Physical exercise augmented cognitive behaviour therapy for older adults with generalised anxiety disorder (PEXACOG): a feasibility study for a randomized controlled trial.

BACKGROUND: Generalised anxiety disorder (GAD) is a frequent and severe disorder among older adults. For older adults with GAD the effect of the recommended treatment, cognitive behaviour therapy (CBT), is reduced. Physical exercise (PE) may enhance the effect of CBT by improving cognitive function and increasing levels of brain-derived neurotrophic factor (BDNF), a predictor of the effect of CBT in patients with anxiety. The aim of the study was to assess the feasibility of a randomized controlled trial (RCT) investigating treatment effect of the combination of CBT and PE for GAD in a sample of older adults, including procedures for assessment and treatment. METHODS: Four participants aged 62-70 years (M = 65.5, SD = 3.2) with a primary diagnosis of GAD were included. Participants received 15 weeks of PE in combination with 10 weeks of CBT. Participants completed self-report measures, and clinical, biological, physiological and neuropsychological tests at pre-, interim- and post-treatment. RESULTS: Procedures, protocols, and results are presented. One participant dropped out during treatment. For the three participants completing, the total adherence to PE and CBT was 80% and 100%, respectively. An independent assessor concluded that the completers no longer fulfilled the criteria for GAD after treatment. Changes in self-report measures suggest symptom reduction related to anxiety and worry. The sample is considered representative for the target population. CONCLUSIONS: The results indicate that combining CBT and PE for older adults with GAD is feasible, and that the procedures and tests are suitable and manageable for the current sample. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02690441. Registered on 24 February 2016, https://clinicaltrials.gov/ct2/show/NCT02690441 .

Reviewing chemical and biological risks in urban agriculture: A comprehensive framework for a food safety assessment of city region food systems.

Attention to urban agriculture (UA) has recently grown among practitioners, scientists, and the public, resulting in several initiatives worldwide. Despite the positive perception of modern UA and locally grown, fresh produce, the potential food safety risks connected to these practices may be underestimated, leading to regulatory gaps. Thus, there is a need for assessment tools to evaluate the food safety risks connected to specific UA initiatives, to assist practitioners in self-evaluation and control, and to provide policy makers and scholars a means to pursue and assess food safety in city regions, avoiding either a lack or an excess of regulation that could ultimately hinder the sector. To address this aim, this paper reviews the most recent and relevant literature on UA food safety assessments. Food safety indicators were identified first. Then, a food safety assessment framework for UA initiatives was developed. The framework uses business surveys and food analyses (if available) as a data source for calculating a food safety index for single UA businesses and the whole UA landscape of a given city region. The proposed framework was designed to allow its integration into the CRFS (City Region Food System) toolkit developed by FAO (Food and Agriculture Organization of the United Nations), RUAF foundation (Resource Centres on Urban Agriculture and Food Security) and Wilfrid Laurier University.

A rare case of perivascular epithelioid cell tumor (PEComa) of the pancreas diagnosed by endoscopic ultrasound.

A 49-year-old woman consulted her general practitioner (GP) regarding epigastric pain that she had experienced for 2 months. Physical examination and laboratory results were unremarkable. An abdominal ultrasound indicated a solid pancreatic tumor, which was confirmed on subsequent CT and MRI. Endoscopic ultrasound (EUS) showed a well-defined heterogeneous, predominantly hypoechoic mass in the pancreatic body, so a neuroendocrine tumor (NET) was suspected. However, EUS-guided fine-needle aspiration (EUS-FNA) was performed and based on (immuno-)histochemical findings, the extremely rare diagnosis of a perivascular epithelioid cell tumor (PEComa) of the pancreas was made. Due to the malignant potential of pancreatic PEComas, laparoscopic left-sided pancreatectomy was performed. We present a case diagnosed by preoperative EUS-FNA highlighting the clinical and endosonographic features which help to distinguish it from its most important differential diagnosis, neuroendocrine tumors (NETs) of the pancreas.

