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In December 2014, Thai Union, the parent company of Chicken of the Sea canned tuna announced that it had reached an agreement to acquire Bumble Bee tuna from Lion Capital. In the course of standard merger review, the Department of Justice subpoenaed the merging parties as well as the parent company of StarKist to investigate possible collusion among the major producers of canned tuna. This led to several class action lawsuits and a criminal conviction for price fixing. This paper describes how these firms were alleged to have colluded and uses retail scanner data to document how prices and promotional activity changed while the cartel was in operation. Avenues for future research are discussed.

While COVID-19 research has seen an explosion in the literature, the impact of pandemic-related societal and lifestyle disruptions on brain health among the uninfected remains underexplored. However, a global increase in the prevalence of fatigue, brain fog, depression and other "sickness behavior"-like symptoms implicates a possible dysregulation in neuroimmune mechanisms even among those never infected by the virus. We compared fifty-seven 'Pre-Pandemic' and fifteen 'Pandemic' datasets from individuals originally enrolled as control subjects for various completed, or ongoing, research studies available in our records, with a confirmed negative test for SARS-CoV-2 antibodies. We used a combination of multimodal molecular brain imaging (simultaneous positron emission tomography / magnetic resonance spectroscopy), behavioral measurements, imaging transcriptomics and serum testing to uncover links between pandemic-related stressors and neuroinflammation. Healthy individuals examined after the enforcement of 2020 lockdown/stay-at-home measures demonstrated elevated brain levels of two independent neuroinflammatory markers (the 18 kDa translocator protein, TSPO, and myoinositol) compared to pre-lockdown subjects. The serum levels of two inflammatory markers (interleukin-16 and monocyte chemoattractant protein-1) were also elevated, although these effects did not reach statistical significance after correcting for multiple comparisons. Subjects endorsing higher symptom burden showed higher TSPO signal in the hippocampus (mood alteration, mental fatigue), intraparietal sulcus and precuneus (physical fatigue), compared to those reporting little/no symptoms. Post-lockdown TSPO signal changes were spatially aligned with the constitutive expression of several genes involved in immune/neuroimmune functions. This work implicates neuroimmune activation as a possible mechanism underlying the non-virally-mediated symptoms experienced by many during the COVID-19 pandemic. Future studies will be needed to corroborate and further interpret these preliminary findings.

We recently showed that patients with different chronic pain conditions (such as chronic low back pain, fibromyalgia, migraine and Gulf War illness) demonstrated elevated brain and/or spinal cord levels of the glial marker 18-kDa translocator protein (TSPO), which suggests that neuroinflammation might be a pervasive phenomenon observable across multiple aetiologically heterogeneous pain disorders. Interestingly, the spatial distribution of this neuroinflammatory signal appears to exhibit a degree of disease specificity (e.g. with respect to the involvement of the primary somatosensory cortex), suggesting that different pain conditions may exhibit distinct ‘neuroinflammatory signatures’. To explore this hypothesis further, we tested whether neuroinflammatory signal can characterize putative aetiological subtypes of chronic low back pain patients based on clinical presentation. Specifically, we explored neuroinflammation in patients whose chronic low back pain either did or did not radiate to the leg (i.e. ‘radicular’ versus ‘axial’ back pain). Fifty-four patients with chronic low back pain, 26 with axial back pain [43.7 ± 16.6 years old (mean ± SD)] and 28 with radicular back pain (48.3 ± 13.2 years old), underwent PET/MRI with 11C-PBR28, a second-generation radioligand for TSPO. 11C-PBR28 signal was quantified using standardized uptake values ratio (validated against volume of distribution ratio; n = 23). Functional MRI data were collected simultaneously to the 11C-PBR28 data (i) to functionally localize the primary somatosensory cortex back and leg subregions; and (ii) to perform functional connectivity analyses (in order to investigate possible neurophysiological correlations of the neuroinflammatory signal). PET and functional MRI measures were compared across groups, cross-correlated with one another and with the severity of ‘fibromyalgianess’ (i.e. the degree of pain centralization, or ‘nociplastic pain’). Furthermore, statistical mediation models were used to explore possible causal relationships between these three variables. For the primary somatosensory cortex representation of back/leg, 11C-PBR28 PET signal and functional connectivity to the thalamus were: (i) higher in radicular compared to axial back pain patients; (ii) positively correlated with each other; (iii) positively correlated with fibromyalgianess scores, across groups; and finally (iv) fibromyalgianess mediated the association between 11C-PBR28 PET signal and primary somatosensory cortex–thalamus connectivity across groups. Our findings support the existence of ‘neuroinflammatory signatures’ that are accompanied by neurophysiological changes and correlate with clinical presentation (in particular, with the degree of nociplastic pain) in chronic pain patients. These signatures may contribute to the subtyping of distinct pain syndromes and also provide information about interindividual variability in neuroimmune brain signals, within diagnostic groups, that could eventually serve as targets for mechanism-based precision medicine approaches.

