Phosphorus-31: A table-top method for 3D B1-field amplitude and phase measurements.

A novel method of high-spatial-resolution, 3D B1-field distribution measurements is presented. The method is independent of the MR-scanner, and it allows for automated acquisitions of complete maps of all magnetic field vector components for both proton and heteronuclear MR coils of arbitrary geometrical shapes. The advantage of the method proposed here, compared with methods based on measurements with an MR-scanner, is that a complete image of both receive and transmit B1-fields, including the phase of the B1-field, can be acquired. The B1 field maps obtained in this manner can be used for absolute quantification of metabolites in MRS experiments, as well as for intensity compensations in imaging experiments, both of which are important concepts in biological and medical MR applications. Another use might be in coil development and testing. A comparison with B1 field magnitude maps obtained with an MR-scanner was included to validate the accuracy of the proposed method.

Brain Parcellation Repeatability and Reproducibility Using Conventional and Quantitative 3D MR Imaging.

BACKGROUND AND PURPOSE: Automatic brain parcellation is typically performed on dedicated MR imaging sequences, which require valuable examination time. In this study, a 3D MR imaging quantification sequence to retrieve R1 and R2 relaxation rates and proton density maps was used to synthesize a T1-weighted image stack for brain volume measurement, thereby combining image data for multiple purposes. The repeatability and reproducibility of using the conventional and synthetic input data were evaluated. MATERIALS AND METHODS: Twelve subjects with a mean age of 54 years were scanned twice at 1.5T and 3T with 3D-QALAS and a conventionally acquired T1-weighted sequence. Using SyMRI, we converted the R1, R2, and proton density maps into synthetic T1-weighted images. Both the conventional T1-weighted and the synthetic 3D-T1-weighted inversion recovery images were processed for brain parcellation by NeuroQuant. Bland-Altman statistics were used to correlate the volumes of 12 brain structures. The coefficient of variation was used to evaluate the repeatability. RESULTS: A high correlation with medians of 0.97 for 1.5T and 0.92 for 3T was found. A high repeatability was shown with a median coefficient of variation of 1.2% for both T1-weighted and synthetic 3D-T1-weighted inversion recovery at 1.5T, and 1.5% for T1-weighted imaging and 4.4% for synthetic 3D-T1-weighted inversion recovery at 3T. However, significant biases were observed between the methods and field strengths. CONCLUSIONS: It is possible to perform MR imaging quantification of R1, R2, and proton density maps to synthesize a 3D-T1-weighted image stack, which can be used for automatic brain parcellation. Synthetic parameter settings should be reinvestigated to reduce the observed bias.

Phenotype Harmonization in the GLIDE2 Oral Health Genomics Consortium.

Genetic risk factors play important roles in the etiology of oral, dental, and craniofacial diseases. Identifying the relevant risk loci and understanding their molecular biology could highlight new prevention and management avenues. Our current understanding of oral health genomics suggests that dental caries and periodontitis are polygenic diseases, and very large sample sizes and informative phenotypic measures are required to discover signals and adequately map associations across the human genome. In this article, we introduce the second wave of the Gene-Lifestyle Interactions and Dental Endpoints consortium (GLIDE2) and discuss relevant data analytics challenges, opportunities, and applications. In this phase, the consortium comprises a diverse, multiethnic sample of over 700,000 participants from 21 studies contributing clinical data on dental caries experience and periodontitis. We outline the methodological challenges of combining data from heterogeneous populations, as well as the data reduction problem in resolving detailed clinical examination records into tractable phenotypes, and describe a strategy that addresses this. Specifically, we propose a 3-tiered phenotyping approach aimed at leveraging both the large sample size in the consortium and the detailed clinical information available in some studies, wherein binary, severity-encompassing, and "precision," data-driven clinical traits are employed. As an illustration of the use of data-driven traits across multiple cohorts, we present an application of dental caries experience data harmonization in 8 participating studies (N = 55,143) using previously developed permanent dentition tooth surface-level dental caries pattern traits. We demonstrate that these clinical patterns are transferable across multiple cohorts, have similar relative contributions within each study, and thus are prime targets for genetic interrogation in the expanded and diverse multiethnic sample of GLIDE2. We anticipate that results from GLIDE2 will decisively advance the knowledge base of mechanisms at play in oral, dental, and craniofacial health and disease and further catalyze international collaboration and data and resource sharing in genomics research.

