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Background: There has been an increased focus on patient involvement in health care worldwide, with studies showing that involving patients in their treatment and care is associated with positive outcomes. However, there is a dearth of knowledge about inpatient preferences and experiences of involvement in neurosurgery in Scandinavian countries. This study aimed to identify inpatients' preferences regarding their involvement in their treatment and the extent to which they experienced being involved in their treatment and care during admission., Methods: A questionnaire survey was administered in a neurosurgical department. Patients' preferences and experiences regarding their involvement in their treatment and care were assessed using a validated questionnaire., Results: One hundred patients were enrolled in the study. Eighty-two percent of them preferred sharing responsibility for their treatment with their doctor, 16% preferred leaving their treatment decisions entirely up to the doctor; and two percent preferred making the final decision about their treatment independently. The average participation score for information, communication, and participation was 4.08, suggesting that the patients experienced a high level of involvement in their care and treatment. Thirty patients reported preferences for changes during admission, while 25 suggested ideas for improvement., Conclusions: The patients mostly preferred shared decision-making about their treatment during hospitalization and generally reported high involvement in their treatment and care. The results showed a desire for improved information sharing and dialog among healthcare professionals, patients, and relatives., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objectives: Spinal cord stimulation (SCS) is a surgical treatment for severe, chronic, neuropathic pain. It is based on one to two lead(s) implanted in the epidural space, stimulating the dorsal column. It has long been assumed that when deactivating SCS, there is a variable interval before the patient perceives the return of the pain, a phenomenon often termed echo or carryover effect. Although the carryover effect has been problematized as a source of error in crossover studies, no experimental investigation of the effect has been published. This open, prospective, international multicenter study aimed to systematically document, quantify, and investigate the carryover effect in SCS., Materials and Methods: Eligible patients with a beneficial effect from their SCS treatment were instructed to deactivate their SCS device in a home setting and to reactivate it when their pain returned. The primary outcome was duration of carryover time defined as the time interval from deactivation to reactivation. Central clinical parameters (age, sex, indication for SCS, SCS treatment details, pain score) were registered and correlated with carryover time using nonparametric tests (Mann-Whitney/Kruskal-Wallis) for categorical data and linear regression for continuous data., Results: In total, 158 patients were included in the analyses. A median carryover time of five hours was found (interquartile range 2.5;21 hours). Back pain as primary indication for SCS, high-frequency stimulation, and higher pain score at the time of deactivation were correlated with longer carryover time., Conclusions: This study confirms the existence of the carryover effect and indicates a remarkably high degree of interindividual variation. The results suggest that the magnitude of carryover may be correlated to the nature of the pain condition and possibly stimulation paradigms., Clinical Trial Registration: The Clinicaltrials.gov registration number for the study is NCT03386058., Competing Interests: Conflict of Interest Bart Billet serves as a consultant for Abbott, Saluda, Bioelectronics, and Medtronic. Helga Angela Gulisano has received lecture fees from Medtronic. Jens Christian Hedemann Sørensen has received consulting fees from Novo Nordic and has a patent application for wireless brain-computer interface and stock options with Cenexum ApS and Neurizon ApS. Kaare Meier has received speaker’s fees from Abbott and has coownership of data base company Neurizon. Kliment Gatzinsky has received honoraria from Boston Scientific for lectures and serves on the advisory boards for Medtronic and Boston Scientific. Thomas Ruland reports consulting fees from Abbott. The remaining authors report no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Human cortex transcriptomic studies have revealed a hierarchical organization of γ-aminobutyric acid-producing (GABAergic) neurons from subclasses to a high diversity of more granular types. Rapid GABAergic neuron viral genetic labeling plus Patch-seq (patch-clamp electrophysiology plus single-cell RNA sequencing) sampling in human brain slices was used to reliably target and analyze GABAergic neuron subclasses and individual transcriptomic types. This characterization elucidated transitions between PVALB and SST subclasses, revealed morphological heterogeneity within an abundant transcriptomic type, identified multiple spatially distinct types of the primate-specialized double bouquet cells (DBCs), and shed light on cellular differences between homologous mouse and human neocortical GABAergic neuron types. These results highlight the importance of multimodal phenotypic characterization for refinement of emerging transcriptomic cell type taxonomies and for understanding conserved and specialized cellular properties of human brain cell types.

Cell replacement therapies for Parkinson's disease (PD) based on transplantation of pluripotent stem cell-derived dopaminergic neurons are now entering clinical trials. Here, we present quality, safety, and efficacy data supporting the first-in-human STEM-PD phase I/IIa clinical trial along with the trial design. The STEM-PD product was manufactured under GMP and quality tested in vitro and in vivo to meet regulatory requirements. Importantly, no adverse effects were observed upon testing of the product in a 39-week rat GLP safety study for toxicity, tumorigenicity, and biodistribution, and a non-GLP efficacy study confirmed that the transplanted cells mediated full functional recovery in a pre-clinical rat model of PD. We further observed highly comparable efficacy results between two different GMP batches, verifying that the product can be serially manufactured. A fully in vivo-tested batch of STEM-PD is now being used in a clinical trial of 8 patients with moderate PD, initiated in 2022., Competing Interests: Declaration of interests M.P. is the owner of Parmar Cells AB. A.K. is the owner of Kirkeby Cell Therapy APS. M.P. and A.K. are co-inventors on patents WO2016162747A2/A3 and WO2019016113A1. M.P., A.K., R.A.B., H.W., H.B., A.B., E.C., D.B.H., G.P., and B.H. have performed paid consultancy for Novo Nordisk A/S, and members of NNCT R&D are current or previous employees of Novo Nordisk A/S. T.C., A.F.A., Y.Z., S.V., and D.B.H. performed the work as employees of Lund University but are currently employed by Novo Nordisk A/S (T.C., A.F.A., and S.V.), Takara Bio (Y.Z.), and D.B.H. at Eli Lilly and Company, where she is also a minor share holder. Novo Nordisk A/S is developing the STEM-PD product for commercial use., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Faba beans ( Vicia faba L.) show exciting prospects as a sustainable source of protein and fibre, with the potential to transition to a more sustainable food production. This study reveals the compositional, nutritional and techno-functional characteristics of two protein isolates from faba beans ( Vicia faba L.), a high-starch fraction and a high-fibre side-stream. During the analysis of those four ingredients, particular attention was paid to the isolates' protein profile and the side-streams' carbohydrate composition. The isoelectric precipitated protein isolate 1 showed a protein content of 72.64 ± 0.31% DM. It exhibited low solubility but superior digestibility and high foam stability. High foaming capacity and low protein digestibility were observed for protein isolate 2, with a protein content of 71.37 ± 0.93% DM. This fraction was highly soluble and consisted primarily of low molecular weight proteins. The high-starch fraction contained 83.87 ± 3.07% DM starch, of which about 66% was resistant starch. Over 65% of the high-fibre fraction was insoluble dietary fibre. The findings of this study provide a detailed understanding of different production fractions of faba beans, which is of great value for future product development., Competing Interests: Author Jens Christian Sørensen was employed by the company SiccaDania A/S. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Objectives: Spinal cord stimulation (SCS) is a surgical treatment modality reserved for a subset of patients with neuropathic pain in which conventional pharmacologic treatment has proven insufficient. Previous studies have suggested a possible negative relationship between opioid use at referral and subsequent success of SCS therapy. The aim of this cohort study was to investigate whether preoperative opioid use was associated with inferior SCS outcomes., Materials and Methods: Data were obtained from the Danish Neurizon Neuromodulation Database and comprised preoperative registrations of analgesic use, postoperative Patients' Global Impression of Change (PGIC) ratings, pre- and postoperative pain intensity scores (Numeric Rating Scale), and detailed surgical data. Patients were dichotomized according to preoperative opioid use (users vs nonusers) with subsequent assessment of the latest PGIC rating, reduction in pain intensity, and current treatment status (implanted/explanted). In addition, daily preoperative opioid dosages were quantified in oral morphine equivalents (OME) and correlated to the treatment outcomes., Results: A total of 467 patients were included; 296 consumed opioids before SCS implantation (median 80 OME/d). Preoperative opioid use was not associated with the latest PGIC rating, reduction in pain intensity (30% or 50%), or risk of undergoing explantation (median follow-up = 3.0 years). Likewise, preoperative median OME per day of opioid users was not correlated with any of the defined outcomes., Conclusions: Preoperative opioid usage did not predict the outcome of SCS therapy in a large cohort of patients permanently implanted with an SCS system. The results do not support withholding otherwise well-indicated SCS therapy in patients with chronic neuropathic pain conditions based merely on preoperative opioid usage., (Copyright © 2022 International Neuromodulation Society. Published by Elsevier Inc. All rights reserved.)

