The effect of exogenous glucose infusion on early embryonic development in lactating dairy cows

peer-reviewedThe objective of this study was to examine the effect of intravenous infusion of glucose on early embryonic development in lactating dairy cows. Nonpregnant, lactating dairy cows (n = 12) were enrolled in the study (276 ± 17 d in milk). On d 7 after a synchronized estrus, cows were randomly assigned to receive an intravenous infusion of either 750 g/d of exogenous glucose (GLUC; 78 mL/h of 40% glucose wt/vol) or saline (CTRL; 78 mL/h of 0.9% saline solution). The infusion period lasted 7 d and cows were confined to metabolism stalls for the duration of the study. Coincident with the commencement of the infusion on d 7 after estrus, 15 in vitro-produced grade 1 blastocysts were transferred into the uterine horn ipsilateral to the corpus luteum. All animals were slaughtered on d 14 to recover conceptuses, uterine fluid, and endometrial tissue. Glucose infusion increased circulating glucose concentrations (4.70 ± 0.12 vs. 4.15 ± 0.12 mmol/L) but did not affect milk production or dry matter intake. Circulating β-hydroxybutyrate concentrations were decreased (0.51 ± 0.01 vs. 0.70 ± 0.01 mmol/L for GLUC vs. CTRL, respectively) but plasma fatty acids, progesterone, and insulin concentrations were unaffected by treatment. Treatment did not affect either uterine lumen fluid glucose concentration or the mRNA abundance of specific glucose transporters in the endometrium. Mean conceptus length, width, and area on d 14 were reduced in the GLUC treatment compared with the CTRL treatment. A greater proportion of embryos in the CTRL group had elongated to all length cut-off measurements between 11 and 20 mm (measured in 1-mm increments) compared with the GLUC treatment. In conclusion, infusion of glucose into lactating dairy cows from d 7 to d 14 post-estrus during the critical period of conceptus elongation had an adverse impact on early embryonic development

A Systematic Study of Hidden Sector Dark Matter: Application to the Gamma-Ray and Antiproton Excesses

In hidden sector models, dark matter does not directly couple to the particle content of the Standard Model, strongly suppressing rates at direct detection experiments, while still allowing for large signals from annihilation. In this paper, we conduct an extensive study of hidden sector dark matter, covering a wide range of dark matter spins, mediator spins, interaction diagrams, and annihilation final states, in each case determining whether the annihilations are s-wave (thus enabling efficient annihilation in the universe today). We then go on to consider a variety of portal interactions that allow the hidden sector annihilation products to decay into the Standard Model. We broadly classify constraints from relic density requirements and dwarf spheroidal galaxy observations. In the scenario that the hidden sector was in equilibrium with the Standard Model in the early universe, we place a lower bound on the portal coupling, as well as on the dark matter's elastic scattering cross section with nuclei. We apply our hidden sector results to the observed Galactic Center gamma-ray excess and the cosmic-ray antiproton excess. We find that both of these excesses can be simultaneously explained by a variety of hidden sector models, without any tension with constraints from observations of dwarf spheroidal galaxies.Comment: 40 pages, 11 figures, matches the JHEP version, references adde

Long‐term anticholinergic, benzodiazepine and Z‐drug use in community‐dwelling older adults: What is the impact on cognitive and neuropsychological performance?

BACKGROUND Long-term use of anticholinergics, benzodiazepines and related drugs (or "Z-drugs") have been associated with cognitive impairment and dementia. However, the relationship of these medications with cognitive function and domain-specific neuropsychological performance in older adults without dementia, is unclear. METHODS 5135 older adults (74.0 ± 8.3 years; 67.4% female) without a diagnosis of dementia were recruited in Ireland to the Trinity-Ulster-Department of Agriculture (TUDA) study. Detailed cognitive and neuropsychological assessment was conducted using the Mini-Mental State Examination (MMSE), Frontal Assessment Battery (FAB) and Repeatable Battery for Assessment of Neuropsychological Status (RBANS). RESULTS A total of 44% (2259 of 5153) used either a potential or definite anticholinergic medication. Overall, 9.7% (n = 500) used a definite anticholinergic medication. Regular benzodiazepine use was reported by 7% (n = 363), whilst 7.5% (n = 387) used a "Z-drug". Use of definite, but not potential anticholinergic medication was associated with poorer performance on all three assessments (β: -0.09; 95% CI: -0.14, -0.03, p = 0.002 for MMSE; β: -0.04; 95% CI: -0.06, -0.02; p < 0.001 for FAB; β: -4.15; 95% CI: -5.64, -2.66; p < 0.001 for RBANS) in addition to all domains of the RBANS. Regular benzodiazepine use was also associated with poorer neuropsychological test performance, especially in Immediate Memory (β: -4.98; 95% CI: -6.81, -3.15; p < 0.001) and Attention (β: -6.81; 95% CI: -8.60, -5.03; p < 0.001) RBANS domains. CONCLUSIONS Regular use of definite anticholinergic medications and benzodiazepines, but not potential anticholinergics or "Z-drugs", was associated with poorer overall and domain-specific neuropsychological performance in older adults

Chemically bound gold nanoparticle arrays on silicon: assembly, properties and SERS study of protein interactions

