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Summary Background : Computed Tomography Angiography (CTA) is utilised in pre-operative work up in adults undergoing microsurgical reconstruction. The evidence for the use of CTA pre-operatively in the paediatric population prior to reconstruction remains unclear so far as there are limited studies. Arguably the use of CTA in place of conventional angiography avoids vessel damage, which can be amplified in the paediatric population due to smaller vessel calibre. Materials and Methods : Four papers satisfying inclusion criteria were identified through PubMed, EMBASE, Cochrane database, Google Scholar and citation searching. Results : There is low grade evidence from multiple case series describing the use of CTA pre-operatively in paediatric extremity trauma prior to microsurgical reconstruction. Literature suggests that CTA may be utilised effectively in such cases. Conclusion : Evidence suggests CTA can be useful in pre-operative work-up for paediatric patients undergoing extremity reconstructive microsurgery. However, the evidence is obtained from several small case series in which selection bias is suspected thus making generalisation to larger populations difficult. Although evidence for the use of pre-operative CTA exists in the adult population which can be sensibly extrapolated into the paediatric population, higher level studies looking further at the application in paediatrics are required.

In this prospective investigation a consecutively referred series of vocational rehabilitation clients was studied using eleven socio-demographic and psycho-social items. Subjected to a factor analyses these items were included in five factors which explained 74% of the variance. By discriminant analysis the items could correctly classify 57% of those subjects who faced major vocational changes or were vocationally inactive. The level of experienced health and belief in vocational return had the heaviest overall predictive impact. The findings may help specialists in medical and vocational rehabilitation to estimate the likelihood of vocational return for somatically impaired subjects.

We present observations that suggest the X-line of guide-field magnetic reconnection is not necessarily orthogonal to the plane in which magnetic reconnection is occurring. The plane of magnetic reconnection is often referred to as the L–N plane, where L is the direction of the reversing and reconnecting magnetic field and N is normal to the current sheet. The X-line is often assumed to be orthogonal to the L–N plane (defined as the M-direction) in the majority of theoretical studies and numerical simulations. The four-satellite Magnetospheric Multiscale (MMS) mission, however, observes a guide-field magnetic reconnection event in Earth’s magnetotail in which the X-line may be oblique to the L–N plane. This finding is somewhat opportune as two of the MMS satellites at the same N location report nearly identical observations with no significant time delays in the electron diffusion region (EDR) even though they have substantial separation in L. A minimum directional derivative analysis suggests that the X-line is between 40° and 60° from M, adding support that the X-line is oblique. Furthermore, the measured ion velocity is inconsistent with the apparent motion of the MMS spacecraft in the L-direction through the EDR, which can be resolved if one assumes a shear in the L–N plane and motion in the M-direction. A nonorthogonal X-line, if somewhat common, would call for revisiting theory and simulations of guide-field magnetic reconnection, reexamination of how the reconnection electric field is supported in the EDR, and reconsidering the large-scale geometry of the X-line.

Thymidine kinase 1 (TK1), involved in DNA precursor synthesis, is used as a serum biomarker in cancer diagnostics in both human and veterinary medicine. We investigated the utility of serum TK1 protein (TK1p) and TK1 activity (TK1a) determinations for prognosis and monitoring of canine hematological malignancies. The combination of TK1p or TK1a with canine C-reactive protein (CRP) determinations was also investigated. Serum samples from 51 client-owned dogs with naive hematological malignancies and from 149 healthy subjects were included. Serum TK1p levels were determined using a prototype TK1-ELISA, TK1a using the [H-3]- dThd phosphorylation assay, and CRP using an immunoturbidimetric assay. Mean TK1p in sera from dogs with tumors was significantly higher than from healthy dogs (mean +/- SD = 3.9 +/- 5.9 vs. 0.45 +/- 0.15 ng/mL). Similarly, TK1a in hematological malignancies was significantly higher than in healthy dogs (mean + SD = 15.1 +/- 31.3 vs. 0.96 +/- 0.33 pmol/min/mL). The receiver-operating characteristic indicated that a combination of TK1p or TK1a with CRP gave higher sensitivity than either biomarker alone for the prognosis of hematological malignancies. Median pretreatment TK1p and TK1a levels were significantly higher than in dogs in remission and correlated with clinical outcome. Kaplan-Meier curve analysis showed that naive dogs with high TK1p, TK1a, and CRP had significantly shorter survival. This study present two new polyclonal antibodies used in an ELISA system to determine TK1p. The study also show that combining TK1p or TK1a with CRP gave higher sensitivity than either biomarker alone. Monitoring patients in the study while undergoing chemotherapy, suggests that the TK1 + CRP combination could be useful in a biomarker panel, possibly aiding the prognosis and therapy monitoring of hematological malignancies in dogs.

