[Five case reports on granulosa cell tumors in cattle with practical information on diagnosis and possible progression]. / Fünf Fallberichte zum Granulosazelltumor beim Rind mit praktischen Hinweisen zur Diagnostik und zum möglichen Verlauf.

INTRODUCTION: Five cases of ovarian tumors (granulosa cell tumors) in cattle are presented from the patient load of the Vetsuisse University of Zurich and Bern. The aim of this work was to demonstrate the variable development of the illness and to indicate diagnostic and therapeutic possibilities to the practicing veterinarians. Case 1 shows bilateral appearance and the development of malignancy and metastases. The main symptoms in case 2 were the development of the mammary gland in a juvenile animal and the behavior modification due to a hormonal imbalance. The cases 3, 4 and 5 underwent surgery, case 4 restarted reproductive activity resulting in five subsequent pregnancies. The initial presumption is a result of a gynecological including ultrasonographic examination and can be verified by the analysis of Müllerian Inhibiting Hormone in serum. The decision to perform surgery should be done rapidly, as normal fertility can be achieved if the tumor is located unilaterally. Tumor growth and potential malignancy can provoke fatal health issues and also make it impossible to use meat of these animals for consumption.

INTRODUCTION: Cinq cas de tumeurs ovariennes (tumeurs des cellules de la granulosa) chez les bovins sont présentés à partir de la patientèle de l'Université Vetsuisse de Zurich et de Berne. Le but de ce travail était de montrer l'évolution variable de la maladie et d'indiquer les possibilités diagnostiques et thérapeutiques aux vétérinaires praticiens. Le cas 1 montre la possibilité d'une apparition bilatérale avec développement d'une tumeur maligne et de métastases. Les principaux symptômes du cas 2 étaient le développement de la glande mammaire chez un animal juvénile et la modification du comportement due à un déséquilibre hormonal. Les cas 3, 4 et 5 ont subi une intervention chirurgicale, le cas 4 a repris une activité de reproduction avec cinq gestations ultérieures. La présomption initiale résulte d'un examen gynécologique et peut être vérifiée par l'analyse de l'hormone anti-müllérienne dans le sérum. La décision d'opérer doit être prise rapidement, car une intervention chirurgicale pour enlever l'ovaire atteint peut, dans l'idéal, permettre une reprise de l'activité de reproduction. La croissance de la tumeur et la malignité potentielle peuvent provoquer des problèmes de santé fatals et rendre la viande de ces animaux impropre à la consommation.

Consistency of convolutional neural networks in dermoscopic melanoma recognition: A prospective real-world study about the pitfalls of augmented intelligence.

BACKGROUND: Deep-learning convolutional neural networks (CNNs) have outperformed even experienced dermatologists in dermoscopic melanoma detection under controlled conditions. It remains unexplored how real-world dermoscopic image transformations affect CNN robustness. OBJECTIVES: To investigate the consistency of melanoma risk assessment by two commercially available CNNs to help formulate recommendations for current clinical use. METHODS: A comparative cohort study was conducted from January to July 2022 at the Department of Dermatology, University Hospital Basel. Five dermoscopic images of 116 different lesions on the torso of 66 patients were captured consecutively by the same operator without deliberate rotation. Classification was performed by two CNNs (CNN-1/CNN-2). Lesions were divided into four subgroups based on their initial risk scoring and clinical dignity assessment. Reliability was assessed by variation and intraclass correlation coefficients. Excisions were performed for melanoma suspicion or two consecutively elevated CNN risk scores, and benign lesions were confirmed by expert consensus (n = 3). RESULTS: 117 repeated image series of 116 melanocytic lesions (2 melanomas, 16 dysplastic naevi, 29 naevi, 1 solar lentigo, 1 suspicious and 67 benign) were classified. CNN-1 demonstrated superior measurement repeatability for clinically benign lesions with an initial malignant risk score (mean variation coefficient (mvc): CNN-1: 49.5(±34.3)%; CNN-2: 71.4(±22.5)%; p = 0.03), while CNN-2 outperformed for clinically benign lesions with benign scoring (mvc: CNN-1: 49.7(±22.7)%; CNN-2: 23.8(±29.3)%; p = 0.002). Both systems exhibited lowest score consistency for lesions with an initial malignant risk score and benign assessment. In this context, averaging three initial risk scores achieved highest sensitivity of dignity assessment (CNN-1: 94%; CNN-2: 89%). Intraclass correlation coefficients indicated 'moderate'-to-'good' reliability for both systems (CNN-1: 0.80, 95% CI:0.71-0.87, p < 0.001; CNN-2: 0.67, 95% CI:0.55-0.77, p < 0.001). CONCLUSIONS: Potential user-induced image changes can significantly influence CNN classification. For clinical application, we recommend using the average of three initial risk scores. Furthermore, we advocate for CNN robustness optimization by cross-validation with repeated image sets. TRIAL REGISTRATION: ClinicalTrials.gov (NCT04605822).

