Cognitive impairment, the central vein sign, and paramagnetic rim lesions in RIS.

OBJECTIVE: The central vein sign (CVS) and "paramagnetic rim lesions" (PRL) are emerging imaging biomarkers in multiple sclerosis (MS) reflecting perivenular demyelination and chronic, smoldering inflammation. The objective of this study was to assess relationships between cognitive impairment (CI) and the CVS and PRL in radiologically isolated syndrome (RIS). METHODS: Twenty-seven adults with RIS underwent 3.0 T MRI of the brain and cervical spinal cord (SC) and cognitive assessment using the minimal assessment of cognitive function in MS battery. The CVS and PRL were assessed in white-matter lesions (WMLs) on T2*-weighted segmented echo-planar magnitude and phase images. Multivariable linear regression evaluated relationships between CI and MRI measures. RESULTS: Global CI was present in 9 (33%) participants with processing speed and visual memory most frequently affected. Most participants (93%) had ⩾ 40% CVS + WML (a threshold distinguishing MS from other WM disorders); 63% demonstrated PRL. Linear regression revealed that CVS + WML predicted performance on verbal memory(ß =-0.024, p = 0.03) while PRL predicted performance on verbal memory (ß = -0.040, p = 0.04) and processing speed (ß = -0.039, p = 0.03). CONCLUSIONS: CI is common in RIS and is associated with markers of perivenular demyelination and chronic inflammation in WML, such as CVS + WML and PRL. A prospective follow-up of this cohort will ascertain the importance of CI, CVS, and PRL as risk factors for conversion from RIS to MS.

A role for the Auxin Response Factors ARF6 and ARF8 homologs in petal spur elongation and nectary maturation in Aquilegia.

The petal spur of the basal eudicot Aquilegia is a key innovation associated with the adaptive radiation of the genus. Previous studies have shown that diversification of Aquilegia spur length can be predominantly attributed to variation in cell elongation. However, the genetic pathways that control the development of petal spurs are still being investigated. Here, we focus on a pair of closely related homologs of the AUXIN RESPONSE FACTOR family, AqARF6 and AqARF8, to explore their roles in Aquileiga coerulea petal spur development. Expression analyses of the two genes show that they are broadly expressed in vegetative and floral organs, but have relatively higher expression in petal spurs, particularly at later stages. Knockdown of the two AqARF6 and AqARF8 transcripts using virus-induced gene silencing resulted in largely petal-specific defects, including a significant reduction in spur length due to a decrease in cell elongation. These spurs also exhibited an absence of nectar production, which was correlated with downregulation of STYLISH homologs that have previously been shown to control nectary development. This study provides the first evidence of ARF6/8 homolog-mediated petal development outside the core eudicots. The genes appear to be specifically required for cell elongation and nectary maturation in the Aquilegia petal spur.

Why Sex Matters: A Cognitive Study of People With Multiple Sclerosis.

BACKGROUND: Cognitive dysfunction affects 40% to 70% of people with multiple sclerosis (MS). Sex may influence a person's cognition. Although a few studies have reported greater cognitive deficits in men than women, it is unclear whether specific cognitive domains are more vulnerable than others to the effects of sex or whether cognition is influenced by neurologic or psychiatric variables. METHODS: A chart review was undertaken of 408 people with MS referred to neuropsychological services. Demographic and MS-related variables were extracted from the patients' records. We used the Minimal Assessment of Cognitive Functioning in Multiple Sclerosis for the neuropsychological assessment. Raw test scores were converted to z scores using Canadian regression-based normative means. A general linear model was conducted on the adjusted scores, controlling for age; years of education; disease course; illness duration; and disability, anxiety, and depression scores. RESULTS: Men were more likely than women to have primary progressive MS (χ=6.415, P=0.011). There were no other sex differences with respect to demographic, neurologic, or psychiatric data. Women performed significantly better than men on the California Verbal Learning Test-Second Edition Total Learning index (F=7.846, P=0.006). CONCLUSIONS: An analysis of a large, consecutive sample of people with MS demonstrated that sex, independent of demographic, neurologic, or psychiatric factors, is an important determinant in cognitive impairment, with men being more impaired than women on tests of verbal learning and memory.

Imaging and Baseline Predictors of Cognitive Performance in Minor Ischemic Stroke and Patients With Transient Ischemic Attack at 90 Days.

