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Objective: [¹⁸F]FE-PE2I (FE-PE2I) is a new radiotracer for dopamine transporter (DAT) imaging with PET. The aim of this study was to evaluate the visual interpretation of FE-PE2I images for the diagnosis of idiopathic Parkinsonian syndrome (IPS). The inter-rater variability, sensitivity, specificity, and diagnostic accuracy for visual interpretation of striatal FE-PE2I compared to [¹²³I]FP-CIT (FP-CIT) single-photon emission computed tomography (SPECT) was evaluated.

Methods: Thirty patients with newly onset parkinsonism and 32 healthy controls with both an FE-PE2I and FP-CIT were included in the study. Four patients had normal DAT imaging, of which three did not fulfil the IPS criteria at the clinical reassessment after 2 years. Six raters evaluated the DAT images blinded to the clinical diagnosis, interpreting the image as being ‘normal’ or ‘pathological’, and assessed the degree of DAT-reduction in the caudate and putamen. The inter-rater agreement was assessed with intra-class correlation and Cronbach’s α. For calculation of sensitivity and specificity, DAT images were defined as correctly classified if categorized as normal or pathological by ≥4/6 raters.

Results: The overall agreement in visual evaluation of the FE-PE2I- and FP-CIT images was high for the IPS patients (α = 0.960 and 0.898, respectively), but lower in healthy controls (FE-PE2I: α = 0.693, FP-CIT: α = 0.657). Visual interpretation gave high sensitivity (both 0.96) but lower specificity (FE-PE2I: 0.86, FP-CIT: 0.63) with an accuracy of 90% for FE-PE2I and 77% for FP-CIT.

Conclusion: Visual evaluation of FE-PE2I PET imaging demonstrates high reliability and diagnostic accuracy for IPS.

In Parkinson's disease, degeneration of substantia nigra dopaminergic neurons is accompanied by damage on other neuronal systems. A severe denervation is for example seen in the locus coerulean noradrenergic system. Little is known about the relation between noradrenergic and dopaminergic degeneration, and the effects of noradrenergic denervation on the function of the dopaminergic neurons of substantia nigra are not fully understood. In this study, N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP4) was injected in rats, whereafter behavior, striatal KCl-evoked dopamine and glutamate releases, and immunohistochemistry were monitored at 3 days, 3 months, and 6 months. Quantification of dopamine-beta-hydroxylase-immunoreactive nerve fiber density in the cortex revealed a tendency towards nerve fiber regeneration at 6 months. To sustain a stable noradrenergic denervation throughout the experimental timeline, the animals in the 6-month time point received an additional DSP4 injection (2 months after the first injection). Behavioral examinations utilizing rotarod revealed that DSP4 reduced the time spent on the rotarod at 3 but not at 6 months. KCl-evoked dopamine release was significantly increased at 3 days and 3 months, while the concentrations were normalized at 6 months. DSP4 treatment prolonged both time for onset and reuptake of dopamine release over time. The dopamine degeneration was confirmed by unbiased stereology, demonstrating significant loss of tyrosine hydroxylase-immunoreactive neurons in the substantia nigra. Furthermore, striatal glutamate release was decreased after DSP4. In regards of neuroinflammation, reactive microglia were found over the substantia nigra after DSP4 treatment. In conclusion, long-term noradrenergic denervation reduces the number of dopaminergic neurons in the substantia nigra and affects the functionality of the nigrostriatal system. Thus, locus coeruleus is important for maintenance of nigral dopaminergic neurons.

BACKGROUND: Urinary bladder cancer is a common malignancy worldwide. Environmental factors and chronic inflammation are correlated with the disease risk. Diagnosis is performed by transurethral resection of the bladder, and patients with muscle invasive disease preferably proceed to radical cystectomy, with or without neoadjuvant chemotherapy. The anti-tumour immune responses, known to be initiated in the tumour and draining lymph nodes, may play a major role in future treatment strategies. Thus, increasing the knowledge of tumour-associated immunological processes is important. Activated CD4⁺ T cells differentiate into four main separate lineages: Th1, Th2, Th17 and Treg, and they are recognized by their effector molecules IFN-γ, IL-13, IL-17A, and the transcription factor Foxp3, respectively. We have previously demonstrated signature CpG sites predictive for lineage commitment of these four major CD4⁺ T cell lineages. Here, we investigate the lineage commitment specifically in tumour, lymph nodes and blood and relate them to the disease stage and response to neoadjuvant chemotherapy.

