Cystic fibrosis newborn screening in Switzerland - evaluation and scenarios for improvement after 11 years of follow-up.

BACKGROUND: Newborn bloodspot screening (NBS) for cystic fibrosis (CF) is important for early diagnosis and treatment. However, screening can lead to false-positive results leading to unnecessary follow-up tests and distress. This study evaluated the 11-year performance of the Swiss CF-NBS programme, estimated optimal cut-offs for immunoreactive trypsinogen (IRT), and examined how simulated algorithms would change performance. METHODS: The Swiss CF-NBS is based on an IRT-DNA algorithm with a second IRT (IRT-2) as safety net. We analysed data from 2011 to 2021, covering 959,006 IRT-1 analyses and 282 children with CF. We studied performance based on European Cystic Fibrosis Society (ECFS) standards including sensitivity, specificity, positive predictive value (PPV), false negative rate, and second heel-prick tests; identified optimal IRT cut-offs using receiver operating characteristics (ROC) curves; and calculated performance for simulated algorithms with different cut-offs for IRT-1, IRT-2, and safety net. RESULTS: The Swiss CF-NBS showed excellent sensitivity (96 %, 10 false negative cases) but moderate PPV (25 %). Optimal IRT-1 and IRT-2 cut-offs were identified at 2.7 (>99th percentile) and 5.9 (>99.8th percentile) z-scores, respectively. Analysis of simulated algorithms showed that removing the safety net from the current algorithm could increase PPV to 30 % and eliminate >200 second heel-prick tests per year, while keeping sensitivity at 95 %. CONCLUSION: The Swiss CF-NBS program performed well over 11 years but did not achieve the ECFS standards for PPV (≥30 %). Modifying or removing the safety net could improve PPV and reduce unnecessary follow-up tests while maintaining the ECFS standards for sensitivity.

Hair cortisol concentrations in bovine neonates born to healthy and ill cows.

INTRODUCTION: The goal of this study was to investigate the hair cortisol concentration (HCC) in healthy and ill cows and their newborn calves. A total of 40 cows and their 42 newborn calves were divided into two groups: group 1 consisted of 19 clinically healthy cows and their 20 newborn calves, and group 2 comprised 21 cows that had had a chronic illness in the third trimester of gestation and their 22 newborn calves. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) system was used to measure the HCC in hair samples that were collected from the cows and calves on the day the calves were born. In both groups, the mean HCCs of the calves was significantly higher than that of the cows (group 1, 31,0 vs. 0,6 pg/mg; group 2, 19,4 vs. 0,8 pg/mg; P.

INTRODUCTION: Le but de cette étude était d'étudier la concentration de cortisol dans les poils (HCC) chez des vaches saines et malades et chez leurs veaux nouveau-nés. Un total de 40 vaches et leurs 42 veaux nouveau-nés ont été divisés en deux groupes: le groupe 1 comprenait 19 vaches cliniquement saines et leurs 20 veaux nouveau-nés, et le groupe 2 comprenait 21 vaches ayant eu une maladie chronique au cours du troisième trimestre de gestation et leurs 22 veaux nouveau-nés. Un système de chromatographie liquide avec spectrométrie de masse en tandem (LC-MS/MS) a été utilisé pour mesurer le HCC dans des échantillons de poils prélevés sur les vaches et les veaux le jour de leur naissance. Dans les deux groupes, le HCC moyen des veaux était significativement plus élevé que celui des vaches (groupe 1, 31,0 pg/mg contre 0,6 pg/mg ; groupe 2, 19,4 pg/mg contre 0,8 pg/mg ; P.

Automated lung cancer assessment on 18F-PET/CT using Retina U-Net and anatomical region segmentation.

OBJECTIVES: To develop and test a Retina U-Net algorithm for the detection of primary lung tumors and associated metastases of all stages on FDG-PET/CT. METHODS: A data set consisting of 364 FDG-PET/CTs of patients with histologically confirmed lung cancer was used for algorithm development and internal testing. The data set comprised tumors of all stages. All lung tumors (T), lymphatic metastases (N), and distant metastases (M) were manually segmented as 3D volumes using whole-body PET/CT series. The data set was split into a training (n = 216), validation (n = 74), and internal test data set (n = 74). Detection performance for all lesion types at multiple classifier thresholds was evaluated and false-positive-findings-per-case (FP/c) calculated. Next, detected lesions were assigned to categories T, N, or M using an automated anatomical region segmentation. Furthermore, reasons for FPs were visually assessed and analyzed. Finally, performance was tested on 20 PET/CTs from another institution. RESULTS: Sensitivity for T lesions was 86.2% (95% CI: 77.2-92.7) at a FP/c of 2.0 on the internal test set. The anatomical correlate to most FPs was the physiological activity of bone marrow (16.8%). TNM categorization based on the anatomical region approach was correct in 94.3% of lesions. Performance on the external test set confirmed the good performance of the algorithm (overall detection rate = 88.8% (95% CI: 82.5-93.5%) and FP/c = 2.7). CONCLUSIONS: Retina U-Nets are a valuable tool for tumor detection tasks on PET/CT and can form the backbone of reading assistance tools in this field. FPs have anatomical correlates that can lead the way to further algorithm improvements. The code is publicly available. KEY POINTS: • Detection of malignant lesions in PET/CT with Retina U-Net is feasible. • All false-positive findings had anatomical correlates, physiological bone marrow activity being the most prevalent. • Retina U-Nets can build the backbone for tools assisting imaging professionals in lung tumor staging.