Quantitative MRI using relaxometry in malignant gliomas detects contrast enhancement in peritumoral oedema.

Malignant gliomas are primary brain tumours with an infiltrative growth pattern, often with contrast enhancement on magnetic resonance imaging (MRI). However, it is well known that tumour infiltration extends beyond the visible contrast enhancement. The aim of this study was to investigate if there is contrast enhancement not detected visually in the peritumoral oedema of malignant gliomas by using relaxometry with synthetic MRI. 25 patients who had brain tumours with a radiological appearance of malignant glioma were prospectively included. A quantitative MR-sequence measuring longitudinal relaxation (R1), transverse relaxation (R2) and proton density (PD), was added to the standard MRI protocol before surgery. Five patients were excluded, and in 20 patients, synthetic MR images were created from the quantitative scans. Manual regions of interest (ROIs) outlined the visibly contrast-enhancing border of the tumours and the peritumoral area. Contrast enhancement was quantified by subtraction of native images from post GD-images, creating an R1-difference-map. The quantitative R1-difference-maps showed significant contrast enhancement in the peritumoral area (0.047) compared to normal appearing white matter (0.032), p = 0.048. Relaxometry detects contrast enhancement in the peritumoral area of malignant gliomas. This could represent infiltrative tumour growth.

Improved Precision of Automatic Brain Volume Measurements in Patients with Clinically Isolated Syndrome and Multiple Sclerosis Using Edema Correction.

BACKGROUND AND PURPOSE: The presence of edema will result in increased brain volume, which may obscure progressing brain atrophy. Similarly, treatment-induced edema reduction may appear as accelerated brain tissue loss (pseudoatrophy). The purpose of this study was to correlate brain tissue properties to brain volume, to investigate the possibilities for edema correction and the resulting improvement of the precision of automated brain volume measurements. MATERIALS AND METHODS: A group of 38 patients with clinically isolated syndrome or newly diagnosed MS were imaged at inclusion and after 1, 2, and 4 years using an MR quantification sequence. Brain volume, relaxation rates (R1 and R2), and proton density were measured by automated software. RESULTS: The reduction of normalized brain volume with time after inclusion was 0.273%/year. The mean SDs were 0.508%, 0.526%, 0.454%, and 0.687% at baseline and 1, 2, and 4 years. Linear regression of the relative change of normalized brain volume and the relative change of R1, R2, and proton density showed slopes of -0.198 (P < .001), 0.156 (P = .04), and 0.488 (P < .001), respectively. After we applied the measured proton density as a correction factor, the mean SDs decreased to 24.2%, 4.8%, 33.3%, and 17.4%, respectively. The observed atrophy rate reduced from 0.273%/year to 0.238%/year. CONCLUSIONS: Correlations between volume and R1, R2, and proton density were observed in the brain, suggesting that a change of brain tissue properties can affect brain volume. Correction using these parameters decreased the variation of brain volume measurements and may have reduced the effect of pseudoatrophy.

Neurofilament light chain in cerebrospinal fluid and prediction of disease activity in clinically isolated syndrome and relapsing-remitting multiple sclerosis.

BACKGROUND AND PURPOSE: Improved biomarkers are needed to facilitate clinical decision-making and as surrogate endpoints in clinical trials in multiple sclerosis (MS). We assessed whether neurodegenerative and neuroinflammatory markers in cerebrospinal fluid (CSF) at initial sampling could predict disease activity during 2 years of follow-up in patients with clinically isolated syndrome (CIS) and relapsing-remitting MS. METHODS: Using multiplex bead array and enzyme-linked immunosorbent assay, CXCL1, CXCL8, CXCL10, CXCL13, CCL20, CCL22, neurofilament light chain (NFL), neurofilament heavy chain, glial fibrillary acidic protein, chitinase-3-like-1, matrix metalloproteinase-9 and osteopontin were analysed in CSF from 41 patients with CIS or relapsing-remitting MS and 22 healthy controls. Disease activity (relapses, magnetic resonance imaging activity or disability worsening) in patients was recorded during 2 years of follow-up in this prospective longitudinal cohort study. RESULTS: In a logistic regression analysis model, NFL in CSF at baseline emerged as the best predictive marker, correctly classifying 93% of patients who showed evidence of disease activity during 2 years of follow-up and 67% of patients who did not, with an overall proportion of 85% (33 of 39 patients) correctly classified. Combining NFL with either neurofilament heavy chain or osteopontin resulted in 87% overall correctly classified patients, whereas combining NFL with a chemokine did not improve results. CONCLUSIONS: This study demonstrates the potential prognostic value of NFL in baseline CSF in CIS and relapsing-remitting MS and supports its use as a predictive biomarker of disease activity.