In this study the potential targeted use of zinc to inactivate proteinase inhibitors (PI) has been investigated as an alternative to the widely applied heat treatment used industrially for inactivation of PI. Zinc was utilized for the reduction of disulfide bonds leading to the structural changes in proteins, thus affecting the decreased affinity between PI and proteinases. The protein disulfide bond reduction mechanism was studied using a newly developed micellar electrokinetic capillary chromatography (MECC) with the glutathione redox reaction with dithiothreitol (DTT) as model system. This model proved efficient in monitoring the reduction of disulfide bonds in the Kunitz trypsin inhibitor (KTI) and Bowman-Birk inhibitor (BBI). The use of zinc as a reductant resulted in a significant reduction of trypsin inhibitor activity (TIA) of 72% for KTI and 85% for BBI, highlighting zinc as a promising potential agent to reduce the activity of PI as an alternative to heat treatment., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The positron emission tomography (PET) tracer [ 18 F]GE-179 binds to the phencyclidine (PCP) site in the open N -methyl-D-aspartate receptor ion channel (NMDAR-IC). To demonstrate that PET can visualise increased [ 18 F]GE-179 uptake by active NMDAR-ICs and that this can be blocked by the PCP antagonist S-ketamine, 15 rats had an electrode unilaterally implanted in their ventral hippocampus. Seven rats had no stimulation, five received pulsed 400 µA supra-threshold 60 Hz stimulation alone, and three received intravenous S-ketamine injection prior to stimulation. Six other rats were not implanted. Each rat had a 90 min [ 18 F]GE-179 PET scan. Stimulated rats had simultaneous depth-EEG recordings of induced seizure activity. [ 18 F]GE-179 uptake (volume of distribution, V T ) was compared between hemispheres and between groups. Electrical stimulation induced a significant increase in [ 18 F]GE-179 uptake at the electrode site compared to the contralateral hippocampus (mean 22% increase in V T , p  =   0.0014) and to non-stimulated comparator groups. Rats injected with S-ketamine prior to stimulation maintained non-stimulated levels of [ 18 F]GE-179 uptake during stimulation. In conclusion, PET visualisation of focal [ 18 F]GE-179 uptake during electrically activated NMDAR-ICs and the demonstration of specificity for PCP sites by blockade with S-ketamine support the in vivo utility of [ 18 F]GE-179 PET as a use-dependent marker of NMDAR-IC activation.

Lentil ( Lens culinaris ) is a high-protein crop with a promising potential as a plant-based protein source for human nutrition. This study investigated nutritional and anti-nutritional properties of whole seed lentil flour (LF) compared to lentil protein isolates (LPIs) prepared in pilot-scale by isoelectric precipitation (LPI-IEP) and ultrafiltration (LPI-UF). Fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) profiles showed significant reductions in total galacto-oligosaccharides (GOS) contents by 58% and 91% in LPI-IEP and LPI-UF, respectively, compared to LF. Trypsin inhibitor activity (TIA) levels based on dry protein mass were lowered by 81% in LPI-IEP and 87% in LPI-UF relative to LF. Depending on the stage of digestion, the in vitro protein digestibility (IVPD) of LPIs was improved by 35-53% compared to LF, with both products showing a similar long-term protein digestibility to that of bovine serum albumin (BSA). This work supports the use of purified LPI products as a novel source of high quality protein for food applications., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Authors.)

Dry fractionated faba bean protein-rich flour (FPR) produced by milling/air classification, and faba bean protein isolate (FPI) produced by acid extraction/isoelectric precipitation were compared in terms of composition, techno-functional properties, nutritional properties and environmental impacts. FPR had a lower protein content (64.1%, dry matter (DM)) compared to FPI (90.1%, DM), due to the inherent limitations of air classification. Of the two ingredients, FPR demonstrated superior functionality, including higher protein solubility (85%), compared to FPI (32%) at pH 7. Foaming capacity was higher for FPR, although foam stability was similar for both ingredients. FPR had greater gelling ability compared to FPI. The higher carbohydrate content of FPR may have contributed to this difference. An amino acid (AA) analysis revealed that both ingredients were low in sulfur-containing AAs, with FPR having a slightly higher level than FPI. The potential nutritional benefits of the aqueous process compared to the dry process used in this study were apparent in the higher in vitro protein digestibility (IVPD) and lower trypsin inhibitor activity (TIA) in FPI compared to FPR. Additionally, vicine/convicine were detected in FPR, but not in FPI. Furthermore, much lower levels of fermentable oligo-, di- and monosaccharides, and polyols (FODMAPs) were found in FPI compared to FPR. The life cycle assessment (LCA) revealed a lower environmental impact for FPR, partly due to the extra water and energy required for aqueous processing. However, in a comparison with cow's milk protein, both FPR and FPI were shown to have considerably lower environmental impacts.

Amines synthesized by plants may be considered a dietary source of bioactive compounds, which are of interest due to possible health promoting effects. Developing Sinapis alba sprouts are known to produce 4-hydroxybenzylamine, but the reaction mechanism has not yet been established. We propose here a suggested metabolic pathway for the formation of 4-hydroxybenzylamine in S. alba plants. The catabolic sequence starts with a reaction between l-glutamine (Gln) as ammonia donor and 4-hydroxybenzyl carbocation, the enzymatic catalyzed hydrolysis product from sinalbin (4-hydroxybenzylglucosinolate). The suggested reactions are compared with alternative plant metabolic reactions used in the biosynthesis of biogenic amines.