Comparison of linear and non-linear decision boundaries to detect feedlot bloat using intensive data collection systems on Angus × Hereford steers.

Ruminal tympany (bloat) has long been an issue for large and small livestock operations. Though improvements in feedlot management practices have reduced its occurrence, it is still highly prevalent and is known to detrimentally affect animal performance, welfare, and in many instances, lead to animal death. Current decision support systems and diet formulation software omit the inclusion of bloat prediction based on animal performance. Here, we aim to predict bloat incidence in implanted and non-implanted feedlot steers from performance data comparing linear (LDB) and non-linear decision boundaries. Eighteen crossbred Angus × Hereford steers: BW (491.13 ± 25.78 kg) and age (12 ± 1 mo) were randomly distributed into implanted and non-implanted treatments. All animals were randomly assigned to one of two pens fit with automated monitoring systems for BW, freshwater intake, and water intake behavior: water intake event visit, no water intake event visit (NWIE), and time spent drinking. DM intake (DMI) was individually recorded from all animals through the Calan Gate system for 135 d (30 d adaptation, 105 d experimental diet). Incidences of bloat were recorded as bloat instances regardless of severity to ensure that early onset detection of bloat was recorded and properly identified in predictive models. Logistic regression with a binomial distribution and a logit link function was utilized to predict the incidences of bloat through LDB. Feature selection and penalization of coefficients were explored through L1 (sum of absolute values) and L2 (sum of squares) penalization to avoid overfitting of models. Additional NLDB and a non-parametric LDB are examined for prediction. Accuracy, specificity, and sensitivity were high for the models reported. No significant differences were observed between LDB and NLDB, with the highest specificity (predicting bloat) value of 0.820 for stepwise feature selection algorithms, and a value of 0.832 for the artificial neural network. Highest accuracy was 0.829 for ridge regression, and 0.847 for the random forest with hyperparameter tuning. DM intake, BW, and NWIE were the three most important variables for the prediction of feedlot bloat showing clear drops in DMI and BW and increases in NWIE when animals bloated. The lack of difference in predictive performance between LDB and NLDB highlights the often-overlooked concept that machine learning algorithms are not always the only/best modeling technique. Additionally, the models reported herein carry acceptable predictive performance for inclusion into management decisions that reduce bloat incidences in feedlot cattle.

EPA Consensus Project Paper: Accuracy of Photogrammetry Devices, Intraoral Scanners, and Conventional Techniques for the Full-Arch Implant Impressions: A Systematic Review.