[Ewing sarcomas and Ewing-like sarcomas : New aspects]. / Ewing-Sarkome und Ewing-artige Sarkome : Neue Aspekte.

Sarcomas of the Ewing family of tumors are aggressive neoplasms occurring in bone and soft tissue of mostly children and young adults. Classical Ewing sarcomas are pathognomonically characterized by fusions between a gene of the RNA-binding TET family (EWSR1 or FUS) with a gene of the ETS-transcription family (FLI1, ERG, ETV1, ETV4 or FEV). Less frequent cases designated as Ewing-like sarcomas show different genetic rearrangements between EWSR1 and non-ETS genes (NFATC2, POU5F1, SMARCA5, PATZ, ZSG, SP3). Moreover, new molecular alterations biologically unrelated to Ewing sarcomas have recently been described in the category of undifferentiated round cell sarcomas including CIC-DUX4 fusions or BCOR alterations, each carrying unique gene expression signatures. In contrast to classical Ewing sarcomas, the morphologic spectrum of these tumor entities is much broader and includes round cell areas as well as spindled and myxoid components. The immunohistochemical profile with inconsistent CD99 positivity makes diagnosis more difficult and requires the use of a broad spectrum of antibodies and elaborate molecular work-up. Further studies for future therapeutic decision making in these newly described round cell sarcomas as well as for molecular subclassification of undifferentiated round cell sarcomas are ongoing.

[Spindle-cell osteosclerotic bone lesion with MDM2 amplification]. / Spindelzellige osteosklerotische Knochenläsion mit MDM2-Amplifikation.

This case report presents an osteosclerotic bone lesion in a 49-year-old man with MDM2 amplification. The final diagnosis shows metastasis to the bones from stomach cancer. In primary bone tumours, the MDM2 amplifications observed have been described for many other tumour entities as well, and therefore do not exclude bone metastasis from a carcinoma.

Congenital prosopagnosia: multistage anatomical and functional deficits in face processing circuitry.

Face recognition is a primary social skill which depends on a distributed neural network. A pronounced face recognition deficit in the absence of any lesion is seen in congenital prosopagnosia. This study investigating 24 congenital prosopagnosic subjects and 25 control subjects aims at elucidating its neural basis with fMRI and voxel-based morphometry. We found a comprehensive behavioral pattern, an impairment in visual recognition for faces and buildings that spared long-term memory for faces with negative valence. Anatomical analysis revealed diminished gray matter density in the bilateral lingual gyrus, the right middle temporal gyrus, and the dorsolateral prefrontal cortex. In most of these areas, gray matter density correlated with memory success. Decreased functional activation was found in the left fusiform gyrus, a crucial area for face processing, and in the dorsolateral prefrontal cortex, whereas activation of the medial prefrontal cortex was enhanced. Hence, our data lend strength to the hypothesis that congenital prosopagnosia is explained by network dysfunction and suggest that anatomic curtailing of visual processing in the lingual gyrus plays a substantial role. The dysfunctional circuitry further encompasses the fusiform gyrus and the dorsolateral prefrontal cortex, which may contribute to their difficulties in long-term memory for complex visual information. Despite their deficits in face identity recognition, processing of emotion related information is preserved and possibly mediated by the medial prefrontal cortex. Congenital prosopagnosia may, therefore, be a blueprint of differential curtailing in networks of visual cognition.

Spatiotemporal group ICA applied to fMRI datasets.

Exploratory data analysis techniques such as independent component analysis (ICA) do not depend on a priori hypotheses and are able to detect unknown, yet structured spatiotemporal processes in neuroimaging data. We present fMRI data of two different subject-groups (young and old), which performed a modified Wisconsin Card Sorting Test (WCST). Spatiotemporal ICA and SPM-generated brain maps of the subject data are compared. For the group analysis a singular value decomposition approach was used. Spatiotemporal ICA reveals a frontoparietal network being activated while subjects performed different variants of the WCST. Contrary to the SPM analysis, ICA analysis revealed significant differences between young and old subjects as well as significant within-group differences.While young subjects showed with increasing task demands (A>>B>>C) increasing activation of the right lateral prefrontal cortex and of the medial orbito-frontal cortex, old subjects showed no such gradient in activation pattern and appeared to be more distributed.

