Heritability estimates of predicted blood β-hydroxybutyrate and nonesterified fatty acids and relationships with milk traits in early-lactation Holstein cows

At the beginning of lactation, high-producing cows commonly experience an unbalanced energy status that is often responsible for the onset of metabolic disorders and impaired health and performance. Blood β-hydroxybutyrate (BHB) and nonesterified fatty acids (NEFA) are indicators of excessive fat mobilization and circulating ketone bodies. Recently, prediction models based on mid-infrared (MIR) spectroscopy have been developed to assess blood BHB and NEFA from routinely collected individual milk samples. This study aimed to estimate genetic parameters of blood BHB and NEFA predicted from milk MIR spectra and to assess their phenotypic and genetic correlations with milk production and composition traits in early-lactation Holstein cows. The data set comprised the first test-day record within lactation and spectra of individual milk samples (n = 22,718) of 13,106 Holstein cows collected from 5 to 35 d in milk (DIM). Blood BHB and NEFA were predicted from milk MIR spectra using previously developed prediction models. Genetic parameters of blood metabolites and milk traits were estimated for the whole observational period (5–35 DIM) and within 6 classes of DIM. Blood BHB and NEFA showed similar genetic variation across DIM, with the highest heritability in the first 10 d after calving (0.31 ± 0.06 and 0.19 ± 0.05 for BHB and NEFA, respectively). The genetic correlation between BHB and NEFA was moderate (0.51 ± 0.05). Genetic correlations of BHB with milk yield, SCS, protein percentage, lactose percentage, and urea nitrogen content were similar to, or at least in the same direction as, the correlations of NEFA with the same traits, whereas opposite correlations were observed with fat percentage and fat-to-protein ratio. Results of the current study suggest that blood BHB and NEFA predicted from milk MIR spectra have genetic variation that is potentially exploitable for breeding purposes. Therefore, they could be used as indicator traits of hyperketonemia in a selection index aimed to reduce the susceptibility of dairy cows to metabolic disorders in early lactation

Safety and efficacy of recombinant human erythropoietin treatment of anaemia associated with multiple myeloma in haemodialysed patients

Recombinant human erythropoietin (rHuEpo) was used to treat the anaemia of four haemodialysed patients (3 males, 1 female) with advanced multiple myeloma; the type of serum M component was IgG kappa in all cases. During the 6-month period preceding rHuEpo therapy the patients received multiple blood transfusions (range 4-22 units of packed red cells per patient). After the first month of treatment haematocrit increased from 23±3 (SD) to 32±4% and during the last 3 months the maintenance dose of rHuEpo was 143±37 U/kg per week to achieve a mean haematocrit of 35±1%. After introduction of rHuEpo, blood transfusions were no longer required and the patients reported an improvement in wellbeing. No apparent worsening of multiple myeloma has been observed over the treatment period ranging from 5 to 34 months (cumulative duration of treatment 55 months). Anti-hypertensive therapy was started in one case and increased in two patients. We conclude that rHuEpo appears to be effective and safe in treating anaemia associated with multiple myeloma in patients requiring haemodialysi

The use of mid-infrared spectra to map genes affecting milk composition.

The aim of this study was to investigate the feasibility of using mid-infrared (MIR) spectroscopy analysis of milk samples to increase the power and precision of genome-wide association studies (GWAS) for milk composition and to better distinguish linked quantitative trait loci (QTL). To achieve this goal, we analyzed phenotypic data of milk composition traits, related MIR spectra, and genotypic data comprising 626,777 SNP on 5,202 Holstein, Jersey, and crossbred cows. We performed a conventional GWAS on protein, lactose, fat, and fatty acid concentrations in milk, a GWAS on individual MIR wavenumbers, and a partial least squares regression (PLS), which is equivalent to a multi-trait GWAS, exploiting MIR data simultaneously to predict SNP genotypes. The PLS detected most of the QTL identified using single-trait GWAS, usually with a higher significance value, as well as previously undetected QTL for milk composition. Each QTL tends to have a different pattern of effects across the MIR spectrum and this explains the increased power. Because SNP tracking different QTL tend to have different patterns of effect, it was possible to distinguish closely linked QTL. Overall, the results of this study suggest that using MIR data through either GWAS or PLS analysis applied to genomic data can provide a powerful tool to distinguish milk composition QTL

