Systematic reviews of complementary therapies - an annotated bibliography. Part 1: Acupuncture

Background Complementary therapies are widespread but controversial. We aim to provide a comprehensive collection and a summary of systematic reviews of clinical trials in three major complementary therapies (acupuncture, herbal medicine, homeopathy). This article is dealing with acupuncture. Potentially relevant reviews were searched through the register of the Cochrane Complementary Medicine Field, the Cochrane Library, Medline, and bibliographies of articles and books. To be included articles had to review prospective clinical trials of acupuncture; had to describe review methods explicitly; had to be published; and had to focus on treatment effects. Information on conditions, interventions, methods, results and conclusions was extracted using a pretested form and summarized descriptively. Results From a total of 48 potentially relevant reviews preselected in a screeening process 39 met the inclusion criteria. 22 were on various pain syndromes or rheumatic diseases. Other topics addressed by more than one review were addiction, nausea, asthma and tinnitus. Almost unanimously the reviews state that acupuncture trials include too few patients. Often included trials are heterogeneous regarding patients, interventions and outcome measures, are considered to have insufficient quality and contradictory results. Convincing evidence is available only for postoperative nausea, for which acupuncture appears to be of benefit, and smoking cessation, where acupuncture is no more effective than sham acupuncture. Conclusions A large number of systematic reviews on acupuncture exists. What is most obvious from these reviews is the need for (the funding of) well-designed, larger clinical trials

Assessing internet-based information used to aid patient decision-making about surgery for perianal Crohn's fistula.

BACKGROUND: Decision-making in perianal Crohn's fistula (pCD) is preference sensitive. Patients use the internet to access healthcare information. The aim of this study was to assess the online information and patient decision aids relating to surgery for pCD. METHODS: A search of Google™ and the Decision Aids Library Inventory (DALI) was performed using a predefined search strategy. Patient-focussed sources providing information about pCD surgery were included in the analysis. Written health information was assessed using the International Patient Decision Aids Standards (IPDAS) and DISCERN criteria. The readability of the source content was assessed using the Flesch-Kincaid score. RESULTS: Of the 201 sources found, 187 were excluded, leaving 14 sources for analysis. Three sources were dedicated to pCD, and six sources mentioned pCD-specific outcomes. The most common surgical intervention reported was seton insertion (n = 13). The least common surgical intervention reported was proctectomy (n = 1). The mean IPDAS and DISCERN scores were 4.43 ± 1.65 out of 12 (range = 2-8) and 2.93 ± 0.73 out of 5 (range = 1-5), respectively. The mean reading ease was US college standard. CONCLUSIONS: We found no patient decision aids relating to surgery for pCD. The online sources relating to surgery for pCD are few, and their quality is poor, as seen in the low IPDAS and DISCERN scores. Less than half of the sources mentioned pCD-specific outcomes, and three sources were solely dedicated to providing information on pCD. Healthcare professionals should look to create a patient tool to assist decision-making in pCD

Nuclear Translocation of Jacob in Hippocampal Neurons after Stimuli Inducing Long-Term Potentiation but Not Long-Term Depression

Background: In recent years a number of potential synapto-nuclear protein messengers have been characterized that are thought to be involved in plasticity-related gene expression, and that have the capacity of importin- mediated and activity-dependent nuclear import. However, there is a surprising paucity of data showing the nuclear import of such proteins in cellular models of learning and memory. Only recently it was found that the transcription factor cyclic AMP response element binding protein 2 (CREB2) transits to the nucleus during long-term depression (LTD), but not during long-term potentiation (LTP) of synaptic transmission in hippocampal primary neurons. Jacob is another messenger that couples NMDA-receptor-activity to nuclear gene expression. We therefore aimed to study whether Jacob accumulates in the nucleus in physiological relevant models of activity-dependent synaptic plasticity. Methodology/Principal Findings: We have analyzed the dynamics of Jacob’s nuclear import following induction of NMDA-receptor dependent LTP or LTD at Schaffer collateral-CA1 synapses in rat hippocampal slices. Using time-lapse imaging of neurons expressing a Jacob-Green-Fluorescent-Protein we found that Jacob rapidly translocates from dendrites to the nucleus already during the tetanization period of LTP, but not after induction of LTD. Immunocytochemical stainings confirmed the nuclear accumulation of endogenous Jacob in comparison to apical dendrites after induction of LTP but not LTD. Complementary findings were obtained after induction of NMDA-receptor dependent chemical LTP and LTD i