Family farming is still the main source of income for many people in the tropical regions of the world. At the same time, modern society is quickly becoming more aware of the welfare of animals for human consumption. The main objective of this study was to illustrate the need to modify certain aspects of the original Welfare Quality® (WQ) protocols developed by the EU-funded WQ project, under the conditions of small community farmers in the tropics. Thirty-four dual purpose farms in the State of Chiapas, Mexico, which had their main production focus on milk but for whom beef production was also of significant value, were evaluated utilising a merged version of the WQ protocols for dairy and beef cattle. Based on their average score, the farms obtained at least an acceptable level in each indicator of welfare. However, after merging indicators from the dairy and beef cattle protocols of WQ in order to adjust it to the prevailing conditions in the tropics, a number of sections are not applicable. This is particularly true of the section related to good housing, where most of the items do not apply due to the absence of infrastructure; the farms obtained a very high score in this section but further studies to verify whether this reflects an accurate assessment of the welfare status should be carried out. In general, the approach of the WQ protocol was useful, however certain aspects are quite different from the conventional intensive farming systems predominantly used in Europe and there is a need to implement a number of modifications.

Background: The number of older people living with cancer and cardiometabolic conditions is increasing, but little is known about how specific combinations of these conditions impact mortality. Methods: A total of 22,692 participants aged 65 years and older from four international cohorts were followed-up for mortality for an average of 10 years (8,596 deaths). Data were harmonized across cohorts and mutually exclusive groups of disease combinations were created for cancer, myocardial infarction (MI), stroke, and diabetes at baseline. Cox proportional hazards models for all-cause mortality were used to estimate the age- and sex-adjusted hazard ratio and rate advancement period (RAP) (in years). Results: At baseline, 23.6% (n = 5,116) of participants reported having one condition and 4.2% (n = 955) had two or more conditions. Data from all studies combined showed that the RAP increased with each additional condition. Diabetes advanced the rate of dying by the most years (5.26 years; 95% confidence interval [CI], 4.53-6.00), but the effect of any single condition was smaller than the effect of disease combinations. Some combinations had a significantly greater impact on the period by which the rate of death was advanced than others with the same number of conditions, for example, 10.9 years (95% CI, 9.4-12.6) for MI and diabetes versus 6.4 years (95% CI, 4.3-8.5) for cancer and diabetes. Conclusions: Combinations of cancer and cardiometabolic conditions accelerate mortality rates in older adults differently. Although most studies investigating mortality associated with multimorbidity used disease counts, these provide little guidance for managing complex patients as they age. © The Author(s) 2018. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved.

SummaryBackground Atopic dermatitis (AD) is characterized by an increased susceptibility to skin infections. Staphylococcus aureus is reported to dominate in AD lesions and reports have revealed the presence of staphylococcal biofilms. These infections contribute to aggravation of the eczema. Sodium hypochlorite is known to reduce bacterial load of skin lesions, as well as disease severity, in patients with AD, but the effect on biofilms is unknown. Objectives To investigate the antimicrobial and antibiofilm effects of sodium hypochlorite against S. aureus isolates derived from patients with AD. Methods Skin biopsies derived from patients with infected AD were examined by scanning electron microscopy (SEM). Using radial diffusion assays, biofilm assays and confocal laser scanning microscopy, we assessed the effect of sodium hypochlorite on S. aureus isolates derived from lesional skin of patients with AD. Results SEM revealed clusters of coccoid bacteria embedded in fibrin and extracellular substances at the skin of a patient with infected AD. At concentrations of 0·01–0·08%, sodium hypochlorite showed antibacterial effects against planktonic cells. Eradication of S. aureus biofilms in vitro was observed in concentrations ranging from 0·01% to 0·16%. Confocal laser scanning microscopy confirmed these results. Finally, when human AD skin was subjected to sodium hypochlorite in an ex vivo model, a dose of 0·04% reduced the bacteria derived from AD skin. Conclusions Sodium hypochlorite has antimicrobial and antibiofilm effects against clinical S. aureus isolates. Our findings suggest usage of a higher concentration than currently used in bleach baths of patients with skin-infected AD.

