Lack of tolerance for the anti-dyskinetic effects of 7-nitroindazole, a neuronal nitric oxide synthase inhibitor, in rats

7-Nitroindazole (7-NI) inhibits neuronal nitric oxide synthase in vivo and reduces l-DOPA-induced dyskinesias in a rat model of parkinsonism. The aim of the present study was to determine if the anti-dyskinetic effect of 7-NI was subject to tolerance after repeated treatment and if this drug could interfere with the priming effect of l-DOPA. Adult male Wistar rats (200-250 g) with unilateral depletion of dopamine in the substantia nigra compacta were treated with l-DOPA (30 mg/kg) for 34 days. On the 1st day, 6 rats received ip saline and 6 received ip 7-NI (30 mg/kg) before l-DOPA. From the 2nd to the 26th day, all rats received l-DOPA daily and, from the 27th to the 34th day, they also received 7-NI before l-DOPA. Animals were evaluated before the drug and 1 h after l-DOPA using an abnormal involuntary movement scale and a stepping test. All rats had a similar initial motor deficit. 7-NI decreased abnormal involuntary movement induced by l-DOPA and the effect was maintained during the experiment before 7-NI, median (interquartile interval), day 26: 16.75 (15.88-17.00); day 28: 0.00 (0.00-9.63); day 29: 13.75 (2.25-15.50); day 30: 0.5 (0.00-6.25); day 31: 4.00 (0.00-7.13), and day 34: 0.5 (0.00-14.63), Friedman followed by Wilcoxon test,vs day 26, P < 0.05;. The response to l-DOPA alone was not modified by the use of 7-NI before the first administration of the drug (l-DOPA vs time interaction, F1,10 = 1.5, NS). The data suggest that tolerance to the anti-dyskinetic effects of a neuronal nitric oxide synthase inhibitor does not develop over a short-term period of repeated administration. These observations open a possible new therapeutic approach to motor complications of chronic l-DOPA therapy in patients with Parkinson&#8217;s disease

What do we know about inequalities in nafld distribution and outcomes?: A scoping review

With prevalence high and rising given the close relationship with obesity and diabetes mellitus, non-alcoholic fatty liver disease (NAFLD) is progressively becoming the most common chronic liver condition worldwide. However, little is known about the health inequalities in NAFLD distribution and outcomes. This review aims to analyze health inequalities in NAFLD distribution globally and to assess the health disparities in NAFLD-related outcomes. We conducted a scoping review of global health inequalities in NAFLD distribution and outcomes according to gender/sex, ethnicity/race, and socioeconomic position from PubMed’s inception to May 2021. Ultimately, 20 articles were included in the review, most (75%) of them carried out in the United States. Males were found to have a higher NAFLD prevalence (three articles), while available evidence suggests that women have an overall higher burden of advanced liver disease and complications (four articles), whereas they are less likely to be liver-transplanted once cirrhosis develops (one article). In the US, the Hispanic population had the highest NAFLD prevalence and poorer outcomes (seven articles), whereas Whites had fewer complications than other ethnicities (two articles). Patients with low socioeconomic status had higher NAFLD prevalence (four articles) and a higher likelihood of progression and complications (five articles). In conclusion, globally there is a lack of studies analyzing NAFLD prevalence and outcomes according to various axes of inequality through joint intersectional appraisals, and most studies included in our review were based on the US population. Available evidence suggests that NAFLD distribution and outcomes show large inequalities by social group. Further research on this issue is warranted.Fil: Talens, Mar. Universitat Pompeu Fabra; EspañaFil: Tumas, Natalia. Universitat Pompeu Fabra; España. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones y Estudio sobre Cultura y Sociedad. Centro de Investigaciones de la Facultad de Psicología - Grupo Vinculado CIPSI; Argentina. University Johns Hopkins; Estados UnidosFil: Lazarus, Jeffrey V.. Universidad de Barcelona; EspañaFil: Benach, Joan. Universidad Autónoma de Madrid; España. University Johns Hopkins; Estados Unidos. Universitat Pompeu Fabra; EspañaFil: Pericàs, Juan M.. Universitat Pompeu Fabra; España. University Johns Hopkins; Estados Unidos. Vall d'Hebron Institute for Research; España. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas; Españ