Sporadic adult onset ataxia of unknown etiology : a clinical, electrophysiological and imaging study.

BACKGROUND: The sporadic adult onset ataxias of unknown etiology (SAOA) denote the non-hereditary degenerative adult onset ataxias that are distinct from multiple system atrophy (MSA). OBJECTIVE: To define and characterize the clinical phenotype of sporadic adult onset ataxia of unknown etiology (SAOA). DESIGN: A survey of clinical features, nerve conduction and evoked potentials, autonomic tests, and magnetic resonance imaging (MRI)-based brain morphometry was conducted in patients with SAOA. PATIENTS: Study subjects were a consecutive sample of 27 patients (11 male, 16 female) who met the diagnostic criteria for SAOA (age 55 +/- 13 years; age at disease onset 47 +/- 14 years; disease duration 8 +/- 7 years). RESULTS: All patients presented with a cerebellar syndrome. The most frequent extracerebellar symptoms were decreased vibration sense in 70% and decreased or absent ankle reflexes in 33% of the patients. Nerve conduction studies revealed a polyneuropathy in 26% of the patients. Somatosensory evoked potentials were abnormal in 44%, and central motor conduction time in 17% of patients. Autonomic testing revealed an affected autonomic nervous system in 58% of patients. Voxel-based brain morphometry showed a predominant reduction of gray matter in the cerebellum which was significantly correlated with disease stages. A loss of white matter was found in both middle cerebellar peduncles and the outer edge of the pons. CONCLUSIONS: The data show that SAOA is a predominantly, but not exclusively cerebellar disorder. Clinical, electrophysiological, and imaging findings showed some similarities with multiple system atrophy which raises the question of an overlap of these two disorders.

Gene-expression signature of adhesion/growth-regulatory tissue lectins (galectins) in transitional cell cancer and its prognostic relevance.

AIMS: Lectins, and especially galectins, appear to be important in malignancy-associated processes. The aim was to analyse comprehensively the presence of galectins in urothelial tumours. METHODS AND RESULTS: Non-cross-reactive antibodies against seven family members from the three subgroups (prototype: galectin-1, -2 and -7; chimera type: galectin-3; tandem-repeat type: galectin-4, -8 and -9) were used. Gene expression was monitored in specimens of normal urothelium, fresh tumour tissue and cell lines by real-time polymerase chain reaction (PCR). The presence and evidence of tumour-associated up-regulation were shown for galectin-1 and -3. This was less clear-cut for galectin-4 and -8. Galectin-7 was expressed in all cell lines; galectin-2 and -9 were detected at comparatively low levels. Galectin-2, -3 and -8 up-regulation was observed in superficial tumours, but not in muscle-invasive tumours (P < 0.05). Immunoreactivity correlated with tumour grading for galectin-1, -2 and -8, and disease-dependent mortality correlated with galectin-2 and -8 expression. Binding sites were visualized using labelled galectins. CONCLUSIONS: The results demonstrate a complex expression pattern of the galectin network in urothelial carcinomas. Galectin-1, -2, -3 and -8 are both potential disease markers and also possible targets for bladder cancer therapy.

Voxel-based morphometry and voxel-based relaxometry in multiple system atrophy-a comparison between clinical subtypes and correlations with clinical parameters.