The etiology of bipolar disorder (BD) is unknown and the neurobiological underpinnings are not fully understood. Both genetic and environmental factors contribute to the risk of BD, which may be linked through epigenetic mechanisms, including those regulated by histone deacetylase (HDAC) enzymes. This study measures in vivo HDAC expression in individuals with BD for the first time using the HDAC-specific radiotracer [11C]Martinostat. Eleven participants with BD and 11 age- and sex-matched control participants (CON) completed a simultaneous magnetic resonance – positron emission tomography (MR-PET) scan with [11C]Martinostat. Lower [11C]Martinostat uptake was found in the right amygdala of BD compared to CON. We assessed uptake in the dorsolateral prefrontal cortex (DLPFC) to compare previous findings of lower uptake in the DLPFC in schizophrenia and found no group differences in BD. Exploratory whole-brain voxelwise analysis showed lower [11C]Martinostat uptake in the bilateral thalamus, orbitofrontal cortex, right hippocampus, and right amygdala in BD compared to CON. Furthermore, regional [11C]Martinostat uptake was associated with emotion regulation in BD in fronto-limbic areas, which aligns with findings from previous structural, functional, and molecular neuroimaging studies in BD. Regional [11C]Martinostat uptake was associated with attention in BD in fronto-parietal and temporal regions. These findings indicate a potential role of HDACs in BD pathophysiology. In particular, HDAC expression levels may modulate attention and emotion regulation, which represent two core clinical features of BD.

Gulf War Illness (GWI) is a chronic disorder affecting approximately 30% of the veterans who served in the 1991 Gulf War. It is characterised by a constellation of symptoms including musculoskeletal pain, cognitive problems and fatigue. The cause of GWI is not definitively known but exposure to neurotoxicants, the prophylactic use of pyridostigmine bromide (PB) pills, and/or stressors during deployment have all been suspected to play some pathogenic role. Recent animal models of GWI have suggested that neuroinflammatory mechanisms may be implicated, including a dysregulated activation of microglia and astrocytes. However, neuroinflammation has not previously been directly observed in veterans with GWI. To measure GWI-related neuroinflammation in GW veterans, we conducted a Positron Emission Tomography (PET) study using [11C]PBR28, which binds to the 18 kDa translocator protein (TSPO), a protein upregulated in activated microglia/macrophages and astrocytes. Veterans with GWI (n = 15) and healthy controls (HC, n = 33, including a subgroup of healthy GW veterans, HCVET, n = 8), were examined using integrated [11C]PBR28 PET/MRI. Standardized uptake values normalized by occipital cortex signal (SUVR) were compared across groups and against clinical variables and circulating inflammatory cytokines (TNF-α, IL-6 and IL-1β). SUVR were validated against volume of distribution ratio (n = 13). Whether compared to the whole HC group, or only the HCVET subgroup, veterans with GWI demonstrated widespread cortical elevations in [11C]PBR28 PET signal, in areas including precuneus, prefrontal, primary motor and somatosensory cortices. There were no significant group differences in the plasma levels of the inflammatory cytokines evaluated. There were also no significant correlations between [11C]PBR28 PET signal and clinical variables or circulating inflammatory cytokines. Our study provides the first direct evidence of brain upregulation of the neuroinflammatory marker TSPO in veterans with GWI and supports the exploration of neuroinflammation as a therapeutic target for this disorder.

IntroductionChronic pain is an extremely prevalent public health issue. However, the underlying mechanisms are poorly understood, thus limiting effective treatment options. Both preclinical studies, and more recent clinical imaging studies, suggest that glia-mediated neuroinflammation may be implicated in chronic pain, and therefore might be a potential treatment target. However, it is currently unknown whether modulating neuroinflammation effectively alleviates pain in humans. This trial tests the hypothesis that minocycline, an FDA-approved tetracycline antibiotic and effective glial cell inhibitor in animals, reduces neuroinflammation and may reduce pain symptoms in humans with chronic low back pain.Methods and analysisThis study is a randomized, double-blind, placebo-controlled clinical trial. Subjects, aged 18-65, with a confirmed diagnosis of chronic (≥ six months) low back pain (cLBP) and a self-reported pain rating of at least four out of ten (for at least half of the days during an average week) are enrolled via written, informed consent. Eligible subjects are randomized to receive a 14-day course of either active drug (minocycline) or placebo. Before and after treatment, subjects are scanned with integrated Positron Emission Tomography/Magnetic Resonance Imaging (PET/MRI) using [11C]PBR28, a second-generation radiotracer for the 18 kDa translocator protein (TSPO), which is highly expressed in glial cells and thus a putative marker of neuroinflammation. Pain levels are evaluated via daily surveys, collected seven days prior to the start of medication, and throughout the 14 days of treatment. General linear models are used to assess pain levels and determine the treatment effect on brain (and spinal cord) TSPO signal.Ethics and disseminationThis study was approved by the Massachusetts General Hospital Institutional Review Board (Protocol Number: 2017P000179) and the U.S. Food and Drug Administration (IND Number: 142546). The results of the study will be disseminated via publications in peer-reviewed journals, presentations at conferences globally, and through various media.Trial registration numberClinicalTrials.gov (NCT03106740)Strengths and limitations of this studyThis is the first project to image the potential neuro-inflammatory effect of minocycline in a chronic pain condition.The use of simultaneous PET/MRI allows us to collect additional, ancillary MRI data that can be used to perform a comprehensive neurophysiological assessment of subjects.The sample size (n∼50 per group) is relatively small to detect a clinical response. An additional limitation is the relatively short treatment duration (i.e., 2-weeks).