BACKGROUND/OBJECTIVES: It is unknown if wine, beer and spirit intake lead to a similar association with diabetes. We studied the association between alcoholic beverage preference and type 2 diabetes incidence in persons who reported to consume alcohol. SUBJECTS/METHODS: Ten European cohort studies from the Consortium on Health and Ageing: Network of Cohorts in Europe and the United States were included, comprising participant data of 62 458 adults who reported alcohol consumption at baseline. Diabetes incidence was based on documented and/or self-reported diagnosis during follow-up. Preference was defined when. >= 70% of total alcohol consumed was either beer, wine or spirits. Adjusted hazard ratios (HRs) were computed using Cox proportional hazard regression. Single-cohort HRs were pooled by random-effects meta-analysis. RESULTS: Beer, wine or spirit preference was not related to diabetes risk compared with having no preference. The pooled HRs were HR 1.06 (95% confidence interval (CI) 0.93, 1.20) for beer, HR 0.99 (95% CI 0.88, 1.11) for wine, and HR 1.19 (95% CI 0.97, 1.46) for spirit preference. Absolute wine intake, adjusted for total alcohol, was associated with a lower diabetes risk: pooled HR per 6 g/day was 0.96 (95% CI 0.93, 0.99). A spirit preference was related to a higher diabetes risk in those with a higher body mass index, in men and women separately, but not after excluding persons with prevalent diseases. CONCLUSIONS: This large individual-level meta-analysis among persons who reported alcohol consumption revealed that the preference for beer, wine, and spirits was similarly associated with diabetes incidence compared with having no preference.

International audience; The aim of the GBAR (Gravitational Behavior of Antimatter at Rest) experiment is to measure the free fall acceleration of an antihydrogen atom, in the terrestrial gravitational field at CERN and therefore test the Weak Equivalence Principle with antimatter. The aim is to measure the local gravity with a 1% uncertainty which can be reduced to few parts of 10-3.

Summary Background In healthy 4-yr-olds 17% were overweight/obese and high fat intake was associated with lower body weight and BMI. Aim The objective was to analyse food intake and the relationship to anthropometry at the age of 8 yrs. Design One-hundred and fourteen 8-yr-olds were investigated. Questionnaires were used for lifestyle, health and food choice combined with a 24-h dietary recall. Serum concentrations of vitamin D (25(OH)D) and phospholipid fatty acid concentrations were measured in 97 children. Results Percentage of overweight/obesity was similar to 4-yr-olds. Saturated fat intake was higher than recommended. Consumption of full fat milk was negatively associated to BMI, like protein and fat intake per kg body weight. A moderate intake of fat fish was associated with higher serum concentrations of omega-3 fatty acids. Serum 25(OH)D levels were correlated to the intake. Junk food was mainly restricted to weekends and associated to higher energy, fat and sucrose intake, without association to anthropometry. Conclusion Food pattern was similar to that at 4 yrs of age suggesting that food habits were established at an early age. High saturated fat intake was not negatively influencing anthropometry. Serum markers reflected the intake of fish, milk and vitamin D.

Aim: Orexins/hypocretins (OX/Hcrt) are hypothalamic neuropeptides linking sleep-wakefulness, appetite and neuroendocrine control. Their role and mechanisms of action on higher brain functions, such as learning and memory, are not clear. Methods: We used field recordings of excitatory post-synaptic potentials (fEPSP) in acute mouse brain slice preparations to study the effects of orexins and pharmacological inhibitors of multiple kinases on long-term synaptic plasticity in the hippocampus. Results: Orexin-A (OX-A) but not orexin-B (OX-B) induces a state-dependent long-term potentiation of synaptic transmission (LTP OX ) at Schaffer collateral-CA1 synapses in hippocampal slices from adult (8- to 12-week-old) mice. In contrast, OX-A applied to slices from juvenile (3- to 4-week-old) animals causes a long-term depression (LTD OX ) in the same pathway. LTP OX is blocked by pharmacological inhibition of orexin receptor-1 (OX1R) and plasticity-related kinases, including serine/threonine- (CaMKII, PKC, PKA, MAPK), lipid- (PI3K), and receptor tyrosine kinases (Trk). Inhibition of OX1R, CaMKII, PKC, PKA and Trk unmasks LTD OX in adult animals. Conclusion: Orexins control not only the bistability of arousal states and threshold for appetitive behaviours but, in an age- and kinase-dependent manner, also bidirectional long-term synaptic plasticity in the hippocampus, providing a possible link between behavioural state and memory functions.