Cerebrospinal fluid levels of neurofilament and tau correlate with brain atrophy in natalizumab-treated multiple sclerosis.

BACKGROUND AND PURPOSE: Brain atrophy is related to clinical deterioration in multiple sclerosis (MS) but its association with intrathecal markers of inflammation or neurodegeneration is unclear. Our aim was to investigate whether cerebrospinal fluid (CSF) markers of inflammation or neurodegeneration are associated with brain volume change in natalizumab-treated MS and whether this change is reflected in non-lesional white matter metabolites. METHODS: About 25 patients with natalizumab-treated MS were followed for 3 years with assessment of percentage brain volume change (PBVC) and absolute quantification of metabolites with proton magnetic resonance spectroscopy (1 H MRS). Analyses of inflammatory [interleukin 1ß (IL-1ß), IL-6, C-X-C motif chemokine 8 (CXCL8), CXCL10, CXCL11, C-C motif chemokine 22] and neurodegenerative [neurofilament light protein (NFL), glial fibrillary acidic protein, myelin basic protein, tau proteins] markers were done at baseline and 1-year follow-up. RESULTS: The mean decline in PBVC was 3% at the 3-year follow-up, although mean 1 H MRS metabolite levels in non-lesional white matter were unchanged. CSF levels of NFL and tau at baseline correlated negatively with PBVC over 3 years (r = -0.564, P = 0.012, and r = -0.592, P = 0.010, respectively). CONCLUSIONS: A significant 3-year whole-brain atrophy was not reflected in mean metabolite change of non-lesional white matter. In addition, our results suggest that CSF levels of NFL and tau correlate with brain atrophy development and may be used for evaluating treatment response in inflammatory active MS.

Laparoscopic Colonic Resection Without Urinary Drainage: Is It "Feasible"?

BACKGROUND: Urinary retention following colorectal surgery is a known and costly morbidity. Increasing effort is being made to streamline patient recovery following colon resection, though the ideal timing and duration of urinary catheterization (UC) and its effect on urinary retention (UR) and urinary tract infection (UTI) remain controversial. METHODS: Our program prospectively enrolled patients undergoing elective segmental colon resection through our "fast track" protocol, in which UC is completely avoided unless required for fluid management or to facilitate dissection. Patient demographics and perioperative data including type of analgesia, duration of anesthesia, timing of UC, and rates of perioperative UR and UTI were prospectively recorded. RESULTS: Sixty-five patients met inclusion criteria. Sigmoid colectomy was the most common procedure (76.9 %). The average duration of anesthesia was 274 min, and epidural analgesia was employed in 32 (49.2 %). Twenty-two patients (33.8 %) required temporary perioperative UC. All patients left the operating room without a urinary catheter. Urinary retention occurred in six patients (9.2 %, three with and three without epidural analgesia). One patient who was not catheterized developed a UTI (1.5 %). There was no perioperative mortality. Overall, 39 (60.0 %) patients successfully underwent segmental colon resection and hospital discharge without any UC. CONCLUSIONS: "Fast track" enhanced recovery after elective segmental colon resection without requiring UC is safe and feasible. Epidural analgesia does not mandate the use of UC. In light of the considerable morbidity and cost of UR and UTI, this approach merits further investigation for this patient population.

Quantitative MRI for Analysis of Active Multiple Sclerosis Lesions without Gadolinium-Based Contrast Agent.

