Premonitory symptoms in migraine: a systematic review and meta-analysis of observational studies reporting prevalence or relative frequency

Background Observational studies on the prevalence of premonitory symptoms in people with migraine, preceding the headache pain (or aura) phase, have shown conflicting results. We conducted a systematic review and meta-analysis to estimate the prevalence, and relative frequency among clinic populations, of premonitory symptoms in people with migraine, overall and of the multifarious individual symptoms, and to review the methodologies used to assess them. Methods We searched PubMed and Embase for studies published from database inception until 31st of May 2022. Two investigators independently screened titles, abstracts, and full texts. We retrieved observational studies that reported the prevalence/relative frequency of one or more premonitory symptoms in people with migraine. Two investigators independently extracted data and assessed risk of bias. Results were pooled using random-effects meta-analysis. Our main outcomes were the percentage of people with migraine who experienced at least one premonitory symptom and the percentages who experienced different individual premonitory symptoms. To describe our outcomes, we used the terms prevalence for data from population-based samples and relative frequency for data from clinic-based samples. We also descriptively and critically assessed the methodologies used to assess these symptoms. Results The pooled estimated prevalence in population-based studies of at least one premonitory symptom was 29% (95% CI: 8–63; I2 99%) and the corresponding pooled estimated relative frequency in clinic-based studies was 66% (95% CI: 45–82; I2 99%). The data from clinic-based studies only supported meta-analysis of 11 of 96 individual symptoms, with relative frequency estimates ranging from 11 to 49%. Risk of bias was determined as high in 20 studies, moderate in seven, and low in two. Conclusions The substantial between-study heterogeneity demands cautious interpretation of our estimates. Studies showed wide methodological variations, and many lacked rigor. Overall, the evidence was insufficient to support reliable prevalence estimation or characterization of premonitory symptoms. More data are needed, of better quality, to confirm the existence of a distinctive premonitory phase of migraine, and its features. Methodological guidelines based on expert consensus are a prerequisite

Robots that can adapt like animals

As robots leave the controlled environments of factories to autonomously function in more complex, natural environments, they will have to respond to the inevitable fact that they will become damaged. However, while animals can quickly adapt to a wide variety of injuries, current robots cannot "think outside the box" to find a compensatory behavior when damaged: they are limited to their pre-specified self-sensing abilities, can diagnose only anticipated failure modes, and require a pre-programmed contingency plan for every type of potential damage, an impracticality for complex robots. Here we introduce an intelligent trial and error algorithm that allows robots to adapt to damage in less than two minutes, without requiring self-diagnosis or pre-specified contingency plans. Before deployment, a robot exploits a novel algorithm to create a detailed map of the space of high-performing behaviors: This map represents the robot's intuitions about what behaviors it can perform and their value. If the robot is damaged, it uses these intuitions to guide a trial-and-error learning algorithm that conducts intelligent experiments to rapidly discover a compensatory behavior that works in spite of the damage. Experiments reveal successful adaptations for a legged robot injured in five different ways, including damaged, broken, and missing legs, and for a robotic arm with joints broken in 14 different ways. This new technique will enable more robust, effective, autonomous robots, and suggests principles that animals may use to adapt to injury

The increase of the functional entropy of the human brain with age

We use entropy to characterize intrinsic ageing properties of the human brain. Analysis of fMRI data from a large dataset of individuals, using resting state BOLD signals, demonstrated that a functional entropy associated with brain activity increases with age. During an average lifespan, the entropy, which was calculated from a population of individuals, increased by approximately 0.1 bits, due to correlations in BOLD activity becoming more widely distributed. We attribute this to the number of excitatory neurons and the excitatory conductance decreasing with age. Incorporating these properties into a computational model leads to quantitatively similar results to the fMRI data. Our dataset involved males and females and we found significant differences between them. The entropy of males at birth was lower than that of females. However, the entropies of the two sexes increase at different rates, and intersect at approximately 50 years; after this age, males have a larger entropy

Current Welfare Problems Facing Horses in Great Britain as Identified by Equine Stakeholders