Using microarray analysis, in situ hybridization and immunocytochemistry, we found that the transcription factor TBX3 is produced in three discrete neuronal populations of the adult mouse brain, the arcuate nucleus (including in NPY but not dopaminergic neurons), the histaminergic tuberomammillary nucleus and in cholinergic neurons of the solitary tract nucleus. The immunoreactive protein had a nuclear location in these neurons, consistent with its function as a transcription factor. Although the function of tbx3 in these neurons is unknown, a review of the literature strongly suggests that these neuronal populations may be abnormal in Ulnar-Mammary syndrome patients with tbx3 mutations, explaining previously overlooked phenotypes in this syndrome, such as obesity, sexual dysfunction and possibly sleep abnormalities.

Tissue engineering and cell therapy require large-scale production of homogeneous populations of lineage-restricted progenitor cells that easily can be induced to differentiate into a specific tissue. We have developed straightforward protocols for the establishment of human embryonic stem (hES) cell-derived mesenchymal progenitor (hES-MP) cell lines. The reproducibility was proven by derivation of multiple hES-MP cell lines from 10 different hES cell lines. To illustrate clinical applicability, a xeno-free hES-MP cell line was also derived. None of the markers characteristic for undifferentiated hES cells were detected in the hES-MP cells. Instead, these cells were highly similar to mesenchymal stem cells with regard to morphology and expression of markers. The safety of hES-MP cells following transplantation was studied in severely combined immunodeficient (SCID) mice. The implanted hES-MP cells gave rise to homogeneous, well-differentiated tissues exclusively of mesenchymal origin and no teratoma formation was observed. These cells further have the potential to differentiate toward the osteogenic, adipogenic, and chondrogenic lineages in vitro. The possibility of easily and reproducibly generating highly expandable hES-MP cell lines from well-characterized hES cell lines with differentiation potential into several mesodermal tissues entails an enormous potential for the field of regenerative medicine.

Although the potential of adult neural stem cells to repair damage via cell replacement has been widely reported, the ability of endogenous stem cells to positively modulate damage is less well studied. We investigated whether medium conditioned by adult hippocampal stem/progenitor cells altered the extent of excitotoxic cell death in hippocampal slice cultures. Conditioned medium significantly reduced cell death following 24 h of exposure to 10 microM NMDA. Neuroprotection was greater in the dentate gyrus, a region neighboring the subgranular zone where stem/progenitor cells reside compared with pyramidal cells of the cornis ammonis. Using mass spectrometric analysis of the conditioned medium, we identified a pentameric peptide fragment that corresponded to residues 26-30 of the insulin B chain which we termed 'pentinin'. The peptide is a putative breakdown product of insulin, a constituent of the culture medium, and may be produced by insulin-degrading enzyme, an enzyme expressed by the stem/progenitor cells. In the presence of 100 pM of synthetic pentinin, the number of mature and immature neurons killed by NMDA-induced toxicity was significantly reduced in the dentate gyrus. These data suggest that progenitors in the subgranular zone may convert exogenous insulin into a peptide capable of protecting neighboring neurons from excitotoxic injury.

Ten (TG)n positive clones, isolated from an equine genomic library and sequenced, contained 12-19 uninterrupted TG repeats. Primers for polymerase chain reaction (PCR) were synthesized and nine of these (TG)n loci (HTG7-15) were successfully amplified and utilized in this study together with five previously reported equine microsatellite loci (HTG2-6). The PCR products were analysed by polyacrylamide gel electrophoresis followed by automated laser fluorescence detection or autoradiography. All microsatellites showed polymorphism and stable Mendelian inheritance. Differences in microsatellite variability between horse breeds were detected. A linkage analysis comprising HTG2-15, one coat colour gene and 16 genetic blood markers enabled addition of HTG2 to linkage group U2 and a new linkage group (U6) was established comprising the loci HTG7 and HTG12. Close linkage was excluded within a set of eight microsatellites. The estimated probability of exclusion in four breeds for a parentage test based on these eight loci varied between 0.96 and 0.99.