BACKGROUND AND PURPOSE: Contrast-enhancing MS lesions are important markers of active inflammation in the diagnostic work-up of MS and in disease monitoring with MR imaging. Because intravenous contrast agents involve an expense and a potential risk of adverse events, it would be desirable to identify active lesions without using a contrast agent. The purpose of this study was to evaluate whether pre-contrast injection tissue-relaxation rates and proton density of MS lesions, by using a new quantitative MR imaging sequence, can identify active lesions. MATERIALS AND METHODS: Forty-four patients with a clinical suspicion of MS were studied. MR imaging with a standard clinical MS protocol and a quantitative MR imaging sequence was performed at inclusion (baseline) and after 1 year. ROIs were placed in MS lesions, classified as nonenhancing or enhancing. Longitudinal and transverse relaxation rates, as well as proton density were obtained from the quantitative MR imaging sequence. Statistical analyses of ROI values were performed by using a mixed linear model, logistic regression, and receiver operating characteristic analysis. RESULTS: Enhancing lesions had a significantly (P < .001) higher mean longitudinal relaxation rate (1.22 ± 0.36 versus 0.89 ± 0.24), a higher mean transverse relaxation rate (9.8 ± 2.6 versus 7.4 ± 1.9), and a lower mean proton density (77 ± 11.2 versus 90 ± 8.4) than nonenhancing lesions. An area under the receiver operating characteristic curve value of 0.832 was obtained. CONCLUSIONS: Contrast-enhancing MS lesions often have proton density and relaxation times that differ from those in nonenhancing lesions, with lower proton density and shorter relaxation times in enhancing lesions compared with nonenhancing lesions.

Feasibility of Catheter Placement Under Ultrasound Guidance for Progressive Preoperative Pneumoperitoneum for Large Incisional Hernia with Loss of Domain.

INTRODUCTION: Large incisional hernias with loss of domain (LIHLD) of the abdominal wall remain a therapeutic challenge due to the difficulty of replacing the contents of the hernia sac into the peritoneal cavity. Preoperative progressive pneumoperitoneum (PPP) is a valuable option. The purpose of this study was to evaluate the feasibility of peritoneal catheter insertion under ultrasound guidance for PPP and to compare the morbidity and mortality of this new technique to previously used techniques in our department. METHODS: Medical records were reviewed retrospectively from February 1989 to April 2013 in a single institution. Three different techniques of PPP were evaluated: surgical subcutaneous implantable port (SIP), surgical peritoneal dialysis catheter (PDC), and radiologic multipurpose drainage catheter (MDC). Collected data included patients' age, sex, body mass index, medical and surgical history, hernia location, PPP technique, length of hospitalization, volume of air injected, morbidity and mortality linked to PPP, and the procedure of hernia repair. RESULTS: Thirty-seven patients with a mean age of 63.1 years were evaluated. Progressive preoperative pneumoperitoneum was performed using SIP, PDC, and MDC for 14, 11, and 12 patients, respectively. Overall morbidity related to the technique was seen in 36 % of SIP, 27 % of PDC, and 0 % of MDC. One patient from the SIP group died on the 3rd postoperative day due to septic shock following aspiration pneumonia. No postoperative mortality in the other groups was observed. CONCLUSION: The MDC is an interesting modification of the original technique and is a safe procedure. It is a minimally invasive technique with a very low risk of perforation of the viscera. Therefore, the use of a non-absorbable prosthesis with MDC technique can be offered for all patients undergoing PPP without increasing the risk of infection.

Professional risks when carrying out cytoreductive surgery for peritoneal malignancy with hyperthermic intraperitoneal chemotherapy (HIPEC): A French multicentric survey.