Diagnosing social anxiety in Parkinson’s disease: Characteristics and frequencies according to two diagnostic criteria

BACKGROUND: Studies found inconsistent frequencies of social anxiety disorder (SAD) in Parkinson’s disease (PD) (9.7%-50%). Previous reports did not test the impact of applying DSM-IV restrictive criteria that recommends the exclusion of secondary cases when diagnosing SAD in PD. OBJECTIVE: Our aim is to estimate the frequency of social anxiety according to DSM-IV criteria and according to an inclusive broader approach. Methods: One hundred and ten PD patients were assessed for the presence of SAD using SCID-I, diagnosis of social anxiety were determined according to two different criteria: following and not following DSM-IV recommendation for exclusion of cases though to be secondary to a general medical condition. RESULTS: SAD was present in 34 (31%) of patients, but 17 (15.5%) were secondary to a general medical condition. Patients with SAD were significantly younger, had earlier disease onset, had more severe PD symptoms, and were more frequently depressed. There was no difference in demographic and clinical features between primary and secondary SAD. DISCUSSION: We conclude that the use of different diagnostic criteria may have a massive impact in the estimation of frequency of SAD in PD

Regional variations in diffuse nitrogen losses from agriculture in the Nordic and Baltic regions

International audienceThis paper describes nitrogen losses from, and the characteristics of, 35 selected catchments (12 to 2000 ha) in the Nordic and Baltic countries. Average annual losses of N in 1994?1997 ranged from 5 to 75 kg ha-1, generally highest and characterised by significant within-country and interannual variations, in Norway and the lowest losses were observed in the Baltic countries. An important finding of the study is that the average nutrient losses varied greatly among the studied catchments. The main explanations for this variability were water runoff, fertiliser use (especially the amount of manure), soil type and erosion (including stream bank erosion). However, there were several exceptions, and it was difficult to find general relationships between the individual factors. For example, there was poor correlation between nitrogen losses and surpluses. Therefore, the results suggest that the observed variability in N losses cannot have been due solely to differences in farm management practices, although the studied catchments do include a wide range of nutrient application levels, animal densities and other relevant elements. There is considerable spatial variation in the physical properties (soil, climate, hydrology, and topography) and the agricultural management of the basins, and the interaction between and relative effects of these factors has an important impact on erosion and nutrient losses. In particular, hydrological processes may have a marked effect on N losses measured in the catchment stream water. The results indicate that significant differences in hydrological pathways (e.g. the relationship between fast- and slow-flow processes) lead to major regional differences in N inputs to surface waters and therefore also in the response to changes in field management practices. Agricultural practices such as crop rotation systems, nutrient inputs and soil conservation measures obviously play a significant role in the site-specific effects, although they cannot explain the large regional differences observed in this study. The interactions between agricultural practices and basic catchment characteristics, including hydrological processes, determine the final losses of nitrogen to surface waters, hence it is necessary to understand these interactions to manage diffuse losses of agricultural nutrients efficiently. Keywords: agriculture, catchments, diffuse sources, nitrogen, losses, Baltic, Nordi

"high Doses Of Riboflavin And The Elimination Of Dietary Red Meat Promote The Recovery Of Some Motor Functions In Parkinson's Disease Patients. C.g. Coimbra And V.b.c. Junqueira. Brazilian Journal Of Medical And Biological Research, 36: 1409-1417, 2003"

