Site of infusion of a commercially available direct-fed microbial on performance and digestibility in lactating Holstein cows

Objective: The objective of this research was to evaluate site of infusion of a commercially available direct-fed microbial (DFM) containing 109 cfu/g of Lactobacillus acidophilus and 109 cfu/g Propionibacterium freudenreichii on DMI, rumen kinetics, ruminal VFA, digestibility, milk production, milk components, and blood metabolites in lactating dairy cows. Materials and Methods: Four Holstein cows equipped with ruminal cannulas were used in a Latin square design experiment with 4 periods. Each 37-d period consisted of 14 d of no treatment to prevent crossover contamination, 14 d of adaptation to treatments, 8 d of sampling, and 1 d for ruminal evacuations. Within each period, cows were assigned to 1 of 4 treatments: (1) cows were fed a TMR formulated to meet or exceed nutrient requirements plus 5 g of lactose twice daily without the addition of DFM (control); (2) cows were fed the TMR with a daily dose of DFM top dressed on the feed twice daily (TD); (3) cows were fed the TMR with ruminal infusion of the DFM administered twice daily (RuI); or (4) cows were fed the TMR plus abomasal infusion of the DFM twice daily (AbI). During the sampling period within each period, DMI and milk production were measured daily with set days for blood and rumen fluid collection. Data were analyzed using the MIXED procedure of SAS with animal within period as a random effect. Dry matter intake was not different among treatments. Results and Discussion: No differences were detected in rumen kinetics, pH, individual VFA or VFA ratios, ammonia, or digestibility. There were no differences in kilograms of milk production (P \u3e 0.87); SCC (P \u3e 0.54); or percentage of butter fat (P \u3e 0.21), milk protein (P \u3e 0.83), lactose (P \u3e 0.91), SNF (P \u3e 0.88), and MUN (P\u3e 0.49). No difference existed in most of the milk fatty acids except for 8:0, which had a greater concentration (P \u3e 0.01) in AbI versus control, TD, and RuI. Implications and Applications: Route of administering DFM overall had no effects on DMI, rumen kinetics, ruminal VFA, digestibility, milk production, or milk components in the present experiment

Differentiation of dementia with Lewy bodies from Alzheimer's disease using a dopaminergic presynaptic ligand

Background: Dementia with Lewy bodies (DLB) is one of the main differential diagnoses of Alzheimer's disease (AD). Key pathological features of patients with DLB are not only the presence of cerebral cortical neuronal loss, with Lewy bodies in surviving neurones, but also loss of nigrostriatal dopaminergic neurones, similar to that of Parkinson's disease (PD). In DLB there is 40-70% loss of striatal dopamine.Objective: To determine if detection of this dopaminergic degeneration can help to distinguish DLB from AD during life.Methods: The integrity of the nigrostriatal metabolism in 27 patients with DLB, 17 with AD, 19 drug naive patients with PD, and 16 controls was assessed using a dopaminergic presynaptic ligand, I-123-labelled 2beta-carbomethoxy-3beta-(4-iodophenyl)-N-(3-fluoropropyl)nortropane (FP-CIT), and single photon emission tomography (SPET). A SPET scan was carried out with a single slice, brain dedicated tomograph (SME 810) 3.5 hours after intravenous injection of 185 MBq FP-CIT. With occipital cortex used as a radioactivity uptake reference, ratios for the caudate nucleus and the anterior and posterior putamen of both hemispheres were calculated. All scans were also rated by a simple visual method.Results: Both DLB and PD patients had significantly lower uptake of radioactivity than patients with (p<0.01) and controls (p<0.001) in the caudate nucleus and the anterior and posterior Putamen.Conclusion: FP-CIT SPET provides a means of distinguishing DLB from AD during life

Gemini Spectroscopy and HST Imaging of the Stellar Cluster Population in Region B of M82