Age- and sex-related alterations in gene transcription have been demonstrated, however the underlying mechanisms are unresolved. Neuroepigenetic pathways regulate gene transcription in the brain. Here, we measure in vivo expression of the epigenetic enzymes, histone deacetylases (HDACs), across healthy human aging and between sexes using [11C]Martinostat positron emission tomography (PET) neuroimaging (n = 41). Relative HDAC expression increases with age in cerebral white matter, and correlates with age-associated disruptions in white matter microstructure. A post mortem study confirmed that HDAC1 and HDAC2 paralogs are elevated in white matter tissue from elderly donors. There are also sex-specific in vivo HDAC expression differences in brain regions associated with emotion and memory, including the amygdala and hippocampus. Hippocampus and white matter HDAC expression negatively correlates with emotion regulation skills (n = 23). Age and sex are associated with HDAC expression in vivo, which could drive age- and sex-related transcriptional changes and impact human behavior., Gene transcription is known to vary with age and sex, although the underlying mechanisms are unresolved. Here, the authors show that epigenetic enzymes known as HDACs, which regulate gene transcription, are increasingly expressed with age in the living human brain, with sex differences also observed.

SummaryBackgroundThe impact of COVID-19 on human health extends beyond the morbidity and death toll directly caused by the SARS-CoV-2 virus. In fact, accumulating evidence indicates a global increase in the incidence of fatigue, brain fog and depression, including among non-infected, since the pandemic onset. Motivated by previous evidence linking those symptoms to neuroimmune activation in other pathological contexts, we hypothesized that subjects examined after the enforcement of lockdown/stay-at-home measures would demonstrate increased neuroinflammation.MethodsWe performed simultaneous brain Positron Emission Tomography / Magnetic Resonance Imaging in healthy volunteers either before (n=57) or after (n=15) the 2020 Massachusetts lockdown, using [11C]PBR28, a radioligand for the glial marker 18 kDa translocator protein (TSPO). First, we compared [11C]PBR28 signal across pre- and post-lockdown cohorts. Then, we evaluated the link between neuroinflammatory signals and scores on a questionnaire assessing mental and physical impacts of the pandemic. Further, we investigated multivariate associations between the spatial pattern of [11C]PBR28 post-lockdown changes and constitutive brain gene expression in post-mortem brains (Allen Human Brain Atlas). Finally, in a subset (n=13 pre-lockdown; n=11 post-lockdown), we also used magnetic resonance spectroscopy to quantify brain (thalamic) levels of myoinositol (mIns), another neuroinflammatory marker.FindingsBoth [11C]PBR28 and mIns signals were overall stable pre-lockdown, but markedly elevated after lockdown, including within brain regions previously implicated in stress, depression and “sickness behaviors”. Moreover, amongst the post-lockdown cohort, subjects endorsing higher symptom burden showed higher [11C]PBR28 PET signal compared to those reporting little/no symptoms. Finally, the post-lockdown [11C]PBR28 signal changes were spatially aligned with the constitutive expression of several genes highly expressed in glial/immune cells and/or involved in neuroimmune signaling.InterpretationOur results suggest that pandemic-related stressors may have induced sterile neuroinflammation in healthy individuals that were not infected with SARS-CoV-2. This work highlights the possible impact of the COVID-19 pandemic-related lifestyle disruptions on human brain health.FundingR01-NS094306-01A1, R01-NS095937-01A1, R01-DA047088-01, The Landreth Family Foundation.