The discovery and application of induced pluripotent stem cells (iPSCs) provide a novel treatment modality for diseases, which remain incurable. Particularly, in the treatment of neurodegenerative diseases such as Parkinson's disease (PD), iPSC‑technology holds an interesting prospect for replacement therapy. Currently, the prognostic improvement of PD is limited and relies on symptomatic treatment. However, the symptomatic dopamine‑replacement therapies lose their long‑duration responses, and novel regenerative treatment modalities are needed. Animal models have provided valuable information and identified pathogenic mechanisms underlying PD but the lack of models that recapitulate the complex pathophysiology of the disease postpones further development of novel therapeutics. This review summarizes the possible uses of iPSCs in PD and discusses the future investigations needed for iPSCs as a possible treatment of PD patients.

Background: Adult onset growth hormone (GH) deficiency (AGDH) is a potentially underdiagnosed condition, caused by damage to the pituitary gland. AGHD is treated with growth hormone replacement therapy. A large variety of clinical symptoms and changes in the metabolic homeostasis can be observed and quantified. New large animal models are needed for future drug development., New Method: In this study, we evaluate methods for a new large non-primate animal model of GH deficiency in post pubertal Göttingen Minipigs (minipig). Lesions in the pituitary gland were made by stereotaxic monopolar thermo-coagulation guided by magnetic resonance imaging (MRI), and pituitary function was evaluated using insulin tolerance test (ITT) with measurements of growth hormone secretion induced by hypoglycemia., Results: Lesions were successfully applied to the pituitary gland without any damage to surrounding tissue including the hypothalamus, which was confirmed by post-operative MRI and post mortem histology. Plasma levels of GH during ITT showed no decrease in secreted levels one week after surgery compared to levels obtained before surgery., Comparison With Existing Methods: Compared to other GH insufficiency models, eloquent brain tissue is spared. Furthermore, alternatively to rodent models, a large animal model would allow the use of human intended equipment to evaluate disease. Using the minipig avoids social, economical and ethical issues, compared with primates., Conclusion: The lesions did not remove all GH production, but proof of concept is demonstrated. In addition, the ITT is presented as a safe and efficient method to diagnose GH deficiency in minipigs., (© 2019 The Authors.)

Mixing of different protein sources can lead to either predictable, synergistic, or antagonistic effects on the protein digestibility. This study investigated the in vitro protein digestibility (IVPD) of protein mixtures between a napin-rich rapeseed (Brassica napus L.) protein concentrate (RP2) and bovine milk whey proteins (WPs; α-LA, alpha-lactalbumin; β-LG, beta-lactoglobulin) at mixing ratios of 20:80, 40:60, 60:40, and 80:20 w/w protein. Enzymatic hydrolysis consisted of pepsin digestion (1 h) followed by short- (+1 h), medium- (+3 h), or long-term (+24 h) pancreatin digestion. IVPD was differentially affected by the WPs type, mixing ratios, and total hydrolysis times. RP2/β-LG protein mixtures showed a partially synergistic effect at mixing ratios of 40:60 and 60:40 w/w, leading to an increased short-term IVPD of 7-10%. LC-MS analysis revealed a markedly improved short-term digestibility of the napin proteins when combined with bovine β-LG. This study demonstrated that specific mixtures between animal and plant protein sources exhibit an improved digestibility due to synergistic protein-protein interactions., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Monogastric animals exhibit different biological responses to structurally diverse glucosinolates and their transformation products, depending on the dietary levels. The transformations of 2-hydroxyalkenyl and aromatic glucosinolates were examined in vitro under gastric conditions, ex vivo in ligated porcine stomachs and in vivo in a rat model. Intact glucosinolates were almost completely transformed in vitro within 1 h at pH 3 (73-88%) and at pH 5 (97-100%) upon addition of Fe 2+ ranging from two-fold molar excess. Glucosinolate transformations reached 78-99% when incubated ex vivo in ligated porcine stomachs. Rat in vivo feeding trials showed major reductions (81-84%) in the intact glucosinolate contents upon passage through the gastrointestinal (GI) tract. Non-enzymatic transformations of glucosinolates occur in the stomach, where pH and the level of Fe 2+ are primary determinants. This is the first study to show a complex formation between iron-progoitrin and iron-sinalbin, facilitating the transformation into nitriles and thionamides., (Copyright © 2019. Published by Elsevier Ltd.)

The nutritional quality of rapeseed press cakes (RPCs) in piglet feed is closely linked to its digestibility and the content of glucosinolates. This study investigates the significance of intact glucosinolate (glc) levels and degree of glc transformations on piglets performance. Four different RPCs were made from a low glc (11 µmol/g seed DM) containing B. napus L. seed variety Lioness (RPC-LW, RPC-LXW, RPC-LC, RPC-LCD). RPC made from the variety Excalibur containing the upper level of glc (24 µmol/g seed DM) of double rapeseed and produced at higher and prolonged temperature (RPC-UXW) served as negative control, while soya bean protein concentrate served as positive control. Piglets (8 kg) were fed ad libitum diets balanced for RPC protein content, with RPC inclusion of 84-98 g/kg (day 0-14) and 151-178 g/kg (day 15-50). Glc transformation was reduced from 42% to 24% (7.3-4.2 µmol/g RPC) when the temperature input was lowered in the warm pressing of oil, while the glc loss was less pronounced (17%) when cold pressing was applied. The following feed pelleting process further reduced Glc concentration from 11% to 40% in warm-pressed RPCs and 54 to 85% in cold-pressed RPCs. The RPC products replaced soya bean protein without any negative effects on performance, except for piglets served cold-pressed RPC, which had a reduction in average daily weight gain (ADG) (5%-7%, p < 0.05, Day 15-50). RPC in the feed led to increased liver weight in all piglets (p = 0.026). This may point at long-term effects from feeding with RPC. Intestinal absorption of intact glcs was proven by their detection in urine. In conclusion, warm-pressed RPC can be used as feed for piglet, while the presence of active myrosinase may have a negative effect on performance and cakes should either be included in lower amounts than used in the present study (18%) or include myrosinase inactivation before use., (© 2019 Blackwell Verlag GmbH.)

Background: Intrathecal (IT) delivery is useful in both basic research and clinical treatments. Here we aim to test a new minimally invasive distribution route to the subarachnoid space (SAS) and the flow of IT administrations. We placed a radioligand into SAS during positron emission tomography (PET) scanning as a proof of concept., New Method: We injected a 11 C-labeled PET-tracer using a surgically placed catheter in the cisterna magna of anesthetized female pigs. The pigs were scanned for 1.5-2 hours in a PET/CT-scanner. The pressure from continuous infusion of artificial CSF (aCSF) promoted distribution of the tracer. The procedure was done under continuous intracranial pressure (ICP) monitoring. The catheter was made accessible both by externalization through the skin and through a subcutaneously placed sterile titanium port connected to the catheter. After image reconstruction, we used PMOD software to assess the tracer distribution throughout SAS. Internalisation of the catheter to a port enables survival studies. Previous studies performing ventriculography have placed a catheter trough brain cortex and parenchyma; such procedures may affect any behavioural or neurological evaluation, and have an increased risk of bleeding per- and post-operatively (Kaiser & Frühauf, 2007)., Results: The PET-CT visualized tracer was evenly distributed in the SAS. Furthermore, the ICP measurement made it possible to adjust infusion speed within acceptable pressure levels., Conclusion: This new method can be useful for testing distribution of PET-tracers, antibiotics, chemotherapeutics and a wide range of other pharmaceuticals targeting the CNS and spinal cord in large animal models, and potentially later in human., (Copyright © 2019. Published by Elsevier B.V.)