We present new spectroscopic observations of the stellar cluster population of region B in the prototype starburst galaxy M82 obtained with the Gillett Gemini-North 8.1-metre telescope. By coupling the spectroscopy with UBVI photometry acquired with the Advanced Camera for Surveys (ACS) on the Hubble Space Telescope (HST), we derive ages, extinctions and radial velocities for seven young massive clusters (YMCs) in region B. We find the clusters to have ages between 70 and 200 Myr and velocities in the range 230 to 350 km/s, while extinctions Av vary between ~1-2.5 mag. We also find evidence of differential extinction across the faces of some clusters which hinders the photometric determination of ages and extinctions in these cases. The cluster radial velocities indicate that the clusters are located at different depths within the disk, and are on regular disk orbits. Our results overall contradict the findings of previous studies, where region B was thought to be a bound region populated by intermediate-age clusters that formed in an independent, offset starburst episode that commenced 600 Myr-1 Gyr ago. Our findings instead suggest that region B is optically bright because of low extinction patches, and this allows us to view the cluster population of the inner M82 disk, which probably formed as a result of the last encounter with M81. This study forms part of a series of papers aimed at studying the cluster population of M82 using deep optical spectroscopy and multi-band photometry.Comment: 12 pages, 8 figures; accepted for publication in The Astrophysical Journa

Tau protein, A beta 42 and S-100B protein in cerebrospinal fluid of patients with dementia with Lewy bodies

The intra vitam diagnosis of dementia with Lewy bodies (DLB) is still based on clinical grounds. So far no technical investigations have been available to support this diagnosis. As for tau protein and beta-amyloid((1-42)) (Abeta42), promising results for the diagnosis of Alzheimer's disease ( AD) have been reported; we evaluated these markers and S-100B protein in cerebrospinal fluid (CSF), using a set of commercially available assays, of 71 patients with DLB, 67 patients with AD and 41 nondemented controls (NDC) for their differential diagnostic relevance. Patients with DLB showed significantly lower tau protein values compared to AD but with a high overlap of values. More prominent differences were observed in the comparison of DLB patients with all three clinical core features and AD patients. Abeta42 levels were decreased in the DLB and AD groups versus NDC, without significant subgroup differences. S-100B levels were not significantly different between the groups. Tau protein levels in CSF may contribute to the clinical distinction between DLB and AD, but the value of the markers is still limited especially due to mixed pathology. We conclude that more specific markers have to be established for the differentiation of these diseases. Copyright (C) 2005 S. Karger AG, Basel

The Asymmetric Wind in M82

We have obtained detailed imaging Fabry-Perot observations of the nearby galaxy M82, in order to understand the physical association between the high-velocity outflow and the starburst nucleus. The observed velocities of the emitting gas in M82 reveal a bipolar outflow of material, originating from the bright starburst regions in the galaxy's inner disk, but misaligned with respect to the galaxy spin axis. The deprojected outflow velocity increases with radius from 525 to 655 km/s. Spectral lines show double components in the centers of the outflowing lobes, with the H-alpha line split by ~300 km/s over a region almost a kiloparsec in size. The filaments are not simple surfaces of revolution, nor is the emission distributed evenly over the surfaces. We model these lobes as a composite of cylindrical and conical structures, collimated in the inner ~500 pc but expanding at a larger opening angle of ~25 degrees beyond that radius. We compare our kinematic model with simulations of starburst-driven winds in which disk material surrounding the source is entrained by the wind. The data also reveal a remarkably low [NII]/H-alpha ratio in the region of the outflow, indicating that photoionization by the nuclear starburst may play a significant role in the excitation of the optical filament gas, particularly near the nucleus.Comment: 42 pages AASTeX with 16 figures; accepted for publication in ApJ; figures reformatted for better printin

Saccadic eye movement changes in Parkinson's disease dementia and dementia with Lewy bodies