Despite growing concerns about the welfare of horses in Great Britain (GB) there has been little surveillance of the welfare status of the horse population. Consequently we have limited knowledge of the range of welfare problems experienced by horses in GB and the situations in which poor welfare occurs. Thirty-one in-depth interviews were conducted with a cross -section of equine stakeholders, in order to explore their perceptions of the welfare problems faced by horses in GB. Welfare problems relating to health, management and riding and training were identified, including horses being under or over weight, stabling 24 hours a day and the inappropriate use of training aids. The interviewees also discussed broader contexts in which they perceived that welfare was compromised. The most commonly discussed context was where horses are kept in unsuitable environments, for example environments with poor grazing. The racing industry and travellers horses were identified as areas of the industry where horse welfare was particularly vulnerable to compromise. Lack of knowledge and financial constraints were perceived to be the root cause of poor welfare by many interviewees. The findings give insight into the range of welfare problems that may be faced by horses in GB, the contexts in which these may occur and their possible causes. Many of the problems identified by the interviewees have undergone limited scientific investigation pointing to areas where further research is likely to be necessary for welfare improvement. The large number of issues identified suggests that some form of prioritisation may be necessary to target research and resources effectively

YKL-40 tissue expression and plasma levels in patients with ovarian cancer

<p>Abstract</p> <p>Background</p> <p>YKL-40 (chitinase-3-like-1) is a member of "mammalian chitinase-like proteins". The protein is expressed in many types of cancer cells and the highest plasma YKL-40 levels have been found in patients with metastatic disease, short recurrence/progression-free intervals, and short overall survival. The aim of the study was to determine the expression of YKL-40 in tumor tissue and plasma in patients with borderline ovarian tumor or epithelial ovarian cancer (OC), and investigate prognostic value of this marker.</p> <p>Methods</p> <p>YKL-40 protein expression was determined by immunohistochemistry in tissue arrays from 181 borderline tumors and 473 OC. Plasma YKL-40 was determined by ELISA in preoperative samples from 19 patients with borderline tumor and 76 OC patients.</p> <p>Results</p> <p>YKL-40 protein expression was found in cancer cells, tumor associated macrophages, neutrophils and mast cells. The tumor cell expression was higher in OC than in borderline tumors (p = 0.001), and associated with FIGO stage (p < 0.0001) and histological subtype (p = 0.0009). Positive YKL-40 expression (≥ 5% staining) was not associated with reduced survival. Plasma YKL-40 was also higher in patients with OC than in patients with borderline tumors (p < 0.0001), and it was positively correlated to serum CA-125 (p < 0.0001) and FIGO stage (p = 0.0001). Univariate Cox analysis of plasma YKL-40 showed association with overall survival (p < 0.0001). Multivariate Cox analysis, including plasma YKL-40, serum CA125, FIGO stage, age and radicality after primary surgery as variables, showed that elevated plasma YKL-40 was associated with a shorter survival (HR = 2.13, 95% CI: 1.40–3.25, p = 0.0004).</p> <p>Conclusion</p> <p>YKL-40 in OC tissue and plasma are related to stage and histology, but only plasma YKL-40 is a prognostic biomarker in patients with OC.</p

The quest for the solar g modes

Solar gravity modes (or g modes) -- oscillations of the solar interior for which buoyancy acts as the restoring force -- have the potential to provide unprecedented inference on the structure and dynamics of the solar core, inference that is not possible with the well observed acoustic modes (or p modes). The high amplitude of the g-mode eigenfunctions in the core and the evanesence of the modes in the convection zone make the modes particularly sensitive to the physical and dynamical conditions in the core. Owing to the existence of the convection zone, the g modes have very low amplitudes at photospheric levels, which makes the modes extremely hard to detect. In this paper, we review the current state of play regarding attempts to detect g modes. We review the theory of g modes, including theoretical estimation of the g-mode frequencies, amplitudes and damping rates. Then we go on to discuss the techniques that have been used to try to detect g modes. We review results in the literature, and finish by looking to the future, and the potential advances that can be made -- from both data and data-analysis perspectives -- to give unambiguous detections of individual g modes. The review ends by concluding that, at the time of writing, there is indeed a consensus amongst the authors that there is currently no undisputed detection of solar g modes.Comment: 71 pages, 18 figures, accepted by Astronomy and Astrophysics Revie

