Resting state connectivity correlates with drug and placebo response in fibromyalgia patients

AbstractFibromyalgia is a chronic pain syndrome characterized by widespread pain, fatigue, and memory and mood disturbances. Despite advances in our understanding of the underlying pathophysiology, treatment is often challenging. New research indicates that changes in functional connectivity between brain regions, as can be measured by magnetic resonance imaging (fcMRI) of the resting state, may underlie the pathogenesis of this and other chronic pain states. As such, this parameter may be able to be used to monitor changes in brain function associated with pharmacological treatment, and might also be able to predict treatment response.We performed a resting state fcMRI trial using a randomized, placebo-controlled, cross-over design to investigate mechanisms of action of milnacipran (MLN), a selective serotonin and norepinephrine reuptake inhibitor (SNRI), in fibromyalgia patients. Our aim was to identify functional connectivity patterns at baseline that would differentially predict treatment response to MLN as compared to placebo. Since preclinical studies of MLN suggest that this medication works by augmenting antinociceptive processes, we specifically investigated brain regions known to be involved in pain inhibition.15 fibromyalgia patients completed the study, consisting of 6 weeks of drug and placebo intake (order counterbalanced) with an interspersed 2 week wash out period. As a main finding we report that reductions in clinical pain scores during MLN were associated with decreased functional connectivity between pro-nociceptive regions and antinociceptive pain regions at baseline, specifically between the rostral part of the anterior cingulate cortex (ACC) and the insular cortex (IC), as well as between the periaqueductal gray (PAG) and the IC: patients with lower preexisting functional connectivity had the greatest reduction in clinical pain. This pattern was not observed for the placebo period. However a more robust placebo response was associated with lower baseline functional connectivity between the ACC and the dorsolateral prefrontal cortex.This study indicates that ACC–IC connectivity might play a role in the mechanism of action of MLN, and perhaps more importantly fcMRI might be a useful tool to predict pharmacological treatment response

Altered fMRI restingâ state connectivity in individuals with fibromyalgia on acute pain stimulation

BackgroundFibromyalgia is a chronic widespread pain condition, with patients commonly reporting other symptoms such as sleep difficulties, memory complaints and fatigue. The use of magnetic resonance imaging (MRI) in fibromyalgia has allowed for the detection of neural abnormalities, with alterations in brain activation elicited by experimental pain and alterations in resting state connectivity related to clinical pain.MethodsIn this study, we sought to monitor state changes in resting brain connectivity following experimental pressure pain in fibromyalgia patients and healthy controls. Twelve fibromyalgia patients and 15 healthy controls were studied by applying discrete pressure stimuli to the thumbnail bed during MRI. Restingâ state functional MRI scanning was performed before and immediately following experimental pressure pain. We investigated changes in functional connectivity to the thalamus and the insular cortex.ResultsAcute pressure pain increased insula connectivity to the anterior cingulate and the hippocampus. Additionally, we observed increased thalamic connectivity to the precuneus/posterior cingulate cortex, a known part of the default mode network, in patients but not in controls. This connectivity was correlated with changes in clinical pain.ConclusionsThese data reporting changes in restingâ state brain activity following a noxious stimulus suggest that the acute painful stimuli may contribute to the alteration of the neural signature of chronic pain.What does this study/add?In this study acute pain application shows an echo in functional connectivity and clinical pain changes in chronic pain.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/122449/1/ejp832_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/122449/2/ejp832.pd

Persistence of collective behavior at high spin in the N=88 nucleus Tb 153

Excited states in the N=88 nucleus Tb153 were observed up to spin ∼40 in an experiment utilizing the Gammasphere array. The Tb153 states were populated in a weak α4n evaporation channel of the Cl37 + Sn124 reaction. Two previously known sequences were extended to higher spins, and a new decoupled structure was identified. The πh11/2 band was observed in the spin region where other N=88 isotopes exhibit effects of prolate to oblate shape changes leading to band termination along the yrast line, whereas Tb153 displays a persistent collective behavior. However, minor perturbations of the very highest state in both signatures of this h11/2 band are observed, which perhaps signal the start of the transition towards band termination

High-spin terminating states in the N=88 Ho 155 and Er 156 isotones

The Sn124(Cl37,6nγ) fusion-evaporation reaction at a bombarding energy of 180 MeV has been used to significantly extend the excitation level scheme of 67155Ho88. The collective rotational behavior of this nucleus breaks down above spin I∼30 and a fully aligned noncollective (band terminating) state has been identified at Iπ=79/2-. Comparison with cranked Nilsson-Strutinsky calculations also provides evidence for core-excited noncollective states at Iπ=87/2- and (89/2+) involving particle-hole excitations across the Z=64 shell gap. A similar core-excited state in 68156Er88 at Iπ=(46+) is also presented

Collective structures up to spin ∼ 65h in the N 90 isotones 158Er and 157Ho

A new collective band with high dynamic moment of inertia in 158Er at spins beyond band termination has been found in addition to the two previously reported ones. The measured transition quadrupole moments (Qt) of these three bands are very similar. These three bands have been suggested to possess a triaxial strongly deformed shape, based on comparisons with calculations using the cranked Nilsson-Strutinsky model and with tilted axis cranking calculations using the Skyrme-Hartree-Fock model. In addition, three collective bands with similar high dynamic moments of inertia, tentatively assigned to 157Ho, have been observed. Thus, it is suggested that all these structures share a common underlying character and that they are most likely associated with triaxial strongly deformed minima which are predicted to be close to the yrast line at spin 50 - 70h

Zoledronate in the prevention of Paget's (ZiPP) : protocol for a randomised trial of genetic testing and targeted zoledronic acid therapy to prevent SQSTM1-mediated Paget's disease of bone.