Neuroinflammation occurs in response to acute ischemic stroke, and has been speculated to underlie secondary poststroke pathologies, such as depression, that often develop over time poststroke. However, no study has examined whether neuroinflammation is present in chronic stroke patients (e.g., ​≥ ​1 year poststroke). This study tested whether neuroinflammation is present in chronic stroke patients, and is associated with neurodegeneration, using [11C]PBR28 PET and diffusion MRI. Eight patients with middle cerebral artery (MCA) ischemic stroke incurred 1–3 years prior and 16 healthy controls underwent [11C]PBR28 PET to measure glial activation and diffusion MRI to measure microstructural integrity by mean diffusivity (MD) and fractional anisotropy (FA) using an integrated PET/MRI scanner. Group differences in [11C]PBR28 binding, MD and FA were analyzed voxelwise across the whole brain excluding the infarct zone defined as voxels containing the infarct in any patient. Compared to controls, patients showed elevations in [11C]PBR28 binding in several brain regions outside the infarct zone, including regions with presumed direct neuroanatomical connections to the infarct (e.g., ipsilesional internal capsule and thalamus) and those without known direct connections (e.g., contralesional thalamus and cingulate gyrus). Patients also showed widespread elevations in MD, with a subset of these regions having reduced FA. In patients, MD was more elevated in regions with co-localized elevations in [11C]PBR28 binding than in contralateral regions without elevations in [11C]PBR28 binding. This pilot study supports the presence of extensive glial activation along with widespread loss in microstructural integrity in non-infarcted tissue in a cohort of patients with chronic MCA stroke. The loss in microstructural integrity was greater in regions with co-localized glial activation. It is possible that stroke risk factors (e.g., hypertension) contributed to these tissue changes in patients., Highlights • Chronic neuroinflammation speculated to underlie secondary poststroke pathologies such as depression. • Measured neuroinflammation in chronic stroke patients using [11C]PBR28 PET. • First study showing extensive neuroinflammation in non-infarcted tissue in chronic stroke patients.

The development of scanners with ultra-high gradient strength, spearheaded by the Human Connectome Project, has led to dramatic improvements in the spatial, angular, and diffusion resolution that is feasible for in vivo diffusion MRI acquisitions. The improved quality of the data can be exploited to achieve higher accuracy in the inference of both microstructural and macrostructural anatomy. However, such high-quality data can only be acquired on a handful of Connectom MRI scanners worldwide, while remaining prohibitive in clinical settings because of the constraints imposed by hardware and scanning time. In this study, we first update the classical protocols for tractography-based, manual annotation of major white-matter pathways, to adapt them to the much greater volume and variability of the streamlines that can be produced from today's state-of-the-art diffusion MRI data. We then use these protocols to annotate 42 major pathways manually in data from a Connectom scanner. Finally, we show that, when we use these manually annotated pathways as training data for global probabilistic tractography with anatomical neighborhood priors, we can perform highly accurate, automated reconstruction of the same pathways in much lower-quality, more widely available diffusion MRI data. The outcomes of this work include both a new, comprehensive atlas of WM pathways from Connectom data, and an updated version of our tractography toolbox, TRActs Constrained by UnderLying Anatomy (TRACULA), which is trained on data from this atlas. Both the atlas and TRACULA are distributed publicly as part of FreeSurfer. We present the first comprehensive comparison of TRACULA to the more conventional, multi-region-of-interest approach to automated tractography, and the first demonstration of training TRACULA on high-quality, Connectom data to benefit studies that use more modest acquisition protocols.

Using positron emission tomography, we recently demonstrated elevated brain levels of the 18kDa translocator protein (TSPO), a glial activation marker, in chronic low back pain (cLBP) patients, compared to healthy controls (HC). Here, we first sought to replicate the original findings in an independent cohort (15 cLBP, 37.8±12.5 y/o; 18 HC, 48.2±12.8 y/o). We then trained random forest (RF) machine learning algorithms based on TSPO imaging features combining discovery and replication cohorts (totaling 25 cLBP, 42.4±13.2 y/o; 27 HC, 48.9±12.6 y/o), in order to explore whether image features other than the mean contain meaningful information that might contribute to the discrimination of cLBP patients and HC. Feature importance was ranked usind SHapley Additive exPlanations (SHAP) values, and the classification performance (in terms of AUC values) of classifiers containing only the mean, other features, or all features was compared using the DeLong test. Both region-of-interest (ROI) and voxelwise analyses replicated the original observation of thalamic TSPO signal elevations in cLBP patients compared to HC (p’s