[No abstract available]37912971299Coimbra, C.G., Junqueira, V.B.C., High doses of riboflavin and the elimination of dietary red meat promote the recovery of some motor functions in Parkinson's disease patients (2003) Brazilian Journal of Medical and Biological Research, 36, pp. 1409-1417Pare, S., Burr, S.I., Ross, S.E., Effect of day-time protein restriction on nutrient intakes of free-living Parkinson's disease patients (1992) American Journal of Clinical Nutrition, 55, pp. 701-707Simon, N., Gantcheva, R., Bruguerolle, B., Viallet, F., The effects of a normal protein diet on levodopa plasma kinetics in advanced Parkinson's disease (2004) Parkinsonism and Related Disorders, 10, pp. 137-142Fahn, S., Elton, R.L., Unified Parkinson's Disease Rating Scale (1987) Recent Developments in Parkinson's Disease, 2, pp. 153-164. , Members of the UPDRS Development Committee Fahn S, Marsden CD, Calne DB & Goldstein M (Editors), MacMillan Health Care Information, Florham Park, NJ, USABaldereschi, M., DiCarlo, A., Vanni, P., Ghetti, A., Carbonin, P., Amaducci, L., Inzitani, D., Italian longitudinal study on aging working group. Lifestyle related risk factors for Parkinson's disease: A populational study (2003) Acta Neurologica Scandinavica, 108, pp. 239-244Tsai, C.H., Lo, S.K., See, L.C., Chen, H.Z., Chen, R.S., Weng, Y.H., Chang, F.C., Lu, C.S., Environmental risk factors of young onset Parkinson's disease (2002) Clinical Neurology and Neurosurgery, 104, pp. 328-333Tanner, C.M., Epidemiological clues to the cause of Parkinson's disease (1994) Movement Disorders 3, pp. 124-146. , Marsden CD & Fahn S (Editors) Butterworth-Heinemann, Oxford, UKGolbe, L.I., Farrel, T.M., Davis, P.H., Case-control study of early life dietary factors in Parkinson's disease (1988) Archives of Neurology, 45, pp. 350-353Abbot, R.D., Ross, G.W., White, C.R., Sanderson, W.T., Burchfiel, C.M., Kashon, M., Sharp, D.S., Petrovitch, H., Environment, lifestyle, and physical precursors of clinical Parkinson's disease: Recent findings from the Honolulu-Asia aging study (2003) Journal of Neurology, 250 (SUPPL. 3), pp. III30-III3

The Prevalence and Correlation of Non-motor Symptoms in Adult Patients with Idiopathic Focal or Segmental Dystonia

Background: Idiopathic focal dystonia is a motor syndrome associated with dysfunction of basal ganglia circuits. Observations have suggested that many other non-motor symptoms may also be part of the clinical picture. The aim was to assess the prevalence and correlation of non-motor symptoms in patients with common idiopathic focal or segmental dystonia. Methods: In a single-center cross-sectional case–control study, we evaluated the presence of pain, neuropsychiatric symptoms, and sleep alterations in 28 patients with blepharospasm, 28 patients with cervical dystonia, 24 patients with writer’s cramp, and 80 control subjects matched for sex, age, and schooling. We obtained clinical and demographic data, and evaluated patients using the Fahn–Marsden Dystonia Rating Scale and other specific scales for dystonia. All subjects completed the following questionnaires: Beck Depression Inventory, Beck Anxiety Inventory, Social Phobia Inventory, Apathy Scale, Epworth Sleepiness Scale, Pittsburgh Sleep Quality Index, Brief Pain Scale, and the World Health Organization Quality of Life brief scale. Results: The patients presented more symptoms of depression, anxiety, and apathy than the control subjects. They also reported worse quality of sleep and more pain complaints. Patients with blepharospasm were the most symptomatic subgroup. The patients had worse quality of life, and the presence of pain and symptoms of apathy and depression were the main influences for these findings, but not the severity of motor symptoms. Discussion: Patients with dystonia, especially those with blepharospasm, showed higher prevalence of symptoms of depression, anxiety, apathy, worse quality of sleep, and pain. These symptoms had a negative impact on their quality of life

Comparing the short-term memory binding test and RAVLT as predictors of hippocampal atrophy

BACKGROUND: The Rey Auditory Verbal Learning Test (RAVLT) assesses the long-term verbal episodic memory, while the short-term memory binding (STMB) tests assess conjunctive memory binding. In the STMB, participants should remember the integration of shapes (or objects) and colors, forming a unique representation in memory. OBJECTIVE: The objective of this study was to compare the STMB and the RAVLT as predictors of hippocampal atrophy. METHODS: All participants underwent neuropsychological assessment and MRI data were collected. Participants were 17 patients with mild cognitive impairment (MCI) and 12 patients with Alzheimer’s disease (AD). All participants performed the RAVLT test and two different paradigms of the STMB test: change detection and free recall. In the change detection task, patients need to recognize if there was a difference in shapes and colors (unbound) or shape-color integrations (bound) between two consecutive screens. In the free recall task, patients were asked to recall aloud objects and colors individually (unbound condition) or object-color integrations (bound condition) that they had just seen in a screen. The groups were compared using ANCOVA analyses, and regression analyses were used to evaluate which cognitive paradigm better predicted the hippocampal atrophy. RESULTS: 10 patients showed no hippocampal atrophy (all were MCI patients) and 19 had atrophy (7 MCI and 12 AD). The group with atrophy was older and showed worse performance in the cognitive tasks. The regression model using the atrophy (positive or negative) as the dependent variable, and the STMB tasks, RAVLT delayed score, age and education as the predictors, indicated that only the STMB change detection bound task was retained in the model (R = 0.517, R2 = 0.268, p = 0.004), explaining 26,8% of the variance. Present findings suggest that the change detection STMB task may be a better marker of neurodegeneration than the other tests