Hair cortisol concentrations in different breeds of cows: Comparison of hair from unshorn and previously shorn areas and from various regions of the body.

INTRODUCTION: The goals of this study were to investigate hair cortisol concentration (HCC) in seven different breeds of cows, to establish reference intervals for HCC in Brown Swiss cows and to compare cortisol concentrations of hair collected from four different areas of the body. Three groups of cows were used. Group 1 comprised 70 healthy cows representing four dairy breeds (Brown Swiss, Swiss Fleckvieh, Holstein Friesian, Water Buffalo) and three beef breeds (Raetian Grey, Limousin, Highland). Group 2 consisted of 60 healthy Brown Swiss cows in which two different hair samples were collected from the thoracic region to establish reference intervals; A samples consisted of hair that had grown for one month in a pre-clipped area, and B samples consisted of hair from a previously unshorn area. Group 3 comprised 21 healthy Brown Swiss cows, in which HCCs were measured in A and B samples from four different body regions (neck, shoulder, thorax, rump). Liquid chromatography tandem mass-spectrometry was used for cortisol measurement. In group 1, the highest HCCs were measured in Holstein Friesian cows at 1,75 pg/mg, which was significantly higher than those of the Brown Swiss, the Swiss Fleckvieh and the Water Buffalo cows. Hair cortisol concentration and daily milk yield of the 40 dairy cows were highly correlated (r = 0,57, P < 0,01). In group 2, the HCCs of 77 % of the A samples and 85 % of the B samp-les were below the laboratory's limit of quantification (LOQ) of 0,50 pg/mg and the results were expressed semiquantitatively as.

INTRODUCTION: Les objectifs de cette étude étaient d'étudier la concentration de cortisol dans les poils (hair cortisol concentration (HCC)) chez sept races de vaches différentes, d'établir des intervalles de référence pour le HCC chez les vaches de race Suisse Brune et de comparer les concentrations de cortisol dans les poils prélevés sur quatre zones différentes du corps. Trois groupes de vaches ont été utilisés. Le groupe 1 comprenait 70 vaches saines représentant quatre races laitières (Brown Swiss, Swiss Fleckvieh, Holstein Friesian, Buffle d'eau) et trois races à viande (Grise rhétique, Limousin, Highland). Le groupe 2 était composé de 60 vaches Brown Swiss en bonne santé, pour lesquelles deux échantillons de poils différents ont été prélevés dans la région thoracique afin d'établir des intervalles de référence ; les échantillons A étaient constitués de poils ayant poussé pendant un mois sur une zone précédemment tondue et les échantillons B étaient constitués de poils provenant d'une zone non tondue auparavant. Le groupe 3 comprenait 21 vaches suisses brunes en bonne santé, chez lesquelles les HCC ont été mesurés dans des échantillons A et B provenant de quatre régions corporelles différentes (cou, épaule, thorax, croupe). La chromatographie liquide en tandem avec spectrométrie de masse a été utilisée pour la mesure du cortisol. Dans le groupe 1, les HCC les plus élevés ont été mesurés chez les vaches Holstein Friesian à 1,75 pg/mg, ce qui était significativement plus élevé que ceux des vaches Brown Swiss, Swiss Fleckvieh et Buffle d'eau. La concentration de cortisol dans les poils et le rendement laitier quotidien des 40 vaches laitières étaient fortement corrélés (r = 0,57, P < 0,01). Dans le groupe 2, les HCC étaient inférieures à la limite de quantification (LOQ) de 0,50 pg/mg dans 77 % des échantillons A et 85 % des échantillons B et ils ont été indiquées de manière semi-quantitative comme < LOQ. Dans les échantillons restants, les HCC se situaient entre 0,50 et 1,20 pg/mg. Les valeurs des échantillons A et B n'étaient pas significativement différentes. Dans le groupe 3, les valeurs médianes des HCC des échantillons mesurables pour les 4 localisations se situaient entre 0,50 et 1,00 pg/mg de poils. Les HCC ne différaient pas significativement entre les différentes localisations corporelles ni entre les échantillons A et B. Les analyses permettent de supposer que les vaches Holstein-Friesian présentent des HCC significativement plus élevées que les vaches Brown Swiss, Swiss Fleckvieh et les bufflonnes d'eau et que cela est dû au moins en partie à leur production laitière élevée.