The weak association between disability levels and "peripheral" (ie, knee) findings suggests that central nervous system alterations may contribute to the pathophysiology of knee osteoarthritis (KOA). Here, we evaluated brain metabolite alterations in patients with KOA, before and after total knee arthroplasty (TKA), using 1H-magnetic resonance spectroscopy (MRS). Thirty-four presurgical patients with KOA and 13 healthy controls were scanned using a PRESS sequence (TE = 30 ms, TR = 1.7 seconds, voxel size = 15 × 15 × 15 mm). In addition, 13 patients were rescanned 4.1 ± 1.6 (mean ± SD) weeks post-TKA. When using creatine (Cr)-normalized levels, presurgical KOA patients demonstrated lower N-acetylaspartate (NAA) (P0.001), higher myoinositol (mIns) (P0.001), and lower Choline (Cho) (P0.05) than healthy controls. The mIns levels were positively correlated with pain severity scores (r = 0.37, P0.05). These effects reached statistical significance also using water-referenced concentrations, except for the Cho group differences (P ≥ 0.067). Post-TKA patients demonstrated an increase in NAA (P0.01), which returned to the levels of healthy controls (P0.05), irrespective of metric. In addition, patients demonstrated postsurgical increases in Cr-normalized (P0.001), but not water-referenced mIns, which were proportional to the NAA/Cr increases (r = 0.61, P0.05). Because mIns is commonly regarded as a glial marker, our results are suggestive of a possible dual role for neuroinflammation in KOA pain and post-TKA recovery. Moreover, the apparent postsurgical normalization of NAA, a putative marker of neuronal integrity, might implicate mitochondrial dysfunction, rather than neurodegenerative processes, as a plausible pathophysiological mechanism in KOA. More broadly, our results add to a growing body of literature suggesting that some pain-related brain alterations can be reversed after peripheral surgical treatment.

Background Cancer survivors have an increased risk of non-cancer-related deaths, particularly metabolic syndrome (MetS). Objective We aimed to assess knowledge deficits regarding metabolism-related diseases among gynecological cancer survivors and the preferred source of health information. Methods Using a mixed methods approach, 70 participants responded to a structured modified version of the MetS questionnaire. We conducted 28 semistructured interviews of gynecological cancer survivors with MetS. Responses were independently coded by 2 researchers, including MetS knowledge, behaviors for self-management, and preferred learning methods. Results Metabolic syndrome was diagnosed in 17% of the participants. More than 50% of the participants wanted to learn about MetS and requested a consultation with healthcare providers, 70% reported that they had heard of MetS, and 61.4% reported that they had MetS-related knowledge (correct answer rate by MetS-related component, ~50%). The level of MetS-related knowledge was poor in both the quantitative and qualitative data. Most of the participants defined MetS-related self-management health behaviors as regular eating and exercise in their own words. Participants mostly wanted exercise management (29% of the participants), followed by dietary life management (27.4%), stress management (17.4%), weight management (13.7%), definition and diagnostic methods of MetS (9.1%), and smoking and drinking management (3.3%). Participants wished to use a handbook in small groups or receive counseling by healthcare providers. Conclusion We observed poor awareness and knowledge level and the need for information regarding MetS among gynecological cancer survivors. Implications for practice An educational handbook or counseling could effectively improve self-management of health-related behaviors.

Fibromyalgia (FM) is a poorly understood chronic condition characterized by widespread musculoskeletal pain, fatigue, and cognitive difficulties. While mounting evidence suggests a role for neuroinflammation, no study has directly provided evidence of brain glial activation in FM. In this study, we conducted a Positron Emission Tomography (PET) study using [(11)C]PBR28, which binds to the translocator protein (TSPO), a protein upregulated in activated microglia and astrocytes. To enhance statistical power and generalizability, we combined datasets collected independently at two separate institutions (Massachusetts General Hospital [MGH] and Karolinska Institutet [KI]). In an attempt to disentangle the contributions of different glial cell types to FM, a smaller sample was scanned at KI with [(11)C]-(L)-deprenyl-D(2) PET, thought to primarily reflect astrocytic (but not microglial) signal. Thirty-one FM patients and 27 healthy controls (HC) were examined using [(11)C]PBR28 PET. 11 FM patients and 11 HC were scanned using [(11)C]-(L)-deprenyl-D(2) PET. Standardized uptake values normalized by occipital cortex signal (SUVR) and distribution volume (V(T)) were computed from the [(11)C]PBR28 data. [(11)C]-(L)-deprenyl-D(2) was quantified using λk(3). PET imaging metrics were compared across groups, and when differing across groups, against clinical variables. Compared to HC, FM patients demonstrated widespread cortical elevations, and no decreases, in [(11)C]PBR28 V(T) and SUVR, most pronounced in the medial and lateral walls of the frontal and parietal lobes. No regions showed significant group differences in [(11)C]-(L)-deprenyl-D(2) signal, including those demonstrating elevated [(11)C]PBR28 signal in patients (p’s≥0.53, uncorrected). The elevations in [(11)C]PBR28 V(T) and SUVR were correlated both spatially (i.e., were observed in overlapping regions) and, in several areas, also in terms of magnitude. In exploratory, uncorrected analyses, higher subjective ratings of fatigue in FM patients were associated with higher [(11)C]PBR28 SUVR in the anterior and posterior middle cingulate cortices (p’s