Tumor treating fields (TTFields) is a new non-invasive approach to cancer treatment. TTFields are low-intensity (1-5 V/m), intermediate frequency (150-200 kHz) alternating electric fields delivered locally to the tumour to selectively kill dividing cells and disrupt cancer growth. TTFields has proven safe and effective for newly diagnosed glioblastoma and is currently being tried for multiple other tumours. This review presents an introduction to TTFields, covering the main indications, the application method, the mechanism of action, the clinical results and the perspectives for implementation in Danish cancer treatment.

Parkinson's disease is characterized by a progressive loss of substantia nigra (SN) dopaminergic neurons and the formation of Lewy bodies containing accumulated alpha-synuclein (α-syn). The pathology of Parkinson's disease is associated with neuroinflammatory microglial activation, which may contribute to the ongoing neurodegeneration. This study investigates the in vivo microglial and dopaminergic response to overexpression of α-syn. We used positron emission tomography (PET) and the 18 kDa translocator protein radioligand, [ 11 C](R)PK11195, to image brain microglial activation and (+)-α-[ 11 C]dihydrotetrabenazine ([ 11 C]DTBZ), to measure vesicular monoamine transporter 2 (VMAT2) availability in Göttingen minipigs following injection with recombinant adeno-associated virus (rAAV) vectors expressing either mutant A53T α-syn or green fluorescent protein (GFP) into the SN (4 rAAV-α-syn, 4 rAAV-GFP, 5 non-injected control minipigs). We performed motor symptom assessment and immunohistochemical examination of tyrosine hydroxylase (TH) and transgene expression. Expression of GFP and α-syn was observed at the SN injection site and in the striatum. We observed no motor symptoms or changes in striatal [ 11 C]DTBZ binding potential in vivo or striatal or SN TH staining in vitro between the groups. The mean [ 11 C](R)PK11195 total volume of distribution was significantly higher in the basal ganglia and cortical areas of the α-syn group than the control animals. We conclude that mutant α-syn expression in the SN resulted in microglial activation in multiple sub- and cortical regions, while it did not affect TH stains or VMAT2 availability. Our data suggest that microglial activation constitutes an early response to accumulation of α-syn in the absence of dopamine neuron degeneration., (© 2018 Wiley Periodicals, Inc.)

Combinations of pressure, temperature and time (100-600 MPa, 30-60 °C, 3-10 min) influence enzyme activity of the myrosinase-glucosinolate system. Seedlings of Brussels sprouts were used as a model, which constitutes a well-defined and homogenous sample matrix with simple cell structures. A response surface methodology approach was used to determine the combined effect of pressure level, temperature and time on glucosinolate concentration and myrosinase activity in Brussels sprouts seedlings. The effects on residual myrosinase activity and intact glucosinolate concentration differed according to combinations of pressure, time and temperature. The results showed that maximum inactivation of myrosinase and preservation of glucosinolate (85% of the untreated level) was obtained after HP treatment at 600 MPa, 60 °C, 10 min. The highest preservation of myrosinase activity compared to untreated seedlings was after HP at 100 MPa, 30 °C, 3 min and 10 min with low degree of cell permeabilization., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Two fractions from pea (Pisum sativum L.), protein isolate (PPI) and dietary fiber (PF), were newly produced by extraction-fractionation method and characterized in terms of particle size distribution and structural morphology using SEM. The newly produced PPI and PF fractions were processed into pasta-like sheets with varying protein to fiber ratios (100/0, 90/10, 80/20, 70/30 and 50/50, respectively) using high temperature compression molding. We studied protein polymerization, molecular structure and protein-fiber interactions, as well as mechanical performance and cooking characteristics of processed PPI-PF blends. Bi-modal particle size distribution and chemical composition of the PPI and PF fractions influenced significantly the physicochemical properties of the pasta-like sheets. Polymerization was most pronounced for the 100 PPI, 90/10 and 80/20 PPI-PF samples as studied by SE-HPLC, and polymerization decreased with addition of the PF fraction. The mechanical properties, as strength and extensibility, were likewise the highest for the 100 PPI and 90/10 PPI-PF blends, while the E-modulus was similar for all the studied blends (around 38 MPa). The extensibility decreased with the increasing amount of PF in the blend. The highest amounts of β-sheets were found in the pasta-like sheets with high amounts of PPI (100, 90 and 80%), by FT-IR. An increase in PF fraction in the blend, resulted into the high amounts of unordered structures as observed by FT-IR, as well as in an increase in the molecular scattering distances observed by SAXS. The water uptake increased and cooking loss decreased with increased proportions of the PF fraction, and the consistency of 10 min cooked pasta-like sheets were alike al dente texture. The new knowledge obtained in this study on the use of extraction-fractionation method to produce novel PPI and PF fractions for developing innovative high nutritious food can be of a great importance. The obtained knowledge on the pea protein and fiber processing behaviour could greatly contribute to a better control of functional properties of various temperature-processed products from yellow pea., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Partial replacement of animal protein sources with plant proteins is highly relevant for the food industry, but potential effects on protein digestibility need to be established. In this study, the in vitro protein digestibility (IVPD) of four protein sources and their mixtures (50:50 w/w ratio) was investigated using a transient pepsin hydrolysis (1 h) followed by pancreatin (1 h). The protein sources consisted of napin-rich rapeseed (Brassica napus L.) protein concentrates (RPCs; RP1, RP2) prepared in pilot scale and major bovine whey proteins (WPs; α-LA, alpha-lactalbumin; β-LG, beta-lactoglobulin). IVPD of individual protein sources was higher for WPs compared to RPCs. The RP2/β-LG mixture resulted in an unexpected high IVPD equivalent to β-LG protein alone. Protein mixtures containing RP1 showed a new IVPD response type due to the negative influence of a high trypsin inhibitor activity (TIA) level. Improved IVPD of RP1 alone and in protein mixtures was obtained by lowering the TIA level using dithiothreitol (DTT). These results showed that napin-rich protein products prepared by appropriate processing can be combined with specific WPs in mixtures to improve the IVPD.

Neuroma pain can be severe, persistent, and treatment resistant. We present a case of a 37-year-old female amputee who suffered from severe neuroma pain, which had proved resistant to pharmacologic treatment, glycerol injections, spinal cord stimulation, radiofrequency thermocoagulation, and repeated surgical removals. After treatment with peripheral nerve stimulation, using a St. Jude Medical Octrode lead implanted percutaneously under ultrasound guidance close to her painful neuroma, her ongoing pain dramatically decreased from 8 to 3 on a numeric rating scale (0-10). Peripheral neuromodulation is a promising relatively new treatment that can be used for neuroma pain.