A genome-wide association study of plasma phosphorylated tau181

Plasma phosphorylated tau at threonine-181 (P-tau181) demonstrates promise as an accessible blood-based biomarker specific to Alzheimer's Disease (AD), with levels recently demonstrating high predictive accuracy for AD-relevant pathology. The genetic underpinnings of P-tau181 levels, however, remain elusive. This study presents the first genome-wide association study of plasma P-tau181 in a total sample of 1153 participants from 2 independent cohorts. No loci, other than those within the APOE genomic region (lead variant = rs429358, beta = 0.32, p =8.44 × 10−25) demonstrated association with P-tau181 at genome-wide significance (p < 5 × 10−08), though rs60872856 on chromosome 2 came close (beta = -0.28, p = 3.23 × 10−07, nearest gene=CYTIP). As the APOE ε4 allele is already a well-established genetic variant associated with AD, this study found no evidence of novel genetic associations relevant to plasma P-tau181, though presents rs60872856 on chromosome 2 as a candidate locus to be further evaluated in future larger size GWAS

Growth of NiO thin films in the presence of water vapor: insights from experiments and theory

NiO-based thin films and nanomaterials are promising candidates for a variety of end-uses, encompassing photo- and electrocatalysts, solar cells, displays, and sensors. This widespread attention has strongly fueled the interest in the fabrication of tailored systems featuring modular chemico-physical properties as a function of the required application. In this study, a single-step chemical vapor deposition (CVD) route for the preparation of pure and fluorine-doped NiO films is presented. Growth experiments were performed under water vapor-containing oxygen atmospheres from a series of Ni(II) β-diketonate–diamine molecular precursors featuring a different fluorination degree of the ligand side chain. A comprehensive experimental and theoretical investigation yielded valuable insights into the growth mechanism, with particular regard to the dependence of the system electronic properties on fluorine doping and content, and to the role exerted by water vapor in the reaction atmosphere. In fact, the interactions of water with the diketonate ligands contribute to weaken Ni–O bonds, favoring precursor activation. The obtainment of F-doped NiO systems from fluorinated derivatives and the simplicity of our process make the adopted strategy a valuable tool to control the system characteristics for a variety of eventual functional applications

Suicide time trends in Brazil from 1980 to 2005

Abstract and keywords in English and Portuguese. Title in Portuguese: Tendência temporal do suicídio no Brasil no período 1980-2005The aim of this study was to describe suicide time trends in Brazil from 1980 to 2005. The data were obtained from the National Mortality Information System and the Brazilian Institute of Geography and Statistics (IBGE). Suicides rates were calculated for the entire period for the country as a whole and the 26 States and Federal District. Annual increases or decreases in mortality rates were also estimated using Prais-Winsten generalized linear regression. The mean suicide rate was 4.12 per 100,000 inhabitants (6.45/100,000 in men and 1.80/100,000 in women). The study showed an increasing suicide trend in men (+1.41% per year, 95%CI: 1.00;1.23) and a decreasing trend in women (-0.53% per year, 95%CI: -0.04;-1.02). Suicide rates increased with age. In general, for all age groups and for both genders, the highest rates were in São Paulo and in the States of the South and Central-West regions. = O objetivo deste estudo foi descrever a tendência temporal das taxas de mortalidade por suicídio no Brasil, no período de 1980 a 2005. Os dados foram obtidos junto ao Sistema de Informações sobre Mortalidade e ao Instituto Brasileiro de Geografia e Estatística. Foram calculadas as taxas médias de suicídio para todo o período, para cada estado, Distrito Federal e para o país como um todo, segundo sexo e faixas etárias. Também foram calculadas as variações médias anuais do suicídio pela regressão linear generalizada de Prais-Winsten. Foi observada, no período, taxa média de suicídio de 4,12 por 100 mil habitantes, variando de 6,45 por 100 mil habitantes entre homens a 1,80 por 100 mil habitantes entre mulheres, com tendência de ascensão entre os homens (+1,41% ao ano, IC95%: 1,00;1,23) e de declínio entre as mulheres (-0,53%, IC95%: -0,04;-1,02). O suicídio aumentou com o avanço da idade em ambos os sexos. De uma maneira geral, para todas as faixas etárias e para ambos os sexos, as maiores taxas foram encontradas em São Paulo e nos estados das regiões Sul e Centro-oeste.Fabíola Stolf Brzozowski, Giovana Bacilieri Soares, Jucemar Benedet, Antonio Fernando Boing, Marco Aurélio Pere