Neurodegeneration in Parkinson's disease dementia (PDD) and dementia with Lewy bodies (DLB) affect cortical and subcortical networks involved in saccade generation. We therefore expected impairments in saccade performance in both disorders. In order to improve the pathophysiological understanding and to investigate the usefulness of saccades for differential diagnosis, saccades were tested in age- and education-matched patients with PDD (n = 20) and DLB (n = 20), Alzheimer's disease (n = 22) and Parkinson's disease (n = 24), and controls (n = 24). Reflexive (gap, overlap) and complex saccades (prediction, decision and antisaccade) were tested with electro-oculography. PDD and DLB patients had similar impairment in all tasks (P > 0.05, not significant). Compared with controls, they were impaired in both reflexive saccade execution (gap and overlap latencies, P 0.05). Patients with Parkinson's disease had, compared with controls, similar complex saccade performance (for all, P > 0.05) and only minimal impairment in reflexive tasks, i.e. hypometric gain in the gap task (P = 0.04). Impaired saccade execution in reflexive tasks allowed discrimination between DLB versus Alzheimer's disease (sensitivity ≥60%, specificity ≥77%) and between PDD versus Parkinson's disease (sensitivity ≥60%, specificity ≥88%) when ±1.5 standard deviations was used for group discrimination. We conclude that impairments in reflexive saccades may be helpful for differential diagnosis and are minimal when either cortical (Alzheimer's disease) or nigrostriatal neurodegeneration (Parkinson's disease) exists solely; however, they become prominent with combined cortical and subcortical neurodegeneration in PDD and DLB. The similarities in saccade performance in PDD and DLB underline the overlap between these conditions and underscore differences from Alzheimer's disease and Parkinson's diseas

Cholinergic and perfusion brain networks in Parkinson disease dementia.

OBJECTIVE: To investigate muscarinic M1/M4 cholinergic networks in Parkinson disease dementia (PDD) and their association with changes in Mini-Mental State Examination (MMSE) after 12 weeks of treatment with donepezil. METHODS: Forty-nine participants (25 PDD and 24 elderly controls) underwent (123)I-QNB and (99m)Tc-exametazime SPECT scanning. We implemented voxel principal components (PC) analysis, producing a series of PC images of patterns of interrelated voxels across individuals. Linear regression analyses derived specific M1/M4 and perfusion spatial covariance patterns (SCPs). RESULTS: We found an M1/M4 SCP of relative decreased binding in basal forebrain, temporal, striatum, insula, and anterior cingulate (F1,47 = 31.9, p < 0.001) in cholinesterase inhibitor-naive patients with PDD, implicating limbic-paralimbic and salience cholinergic networks. The corresponding regional cerebral blood flow SCP showed relative decreased uptake in temporoparietal and prefrontal areas (F1,47 = 177.5, p < 0.001) and nodes of the frontoparietal and default mode networks (DMN). The M1/M4 pattern that correlated with an improvement in MMSE (r = 0.58, p = 0.005) revealed relatively preserved/increased pre/medial/orbitofrontal, parietal, and posterior cingulate areas coinciding with the DMN and frontoparietal networks. CONCLUSION: Dysfunctional limbic-paralimbic and salience cholinergic networks were associated with PDD. Established cholinergic maintenance of the DMN and frontoparietal networks may be prerequisite for cognitive remediation following cholinergic treatment in this condition.Medical Research Council UK [grant number G9817682], and by the National Institute for Health Research (NIHR) Research for Public Benefit, Wellcome Trust (WT088441MA Fellowship funding J-P.T). NIHR Dementia Biomedical Research Unit at Cambridge University Hospitals NHS Foundation Trust and the University of Cambridge. The NIHR Newcastle Biomedical Research Centre in Ageing and Chronic Disease and Biomedical Research Unit in Lewy Body Dementia based at Newcastle upon Tyne Hospitals NHS Foundation Trust and Newcastle University.This is the final version of the article. It first appeared from Wolters Kluwer via http://dx.doi.org/10.​1212/​WNL.​000000000000283

Incidence and Prediction of Falls in Dementia: A Prospective Study in Older People

