Metabolic disorders exacerbate the formation of glial scar after stroke.

Metabolic disorders are risk factors for stroke exacerbating subsequent complications. Rapidly after brain injury, a glial scar forms, preventing excessive inflammation and limiting axonal regeneration. Despite the growing interest in wound healing following brain injury, the formation of a glial scar in the context of metabolic disorders is poorly documented. In this study, we used db/db mice to investigate the impact of metabolic perturbations on brain repair mechanisms, with a focus on glial scarring. First, we confirmed the development of obesity, poor glucose regulation, hyperglycaemia and liver steatosis in these mice. Then, we observed that 3 days after a 30-min middle cerebral artery occlusion (MCAO), db/db mice had larger infarct area compared with their control counterparts. We next investigated reactive gliosis and glial scar formation in db/+ and db/db mice. We demonstrated that astrogliosis and microgliosis were exacerbated 3 days after stroke in db/db mice. Furthermore, we also showed that the synthesis of extracellular matrix (ECM) proteins (i.e., chondroitin sulphate proteoglycan, collagen IV and tenascin C) was increased in db/db mice. Consequently, we demonstrated for the first time that metabolic disorders impair reactive gliosis post-stroke and increase ECM deposition. Given that the damage size is known to influence glial scar, this study now raises the question of the direct impact of hyperglycaemia/obesity on reactive gliosis and glia scar. It paves the way to promote the development of new therapies targeting glial scar formation to improve functional recovery after stroke in the context of metabolic disorders.

Selection and use of reference panels: a case study highlighting current gaps in the materials available for foot and mouth disease.

The World Organisation for Animal Health (OIE) Manual of Diagnostic Tests and Vaccines for Terrestrial Animals describes a diverse array of assays that can be used to detect, characterise and monitor the presence of infectious agents of farmed livestock. These methods have been developed in different laboratories, at different times, and often include tests or kits provided by the commercial sector. Reference panels are essential tools that can be used during assay development and in validation exercises to compare the performance of these varied (and sometimes competing) diagnostic technologies. World Organisation for Animal Health Reference Laboratories already provide approved international standard reagents to help calibrate diagnostic tests for a range of diseases, but there remain important gaps in their availability for comparative purposes and the calibration of test results across different laboratories. Using foot and mouth disease (FMD) as an example, this review highlights four specific areas where new reference reagents are required. These are to: reduce bias in estimates of the diagnostic sensitivity and inter-serotypic specificity of tests used to detect diverse strains of FMD virus (FMDV), provide bio-safe positive controls for new point-of-care test formats that can be deployed outside high containment, harmonise FMDV antigens for post-vaccination serology, and address inter-laboratory differences in serological assays used to measure virus-specific FMD antibody responses. Since there are often limited resources to prepare and distribute these materials, sustainable progress in this arena will only be achievable if there is consensus and coordination of these activities among OIE Reference Laboratories.

Le Manuel des tests de diagnostic et des vaccins pour les animaux terrestres de l'Organisation mondiale de la santé animale (OIE) décrit une vaste panoplie d'essais utilisables pour la détection, la caractérisation et la surveillance des agents pathogènes affectant les animaux d'élevage. Ces méthodes ont été mises au point par des laboratoires différents à diverses périodes et intègrent souvent des tests ou des kits fournis par le secteur privé. Les panels de référence sont des outils essentiels aussi bien lors de la conception d'un essai que lors d'exercices de validation, leur but étant alors de comparer les performances de technologies diagnostiques variées (et parfois concurrentes). Les Laboratoires de référence de l'OIE fournissent des réactifs de référence internationaux validés afin d'aider à calibrer les tests de diagnostic pour un certain nombre de maladies animales ; toutefois, on constate que nombre de ces réactifs ne sont pas disponibles pour la comparaison et le calibrage interlaboratoires des résultats de tests. À partir de l'exemple de la fièvre aphteuse, les auteurs soulignent quatre domaines spécifiques pour lesquels il conviendrait de disposer de nouveaux réactifs de référence. Il s'agit des réactifs nécessaires pour : (1) réduire les biais dans l'estimation de la sensibilité diagnostique et de la spécificité pour différents sérotypes des tests utilisés pour détecter diverses souches du virus de la fièvre aphteuse ; (2) fournir des contrôles positifs sûrs au plan biologique pour les nouveaux formats de tests utilisables sur le lieu d'intervention et non plus dans des laboratoires de confinement à haute sécurité ; (3) harmoniser les antigènes du virus de la fièvre aphteuse pour la sérologie post-vaccinale ; (4) résoudre le problème des différences obtenues entre laboratoires lors d'essais sérologiques visant à mesurer la réponse en anticorps spécifiques du virus de la fièvre aphteuse. Compte tenu des ressources souvent limitées consacrées à la préparation et à la distribution de ces réactifs, des progrès durables ne seront obtenus que s'il existe un consensus en la matière et une coordination de ces activités parmi les Laboratoires de référence de l'OIE.