Nucleus accumbens (NAcc) has been implicated in several psychiatric disorders such as treatment resistant depression (TRD), and obsessive-compulsive disorder (OCD), and has been an ongoing experimental target for deep brain stimulation (DBS) in both rats and humans. In order to translate basic scientific results from rodents to the human setting a large animal model is needed to thoroughly study the effect of such therapeutic interventions. The aim of the study was, accordingly, to describe the basic anatomy of the Göttingen minipig NAcc and its retrograde connections. Tracing was carried out by MRI-guided stereotactic unilateral fluorogold injections in the NAcc of Göttingen minipigs. After 2 weeks the brains were sectioned and subsequently stained with Nissl-, autometallographic (AMG) development of myelin, and DARPP-32 and calbindin immunohistochemistry. The minipig NAcc was divided in a central core and an outer medial, ventral and lateral shell. We confirmed the NAcc to be a large and well-segregated structure toward its medial, ventral and lateral borders. The fluorogold tracing revealed inputs to NAcc from the medial parts of the prefrontal cortex, BA 25 (subgenual cortex), insula bilaterally, amygdala, the CA1-region of hippocampus, entorhinal cortex, subiculum, paraventricular and anterior parts of thalamus, dorsomedial parts of hypothalamus, substantia nigra, ventral tegmental area (VTA), the retrorubral field and the dorsal and median raphe nuclei. In conclusion the Göttingen minipig NAcc is a large ventral striatal structure that can be divided into a core and shell with prominent afferent connections from several subrhinal and infra-/prelimbic brain areas.

Objective: The present work proposes a new clinical approach to TTFields therapy of glioblastoma. The approach combines targeted surgical skull removal (craniectomy) with TTFields therapy to enhance the induced electrical field in the underlying tumor tissue. Using computer simulations, we explore the potential of the intervention to improve the clinical efficacy of TTFields therapy of brain cancer., Methods: We used finite element analysis to calculate the electrical field distribution in realistic head models based on MRI data from two patients: One with left cortical/subcortical glioblastoma and one with deeply seated right thalamic anaplastic astrocytoma. Field strength was assessed in the tumor regions before and after virtual removal of bone areas of varying shape and size (10 to 100 mm) immediately above the tumor. Field strength was evaluated before and after tumor resection to assess realistic clinical scenarios., Results: For the superficial tumor, removal of a standard craniotomy bone flap increased the electrical field strength by 60-70% in the tumor. The percentage of tissue in expected growth arrest or regression was increased from negligible values to 30-50%. The observed effects were highly focal and targeted at the regions of pathology underlying the craniectomy. No significant changes were observed in surrounding healthy tissues. Median field strengths in tumor tissue increased with increasing craniectomy diameter up to 50-70 mm. Multiple smaller burr holes were more efficient than single craniectomies of equivalent area. Craniectomy caused no significant field enhancement in the deeply seated tumor, but rather a focal enhancement in the brain tissue underlying the skull defect., Conclusions: Our results provide theoretical evidence that small and clinically feasible craniectomies may provide significant enhancement of TTFields intensity in cerebral hemispheric tumors without severely compromising brain protection or causing unacceptable heating in healthy tissues. A clinical trial is being planned to validate safety and efficacy., Competing Interests: Anders Rosendal Korshoej has received funding from Novocure Ltd. to support the clinical trial 'Enhancing Optune Therapy with Targeted Craniotomy' (clinicaltrials.gov identifier NCT02893137). The remaining authors have no competing interests.

Background: Ventriculostomy/external ventricular drain (EVD) is a common neurosurgical procedure. Various techniques are used to fixate the drain and the objective of this study was, in a retrospective setting, to compare the incidence of complications when using bolt-connected EVD (BC-EVD) versus tunneled EVD (T-EVD)., Methods: All patients subjected to an EVD performed through a new burr hole from 2009 through 2010 at two Depts. of Neurosurgery in Denmark (Odense and Aarhus) were retrospectively identified. Patient files were evaluated for EVD fixation technique (tunneled or bolt-connected EVD) and complications including unintended removal, catheter obstruction, infection, CSF leakage, and mechanical problems., Results: A total of 271 patients with 272 separate EVDs met the inclusion criteria. There was a statistically higher rate of complications leading to reinsertion in the tunneled EVD group (40 %), compared to the bolt-connected EVD group (6.5 %). There was no significant difference in infection rates., Conclusions: Tunneled EVD has a relatively high frequency of complications leading to reinsertion. The use of Bolt-connected EVD technique can lower this frequency significantly. The number needed to treat is three for preventing a complication requiring reinsertion. Infection rates are low for both types of ventriculostomies. Accordingly, we recommend use of Bolt-connected EVDs in neurosurgical practice.

Parkinson's disease (PD) is a common neurodegenerative disorder, resulting from progressive loss of dopaminergic neurons in the substantia nigra pars compacta (SNc). Neuroprotective therapies in PD are still not available, perhaps because animal models do not imitate the chronic and progressive nature of the clinical state of PD. To address this, we performed a feasibility study aimed at establishing a chronic non-primate large animal PD model in Göttingen minipigs based on continuous infusion of the neurotoxin 1-methyl-4-phenyl‑1,2,3,6-tetrahydropyridine (MPTP). Twelve female Göttingen minipigs were divided into groups of 2-4 animals and implanted with infusion pumps for continuous intramuscular MPTP delivery of 4-24 mg MPTP/day for 11 weeks. The animals showed parkinsonian symptoms with bradykinesia, rigidity, coordination and chewing difficulties. Symptoms were stable in the 12 and 18 mg MPTP/day groups, whereas the remaining groups showed partial or full behavioral recovery. Digital gait analysis, high performance liquid chromatography (HPLC) measurements and stereological counts of tyrosine hydroxylase-positive (TH+) neurons in the SNc revealed a dose-related decrease in gait velocity, striatal metabolite levels and neuron numbers with increasing doses of MPTP. No neuronal inclusions were observed, but alpha-synuclein staining intensified with increased cumulative MPTP dosages. We conclude that this large-animal model of chronic MPTP administration in Göttingen minipigs shows trends of stable parkinsonian deficits at 18 mg MPTP/day in all modalities examined. This PD model shares many of the characteristics seen in patients and, although preliminary, holds considerable promise for future pre-clinical trials of neuroprotective therapies.

Objectives: Spinal cord stimulation (SCS) is increasingly used to treat various chronic pain conditions. One undetermined issue is to what extent SCS alters the processing of sensory information from the periphery, including those stimuli that are mediated by small-fiber populations. We aimed to investigate these possible changes using quantitative sensory testing (QST)., Methods: Fourteen patients in long-term SCS treatment for complex regional pain syndrome (n=5) or pain following peripheral nerve injury (n=9) were examined with QST. All patients answered questions about their pain and underwent QST while the SCS treatment was activated and deactivated (12 h interval between the sessions) in a randomized, double-blinded crossover setting. Both the painful side and the corresponding contralateral side were examined., Results: Thermal and mechanical thresholds were similar during SCS activation and deactivation. The same result was found for intensity of pain and areas with painful symptoms even though all patients had documented long-term benefit of the treatment., Discussion: The results support existing evidence suggesting that SCS does not change sensory characteristics, which is important information for both patients and clinicians. Changes in pain intensity after deactivation of SCS may be different in short-term and long-term SCS treatment.