PURPOSE: The objective of this systematic review was to evaluate and compare the accuracy of digital impression techniques and conventional methods for full-arch implant impressions. METHODS: An electronic literature search in the databases Medline (Pubmed), Web of Science, and Embase was performed to identify in vitro and in vivo publications (between 2016 and 2022) directly comparing digital and conventional abutment-level impression techniques. All selected articles passed through the data extraction procedure according to defined parameters in inclusion and exclusion criteria. Measurements on linear, angular and/or surface deviations were performed in all selected articles. RESULTS: Nine studies met the inclusion criteria and were selected for this systematic review. 3 articles were clinical studies and 6 studies were in vitro. Accuracy difference mean values of the trueness up to 162+/-77µm between digital and conventional techniques were reported in the clinical studies and up to 43µm in laboratory studies. Methodological heterogeneity was observed in both, in vivo and in vitro studies. CONCLUSIONS: Intraoral scanning and photogrammetric method showed comparable accuracy for registering implant positions in the full-arch edentulous cases. A tolerable implant prosthesis misfit threshold and objective misfit assessment criteria (for linear and angular deviations) should be verified in clinical studies.

Physiological stretching induces a differential extracellular matrix gene expression response in acetabular labrum cells.

The acetabular labrum is a fibrocartilaginous ring surrounding the acetabulum and is important for hip stability and contact pressure dissipation through a sealing function. Injury of the labrum may contribute to hip-joint degeneration and development of secondary osteoarthritis. Understanding how extracellular matrix (ECM) production and remodelling is regulated is of key importance for successful tissue restoration. The present study hypothesised that physiological stretching enhanced the metabolic activity and altered the ECM gene expression in labrum cells. Primary bovine labrum cells were physiologically stretched for up to 5 d. 24 h after the last stretch cycle, changes in metabolic activity were measured using the PrestoBlue™ HS Cell Viability Reagent and ECM gene expression was examined using the quantitative polymerase chain reaction method. Targets of interest were further investigated using immunofluorescence and enzyme-linked immunosorbent assay. Metabolic activity was not affected by the stretching (0.9746 ± 0.0614, p > 0.05). Physiological stretching upregulated decorin (DCN) (1.8548 ± 0.4883, p = 0.002) as well as proteoglycan 4 (PRG4) (1.7714 ± 0.6600, p = 0.029) and downregulated biglycan (BGN) (0.7018 + 0.1567, p = 0.008), cartilage oligomeric matrix protein (COMP) (0.5747 ± 0.2650, p = 0.029), fibronectin (FN1) (0.5832 ± 0.0996, p < 0.001) and spondin 1 (SPON1) (0.6282 ± 0.3624, p = 0.044) gene expression. No difference in PRG4 and DCN abundance or release could be measured. The here identified mechanosensitive targets are known to play relevant roles in tissue organisation. Therefore, physiological stretching might play a role in labrum tissue homeostasis and regeneration.

Fragmentation of propionitrile (CH3CH2CN) by low energy electrons.

Propionitrile (CH3CH2CN, PN) is a molecule relevant for interstellar chemistry. There is credible evidence that anions, molecules, and radicals that may originate from PN could also be involved in the formation of more complex organic compounds. In the present investigation, dissociative electron attachment to CH3CH2CN has been studied in a crossed electron-molecular beam experiment in the electron energy range of about 0-15 eV. In the experiment, seven anionic species were detected: C3H4N-, C3H3N-, C3H2N-, C2H2N-, C2HN-, C2N-, and CN-. The anion formation is most efficient for CN- and anions originating from the dehydrogenation of the parent molecule. A discussion of possible reaction channels for all measured negative ions is provided. The experimental results are compared with calculations of thermochemical thresholds of the detected anions.

Comparison of novel approaches for expedited pathogen identification and antimicrobial susceptibility testing against routine blood culture diagnostics.

Blood stream infections pose a major challenge for clinicians as the immediate application of an appropriate antibiotic treatment is the vital factor to safe the patients' lives. This preliminary study compares three different systems promising fast pathogen identification and susceptibility testing in comparison to conventional blood culture (BC): (i) the rapid antimicrobial susceptibility testing protocol according to EUCAST in combination with the Sepsityper® kit (sRAST), (ii) the direct inoculation method on the VITEK® 2 system (dVIT) and (iii) testing with the Accelerate Pheno® system (AccPh). All methods were assessed in terms of accuracy, time to result and usability. Twenty-three BC samples obtained from patients suffering from proven sepsis were analysed in detail. Pathogen identification was successful in 95·6, 91·3 and 91·3% in sRAST, dVIT and AccPh, respectively. Categorical agreement in antimicrobial susceptibility testing was 89·5, 96 and 96·6%, respectively. Time to result from sample entry to reporting ranged from an average of 4·6 h for sRAST and 6·9 h for AccPh to 10·6 h for dVIT. These results imply a significant shortening of reporting times at considerably high agreement rates for these new diagnostic approaches.