BACKGROUND: Over the last two decades, many surgical teams have developed programs to treat peritoneal carcinomatosis with extensive cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC). Currently, there are no specific recommendations for HIPEC procedures concerning environmental contamination risk management, personal protective equipment (PPE), or occupational health supervision. METHODS: A survey of the institutional practices among all French teams currently performing HIPEC procedures was carried out via the French network for the treatment of rare peritoneal malignancies (RENAPE). RESULTS: Thirty three surgical teams responded, 14 (42.4%) which reported more than 10 years of HIPEC experience. Some practices were widespread, such as using HIPEC machine approved by the European Community (100%), individualized or centralized smoke evacuation (81.8%), "open" abdominal coverage during perfusion (75.8%), and maintaining the same surgeon throughout the procedure (69.7%). Others were more heterogeneous, including laminar flow air circulation (54.5%) and the provision of safety protocols in the event of perfusate spills (51.5%). The use of specialized personal protective equipment is ubiquitous (93.9%) but widely variable between programs. CONCLUSION: Protocols regarding cytoreductive surgery/HIPEC and the associated professional risks in France lack standardization and should be established.

Approach to the male patient with sexual dysfunction.

The management of the male patient with sexual dysfunction (SD) requires special knowledge and abilities. Generally, SD is best approached from the physiologic perspective, keeping in mind that sexual functioning has important psychosocial dimensions. The history obtained from the patient and, if possible, from his partner should seek information not only on the SD, but also on coexisting neurologic or medical disorders. A list of drugs should be obtained, as many prescription drugs, even in low doses, can influence sexual function. The clinical examination, including sensory, motor, and reflex testing of the lumbosacral segments, may reveal pertinent somatic abnormalities, which in the case of a suspected peripheral nervous system lesion may be supported by clinical neurophysiologic testing. The first-line diagnostic approach includes defining the type of sexual dysfunction to allow the most appropriate therapy. Metabolic and other systemic diseases need to be ruled out. Patients suspected of having psychologic, structural, urologic, endocrinologic, or vascular etiology of SD should be referred to the appropriate specialist.

Deficient habituation to repeated rectal distensions in irritable bowel syndrome patients with visceral hypersensitivity.

BACKGROUND: Irritable bowel syndrome (IBS) patients show evidence of altered central processing of visceral signals. One of the proposed alterations in sensory processing is an altered engagement of endogenous pain modulation mechanisms. The aim was to test the hypothesis that IBS patients with (IBS-S) and without visceral hypersensitivity (IBS-N) differ in their ability to engage endogenous pain modulation mechanism during habituation to repeated visceral stimuli. METHODS: Brain blood oxygen level dependent (BOLD) response was measured during repeated rectal distension and its anticipation in 33 IBS patients with and without visceral hypersensitivity and 18 healthy controls (HCs). BOLD response to early and late phase of the distension series was compared within and between groups. KEY RESULTS: While BOLD response was similar during the early phase of the experiment, IBS-S showed greater BOLD response than IBS-N and HCs during the late phase of the distension series. IBS-S showed increasing BOLD response both to the anticipation and delivery of low intensity rectal distensions in brain regions including insula, anterior and mid cingulate cortex. IBS-N showed decreasing BOLD response to repeated rectal distensions in brain regions including insula, prefrontal cortex and amygdala. CONCLUSIONS & INFERENCES: These findings are consistent with compromised ability of IBS-S to respond to repeated delivery of rectal stimuli, both in terms of sensitization of sensory pathways and habituation of emotional arousal. The fact that both IBS subgroups met Rome criteria, and did not differ in terms of reported symptom severity demonstrates that similar symptom patterns can result from different underlying neurobiological mechanisms.

Interactions between polymorphisms in the aryl hydrocarbon receptor signalling pathway and exposure to persistent organochlorine pollutants affect human semen quality.

Persistent organic pollutants (POPs) may affect male reproductive function. Many dioxin-like POPs exert their effects by activation of the aryl hydrocarbon receptor (AHR) signalling pathway. We analysed whether gene-environment interactions between polymorphisms in AHR (R554K) and AHR repressor (AHRR P185A) and serum levels of markers of POP exposure 1,1-bis-(4-chlorophenyl)-2,2-dichloroethene (p,p'-DDE) and 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153) are associated with 21 parameters of male reproductive function in 581 proven-fertile European and Greenlandic men. In Greenlandic men, AHR variants significantly modified the association between serum levels of both p,p'-DDE and CB-153 and inhibin B levels, sperm chromatin integrity, and seminal zinc levels. In the total cohort, interactions between AHRR variants and serum levels of CB-153 were associated with sperm chromatin integrity and the expression of the pro-apoptotic marker protein Fas. The data indicate that susceptibility to adverse effects of POP exposure on male reproductive function is dependent on polymorphisms in genes involved in AHR signalling.

