Allocentric representation in the human amygdala and ventral visual stream

The hippocampus and the entorhinal cortex are considered the main brain structures for allocentric representation of the external environment. Here, we show that the amygdala and the ventral visual stream are involved in allocentric representation. Thirty-one young men explored 35 virtual environments during high-resolution functional magnetic resonance imaging (fMRI) of the medial temporal lobe (MTL) and were subsequently tested on recall of the allocentric pattern of the objects in each environment-in other words, the positions of the objects relative to each other and to the outer perimeter. We find increasingly unique brain activation patterns associated with increasing allocentric accuracy in distinct neural populations in the perirhinal cortex, parahippocampal cortex, fusiform cortex, amygdala, hippocampus, and entorhinal cortex. In contrast to the traditional view of a hierarchical MTL network with the hippocampus at the top, we demonstrate, using recently developed graph analyses, a hierarchical allocentric MTL network without a main connector hub

Immunogold Detection of L-glutamate and D-serine in Small Synaptic-Like Microvesicles in Adult Hippocampal Astrocytes

Glutamate and the N-methyl-D-aspartate receptor ligand D-serine are putative gliotransmitters. Here, we show by immunogold cytochemistry of the adult hippocampus that glutamate and D-serine accumulate in synaptic-like microvesicles (SLMVs) in the perisynaptic processes of astrocytes. The estimated concentration of fixed glutamate in the astrocytic SLMVs is comparable to that in synaptic vesicles of excitatory nerve terminals (∼45 and ∼55 mM, respectively), whereas the D-serine level is about 6 mM. The vesicles are organized in small spaced clusters located near the astrocytic plasma membrane. Endoplasmic reticulum is regularly found in close vicinity to SLMVs, suggesting that astrocytes contain functional nanodomains, where a local Ca2+ increase can trigger release of glutamate and/or D-serin

Combined cognitive and vocational interventions after mild to moderate traumatic brain injury: study protocol for a randomized controlled trial

Background A considerable proportion of patients with mild to moderate traumatic brain injury (TBI) experience long-lasting somatic, cognitive, and emotional symptoms that may hamper their capacity to return to work (RTW). Although several studies have described medical, psychological, and work-related factors that predict RTW after TBI, well-controlled intervention studies regarding RTW are scarce. Furthermore, there has traditionally been weak collaboration among health-related rehabilitation services, the labor and welfare sector, and workplaces. Methods/design This study protocol describes an innovative randomized controlled trial in which we will explore the effect of combining manualized cognitive rehabilitation (Compensatory Cognitive Training [CCT]) and supported employment (SE) on RTW and related outcomes for patients with mild to moderate TBI in real-life competitive work settings. The study will be carried out in the southeastern region of Norway and thereby be performed within the Norwegian welfare system. Patients aged 18–60 years with mild to moderate TBI who are employed in a minimum 50% position at the time of injury and sick-listed 50% or more for postconcussive symptoms 2 months postinjury will be included in the study. A comprehensive assessment of neurocognitive function, self-reported symptoms, emotional distress, coping style, and quality of life will be performed at baseline, immediately after CCT (3 months after inclusion), following the end of SE (6 months after inclusion), and 12 months following study inclusion. The primary outcome measures are the proportion of participants who have returned to work at 12-month follow-up and length of time until RTW, in addition to work stability as well as work productivity over the first year following the intervention. Secondary outcomes include changes in self-reported symptoms, emotional and cognitive function, and quality of life. Additionally, a qualitative RTW process evaluation focused on organizational challenges at the workplace will be performed. Discussion The proposed study will combine cognitive and vocational rehabilitation and explore the efficacy of increased cross-sectoral collaboration between specialized health care services and the labor and welfare system. If the intervention proves effective, the project will describe the cost-effectiveness and utility of the program and thereby provide important information for policy makers. In addition, knowledge about the RTW process for persons with TBI and their workplaces will be provided. Trial registration ClinicalTrials.gov, NCT03092713. Registered on 10 March 2017

Fractional exhaled nitric oxide as a potential biomarker for radiation pneumonitis in patients with non-small cell lung cancer:A pilot study

Introduction The aim of the study was to investigate repetitive fractional exhaled nitric oxide (FeNO) measurements during high-dose radiation therapy (HDRT) and to evaluate the use of FeNO to predict symptomatic radiation pneumonitis (RP) in patients being treated for non-small cell lung cancer (NSCLC). Materials and methods A total of 50 patients with NSCLC referred for HDRT were enrolled. FeNO was measured at baseline, weekly during HDRT, one month- and every third month after HDRT for a one-year follow-up period. The mean FeNO(visit 0-6) was calculated using the arithmetic mean of the baseline and weekly measurements during HDRT. Patients with grade ≥ 2 of RP according to the Common Terminology Criteria for Adverse Events (CTCAE) were considered symptomatic. Results A total of 42 patients completed HDRT and weekly FeNO measurements. Grade ≥ 2 of RP was diagnosed in 24 (57%) patients. The mean FeNO(visit 0-6) ± standard deviation in patients with and without RP was 15.0 ± 7.1 ppb (95%CI: 12.0–18.0) and 10.3 ± 3.4 ppb (95%CI: 8.6–11.9) respectively with significant differences between the groups (p = 0.0169, 95%CI: 2.3–2.6). The leave-one-out cross-validated cut-off value of the mean FeNO(visit 0-6) ≥ 14.8 ppb was predictive of grade ≥ 2 RP with a specificity of 71% and a positive predictive value of 78%. Conclusions The mean FeNO(visit 0-6) in patients with symptomatic RP after HDRT for NSCLC was significantly higher than in patients without RP and may serve as a potential biomarker for RP