[Establishment of key indicators and limit values for assessment of claw health of cattle in Switzerland]. / Erarbeitung von Kennzahlen und Grenzwerten zur Klauengesundheit beim Schweizer Rindvieh.

INTRODUCTION: Herd medicine is a field of buiatrics characterized by regular and systematic visits by the veterinarian to improve the health and performance of the animals, the quality of animal products and finally the satisfaction of the farm staff. Internationally established key indicators, such as age at first calving, heat recognition rate or the percentage of cows with clinical mastitis per month (%),26 have been available for a long time in the areas of fertility and udder health. These key indicators help veterinarians to recognize and define health problems at herd level at an early stage and to work out measures for their improvement. Such key indicators are currently lacking in the field of claw health, hence making standardized identification of problem farms considerably more difficult. Considering the permanent negative influence of claw health problems on fertility, performance and overall animal welfare, it becomes clear how valuable claw health indicators will be in the future. The aim of this study was, therefore, to develop both primary and secondary indicators of claw health and to define corresponding limit values for Switzerland. Based on a literature search, several primary and secondary indicators were developed (1˚K: Herd problem Yes/No, 2˚K: Classification of the problem). These were discussed in an expert panel consisting of practicing veterinarians, staff of the Swiss bovine herd health service and university professors with regard to their possible practical implementation and relevance. Finally, 3 primary and 10 secondary indicators were judged to be suitable to assess a herd with regard to claw health. The primary key indicators were: proportion of cows leaving the herd due to a claw problem, proportion of lame cows of a herd, and proportion of cattle with at least one claw disease. The corresponding provisional limit values (exceeding the value = problem) for Switzerland were worked out by means of surveys among farmers, hoof trimmers, veterinary students and veterinarians. In addition, recommendations from the literature and current prevalence studies were used to adapt the defined limit values to the situation on Swiss farms. In the coming years, the claw health project «Gesunde Klauen - das Fundament für die Zukunft¼ will collect current prevalence values of claw diseases, and the limit values will then be adjusted and specified accordingly.