3D printing of resilient biogels for omnidirectional and exteroceptive soft actuators.

Soft robotics greatly benefits from nature as a source of inspiration, introducing innate means of safe interaction between robotic appliances and living organisms. In contrast, the materials involved are often nonbiodegradable or stem from nonrenewable resources, contributing to an ever-growing environmental footprint. Furthermore, conventional manufacturing methods, such as mold casting, are not suitable for replicating or imitating the complexity of nature's creations. Consequently, the inclusion of sustainability concepts alongside the development of new fabrication procedures is required. We report a customized 3D-printing process based on fused deposition modeling, printing a fully biodegradable gelatin-based hydrogel (biogel) ink into dimensionally stable, complex objects. This process enables fast and cost-effective prototyping of resilient, soft robotic applications from gels that stretch to six times their original length, as well as an accessible recycling procedure with zero waste. We present printed pneumatic actuators performing omnidirectional movement at fast response times (less than a second), featuring integrated 3D-printed stretchable waveguides, capable of both proprio- and exteroception. These soft devices are endowed with dynamic real-time control capable of automated search-and-wipe routines to detect and remove obstacles. They can be reprinted several times or disposed of hazard-free at the end of their lifetime, potentially unlocking a sustainable future for soft robotics.

[200 years of the animal hospital Zurich: A cross-section through the lectures of the exam year 1864]. / 200 Jahre Tierspital Zürich: Ein Querschnitt durch die Vorlesungen des Examenjahrgangs 1864.

INTRODUCTION: The current study analyzed eleven lecture transcripts from the Zurich Veterinary School of the years -1861-1864. The work presents the staff and organizational situation of the school at that time. Lectures concerned mostly clinical subjects, especially special pathology and therapy. The texts were transcribed, summarized and analyzed according to the criteria species, diagnosis and therapy. The drugs were listed. Therapy concepts follow the principles of humoral pathology, but transition to cellular pathology was imminent. The pathogens of infectious diseases are not identified yet, but are suspected to be called «contagions¼.

INTRODUCTION: On dispose de 11 manuscrits de cours des années ­1861­1864 à l'école vétérinaire de Zürich. On présente la situation de l'époque de l'école au point de vue du personnel et de l'organisation. Les cours concernent principalement les branches cliniques, en particulier la pathologie spéciale et la thérapie. Les manuscrits ont été transcrits, résumés et analysés en tenant compte des critères de l'espèce animale, du diagnostic et du traitement. On a établi une liste des médicaments. Les concepts thérapeutiques étaient basés sur les principes de la pathologie humorale mais la transition vers la pathologie cellulaire se dessine. Les agents infectieux n'étaient pas encore identifiés mais on les pressent avec le terme de «contagions¼.

Investigation of gamma secretase gene complex mutations in German population with Hidradenitis suppurativa designate a complex polygenic heritage.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory disease affecting apocrine gland-bearing skin in the axilla, groin and under the breasts. Mutations of the gamma secretase gene complex, which is essential in the activation of Notch signalling pathways, were shown in some families with HS and in a few sporadic cases. Although an imbalance in Notch signalling is implicated in the pathogenesis, the exact mechanism of HS development is yet unknown. OBJECTIVES: We aim to investigate the genetic basis of HS by determining the presence of mutations of gamma secretase gene complex in a cohort of HS patients and by searching for a disease-causing pathogenic variant in a multi-generational HS family using parametric linkage analysis. METHODS: Thirty-eight patients clinically diagnosed with HS were included in this study. All exons and exon-intron boundaries of the genes encoding gamma secretase complex consisting of six genes: APH1A, APH1B, PSENEN, NCSTN, PSEN1 and PSEN2 were sequenced by Sanger technique. Genetic mapping with parametric linkage analysis for the patients in the family was performed with eight affected and four healthy individuals. The logarithm of odds was calculated. RESULTS: In a sporadic patient with early-onset, severe lesions in axilla and groin, a novel single-nucleotide deletion causing frameshift in exon 1 of the NCSTN gene was identified ((NM_015331.3): c.38delG, p.(Gly13Glufs*15)). The LOD score of 1.5 was never exceeded in any region of the genome, pointing towards intricate multi-genic inheritance pattern within the affected family. CONCLUSIONS: The gamma secretase gene complex mutations were rare in our cohort (3.2%). Besides, our analysis indicates a possible complex multi-genic inheritance in a seemingly autosomal dominantly inherited large HS family. Genetics of both familial and sporadic HS may be complicated in most cases, and the role of other potential genes such as autoinflammatory and modifier genes as well as environmental factors may influence the pathogenesis.