Primary Objective: The aim of this study was to examine the effect of a systematic reality orientation program (RO) introduced in a neurointensive care unit on duration of posttraumatic amnesia (PTA) and outcomes of patients with traumatic brain injury (TBI)., Research Design: This study used a quasiexperimental, prospective design., Methods and Procedures: Twenty-four patients (intervention) with a significant TBI classified as moderate-to-severe injuries as measured by scores of less than 12 on the Glasgow Coma Scale underwent an RO program compared with a similar group of 38 patients (control) who received a conventional rehabilitation program. The Rancho Los Amigos Score was used to assess the cognitive level 24 hours after the end of sedation, and the Galveston Orientation and Amnesia Test was used daily to assess orientation and duration of PTA. The Glasgow Outcome Scale Extended was then used as an indicator of clinical outcome after 12 months., Main Outcomes and Results: The preliminary results indicated that patients who received the RO had a higher mean of the Glasgow Outcome Scale Extended (SD = 1.53) than those receiving the usual care (SD = 1.35) despite that the groups differed significantly (p = .01) in PTA duration., Conclusion: Patients with TBI may benefit from early assessment and systematic RO nursing intervention. The RO may facilitate patients with PTA to regain orientation and interact with their surroundings in the neurointensive care unit to optimize the recovery. However, further studies with focus on timing, intensity, and duration are needed to evaluate the influence of an early RO approach on PTA and outcomes in patients experiencing TBI.

Glyphosate is widely used in coffee plantations to control weeds. Lacking selectivity, glyphosate spray drift is suspected to cause adverse effects in coffee plants. Symptoms caused by glyphosate can be similar to those produced by other stress factors. However, shikimic acid accumulation should be a useful biomarker for glyphosate exposure as shown for other crops. The aim of this study was to assess the sensitivity of coffee plants towards glyphosate on different biological response variables and to evaluate the use of shikimic acid as biomarker. Dose-response experiments yielded ED50 values (50% effect dose) in the range of 38-550 ga.e.ha(-1) depending on the quantitative or qualitative variable monitored. The frequency of plants showing symptoms was the most sensitive variable. The best sampling time for shikimic acid accumulation was 1-2 weeks after glyphosate application, depending on experimental conditions. The highest shikimic acid accumulation was observed in young leaves. Shikimic acid is a suitable biomarker for a glyphosate exposure in coffee, using only young leaves for the analysis. Young coffee plants are susceptible to glyphosate damage. If symptoms are absent the risk of severe crop damage or yield loss is low., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Most patients who die after traumatic brain injury (TBI) show evidence of ischemic brain damage. Nevertheless, it has proven difficult to demonstrate cerebral ischemia in TBI patients. After TBI, both global and localized changes in cerebral blood flow (CBF) are observed, depending on the extent of diffuse brain swelling and the size and location of contusions and hematoma. These changes vary considerably over time, with most TBI patients showing reduced CBF during the first 12 hours after injury, then hyperperfusion, and in some patients vasospasms before CBF eventually normalizes. This apparent neurovascular uncoupling has been ascribed to mitochondrial dysfunction, hindered oxygen diffusion into tissue, or microthrombosis. Capillary compression by astrocytic endfeet swelling is observed in biopsies acquired from TBI patients. In animal models, elevated intracranial pressure compresses capillaries, causing redistribution of capillary flows into patterns argued to cause functional shunting of oxygenated blood through the capillary bed. We used a biophysical model of oxygen transport in tissue to examine how capillary flow disturbances may contribute to the profound changes in CBF after TBI. The analysis suggests that elevated capillary transit time heterogeneity can cause critical reductions in oxygen availability in the absence of 'classic' ischemia. We discuss diagnostic and therapeutic consequences of these predictions.

An important component for successful translation of cell replacement-based therapies into clinical practice is the utilization of large animal models to conduct efficacy and/or safety cell dosing studies. Over the past few decades, several large animal models (dog, cat, nonhuman primate) were developed and employed in cell replacement studies; however, none of these models appears to provide a readily available platform to conduct effective and large-scale preclinical studies. In recent years, numerous pig models of neurodegenerative disorders were developed using both a transgenic approach as well as invasive surgical techniques. The pig model (naïve noninjured animals) was recently used successfully to define the safety and optimal dosing of human spinal stem cells after grafting into the central nervous system (CNS) in immunosuppressed animals. The data from these studies were used in the design of a human clinical protocol used in amyotrophic lateral sclerosis (ALS) patients in a Phase I clinical trial. In addition, a highly inbred (complete major histocompatibility complex [MHC] match) strain of miniature pigs is available which permits the design of comparable MHC combinations between the donor cells and the graft recipient as used in human patients. Jointly, these studies show that the pig model can represent an effective large animal model to be used in preclinical cell replacement modeling. This review summarizes the available pig models of neurodegenerative disorders and the use of some of these models in cell replacement studies. The challenges and potential future directions in more effective use of the pig neurodegenerative models are also discussed., (© 2014 Wiley Periodicals, Inc.)

Objectives: Spinal cord stimulation (SCS) is known to be an effective treatment for a range of neuropathic pain (NeP) conditions, although further clinical evidence is required. Clinical observations suggest that 1 aspect of the treatment effect is a reduction in the area with spontaneous NeP. The aim of this study was to quantify the areas of spontaneous NeP in SCS patients and to correlate these with changes in pain intensity and quality of life., Methods: Twenty-six SCS patients with NeP rated their pain intensity on a numerical rating scale (0 to 10) and completed the SF-36 health survey. In addition, their areas of spontaneous pain were photographically documented before and during SCS treatment, and the areas were transferred to phantom drawings and digitally quantified., Results: Areas of spontaneous NeP were reduced by 62% (interquartile range, -15 to 78). Pain intensity was reduced from 7.5 ± 1.1 before to 4.9 ± 1.7 during treatment (mean ± SD) and most domains of the SF-36 health survey also improved with SCS treatment. Using linear regression, no correlation was found between relative reduction in areas of spontaneous NeP and relative reduction in pain intensity as well as in absolute improvement in quality of life assessed by SF-36. A correlation was found between improvement in pain intensity and in quality of life., Discussion: The results indicate that the main impact of SCS on the patients' quality of life is not the reduction of the painful areas, but rather the reduced pain intensity in the remaining area.