INTRODUCTION: La médecine de troupeau est un domaine de la buiatrie caractérisé par des visites régulières et systématiques du vétérinaire afin d'améliorer la santé et les performances des animaux, la qualité des produits animaux et finalement la satisfaction du personnel des exploitations. Des chiffres-clés établis au niveau international, tels que l'âge au premier vêlage, le taux de reconnaissance des chaleurs ou le pourcentage de vaches atteintes de mammite clinique par mois (%), sont disponibles depuis longtemps dans les domaines de la fertilité et de la ­santé du pis. Ces chiffres-clés aident les vétérinaires à reconnaître et à définir les problèmes de santé au niveau du troupeau à un stade précoce et à élaborer des mesures pour leur amélioration. De tels chiffres-clés font actuellement défaut dans le domaine de la santé des onglons, ce qui rend l'identification standardisée des exploitations à problèmes considérablement plus difficile. Compte tenu de l'influence négative permanente des problèmes de santé des onglons sur la fertilité, les performances et le bien-être des animaux en général, il est clair à quel point les indicateurs de santé des onglons seront précieux à l'avenir. L'objectif de ce travail était donc de développer des indicateurs primaires et secondaires de la santé des onglons et de définir les valeurs limites correspondantes pour la Suisse. Sur la base d'une recherche documentaire, plusieurs indicateurs primaires et secondaires ont été développés (1˚K: problème de troupeau Oui/Non, 2˚K: classification du problème). Ceux-ci ont été discutés dans un groupe d'experts composé de vétérinaires praticiens, de personnel du service suisse de santé des troupeaux bovins et de professeurs d'université en ce qui concerne leur pertinence et leur éventuelle mise en œuvre pratique. En fin de compte, 3 indicateurs primaires et 10 indicateurs secondaires ont été jugés appropriés pour évaluer un troupeau en ce qui concerne la santé des onglons. Les principaux indicateurs clés étaient: la proportion de vaches quittant le troupeau en raison d'un problème d'onglons, la proportion de vaches d'un troupeau boiteuses et la proportion de bovins atteints d'au moins une maladie des onglons. Les valeurs limites provisoires correspondantes (dépassant la valeur = problème) pour la Suisse ont été élaborées au moyen d'enquêtes auprès des éleveurs, des ongleurs, des étudiants en médecine vétérinaire et des vétérinaires. En outre, les recommandations de la littérature et des études de prévalence actuelles ont été utilisées pour adapter les valeurs limites définies à la situation des exploitations agricoles suisses. Dans les années à venir, le projet de santé des onglons «Des onglons sains- le fondement pour l'avenir¼ collectera les valeurs de prévalence actuelles des maladies des onglons et les valeurs limites seront ensuite ajustées et spécifiées en conséquence.

Towards redox-switchable organocatalysts based on bidentate halogen bond donors.

Redox-active bidentate halogen bond donors based on halopyridinium groups as halogen-bond donating units were synthesized and their structures were elucidated by X-ray diffraction analyses and DFT calculations. Via reversible twofold reduction, these dicationic species can be transformed to neutral compounds which should be much weaker Lewis acids. The corresponding electrochemical data were obtained, and CV as well as UV-vis and NMR techniques were also used to determine binding constants of these halogen bond donors to halides. While all titrations agree on the relative order of binding strengths (with chloride being bound strongest), there are marked deviations in the overall affinity constants which are discussed. In contrast to earlier azo-bridge analogues, the ethylene-linked variants presented herein do not oxidize halides, and thus the novel halogen bond donors could also be used as Lewis acidic organocatalysts in a halide abstraction benchmark reaction, yielding a performance similar to bis(haloimidazolium)-derived catalysts.

The Prion-like Properties of Amyloid-beta Peptide and Tau: Is there Any Risk of Transmitting Alzheimer's Disease During Neurosurgical Interventions?

Recent studies have recognized similarities between the peptides involved in the neuropathology of Alzheimer's disease and prions. The Tau protein and the Amyloid ß peptide represent the theoretical pillars of Alzheimer's disease development. It is probable that there is a shared mechanism for the transmission of these substances and the prion diseases development; this presumption is based on the presentation of several cases of individuals without risk factors who developed dementia decades after a neurosurgical procedure. This article aims to present the role of Aß and Tau, which underlie the pathophysiologic mechanisms involved in the AD and their similarities with the prion diseases infective mechanisms by means of the presentation of the available evidence at molecular (in-vitro), animal, and human levels that support the controversy on whether these diseases might be transmitted in neurosurgical interventions, which may constitute a wide public health issue.

[Improvement of claw health of cattle in Switzerland]. / Verbesserung der Klauengesundheit beim Rind in der Schweiz.