RESULTS: Blood, tumour and regional lymph nodes were obtained from patients at time of transurethral resection of the bladder and at radical cystectomy. Tumour-infiltrating CD4⁺ lymphocytes were significantly hypomethylated in all four investigated lineage loci compared to CD4⁺ lymphocytes in lymph nodes and blood (lymph nodes vs tumour-infiltrating lymphocytes: IFNG -4229 bp p < 0.0001, IL13 -11 bp p < 0.05, IL17A -122 bp p < 0.01 and FOXP3 -77 bp p > 0.05). Examination of individual lymph nodes displayed different methylation signatures, suggesting possible correlation with future survival. More advanced post-cystectomy tumour stages correlated significantly with increased methylation at the IFNG -4229 bp locus. Patients with complete response to neoadjuvant chemotherapy displayed significant hypomethylation in CD4⁺ T cells for all four investigated loci, most prominently in IFNG p < 0.0001. Neoadjuvant chemotherapy seemed to result in a relocation of Th1-committed CD4⁺ T cells from blood, presumably to the tumour, indicated by shifts in the methylation patterns, whereas no such shifts were seen for lineages corresponding to IL13, IL17A and FOXP3.

CONCLUSION: Increased lineage commitment in CD4⁺ T cells, as determined by demethylation in predictive CpG sites, is associated with lower post-cystectomy tumour stage, complete response to neoadjuvant chemotherapy and overall better outcome, suggesting epigenetic profiling of CD4⁺ T cell lineages as a useful readout for clinical staging.

BACKGROUND: Partial Achilles tendon ruptures are not always easy to diagnose. A history including a sudden onset of pain, and/or relative weakness in plantar flexion force, are indicators. The most loaded side of the Achilles tendon is the dorsal side (skin side). OBJECTIVE: To evaluate the ultrasound (US) and Doppler (CD) findings in patients with a suspected partial rupture in the Achilles tendon. Material and METHODS: Seventeen patients (16 men and 1 woman) with a mean age of 36 years (range 23-71) were examined clinically and by US+CD because of midportion Achilles tendon pain. There was an acute onset in 14/17 patients, and all had painful weakness during tendon loading activity. RESULTS: In all patients the US examination showed a partial Achilles tendon rupture, presented as a disrupted dorsal (skin side) tendon line and an irregular tendon structure mainly located in the dorsal and mid-tendon. The size of the rupture varied from 1/3 to 2/3 of the tendon thickness. In the dorsal part of the tendon, corresponding to the region with disrupted tendon line and irregular structure, CD examination showed high blood flow-most often of a longitudinal character. Six of the patients were surgically treated, and macroscopical examination verified the ultrasound findings, showing disruption on the dorsal side, and a partial rupture in the dorsal and mid- tendon. CONCLUSIONS: Ultrasound and Doppler examination can be helpful tools to diagnose partial midportion Achilles tendon ruptures. The characteristic findings of a disrupted dorsal tendon line, and high blood flow in the structurally abnormal dorsal tendon, indicate a partial rupture.