Andrological findings in infertile men with two (biallelic) CFTR mutations: results of a multicentre study in Germany and Austria comprising 71 patients.

STUDY QUESTION: When should cystic fibrosis transmembrane conductance regulator (CFTR) mutation analysis be recommended in infertile men based on andrological findings? SUMMARY ANSWER: CFTR mutation analysis is recommended in all men with unexplained azoospermia in the presence of normal gonadotropin levels. WHAT IS KNOWN ALREADY: While 80-97% of men with congenital bilateral absence of the vas deferens (CBAVD) are thought to carry CFTR mutations, there is uncertainty about the spectrum of clinical and andrological abnormalities in infertile men with bilallelic CFTR mutations. This information is relevant for evidence-based recommendations to couples requesting assisted reproduction. STUDY DESIGN, SIZE, DURATION: We studied the andrological findings of patients with two CFTR mutations who were examined in one of the cooperating fertility centres in Germany and Austria. In the period of January till July 2019, the completed and anonymized data sheets of 78 adult male patients were returned to and analysed by the project leader at the Institute of Human Genetics in Innsbruck, Austria. PARTICIPANTS/MATERIALS, SETTING, METHODS: Minimum study entry criteria were the presence of two (biallelic) CFTR mutations and results of at least one semen analysis. Andrological assessments were undertaken by standardized data sheets and compared with normal reference values. Seventy-one patients were eligible for the study (n = 30, 42% from Germany, n = 26, 37% from Austria, n = 15, 21% other nations). MAIN RESULTS AND THE ROLE OF CHANCE: Gonadotropin levels (FSH, LH) were normal, 22% of patients had reduced testosterone values. Mean right testis volume was 23.38 ml (SD 8.77), mean left testis volume was 22.59 ml (SD 8.68) and thereby statistically increased compared to normal (P < 0.01). although the means remained in the reference range of 12-25 ml. Semen analysis revealed azoospermia in 70 of 71 (99%) patients and severe oligozoospermia <0.1 × 106/ml in one patient. Four semen parameters, i.e. ejaculate volume, pH, α-glucosidase and fructose values, were significantly reduced (P < 0.01). Only 18% of patients had a palpatory and sonographically diagnosed CBAVD, while in 31% the diagnosis of CBAVD was uncertain, in 12% patients, the vas deferens was present but hypoplastic, and in 39% the vas deferens was normally present bilaterally. Seminal vesicles were not detectable in 37% and only unilaterally present in 37% of patients. Apart from total testes volume, clinical findings were similar in patients with two confirmed pathogenic CFTR mutations (Group I) compared with patients who carried one pathogenic mutation and one CFTR variant of unknown significance (Group II). LIMITATIONS, REASONS FOR CAUTION: We could not formally confirm the in trans position of genetic variants in most patients as no family members were available for segregation studies. Nonetheless, considering that most mutations in our study have been previously described without other rare variants in cis, and in view of the compatible andrological phenotype, it is reasonable to assume that the biallelic genotypes are correct. WIDER IMPLICATIONS OF THE FINDINGS: Our study reveals that CFTR mutation analysis has a broader indication than just the absence of the vas deferens. We recommend to completely sequence the CFTR gene if there is a suspicion of obstructive azoospermia, and to extend this analysis to all patients with unexplained azoospermia in the presence of normal gonadotropin levels. STUDY FUNDING/COMPETING INTEREST(S): German Research Foundation Clinical Research Unit 'Male Germ Cells: from Genes to Function' (DFG CRU326, grants to F.T.). There are no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

A Comprehensive Multi-Analyte Method for Hair Analysis: Substance-Specific Quantification Ranges and Tool for Task-Oriented Data Evaluation.