En el Manual de pruebas de diagnóstico y vacunas para los animales terrestres de la Organización Mundial de Sanidad Animal (OIE) se describe todo un conjunto de ensayos que se pueden emplear para detectar y caracterizar agentes infecciosos del ganado doméstico y hacer así controles sistemáticos de su eventual presencia. Estos métodos, concebidos en distintos laboratorios en distintos momentos, suelen acompañarse de pruebas o estuches analíticos que proporcionan empresas privadas. Los paneles de referencia son una herramienta esencial, que se puede emplear durante la concepción de ensayos y en los procesos de validación para comparar el funcionamiento de estas diferentes técnicas de diagnóstico, que a veces compiten unas con otras. Los laboratorios de referencia de la OIE ya facilitan reactivos de referencia internacional aprobados que ayudan a calibrar las pruebas de diagnóstico de una serie de enfermedades, pero todavía hay importantes carencias por lo que respecta a la posibilidad de procurárselos con fines de comparación y a la calibración de los resultados que obtienen diferentes laboratorios. Sirviéndose del ejemplo de la fiebre aftosa, los autores destacan cuatro aspectos específicos para los que hacen falta nuevos reactivos de referencia. Se trata de los siguientes: reducir el sesgo a la hora de calcular la sensibilidad de diagnóstico y la especificidad interserotípica de las pruebas empleadas para detectar diversas cepas del virus de la fiebre aftosa; proporcionar controles positivos que ofrezcan seguridad biológica para nuevos modalidades de ensayo utilizables en el lugar de consulta, esto es, en condiciones que no sean de alta contención; armonizar los antígenos víricos para la práctica de análisis serológicos tras la vacunación; y solventar las diferencias entre laboratorios por lo que respecta a los ensayos serológicos empleados para medir la respuesta de anticuerpos específicos contra el virus de la fiebre aftosa. Dado que suele haber escasos recursos para preparar y distribuir este tipo de material, solo será posible avanzar duraderamente en la materia si los laboratorios de referencia de la OIE consensúan y coordinan estas actividades.

Food toxins and the Caribbean Parkinson plus types.

In the 90's, clinico pathological studies have considerably improved the diagnosis of specific and rare neurodegenerative diseases. After a training in Parkinsons' disease in Paris, the author moved to French West Indies (Guadeloupe) and observed a high incidence of atypical parkinsonism with dementia, unresponsive to levodopa. Similar features were observed in Martinique. An environmental origin has been suspected with the exposure to toxins of annonaceae leaves and seeds. The candidate toxins are acetogenins acting as mitochondrial poison. This was demonstrated in neuronal cell cultures, and in animals. However, the agency for food security did not conclude that Annonaceae should not be used for herbal (medicinal) tea, even if the population is now aware about the possible risk of parkinsonism after exposure to annonaceae acetogenins.

Adiponectin, leptin and insulin in breast milk: associations with maternal characteristics and infant body composition in the first year of life.

BACKGROUND/OBJECTIVES: Breastfeeding may protect against excessive weight gain during infancy. However, the breast milk components responsible for this effect are unknown. We examined the variation of three breast milk hormones (adiponectin, leptin and insulin) according to maternal characteristics and determined their association with infant body composition. SUBJECTS/METHODS: We studied a representative subset of 430 breastfed infants in the CHILD birth cohort. Breast milk was collected at 4 months postpartum and hormone concentrations were measured using the MesoScale Discovery System. Weight-for-length (WFL) and body mass index (BMI) z-scores were calculated according to the World Health Organization reference standard from infant anthropometrics measured at 4 months and 1 year. Maternal BMI and demographics were self-reported. RESULTS: Breast milk hormone concentrations varied widely between mothers. The geometric mean (range) was 19.4 (3.7-74.4) ngml-1 for adiponectin; 361 (31-3968) pgml-1 for leptin; and 589 (53-5557) pgml-1 for insulin. Maternal BMI was positively correlated with breast milk insulin (r=+0.40, P<0.0001) and leptin (r=+0.71, P<0.0001), but not adiponectin (r=-0.02, P=0.68). Breast milk hormone concentrations were also associated with maternal ethnicity, parity and breastfeeding exclusivity at sample collection. Independent of these factors and maternal diabetes, smoking and breastfeeding duration, higher breast milk leptin was associated with lower infant WFL z-score at 4 months (ß -0.67, 95% confidence interval (CI): -1.17, -0.17 for highest vs lowest quintile) and 1 year (ß -0.58, 95% CI: -1.02, -0.14). Insulin showed a U-shaped association, with intermediate concentrations predicting the lowest infant WFL z-score at 4 months (ß -0.51, 95% CI: -0.87, -0.15 for third vs lowest quintile) and 1 year (ß -0.35, 95% CI: -0.66, -0.04). Similar results were seen with infant BMI. Breast milk adiponectin was not significantly associated with infant body composition. CONCLUSIONS: Breast milk hormone concentrations were associated with several fixed and modifiable maternal characteristics. Higher concentrations of leptin and intermediate concentrations of insulin were associated with lower infant WFL in the first year of life.