Multiple system atrophy (MSA) is a neurodegenerative disease affecting basal ganglia, brainstem, cerebellum, and intermediolateral cell columns of the spinal cord. Clinically, a cerebellar (MSA-C) and a parkinsonian variant of MSA (MSA-P) are distinguished. We used voxel-based morphometry (VBM) and voxel-based relaxometry (VBR) in 48 MSA patients (32 MSA-C, 16 MSA-P) and 46 controls. In MSA-C, VBM revealed gray matter loss in cerebellum, right thalamus, both putamina and several cortical regions including insular cortex. Gray matter loss in the cerebellum and insular cortex was correlated with disease duration and severity. There was white matter loss in the brainstem, which was correlated with disease duration and severity. VBR analysis in MSA-C showed decreased relaxation rate R2 in cerebellum, pontine brainstem and cortical regions including insular cortex. In MSA-P, gray matter was reduced in cerebellum, dorsal midbrain, both putamina, and several cortical regions including insular cortex. A correlation with disease duration and severity was detected only for some small cortical areas. Direct comparison of MSA-C and MSA-P showed differences only in infratentorial brain regions where structural abnormalities were more pronounced in MSA-C than in MSA-P. In MSA-C, there was a stronger reduction of gray matter in the basal parts of the cerebellum, of white matter in the brainstem and of the relaxation rate R2 in the cerebellum and brainstem.

[Soft tissue carcinoma. Epidemiology, diagnostics and therapy]. / Weichteilsarkome. Epidemiologie, Diagnostik und Therapie.

The treatment of soft tissue sarcoma requires an individually tailored, multimodal therapy due to the high variability in the clinical situation. Resection is the usual treatment for patients with superficial, low grade tumors with a diameter of <5 cm. For intermediate grade, differentiated lesions, resection with negative resection edges combined with radiotherapy attains an almost 80% total survival rate. For patients with high grade sarcoma of >5 cm, local control can be attained by resection and radiotherapy, however every second patient will develop metastases. Patients with a local recurrence should consider a new resection. Radiotherapy is the more effective the lower the remaining postoperative tumor burden.

[Soft tissue sarcoma--epidemiology, diagnosis and treatment]. / Lassen Sie beim geringsten Verdacht auf ein Weichteilsarkom den Spezialisten ran! Die Güte der Operation entscheidet über die Prognose.

On account of the considerable variability of the clinical situation, treatment of soft tissue sarcoma requires an individually oriented multimodal approach. In the case of patients with superficial low-grade tumors measuring less than 5 cm in diameter, resection alone is usually adequate. In the event of medium-grade lesions, resection with negative margins, resection in combination with radiotherapy achieves excellent local control rates associated with an overall survival rate of almost 80%. In patients with high-grade sarcomas measuring more than 5 cm in diameter, local control can be achieved with resection and radiotherapy, although every second such patient develops metastases. For patients with local recurrence, further resection should be considered/performed. Radiotherapy is all the more effective, the smaller the postoperative tumor cell burden.

Second generation of meniscus transplantation: in-vivo study with tissue engineered meniscus replacement.

INTRODUCTION: The options available after meniscus loss offer only limited chances for a long-term success. In the following experimental study, we investigated the effect of meniscus tissue engineering on properties of the collagen meniscus implant (CMI). METHODS: Autologous fibrochondrocytes, obtained per biopsy from adult Merino sheep (n=25), were released from the matrix, cultured in-vitro and seeded into CMI scaffolds (n=10, group 1). Following a 3-week in-vitro culture, the tissue engineered menisci were used for autologous transplantation. Macroscopical and histological evaluation were performed in comparison with non-seeded CMI controls (n=10, group 2) and with meniscus-resected controls (n=5, group 3) after 3 weeks (each 1 animal group 1 and 2) and 3 months. RESULTS: The lameness score did not show any difference between the groups. Meniscus tissue was found in seven knee joints (group 1), in five knee joints (group 2) and in two knee joints (group 3). The size of the transplants reduced from 25.9+/-4.5 to 20.1+/-10.8 mm (group 1) and from 25.9+/-1.5 to 14.4+/-12.5 mm (group 2). Histologically, enhanced vascularisation, accelerated scaffold re-modelling, higher content of extra-cellular matrix and lower cell number were noted in the pre-seeded menisci in comparison with non-seeded controls. Dense high-cellular fibrous scar tissue was found in two of five cases in the resection control group. CONCLUSION: Tissue engineering of meniscus with autologous fibrochondrocytes demonstrates a macroscopic and histological improvement of the transplants. However, further development of the methods, especially of the scaffold and of the cell-seeding procedure must prove the feasibility of this procedure for human applications.