We prospectively studied calf muscle strength in 7 men and 4 women (mean age, 40.9 +/- 10.1 years) who had surgical treatment for chronic Achilles tendinosis. Surgery was followed by immobilization in a weightbearing below-the-knee plaster cast for 2 weeks followed by a stepwise increasing strength training program. Strength measurements (peak torque and total work) were done preoperatively (Week 0) and at 16, 26, and 52 weeks postoperatively. We measured isokinetic concentric plantar flexion strength at 90 and 225 deg/sec and eccentric flexion strength at 90 deg/sec on both the injured and noninjured sides. Preoperatively, concentric and eccentric strength were significantly lower on the injured side at 90 and 225 deg/sec. Postoperatively, concentric peak torque on the injured side decreased significantly between Weeks 0 and 16 and increased significantly between Weeks 26 and 52 at 90 deg/sec but was significantly lower than that on the noninjured side at all periods and at both velocities. The eccentric strength was significantly lower on the injured side at Week 26 but increased significantly until at Week 52 no significant differences between the sides could be demonstrated. It seems, therefore, that the recovery in concentric and eccentric calf muscle strength after surgery for Achilles tendinosis is slow. We saw no obvious advantages in recovery of muscle strength with a short immobilization time (2 weeks) versus a longer (6 weeks) period used in a previous study.

Treatment with ultrasound and Doppler-guided arthroscopic shaving of the region with vessels and nerves outside the dorsal tendon has shown promising clinical results in patients with proximal patellar tendinopathy/Jumper´s knee. The results concerning only a limited patient material has been published in a scientific paper. Results on larger materials are under evaluation for later publication. Proper understanding of the ultrasound and Doppler findings, to enable for a precise and minimal arthroscopic shaving procedure on the dorsal side of the tendon, are cornerstones using this new type of treatment.

Manual scoring of polysomnography data is labor-intensive and time-consuming, and most existing software does not account for subjective differences and user variability. Therefore, we evaluated a supervised machine learning algorithm, Somnivore (TM), for automated wake-sleep stage classification. We designed an algorithm that extracts features from various input channels, following a brief session of manual scoring, and provides automated wake-sleep stage classification for each recording. For algorithm validation, polysomnography data was obtained from independent laboratories, and include normal, cognitively-impaired, and alcohol-treated human subjects (total n = 52), narcoleptic mice and drug-treated rats (total n = 56), and pigeons (n = 5). Training and testing sets for validation were previously scored manually by 1-2 trained sleep technologists from each laboratory. F-measure was used to assess precision and sensitivity for statistical analysis of classifier output and human scorer agreement. The algorithm gave high concordance with manual visual scoring across all human data (wake 0.91 +/- 0.01; N1 0.57 +/- 0.01; N2 0.81 +/- 0.01; N3 0.86 +/- 0.01; REM 0.87 +/- 0.01), which was comparable to manual inter-scorer agreement on all stages. Similarly, high concordance was observed across all rodent (wake 0.95 +/- 0.01; NREM 0.94 +/- 0.01; REM 0.91 +/- 0.01) and pigeon (wake 0.96 +/- 0.006; NREM 0.97 +/- 0.01; REM 0.86 +/- 0.02) data. Effects of classifier learning from single signal inputs, simple stage reclassification, automated removal of transition epochs, and training set size were also examined. In summary, we have developed a polysomnography analysis program for automated sleep-stage classification of data from diverse species. Somnivore enables flexible, accurate, and high-throughput analysis of experimental and clinical sleep studies.

PURPOSE: Recent development of magnetic resonance imaging (MRI) offers new possibilities to assess ocular blood flow. This prospective study evaluates the feasibility of phase-contrast MRI (PCMRI) to measure flow rate in the ophthalmic artery (OA) and establish reference values in healthy young (HY) and elderly (HE) subjects.

METHODS: Fifty HY subjects (28 females, 21-30 years of age) and 44 HE (23 females, 64-80 years of age) were scanned on a 3-Tesla MR system. The PCMRI sequence had a spatial resolution of 0.35 mm per pixel, with the measurement plan placed perpendicularly to the OA. Mean flow rate (Qmean), resistive index (RI), and arterial volume pulsatility of OA (ΔVmax) were measured from the flow rate curve. Accuracy of PCMRI measures was investigated using a vessel-phantom mimicking the diameter and the flow rate range of the human OA.