Local community participation is an important objective for many health promotion interventions, but it hinges on the incentives for local organizations to participate. Both aspects might be explored with information obtained from economic evaluations, illustrated in this study with data from a cost-effectiveness analysis of an elderly safety promotion programme implemented in Sweden. Previously, resource mobilization has been used as a process indicator for successful community participation. We propose that resource mobilization can be measured as the proportion of total intervention costs paid by collaborators. In the case presented here, local collaborators contributed 50 per cent of the total intervention costs (SEK 6.45 million, in Swedish krona 2004; 1 USD = 7.35 SEK), while participants, i.e. the elderly in the intervention area, contributed 13 per cent and the remainder, 37 per cent, was paid by project funds. In a subsector financial analysis, the distribution of costs and financial benefits from interventions among different sectors in society is described. The estimated financial benefits in the case were divided between the health-care system (SEK 2.5 million), the local authority (SEK 3.7 million) and the elderly and their relatives (SEK 0.3 million). The only net beneficiary was the local authority. In the case presented here, the health promotion objective of local community participation was achieved as half of the total costs was mobilized from local collaborators. The local community participation objective was supported by financial incentives for at least one key collaborator.

Cranial radiation therapy is commonly used in the treatment of childhood cancers. It is associated with cognitive impairments tentatively linked to the hippocampus, a neurogenic region of the brain important in memory function and learning. Hippocampal neurogenesis is positively regulated by voluntary exercise, which is also known to improve hippocampal-dependent cognitive functions. In this work, we irradiated the brains of C57/BL6 mice on postnatal day 9 and evaluated both the acute effects of irradiation and the effects of voluntary running on hippocampal neurogenesis and behavior 3 months after irradiation. Voluntary running significantly restored precursor cell and neurogenesis levels after a clinically relevant, moderate dose of irradiation. We also found that irradiation perturbed the structural integration of immature neurons in the hippocampus and that this was reversed by voluntary exercise. Furthermore, irradiation-induced behavior alterations observed in the open-field test were ameliorated. Together, these results clearly demonstrate the usefulness of physical exercise for functional and structural recovery from radiation-induced injury to the juvenile brain, and they suggest that exercise should be evaluated in rehabilitation therapy of childhood cancer survivors.

Development of strategies that allow for identification of secreted factors in conditioned media is of significance for a wide range of research areas. Secreted factors are involved in intercellular communication and might also be biomarkers of potential clinical importance, used for early detection and diagnosis of disease. The aim of this study was to investigate whether metabolic labeling combined with mass spectrometry could be used to identify secreted proteins in serum-containing conditioned medium. Earlier proteomic studies of conditioned media have been performed on cells cultured in serum-free media. In the present study the fact that only the proteins derived from the cells contain the incorporated isotopically labeled amino acid was taken advantage of, making it possible to differentiate released proteins from medium proteins. The second objective was to examine whether any quantitative differences in the secretion profiles between primary astrocytes and astrocytes in a scratch injury model of reactive astrogliosis could be found. To our knowledge, this is the first study to identify secreted proteins in serum-containing medium using a proteomic approach involving stable isotope labeling by amino acids in cell cultures and mass spectrometry.

Research focusing on glutamate as a major contributor to schizophrenia has attained increasing prominence over the past decade. Analogous to an NMDA-receptor hypofunction in schizophrenia, growing evidence suggest that the disease is related to an excess of brain kynurenic acid (KYNA), an endogenous antagonist at the glycine-site of the NMDA receptor. Previous studies have shown tha t MK-801, an NMDA-receptor antagonist with psychotomimetic properties, induces alteration of several genes and protein levels in cortex and thalamus previously found to be changed in the brains of patients with schizophrenia. In the present study, we use p roteomics to investigate whether an increased KYNA turnover in the brain, induced by subchronic treatment of kynurenine and probenecid, w ould interfere with the protein synthesis in the cortex and thalamus in the rat brain. The levels of four proteins in the cortex wer e increased in the group treated with kynurenine and probenecid compared to vehicle-treated controls. The proteins were; 1, Ubiquitin carbo xy- terminal hydrolase L1 (UCHL1), 2, Similar to NADH dehydrogenase, 3, Cytochrome c oxidase and 4, protein with an undetermined identity. No protein changes were observed in the thalamus. Two of these proteins are implicated in mitochondrial energy produc tions and mRNA from one of them – cytochrome c oxidase – has previously been shown to be increased in the cortex from patients with schizophrenia. Present result show that increased turnover of the endogenous NMDA receptor antagonist KYNA is able to affect cortical protein synthesis to a condition as observed in patients with schizophrenia.