Patterns of allergic sensitization and atopic dermatitis from 1 to 3 years: Effects on allergic diseases.

BACKGROUND: While allergic sensitization and atopic dermatitis (AD) are known to increase the risk for allergic diseases, the impact of different temporal and clinical patterns of sensitization and AD is less well defined. OBJECTIVE: We investigated patterns of sensitization and AD from early infancy to age 3, and the differential risk of developing allergic diseases within each pattern in a general cohort. METHODS: Children (n = 2629) from the Canadian Healthy Infant Longitudinal Development (CHILD) Study underwent skin prick tests and were assessed clinically for AD at ages 1 and 3 years. We applied an unsupervised latent class analysis (LCA) to the following 5 factors at these ages: AD, food sensitization, inhalant sensitization, poly-sensitization to foods and poly-sensitization to inhalants. The risks for developing asthma, allergic rhinitis and food allergy at 3 years were evaluated for each identified group. RESULTS: Five distinct classes were revealed by LCA: healthy (81.8%), atopic dermatitis (7.6%), inhalant sensitization (3.5%), transient sensitization (4.1%) and persistent sensitization (3.2%). Using healthy children as the baseline, children in the "atopic dermatitis" group had the next lowest risk for all allergic outcomes at 3 years; those in the "inhalant sensitization" group had the highest risk for allergic rhinitis; children in the "transient sensitization" group were at an increased risk for food allergy; while children in the "persistent sensitization" group had the highest risk for all allergic diseases. CONCLUSION AND CLINICAL RELEVANCE: There is substantial heterogeneity among allergen-sensitized children. Researchers and clinicians need to be aware of the non-specificity associated with labelling children simply as "atopic" and "non-atopic" without considering the timing of their atopic history, type of sensitization and AD status. Children with AD who were poly-sensitized to foods at an early age appear to be at greatest risk of developing other allergic diseases.

Short communication: Relationships among plasma and milk vitamin B12, plasma free fatty acids, and blood ß-hydroxybutyrate concentrations in early lactation dairy cows.

This study was undertaken to evaluate the relationship between plasma and milk concentrations of vitamin B12 as well as the relationship between plasma or milk concentrations of vitamin B12 and plasma concentration of free fatty acids (FFA) or blood concentration of ß-hydroxybutyrate (BHB) of early lactating Ayrshire (AY) and Holstein (HO) cows. A total of 44 dairy herds (7 AY and 37 HO herds) and 62 AY (21 in first, 19 in second, and 22 in third and more lactations) and 228 HO (51 in first, 74 in second, and 103 in third and more lactation) cows between 3 and 40 d in milk were involved in the study. Hand-stripped milk samples and blood samples were taken 6 h after the morning milking. Milk and plasma samples were analyzed for vitamin B12 concentration and plasma samples were analyzed for FFA concentration. A handheld device was used for blood BHB concentration determination. Thresholds for elevated plasma FFA concentration and hyperketonemia were set at ≥0.70 and ≥1.2 mmol/L, respectively. Vitamin B12 concentration in milk of AY primiparous cows [2,557 (1,995-3,276) pg/mL] was lower than in milk from HO primiparous cows [3,876 (3,356-4,478) pg/mL], whereas no difference was observed among other parities and breeds. Regardless of breeds, plasma concentration of vitamin B12 of first and second parities was lower than plasma concentration of third and more lactation cows. Milk vitamin B12 concentration was positively correlated with plasma vitamin B12 concentration, but the relationship was stronger for AY (ρ averaging 0.63) than for HO cows (ρ averaging 0.36). For AY and HO breeds, a significant relationship between milk or plasma vitamin B12 concentrations and plasma FFA concentration (ρ between 0.29 and 0.59) was observed. Moreover, cows with elevated plasma FFA concentration had greater milk and plasma vitamin B12 concentrations than cows with normal plasma FFA concentration. No relationship between vitamin B12 concentration in milk or plasma and blood BHB concentration and hyperketonemia was noted. In summary, milk is not well correlated with plasma vitamin B12 concentration for HO. It could be hypothesized that elevated plasma concentration of FFA could have a negative effect on the use of vitamin B12 by cow cells, which increases the concentration of the vitamin in plasma and its secretion in milk.