INTRODUCTION: The modern technique of cattle hoof care was founded by E. Toussaint Raven in 1977. Environmental risk factors on cattle claws altered in the past 43 years. The change from free ranging to indoor housing, the intensified feeding and the breeding towards traits of high performance have significantly increased the mechanical and chemical stress on the claws. In modern free-stalls, dairy cows are required to walk on hard flooring to feed, drink and get milked. Good hoof health is a basic requirement for cattle welfare. Professional and regular hoof trimming is still considered the most effective measure to promote hoof health in dairy cattle. In order to meet today's requirements and to promote claw health, the Swiss Hoof Trimmers Association (SKV), in collaboration with the Vetsuisse faculties, Universities of Berne and Zurich, and the Bovine Health Service (RGD, Bern) developed and described the Swiss technique of functional claw trimming. The aim was to establish a consistent method, which takes into account the size and bodyweight of the modern cow, the anatomical and physiological characteristics of their claws and includes adaptations counteracting very relevant diseases such as digital dermatitis. The result is a workflow described and illustrated with coloured pictures and consisting of five individual steps based on the technique of E. Toussaint Raven, Additionally, the upcoming Swiss national resource project on long-term improvement of claw health is presented in some detail. The key point of this project is the electronic documentation of clinical findings by the trained professional claw trimmers. This data will later (i) be used to assess the foot health of Swiss cows, (ii) allow to determine the prevalence of foot diseases of cattle in Switzerland and (iii) to monitor the effect of the implementation of foot health concepts. The aim of this work is to combine the findings from science and the practical experience of hoof trimmers in one method, to standardize the applied hoof care in Switzerland and to adapt it to today's hoof health requirements.

INTRODUCTION: La technique moderne du soin des pieds des bovins et du parage des onglons a été fondée par E. Toussaint Raven en 1977. Au cours des 43 dernières années, le passage d'une détention au pâturage à une détention à l>intérieur, l'intensification de l'alimentation et la sélection vers des caractéristiques de hautes performances ont provoqué une augmentation sensible du stress mécanique et chimique exercé sur les onglons. Dans les stabulations libres modernes, les vaches laitières doivent se déplacer activement sur un sol dur pour se nourrir, boire et se faire traire. Pour cela, une marche indolore est une exigence de base. Un parage professionnel et régulier est toujours considéré comme la mesure la plus efficace pour promouvoir la santé des onglons chez les bovins laitiers. Afin de répondre aux exigences actuelles et de promouvoir la santé des onglons, l' Association suisse des pareurs d'onglons (ASPO), en collaboration avec les facultés Vetsuisse des universités de Berne et de Zurich et le Service sanitaire bovin (SSB, Bern) a développé et décrit une technique suisse de parage fonctionnel des onglons. L'objectif était d'établir une méthode cohérente, qui tienne compte de la taille et du poids corporel de la vache moderne, des caractéristiques anatomiques et physiologiques de ses onglons et qui inclue en même temps des innovations pour lutter contre des maladies très importantes telles que la dermatite digitée. Le résultat est un processus de travail composé de cinq étapes individuelles adaptées selon E. Toussaint Raven, décrites et illustrées dans un tableau avec des illustrations en couleurs. En outre, un projet de ressource nationale suisse sur l'amélioration à long terme de la santé des onglons est présenté en détail. Dans ce cadre, la documentation électronique des découvertes pathologiques faites pendant le parage des onglons par des ongleurs professionnels et formés représente le cœur de ce projet. Ces données seront ensuite utilisées (i) pour évaluer la santé des pieds des vaches suisses, (ii) pour permettre de déterminer la prévalence des maladies des pieds des bovins en Suisse et (iii) pour surveiller l'effet de la mise en œuvre des concepts de santé des onglons. Le but de ce travail est de combiner les résultats de la recherche et l'expérience pratique des ongleurs en une seule méthode, de standardiser les soins pratiqués en Suisse et de les adapter aux exigences actuelles en matière de santé des onglons.

The correct blood volume for paediatric blood cultures: a conundrum?

