Reduced insular γ‐aminobutyric acid in fibromyalgia

Objective Recent scientific findings have reinvigorated interest in examining the role of γ‐aminobutyric acid (GABA), the major inhibitory central nervous system neurotransmitter, in chronic pain conditions. Decreased inhibitory neurotransmission is a proposed mechanism in the pathophysiology of chronic pain syndromes such as fibromyalgia (FM). The purpose of this study was to test the hypothesis that decreased levels of insular and anterior cingulate GABA would be present in FM patients, and that the concentration of this neurotransmitter would be correlated with pressure–pain thresholds. Methods Sixteen FM patients and 17 age‐ and sex‐matched healthy controls underwent pressure–pain testing and a 3T proton magnetic resonance spectroscopy session in which the right anterior insula, right posterior insula, anterior cingulate, and occipital cortex were examined in subjects at rest. Results GABA levels in the right anterior insula were significantly lower in FM patients compared with healthy controls (mean ± SD 1.17 ± 0.24 arbitrary institutional units versus 1.42 ± 0.32 arbitrary institutional units; P = 0.016). There was a trend toward increased GABA levels in the anterior cingulate of FM patients compared with healthy controls ( P = 0.06). No significant differences between groups were detected in the posterior insula or occipital cortex ( P > 0.05 for all comparisons). Within the right posterior insula, higher levels of GABA were positively correlated with pressure–pain thresholds in the FM patients (Spearman's rho = 0.63; P = 0.02). Conclusion Diminished inhibitory neurotransmission resulting from lower concentrations of GABA within the right anterior insula may play a role in the pathophysiology of FM and other central pain syndromes.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90292/1/33339_ftp.pd

Effect of music on post-exercise recovery rate in young healthy individuals

Background: Music has been used in exercise classes for many decades. The role of music in increasing the exercise performance is well recognized but there is very little information about effect of music on post-exercise recovery time.Methods: The present study was conducted to see the effect of musical sounds on post-exercise recovery time following moderate exercise with Harvard step test in young healthy volunteers. 30 young healthy volunteers (17 males, 13 females) aged between 17 to 20 years were recruited for the study. Pulse rate, systolic BP, diastolic BP were recorded prior to exercise in lying down position. The participants were subjected to moderate exercise by Harvard step test for 3 minutes on 3 consecutive days. They were allowed to rest in silence on 1st day, rest with hearing slow music on 2nd day and rest with hearing fast music on 3rd day. During the post-exercise relaxation time PR, SBP and DBP were measured immediately and after every 1 min. until the parameters returned to resting values. Data was statistically analysed using ANOVA test and 0.05 level of significance was set prior to the study.Results: The result showed that with slow music, recovery time of pulse rate (5.2 ± 2.1), systolic blood pressure (3.9 ± 1.1) and diastolic blood pressure (3.2 ± 1.7) were significantly faster as compared to both no music and fast music.Conclusion: The study concluded that music hastens post-exercise recovery and slow music has greater relaxation effect than fast or no music.

Spectrum of clinical and biochemical profile and its importance in diabetic ketoacidosis: a tertiary care hospital experience in Gujarat

Background: Diabetes mellitus (DM) is a disorder of multiple etiologies, and diabetic ketoacidosis (DKA) is one of the life-threatening complications of DM. This study was aimed to study the clinical and biochemical profile of DKA patients. Methods: We conducted this retrospective study at a tertiary care hospital in Gujarat. We included total 100 patients above the age of 18 years having DM, presented with DKA. A detailed history, clinical examination and biochemical tests were carried out: random blood sugar, urinalysis, arterial blood gas analysis, serum ketone, HbA1c, serum creatinine, serum electrolytes- potassium and sodium and serum osmolality. The results were analysed using Microsoft excel. Results: Out of total 100 patients, 76 (76%) patients had type 1 DM and 24 (24%) had type 2 DM, 42 (42%) were in the age group of 18-30 years. The mean age was 39.75±12.14 years. There were 56 (56%) males and 44 (44%) females with male: female ratio of 1.3:1. Most common clinical features of DKA were nausea/vomiting (88%), breathlessness (43%) and fever (35%). The main biochemical parameters altered were blood sugar (>400 mg/dl in 41%) and serum ketones (≥5 in 84%) as well as majority of patients (64%) had their HbA1c level between 11-15% with the mean HbA1c value of 12.25±2.43%. Conclusions: DKA is a frequently observed emergency with high mortality rate. Education regarding symptoms of ketoacidosis, not missing insulin doses especially during illness, strict adherence to treatment and lifestyle modifications can greatly reduce DKA occurrence

Individual differences in perception of the speech-to-song illusion are linked to musical aptitude but not musical training

