 1.58; 95% confidence interval CI 1.31–1.91) serum albumin <3 g/dL (HR 1.42; 95% CI 1.08–1.86), Rutherford 6 (not only heel) (HR 1.68; 95% CI 1.33–2.14), wound infection (HR 1.24; 95% CI 1.03–1.50), EVT not based on angiosome concept (HR 1.28; 95% CI 1.06–1.55), and below the ankle (BTA) 0 vessel runoff after EVT (HR 1.45; 95% CI 1.14–1.86) were independent predictors of delayed wound healing. Conclusions Non-ambulatory status, low albumin level, Rutherford 6 (not only heel), wound infection, indirect intervention, and poor BTA runoff were independent predictors for delayed wound healing after EVT in patients with CLI secondary to infrapopliteal lesions, and their use in risk stratification allows estimation of the wound healing rate.
Fine tuning of cell signals by glycosylation Furukawa, Koichi; Ohkawa, Yuki; Yamauchi, Yoshio ...
Journal of Biochemistry/The journal of biochemistry,
06/2012, Volume:
151, Issue:
6
Journal Article
Peer reviewed
Open access
Carbohydrates on the glycoproteins and glycosphingolipids expressed on the cell surface membrane play crucial roles in the determination of cell fates by being involved in the fine tuning of cell ...signalling as reaction molecules in the front line to various extrinsic stimulants. In glycoproteins, modification of proteins is performed by substitution of sugar chains to one or multiple sites of individual proteins, leading to quantitative and qualitative changes of receptor functions in the cell membrane. As for glycosphingolipids, majority of them consist of two moieties, i.e. carbohydrates and ceramides, and are localized in the microdomains such as lipid rafts or detergent-resistant microdomains. They generate and/or modulate cell signals to determine the cell fates by interacting with various carbohydrate-recognizing proteins. Modes of glycosylation and mechanisms by which glycosylation is involved in the regulation of cell signals are now hot subjects in glycobiology.
Objective To investigate the relationship between body mass index (BMI) and long-term outcomes of patients with CLI after endovascular treatment (EVT). Design Retrospective multicenter study. ...Subjects 1088 consecutive patients (1306 limbs, mean age 72 ± 10 years) with CLI who underwent EVT for isolated infrapopliteal artery lesions were evaluated. These subjects were identified in the J-BEAT III registry. Methods The patients were divided into groups based on BMI <18.5 kg/m2 (underweight, n = 188; 219 limbs), 18.5 to 24.9 kg/m2 (normal weight, n = 718; 868 limbs), and >25.0 kg/m2 (overweight/obese, n = 182; 219 limbs). The endpoints were overall survival and freedom from major adverse limb events (MALE). Results The median follow up period was 1.5 years (range: 1 month–8.7 years). The 3 year overall survival rates were 33.3%, 61.2%, and 69.8% in underweight, normal, and overweight/obese patients, respectively. The survival rate was significantly lower in underweight patients and significantly higher in overweight/obese patients compared with patients of normal weight (both p < .0001). The 3 year rates of freedom from MALE did not differ significantly among the three groups (36.4%, 45.4%, and 52.3%, respectively, p = .32). Age, BMI <18.5 kg/m2 , heart failure, aortic valve stenosis, renal failure, triglyceride levels, serum albumin <3.0 g/dL, anticoagulant treatment, non-ambulatory status, and Rutherford 6 classification all were significantly associated with overall survival. Conclusions BMI has a complex correlation with mortality in patients with CLI after EVT for isolated infrapopliteal artery lesions. Underweight patients with CLI have an extremely poor prognosis. Such patients have many other factors associated with mortality, but low BMI was identified as an independent predictor of a poor prognosis in patients with CLI. Similarly, normal weight patients had a small but significant increase in mortality compared with overweight/obese patients.
The adsorption of Pt or Au on Ge(110) and subsequent annealing resulted in formation of well-ordered monodirectional nanowires (NWs) throughout the surface over a cm-scale. The NWs were aligned along ...the 11¯0 direction, independent of the surface reconstruction of Ge(110). Metastable-atom deexcitation spectroscopy of Pt-NWs revealed that the topmost part of the NWs comprised Ge atoms, suggesting the exchange of the Ge and metal atoms, leaving an ultrathin Ge layer on top of the NWs. The increase in the electronic density of state near the Fermi energy was observed from both the MDS and UPS spectra of the Pt-NWs, suggesting a metallicity of the NWs.
Summary
There is a lack of evidence regarding the optimal intra‐operative glycaemic level of patients with ornithine transcarbamylase deficiency to prevent cerebral oedema due to protein catabolism ...and hyperammonemia. We describe a case of a two‐year‐old girl with ornithine transcarbamylase deficiency who underwent cardiac surgery requiring cardiopulmonary bypass. A high‐dose dextrose infusion to prevent protein catabolism was given throughout surgery, which caused uncontrollable hyperglycaemia unresponsive to high‐dose insulin administration. Factors contributing to the hyperglycaemia may have included surgical stress, steroid administration and hypothermia. During invasive surgery, anaesthetists should carefully adjust the rates of dextrose and insulin infusions, guided by close monitoring of blood ammonia, glucose and lactate.
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