Exploring Recollection and Familiarity Impairments in Parkinson´s disease

There is conflicting evidence on whether patients diagnosed with Parkinson's disease (PD) have cognitive deficits associated with episodic memory and particularly with recognition memory. The aim of the present study was to explore whether PD patients exhibit deficits in recollection and familiarity, the two processes involved in recognition. A sample of young healthy participants (22) was tested to verify that the experimental tasks were useful estimators of recognition processes. Two further samples ¿ one of elderly controls (16) and one of PD patients (20) ¿ were the main focus of this research. All participants were exposed to an associative recognition task aimed at estimating recollection followed by a two-alternative forced-choice (2AFC) test designed to estimate familiarity. The analyses showed a deficit in associative recognition in PD patients and no difference between elderly controls and PD patients in the 2AFC test. By contrast, young healthy participants were better than elderly controls and PD patients in both components of recognition. Further analyses of results of the 2AFC test indicated that the measure chosen to estimate conceptual familiarity was adequate

Quantification of SNAP-25 with mass spectrometry and Simoa: a method comparison in Alzheimer's disease

BACKGROUND: Synaptic dysfunction and degeneration are central to Alzheimer's disease (AD) and have been found to correlate strongly with cognitive decline. Thus, studying cerebrospinal fluid (CSF) biomarkers reflecting synaptic degeneration, such as the presynaptic protein synaptosomal-associated protein 25 (SNAP-25), is of importance to better understand the AD pathophysiology. METHODS: We compared a newly developed Single molecule array (Simoa) immunoassay for SNAP-25 with an in-house immunoprecipitation mass spectrometry (IP-MS) method in a well-characterized clinical cohort (n = 70) consisting of cognitively unimpaired (CU) and cognitively impaired (CI) individuals with and without Aβ pathology (Aβ+ and Aβ-). RESULTS: A strong correlation (Spearman's rank correlation coefficient (rs) > 0.88; p < 0.0001) was found between the Simoa and IP-MS methods, and no statistically significant difference was found for their clinical performance to identify AD pathophysiology in the form of Aβ pathology. Increased CSF SNAP-25 levels in CI Aβ+ compared with CU Aβ- (Simoa, p ≤ 0.01; IP-MS, p ≤ 0.05) and CI Aβ- (Simoa, p ≤ 0.01; IP-MS, p ≤ 0.05) were observed. In independent blood samples (n = 32), the Simoa SNAP-25 assay was found to lack analytical sensitivity for quantification of SNAP-25 in plasma. CONCLUSIONS: These results indicate that the Simoa SNAP-25 method can be used interchangeably with the IP-MS method for the quantification of SNAP-25 in CSF. Additionally, these results confirm that CSF SNAP-25 is increased in relation to amyloid pathology in the AD continuum

P-tau235: a novel biomarker for staging preclinical Alzheimer's disease

Alzheimer’s disease (AD) is characterised by a long preclinical phase. Although phosphorylated tau (p-tau) species such as p-tau217 and p-tau231 provide accurate detection of early pathological changes, other biomarkers capable of staging disease progression during preclinical AD are still needed. Combining exploratory and targeted mass spectrometry methods in neuropathologically confirmed brain tissue, we observed that p-tau235 is a prominent feature of AD pathology. In addition, p-tau235 seemed to be preceded by p-tau231, in what appeared to be a sequential phosphorylation event. To exploit its biomarker potential in cerebrospinal fluid (CSF), we developed and validated a new p-tau235 Simoa assay. Using three clinical cohorts, we demonstrated that (i) CSF p-235 increases early in AD continuum, and (ii) changes in CSF p-tau235 and p-tau231 levels during preclinical AD are consistent with the sequential phosphorylation evidence in AD brain. In conclusion, CSF p-tau235 appears to be not only a highly specific biomarker of AD but also a promising staging biomarker for the preclinical phase. Thus, it could prove useful tracking disease progression and help enriching clinical trial recruitment