The biogenesis of the Salmonella-containing vacuole within mammalian cells has been intensively studied over recent years. However, the ability of Salmonella to sense and adapt to the intracellular environment of different types of host cells has received much less attention. To address this issue, we report the transcriptome of Salmonella enterica serovar Typhimurium SL1344 within epithelial cells and show comparisons with Salmonella gene expression inside macrophages. We report that S. Typhimurium expresses a characteristic intracellular transcriptomic signature in response to the environments it encounters within different cell types. The signature involves the upregulation of the mgtBC, pstACS and iro genes for magnesium, phosphate and iron uptake, and Salmonella pathogenicity island 2 (SPI2). Surprisingly, in addition to SPI2, the invasion-associated SPI1 pathogenicity island and the genes involved in flagellar biosynthesis were expressed inside epithelial cells at later stages of the infection, while they were constantly downregulated in macrophage-like cells. To our knowledge, this is the first report of the simultaneous transcription of all three Type Three Secretion Systems (T3SS) within an intracellular Salmonella population. We discovered that S. Typhimurium strain SL1344 was strongly cytotoxic to epithelial cells after 6 h of infection and hypothesize that the time-dependent changes in Salmonella gene expression within epithelial cells reflects the bacterial response to host cells that have been injured by the infection process.

Supported phospholipid bilayers constitute a biomimetic platform for cell behavior studies and a new approach to the design of cell culture substrates. Phosphocholine bilayers are resistant to cell attachment, but can be functionalized with bioactive molecules to promote specific cell interactions. Here, we explore phosphocholine bilayers, functionalized with the laminin-derived IKVAV pentamer, as substrates for attachment, growth, and differentiation of neural progenitor cells (AHPs). By varying peptide concentration (0-10%), we discovered a strongly nonlinear relationship between cell attachment and IKVAV concentration, with a threshold of 1% IKVAV required for attachment, and saturation in cell binding at 3% IKVAV. This behavior, together with the 10-fold reduction in cell attachment when using a jumbled peptide sequence, gives evidence for a specific interaction between IKVAV and its AHP cell-surface receptor. After 8 days in culture, the peptide-functionalized bilayers promoted a high degree of cell cluster formation. This is in contrast to the predominant monolayer growth, observed for these cells on the standard laminin coated growth substrates. The peptide-functionalized bilayer did not induce differentiation levels over those observed for the laminin coated substrates. These results are promising in that peptide-functionalized bilayers can allow attachment and growth of stem cells without induction of differentiation.

We demonstrate that X chromosome-linked inhibitor of apoptosis protein (XIAP) counteracts oxidative stress in two essentially different disease-related models of brain injury, hypoxia-ischemia and irradiation, as judged by lower expression of nitrotyrosine (5-fold) and 4-hydroxy-2-nonenal (10-fold) in XIAP-overexpressing compared with wild-type mice. XIAP overexpression induced up-regulation of at least three antioxidants residing in mitochondria, superoxide dismutase 2, thioredoxin 2 and lysine oxoglutarate reductase. Cytochrome c release from mitochondria was reduced in XIAP-overexpressing mice. Hence, in addition to blocking caspases, XIAP can regulate reactive oxygen species in the brain, at least partly through up-regulation of mitochondrial antioxidants. XIAP-induced prevention of oxidative stress was not secondary to tissue protection because although XIAP overexpression provides tissue protection after hypoxia-ischemia, it does not prevent tissue loss after irradiation. This is a previously unknown role of XIAP and may provide the basis for development of novel protective strategies for both acute and chronic neurodegenerative diseases, where oxidative stress is an integral component of the injury mechanisms involved.

