Relationship between Freezing of Gait and Anxiety in Parkinson\u27s Disease Patients: A Systemic Literature Review

Freezing of gait (FOG) is experienced by a significant number of patients with Parkinson\u27s disease (PD). The pathophysiology of this disabling motor symptom remains unclear, and there are no effective therapies. Anxiety has previously been posited as a contributing factor to gait freezing. There have been few studies directly investigating this topic, and a comprehensive literature review is lacking. The objective of this paper was to systematically review the evidence associating anxiety with the presence, severity, and progression of FOG in PD patients. The PubMed, EMBASE, and PsycINFO databases were searched up to September 19, 2018, for English-language, peer-reviewed articles that explored anxiety and FOG as outcome measures in a PD population base. Review articles, case reports, and articles that assessed gait disorders other than FOG were excluded, yielding a total of 26 articles in the final analysis. Of these 26 studies, 16 had a significant relationship between anxiety outcome measure and either presence or severity of FOG. There was great variability among studies in terms of outcome measures for both FOG and anxiety. Despite this heterogeneity, most studies relate anxiety and FOG. Standardized, high-validity outcome measures of anxiety and FOG are needed. Future exploration should aim to clarify the role of anxiety in FOG as a causal factor, pathophysiological marker, and manifestation of a common pathophysiological process versus a consequence of FOG itself. Clarifying the relationship between anxiety and FOG could reveal anxiety reduction as a therapy for FOG

Low-Energy Effective Action in Non-Perturbative Electrodynamics in Curved Spacetime

We study the heat kernel for the Laplace type partial differential operator acting on smooth sections of a complex spin-tensor bundle over a generic $n$-dimensional Riemannian manifold. Assuming that the curvature of the U(1) connection (that we call the electromagnetic field) is constant we compute the first two coefficients of the non-perturbative asymptotic expansion of the heat kernel which are of zero and the first order in Riemannian curvature and of arbitrary order in the electromagnetic field. We apply these results to the study of the effective action in non-perturbative electrodynamics in four dimensions and derive a generalization of the Schwinger's result for the creation of scalar and spinor particles in electromagnetic field induced by the gravitational field. We discover a new infrared divergence in the imaginary part of the effective action due to the gravitational corrections, which seems to be a new physical effect.Comment: LaTeX, 42 page

Effect of inoculants of different composition on the quality of rye silages harvested at different stages of maturity

Winter rye (Secale cereale L.), one of the small-grain winter annuals, can be used as a cover crop for protection against soil erosion for absorption of unused soil nitrogen, and for cattle feed by preserving as silage. The experiment was conducted with the objective to evaluate the potential of the blend of homofermentative and hetero- and homofermentative lactic acid bacteria (LAB) as a rye silage additive. Early-cut rye (at boot stage, wilted) and whole-crop rye (at milk and soft dough stages of grain) were ensiled in laboratory mini-silos with (1) a blend of homofermentative LAB strains containing Lactobacillus plantarum (DSM26571), Enterococcus faecium (DSM22502), and Lactococcus lactis (NCIMB30117), (2) a blend of hetero- and homofermentative LAB strains containing Lactobacillus plantarum (DSM26571), Enterococcus faecium (DSM22502), and Lactobacillus buchneri (DSM22501), or (3) a blend of hetero- and homofermentative LAB strains containing Lactobacillus buchneri (DSM22501) and Lactococcus lactis (DSM11037). They were compared to ensiling without additive. After 60 days of fermentation at room temperature, mini-silos were opened, sampled for proximate analysis, forage hygiene, fermentation profile, and subjected to an aerobic stability (AS) test. Although the addition of homofermentative LAB strains was effective in reducing fermentation losses, it impaired the aerobic stability of rye silages. The combination of hetero- and homofermentative LAB strains was effective in reducing the aerobic deterioration of the rye silages by supporting a low pH value and inhibiting the proliferation of yeast and moulds

Gauged Gravity via Spectral Asymptotics of non-Laplace type Operators

We construct invariant differential operators acting on sections of vector bundles of densities over a smooth manifold without using a Riemannian metric. The spectral invariants of such operators are invariant under both the diffeomorphisms and the gauge transformations and can be used to induce a new theory of gravitation. It can be viewed as a matrix generalization of Einstein general relativity that reproduces the standard Einstein theory in the weak deformation limit. Relations with various mathematical constructions such as Finsler geometry and Hodge-de Rham theory are discussed.Comment: Version accepted by J. High Energy Phys. Introduction and Discussion significantly expanded. References added and updated. (41 pages, LaTeX: JHEP3 class, no figures

Evidence of a high incidence of subclinically affected calves in a herd of cattle with fatal cases of Bovine Neonatal Pancytopenia (BNP).