Spatial attention: more than intrinsic alerting?

It has been proposed that the right hemisphere alerting network co-activates, either directly or via the brainstem, the attention system in the parietal cortex involved in spatial attention. The observation that impaired alertness and sustained attention can predict the outcome of neglect might suggest such a relationship, too. In the present fMRI study, we intended to analyse and compare the functional anatomy of two attentional conditions both involving intrinsic (endogenous) alerting and fixation but differing with respect to the degree of spatially distributed attention by using the same paradigm under two different attentional conditions. In a group of ten participants, both a focused and a distributed visuospatial attention condition evoked similar patterns of activation in dorsolateral prefrontal regions, in the anterior cingulate gyrus, in the superior and inferior parietal cortex as well as in the superior temporal gyrus and in the thalamus. These activation foci were stronger in the right hemisphere under both conditions. After subtraction of the alertness condition with focused spatial attention, distributed spatial attention with stimuli appearing at unpredictable locations within both visual fields induced additional bilateral activations only in the left and right superior parietal cortex and in the right precuneus suggesting that these regions are specific for a more widespread dispersion of spatial attention.

Linking retinotopic fMRI mapping and anatomical probability maps of human occipital areas V1 and V2.

Using functional MRI, we characterized field sign maps of the occipital cortex and created three-dimensional maps of these areas. By averaging the individual maps into group maps, probability maps of functionally defined V1 or V2 were determined and compared to anatomical probability maps of Brodmann areas BA17 and BA18 derived from cytoarchitectonic analysis (Amunts, K., Malikovic, A., Mohlberg, H., Schormann, T., Zilles, K., 2000. Brodmann's areas 17 and 18 brought into stereotaxic space-where and how variable? NeuroImage 11, 66-84). Comparison of areas BA17/V1 and BA18/V2 revealed good agreement of the anatomical and functional probability maps. Taking into account that our functional stimulation (due to constraints of the visual angle of stimulation achievable in the MR scanner) only identified parts of V1 and V2, for statistical evaluation of the spatial correlation of V1 and BA17, or V2 and BA18, respectively, the a priori measure kappa was calculated testing the hypothesis that a region can only be part of functionally defined V1 or V2 if it is also in anatomically defined BA17 or BA18, respectively. kappa = 1 means the hypothesis is fully true, kappa = 0 means functionally and anatomically defined visual areas are independent. When applying this measure to the probability maps, kappa was equal to 0.84 for both V1/BA17 and V2/BA18. The data thus show a good correspondence of functionally and anatomically derived segregations of early visual processing areas and serve as a basis for employing anatomical probability maps of V1 and V2 in group analyses to characterize functional activations of early visual processing areas.

Transpalpebral tonometry: reliability and comparison with Goldmann applanation tonometry and palpation in healthy volunteers.