BACKGROUND. Patients with schizophrenia (SCZ) experience chronic cognitive deficits. Histone deacetylases (HDACs) are enzymes that regulate cognitive circuitry; however, the role of HDACs in cognitive disorders, including SCZ, remains unknown in humans. We previously determined that HDAC2 mRNA levels were lower in dorsolateral prefrontal cortex (DLPFC) tissue from donors with SCZ compared with controls. Here we investigated the relationship between in vivo HDAC expression and cognitive impairment in patients with SCZ and matched healthy controls using [(11)C]Martinostat positron emission tomography (PET). METHODS. In a case-control study, relative [((11))C]Martinostat uptake was compared between 14 patients with SCZ or schizoaffective disorder (SCZ/SAD) and 17 controls using hypothesis-driven region-of-interest analysis and unbiased whole brain voxel-wise approaches. Clinical measures, including the MATRICS consensus cognitive battery, were administered. RESULTS. Relative HDAC expression was lower in the DLPFC of patients with SCZ/SAD compared with controls, and HDAC expression positively correlated with cognitive performance scores across groups. Patients with SCZ/SAD also showed lower relative HDAC expression in the dorsomedial prefrontal cortex and orbitofrontal gyrus, and higher relative HDAC expression in the cerebral white matter, pons, and cerebellum compared with controls. CONCLUSIONS. These findings provide in vivo evidence of HDAC dysregulation in patients with SCZ and suggest that altered HDAC expression may impact cognitive function in humans. FUNDING. National Institute of Mental Health (NIMH), Brain and Behavior Foundation, Massachusetts General Hospital (MGH), Athinoula A. Martinos Center for Biomedical Imaging, National Institute of Biomedical Imaging and Bioengineering (NIBIB), NIH Shared Instrumentation Grant Program.

The indoor air quality of subway systems can significantly affect the health of passengers since these systems are widely used for short-distance transit in metropolitan urban areas in many countries. The particles generated by abrasion during subway operations and the vehicle-emitted pollutants flowing in from the street in particular affect the air quality in underground subway stations. Thus the continuous monitoring of particulate matter (PM) in underground station is important to evaluate the exposure level of PM to passengers. However, it is difficult to obtain indoor PM data because the measurement systems are expensive and difficult to install and operate for significant periods of time in spaces crowded with people. In this study, we predicted the indoor PM concentration using the information of outdoor PM, the number of subway trains running, and information on ventilation operation by the artificial neural network (ANN) model. As well, we investigated the relationship between ANN's performance and the depth of underground subway station. ANN model showed a high correlation between the predicted and actual measured values and it was able to predict 67∼80% of PM at 6 subway station. In addition, we found that platform shape and depth influenced the model performance.

This cross-sectional study evaluated a convenience sample comprising 182 ovarian cancer survivors to identify symptom clusters according to the cancer survivorship stage and to determine their effects on quality of life using the European Organization for Research and Treatment of Cancer Quality of Life–C30 and –OV28 questionnaires. Factor and multiple regression analyses were performed to identify symptom clusters according to the cancer survivorship stage and the symptom clusters that affected the quality of life in each cancer survivorship stage, respectively. Participants in the acute, extended, and permanent survival stages accounted for 33%, 36.3%, and 30.7% of subjects, respectively. Overall, the most common symptom cluster was fatigue-diarrhea, and the symptom clusters affecting the quality of life differed according to the cancer survivorship stage. Thus, to improve the quality of life of ovarian cancer survivors, the main symptom clusters of each cancer survivorship stage must be identified, and management strategies for the related symptoms must be designed.

BACKGROUND: Chronic pain and mood disorders share common neuroanatomical substrates involving disruption of the reward system. Although increase in negative affect (NA) and decrease in positive affect (PA) are well-known factors complicating the clinical presentation of chronic pain patients, our understanding of the mechanisms underlying the interaction between pain and PA/NA remains limited. Here, we used a validated task probing behavioral and neural responses to monetary rewards and losses in conjunction with functional magnetic resonance imaging (fMRI) to test the hypothesis that dysfunction of the striatum, a key mesolimbic structure involved in the encoding of motivational salience, relates to mood alterations comorbid with chronic pain. METHODS: Twenty-eight chronic musculoskeletal pain patients (chronic low back pain, n=15; fibromyalgia, n=13) and 18 healthy controls underwent fMRI while performing the Monetary Incentive Delay (MID) task. Behavioral and neural responses were compared across groups and correlated against measures of depression (Beck Depression Inventory) and hedonic capacity (Snaith-Hamilton Pleasure Scale). RESULTS: Compared to controls, patients demonstrated higher anhedonia and depression scores, and a dampening of striatal activation and incentive-related behavioral facilitation (reduction in reaction times) during reward and loss trials of the MID task (ps