Effect of feeding system and grain source on lactation characteristics and milk components in dairy cattle.

The objective of this study was to examine the effect of feeding systems [component and total mixed rations (TMR)] and dietary grain sources (barley, commercial concentrate, corn grain, and high-moisture corn) on lactation characteristics and milk composition. A total of 852,242 test-day records, information on animal characteristics, feed composition, and feeding systems from 104,129 Holstein cows in 4,319 herds covering a period of 5 yr were obtained from Quebec's Dairy Herd Improvement Association (Valacta). We performed descriptive statistics and graphical representations of the data for each type of feeding system and grain source by parity (1 to 3). The milk records were binned in 15-d in milk blocks. Mixed models using a combination of forward and backward stepwise selections were developed to predict milk and milk component yields. The TMR-fed cows had greater yield of milk, fat, protein, and lactose and lower milk urea N (MUN) concentration than component-fed cows at all parities. Cows fed a TMR had higher peak milk yields and greater persistency after peak lactation compared with component-fed cows. In addition, greater yields of milk fat and protein from peak to mid-lactation were found in TMR- versus component-fed cows. In general, greater milk fat and protein yields as well as lower MUN concentration were observed in cows fed corn grain or high-moisture corn compared with barley or commercial concentrate, but parity influenced these relationships. The feeding system by day in milk blocks interaction was significant in models of milk and components yields for all parities, but only for second-lactation cows for MUN concentration. This means that effect of TMR and component feeding differs with stage of lactation. In conclusion, feeding TMR and corn-based diets are associated with greater yield of milk and milk components under commercial conditions.

In situ analysis of Bacillus licheniformis biofilms: amyloid-like polymers and eDNA are involved in the adherence and aggregation of the extracellular matrix.

AIMS: This study attempts to determine which of the exopolymeric substances are involved in the adherence and aggregation of a Bacillus licheniformis biofilm. METHODS AND RESULTS: The involvement of extracellular proteins and eDNA were particularly investigated using DNase and proteinase K treatment. The permeability of the biofilms increased fivefold after DNase I treatment. The quantification of the matrix components showed that, irrespective to the enzyme tested, eDNA and amyloid-like polymers were removed simultaneously. Size-exclusion chromatography analyses supported these observations and revealed the presence of associated nucleic acid and protein complexes in the biofilm lysates. These data suggest that some extracellular DNA and amyloid-like proteins were closely interlaced within the matrix. Finally, confocal laser scanning microscopy imaging gave supplementary clues about the 3D organization of the biofilms, confirming that eDNA and exoproteins were essentially layered under and around the bacterial cells, whereas the amyloid-like fractions were homogeneously distributed within the matrix. CONCLUSION: These results confirm that some DNA-amyloid complexes play a key role in the modulation of the mechanical resistance of B. licheniformis biofilms. SIGNIFICANCE AND IMPACT OF THE STUDY: The study highlights the need to consider the whole structure of biofilms and to target the interactions between matrix components. A better understanding of B. licheniformis biofilm physiology and the structural organization of the matrix will strengthen strategies of biofilm control.

Secret talk between adipose tissue and central nervous system via secreted factors-an emerging frontier in the neurodegenerative research.

First seen as a storage organ, the white adipose tissue (WAT) is now considered as an endocrine organ. WAT can produce an array of bioactive factors known as adipokines acting at physiological level and playing a vital role in energy metabolism as well as in immune response. The global effect of adipokines in metabolic activities is well established, but their impact on the physiology and the pathophysiology of the central nervous system (CNS) remains poorly defined. Adipokines are not only produced by the WAT but can also be expressed in the CNS where receptors for these factors are present. When produced in periphery and to affect the CNS, these factors may either cross the blood brain barrier (BBB) or modify the BBB physiology by acting on cells forming the BBB. Adipokines could regulate neuroinflammation and oxidative stress which are two major physiological processes involved in neurodegeneration and are associated with many chronic neurodegenerative diseases. In this review, we focus on four important adipokines (leptin, resistin, adiponectin, and TNFα) and one lipokine (lysophosphatidic acid-LPA) associated with autotaxin, its producing enzyme. Their potential effects on neurodegeneration and brain repair (neurogenesis) will be discussed. Understanding and regulating these adipokines could be an interesting lead to novel therapeutic strategy in order to counteract neurodegenerative disorders and/or promote brain repair.