The aim of the present study was to quantify a large number of analytes including opioids, stimulants, benzodiazepines, z-drugs, antidepressants and neuroleptics within a single sample workup followed by a single analytical measurement. Expected drug concentrations in hair are strongly substance dependent. Therefore, three different calibration ranges were implemented: 0.5 to 600 pg/mg (group 1), 10 to 12,000 pg/mg (group 2) and 50 to 60,000 pg/mg (group 3). In order to avoid saturation effects, different strategies were applied for selected transitions including the use of parent mass ions containing one or two 13C-isotopes and detuning of the declustering potential and/or collision energy. Drugs were extracted from pulverized hair by a two-step extraction protocol and measured by liquid chromatrography--tandem mass spectrometry (LC--MS-MS) using Scheduled MRM™ Algorithm Pro. In total, 275 MRM transitions including 43 deuterated standards were measured. The method has been fully validated according to international guidelines. A MultiQuant™ software based tool for task-oriented data evaluation was established, which allows extracting selected information from the measured data sets. The matrix effects and recoveries were within the allowed ranges for the majority of the analytes. The lower limits of quantification (LLOQs) were for ∼72% of the analytes in the low-pg/mg range (0.5-5 pg/mg) and for ∼24% of the analytes between 10 and 50 pg/mg. These LLOQs considered cut-offs by the Society of Hair Testing (SoHT), if recommended. The herein established multi-analyte approach meets the specific requirements of forensic hair testing and can be used for the rapid and robust measurement of a wide range of psychoactive substances. The analyte-specific wide concentration ranges open up a wide field of applications.

Psychiatric symptoms and expression of glucocorticoid receptor gene in cocaine users: A longitudinal study.

BACKGROUND: Chronic cocaine users (CU) display reduced peripheral expression of the glucocorticoid receptor gene (NR3C1), which is potentially involved in stress-related psychiatric symptoms frequently occurring in CU. However, it is unknown whether psychiatric symptoms and lower NR3C1 expression are related to each other and whether reduction of drug consumption reverse them. METHOD: At baseline, NR3C1 mRNA expression was measured in 68 recreational CU, 30 dependent CU, and 68 stimulant-naïve controls. Additionally, the Revised Symptom Checklist (SCL-90R) and the Barratt Impulsiveness Scale (BIS) were assessed. At a one-year follow-up, the association between change in NR3C1 expression and psychiatric symptoms was examined in 48 stimulant-naïve controls, 19 CU who increased and 19 CU who decreased their consumption. At both test sessions, cocaine concentrations in hair samples were determined. Mixed-effects models were used to investigate how changes in drug use intensity affect severity of psychiatric symptoms and NR3C1 expression over time. RESULTS: At baseline, recreational and dependent CU displayed elevated impulsivity and considerable symptom burden across most of the SCL-90R subscales. Time-group interaction effects were found for several impulsivity scores, SCL-90R Global Severity Index, Paranoid Thoughts, and Depression subscales as well as for NR3C1 expression. Pairwise comparisons showed that decreasing CU specifically improved in these SCL-90R subscales, while their NR3C1 expression was adapted. Finally, changes in NR3C1 expression were negatively correlated with changes in impulsivity but not SCL-90R scores. CONCLUSION: Our findings suggest that NR3C1 expression changes and some psychiatric symptoms are reversible upon reduction of cocaine intake, thus favouring abstinence-oriented treatment approaches.

Sensitivity to gains during risky decision-making differentiates chronic cocaine users from stimulant-naïve controls.

BACKGROUND: Chronic cocaine use has been consistently associated with decision-making impairments that contribute to the development and maintenance of drug-taking. However, the underlying cognitive processes of risk-seeking behaviours observed in chronic cocaine users (CU) have so far remained unclear. Here we therefore tested whether CU differ from stimulant-naïve controls in their sensitivity to gain, loss, and probability of loss information when making decisions under risk. METHOD: A sample of 96 participants (56 CU and 40 controls) performed the no-feedback version of the Columbia Card Task, designed to assess risk-taking in relation to gain, loss, and probability of loss information. Additionally, cognitive performance and impulsivity were determined. Current and recent substance use was objectively assessed by toxicological urine and hair analysis. RESULTS: Compared to controls, CU showed increased risk-seeking in unfavourable decision scenarios in which the loss probability was high and the returns were low, and a tendency for increased risk aversion in more favourable decision scenarios. In comparison to controls, CU were less sensitive to gain, but similarly sensitive to loss and probability of loss information. Further analysis revealed that individual differences in sensitivity to loss and probability of loss information were related to cognitive performance and impulsivity. CONCLUSION: Reduced sensitivity to gains in people with CU may contribute to their propensity for making risky decisions. While these alterations in gain sensitivity might directly relate to cocaine use per se, the individual psychopathological profile of CU might moderate sensitivity to loss information.

Hair cortisol concentration in clinically healthy slaughter calves with and -without chronic bronchopneumonic -lesions.