RESULTS: Flow rate could be assessed in 97% of the OAs. Phantom investigations showed good agreement between the reference and PCMRI measurements with an error of <7%. No statistical difference was found in Qmean between HY and HE individuals (HY: mean ± SD = 10.37 ± 4.45 mL/min; HE: 10.81 ± 5.15 mL/min, P = 0.655). The mean of ΔVmax (HY: 18.70 ± 7.24 μL; HE: 26.27 ± 12.59 μL, P < 0.001) and RI (HY: 0.62 ± 0.08; HE: 0.67 ± 0.1, P = 0.012) were significantly different between HY and HE.

CONCLUSIONS: This study demonstrated that the flow rate of OA can be quantified using PCMRI. There was an age difference in the pulsatility parameters; however, the mean flow rate appeared independent of age. The primary difference in flow curves between HE and HY was in the relaxation phase of the systolic peak.

BACKGROUND: A precise definition of ventricular enlargement is important in the diagnosis of hydrocephalus as well as in assessing central atrophy. The Evans index (EI), a linear ratio between the maximal frontal horn width and the cranium diameter, has been extensively used as an indirect marker of ventricular volume (VV). With modern imaging techniques, brain volume can be directly measured. OBJECTIVE: To determine reference values of intracranial volumes in healthy elderly individuals and to correlate volumes with the EI. METHODS: Magnetic resonance imaging (3 T) was performed in 46 healthy white elderly subjects (mean age +/- standard deviation, 71 +/- 6 years) and in 20 patients (74 +/- 7 years) with large ventricles according to visual inspection. VV, relative VV (RVV), and EI were assessed. Ventricular dilation was defined using VV and EI by a value above the 95th percentile range for healthy elderly individuals. RESULTS: In healthy elderly subjects, we found VV = 37 +/- 18 mL, RVV = 2.47 +/- 1.17%, and EI = 0.281 +/- 0.027. Including the patients, there was a strong correlation between EI and VV (R = 0.94) as well as between EI and RVV (R = 0.95). However, because of a wide 95% prediction interval (VV: +/-45 mL; RVV: +/- 2.54%), EI did not give a sufficiently good estimate of VV and RVV. CONCLUSION: VV (or RVV) and the EI reflect different properties. The exclusive use of EI in clinical studies as a marker of enlarged ventricles should be questioned. We suggest that the definition of dilated ventricles in white elderly individuals be defined as VV >77 mL or RVV >4.96 %. Future studies should compare intracranial volumes with clinical characteristics and prognosis.

BACKGROUND AND PURPOSE: Brain size is commonly described in relation to ICV, whereby accurate assessment of this quantity is fundamental. Recently, an optimized MR sequence (QRAPMASTER) was developed for simultaneous quantification of T1, T2, and proton density. ICV can be measured automatically within minutes from QRAPMASTER outputs and a dedicated software, SyMRI. Automatic estimations of ICV were evaluated against the manual segmentation.

MATERIALS AND METHODS: In 19 healthy subjects, manual segmentation of ICV was performed by 2 neuroradiologists (Obs1, Obs2) by using QBrain software and conventional T2-weighted images. The automatic segmentation from the QRAPMASTER output was performed by using SyMRI. Manual corrections of the automatic segmentation were performed (corrected-automatic) by Obs1 and Obs2, who were blinded from each other. Finally, the repeatability of the automatic method was evaluated in 6 additional healthy subjects, each having 6 repeated QRAPMASTER scans. The time required to measure ICV was recorded.

RESULTS: No significant difference was found between reference and automatic (and corrected-automatic) ICV (P > .25). The mean difference between the reference and automatic measurement was -4.84 ± 19.57 mL (or 0.31 ± 1.35%). Mean differences between the reference and the corrected-automatic measurements were -0.47 ± 17.95 mL (-0.01 ± 1.24%) and -1.26 ± 17.68 mL (-0.06 ± 1.22%) for Obs1 and Obs2, respectively. The repeatability errors of the automatic and the corrected-automatic method were <1%. The automatic method required 1 minute 11 seconds (SD = 12 seconds) of processing. Adding manual corrections required another 1 minute 32 seconds (SD = 38 seconds).

CONCLUSIONS: Automatic and corrected-automatic quantification of ICV showed good agreement with the reference method. SyMRI software provided a fast and reproducible measure of ICV.