In the speech-to-song illusion, certain spoken phrases are perceived as sung after repetition. One possible explanation for this increase in musicality is that, as phrases are repeated, lexical activation dies off, enabling listeners to focus on the melodic and rhythmic characteristics of stimuli and assess them for the presence of musical structure. Here we tested the idea that perception of the illusion requires implicit assessment of melodic and rhythmic structure by presenting individuals with phrases that tend to be perceived as song when repeated, as well as phrases that tend to continue to be perceived as speech when repeated, measuring the strength of the illusion as the rating difference between these two stimulus categories after repetition. Illusion strength varied widely and stably between listeners, with large individual differences and high split-half reliability, suggesting that not all listeners are equally able to detect musical structure in speech. Although variability in illusion strength was unrelated to degree of musical training, participants who perceived the illusion more strongly were proficient in several musical skills, including beat perception, tonality perception, and selective attention to pitch. These findings support models of the speech-to-song illusion in which experience of the illusion is based on detection of musical characteristics latent in spoken phrases

Pubertal lipid levels are significantly lower in youth with type 1 diabetes who experienced partial clinical remission

Importance: The physiologic changes in lipids during puberty in type 1 diabetes (T1D) is unclear as subjects in previous studies were not stratified by partial clinical remission (PCR) status. Aim: To determine the effect of PCR on lipid changes during puberty in youth with T1D. Subjects and Methods: A retrospective cross-sectional study of 194 subjects consisting of 71 controls of age 12.9±1.3y and 123 subjects with T1D stratified into remitters (n=44, age 13.0±0.8y) and non-remitters (n=79, age 11.2±0.6y). PCR was defined as insulin-dose adjusted HbA1c of ≤9. Pubertal status was determined by Tanner staging. Results: Among the pubertal cohort, low-density lipoprotein cholesterol concentration was significantly higher in the non-remitters compared to the remitters, 91.1±25.6mg/dL vs 77.2±25.8mg/dL, p=0.018; and the normal-weight controls, 91.1±25.6mg/dL vs 70.4±22.9 mg/dL, p=0.009; but was similar between the overweight/obese controls and non-remitters, 89.7±28.9mg/dL vs 91.1± 25.6mg/dL, p=0.81, and similarly between the normal-weight controls and remitters, 70.4±22.9mg/dL vs 77.2±25.8mg/dL, p=0.39. Total cholesterol was also significantly higher in the non-remitters compared to the remitters, 167.8±30.5 mg/dL vs 149.8±32.1mg/dL, p=0.012; and normal-weight controls, 167.8±30.5mg/dL vs 143.2±30.1mg/dL, p=0.011; but similar between the non-remitters and overweight/obese controls, p=0.098; and remitters and normal-weight controls, p=0.51. Non-HDL cholesterol was equally significantly higher in non-remitters compared to remitters, 111.3±30.1mg/dL vs 95.9±29.1mg/dL, p=0.028; and normal-weight controls, 111.3±30.1mg/dL vs 86.2± 32.2mg/dL, p=0.028; but similar between non-remitters and overweight/obese controls, p=0.48; and remitters versus normal-weight controls, p=0.39. Conclusions: Puberty-related reductions in LDL, TC, and non-HDL occur in remitters and normal-weight controls, but not in non-remitters and overweight/obese controls

Altered functional connectivity during speech perception in Congenital Amusia

Individuals with congenital amusia have a lifelong history of unreliable pitch processing. Accordingly, they downweight pitch cues during speech perception and instead rely on other dimensions such as duration. We investigated the neural basis for this strategy. During fMRI, individuals with amusia (N=15) and controls (N=15) read sentences where a comma indicated a grammatical phrase boundary. They then heard two sentences spoken that differed only in pitch and/or duration cues, and selected the best match for the written sentence. Prominent reductions in functional connectivity were detected in the amusia group, between left prefrontal language-related regions and right hemisphere pitch-related regions, which reflected the between-group differences in cue weights in the same groups of listeners. Connectivity differences between these regions were not present during a control task. Our results indicate that the reliability of perceptual dimensions is linked with functional connectivity between frontal and perceptual regions, and suggest a compensatory mechanism

RNA-Seq identifies SPGs as a ventral skeletal patterning cue in sea urchins

The sea urchin larval skeleton offers a simple model for formation of developmental patterns. The calcium carbonate skeleton is secreted by primary mesenchyme cells (PMCs) in response to largely unknown patterning cues expressed by the ectoderm. To discover novel ectodermal cues, we performed an unbiased RNA-Seq-based screen and functionally tested candidates; we thereby identified several novel skeletal patterning cues. Among these, we show that SLC26a2/7 is a ventrally expressed sulfate transporter that promotes a ventral accumulation of sulfated proteoglycans, which is required for ventral PMC positioning and skeletal patterning. We show that the effects of SLC perturbation are mimicked by manipulation of either external sulfate levels or proteoglycan sulfation. These results identify novel skeletal patterning genes and demonstrate that ventral proteoglycan sulfation serves as a positional cue for sea urchin skeletal patterning