BACKGROUND/AIM: TGDc-01 is a new, portable, transpalpebral tonometry device. The aim of this study was to evaluate the reproducibility of this method, including intraobserver and interobserver deviations, and to compare the results with those of Goldmann applanation tonometry and palpation of intraocular pressure (IOP). METHODS: A total of 40 eyes of 20 healthy volunteers were included. Two independent parallel observers (1 and 2) performed three replicate measurements per eye, respectively, both using TGDc01 tonometry, one observer (3) performed three replicate measurements using Goldmann applanation tonometry, and one observer (4) measured the IOP via palpation. Intraindividual deviations within and between both observers using TGDc-01 tonometry and between all three methods were investigated about clinically relevance by comparison of medians and quartiles, statistically significance by pairwise sign tests. Comparisons between observers and methods were based on averaged IOP values of the three individual measurements for each observer and each patient. Intraobserver deviations were analysed by means of Friedman tests. RESULTS: Observers 1 and 2 showed a statistically significant intraobserver deviation when using TGCc-01 (Friedman p = 0.007 for observer 1 and p = 0.002 for observer 2). There was no statistically significant interobserver deviation between observers 1 and 2 (sign test p = 0.200); however, in 45% of the eyes interobserver deviations were larger than plus or minus 3 mm Hg. The median intraindividual deviation between TGDc-01 and Goldmann (TGDc-01 minus Goldmann) was 0 mm Hg (interquartile range -1; 2 mm Hg; sign test p = 0.522); but deviations were larger than plus or minus 3 mm Hg for 38% of the 40 eyes. Median intraindividual deviation between TGDc-01 and palpation (TGDc-01 minus palpation) was -2 mm Hg (interquartile range -4; 1 mm Hg; sign test p = 0.018), but deviations were larger than plus or minus 3 mmHg for 43% of eyes. Median intraindividual deviation between Goldmann and palpation (palpation minus Goldmann) was 2 mm Hg (interquartile range -2; 4 mm Hg; p = 0.429), but deviations were larger than plus or minus 3 mm Hg in 48% of the eyes. CONCLUSION: Interobserver deviations using TGDc-01 tonometry and intraindividual deviations between TGDc-01 tonometry, Goldmann applanation tonometry, and palpation of IOP were found to be clinically relevant. Thus, according to our results TGDc-01 could not be established as a substitute or diagnostic alternative method for Goldmann applanation tonometry. But as deviations between TGDc01 and Goldmann turned out smaller than between palpation of IOP and Goldmann, TGDc-01 seems to provide a better choice for tonometry in patients, in whom Goldmann applanation tonometry is not possible.

[Prediction of response to neoadjuvant chemotherapy in Barrett's carcinoma by quantitative gene expression analysis]. / Prädiktion des Ansprechens von Barrett-Carcinomen auf neoadjuvante Chemotherapie: Genexpressionsanalyse auf RNA-Ebene durch quantitative RT-PCR.

The potential of gene expression profiles to predict the response to neoadjuvant chemotherapy in patients with advanced adenocarcinoma of the esophagus was analyzed. Paraffin-embedded endoscopic esophageal tumor biopsies of 38 patients with advanced esophageal adenocarcinoma (Barrett's adenocarcinoma) were included. All patients underwent two cycles of cisplatin and fluorouracil (5-FU) therapy with or without additional paclitaxel (taxol) followed by abdominothoracal esophagectomy. RNA expression levels of 5-FU-metabolism associated genes thymidylate synthase (TS), thymidine phosphorylase (TP), dihydropyrimidine dehydrogenase (DPD), methylenetetrahydrofolate reductase (MTHFR), MAP7, ELF3, as well as of platinum and taxane associated related genes caldesmon, excision cross-complementing genes (ERCC1 and ERCC4) HER2-neu, DNA damage-inducible gene 45 (GADD45) and multidrug resistance genes (MDR1, MRP1) were determined using real-time RT-PCR. Expression levels were correlated with the histopathological response to chemotherapy assessed in surgically resected specimens. Responding patients showed significantly higher pretherapeutic expression levels of MTHFR (p = 0.012), Caldesmon (p = 0.016), MRP1 (p = 0.007) and MDR1 (p = 0.025). In addition, patients with high pretherapeutic MTHFR and MRP1 levels had a survival benefit after surgery (p = 0.013 and p = 0.015, respectively). Additionally, intratumoral heterogeneity of gene expression of selected genes (TP, DPD, MTHFR, HER2-neu, Caldesmon, ERCC4, MRP1) was additionally verified in 9 untreated Barrett's adenocarcinoma by examination of 5 distinct tumor areas and was observed in 12.7% (5.6%-23.5%, CI 95%) of all cases analyzed. Our results indicate that determination of mRNA levels of a few genes may be useful for the prediction of the success of neoadjuvant chemotherapy in individual cancer patients with advanced adenocarcinoma of the esophagus.