BACKGROUND AND PURPOSE: Automatic assessment of brain volumes is needed in researchand clinical practice. Manual tracing is still the criterionstandard but is time-consuming. It is important to validatethe automatic tools to avoid the problems of clinical studiesdrawing conclusions on the basis of brain volumes estimatedwith methodologic errors. The objective of this study was toevaluate a new commercially available fully automatic softwarefor MR imaging of brain volume assessment. Automatic and expertmanual brain volumes were compared.

MATERIALS AND METHODS: MR imaging (3T, axial T2 and FLAIR) was performed in 41 healthyelderly volunteers (mean age, 70 ± 6 years) and 20 patientswith hydrocephalus (mean age, 73 ± 7 years). The softwareQ_Brain was used to manually and automatically measure the followingbrain volumes: ICV, BTV, VV, and WMHV. The manual method hasbeen previously validated and was used as the reference. Agreementbetween the manual and automatic methods was evaluated by usinglinear regression and Bland-Altman plots.

RESULTS: There were significant differences between the automatic andmanual methods regarding all volumes. The mean differences wereICV = 49 ± 93 mL (mean ± 2SD, n = 61), BTV = 11± 70 mL, VV = –6 ± 10 mL, and WMHV = 2.4± 9 mL. The automatic calculations of brain volumes tookapproximately 2 minutes per investigation.

CONCLUSIONS: The automatic tool is promising and provides rapid assessmentof brain volumes. However, the software needs improvement beforeit is incorporated into research or daily use. Manual segmentationremains the reference method.

Objectives: To investigate whether surveillance of pulmonary nodules detected with low-dose CT (LDCT) impacted health-related quality of life and psychosocial consequences in the Swedish population-based study, Swedish CArdioPulmonary bioImage Study (SCAPIS).

Design: A prospective cross-sectional study.

Settings and participants: This multicentre (five sites) observational study, which included a cohort from SCAPIS, consisted of 632 participants with indeterminate pulmonary nodules detected with LDCT. These participants continued surveillance for up to 36 months, during which lung cancer was not detected (surveillance group). Additionally, 972 participants with a negative pulmonary LDCT scan were included as a control group. Matching criteria were LDCT date (±2 weeks), gender and site.

Outcome measures: All participants completed a health-related quality of life questionnaire (RAND-36) and the Consequences of Screening (COS) questionnaire, an average of 3 years after LDCT was conducted at entry into SCAPIS.

Results: Participants were 51-70 years old at study commencement. Overall, the two groups did not differ in demographic or psychosocial variables, smoking habits or pulmonary medical history. Individuals from countries other than Sweden and those with low socioeconomic status were less likely to participate (p<0.001). No effects on health-related quality of life were observed via RAND-36. In COS, the surveillance group demonstrated a higher OR for anxiety about lung cancer (OR 3.96, 95% CI 2.35 to 6.66, p<0.001), experiencing a sense of dejection (OR 1.35, 95% CI 1.06 to 1.72, p=0.015) and thoughts about existential values (OR 1.30, 95% CI 1.04 to 1.60, p=0.018).

Conclusions: Lung surveillance with LDCT contributed to significant experiences of sense of dejection, anxiety about lung cancer and development of thoughts about existential values among participants in the surveillance group compared with the controls. The risk of side effects should be communicated for informed decision-making about (non-)attendance in lung cancer screening.

Objective: To explore possible associations between adipose tissue (AT) blood flow (ATBF), AT depot sizes and adipocyte-derived hormones (adipokines) in women.

Subjects: In all, 43 healthy women were divided into four groups: normal-weight (n=11) and obese (n=11) pre-menopausal women and normal-weight (n=10) and obese (n=11) post-menopausal women.

Methods: Fasting levels of adipokines were obtained, and a single-slice computed tomography scan at the level of L4-L5 was used to estimate fat depot sizes. ATBF was assessed by xenon washout while in a fasting state and after oral glucose load. We also measured glucose, insulin and non-esterified fatty acids.