Prevalence of elevated milk ß-hydroxybutyrate concentrations in Holstein cows measured by Fourier-transform infrared analysis in Dairy Herd Improvement milk samples and association with milk yield and components.

The purpose was to describe the prevalence and effect of elevated milk ß-hydroxybutyrate (BHB) as detected by routine Fourier-transform infrared analysis in Dairy Herd Improvement milk samples. Data collected over 4 yr included cow information as well as milk yield and composition from 498,310 samples from postparturient Holstein cows (5-35d in milk) from 4,242 herds. The following thresholds were used to classify cows based on their early lactation milk BHB concentration: <0.15mmol/L=negative; 0.15 to 0.19mmol/L=suspect; and ≥0.20mmol/L=positive. Overall prevalence (suspect + positive) was 22.6% and was higher for older cows (18.7, 19.5, and 27.6%, for cows in their first, second, and third or greater lactation, respectively). Distribution with regards to days in milk was different among parity groups, with first-lactation cows having highest prevalence (30%) in the first week after calving; cows in their second and third and greater parity had the highest prevalence in the second week after calving, at 25.8 and 34.6%, respectively. Season of calving affected the prevalence of elevated milk BHB, with cows calving in the fall and spring seasons showing higher prevalence. Distribution among herds was highly variable, as 45% of herds had a prevalence of 20% or less, 47% of herds had a prevalence between 21 and 40%, 6% of herds had a prevalence between 40 and 50%, and 2% of herds had a prevalence of 50% or above. Positive cows had lower milk yield, protein concentration and yield, and lower Transition Cow Index than negative cows, but also higher fat concentration and yield, as well as higher somatic cell count than negative cows. Suspect cows were generally intermediate. The present analysis highlights the opportunity for elevated milk BHB monitoring at the herd level through routine BHB testing in Dairy Herd Improvement milk samples.

The Canadian healthy infant longitudinal development birth cohort study: biological samples and biobanking.

BACKGROUND: It is hypothesised that complex interactions between genetic and environmental factors give rise to allergy and asthma in childhood. The Canadian Healthy Infant Longitudinal Development (CHILD) study was designed to explore these factors. METHODS: CHILD is a longitudinal, general population birth cohort study following infants from mid-pregnancy to age 5 years. Over this time period, biological samples, questionnaires, clinical measures and environmental data are collected. RESULTS: A total of 3624 families have been recruited, and many thousands of samples and questionnaires have been collected, annotated, and archived. This report outlines the rationale and methodology for collecting and storing diverse biological samples from parents and children in this study, and the mechanisms for their release for analyses. CONCLUSIONS: The CHILD sample and data repository is a tremendous current and future resource and will provide a wealth of information not only informing studies of asthma and allergy, but also potentially in many other aspects of health relevant for Canadian infants and children.

Weight, height, and relative-reliability indicators as a management tool for reducing age at first breeding and calving of dairy heifers.

In Québec first calving occurs on average at 27 mo, whereas the target is 23 to 24.5 mo to maximize herd profitability. The aim of this study was to quantify current and future heifer growth using individual heifer random regressions and to generate indicators (such as heifer weight and height at 15 and 24 mo, average daily gain before and after 15 mo, age at which optimal weight for breeding is attained, i.e., 55% of mature weight, and reliability of the 15- and 24-mo weight predictions) that could be used as a practical on-farm tool. Dairy heifer weight estimated by heart girth circumference and height measured at the withers (from 0 to 27 mo) were obtained from the Valacta database (DHI agency, Ste-Anne-de-Bellevue, QC, Canada) from 1995 to 2012. Indicators were calculated based on the current situation of Holstein (HO), Ayrshire (AY), Jersey (JE), and Brown Swiss (BS) heifer growth in Québec. Heifers with less than 2 records were excluded from the analysis. Mature weights were determined by weight at calving of cows from third or greater lactation for a given breed and were 710 kg for HO, 625 kg for AY, 470 kg for JE, and 670 kg for BS. Estimated weights at 15 and 24 mo were 425 and 627, 334 and 482, 297 and 429, and 379 and 560 kg for HO, AY, JE, and BS, respectively, which are heavy enough for breeding and calving, except for AY. Relative reliabilities of the 15- and 24-mo weight predictions were on average 89 and 60%, respectively, based on measurements up to 15 mo. For HO, AY, JE, and BS, wither heights at 15 and 24 mo were 134 and 143, 125 and 134, 122 and 131, and 130 and 140 cm, respectively. Age at optimal breeding weight was 13.6, 15.5, 12.6, and 14.5 mo for HO, AY, JE, and BS, respectively. These data suggest that it is realistic to expect a first calving at 24 mo for HO, JE, and BS. A growth delay was observed for AY; average daily gain was 655 and 538 g/d before and after 15 mo, respectively. The average daily gain before and after 15 mo was 848 and 747 g/d for HO, 603 and 486 g/d for JE, and 775 and 662 g/d for BS, respectively. These indicators could be calculated for an individual heifer and on a herd-level basis and used on farm as a management tool for reducing age at first breeding and at first calving.