Effects of gadolinium contrast agent administration on automatic brain tissue classification of patients with multiple sclerosis.

BACKGROUND AND PURPOSE: The administration of gadolinium contrast agent is a common part of MR imaging examinations in patients with MS. The presence of gadolinium may affect the outcome of automated tissue classification. The purpose of this study was to investigate the effects of the presence of gadolinium on the automatic segmentation in patients with MS by using the synthetic tissue-mapping method. MATERIALS AND METHODS: A cohort of 20 patients with clinically definite multiple sclerosis were recruited, and the T1 and T2 relaxation times and proton density were simultaneously quantified before and after the administration of gadolinium. Synthetic tissue-mapping was used to measure white matter, gray matter, CSF, brain parenchymal, and intracranial volumes. For comparison, 20 matched controls were measured twice, without gadolinium. RESULTS: No differences were observed for the control group between the 2 measurements. For the MS group, significant changes were observed pre- and post-gadolinium in intracranial volume (-13 mL, P < .005) and cerebrospinal fluid volume (-16 mL, P < .005) and the remaining, unclassified non-WM/GM/CSF tissue volume within the intracranial volume (+8 mL, P < .05). The changes in the patient group were much smaller than the differences, compared with the controls, which were -129 mL for WM volume, -22 mL for GM volume, +91 mL for CSF volume, 24 mL for the remaining, unclassified non-WM/GM/CSF tissue volume within the intracranial volume, and -126 mL for brain parenchymal volume. No significant differences were observed for linear regression values against age and Expanded Disability Status Scale. CONCLUSIONS: The administration of gadolinium contrast agent had a significant effect on automatic brain-tissue classification in patients with MS by using synthetic tissue-mapping. The observed differences, however, were much smaller than the group differences between MS and controls.

Scaling of the mean and variance of population dynamics under fluctuating regimes.

Theoretical ecologists have long sought to understand how the persistence of populations depends on the interactions between exogenous (biotic and abiotic) and endogenous (e.g., demographic and genetic) drivers of population dynamics. Recent work focuses on the autocorrelation structure of environmental perturbations and its effects on the persistence of populations. Accurate estimation of extinction times and especially determination of the mechanisms affecting extinction times is important for biodiversity conservation. Here we examine the interaction between environmental fluctuations and the scaling effect of the mean population size with its variance. We investigate how interactions between environmental and demographic stochasticity can affect the mean time to extinction, change optimal patch size dynamics, and how it can alter the often-assumed linear relationship between the census size and the effective population size. The importance of the correlation between environmental and demographic variation depends on the relative importance of the two types of variation. We found the correlation to be important when the two types of variation were approximately equal; however, the importance of the correlation diminishes as one source of variation dominates. The implications of these findings are discussed from a conservation and eco-evolutionary point of view.

Effect of hypnotherapy and educational intervention on brain response to visceral stimulus in the irritable bowel syndrome.

BACKGROUND: Gut-directed hypnotherapy can reduce IBS symptoms, but the mechanisms underlying this therapeutic effect remain unknown. AIM: To determine the effect of hypnotherapy and educational intervention on brain responses to cued rectal distensions in IBS patients. METHODS: Forty-four women with moderate-to-severe IBS and 20 healthy controls (HCs) were included. Blood oxygen level dependent (BOLD) signals were measured by functional Magnetic Resonance Imaging (fMRI) during expectation and delivery of high- (45 mmHg) and low-intensity (15 mmHg) rectal distensions. Twenty-five patients were assigned to hypnotherapy (HYP) and 16 to educational intervention (EDU). Thirty-one patients completed treatments and posttreatment fMRI. RESULTS: Similar symptom reduction was achieved in both groups. Clinically successful treatment (all responders) was associated with significant BOLD attenuation during high-intensity distension in the dorsal and ventral anterior insula (cluster size 142, P = 0.006, and cluster size 101, P = 0.005 respectively). Moreover HYP responders demonstrated a pre-post treatment BOLD attenuation in posterior insula (cluster sizes 59, P = 0.05) while EDU responders had a BOLD attenuation in prefrontal cortex (cluster size 60, P = 0.05). Pre-post differences for expectation conditions were almost exclusively seen in the HYP group. Following treatment, the brain response to distension was similar to that observed in HCs, suggesting that the treatment had a normalising effect on the central processing abnormality of visceral signals in IBS. CONCLUSIONS: The abnormal processing and enhanced perception of visceral stimuli in IBS can be normalised by psychological interventions. Symptom improvement in the treatment groups may be mediated by different brain mechanisms. CLINICAL TRIAL NUMBER: NCT01815164.