Results: Total, subcutaneous and visceral AT areas strongly correlated with ATBF (all P<0.001). Circulating leptin levels strongly and inversely correlated with ATBF (P=0.001), but this association did not remain after adjustment for body mass index. Adiponectin was not associated with blood flow.

Conclusion: ATBF is closely linked to subcutaneous and visceral AT size. Further analyses are needed to determine possible mediators of this association, including mechanistic studies to assess a putative role for leptin as a significant modulator of blood flow. International Journal of Obesity advance online publication, 26 July 2011; doi:10.1038/ijo.2011.152.

OBJECTIVE: Idiopathic environmental intolerance (IEI) to smells is a prevalent medically unexplained illness. Sufferers attribute severe symptoms to low doses of non-toxic chemicals. Despite the label, IEI is not characterized by acute chemical senses. Theoretical models suggest that sensitized responses in the limbic system of the brain constitute an important mechanism behind the symptoms. The aim was to investigate whether and how brain reactions to low-levels of olfactory and trigeminal stimuli differ in individuals with and without IEI. METHODS: Brain responses to intranasally delivered isoamyl acetate and carbon dioxide were assessed in 25 women with IEI and 26 non-ill controls using functional magnetic resonance imaging. RESULTS: The IEI group had higher blood-oxygenated-level-dependent (BOLD) signal than controls in the thalamus and a number of, mainly, parietal areas, and lower BOLD signal in the superior frontal gyrus. The IEI group did not rate the exposures as more intense than the control group did, and there were no BOLD signal differences between groups in the piriform cortex or olfactory regions of the orbitofrontal cortex. CONCLUSIONS: The IEI reactions were not characterized by hyper-responsiveness in sensory areas. The results can be interpreted as a limbic hyperreactivity and speculatively as an inability to inhibit salient extemal stimuli.

Judging two events in combination (A&B) as more probable than one of the events (A) is known as a conjunction fallacy. According to dual-process explanations of human judgment and decision making, the fallacy is due to the application of a heuristic, associative cognitive process. Avoiding the fallacy has been suggested to require the recruitment of a separate process that can apply normative rules. We investigated these assumptions using functional magnetic resonance imaging (fMRI) during conjunction tasks. Judgments, whether correct or not, engaged a network of brain regions identical to that engaged during similarity judgments. Avoidance of the conjunction fallacy additionally, and uniquely, involved a fronto-parietal network previously linked to supervisory, analytic control processes. The results lend credibility to the idea that incorrect probability judgments are the result of a representativeness heuristic that requires additional neurocognitive resources to avoid.

Chemical intolerance is a surprisingly prevalent condition or affliction characterized by adverse reactions to low levels of chemical, often odorous stimulation. Sufferers often assume that their plight is due to an uncommon sensory acuteness, yet studies repeatedly fail to reveal altered detection thresholds. Here, we investigated whether self-reported chemical intolerance is associated with altered sensory sensitivity or response bias. The sensory acuity (sensitivity; A) and sensory decision rule (criterion; B) to n-butanol was assessed using the method of constant stimuli in 82 participants with different degrees of chemical intolerance (low to high). Higher self-reported chemical intolerance was associated with a lower criterion, but not with sensitivity.

Treatment of patients with metastatic melanoma with either dacarbazine (DTIC) or interferon-[alpha] (IFN[alpha]) as single drugs, or in combination, results in a response rate of approximately 15–20%. This study evaluated the activity and toxicity following treatment with a combination of DTIC, IFN[alpha]2b and verapamil (VPL). Thirty patients with disseminated metastatic melanoma received DTIC 250 mg/m2 on days 1–5 of a 4 week schedule, IFN[alpha]2b 3 MIU on days 1–5 each week, and VPL 80 mg three times a day throughout the cycle, until either disease progression or serious toxicity was observed. Among the 28 evaluable patients, there were four complete responses (CRs), five partial responses (PRs) and eight patients with stable disease (SD). The overall response rate (CR + PR) was 32%. Two patients with a CR were long-term survivors (45 and 34 months) and a third is still in complete remission after 49 months. The fourth CR patient relapsed and died with progressive brain metastases after 8 months. Among the eight patients with SD, one survived for 22 months and another for 34 months. Despite one toxic death, these results suggest that this treatment regimen is well tolerated and seems to be more effective than DTIC alone in a subset of patients. A controlled randomized study would be required to determine the value of adding VPL and IFN[alpha]2b to DTIC.

