GABRD encoding a protein for extra- or peri-synaptic GABAA receptors is a susceptibility locus for generalized epilepsies

A major challenge in understanding complex idiopathic generalized epilepsies has been the characterization of their underlying molecular genetic basis. Here, we report that genetic variation within the GABRD gene, which encodes the GABAA receptor delta subunit, affects GABA current amplitude consistent with a model of polygenic susceptibility to epilepsy in humans. We have found a GABRD Glu177Ala variant which is heterozygously associated with generalized epilepsy with febrile seizures plus. We also report an Arg220His allele in GABRD which is present in the general population. Compared with wild-type receptors, alpha1beta2Sdelta GABAA receptors containing delta Glu177Ala or Arg220His have decreased GABAA receptor current amplitudes. As GABAA receptors mediate neuronal inhibition, the reduced receptor current associated with both variants is likely to be associated with increased neuronal excitability. Since delta subunit-containing receptors localize to extra- or peri-synaptic membranes and are thought to be involved in tonic inhibition, our results suggest that alteration of this process may contribute to the common generalized epilepsies.     

Vancomycin-resistant enterococcal bacteremia: comparison of clinical features and outcome between Enterococcus faecium and Enterococcus faecalis.

BACKGROUND AND PURPOSE: Vancomycin-resistant enterococci (VRE) have emerged as important nosocomial pathogens. This study was conducted to clarify the clinical features and outcome of patients with vancomycin-resistant enterococcal bacteremia. METHODS: Patients with vancomycin-resistant enterococcal bacteremia treated at a medical center in northern Taiwan between November 1998 and July 2006 were reviewed. Clinical and bacteriological characteristics of Enterococcus faecium and Enterococcus faecalis were compared. RESULTS: Twelve patients (6 males and 6 females) were included for analyses. The mean age was 69.3 years (range, 40 to 86 years), and 8 cases (66.7%) were older than 65 years. All patients had underlying disease. Two patients received total hip replacement before development of VRE bacteremia. Twelve patients had prior exposure to broad-spectrum antimicrobial therapy. Ten patients had prior intensive care unit stay and prior mechanical ventilation before VRE bacteremia. All of the patients (n = 12) had an intravascular catheter in place. Bacteremia was caused by E. faecalis in 4 patients and by E. faecium in eight. The portals of entry included urinary tract (8.3%), skin, soft tissue and bone (41.7%) and unknown sources (50.0%). E. faecium showed a higher rate of resistance to ampicillin and teicoplanin than E. faecalis (87.5% vs 0.0%, p=0.01). The 60-day mortality rate was higher in patients with E. faecium bacteremia than E. faecalis bacteremia (62.5% vs 0.0%), although statistical significance was not obtained (p=0.08). CONCLUSIONS: VRE bacteremia may have an impact on the mortality and morbidity of hospitalized patients. Patients with bacteremia caused by vancomycin-resistant E. faecium had a grave prognosis, especially immunosuppressed patients. The prudent use of antibiotics and strict enforcement of infection control may prevent further emergence and spread of VRE.     

遗传算法在256阵元相控阵高强度聚焦超声治疗系统多焦点控制中的应用

阐述了遗传算法优化多点超声聚焦的方法以及球面相控阵声场计算方法。对实验室研发的256阵元相控阵聚焦超声治疗系统作了简介。利用此遗传算法和声场计算方法，对轴上和离轴单焦点以及轴对称六焦点和非轴对称四焦点进行了256阵元相控阵的声场仿真，并观察了实验室研发的256阵元相控阵聚焦超声治疗系统作用于有机玻璃和透明仿体的实验结果。用遗传算法和声场计算方法的仿真和系统实验结果表明，此方法可在实际聚焦手术中准确地控制3维单焦点和3维多焦点。     

Defective Treg response in acute kidney injury was caused by a reduction in TIM-3+ Treg cells

Background: Despite years of research, the treatment of acute kidney injury (AKI) remains a significant challenge. Animal studies presented causal links between elevated regulatory T cell (Treg) response and better prognosis in AKI. Previous studies in mice and humans showed that TIM-3+ Treg cells were more potent than TIM-3- Treg cells. In this study, we investigated the role of TIM-3 in Treg in AKI patients.

Methods: Peripheral blood from AKI patients and healthy controls were gathered, and TIM-3+ Treg subset was examined.

Results: Compared to healthy controls, the AKI patients presented a significant upregulation in the frequency of circulating CD4+CD25+ T cells; however, the majority of this increase was from the CD4+CD25+TIM-3- subset, and the frequency of CD4+CD25+TIM-3+ T cells was downregulated in AKI patients. In both healthy controls and AKI patients, the CD4+CD25+TIM-3+ T cells expressed higher levels of Foxp3, and were more potent at expressing LFA-1, LAG-3, CTLA-4, IL-10 and TGF-β. In addition, the CD4+CD25+TIM-3+ T cells from both healthy controls and AKI patients presented higher capacity to suppress CD4+CD25- T cell proliferation than the CD4+CD25+TIM-3- T cells. Interestingly, the total CD4+CD25+ T cells from AKI patients presented significantly lower inhibitory capacity than those from healthy controls, indicating that the low frequency of CD4+CD25+TIM-3+ T cells was restricting the efficacy of the Treg responses in AKI patients.