INTRODUCTION: The hypothesis of this study was that healthy calves undergo less stress and thus have lower hair cortisol concentrations than calves with chronic bronchopneumonic lesions. Fifty healthy calves (group 1) and 50 calves with chronic bronchopneumonic lesions (group 2) were used immediately after slaughter, at which time hair samples and both adrenal glands were collected. The hair samples and the left adrenal gland were used for cortisol measurement and the right adrenal gland was used for histological and morphometrical examinations. The median hair cortisol concentrations of calves in groups 1 and 2 were 1.6 and 1.9 pg/mg hair, respectively, and did not differ significantly. The same was true for the mean cortisol concentration of the adrenal gland (1.1 and 1.4 µg/g tissue) and for the adrenal cortisol content (3.7 and 4.6 µg). The weights of the cortex (3.3, mean, and 3.5 g, median) and medulla (1.7 and 1.8 g, both median) did not differ significantly between the groups. This study did not detect differences in hair and adrenal cortisol concentrations between clinically healthy slaughter calves with and without chronic bronchopneumonic lesions. In further studies, calves with clinical signs should be taken into account.

INTRODUCTION: L'hypothèse de cette étude était que les veaux en bonne santé sont soumis à moins de stress et ont donc des concentrations de cortisol dans les poils plus faibles que les veaux présentant des lésions broncho-pneumoniques chroniques. Cinquante veaux sains (groupe 1) et 50 veaux présentant des lésions broncho-pneumoniques chroniques (groupe 2) ont été utilisés immédiatement après l'abattage, moment auquel des échantillons de poils et les deux glandes surrénales ont été prélevés. Les échantillons de poil et la glande surrénale gauche ont été utilisés pour la mesure du cortisol et la glande surrénale droite a été utilisée pour des examens histologiques et morphométriques. Les concentrations médianes de cortisol dans les poils des veaux des groupes 1 et 2 étaient respectivement de 1,6 et 1,9 pg/mg de poil et ne différaient pas significativement. Il en a été de même pour la concentration moyenne en cortisol de la glande surrénale (1,1 et 1,4 µg/g de tissu) et pour la teneur en cortisol surrénalien (3,7 et 4,6 µg). Les poids du cortex (3,3, moyenne et 3,5 g, médiane) et de la médulla (1,7 et 1,8 g, médiane) ne différaient pas significativement entre les groupes. Cette étude n'a pas mis en évidence de différences dans les concentrations de cortisol dans les poils et les surrénales entre les veaux abattus cliniquement en bonne santé avec ou sans lésions broncho-pneumoniques chroniques. Dans des études ultérieures, les veaux présentant des signes cliniques doivent être pris en compte.

Nocturnal Gamma-Hydroxybutyrate Reduces Cortisol-Awakening Response and Morning Kynurenine Pathway Metabolites in Healthy Volunteers.

BACKGROUND: Gamma-hydroxybutyrate (GHB; or sodium oxybate) is an endogenous GHB-/gamma-aminobutyric acid B receptor agonist. It is approved for application in narcolepsy and has been proposed for the potential treatment of Alzheimer's disease, Parkinson's disease, fibromyalgia, and depression, all of which involve neuro-immunological processes. Tryptophan catabolites (TRYCATs), the cortisol-awakening response (CAR), and brain-derived neurotrophic factor (BDNF) have been suggested as peripheral biomarkers of neuropsychiatric disorders. GHB has been shown to induce a delayed reduction of T helper and natural killer cell counts and alter basal cortisol levels, but GHB's effects on TRYCATs, CAR, and BDNF are unknown. METHODS: Therefore, TRYCAT and BDNF serum levels, as well as CAR and the affective state (Positive and Negative Affect Schedule [PANAS]) were measured in the morning after a single nocturnal dose of GHB (50 mg/kg body weight) in 20 healthy male volunteers in a placebo-controlled, balanced, randomized, double-blind, cross-over design. RESULTS: In the morning after nocturnal GHB administration, the TRYCATs indolelactic acid, kynurenine, kynurenic acid, 3-hydroxykynurenine, and quinolinic acid; the 3-hydroxykynurenine to kynurenic acid ratio; and the CAR were significantly reduced (P < 0.05-0.001, Benjamini-Hochberg corrected). The quinolinic acid to kynurenic acid ratio was reduced by trend. Serotonin, tryptophan, and BDNF levels, as well as PANAS scores in the morning, remained unchanged after a nocturnal GHB challenge. CONCLUSIONS: GHB has post-acute effects on peripheral biomarkers of neuropsychiatric disorders, which might be a model to explain some of its therapeutic effects in disorders involving neuro-immunological pathologies. This study was registered at ClinicalTrials.gov as NCT02342366.