Cognitive impairment is an important symptom of Parkinson’s disease (PD) and predicting future cognitive decline is crucial for clinical practice. Here, we aim to identify latent sub-groups of longitudinal trajectories of cognitive change in PD patients, and explore predictors of differences in cognitive change. Longitudinal cognitive performance data from 349 newly diagnosed PD patients and 145 healthy controls from the Parkinson Progression Marker Initiative were modeled using a multivariate latent class linear mixed model. Resultant latent classes were compared on a number of baseline demographics, and clinical variables, as well as cerebrospinal fluid (CSF) biomarkers and striatal dopamine transporter (DAT) density markers of neuropathology. Trajectories of cognitive change in PD were best described by two latent classes. A large subgroup (90%), which showed a subtle impairment in cognitive performance compared to controls but remained stable over the course of the study, and a small subgroup (10%) which rapidly declined in all cognitive performance measures. Rapid decliners did not differ significantly from the larger group in terms of disease duration, severity or motor symptoms at baseline. However, rapid decliners had lower CSF amyloidß42 levels, a higher prevalence of sleep disorder and pronounced loss of caudate DAT density at baseline. These data suggest the existence of a distinct minority sub-type of PD in which rapid cognitive change in PD can occur uncoupled from motor symptoms or disease severity, likely reflecting early pathological change that extends from motor areas of the striatum into associative compartments and cortex.

OBJECTIVE: The aim of this study was to evaluate whether mobile kidney pain provocation ultrasonography together with intravenous pyelography in supine and standing positions and a full medical history can confirm the diagnosis of the clinical condition of symptomatic mobile kidney and aid the selection of patients for surgical treatment.

MATERIALS AND METHODS: In a consecutive study, 43 patients with the clinical picture of symptomatic mobile kidney, a positive mobile kidney pain provocation ultrasonography and a renal descent of at least 2 lumbar vertebral heights on intravenous pyelography in the standing position, were operated on with nephropexy. Patients' pain relief after nephropexy was evaluated by clinical follow-up, a questionnaire and visual analogue scale (VAS) scoring.

RESULTS: Reduction of pain after nephropexy was associated with a significant decrease in VAS scoring from a median of 8 (range 4-10) preoperatively to a median of 0 (range 0-7) postoperatively (p < 0.001). Thirty-four patients (79%) were cured of their pain and seven patients (16%) experienced substantial relief from their pain symptoms. In two patients (5%) the symptoms were unchanged.

CONCLUSION: The results indicate that mobile kidney pain provocation ultrasonography and intravenous pyelography in supine and standing positions can verify the diagnosis of symptomatic mobile kidney and aid the selection of patients who will benefit from nephropexy.

Symtomatic mobile kidney is a rare condition and diagnosis is difficult. Typical symptoms are position dependent back-flank-abdominal pain with increase of pain when walking, jogging and lifting or other physical activities which increase the descent of the kidney. Triple diagnostic with typical pain history, an intravenous pyelography with a renal descent of ≥ 2 lumbar vertebral heights in the erect position, and an ultrasound with a positive pain provocation can establish the diagnosis of symptomatic mobile kidney. In our study nephropexy gives freedom of pain for 75% of patients and substantial relief for 15% of patients with severe pain.

Background: Sick-leave rates are high due to stress-related illnesses, but little is still known about the process of recovery from these conditions. The aim of this study was to explore the experiences of the recovery process, 6 to 10 years after treatment in people previously diagnosed with exhaustion disorder (ED), focusing on facilitators and barriers for the process of recovery from ED, and recovery activities experienced as helpful during the recovery process.

Method: Thirty-eight participants (average age: 52 years, 32 females) previously diagnosed with ED were interviewed with semi-structured interviews 6–10 years after undergoing treatment. The interviews were analyzed with thematic analysis.