BACKGROUND: Bloodstream infections (BSIs) are a major cause of morbidity and mortality in paediatric patients. For fast and accurate diagnosis, blood culture (BC) is the reference standard. However, the procedure for blood sampling in paediatric patients, particularly the optimal blood volume, is the subject of controversy stemming from a lack of knowledge of the bacterial load and because of several obstacles such as low intravascular volume and the risk of causing anaemia. AIMS: The aim of this narrative review is to summarize current knowledge on blood sampling in paediatric patients for BC purposes, in particular blood volume and number and type of BC bottles needed for reasonable future guidelines/recommendations. SOURCES: A comprehensive literature search of PubMed, including all publications in English, was performed in June 2019 using the search terms 'blood culture', 'blood volume', 'bloodstream infection', 'diagnostic', 'paediatric' and/or 'sepsis'. CONTENT: The amount of inoculated blood determines the sensitivity, specificity and time to positivity of a BC, and low-level bacteraemia (≤10 cfu/mL) in paediatric patients is presumed to be more common than reported. Current approaches for 'adequate' blood volume for paediatric BC are mainly weight- or age-dependent. Of these recommendations, the scheme devised by Gaur and colleagues seems most appropriate and calls for a sample of 1-1.5 mL for children weighing <11 kg and 7.5 mL for a patient weight of 11-17 kg to be drawn into one BC bottle. Inclusion of a more detailed grading in the weight range 4-14 kg, as published by Gonsalves and colleagues, might be useful. IMPLICATIONS: This review could be important for future guidelines on paediatric BC collection and thus could contribute to improving patient management and lowering the economic and global health burden associated with BSI. Furthermore, upcoming molecular-based approaches with low sample volumes might be an interesting alternative.

Correction: Interleukin-22-deficiency and microbiota contribute to the exacerbation of Toxoplasma gondii-induced intestinal inflammation.

The original version of this Article omitted the author Dr Mathias Chamaillard from the l'Institut de Pasteur, Lille, France. This has been corrected in both the PDF and HTML versions of the Article.

Interleukin-22-deficiency and microbiota contribute to the exacerbation of Toxoplasma gondii-induced intestinal inflammation.

Upon oral infection with Toxoplasma gondii cysts (76 K strain) tachyzoites are released into the intestinal lumen and cross the epithelial barrier causing damage and acute intestinal inflammation in C57BL/6 (B6) mice. Here we investigated the role of microbiota and IL-22 in T.gondii-induced small intestinal inflammation. Oral T.gondii infection in B6 mice causes inflammation with IFNγ and IL-22 production. In IL-22-deficient mice, T.gondii infection augments the Th1 driven inflammation. Deficiency in either IL-22bp, the soluble IL-22 receptor or Reg3γ, an IL-22-dependent antimicrobial lectin/peptide, did not reduce inflammation. Under germ-free conditions, T.gondii-induced inflammation was reduced in correlation with parasite load. But intestinal inflammation is still present in germ-free mice, at low level, in the lamina propria, independently of IL-22 expression. Exacerbated intestinal inflammation driven by absence of IL-22 appears to be independent of IL-22 deficiency associated-dysbiosis as similar inflammation was observed after fecal transplantation of IL-22-/- or WT microbiota to germ-free-WT mice. Our results suggest cooperation between parasite and intestinal microbiota in small intestine inflammation development and endogenous IL-22 seems to exert a protective role independently of its effect on the microbiota. In conclusion, IL-22 participates in T.gondii induced acute small intestinal inflammation independently of microbiota and Reg3γ.

Targeting Beta-Amyloid at the CSF: A New Therapeutic Strategy in Alzheimer's Disease.

Although immunotherapies against the amyloid-ß (Aß) peptide tried so date failed to prove sufficient clinical benefit, Aß still remains the main target in Alzheimer's disease (AD). This article aims to show the rationale of a new therapeutic strategy: clearing Aß from the CSF continuously (the "CSF-sink" therapeutic strategy). First, we describe the physiologic mechanisms of Aß clearance and the resulting AD pathology when these mechanisms are altered. Then, we review the experiences with peripheral Aß-immunotherapy and discuss the related hypothesis of the mechanism of action of "peripheral sink." We also present Aß-immunotherapies acting on the CNS directly. Finally, we introduce alternative methods of removing Aß including the "CSF-sink" therapeutic strategy. As soluble peptides are in constant equilibrium between the ISF and the CSF, altering the levels of Aß oligomers in the CSF would also alter the levels of such proteins in the brain parenchyma. We conclude that interventions based in a "CSF-sink" of Aß will probably produce a steady clearance of Aß in the ISF and therefore it may represent a new therapeutic strategy in AD.