Decreased muscle concentrations of ATP and PCR in the quadriceps muscle of fibromyalgia patients--a 31P-MRS study.

BACKGROUND AND METHODS: Fibromyalgia (FMS) has a prevalence of approximately 2% in the population. Central alterations have been described in FMS, but there is not consensus with respect to the role of peripheral factors for the maintenance of FMS. 31P magnetic resonance spectroscopy (31P-MRS) has been used to investigate the metabolism of phosphagens in muscles of FMS patients, but the results in the literature are not in consensus. The aim was to investigate the quantitative content of phosphagens and pH in resting quadriceps muscle of patients with FMS (n = 19) and in healthy controls (CONTROLS; n = 14) using (31) P-MRS. It was also investigated whether the concentrations of these substances correlated with measures of pain and/or physical capacity. RESULTS: Significantly lower concentrations of adenosine triphosphate (ATP) and phosphocreatinine (PCr; 28-29% lower) were found in FMS. No significant group differences existed with respect to inorganic phosphate (Pi), Pi/PCr and pH. The quadriceps muscle fat content was significantly higher in FMS than in CONTROLS [FMS: 9.0 ± 0.5% vs. CONTROLS: 6.6 ± 0.6%; (mean ± standard error); P = 0.005]. FMS had significantly lower hand and leg capacity according to specific physical test, but there were no group differences in body mass index, subjective activity level and in aerobic fitness. In FMS, the specific physical capacity in the leg and the hand correlated positively with the concentrations of ATP and PCr; no significant correlations were found with pain intensities. CONCLUSIONS: Alterations in intramuscular ATP, PCr and fat content in FMS probably reflect a combination of inactivity related to pain and dysfunction of muscle mitochondria.

IL-4 and IL-13 inhibit IL-1ß and TNF-α induced kinin B1 and B2 receptors through a STAT6-dependent mechanism.

BACKGROUND AND PURPOSE: Bone resorption induced by interleukin-1ß (IL-1ß) and tumour necrosis factor (TNF-α) is synergistically potentiated by kinins, partially due to enhanced kinin receptor expression. Inflammation-induced bone resorption can be impaired by IL-4 and IL-13. The aim was to investigate if expression of B1 and B2 kinin receptors can be affected by IL-4 and IL-13. EXPERIMENTAL APPROACH: We examined effects in a human osteoblastic cell line (MG-63), primary human gingival fibroblasts and mouse bones by IL-4 and IL-13 on mRNA and protein expression of the B1 and B2 kinin receptors. We also examined the role of STAT6 by RNA interference and using Stat6(-/-) mice. KEY RESULTS: IL-4 and IL-13 decreased the mRNA expression of B1 and B2 kinin receptors induced by either IL-1ß or TNF-α in MG-63 cells, intact mouse calvarial bones or primary human gingival fibroblasts. The burst of intracellular calcium induced by either bradykinin (B2 agonist) or des-Arg(10) -Lys-bradykinin (B1 agonist) in gingival fibroblasts pretreated with IL-1ß was impaired by IL-4. Similarly, the increased binding of B1 and B2 ligands induced by IL-1ß was decreased by IL-4. In calvarial bones from Stat6-deficient mice, and in fibroblasts in which STAT6 was knocked down by siRNA, the effect of IL-4 was decreased. CONCLUSIONS AND IMPLICATIONS: These data show, for the first time, that IL-4 and IL-13 decrease kinin receptors in a STAT6-dependent mechanism, which can be one important mechanism by which these cytokines exert their anti-inflammatory effects and impair bone resorption.