Sustained remission of symptoms and improved health-related quality of life in patients with cryopyrin-associated periodic syndrome treated with canakinumab: results of a double-blind placebo-controlled randomized withdrawal study

Abstract Introduction To assess the effect of canakinumab, a fully human anti-interleukin-1β antibody, on symptoms and health-related quality of life (HRQoL) in patients with cryopyrin-associated periodic syndrome (CAPS). Methods In this 48-week, phase 3 study, patients with CAPS received canakinumab 150 mg subcutaneously at 8-week intervals. All patients (n = 35) received canakinumab during weeks 1 through 8; weeks 9 through 24 constituted a double-blind placebo-controlled withdrawal phase, and weeks 24 through 48 constituted an open-label phase in which all patients received canakinumab. Patient and physician assessments of symptoms, levels of inflammatory markers, and HRQoL were performed. Results Rapid symptom remission was achieved, with 89% of patients having no or minimal disease activity on day 8. Responses were sustained in patients receiving 8-weekly canakinumab. Responses were lost during the placebo-controlled phase in the placebo group and were regained on resuming canakinumab therapy in the open-label phase. Clinical responses were accompanied by decreases in serum levels of C-reactive protein, serum amyloid A protein, and interleukin-6. HRQoL scores at baseline were considerably below those of the general population. Improvements in all 36-item Short-Form Health Survey (SF-36) domain scores were evident by day 8. Scores approached or exceeded those of the general U.S. population by week 8 and remained stable during canakinumab therapy. Improvements in bodily pain and role-physical were particularly marked, increasing by more than 25 points from baseline to week 8. Therapy was generally well tolerated. Conclusions Canakinumab, 150 mg, 8-weekly, induced rapid and sustained remission of symptoms in patients with CAPS, accompanied by substantial improvements in HRQoL. Trial registration Clintrials.gov NCT0046598

Recovery of Encapsulated Adult Neural Progenitor Cells from Microfluidic-Spun Hydrogel Fibers Enhances Proliferation and Neuronal Differentiation

Because of the limitations imposed by traditional two-dimensional (2D) cultures, biomaterials have become a major focus in neural and tissue engineering to study cell behavior in vitro. 2D systems fail to account for interactions between cells and the surrounding environment; these cell–matrix interactions are important to guide cell differentiation and influence cell behavior such as adhesion and migration. Biomaterials provide a unique approach to help mimic the native microenvironment in vivo. In this study, a novel microfluidic technique is used to encapsulate adult rat hippocampal stem/progenitor cells (AHPCs) within alginate-based fibrous hydrogels. To our knowledge, this is the first study to encapsulate AHPCs within a fibrous hydrogel. Alginate-based hydrogels were cultured for 4 days in vitro and recovered to investigate the effects of a 3D environment on the stem cell fate. Post recovery, cells were cultured for an additional 24 or 72 h in vitro before fixing cells to determine if proliferation and neuronal differentiation were impacted after encapsulation. The results indicate that the 3D environment created within a hydrogel is one factor promoting AHPC proliferation and neuronal differentiation (19.1 and 13.5%, respectively); however, this effect is acute. By 72 h post recovery, cells had similar levels of proliferation and neuronal differentiation (10.3 and 8.3%, respectively) compared to the control conditions. Fibrous hydrogels may better mimic the natural micro-environment present in vivo and be used to encapsulate AHPCs, enhancing cell proliferation and selective differentiation. Understanding cell behavior within 3D scaffolds may lead to the development of directed therapies for central nervous system repair and rescue

Recipient mucosal-associated invariant T cells control GVHD within the colon

Mucosal-associated invariant T (MAIT) cells are a unique innate-like T cell subset that responds to a wide array of bacteria and yeast through recognition of riboflavin metabolites presented by the MHC class I–like molecule MR1. Here, we demonstrate using MR1 tetramers that recipient MAIT cells are present in small but definable numbers in graft-versus-host disease (GVHD) target organs and protect from acute GVHD in the colon following bone marrow transplantation (BMT). Consistent with their preferential juxtaposition to microbial signals in the colon, recipient MAIT cells generate large amounts of IL-17A, promote gastrointestinal tract integrity, and limit the donor alloantigen presentation that in turn drives donor Th1 and Th17 expansion specifically in the colon after BMT. Allogeneic BMT recipients deficient in IL-17A also develop accelerated GVHD, suggesting MAIT cells likely regulate GVHD, at least in part, by the generation of this cytokine. Indeed, analysis of stool microbiota and colon tissue from IL-17A–/– and MR1–/– mice identified analogous shifts in microbiome operational taxonomic units (OTU) and mediators of barrier integrity that appear to represent pathways controlled by similar, IL-17A–dependent mechanisms. Thus, MAIT cells act to control barrier function to attenuate pathogenic T cell responses in the colon and, given their very high frequency in humans, likely represent an important population in clinical BMT