A highly reproducible and facile method for formation of ordered 2 dimensional arrays of CTAB protected 50 nm gold nanoparticles bonded to silicon wafers is described. The silicon wafers have been chemically modified with long-chain silanes terminated with thiol that penetrate the CTAB bilayer and chemically bind to the underlying gold nanoparticle. The silicon wafer provides a reproducibly smooth, chemically functionalizable and non-fluorescent substrate with a silicon phonon mode which may provide a convenient internal frequency and intensity calibration for vibrational spectroscopy. The CTAB bilayer provides a potentially biomimetic environment for analyte, yet allows a sufficiently small nanoparticle separation to achieve a significant electric field enhancement. The arrays have been characterized using SEM and Raman spectroscopy. These studies reveal that the reproducibility of the arrays is excellent both between batches (< 10% RSD) and across a single batch (< 5% RSD). The arrays also exhibit good stability, and the effect of temperature on the arrays was also investigated. The interaction of protein and amino acid with the nanoparticle arrays was investigated using Raman microscopy to investigate their potential in bio-SERS spectroscopy. Raman of phenylalanine and the protein bovine pancreatic trypsin inhibitor, BPTI were studied using 785 nm excitation, coincident with the surface plasmon absorbance of the array. The arrays exhibit SERS enhancements of the order of 2.6 x 104 for phenylalanine, the standard deviation on the relative intensity of the 1555 cm-1 mode of phenylalanine is less than 10% for 100 randomly distributed locations across a single substrate and less than 20% between different substrates. Significantly, comparisons of the Raman spectra of the protein and phenlyalanine in solution and immobilized on the nanoparticle arrays indicates that the protein is non-randomly orientated on the arrays. Selective SERS enhancements suggest that aromatic residues penetrate through the bilayer inducing conformational changes in the protein

Reduced Kidney Function is Associated with Poorer Domain‐Specific Cognitive Performance in Community‐Dwelling Older Adults

OBJECTIVES: Whilst chronic kidney disease has been associated with cognitive impairment, the association between reduced estimated Glomerular Filtration Rate (eGFR) and domain‐specific cognitive performance is less clear and may represent an important target for the promotion of optimal brain health in older adults. METHODS: Participants aged >60 years from the Trinity‐Ulster‐Department of Agriculture study underwent detailed cognitive assessment using the Mini‐Mental State Examination (Mini‐Mental State Examination (MMSE)), Frontal Assessment Battery (FAB) and Repeatable Battery for Assessment of Neuropsychological Status (RBANS). Poisson and linear regression models assessed the relationship between eGFR strata and cognitive performance. RESULTS: In 4887 older adults (73.9 ± 8.3 years; 67.7% female), declining eGFR strata was associated with greater likelihood of error on the MMSE/FAB and poorer overall performance on the RBANS. Following robust covariate adjustment, findings were greatest for GFR 80 years. CONCLUSIONS: Reduced kidney function was associated with poorer global and domain‐specific neuropsychological performance. Associations were strongest with eGFR <45 ml/min/1.73 m(2) and in those aged 60–70 years, suggesting that this population may potentially benefit from potential multi‐domain interventions aimed at promoting optimal brain health in older adults

Association of dietary flavan-3-ol intakes with plasma phenyl-γ-valerolactones: analysis from the TUDA cohort of healthy older adults

Background: Dietary polyphenols, including flavan-3-ols (F3O), are associated with better health outcomes. The relationship of plasma phenyl-γ-valerolactones (PVLs), the products of colonic bacterial metabolism of F3O, with dietary intakes is unclear. Objectives: To investigate whether plasma PVLs are associated with self-reported intakes of total F3O and procyanidins+(epi)catechins. Design: We measured 9 PVLs by uHPLC-MS-MS in plasma from adults (&gt;60y) in the Trinity-Ulster-Department of Agriculture (TUD study (2008 to 2012; n=5,186) and a follow-up subset (2014 to 2018) with corresponding dietary data (n=557). Dietary (poly)phenols collected by FFQ were analyzed using Phenol-Explorer. Results: Mean (95% confidence interval [CI]) intakes were estimated as 2283 (2213, 2352) mg/d for total (poly)phenols, 674 (648, 701) for total F3O, and 152 (146, 158) for procyanidins+(epi)catechins. Two PVL metabolites were detected in plasma from the majority of participants, 5-(hydroxyphenyl)-γ-VL-sulfate (PVL1) and 5-(4'-hydroxyphenyl)-γ-VL-3'-glucuronide (PVL2). The 7 other PVLs were detectable only in 1-32% of samples. Self-reported intakes (mg/d) of F3O (r = 0.113, P = 0.017) and procyanidin+(epi)catechin (r = 0.122, P = 0.010) showed statistically significant correlations with the sum of PVL1 and PVL 2 (PVL1+2). With increasing intake quartiles (Q1-Q4), mean (95% CI) PVL1+2 increased; from 28.3 (20.8, 35.9) nmol/L in Q1 to 45.2 (37.2, 53.2) nmol/L in Q4; P = 0.025, for dietary F3O, and from 27.4 (19.1, 35.8) nmol/L in Q1 to 46.5 (38.2, 54.9) nmol/L in Q4; P = 0.020, for procyanidins+(epi)catechins. Conclusions: Of 9 PVL metabolites investigated, 2 were detected in most samples and were weakly associated with intakes of total F3O and procyanidins+(epi)catechins. Future controlled feeding studies are required to validate plasma PVLs as biomarkers of these dietary polyphenols