Astrocytic processes compensate for the apparent lack of GABA transporters in the axon terminals of cerebellar Purkinje cells.

The aim of the present study was to evaluate the expression of two high affinity GABA transporters (GAT-1 and GAT-3) in the rat cerebellum using immunocytochemistry and affinity purified antibodies. GAT-1 immunoreactivity was prominent in punctate structures and axons in all layers of the cerebellar cortex, and was especially prominent around the somata of Purkinje cells. In contrast, the deep cerebellar nuclei showed few if any GAT-1 immunoreactive puncta. Weak GAT-3 immunoreactive processes were present in the cerebellar cortex, whereas GAT-3 immunostaining was prominent around the somata of neurons in the deep cerebellar nuclei. Electron microscopic preparations of the cerebellar cortex demonstrated that GAT-1 immunoreactive axon terminals formed symmetric synapses with somata, axon initial segments and dendrites of Purkinje cells and the dendrites of granule cells. Astrocytic processes in the cerebellar cortex were also immunolabeled for GAT-1. However, Purkinje cell axon terminals that formed symmetric synapses with neurons in the deep cerebellar nuclei lacked GAT-1 immunoreactivity. Instead, weak GAT-1 and strong GAT-3 immunoreactivities were expressed by astrocytic processes that enveloped the Purkinje cell axon terminals. In addition, GAT-3-immunoreactivity appeared in astrocytic processes in the cerebellar cortex. These observations demonstrate that GAT-1 is localized to axon terminals of three of the four neuronal types that were previously established as being GABAergic, i.e. basket, stellate and Golgi cells. GAT-1 and GAT-3 are expressed by astrocytes. The failure to identify a GABA transporter in Purkinje cells is consistent with previous data that indicated that Purkinje cells lacked terminal uptake mechanisms for GABA. The individual glial envelopment of Purkinje cell axon terminals in the deep cerebellar nuclei and the dense immunostaining of GAT-3, and to a lesser extent GAT-1, expressed by astrocytic processes provide a compensatory mechanism for the removal of GABA from the synaptic cleft of synapses formed by Purkinje cell axon terminals

Identifying critically important vascular access outcomes for trials in haemodialysis : an international survey with patients, caregivers and health professionals

BACKGROUND: Vascular access outcomes reported across haemodialysis (HD) trials are numerous, heterogeneous and not always relevant to patients and clinicians. This study aimed to identify critically important vascular access outcomes. METHOD: Outcomes derived from a systematic review, multi-disciplinary expert panel and patient input were included in a multilanguage online survey. Participants rated the absolute importance of outcomes using a 9-point Likert scale (7-9 being critically important). The relative importance was determined by a best-worst scale using multinomial logistic regression. Open text responses were analysed thematically. RESULTS: The survey was completed by 873 participants [224 (26%) patients/caregivers and 649 (74%) health professionals] from 58 countries. Vascular access function was considered the most important outcome (mean score 7.8 for patients and caregivers/8.5 for health professionals, with 85%/95% rating it critically important, and top ranked on best-worst scale), followed by infection (mean 7.4/8.2, 79%/92% rating it critically important, second rank on best-worst scale). Health professionals rated all outcomes of equal or higher importance than patients/caregivers, except for aneurysms. We identified six themes: necessity for HD, applicability across vascular access types, frequency and severity of debilitation, minimizing the risk of hospitalization and death, optimizing technical competence and adherence to best practice and direct impact on appearance and lifestyle. CONCLUSIONS: Vascular access function was the most critically important outcome among patients/caregivers and health professionals. Consistent reporting of this outcome across trials in HD will strengthen their value in supporting vascular access practice and shared decision making in patients requiring HD

Patterns of Tobacco-Use Behavior Among Chinese Smokers with Medical Conditions

Understanding the characteristics of Chinese American smokers with medical conditions and factors associated with their tobacco-use behaviors will guide effective cessation programs. In 2008, the authors described socio-demographic profiles of Chinese smokers with medical conditions treated during the period 2002–2006, documented their tobacco-use behaviors (i.e., average daily cigarette use, nicotine dependence, and number of past-year quit attempts), and drew comparisons between subjects recruited from hospitals (IP) and ambulatory settings (OP). Compared to OP, IP were significantly older, less educated, less acculturated, and more likely to be retired. Of the two groups, IP had poorer disease profiles, smoked less (4.4 vs. 11.9 cigarettes per day), and had lower nicotine-addiction scores (5.5 vs. 6.7). There was no difference between groups in past-year quit attempts. After adjustments, the data revealed that being employed and OP was associated with higher average daily cigarette use; IP were less nicotine dependent than OP; and for both groups, years of smoking was negatively associated with past-year quit attempts. Our study suggests that, more than acculturation level, health status influences the Chinese smoker’s level of cigarette use and nicotine addiction. Given the severity of their disease profiles, IP should be aggressively targeted for intervention, as they are more likely to be light smokers and to be less nicotine dependent than OP. Future tobacco treatment studies should pay attention to health status among smokers in health-care settings in order to provide a more accurate assessment of treatment needs and of barriers to successful smoking cessation

TextNAS: A Neural Architecture Search Space tailored for Text Representation

Learning text representation is crucial for text classification and other language related tasks. There are a diverse set of text representation networks in the literature, and how to find the optimal one is a non-trivial problem. Recently, the emerging Neural Architecture Search (NAS) techniques have demonstrated good potential to solve the problem. Nevertheless, most of the existing works of NAS focus on the search algorithms and pay little attention to the search space. In this paper, we argue that the search space is also an important human prior to the success of NAS in different applications. Thus, we propose a novel search space tailored for text representation. Through automatic search, the discovered network architecture outperforms state-of-the-art models on various public datasets on text classification and natural language inference tasks. Furthermore, some of the design principles found in the automatic network agree well with human intuition

Best practices for fNIRS publications

The application of functional near-infrared spectroscopy (fNIRS) in the neurosciences has been expanding over the last 40 years. Today, it is addressing a wide range of applications within different populations and utilizes a great variety of experimental paradigms. With the rapid growth and the diversification of research methods, some inconsistencies are appearing in the way in which methods are presented, which can make the interpretation and replication of studies unnecessarily challenging. The Society for Functional Near-Infrared Spectroscopy has thus been motivated to organize a representative (but not exhaustive) group of leaders in the field to build a consensus on the best practices for describing the methods utilized in fNIRS studies. Our paper has been designed to provide guidelines to help enhance the reliability, repeatability, and traceability of reported fNIRS studies and encourage best practices throughout the community. A checklist is provided to guide authors in the preparation of their manuscripts and to assist reviewers when evaluating fNIRS papers

Anticancer Gene Transfer for Cancer Gene Therapy

Gene therapy vectors are among the treatments currently used to treat malignant tumors. Gene therapy vectors use a specific therapeutic transgene that causes death in cancer cells. In early attempts at gene therapy, therapeutic transgenes were driven by non-specific vectors which induced toxicity to normal cells in addition to the cancer cells. Recently, novel cancer specific viral vectors have been developed that target cancer cells leaving normal cells unharmed. Here we review such cancer specific gene therapy systems currently used in the treatment of cancer and discuss the major challenges and future directions in this field