An assessment tool to help producers improve cow comfort on their farms.

Effective management and an appropriate environment are essential for dairy cattle health and welfare. Codes of practice provide dairy producers with best practice guidance for the care and handling of their cattle. New Canadian recommendations have been established for the dairy industry. The objectives of this study were to develop an on-farm assessment tool that helps producers assess how well they are meeting their code of practice and that identifies management and environment modifications that could improve dairy cow comfort on their farms. The assessment tool addressed critical areas of dairy cow comfort, including accommodation and housing (stall design, space allowance, stall management, pen management, milking parlor, and transfer alleys), feed and water (body condition scoring, nutrition), and health and welfare (lameness, claw health, and hoof-trimming). Targets of good practices were identified from the requirements and recommendations of the code of practice. Each farm received a score for each target, ranging from 0 (target not reached) to 100 (target reached). One hundred tiestall and 110 freestall farms were surveyed in 3 provinces of Canada (Quebec, Ontario, and Alberta). The duration of the assessment, in 2 visits lasting, on average, 8 and 9h (range between freestall and tiestall farms) and 4 and 4.1h, was beyond the targeted 3 to 4h due mainly to the animal-based measures; strategies to reduce the duration of the assessment were discussed. Standard operating procedures were developed to ensure consistency in measuring and recording data. Periodical checks were conducted by trainers to ensure all 15 assessors remained above target agreement of weighted kappa ≥0.6. Average scores for all critical areas ranged from 25 to 89% for freestall farms and from 48 to 95% for tiestall farms. These scores need to be considered with caution when comparing farms because scores could not always be calculated the same way between housing systems. An evaluation report was provided and discussed with each producer, identifying strengths and areas for improvement that could benefit dairy cow comfort on their farms. The producers were convinced of the effectiveness of our tool for assessing cow comfort (freestall: 86%; tiestall: 95%) and in assisting them to make decisions for improvements (freestall: 83%; tiestall: 93%). Our cow comfort assessment tool served as background material for the Dairy Farmers of Canada animal care assessment program.

Iron deposits in post-mortem brains of patients with neurodegenerative and cerebrovascular diseases: a semi-quantitative 7.0 T magnetic resonance imaging study.

BACKGROUND AND PURPOSE: Accumulation of iron (Fe) is often detected in brains of people suffering from neurodegenerative diseases. However, no studies have compared the Fe load between these disease entities. The present study investigates by T2*-weighted gradient-echo 7.0 T magnetic resonance imaging (MRI) the Fe content in post-mortem brains with different neurodegenerative and cerebrovascular diseases. METHODS: One hundred and fifty-two post-mortem brains, composed of 46 with Alzheimer's disease (AD), 37 with frontotemporal lobar degeneration (FTLD), 11 with amyotrophic lateral sclerosis, 13 with Lewy body disease, 14 with progressive supranuclear palsy, 16 with vascular dementia (VaD) and 15 controls without a brain disease, were examined. The Fe load was determined semi-quantitatively on T2*-weighted MRI serial brain sections in the claustrum, caudate nucleus, putamen, globus pallidus, thalamus, subthalamic nucleus, hippocampus, mamillary body, lateral geniculate body, red nucleus, substantia nigra and dentate nucleus. The disease diagnosis was made on subsequent neuropathological examination. RESULTS: The Fe load was significantly increased in the claustrum, caudate nucleus and putamen of FTLD brains and to a lesser degree in the globus pallidus, thalamus and subthalamic nucleus. In the other neurodegenerative diseases no Fe accumulation was observed, except for a mild increase in the caudate nucleus of AD brains. In VaD brains no Fe increase was detected. CONCLUSIONS: Only FTLD displays a significant Fe load, suggesting that impaired Fe homeostasis plays an important role in the pathogenesis of this heterogeneous disease entity.

Accuracy of milk ketone bodies from flow-injection analysis for the diagnosis of hyperketonemia in dairy cows.