BACKGROUND AND PURPOSE: Few studies have examined predictors of cognitive impairment after minor ischemic stroke and transient ischemic attack (TIA). We examined clinical and imaging features associated with worse cognitive performance at 90 days. METHODS: TIA or patients with minor stroke underwent neuropsychological testing 90 days post event. Z scores were calculated for cognitive tests, and then grouped into domains of executive function (EF), psychomotor processing speed (PS), and memory. White matter hyperintensity and diffusion-weighted imaging volumes were measured on baseline magnetic resonance imaging. Ninety-day outcomes included modified Rankin Scale (mRS) and Centre for Epidemiological Studies Depression Scale (CES-D) score. RESULTS: Ninety-two patients were included, 76% male, 54% TIA, and mean age 65.1±12.0. Sixty-four percent were diffusion-weighted imaging positive. Median domain z scores were not significantly different from published norms (P>0.05): memory -0.03, EF -0.12, and PS -0.05. Patient performance ≥1 SD below normal was 20% on memory, 16% on PS, and 17% on EF. Cognitive scores did not differ by diagnosis (stroke versus TIA), stroke pathogenesis, presence of obstructive sleep apnea, and diffusion-weighted imaging or white matter hyperintensity volumes. In multivariable analyses, lower EF was associated with previous cortical infarct on magnetic resonance imaging (P=0.03), mRS score of >1; P=0.0003 and depressive symptoms (CES-D ≥16; P=0.03). Lower PS scores were associated with previous cortical infarct (P=0.02), acute bilateral positive diffusion-weighted imaging (P=0.02), mRS score of >1 (P=0.003), and CES-D ≥16 (P=0.03). CONCLUSIONS: Despite average-range cognitive performance in this TIA and population with minor stroke, we found associations of EF and PS with evidence of previous stroke, postevent disability, and depression.

Community biofilm-formation, stratification and productivity in serially-transferred microcosms.

The establishment of O2 gradients in liquid columns by bacterial metabolic activity produces a spatially-structured environment. This produces a high-O2 region at the top that represents an un-occupied niche which could be colonised by biofilm-competent strains. We have used this to develop an experimental model system using soil-wash inocula and a serial-transfer approach to investigate changes in community-based biofilm-formation and productivity. This involved 10 transfers of mixed-community or biofilm-only samples over a total of 10-60 days incubation. In all final-transfer communities the ability to form biofilms was retained, though in longer incubations the build-up of toxic metabolites limited productivity. Measurements of microcosm productivity, biofilm-strength and attachment levels were used to assess community-aggregated traits which showed changes at both the community and individual-strain levels. Final-transfer communities were stratified with strains demonstrating a plastic phenotype when migrating between the high and low-O2 regions. The majority of community productivity came from the O2-depleted region rather than the top of the liquid column. This model system illustrates the complexity we expect to see in natural biofilm-forming communities. The connection between biofilms and the liquid column seen here has important implications for how these structures form and respond to selective pressure.

Dilution of rice with other gluten free grains to lower inorganic arsenic in foods for young children in response to European Union regulations provides impetus to setting stricter standards.

There has been an increasing realisation that young infants are exposed to elevated concentrations of the carcinogen inorganic arsenic, relative to adults. This is because many infant food products are rice based, and rice is ~10-fold elevated in inorganic arsenic compared to most other foods. The European Commission (EC) has acted on this concern setting stricter standards for infants, 100 µg of inorganic arsenic per kg of food (100 µg/kg), as compared to adults (200 µg/kg), for rice based foods, a law that was brought into place in 1st January 2016. Here we investigate how this law has impacted on inorganic arsenic in baby food products in the UK market, and compare the findings to previous baby food surveys taken before and just after the law came into place. We find that for a wide range of UK infant products that the new regulations are being adhered to, with all samples surveyed, being under 100 µg/kg inorganic arsenic. The prevalence of pure rice products had decreased in the UK, and there appears to be careful sourcing of the rice used in these products to ensure conformity with regulations. There has been an increased presence of mixed cereal products, with rice and maize as the main ingredient, appearing on the UK market, with varying rice contents for infant porridges, cakes and mueslis, with the latter being a relatively innovative product for infant foods. There was a highly significant correlation (P<0.0001) between rice content and inorganic arsenic concentration across all infant foods. When UK infant rice cakes, breakfast cereals and porridges were compare to their general, i.e. not labelled specifically for being for infant consumption, equivalent it was found that the adult foods generally exceeded the 100 µg/kg inorganic arsenic standard for infant foods. Thus, infants should not be given rice products not specifically labelled as being for them if a lower inorganic arsenic diet is to be maintained.