Unlabelled: Pain is a serious consequence of spinal cord injury (SCI). Our aim was to investigate the temporal aspects of different types of pain following traumatic SCI and to determine possible predictors of neuropathic pain. Prospective data on 90 patients were collected at 1, 6, and 12 months after traumatic SCI. The patients completed questionnaires on pain severity, descriptors, and impact and underwent clinical examination with bedside sensory testing. Eighty-eight patients completed the 12-month follow-up. Approximately 80% of patients reported any type of pain at all 3 time points. Neuropathic pain related to SCI increased over time, and musculoskeletal pain decreased slightly, with both being present in 59% of patients at 12 months; other neuropathic pain not related to SCI and visceral pain were present in 1 to 3%. At-level neuropathic pain present at 1 month resolved in 45% and below-level pain resolved in 33%. Early (1 month) sensory hypersensitivity (particularly cold-evoked dysesthesia) was a predictor for the development of below-level, but not at-level, SCI pain at 12 months. In conclusion, the present study demonstrates phenotypical differences between at-level and below-level SCI pain, which is important for future studies aiming to uncover underlying pain mechanisms., Perspective: The finding that early sensory hypersensitivity predicts later onset of below-level central neuropathic pain may help to identify patients at risk of developing neuropathic pain conditions after traumatic spinal cord injury. Information about onset of pain may help to identify different phenotypes in neuropathic pain conditions., (Copyright © 2014 American Pain Society. Published by Elsevier Inc. All rights reserved.)

The mortality after aneurysmal subarachnoid hemorrhage (SAH) is 50%, and most survivors suffer severe functional and cognitive deficits. Half of SAH patients deteriorate 5 to 14 days after the initial bleeding, so-called delayed cerebral ischemia (DCI). Although often attributed to vasospasms, DCI may develop in the absence of angiographic vasospasms, and therapeutic reversal of angiographic vasospasms fails to improve patient outcome. The etiology of chronic neurodegenerative changes after SAH remains poorly understood. Brain oxygenation depends on both cerebral blood flow (CBF) and its microscopic distribution, the so-called capillary transit time heterogeneity (CTH). In theory, increased CTH can therefore lead to tissue hypoxia in the absence of severe CBF reductions, whereas reductions in CBF, paradoxically, improve brain oxygenation if CTH is critically elevated. We review potential sources of elevated CTH after SAH. Pericyte constrictions in relation to the initial ischemic episode and subsequent oxidative stress, nitric oxide depletion during the pericapillary clearance of oxyhemoglobin, vasogenic edema, leukocytosis, and astrocytic endfeet swelling are identified as potential sources of elevated CTH, and hence of metabolic derangement, after SAH. Irreversible changes in capillary morphology and function are predicted to contribute to long-term relative tissue hypoxia, inflammation, and neurodegeneration. We discuss diagnostic and therapeutic implications of these predictions.

Objectives: €‚ Spinal cord stimulation (SCS) is increasingly gaining widespread use as a treatment for chronic pain. A widely used electronic registry could play a pivotal role in improving this complex and cost-€intensive treatment. We aimed to construct a comprehensive, universally available data base for SCS., Materials and Methods: €‚ The design considerations behind a new online data base for SCS are presented; basic structure, technical issues, research applications, and future perspectives are described., Results: €‚ The Aarhus Neuromodulation Database covers core SCS treatment parameters, including procedure-€related details and complications, and features recording of key success parameters such as pain intensity, work status, and quality of life. It combines easy access to patient information with exhaustive data extraction options, and it can readily be adapted and expanded to suit different needs, including other neuromodulation treatment modalities., Conclusions: €‚ We believe that the data base described in this article offers a powerful and versatile data collection tool suited for both clinicians and researchers in the field. The basic data base structure is immediately available on a no€-cost basis, and we invite our colleagues to make use of the data base as part of the efforts to further the field of neuromodulation., (© 2012 International Neuromodulation Society.)

Background: Serum amyloid A (SAA) is useful as a diagnostic marker of systemic inflammation in horses, but only heterologous assays based on non-equine calibration and standardization are available for measurements of equine SAA. More accurate measurements could be obtained using purified species-specific SAA in native conformation for assay calibration and standardization. Further knowledge about the biochemical properties of SAA would facilitate a future production of native species-specific calibration material Therefore, the aim of the study was an investigation of the solubility and potentials for purification of equine SAA based on biochemical properties.Freeze dried equine acute phase serum was dissolved in 70% 2-propanol, 8 M urea, and milli-Q water, respectively. Supercritical fluid extraction (SFE), size-exclusive chromatography (FPLC-SEC), and preparative isoelectric focusing (IEF) were performed in the attempt to purify. Immunostaining of IEF blots were used for isoform-specific detection of SAA in the preparations and purity was assessed by silverstained SDS-PAGE., Findings: SAA was soluble in 70% 2-propanol, 8 M urea and Milli-Q water. SAA was not separated in the lipophilic or ampipathic fractions following SFE. SAA was included in a FPLC-SEC-fraction of 237 kDa, despite the molecular weight known to be much smaller, suggesting binding to other serum constituents. SAA precipitated following separation of other serum proteins by preparative IEF., Discussion: No effective purification of SAA was achieved in the present study, but findings important for future investigations were made. The study suggested that SAA is not exclusively hydrophobic, but appears less hydrophobic when interacting with other serum components. These results suggest more complex aspects of solubility than previously believed, and indicate potentials for purification of native SAA.

A range of compounds with negative nutritional impact - 'anti-nutrients' - are found in most plant foods. The contents of anti-nutrients in processed foods depend on the ingredients and processing. Anti-nutrients in complementary foods for children can have a negative impact on nutritional status. The aim of this study was to screen complementary foods from developing countries for the anti-nutritional compounds, phytate, polyphenols, inhibitors of trypsin and chymotrypsin, and lectins. Commercial products based on whole grain cereals were included as a 'worst-case' scenario for anti-nutrient exposure in Europe. Contents of minerals (iron, zinc and calcium), in which absorption or utilisation is affected by anti-nutrients, were analysed. Thirty-six products representing foods used in food aid programmes, local blended foods, fortified instant porridges and 'baby foods' were analysed. The content of minerals indicated that the fortification of a number of products did not meet the declared levels of iron, zinc and calcium. The phytate content ranged from 68 to 1536 mg/100 g, confirming a persistent problem of high levels of phytate in processed cereal- and legume-based products. The phytate : Fe molar ratio exceeded the recommended level of <1.0 in 32 of the 36 products. The total polyphenols varied from 1.3 to 9.3 mg gentisic acid equivalents g(-1) . Screening low-molecular weight soluble polyphenols may be more relevant in complementary foods than total polyphenolic compounds. Trypsin and chymotrypsin inhibitors and lectins were found in residual amounts in most products, indicating efficient degradation by heat processing. However, young infants and malnourished children may have reduced pancreatic function, and upper limits for residual trypsin inhibitors are needed., (© 2012 Blackwell Publishing Ltd.)