The objectives of this study were (1) to determine the correlations between blood ß-hydroxybutyrate (BHBA) and milk components [BHBA, acetone, fat, protein, and fat:protein (F:P) ratio], and (2) to establish optimal thresholds for milk components to predict hyperketonemia in dairy cows. Data on 163 cows from 37 herds were used in this cross-sectional study. Herds were visited once during the study period, and cows between 2 and 90 d in milk were blood sampled within 4h of milk sampling for the Dairy Herd Improvement test. Blood BHBA concentrations were measured using a cow-side electronic meter, Precision Xtra, which was considered the gold standard test in this study. Milk BHBA and acetone concentrations were measured in Dairy Herd Improvement milk samples by flow-injection analysis; whereas, milk fat and protein were tested using Fourier transform infrared spectroscopy. Hyperketonemia was defined by a blood BHBA concentration ≥ 1.4 mmol/L. The prevalence of hyperketonemia (based on blood BHBA values) in this study population was 21.0%. Pearson correlation coefficients between blood BHBA and milk BHBA, acetone, fat, protein, and F:P ratio were 0.89, 0.73, 0.21, 0.04, and 0.17, respectively. Receiver operating characteristic curves were generated and thresholds for each individual milk component were determined based on the maximal sum of sensitivity and specificity. Optimal threshold values for hyperketonemia were milk BHBA ≥ 0.20 mmol/L, acetone ≥ 0.08 mmol/L, fat ≥ 4.2%, and F:P ratio ≥ 1.3. Based on these thresholds, milk BHBA and acetone had greater sensitivity (84 and 87%, respectively) and greater specificity (96 and 95%, respectively) than the other milk components (fat, protein, and F:P). Series and parallel testing slightly improved the accuracy of milk BHBA and acetone values to predict hyperketonemia. A multivariable model that accounted for milk BHBA and milk acetone values simultaneously had the highest accuracy of all tested models for predicting hyperketonemia. These results support that milk BHBA and milk acetone values from flow-injection analysis are accurate diagnostic tools for hyperketonemia in dairy cows and could potentially be used for herd-level hyperketonemia surveillance programs.

Short dry period management improves peripartum ruminal adaptation in dairy cows.

The present study aimed to determine whether the improvement in postpartum energy balance frequently reported in cows under short dry period management could be due to an improvement in ruminal function related to the reduction in the number of diet changes before calving. Six multiparous and 6 primiparous Holstein cows equipped with ruminal cannula were assigned to 6 blocks of 2 cows each according to parity, projected milk production at 305 d, and expected calving date. Within each block, cows were randomly assigned to either a conventional (CDP; 63.2 ± 2.0 d) or a short dry period (SDP; 35.2 ± 2.0 d) management in a randomized complete block design. The CDP cows were fed a far-off diet until 28 d before calving, followed by a prepartum diet, whereas SDP cows received only the prepartum diet. After calving, both groups were fed the same lactation diet. Milk yield and dry matter intake (DMI) were recorded daily and milk composition, weekly. Blood samples were taken twice a week during the first 4 wk postcalving and weekly otherwise. Omasal and ruminal samples were collected approximately 3 wk prior and 3 wk after calving. From 28 d before calving until calving, when the 2 groups of cows were fed the same prepartum diet, there was no effect of the dry period length management on DMI, plasma concentrations of ß-hydroxybutyrate, nonesterified fatty acids, and glucose and nutrient digestibility in the rumen. However, CDP cows tended to have lower ruminal pH and higher ruminal concentrations of total volatile fatty acids than SDP cows. From calving to 60 d in milk, daily DMI was higher for SDP than for CDP cows (22.3 ± 0.44 vs. 20.7 ± 0.30 kg), but milk production and milk concentrations and yields of fat, protein, and total solids were not affected by the dry period length management. After calving, body weight loss was reduced and body condition score tended to increase more rapidly for SDP than for CDP cows. Nutrient digestibility in the rumen, expressed in kilograms per day, was greater or tended to be greater for SDP cows, but differences were no longer significant when expressed per unit of nutrient ingested. The decrease in plasma nonesterified fatty acids and ß-hydroxybutyrate in SDP cows without effect on milk yield suggests an improved energy balance likely due to greater DMI. Results from the present study seem to indicate that reducing the number of diet changes before calving could facilitate ruminal adaptation to the lactation diet and improve energy balance postpartum.

Genetic analysis of milk ß-hydroxybutyrate and its association with fat-to-protein ratio, body condition score, clinical ketosis, and displaced abomasum in early first lactation of Canadian Holsteins.