Results: Three themes resulted from the analysis. The first theme, “A long and rocky road”, summarizes the fluctuating path to feeling better and emphasizes barriers and facilitators that affected the process of recovery, with a focus on external life events and the participants’ own behaviors. Facilitators were changing workplace, receiving support, a reduction in stressors, and changed behaviors. Barriers were a poor work environment, caregiver responsibilities, negative life events and lack of support. The second theme “Recovery activities are needed every step of the way” describes how both the need for recovery activities and the types of activities experienced as helpful changed during the recovery process, from low-effort recovery activities for long periods of time to shorter and more active recovery activities. Recovery activities were described as important for self-care but hard to prioritize in everyday life. The last theme, “Reorienting to a new place”, captures the struggle to cope with the remaining impact of ED, and how internal facilitators in terms of understanding and acceptance were important to reorient and adjust to a new way of functioning.

Conclusions: Recovering from ED is a long and ongoing process where recovery activities are needed every step of the way. Our results highlight the importance of supporting personal recovery and long-term behavioral change, addressing individual stressors that may perpetuate the condition, and adjusting recovery activities according to where the person is in the recovery process.

Trial registration: ClinicalTrials.gov: NCT0073772. Registered on March 8, 2017. This study was pre-registered on Open Science Framework (osf.io).

Functional homotopy reflects the link between spontaneous activity in a voxel and its counterpart in the opposite hemisphere. Alterations in homotopic functional connectivity (FC) are seen in normal aging, with highest and lowest homotopy being present in sensory-motor and higher-order regions, respectively. Homotopic FC relates to underlying structural connections, but its neurobiological underpinnings remain unclear. The genu of the corpus callosum joins symmetrical parts of the prefrontal cortex (PFC) and is susceptible to age-related degeneration, suggesting that PFC homotopic connectivity is linked to changes in white-matter integrity. We investigated homotopic connectivity changes and whether these were associated with white-matter integrity in 338 individuals. In addition, we examined whether PFC homotopic FC was related to changes in the genu over 10 years and working memory over 5 years. There were increases and decreases in functional homotopy, with the former being prevalent in subcortical and frontal regions. Increased PFC homotopic FC was partially driven by structural degeneration and negatively associated with working memory, suggesting that it reflects detrimental age-related changes. (C) 2020 The Author(s). Published by Elsevier Inc.

How acute hyperglycaemia affects memory functions and functional brain responses in individuals with and without type 2 diabetes is unclear. Our aim was to study the association between acute hyperglycaemia and working, semantic, and episodic memory in participants with type 2 diabetes compared to a sex- A nd age-matched control group. We also assessed the effect of hyperglycaemia on working memory-related brain activity. A total of 36 participants with type 2 diabetes and 34 controls (mean age, 66 years) underwent hyperglycaemic clamp or placebo clamp in a blinded and randomised order. Working, episodic, and semantic memory were tested. Overall, the control group had higher working memory (mean z-score 33.15 ± 0.45) than the group with type 2 diabetes (mean z-score 31.8 ± 0.44, p = 0.042) considering both the placebo and hyperglycaemic clamps. Acute hyperglycaemia did not influence episodic, semantic, or working memory performance in either group. Twenty-two of the participants (10 cases, 12 controls, mean age 69 years) were randomly invited to undergo the same clamp procedures to challenge working memory, using 1-, 2-, and 3-back, while monitoring brain activity by blood oxygen level-dependent functional magnetic resonance imaging (fMRI). The participants with type 2 diabetes had reduced working memory during the 1- A nd 2-back tests. fMRI during placebo clamp revealed increased BOLD signal in the left lateral frontal cortex and the anterior cingulate cortex as a function of working memory load in both groups (3>2>1). During hyperglycaemia, controls showed a similar load-dependent fMRI response, whereas the type 2 diabetes group showed decreased BOLD response from 2-to 3-back. These results suggest that impaired glucose metabolism in the brain affects working memory, possibly by reducing activity in important frontal brain areas in persons with type 2 diabetes.