Background: Brain death and complications to brain death affects the function of organs in the potential donor. Previous animal models of brain death have not been able to fully elucidate the mechanisms behind this organ dysfunction, and none of the available animal models mimic the most common insult prior to brain death: intracerebral haemorrhage. The objective of this study was to develop a large animal model of brain death based on a controlled intracerebral haemorrhage and verified by computerised tomographic angiography (CTA)., Methods: Twenty pigs (range: 26.6-31.2 kg) were randomised to brain death or control. Brain death was induced by infusion of blood through a stereotaxically placed needle in the internal capsule. Brain death was confirmed by the measured intracranial pressure (ICP), lack of corneal and pupillary light reflexes, and atropine test. CTA was performed 120-180 min after brain death. The pigs were observed for 8 h after brain death., Results: Brain death was declared when the ICP exceeded mean arterial pressure after a median of 36 min (range: 28-51 min). Significant increases in heart rate, and mean arterial pressure (MAP) were followed by a steep decrease. With fluid therapy, the animals demonstrated haemodynamic stability. Reflexes disappeared, and atropine did not induce an increase in heart rate in the brain dead animals. CTA confirmed loss of cerebral circulation., Conclusion: This study offers a standardised, clinically relevant porcine model of brain death induced by a haemorrhagic attack. Brain death was verified by the disappearance of corneal and pupil reflex, atropine test, and CTA., (© 2012 The Authors. Acta Anaesthesiologica Scandinavica © 2012 The Acta Anaesthesiologica Scandinavica Foundation.)

Bovine chymosin constitutes a traditional ingredient for enzymatic milk coagulation in cheese making, providing a strong clotting capacity and low general proteolytic activity. Recently, these properties were surpassed by camel chymosin, but the mechanistic difference behind their action is not yet clear. We used capillary electrophoresis and reversed-phase liquid chromatography-mass spectrometry to compare the first site of hydrolysis of camel and bovine chymosin on bovine κ-casein (CN) and to determine the kinetic parameters of this reaction (pH 6.5; 32 °C). The enzymes showed identical specificities, cleaving the Phe105-Met106 bond of κ-CN to produce para-κ-CN and caseinomacropeptide. Initial formation rates of both products validated Michaelis-Menten modeling of the kinetic properties of both enzymes. Camel chymosin bound κ-CN with ∼30% lower affinity (K(M)) and exhibited a 60% higher turnover rate (k(cat)), resulting in ∼15% higher catalytic efficiency (k(cat)/K(M)) as compared to bovine chymosin. A local, less dense negatively charged cluster on the surface of camel chymosin may weaken electrostatic binding to the His-Pro cluster of κ-CN to simultaneously impart reduced substrate affinity and accelerated enzyme-substrate dissociation as compared to bovine chymosin.

Background: Deep brain stimulation (DBS) in the ventral tuberal hypothalamus (VTH) is currently under investigation for the treatment of severe obesity. Stimulation impact on a number of closely related hypothalamic neural systems could potentially influence normal hypothalamic function and thereby generate adverse side effects., Objective: To assess the feasibility and safety of VTH DBS in a non-primate large animal model., Methods: In the VTH of 6 Göttingen minipigs, quadropolar leads were implanted bilaterally (n = 2) or unilaterally (n = 4), using optimized MRI sequences allowing identification of major diencephalic landmarks. Heart rate, weight, behavior and nighttime locomotor activity were recorded throughout the study period. Two of the unilaterally implanted minipigs were examined with [15O]H2O positron emission tomography (PET) scans performed in DBS-off and DBS-on mode., Results: VTH DBS elicited an amplitude-dependent increase in heart rate and transient aggressive behavior. PET demonstrated that VTH DBS caused a global increase in cerebral blood flow velocities and decreased mean transit time., Conclusions: VTH DBS results in behavioral and physiological changes, which may derive from activation of closely related limbic and autonomic networks. Caution and further studies of longer length should be requested before this procedure is used more widely in humans., (Copyright © 2012 S. Karger AG, Basel.)

The increasing resolution of tract-tracing studies has led to the definition of segments along the transverse axis of the hippocampal pyramidal cell layer, which may represent functionally defined elements. This review will summarize evidence for a morphological and functional differentiation of pyramidal cells along the radial (deep to superficial) axis of the cell layer. In many species, deep and superficial sublayers can be identified histologically throughout large parts of the septotemporal extent of the hippocampus. Neurons in these sublayers are generated during different periods of development. During development, deep and superficial cells express genes (Sox5, SatB2) that also specify the phenotypes of superficial and deep cells in the neocortex. Deep and superficial cells differ neurochemically (e.g. calbindin and zinc) and in their adult gene expression patterns. These markers also distinguish sublayers in the septal hippocampus, where they are not readily apparent histologically in rat or mouse. Deep and superficial pyramidal cells differ in septal, striatal, and neocortical efferent connections. Distributions of deep and superficial pyramidal cell dendrites and studies in reeler or sparsely GFP-expressing mice indicate that this also applies to afferent pathways. Histological, neurochemical, and connective differences between deep and superficial neurons may correlate with (patho-) physiological phenomena specific to pyramidal cells at different radial locations. We feel that an appreciation of radial subdivisions in the pyramidal cell layer reminiscent of lamination in other cortical areas may be critical in the interpretation of studies of hippocampal anatomy and function., (© The Author(s) 2011. This article is published with open access at Springerlink.com)

Background: Deep brain stimulation (DBS) in experimental animals has promoted new indications and refined existing treatments. Implantation of downscaled clinical DBS leads directly compatible with commercially available implantable pulse generators can however be challenging. Accordingly, we have developed a lead implantation device (LID) and technique for minimally invasive implantation of experimental multicontact DBS leads in large research animals., Materials and Methods: The LID carries a small-diameter biocompatible polyimide guide tube which is first used for inserting the stimulating end of the lead and then implanted subcutaneously with the rest of the lead. The functionality of the device was tested by implanting 2 different designs of experimental DBS leads in 12 Göttingen minipigs for up to 12 weeks. The brains were histologically analyzed in order to assess implantation accuracy and local tissue reaction., Results and Conclusions: The LID was easy to handle and capable of accurate stereotaxic implantation of downscaled experimental DBS leads in the predetermined target brain structures with minimal surrounding tissue reaction. The device may benefit future large animal DBS research as it allows for precise implantation of DBS leads and may have implications for further refinement of clinical DBS leads., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Chronic subdural haematoma is a common disease causing morbidity and mortality. Recurrence after surgical treatment is common, varying from 5% to 30% of cases. Several methods for reducing recurrence have been advocated. The aim of this study was to investigate the effect of post-operative subdural drainage. Three hundred forty-four patients were included in a retrospective study. Treatment was performed by burr hole irrigation. Groups were separated into those with post-operative drainage compared to those without. Recurrence occurred in 14% in the drained group, significantly less than 26% in the undrained group (p=0.011). There were no differences in the complication rates. Post-operative drainage reduces recurrence of chronic subdural haematoma without increasing the complication rate. These results support those reported in several other studies. We recommend the use of post-operative subdural drainage.

The Göttingen minipig has been established as a translational research animal for neurological and neurosurgical disorders. This animal has a large gyrencephalic brain suited for examination at sufficient resolution with conventional clinical scanning modalities. The large brain, further, allows use of standard neurosurgical techniques and can accommodate clinical neuromodulatory devises such as deep brain stimulation (DBS) electrodes and encapsulated cell biodelivery devices making the animal ideal for basic scientific studies on neuromodulation mechanisms and preclinical tests of new neuromodulation technology for human use. The use of the Göttingen minipig is economical and does not have the concerns of the public associated with the experimental use of primates, cats, and dogs, thus providing a cost-effective research model for translation of rodent data before clinical trials are initiated., (Copyright © 2011 Elsevier B.V. All rights reserved.)