Spatial and temporal variations in fish assemblage: testing the zonation concept in small reservoirs / Variações espaciais e temporais na assembleia de peixes: testando o conceito de zonação em pequenos reservatórios

Abstract Large reservoirs usually present spatial gradients in fish assemblage, distinguishing three strata (littoral, pelagic, and bathypelagic) along the vertical and horizontal axes, and three zones (fluvial, transitional, and lacustrine) along the longitudinal axis. The main objective of this study was to assess if small reservoirs also present the spatial gradients in fish assemblage attributes and structure as already observed in large reservoirs. Fish surveys were conducted quarterly, from 2003 to 2008, in the Mourão Reservoir (Mourão River, Paraná, Brazil), using gillnets with different mesh sizes, arranged in all strata of all three zones. Community attributes (species richness and evenness) were calculated for each sample, and differences were tested using three-way ANOVA (factors: zone, strata, year). Community composition was summarized using Correspondence Analysis (CA) and differences were tested with three-way ANOVA for each axis, controlling the same three factors. Because of the high variability in reservoir water level through time, all analyses were made considering temporal variations. Species richness presented a decreasing trend from fluvial to lacustrine zones, and higher values in littoral strata, possibly because upper reaches and littoral regions provide better conditions for fish to feed and to reproduce. Evenness was considerably low, presenting high variability, and no evident pattern. The expected longitudinal gradient was not found in this study indicating longitudinal similarity, contrary to observed in large reservoirs. Vertical and horizontal gradients were observed in all sampling stations, indicating that abiotic and biotic conditions are influencing fish distributions within the reservoir.

Resumo Grandes reservatórios, em geral, apresentam gradientes espaciais da assembleia de peixes, distinguindo três estratos (litoral, pelágico e batipelágico) ao longo dos eixos vertical e horizontal, e três zonas (fluvial, transição e lacustre) ao longo do eixo longitudinal. O principal objetivo deste estudo foi avaliar se pequenos reservatórios também apresentam tais gradientes espaciais, nos atributos e na estrutura da assembleia de peixes, como já observado em grandes reservatórios. As coletas dos peixes foram realizadas trimestralmente, de 2003 a 2008, no reservatório de Mourão (Rio Mourão, Paraná, Brasil), com redes de espera com diferentes tamanhos de malha, dispostas em todos os estratos de todas as três zonas. Atributos da assembleia (riqueza de espécies e equitabilidade) foram calculados para cada amostra, e as diferenças foram testadas utilizando ANOVA tri-fatorial (fatores: zona, estratos, anos). A estrutura da assembleia foi sumarizada usando uma Análise de Correspondência (CA) e as diferenças foram testadas com ANOVA tri-fatorial para cada eixo, controlando os mesmos três fatores. Devido à alta variabilidade no nível da água do reservatório ao longo do tempo, todas as análises foram feitas considerando as variações temporais. A riqueza de espécies apresentou tendência decrescente, da zona fluvial até a lacustre, com valores maiores no estrato litoral, possivelmente porque locais à montante e regiões litorâneas proporcionam melhores condições de alimentação e reprodução para os peixes. A equitabilidade foi consideravelmente baixa, apresentando alta variabilidade e nenhum padrão evidente. O gradiente longitudinal esperado não foi encontrado neste estudo, indicando similaridade longitudinal, ao contrário do observado em grandes reservatórios. Gradientes verticais e horizontais foram observadas em todas as áreas amostradas, sugerindo que as condições bióticas e abióticas estão influenciando a distribuição dos peixes ao longo do reservatório.

Effect of ionic strength and seawater cations on hagfish slime formation.

The defensive slime of hagfish consists of a polyanionic mucin hydrogel that synergistically interacts with a fiber network forming a coherent and elastic hydrogel in high ionic strength seawater. In seawater, the slime deploys in less than a second entrapping large quantities of water by a well-timed thread skein unravelling and mucous gel swelling. This rapid and vast hydrogel formation is intriguing, as high ionic strength conditions generally counteract the swelling speed and ratio of polyelectrolyte hydrogels. In this work we investigate the effect of ionic strength and seawater cations on slime formation dynamics and functionality. In the absence of ionic strength skeins swell radially and unravel uncontrolled, probably causing tangling and creating a confined thread network that entraps limited water. At high ionic strength skeins unravel, but create a collapsed and dense fiber network. High ionic strength conditions therefore seem crucial for controlled skein unraveling, however not sufficient for water retention. Only the presence of naturally occurring Ca2+ or Mg2+-ions allowed for an expanded network and full water retention probably due to Ca2+-mediated vesicle rupture and cross-linking of the mucin. Our study demonstrates that hagfish slime deployment is a well-timed, ionic-strength, and divalent-cation dependent dynamic hydrogel formation process.