Towards sustainable aquafeeds: Evaluating substitution of fishmeal with lipid-extracted microalgal co-product (Nannochloropsis oculata) in diets of juvenile Nile tilapia (Oreochromis niloticus).

Microalgae companies increasingly seek markets for defatted biomass that is left over after extracting omega-3 rich oil for human nutraceuticals and crude oil for fuels. Such a protein-rich co-product is a promising alternative to unsustainably sourced fishmeal in aquaculture diets. We report the first evaluation of co-product of the marine microalga Nannochloropsis oculata (N. oculata co-product) for replacing fishmeal in diets of Nile tilapia, a globally important aquaculture species. We conducted a nutrient digestibility experiment with N. oculata dried whole cells and N. oculata co-product, followed by an 84-day nutritional feeding experiment with N. oculata co-product. N. oculata co-product, more nutrient-dense than whole cells, had the highest digestibility for lysine, an essential amino acid that is often deficient in terrestrial crop meals; and for 20:5 n-3 EPA, making it a good option for EPA supplementation in tilapia feed. N. oculata co-product, despite containing higher amounts of protein than whole cells, had significantly lower digestibility for crude protein than whole cells. Apparent digestibility coefficients (ADC) of methionine were significantly lower in N. oculata co-product than in whole cells. The nutritional feeding experiment compared diets with N. oculata co-product that replaced fishmeal as follows: 0% replacement in reference diet (fishmeal as 7% of total diet) and test diets with 33%, 66% and 100% replacement of fishmeal (3%, 5.5%, and 8% of total diet, respectively). Results showed the 33% replacement diet yielded fish growth, feed conversion, and survival similar to the reference diet. Reduced digestibility and growth at greater N. oculata co-product inclusion levels may have been due to higher levels of anti-nutrients in co-product than whole cells. All diets yielded a n3:n6 ratio of tilapia fillet that is favorable for human consumption. Depositions of macro minerals and several trace elements in the fillet were not significantly different across diets. Thus, N. oculata co-product, when replacing 33% of fishmeal in tilapia feed, led to fish performance and flesh composition comparable to that of fish fed the reference diet, but its nutrient digestibility needs to be improved to achieve higher replacement levels.

Neurovascular decoupling is associated with severity of cerebral amyloid angiopathy.

OBJECTIVES: We used functional MRI (fMRI), transcranial Doppler ultrasound, and visual evoked potentials (VEPs) to determine the nature of blood flow responses to functional brain activity and carbon dioxide (CO2) inhalation in patients with cerebral amyloid angiopathy (CAA), and their association with markers of CAA severity. METHODS: In a cross-sectional prospective cohort study, fMRI, transcranial Doppler ultrasound CO2 reactivity, and VEP data were compared between 18 patients with probable CAA (by Boston criteria) and 18 healthy controls, matched by sex and age. Functional MRI consisted of a visual task (viewing an alternating checkerboard pattern) and a motor task (tapping the fingers of the dominant hand). RESULTS: Patients with CAA had lower amplitude of the fMRI response in visual cortex compared with controls (p = 0.01), but not in motor cortex (p = 0.22). In patients with CAA, lower visual cortex fMRI amplitude correlated with higher white matter lesion volume (r = -0.66, p = 0.003) and more microbleeds (r = -0.78, p < 0.001). VEP P100 amplitudes, however, did not differ between CAA and controls (p = 0.45). There were trends toward reduced CO2 reactivity in the middle cerebral artery (p = 0.10) and posterior cerebral artery (p = 0.08). CONCLUSIONS: Impaired blood flow responses in CAA are more evident using a task to activate the occipital lobe than the frontal lobe, consistent with the gradient of increasing vascular amyloid severity from frontal to occipital lobe seen in pathologic studies. Reduced fMRI responses in CAA are caused, at least partly, by impaired vascular reactivity, and are strongly correlated with other neuroimaging markers of CAA severity.