Fear of movement and emotional distress as prognostic factors for disability in patients with shoulder pain: a prospective cohort study

Background: Shoulder pain is a prevalent and often long-lasting musculoskeletal disorder. The overall prognosis of shoulder pain is highly variable with 40-50% of patients reporting persistent pain 6-12 months after consulting a clinician. The evidence for psychological prognostic factors for patients with shoulder pain is inconsistent. Therefore, the objective of this study was to investigate the association between fear of movement and emotional distress at presentation and self-reported disability over one year of follow-up. Methods: This is a prospective cohort study of consecutive patients referred to secondary outpatient care due to shoulder pain. Consenting patients underwent a physical examination and completed a comprehensive questionnaire at baseline, three months-, and one-year follow-up. Associations between baseline fear of movement (0-10) or emotional distress (1-4), respectively, and patient reported disability measured using Quick Disability of the Arm and Shoulder (QuickDASH, 0-100) over one year were analyzed with linear mixed-effects models (LMM) for repeated measures (baseline, 3 months and 1 year), adjusting for established prognostic factors. Results: A total of 138 patients were recruited between March 2015 and January 2018, with response rates of 84.7% (n = 117) and 79.7% (n = 1 00) at three months and one year, respectively. Adjusted associations revealed that for every point increase in baseline fear of movement, the QuickDASH score increased (worsened) by 1.10 points (95% CI 0.2-2.0) over the follow-up year. For every point increase in baseline emotional distress, the QuickDASH score increased by 19.9 points (95% CI 13.9-25.9) from baseline over the follow-up year. Conclusion: Higher fear of movement and emotional distress scores at baseline were significantly associated with higher disability over one year in patients with shoulder pain referred to secondary care. Our study indicates that these psychological factors affect prognosis and should be considered by clinicians and researchers working with ipatients with shoulder pain

Re-evaluation of histological diagnoses of malignant mesothelioma by immunohistochemistry

<p>Abstract</p> <p>Background</p> <p>In order to provide reliable tissue material for malignant mesothelioma (MM) studies, we re-evaluated biopsies and autopsy material from 61 patients with a diagnosis of MM from the period of 1980-2002.</p> <p>Methods</p> <p>Basic positive (Calretinin, EMA, Podoplanin, Mesothelin) and negative (CEA, Ber-Ep4) immunohistochemical (IHC) marker reactions were determined. If needed, more markers were used. Histological diagnoses were made by three pathologists. Survival data were calculated.</p> <p>Results</p> <p>49 cases (80%) were considered being MM by a high degree of likelihood, five more cases possible MM. Of the remaining seven cases, three were diagnosed as adenocarcinoma, three as pleomorphic lung carcinoma, in one peritoneal case a clear entity diagnosis could not be given. One of the possible MM cases and two of the lung carcinoma cases had this already as primary diagnoses, but were registered as MM.</p> <p>With a sensitivity of 100%, Calretinin and CEA were the most reliable single markers. The amount of MM cells with positive immunoreactivity (IR) for Podoplanin and Mesothelin showed most reliable inverse relation to the degree of atypia.</p> <p>In the confirmed MM cases, there had been applied either no IHC or between one and 18 markers.</p> <p>The cases not confirmed by us had either lacked IHC (n = 1), non-specific markers were used (n = 4), IR was different (n = 1), or specific markers had not shown positive IR in the right part of the tumour cells (n = 3).</p> <p>46 of the 49 confirmed and three of the not confirmed cases had been diagnosed by us as most likely MM before IHC was carried out.</p> <p>Conclusions</p> <p>In order to use archival tissue material with an earlier MM diagnosis for studies, histopathological re-evaluation is important. In possible sarcomatous MM cases without any positive IR for positive MM markers, radiology and clinical picture are essential parts of diagnostics. IHC based on a panel of two positive and two negative MM markers has to be adapted to the differential diagnostic needs in each single case. New diagnostic tools and techniques are desirable for cases where IHC and other established methods cannot provide a clear entity diagnosis, and in order to improve MM treatment.</p

Frequency of fatigue and its changes in the first 6 months after traumatic brain injury: results from the CENTER-TBI study.

BACKGROUND: Fatigue is one of the most commonly reported subjective symptoms following traumatic brain injury (TBI). The aims were to assess frequency of fatigue over the first 6 months after TBI, and examine whether fatigue changes could be predicted by demographic characteristics, injury severity and comorbidities. METHODS: Patients with acute TBI admitted to 65 trauma centers were enrolled in the study Collaborative European NeuroTrauma Effectiveness Research in TBI (CENTER-TBI). Subjective fatigue was measured by single item on the Rivermead Post-Concussion Symptoms Questionnaire (RPQ), administered at baseline, three and 6 months postinjury. Patients were categorized by clinical care pathway: admitted to an emergency room (ER), a ward (ADM) or an intensive care unit (ICU). Injury severity, preinjury somatic- and psychiatric conditions, depressive and sleep problems were registered at baseline. For prediction of fatigue changes, descriptive statistics and mixed effect logistic regression analysis are reported. RESULTS: Fatigue was experienced by 47% of patients at baseline, 48% at 3 months and 46% at 6 months. Patients admitted to ICU had a higher probability of experiencing fatigue than those in ER and ADM strata. Females and individuals with lower age, higher education, more severe intracranial injury, preinjury somatic and psychiatric conditions, sleep disturbance and feeling depressed postinjury had a higher probability of fatigue. CONCLUSION: A high and stable frequency of fatigue was found during the first 6 months after TBI. Specific socio-demographic factors, comorbidities and injury severity characteristics were predictors of fatigue in this study