The aim of this study was to estimate genetic parameters for milk ß-hydroxybutyrate (BHBA) in early first lactation of Canadian Holstein cows and to examine its genetic association with indicators of energy balance (fat-to-protein ratio and body condition score) and metabolic diseases (clinical ketosis and displaced abomasum). Data for milk BHBA recorded between 5 and 100 d in milk was obtained from Valacta (Sainte-Anne-de-Bellevue, Québec, Canada), the Canadian Dairy Herd Improvement organization responsible for Québec and Atlantic provinces. Test-day milk samples were analyzed by mid-infrared spectrometry using previously developed calibration equations for milk BHBA. Test-day records of fat-to-protein ratio were obtained from the routine milk recording scheme. Body condition score records were available from the routine type classification system. Data on clinical ketosis and displaced abomasum recorded by producers were available from the national dairy cattle health system in Canada. Data were analyzed using linear animal models. Heritability estimates for milk BHBA at different stages of early lactation were between 0.14 and 0.29. Genetic correlations between milk BHBA were higher between adjacent lactation intervals and decreased as intervals were further apart. Correlations between breeding values for milk BHBA and routinely evaluated traits revealed that selection for lower milk BHBA in early lactation would lead to an improvement of several health and fertility traits, including SCS, calving to first service, number of services, first service to conception, and days open. Also, lower milk BHBA was associated with a longer herd life, better conformation, and better feet and legs. A higher genetic merit for milk yield was associated with higher milk BHBA, and, therefore, a greater susceptibility to hyperketonemia. Milk BHBA at the first test-day was moderately genetically correlated with fat-to-protein ratio (0.49), body condition score (-0.35), and clinical ketosis (0.48), whereas the genetic correlation with displaced abomasum was near zero (0.07). Milk BHBA can be routinely analyzed in milk samples at test days, and, therefore, provides a practical tool for breeding cows less susceptible to hyperketonemia.

Fate of organic matter during moderate heat treatment of sludge: kinetics of biopolymer and hydrolytic activity release and impact on sludge reduction by anaerobic digestion.

Temperature-phased anaerobic digestion with a 50-70 °C pre-treatment is widely proposed for sludge. Here, such a sludge pre-treatment (65 °C) was studied against the physical, enzymatic and biodegradation processes. The soluble and particulate fractions were analysed in terms of biochemical composition and hydrolytic enzymatic activities. Two kinetics of organic matter solubilisation were observed: a rapid transfer of the weak-linked biopolymers to the water phase, including sugars, proteins or humic acid-like substances, to the water phase, followed by a slow and long-term solubilisation of proteins and humic acid-like substances. In addition, during the heat treatment a significant pool of thermostable hydrolytic enzymes including proteases, lipases and glucosidases remains active. Consequently, a global impact on organic matter was the transfer of the biodegradable chemical oxygen demand (COD) from the particulate to the soluble fraction as evaluated by the biological methane potential test. However, the total biodegradable COD content of the treated sludge remained constant. The heat process improves the bio-accessibility of the biodegradable molecules but doesn't increase the inherent sludge biodegradability, suggesting that the chemistry of the refractory proteins and humic acids seems to be the real limit to sludge digestion.

Superficial siderosis of the central nervous system: a post-mortem 7.0-tesla magnetic resonance imaging study with neuropathological correlates.

BACKGROUND: Superficial siderosis (SS) is a rare finding on T2*-weighted magnetic resonance imaging (MRI), regarded as a radiological marker of cerebral amyloid angiopathy (CAA). The present study investigates with 7.0-tesla MRI the prevalence of SS and its underlying pathological substrate in a consecutive series of post-mortem brains of elderly patients with various neurodegenerative and cerebrovascular lesions. MATERIALS AND METHODS: The prevalence of SS and associated lesions was screened using 7.0-tesla MRI and their neuropathological correlates in 120 post-mortem brains of patients with various neurodegenerative and cerebrovascular diseases. RESULTS: Eighty-three separate zones of SS were detected in 45 brains (37.5%), including 25 areas of disseminated SS (dSS) and 58 areas of focal SS (fSS), restricted to less than 3 sulci. dSS was spatially related to sequels of 14 lobar haematomas and 11 cerebral infarcts, while fSS was connected to 19 microbleeds and 39 micro-infarcts (p < 0.001). Comparison of the 15 CAA to the 30 non-CAA brains showed that dSS was due to an old lobar haematoma in 53% of the former group compared to 3% of the latter group (p = 0.003). fSS was due to a microbleed in 7% of the CAA brains and to 40% of the non-CAA brains (p = 0.03). CONCLUSIONS: SS is associated with both haemorrhagic and ischaemic underlying lesions. It is frequently observed on T2*-weighted 7.0-tesla MRI, and two types of SS may be described. Clinicians should keep in mind that SS may be found in other settings than CAA.