Purpose: Adult hippocampal neurogenesis is enhanced in several models for temporal lobe epilepsy (TLE). In this study, we used low-dose whole brain radiation to suppress hippocampal neurogenesis and then studied the effect of this treatment on epileptogenesis in a kindling model for TLE. Methods: Half of the rats were exposed to a radiation dose of 8 Gy one day before the initiation of a rapid kindling protocol. Afterdischarge threshold (ADT), afterdischarge duration (ADD), clinical seizure severity, and inflammation were compared between groups. On the first and third day after radiation, rats were injected with 5'-bromo-2'-deoxyuridine (BrdU) to evaluate neurogenesis. Seven and 21 days after radiation, numbers of doublecortin (DCX) positive neuroblasts in subgranular zone and granule cell layer were compared between groups. Results: We showed that radiation significantly suppressed neurogenesis and neuroblast production during kindling acquisition. Radiation prevented an increase in ADT that became significantly lower in radiated rats. On the third and fourth kindling acquisition day radiated rats developed more severe seizures more rapidly, which resulted in a significantly higher mean severity score on these days. Differences in ADD could not be demonstrated. Discussion: Our results demonstrate that brain radiation with a relatively low dose effectively suppressed the generation of new granule cells and transiently enhanced excitability during kindling acquisition. Although seizure-induced neurogenesis was lower in the radiated rats we could not detect a strong effect on the final establishment of the permanent fully kindled state, which argues against a prominent role of seizure-induced neurogenesis in epileptogenesis.

During brain development, one of the most important structures is the subventricular zone (SVZ), from which most neurons are generated. In adulthood the SVZ maintains a pool of progenitor cells that continuously replace neurons in the olfactory bulb. Neurodegenerative diseases induce a substantial upregulation or downregulation of SVZ progenitor cell proliferation, depending on the type of disorder. Far from being a dormant layer, the SVZ responds to neurodegenerative disease in a way that makes it a potential target for therapeutic intervention.

1. The subventricular zone (SVZ) of the forebrain that overlies the caudate nucleus is one of the principal brain regions in which neurogenesis occurs in the human brain, throughout life. 2. In response to the degeneration that occurs in the caudate nucleus in Huntington's disease, or in the caudate nucleus or cortex in stroke models, the SVZ increases the production of progenitor cells that migrate towards the site of the damage where they can differentiate into mature neurons and glial cells. The SVZ contains three main cell types and these are progenitor cells, glial cells and migratory neuroblasts; glial cells are the most common cell type and, in response to Huntington's disease, most of the SVZ cell proliferation is glial, but the number of precursor and neuroblasts is also increased. 3. The SVZ is enriched in neuroactive compounds, such as neuropeptide Y and gamma-aminobutyric acid receptor subunits gamma2, which stimulate ongoing neurogenesis. Interestingly, these stimulating cues are upregulated in the SVZ in response to Huntington's disease. Thus, the SVZ comprises heterogeneous cell types that are maintained in an environment that is permissive to neurogenesis and gliogenesis, and responds to neurodegenerative changes in adjacent brain regions by increasing progenitor cell proliferation and neurogenesis in an attempt to replace the cells that die as a result of neurodegeneration.

The rostral migratory stream (RMS) is the main pathway by which newly born subventricular zone cells reach the olfactory bulb (OB) in rodents. However, the RMS in the adult human brain has been elusive. We demonstrate the presence of a human RMS, which is unexpectedly organized around a lateral ventricular extension reaching the OB, and illustrate the neuroblasts in it. The RMS ensheathing the lateral olfactory ventricular extension, as seen by magnetic resonance imaging, cell-specific markers, and electron microscopy, contains progenitor cells with migratory characteristics and cells that incorporate 5-bromo-2′-deoxyuridine and become mature neurons in the OB.

Background and aims: The importance of efficient and safe treatment of Crohns disease is highlighted by its chronicity. Both medical and surgical treatments have shown good results in the symptomatic control of limited ileocaecal Crohns disease. The aim of this study was to compare medical treatment with surgical treatment of ileocaecal Crohns disease. Methods: Thirty-six patients from seven hospitals with primary ileocaecal Crohns disease were randomized to either medical or surgical treatment. The medical treatment was induction of remission with budesonide and thereafter maintenance treatment with azathioprine. The surgical treatment was open ileocaecal resection. Crohns disease activity index over time, expressed as area under the curve at 1, 3 and 5 years, was the primary endpoint. Subjective health measured with the 36-item Short Form Survey Instrument (SF36) and a visual analogue scale (VAS) were secondary endpoints. Results: There were no differences between the treatment groups in Crohns disease activity index over time. General health, measured as SF36 score, was higher in patients receiving surgical treatment than in those receiving medical treatment at 1 year, but there was no corresponding difference in VAS. Due to the slow inclusion rate and changes in clinical practice, the study was t = erminated prematurely. Conclusion: The study ended up being underpowered and should be interpreted with caution, but there was no clinically significant difference between the two treatment arms. Further studies are needed to address this important clinical question.