BACKGROUND: Bovine Neonatal Pancytopenia (BNP) is a disease of calves characterised by bone marrow trilineage hypoplasia, mediated by ingestion of alloantibodies in colostrum. Suspected subclinical forms of BNP have been reported, suggesting that observed clinical cases may not represent the full extent of the disease. However to date there are no objective data available on the incidence of subclinical disease or its temporal distribution. This study aimed to 1) ascertain whether subclinical BNP occurs and, if so, to determine the incidence on an affected farm and 2) determine whether there is evidence of temporal clustering of BNP cases on this farm. To achieve these aims, haematological screening of calves born on the farm during one calving season was carried out, utilising blood samples collected at defined ages. These data were then analysed in comparison to data from both known BNP-free control animals and histopathologically confirmed BNP cases. An ordinal logistic regression model was used to create a composite haematology score to predict the probabilities of calves being normal, based on their haematology measurements at 10–14 days old. RESULTS: This study revealed that 15% (21 of 139) of the clinically normal calves on this farm had profoundly abnormal haematology (<5% chance of being normal) and could be defined as affected by subclinical BNP. Together with clinical BNP cases, this gave the study farm a BNP incidence of 18%. Calves with BNP were found to be distributed throughout the calving period, with no clustering, and no significant differences in the date of birth of cases or subclinical cases were found compared to the rest of the calves. This study did not find any evidence of increased mortality or increased time from birth to sale in subclinical BNP calves but, as the study only involved a single farm and adverse effects may be determined by other inter-current diseases it remains possible that subclinical BNP has a detrimental impact on the health and productivity of calves under certain circumstances. CONCLUSIONS: Subclinical BNP was found to occur at a high incidence in a herd of cattle with fatal cases of BNP

Cytotoxicity evaluation of haloperidol, clozapine and a new molecule with antipsychotic potential, PT-31, in NIH-3T3 cells

Schizophrenia is an illness that affects 26 million people worldwide. However, conventional antipsychotics present side effects and toxicity, highlighting the need for new antipsychotics. We aimed to evaluate the cytotoxicity of haloperidol (HAL), clozapine (CLO), and a new molecule with antipsychotic potential, PT-31, in NIH-3T3 cells. The neutral red uptake assay and the MTT assay were performed to evaluate cell viability and mitochondrial activity, morphological changes were assessed, and intracellular reactive oxygen species (ROS) detection was performed. HAL and CLO (0.1 μM) showed a decrease in cell viability in the neutral red uptake assay and in the MTT assay. In addition, cell detachment, content decrease, rounding and cell death were also observed at 0.1 μM for both antipsychotics. An increase in ROS was observed for HAL (0.001, 0.01 and 1 μM) and CLO (0.01 and 1 μM). PT-31 did not alter cell viability in any of the assays, although it increased ROS at 0.01 and 1 μM. HAL and CLO present cytotoxicity at 0.1 μM, possibly through apoptosis and necrosis. In contrast, PT-31 does not present cytotoxicity to NIH-3T3 cells. Further studies must be performed for a better understanding of these mechanisms and the potential risk of conventional antipsychotics

Epigenetic effects of the continuous exposure to peroxisome proliferator WY-14,643 in mouse liver are dependent upon peroxisome proliferator activated receptor α

Peroxisome proliferators are potent rodent liver carcinogens that act via a non-genotoxic mechanism. The mode of action of these agents in rodent liver includes increased cell proliferation, decreased apoptosis, secondary oxidative stress and other events; however, it is not well understood how peroxisome proliferators are triggering the plethora of the molecular signals leading to cancer. Epigenetic changes have been implicated in the mechanism of liver carcinogenesis by a number of environmental agents. Short-term treatment with peroxisome proliferators and other non-genotoxic carcinogens leads to global and locus-specific DNA hypomethylation in mouse liver, events that were suggested to correlate with a burst of cell proliferation. In the current study, we investigated the effects of long-term exposure to a model peroxisome proliferator WY-14,643 on DNA and histone methylation. Male SV129 mice were fed a control or WY-14,643-containing (1000 ppm) diet for 1 wk, 5 wks or 5 months. Treatment with WY-14,643 led to progressive global hypomethylation of liver DNA as determined by an HpaII-based cytosine extension assay with the maximum effect reaching over 200% at 5 months. Likewise, trimethylation of histone H4 lysine 20 and H3 lysine 9 was significantly decreased at all time points. The majority of cytosine methylation in mammals resides in repetitive DNA sequences. In view of this, we measured the effect of WY-14,643 on the methylation status of major and minor satellites, as well as in IAP, LINE1 and LINE2 elements in liver DNA. Exposure to WY-14,643 resulted in a gradual loss of cytosine methylation in major and minor satellites, IAP, LINE1 and LINE2 elements. The epigenetic changes correlated with the temporal effects of WY-14,643 on cell proliferation rates in liver, but no sustained effect on c-Myc promoter methylation was observed. Finally, WY-14,643 had no effect on DNA and histone methylation status in Pparα-null mice at any of the time points considered in this study. These data indicate the importance of epigenetic alterations in the mechanism of action of peroxisome proliferators and the key role of PPARα

Non-commutative Corrections in Spectral Matrix Gravity

We study a non-commutative deformation of general relativity based on spectral invariants of a partial differential operator acting on sections of a vector bundle over a smooth manifold. We compute the first non-commutative corrections to Einstein equations in the weak deformation limit and analyze the spectrum of the theory. Related topics are discussed as well.Comment: 32 Pages, LaTex. Some nonessential typos in intermediate calculations in sect. 3 and 4 are corrected. The final results are the sam

The impact of negative selection on thymocyte migration in the medulla

Developing thymocytes are screened for self-reactivity before they exit the thymus, but how thymocytes scan the medulla for self antigens is unclear. Using two-photon microscopy, we observed that medullary thymocytes migrated rapidly and made frequent, transient contacts with dendritic cells. In the presence of a negative selecting ligand, thymocytes slowed, became confined to areas of approximately 30 mum in diameter and had increased contact with dendritic cells surrounding confinement zones. One third of polyclonal medullary thymocytes also showed confined, slower migration and may correspond to autoreactive thymocytes. Our data suggest that many autoreactive thymocytes do not undergo immediate arrest and death after encountering a negative selecting ligand but instead adopt an altered migration program while remaining in the medullary microenvironment