Falls are a major cause of morbidity and mortality in dementia, but there have been no prospective studies of risk factors for falling specific to this patient population, and no successful falls intervention/prevention trials. This prospective study aimed to identify modifiable risk factors for falling in older people with mild to moderate dementia.179 participants aged over 65 years were recruited from outpatient clinics in the UK (38 Alzheimer's disease (AD), 32 Vascular dementia (VAD), 30 Dementia with Lewy bodies (DLB), 40 Parkinson's disease with dementia (PDD), 39 healthy controls). A multifactorial assessment of baseline risk factors was performed and fall diaries were completed prospectively for 12 months. Dementia participants experienced nearly 8 times more incident falls (9118/1000 person-years) than controls (1023/1000 person-years; incidence density ratio: 7.58, 3.11-18.5). In dementia, significant univariate predictors of sustaining at least one fall included diagnosis of Lewy body disorder (proportional hazard ratio (HR) adjusted for age and sex: 3.33, 2.11-5.26), and history of falls in the preceding 12 months (HR: 2.52, 1.52-4.17). In multivariate analyses, significant potentially modifiable predictors were symptomatic orthostatic hypotension (HR: 2.13, 1.19-3.80), autonomic symptom score (HR per point 0-36: 1.055, 1.012-1.099), and Cornell depression score (HR per point 0-40: 1.053, 1.01-1.099). Higher levels of physical activity were protective (HR per point 0-9: 0.827, 0.716-0.956).The management of symptomatic orthostatic hypotension, autonomic symptoms and depression, and the encouragement of physical activity may provide the core elements for the most fruitful strategy to reduce falls in people with dementia. Randomised controlled trials to assess such a strategy are a priority

A spectroscopic census of the M82 stellar cluster population

We present a spectroscopic study of the stellar cluster population of M82, the archetype starburst galaxy, based primarily on new Gemini-North multi-object spectroscopy of 49 star clusters. These observations constitute the largest to date spectroscopic dataset of extragalactic young clusters, giving virtually continuous coverage across the galaxy; we use these data to deduce information about the clusters as well as the M82 post-starburst disk and nuclear starburst environments. Spectroscopic age-dating places clusters in the nucleus and disk between (7, 15) and (30, 270) Myr, with distribution peaks at ~10 and ~140 Myr respectively. We find cluster radial velocities in the range (-160, 220) km/s (wrt the galaxy centre) and line of sight Na I D interstellar absorption line velocities in (-75, 200) km/s, in many cases entirely decoupled from the clusters. As the disk cluster radial velocities lie on the flat part of the galaxy rotation curve, we conclude that they comprise a regularly orbiting system. Our observations suggest that the largest part of the population was created as a result of the close encounter with M81 ~220 Myr ago. Clusters in the nucleus are found in solid body rotation on the bar. The possible detection of WR features in their spectra indicates that cluster formation continues in the central starburst zone. We also report the potential discovery of two old populous clusters in the halo of M82, aged >8 Gyr. Using these measurements and simple dynamical considerations, we derive a toy model for the invisible physical structure of the galaxy, and confirm the existence of two dominant spiral arms.Comment: Accepted for publication in the Astrophysical Journa

The challenges of COVID-19 for people with dementia with Lewy bodies and family caregivers.

Introduction During the current SARS-CoV-2 pandemic dementia has been identified as disproportionally common in adults aged over 65 who develop severe COVID-19.1 Observational data from the International Severe Acute Respiratory and Emerging Infections Consortium also confirms a high prevalence of dementia in older adults hospitalised with COVID-19.2 It is so far unclear whether there is any direct effect of dementia pathologies as dementia is a disease of old age, and thus likely to be associated with a variety of comorbidities, in particular, frailty, which may further exacerbate the risk of severe infection. In addition up to one third of COVID patients have demonstrated neurological sequelae3 and there may be both direct (viral infection within the brain, vascular effects) and indirect effects (e.g. host immunological response, impact of treatment) of SARS-CoV-2 on the brain.4 It is therefore possible that SARS-CoV-2 infection may accentuate any pre-existing neurodegenerative disease