The determination of ethyl glucuronide in hair: Experiences from nine consecutive interlaboratory comparison rounds.

The increasing request for hair ethyl glucuronide (HEtG) in alcohol consumption monitoring according to cut-off levels set by the Society of Hair Testing (SoHT) has triggered a proficiency testing program based on interlaboratory comparisons (ILC). Here, the outcome of nine consecutive ILC rounds organised by the SoHT on the determination of HEtG between 2011 and 2017 is summarised regarding interlaboratory reproducibility and the influence of procedural variants. Test samples prepared from cut hair (1mm) with authentic (in-vivo incorporated) and soaked (in-vitro incorporated) HEtG concentrations up to 80pg/mg were provided for 27-35 participating laboratories. Laboratory results were evaluated according to ISO 5725-5 and provided robust averages and relative reproducibility standard deviations typically between 20 and 35% in reasonable accordance with the prediction of the Horwitz model. Evaluation of results regarding the analytical techniques revealed no significant differences between gas and liquid chromatographic methods In contrast, a detailed evaluation of different sample preparations revealed significantly higher average values in case when pulverised hair is tested compared to cut hair. This observation was reinforced over the different ILC rounds and can be attributed to the increased acceptance and routine of hair pulverisation among laboratories. Further, the reproducibility standard deviations among laboratories performing pulverisation were on average in very good agreement with the prediction of the Horwitz model. Use of sonication showed no effect on the HEtG extraction yield.

Endogenous cortisol in keratinized matrices: Systematic determination of baseline cortisol levels in hair and the influence of sex, age and hair color.

The measurement of hair cortisol is increasingly used to measure long-term cumulative cortisol levels and investigate its role as an important stress mediator. In this study a comparative statistical analysis of five independent studies (all analyzed in our laboratory) was performed to investigate baseline ranges of cortisol values in hair and evaluate potential influences of sex, age and hair color. Cortisol concentrations in hair of 554 subjects were measured and a comparative statistical analysis was performed. The analysis showed that cortisol levels significantly differ depending on age. The toddler group (7 months (0.6 years) to 3 years) showed significantly higher values (median 10pg/mg, p-value<0.0001, d=0.78) than the adolescent group. The adolescent groups showed significantly lower (p-value<0.0001, d=0.58 and p<0.0001, d=0.13) values (median 2.4pg/mg and 2.8pg/mg) than the adult group (median 5.8pg/mg). Furthermore, in the adult group men showed significantly higher cortisol values than women (p-value<0.05, d=0.17). This effect could not be seen in the adolescent group. Black hair showed higher cortisol concentrations than blond hair (p-value<0.0001, d=1.3). In addition, two rounds of interlaboratory comparisons for hair cortisol samples between four laboratories revealed very consistent results. Our results demonstrate that baseline cortisol levels are generally low in hair thus making a standardized and well-elaborated analytical method indispensable for accurate determination. Age-dependent normative baseline cortisol levels (toddlers, adolescents and adults) are highly recommended based on the comparative analysis comprising five independent studies.

Spatial and temporal variations in fish assemblage: testing the zonation concept in small reservoirs.

Large reservoirs usually present spatial gradients in fish assemblage, distinguishing three strata (littoral, pelagic, and bathypelagic) along the vertical and horizontal axes, and three zones (fluvial, transitional, and lacustrine) along the longitudinal axis. The main objective of this study was to assess if small reservoirs also present the spatial gradients in fish assemblage attributes and structure as already observed in large reservoirs. Fish surveys were conducted quarterly, from 2003 to 2008, in the Mourão Reservoir (Mourão River, Paraná, Brazil), using gillnets with different mesh sizes, arranged in all strata of all three zones. Community attributes (species richness and evenness) were calculated for each sample, and differences were tested using three-way ANOVA (factors: zone, strata, year). Community composition was summarized using Correspondence Analysis (CA) and differences were tested with three-way ANOVA for each axis, controlling the same three factors. Because of the high variability in reservoir water level through time, all analyses were made considering temporal variations. Species richness presented a decreasing trend from fluvial to lacustrine zones, and higher values in littoral strata, possibly because upper reaches and littoral regions provide better conditions for fish to feed and to reproduce. Evenness was considerably low, presenting high variability, and no evident pattern. The expected longitudinal gradient was not found in this study indicating longitudinal similarity, contrary to observed in large reservoirs. Vertical and horizontal gradients were observed in all sampling stations, indicating that abiotic and biotic conditions are influencing fish distributions within the reservoir.