We recently showed elevated levels of the 18kDa translocator protein (TSPO), a marker of neuroinflammation, in chronic low back pain patients (cLBP) compared to healthy controls(Loggia et al., 2015). Here, we test whether TSPO signal 1) can further subtype cLBP patients based on their clinical presentation, and 2) is associated with functional connectivity measures (because neuroinflammation may affect neuronal communication(Clark et al., 2015)). Patients with axial (cLBPAX; n=26; 43.7±16.6 y.o.) or radicular cLBP (cLBPRAD; n=28; 48.3±13.2 y.o.) received an integrated PET/MRI scan with the TSPO ligand [11C]PBR28. TSPO signal was quantified using standardized uptake values normalized by whole-brain signal (SUVR). Functional connectivity from primary somatosensory cortex (S1) (i.e., a region significant in the PET group comparison) was calculated from BOLD resting-state fMRI data. Connectivity and PET measures were compared across groups, correlated with and against each other and against the Fibromyalgia Screening Questionnaire (FSQ) scores, measure of pain “centralization”. Because two different scanners were used (BrainPET: 10 cLBPAX, 15 cLBPRAD; Biograph mMR: 16 cLBPAX, 13 cLBPRAD), scanner was included as a covariate in all analyses. Moreover, PET analyses also included Ala147Thr TSPO genotype, which predicts binding affinity to [11C]PBR28. In S1, TSPO signal and functional connectivity to the thalamus were: 1) higher in cLBPRAD compared to cLBPAX; 2) positively correlated with each other and 3) positively correlated with FSQ scores. Our data support the existence of different “neuroinflammatory signatures” in patients with different clinical presentation and that S1 neuroinflammatory signal is more pronounced in patients with higher pain “centralization”. Further, because S1 TSPO signal was correlated to S1-thalamus connectivity, our data support an association between neuroinflammatory changes and changes in neuronal communication, possibly indicating that the observed alterations reflect “neurogenic neuroinflammation”. Future studies are needed to determine whether neuroinflammation and related connectivity changes are possible therapeutic targets for chronic pain. 1R21NS087472-01A1; 1R01NS095937-01A; 1R01NS094306-01A1; W81XWH-14-1-0543.

The weak association between disability levels and “peripheral” (i.e., knee) findings suggests that central nervous system alterations may contribute to the pathophysiology of knee osteoarthritis (KOA). Here, we evaluated brain metabolite alterations in KOA patients, before and after total knee arthroplasty (TKA), using 1H-magnetic resonance spectroscopy (MRS). Thirty-four pre-surgical KOA patients and 13 healthy controls were scanned using a PRESS sequence (TE=30ms, TR=1.7s, voxel size=15 × 15 × 15mm). Additionally, a subset of patients (n=13) were re-scanned 4.1±1.6 (mean±SD) weeks post-TKA. When using Creatine (Cr)-normalized levels, pre-surgical KOA patients demonstrated lower N-acetylaspartate (NAA) (p≤0.01) and higher myoinositol (mIns) (p≤0.001), compared to healthy controls. The mIns levels were positively correlated with pain severity scores (r=0.37, p 0.05), irrespective of metric. Additionally, patients demonstrated post-surgical increases in Cr-normalized (p

Contributions of exhaust and non-exhaust sources to traffic-related particulate matter (PM) pollution in the atmosphere are almost identical and the most important non-exhaust source is known to be brake wear particles. In order to understand the properties and harmful effects of wear particles on people, accurate information on size distribution of brake wear particles is needed. Our previous study investigated the measured changes in size distribution of nanoparticles of 500 nm or smaller to understand the origin of nanoparticles due to temperature increases on the friction surface. The present study was intended to investigate the characteristics of size distribution (5.6 nm–32 μm) of PM released under different braking conditions by using different instruments. The measurement results under 9 braking conditions using 3 different instruments showed that the size distribution characteristics of particles can be divided into two main types according to braking energy. The first type is of PM up to 10 μm in size and with a peak number concentration at 0.2–0.75 μm regardless of braking energy, while the second type is of PM around 10 nm in size generated only when braking energy increased and particles that increased up to 100 nm. In addition, we found that the size distributions measured by the optical particle counter (OPC) and the aerodynamic particle sizer (APS) were consistent by assuming a mean diameter ratio of two instruments.