Perovskite-Inspired Photovoltaic Materials: Toward Best Practices in Materials Characterization and Calculations

Recently, there has been an explosive growth in research based on hybrid lead–halide perovskites for photovoltaics owing to rapid improvements in efficiency. The advent of these materials for solar applications has led to widespread interest in understanding the key enabling properties of these materials. This has resulted in renewed interest in related compounds and a search for materials that may replicate the defect-tolerant properties and long lifetimes of the hybrid lead-halide perovskites. Given the rapid pace of development of the field, the rises in efficiencies of these systems have outpaced the more basic understanding of these materials. Measuring or calculating the basic properties, such as crystal/electronic structure and composition, can be challenging because some of these materials have anisotropic structures, and/or are composed of both heavy metal cations and volatile, mobile, light elements. Some consequences are beam damage during characterization, composition change under vacuum, or compound effects, such as the alteration of the electronic structure through the influence of the substrate. These effects make it challenging to understand the basic properties integral to optoelectronic operation. Compounding these difficulties is the rapid pace with which the field progresses. This has created an ongoing need to continually evaluate best practices with respect to characterization and calculations, as well as to identify inconsistencies in reported values to determine if those inconsistencies are rooted in characterization methodology or materials synthesis. This article describes the difficulties in characterizing hybrid lead–halide perovskites and new materials and how these challenges may be overcome. The topic was discussed at a seminar at the 2015 Materials Research Society Fall Meeting & Exhibit. This article highlights the lessons learned from the seminar and the insights of some of the attendees, with reference to both recent literature and controlled experiments to illustrate the challenges discussed. The focus in this article is on crystallography, composition measurements, photoemission spectroscopy, and calculations on perovskites and new, related absorbers. We suggest how the reporting of the important artifacts could be streamlined between groups to ensure reproducibility as the field progresses

AID-Targeting and Hypermutation of Non-Immunoglobulin Genes Does Not Correlate with Proximity to Immunoglobulin Genes in Germinal Center B Cells

Upon activation, B cells divide, form a germinal center, and express the activation induced deaminase (AID), an enzyme that triggers somatic hypermutation of the variable regions of immunoglobulin (Ig) loci. Recent evidence indicates that at least 25% of expressed genes in germinal center B cells are mutated or deaminated by AID. One of the most deaminated genes, c-Myc, frequently appears as a translocation partner with the Ig heavy chain gene (Igh) in mouse plasmacytomas and human Burkitt's lymphomas. This indicates that the two genes or their double-strand break ends come into close proximity at a biologically relevant frequency. However, the proximity of c-Myc and Igh has never been measured in germinal center B cells, where many such translocations are thought to occur. We hypothesized that in germinal center B cells, not only is c-Myc near Igh, but other mutating non-Ig genes are deaminated by AID because they are near Ig genes, the primary targets of AID. We tested this “collateral damage” model using 3D-fluorescence in situ hybridization (3D-FISH) to measure the distance from non-Ig genes to Ig genes in germinal center B cells. We also made mice transgenic for human MYC and measured expression and mutation of the transgenes. We found that there is no correlation between proximity to Ig genes and levels of AID targeting or gene mutation, and that c-Myc was not closer to Igh than were other non-Ig genes. In addition, the human MYC transgenes did not accumulate mutations and were not deaminated by AID. We conclude that proximity to Ig loci is unlikely to be a major determinant of AID targeting or mutation of non-Ig genes, and that the MYC transgenes are either missing important regulatory elements that allow mutation or are unable to mutate because their new nuclear position is not conducive to AID deamination