Introduction Paget’s disease of bone (PDB) is characterised by increased and disorganised bone remodelling affecting one or more skeletal sites. Complications include bone pain, deformity, deafness and pathological fractures. Mutations in sequestosome-1 (SQSTM1) are strongly associated with the development of PDB. Bisphosphonate therapy can improve bone pain in PDB, but there is no evidence that treatment alters the natural history of PDB or prevents complications. The Zoledronate in the Prevention of Paget’s disease trial (ZiPP) will determine if prophylactic therapy with the bisphosphonate zoledronic acid (ZA) can delay or prevent the development of PDB in people who carry SQSTM1 mutations. Methods and analysis People with a family history of PDB aged >30 years who test positive for SQSTM1 mutations are eligible to take part. At the baseline visit, participants will be screened for the presence of bone lesions by radionuclide bone scan. Biochemical markers of bone turnover will be measured and questionnaires completed to assess pain, health-related quality of life (HRQoL), anxiety and depression. Participants will be randomised to receive a single intravenous infusion of 5 mg ZA or placebo and followed up annually for between 4 and 8 years at which point baseline assessments will be repeated. The primary endpoint will be new bone lesions assessed by radionuclide bone scan. Secondary endpoints will include changes in biochemical markers of bone turnover, pain, HRQoL, anxiety, depression and PDB-related skeletal events

Representational predicaments for employees: Their impact on perceptions of supervisors\u27 individualized consideration and on employee job satisfaction

A representational predicament for a subordinate vis-à-vis his or her immediate superior involves perceptual incongruence with the superior about the subordinate\u27s work or work context, with unfavourable implications for the employee. An instrument to measure the incidence of two types of representational predicament, being neglected and negative slanting, was developed and then validated through an initial survey of 327 employees. A subsequent substantive survey with a fresh sample of 330 employees largely supported a conceptual model linking being neglected and negative slanting to perceptions of low individualized consideration by superiors and to low overall job satisfaction. The respondents in both surveys were all Hong Kong Chinese. Two case examples drawn from qualitative interviews illustrate and support the conceptual model. Based on the research findings, we recommend some practical exercises to use in training interventions with leaders and subordinates. © 2013 Copyright Taylor and Francis Group, LLC

The Soft X-ray Imager (SXI) on the SMILE Mission

The Soft X-ray Imager (SXI) is part of the scientific payload of the Solar wind Magnetosphere Ionosphere Link Explorer (SMILE) mission. SMILE is a joint science mission between the European Space Agency (ESA) and the Chinese Academy of Sciences (CAS) and is due for launch in 2025. SXI is a compact X-ray telescope with a wide field-of-view (FOV) capable of encompassing large portions of Earth’s magnetosphere from the vantage point of the SMILE orbit. SXI is sensitive to the soft X-rays produced by the Solar Wind Charge eXchange (SWCX) process produced when heavy ions of solar wind origin interact with neutral particles in Earth’s exosphere. SWCX provides a mechanism for boundary detection within the magnetosphere, such as the position of Earth’s magnetopause, because the solar wind heavy ions have a very low density in regions of closed magnetic field lines. The sensitivity of the SXI is such that it can potentially track movements of the magnetopause on timescales of a few minutes and the orbit of SMILE will enable such movements to be tracked for segments lasting many hours. SXI is led by the University of Leicester in the United Kingdom (UK) with collaborating organisations on hardware, software and science support within the UK, Europe, China and the United States

Effect of diet composition on postweaning colibacillosis in piglets

The weaning of piglets is often associated with digestive disorders, particularly diarrhea—postweaning colibacillosis (PWC)—which is caused by infection with enterotoxigenic strains of Escherichia coli. It has been shown previously that a diet for newly weaned pigs based on cooked white rice and animal protein decreases the occurrence of PWC, whereas the addition of carboxymethylcellulose (CMC) to this diet enhances PWC. The aims of the current work were to 1) determine whether substitution of animal protein with plant proteins in the cooked-white-rice diet influenced its protective effects on PWC and 2) confirm that an increase in viscosity of the digesta by adding CMC to the diet favors the development of PWC—with (Exp. 1) or without (Exp. 2) experimental infection of piglets with E. coli. The diets were 1) cooked white rice and animal protein sources (RAP), 2) RAP + CMC added at 40 g of CMC/kg (air-dry basis) of diet, 3) cooked white rice and plant protein sources (RPP), and 4) wheat and plant protein sources (WPP). Experiments 1 and 2 were conducted using 32 and 24 piglets (eight and six per treatment), respectively. Piglets were weaned at 21 d (d 1), and fed ad libitum until slaughter on d 9. In Exp. 1, piglets were orally infected with enterotoxigenic E. coli on d 4, 5, 6, and 7. On d 8 of Exp. 1, the E. coli scores in feces of pigs fed RAP + CMC were higher than with RAP (P < 0.01). On d 9 after weaning, feces from pigs fed diet RAP were normal or moist, whereas feces from pigs fed RAP + CMC were wet to diarrheic. On d 7 of Exp. 2, pigs fed diets RAP + CMC and WPP had wetter feces than pigs fed diets RAP or RPP (P < 0.05). On d 8, the E. coli scores in feces were higher (P < 0.01) with pigs fed RAP + CMC than with all other diets. The E. coli scores in the digesta were also higher with pigs fed RAP + CMC, and to a lesser extent with diet WPP, than with pigs fed RAP or RPP (P < 0.01). The large intestine was heavier in pigs fed diets RPP and WPP, and the digesta were more acidic (P < 0.05). This study confirmed that diet RAP was protective against PWC, and that substitution of animal proteins with plant protein in a rice-based diet did not diminish its protective effects. The addition of CMC to cooked white rice increased digesta viscosity and enhanced PWC. Consequently, this diet represents a useful model for studying this condition