Diagnostic difficulties of Lactobacillus casei bacteraemia in immunocompetent patients: A case report

This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Abiotrophia defectiva knee prosthesis infection: A case report

<p>Abstract</p> <p>Background</p> <p><it>Abiotrophia </it>species have rarely been implicated in osteoarticular infections. We report one case of an <it>A. defectiva </it>knee prosthesis infection.</p> <p>Case presentation</p> <p>A 71-year-old man of Italian origin presented with pain and swelling of the knee four years after the implantation of a total knee replacement prosthesis. While standard culturing of the synovial fluid resulted in no isolation of microorganisms, the direct inoculation of the synovial fluid into a rich culture medium resulted in the identification of <it>A. defectiva </it>by polymerase chain reaction sequencing. Repeated attempts of culturing microorganisms from blood were negative, and echocardiograms and colonoscopies were unremarkable. High-dose amoxicillin for nine months and a two-stage replacement of the knee prosthesis led to full patient recovery by the time of the 12-month follow-up examination.</p> <p>Conclusions</p> <p>Because <it>Abiotrophia </it>spp. are fastidious microorganisms, it is likely that cases of <it>Abiotrophia </it>orthopedic infection are misdiagnosed as culture-negative infections. Direct inoculation of synovial fluids into rich broth medium and further polymerase chain reaction-based detection of culture-negative synovial fluids are key tests for accurate documentation and detection of these infections.</p

Circuit dissection of the role of somatostatin in itch and pain

Stimuli that elicit itch are detected by sensory neurons that innervate the skin. This information is processed by the spinal cord; however, the way in which this occurs is still poorly understood. Here we investigated the neuronal pathways for itch neurotransmission, particularly the contribution of the neuropeptide somatostatin. We find that in the periphery, somatostatin is exclusively expressed in Nppb+ neurons, and we demonstrate that Nppb+somatostatin+ cells function as pruriceptors. Employing chemogenetics, pharmacology and cell-specific ablation methods, we demonstrate that somatostatin potentiates itch by inhibiting inhibitory dynorphin neurons, which results in disinhibition of GRPR+ neurons. Furthermore, elimination of somatostatin from primary afferents and/or from spinal interneurons demonstrates differential involvement of the peptide released from these sources in itch and pain. Our results define the neural circuit underlying somatostatin-induced itch and characterize a contrasting antinociceptive role for the peptide

Standardisation of intestinal ultrasound scoring in clinical trials for luminal Crohn's disease

Background: Intestinal ultrasound (IUS) is a valuable tool for assessment of Crohn’s disease (CD). However, there is no widely accepted luminal disease activity index. / Aims: To identify appropriate IUS protocols, indices, items, and scoring methods for measurement of luminal CD activity and integration of IUS in CD clinical trials. / Methods: An expert international panel of adult and paediatric gastroenterologists (n = 15) and radiologists (n = 3) rated the appropriateness of 120 statements derived from literature review and expert opinion (scale of 1-9) using modified RAND/UCLA methodology. Median panel scores of 1 to ≤3.5, >3.5 to <6.5 and ≥6.5 to 9 were considered inappropriate, uncertain and appropriate ratings respectively. The statement list and survey results were discussed prior to voting. / Results: A total of 91 statements were rated appropriate with agreement after two rounds of voting. Items considered appropriate measures of disease activity were bowel wall thickness (BWT), vascularity, stratification and mesenteric inflammatory fat. There was uncertainty if any of the existing IUS disease activity indices were appropriate for use in CD clinical trials. Appropriate trial applications for IUS included patient recruitment qualification when diseased segments cannot be adequately assessed by ileocolonoscopy and screening for exclusionary complications. At outcome assessment, remission endpoints including BWT and vascularity, with or without mesenteric inflammatory fat, were considered appropriate. Components of an ideal IUS disease activity index were identified based upon panel discussions. / Conclusions: The panel identified appropriate component items and applications of IUS for CD clinical trials. Empiric evidence, and development and validation of an IUS disease activity index are needed