Negative affect (NA) is a significant cause of disability for chronic pain patients. While little is known about the mechanism underlying pain-comorbid NA, previous studies have implicated neuroinflammation in the pathophysiology of both depression and chronic pain. Here, we tested the hypothesis that NA in pain patients is linked to elevations in the brain levels of the glial marker 18kDa translocator protein (TSPO), and changes in functional connectivity. 25 cLBP patients (42.4±13 years old; 13F, 12M) with chronic low back pain (cLBP) and 27 healthy control subjects (48.9±13 years old; 14F, 13M) received an integrated (i.e., simultaneous) positron emission tomography (PET) / magnetic resonance imaging (MRI) brain scan with the second-generation TSPO ligand [11C]PBR28. The relationship between [11C]PBR28 signal and NA was assessed first with regression analyses against Beck Depression Inventory (BDI) scores in patients, and then by comparing cLBP patients with little-to-no, or mild-to-moderate depression against healthy controls. Further, the relationship between PET signal, BDI and frontolimbic functional connectivity was evaluated in patients with mediation models. PET signal was positively associated with BDI scores in patients, and significantly elevated in patients with mild-to-moderate (but not low) depression compared to controls, in anterior middle and pregenual anterior cingulate cortices (aMCC, pgACC). In the pgACC, PET signal was also associated with this region’s functional connectivity to the dorsolateral PFC (pgACC-dlPFC), and mediated of the association between pgACC-dlPFC connectivity and BDI. These observations support a role for glial activation in pain-comorbid NA, identifying in neuroinflammation a potential therapeutic target for this condition.

Exposure to airborne particulate matter (PM) causes several diseases in the human body. The smaller particles, which have relatively large surface areas, are actually more harmful to the human body since they can penetrate deeper parts of the lungs or become secondary pollutants by bonding with other atmospheric pollutants, such as nitrogen oxides. The purpose of this study is to present the number of PM inhaled by subway users as a possible reference material for any analysis of the hazards to the human body arising from the inhalation of such PM. Two transfer stations in Seoul, Korea, which have the greatest number of users, were selected for this study. For 0.3–0.422 μm PM, particle number concentration (PNC) was highest outdoors but decreased as the tester moved deeper underground. On the other hand, the PNC between 1 and 10 μm increased as the tester moved deeper underground and showed a high number concentration inside the subway train as well. An analysis of the particles to which subway users are actually exposed to (inhaled particle number), using particle concentration at each measurement location, the average inhalation rate of an adult, and the average stay time at each location, all showed that particles sized 0.01–0.422 μm are mostly inhaled from the outdoor air whereas particles sized 1–10 μm are inhaled as the passengers move deeper underground. Based on these findings, we expect that the inhaled particle number of subway users can be used as reference data for an evaluation of the hazards to health caused by PM inhalation.

The indoor air quality of subway systems can significantly affect the health of passengers since these systems are widely used for short-distance transit in metropolitan urban areas in many countries. The particles generated by abrasion during subway operations and the vehicle-emitted pollutants flowing in from the street in particular affect the air quality in underground subway stations. Thus the continuous monitoring of particulate matter (PM) in underground station is important to evaluate the exposure level of PM to passengers. However, it is difficult to obtain indoor PM data because the measurement systems are expensive and difficult to install and operate for significant periods of time in spaces crowded with people. In this study, we predicted the indoor PM concentration using the information of outdoor PM, the number of subway trains running, and information on ventilation operation by the artificial neural network (ANN) model. As well, we investigated the relationship between ANN's performance and the depth of underground subway station. ANN model showed a high correlation between the predicted and actual measured values and it was able to predict 67∼80% of PM at 6 subway station. In addition, we found that platform shape and depth influenced the model performance.

In this study, we measured the size distribution of particles ranging in size from 5.6 to 560 nm that were emitted between brake disks and pads under various braking conditions to observe and analyze changes to the resulting particle size distribution over braking time. A peak of 178-275 nm (200 nm peak) was observed in all braking conditions. However, the generation of spherical particles of a 10 nm range was observed only when the disk speed and brake force were above certain levels and intensified only when speed and brake force further increased. The total number concentration of ultrafine particles (no larger than 0.1 μm; PM0.1) generated was found to correlate with disk speed and brake force. Thus, the generation of nanoparticles resulting from disk speed and brake force was attributable primarily to increases in the contact surface temperature. The critical temperature for the generation of nanoparticles of a 10 nm range was found to be about 70 °C, which is the average temperature between the surface and the inside of the disk. If the speed or brake force was higher, that is, the temperature of the contact surface reached a certain level, evaporation and condensation took place. Vapor then left the friction surface, met with the air, and quickly cooled to form nanoparticles through nucleation. When the newly generated particles became highly concentrated, they grew through coagulation to form agglomerates or the vapor condensed directly onto the surface of existing particles of about 200 nm (formed by mechanical friction).