Clearing Extracellular Alpha-Synuclein from Cerebrospinal Fluid: A New Therapeutic Strategy in Parkinson's Disease.

This concept article aims to show the rationale of targeting extracellular α-Synuclein (α-Syn) from cerebrospinal fluid (CSF) as a new strategy to remove this protein from the brain in Parkinson's disease (PD). Misfolding and intracellular aggregation of α-synuclein into Lewy bodies are thought to be crucial in the pathogenesis of PD. Recent research has shown that small amounts of monomeric and oligomeric α-synuclein are released from neuronal cells by exocytosis and that this extracellular alpha-synuclein contributes to neurodegeneration, progressive spreading of alpha-synuclein pathology, and neuroinflammation. In PD, extracellular oligomeric-α-synuclein moves in constant equilibrium between the interstitial fluid (ISF) and the CSF. Thus, we expect that continuous depletion of oligomeric-α-synuclein in the CSF will produce a steady clearance of the protein in the ISF, preventing transmission and deposition in the brain.

EFhd2/Swiprosin-1 is a common genetic determinator for sensation-seeking/low anxiety and alcohol addiction.

In many societies, the majority of adults regularly consume alcohol. However, only a small proportion develops alcohol addiction. Individuals at risk often show a high sensation-seeking/low-anxiety behavioural phenotype. Here we asked which role EF hand domain containing 2 (EFhd2; Swiprosin-1) plays in the control of alcohol addiction-associated behaviours. EFhd2 knockout (KO) mice drink more alcohol than controls and spontaneously escalate their consumption. This coincided with a sensation-seeking and low-anxiety phenotype. A reversal of the behavioural phenotype with ß-carboline, an anxiogenic inverse benzodiazepine receptor agonist, normalized alcohol preference in EFhd2 KO mice, demonstrating an EFhd2-driven relationship between personality traits and alcohol preference. These findings were confirmed in a human sample where we observed a positive association of the EFhd2 single-nucleotide polymorphism rs112146896 with lifetime drinking and a negative association with anxiety in healthy adolescents. The lack of EFhd2 reduced extracellular dopamine levels in the brain, but enhanced responses to alcohol. In confirmation, gene expression analysis revealed reduced tyrosine hydroxylase expression and the regulation of genes involved in cortex development, Eomes and Pax6, in EFhd2 KO cortices. These findings were corroborated in Xenopus tadpoles by EFhd2 knockdown. Magnetic resonance imaging (MRI) in mice showed that a lack of EFhd2 reduces cortical volume in adults. Moreover, human MRI confirmed the negative association between lifetime alcohol drinking and superior frontal gyrus volume. We propose that EFhd2 is a conserved resilience factor against alcohol consumption and its escalation, working through Pax6/Eomes. Reduced EFhd2 function induces high-risk personality traits of sensation-seeking/low anxiety associated with enhanced alcohol consumption, which may be related to cortex function.

Sacroiliac Pain: A Clinical Approach for the Neurosurgeon.

Pain originating from sacroiliac joint may also cause pain in the lumbar and gluteal region in 15% of the population. The clinical manifestation represents a public health problem due to the great implications on the quality of life and health-related costs. However, this is a diagnosis that is usually ignored in the general clinical practice; probably because of the unknown etiology, making harder to rule out the potential etiologies of this pathology, or maybe because the clinical criteria that support this pathology are unknown. By describing several diagnostic techniques, many authors have studied the prevalence of this pathology, finding more positive data than expected; coming to the conclusion that even though there is no diagnostic gold standard yet, an important amount of cases might be detected by properly applying several tests at the physical examination. Thus, it is necessary to have knowledge of the physiopathology and clinical presentation so that diagnosis can be made to those patients that manifest this problem. We present a clinical approach for the neurosurgeon.