LV-pIN-KDEL: a novel lentiviral vector demonstrates the morphology, dynamics and continuity of the endoplasmic reticulum in live neurones

BACKGROUND The neuronal endoplasmic reticulum (ER) is an extensive, complex endomembrane system, containing Ca2+ pumps, and Ca2+ channels that permit it to act as a dynamic calcium store. Currently, there is controversy over the continuity of the ER in neurones, how this intersects with calcium signalling and the possibility of physical compartmentalisation. Unfortunately, available probes of ER structure such as vital dyes are limited by their membrane specificity. The introduction of ER-targeted GFP plasmids has been a considerable step forward, but these are difficult to express in neurones through conventional transfection approaches. To circumvent such problems we have engineered a novel ER-targeted GFP construct, termed pIN-KDEL, into a 3rd generation replication-defective, self-inactivating lentiviral vector system capable of mediating gene transduction in diverse dividing and post-mitotic mammalian cells, including neurones. RESULTS Following its expression in HEK293 (or COS-7) cells, LV-pIN-KDEL yielded a pattern of fluorescence that co-localised exclusively with the ER marker sec61beta but with no other major organelle. We found no evidence for cytotoxicity and only rarely inclusion body formation. To explore the utility of the probe in resolving the ER in live cells, HEK293 or COS-7 cells were transduced with LV-pIN-KDEL and, after 48 h, imaged directly at intervals from 1 min to several hours. LV-pIN-KDEL fluorescence revealed the endoplasmic reticulum as a tubular lattice structure whose morphology can change markedly within seconds. Although GFP can be phototoxic, the integrity of the cells and ER was retained for several weeks and even after light exposure for periods up to 24 h. Using LV-pIN-KDEL we have imaged the ER in diverse fixed neuronal cultures and, using real-time imaging, found evidence for extensive, dynamic remodelling of the neuronal ER in live hippocampal cultures, brain slices, explants and glia. Finally, through a Fluorescence Loss in Photobleaching (FLIP) approach, continuous irradiation at a single region of interest removed all the fluorescence of LV-pIN-KDEL-transduced nerve cells in explant cultures, thus, providing compelling evidence that in neurons the endoplasmic reticulum is not only dynamic but also continuous. CONCLUSION The lentiviral-based ER-targeted reporter, LV-pIN-KDEL, offers considerable advantages over present systems for defining the architecture of the ER, especially in primary cells such as neurones that are notoriously difficult to transfect. Images and continuous photobleaching experiments of LV-pIN-KDEL-transduced neurones demonstrate that the endoplasmic reticulum is a dynamic structure with a single continuous lumen. The introduction of LV-pIN-KDEL is anticipated to greatly facilitate a real-time visualisation of the structural plasticity and continuous nature of the neuronal ER in healthy and diseased brain tissue

Non-hexagonal neural dynamics in vowel space

Are the grid cells discovered in rodents relevant to human cognition? Following up on two seminal studies by others, we aimed to check whether an approximate 6-fold, grid-like symmetry shows up in the cortical activity of humans who "navigate" between vowels, given that vowel space can be approximated with a continuous trapezoidal 2D manifold, spanned by the first and second formant frequencies. We created 30 vowel trajectories in the assumedly flat central portion of the trapezoid. Each of these trajectories had a duration of 240 milliseconds, with a steady start and end point on the perimeter of a "wheel". We hypothesized that if the neural representation of this "box" is similar to that of rodent grid units, there should be an at least partial hexagonal (6-fold) symmetry in the EEG response of participants who navigate it. We have not found any dominant n-fold symmetry, however, but instead, using PCAs, we find indications that the vowel representation may reflect phonetic features, as positioned on the vowel manifold. The suggestion, therefore, is that vowels are encoded in relation to their salient sensory-perceptual variables, and are not assigned to arbitrary gridlike abstract maps. Finally, we explored the relationship between the first PCA eigenvector and putative vowel attractors for native Italian speakers, who served as the subjects in our study