Conclusions: We demonstrated that TIM-3 downregulation impaired the function of Treg cells in AKI. The therapeutic potential of CD4+CD25+TIM-3+ T cells in AKI should be investigated in future studies.     

教育心理学和教学效益相关性的研究

本研究在罗马尼亚Oradea大学医药学院进行，始于1998年，结束于2003年。研究的出发点为该学院的学生们提出不少的教师，包括一些国内外知名的学者和医生，因缺乏教育心理学知识，不能很好地理解学生，组织教学和传授知识。因此，本研究设置了问卷调查，学院向教员开设了教育心理学课程(1998年10月～1999年7月)，与学生和教师座谈，统计并比较学生的考试成绩，特别地跟踪研究全国年度(1999年～2003年)医学证书汇考结果。研究结果客观地证实了教育心理学能够提高学习(工作)效益和成果，因为教育心理学知识使得教师(和医师)更好地与学生(或病人)沟通、理解和组织、合作。     

Gemins modulate the expression and activity of the SMN complex

Reduction in the expression of the survival of motor neurons (SMN) protein results in spinal muscular atrophy (SMA), a common motor neuron degenerative disease. SMN is part of a large macromolecular complex (the SMN complex) that includes at least six additional proteins called Gemins (Gemin2-7). The SMN complex is expressed in all cells and is present throughout the cytoplasm and in the nucleus where it is concentrated in Gems. The SMN complex plays an essential role in the production of spliceosomal small nuclear ribonucleoproteins (snRNPs) and likely other RNPs. To study the roles of the individual proteins, we systematically reduced the expression of SMN and each of the Gemins (2-6) by RNA interference. We show that the reduction of SMN leads to a decrease in snRNP assembly, the disappearance of Gems, and to a drastic reduction in the amounts of several Gemins. Moreover, reduction of Gemin2 or Gemin6 strongly decreases the activity of the SMN complex. These findings demonstrate that other components of the SMN complex, in addition to SMN, are critical for the activity of the complex and suggest that Gemin2 and Gemin6 are potentially important modifiers of SMA as well as potential disease genes for non-SMN motor neuron diseases.     

Gene therapy in soft tissue reconstruction

Gene therapy is defined as the introduction of a therapeutic gene into a cell, whose expression can lead to a cure of a disease or offer a transient advantage for tissue growth and regeneration. The delivery of genes can be undertaken for a number of purposes, usually it is attempted to enhance or add a function to a cell or a tissue or to delete or reduce another function. In this brief overview we describe various vehicles and techniques that have been developed to deliver therapeutic genes into cells, such as viral vectors and physical/chemical gene delivery methods including naked DNA and particle-mediated gene transfer, the microseeding technique and the application of lipids. Furthermore we review the potential utility of gene therapy from the perspective of a reconstructive surgeon. Several tissues will be discussed, particularly muscle, tendon, nerve, bone, skin and wounds.     

Functional magnetic resonance imaging evidence for binocular interactions in human visual cortex

Using functional magnetic resonance imaging (fMRI), we explored the binocular interactions occurring when subjects viewed dichoptically presented checkerboard stimuli. A flickering radial checkerboard was presented to each eye of the subject, while T2*-weighted images were acquired over the visual cortex with gradient-echo, echoplanar sequences. We compared responses in striate and extrastriate visual cortex under four conditions: both eyes were stimulated at the same time (binocular condition), each eye was stimulated in alternation (monocular condition) or first the one eye then the other eye was stimulated (left eye first - right eye trailing, or vice versa). The results indicate that only the striate area, in and near the calcarine fissure, shows significant differences for these stimulation conditions. These differences are not evident in more remote extrastriate or associational visual areas, although the BOLD response in the stimulation-rest comparison was robust. These results suggest that the effect could be related to inhibitory interactions across ocular dominance columns in striate visual cortex.     

Synthesis and characterization of amphiphilic and microphase-separated graft copolymers, 1. Synthesis and bulk characterization of polystyrene-graft-ω-stearyl-poly(ethylene oxide)

Using the rigid and hydrophobic polystyrene (PS) chain as backbone, onto which flexible and hydrophilic stearyl-poly(ethylene oxide) (SPEO) chains are grafted, a new kind of amphiphilic, microphase-separated graft copolymer was synthesized using the macromonomer technique. Stearyl-poly(ethylene oxide) macromonomers with acryloyl end-group (SPEO-A) were prepared through an end-group exchange reaction of α-stearyl-ω-hydroxypoly(ethylene oxide) (SPEO-OH) and acryloyl chloride in the presence of triethylamine. The radical copolymerization of styrene with SPEO-A was carried out under various experimental conditions. Following a careful examination of their purity, the structure of the prepared copolymers was characterized by means of IR, ¹H NMR and GPC analyses. A new feasible method using first derivative UV spectrometry was developed for quantitative determination of the bulk composition of the graft copolymers. Copolymers with a wide range of bulk composition and satisfactory grafting degree were obtained.