Possible Treatment of Parkinson's Disease with Intrathecal Medication in the MPTP Model

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73916/1/j.1749-6632.1988.tb31828.x.pd

Effects of N-acetyl-seryl-asparyl-lysyl-proline on blood pressure, renal damage, and mortality in systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is an autoimmune disease with a high prevalence of hypertension. NZBWF1 (SLE-Hyp) mice develop hypertension that can be prevented by modulating T cells. The peptide N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) decreases renal damage and improves renal function in a model of SLE without hypertension (MRL/lpr). However, it is not known whether Ac-SDKP prevents hypertension in NZBWF1 mice. We hypothesized that in SLE-Hyp, Ac-SDKP prevents hypertension and renal damage by modulating T cells. Animals were divided into four groups: (1) control + vehicle, (2) control + Ac-SDKP, (3) SLE + vehicle, and (4) SLE + Ac-SDKP Systolic blood pressure (SBP), albuminuria, renal fibrosis, and T-cell phenotype were analyzed. SBP was higher in SLE compared to control mice and was not decreased by Ac-SDKP treatment. Half of SLE mice developed an acute and severe form of hypertension accompanied by albuminuria followed by death. Ac-SDKP delayed development of severe hypertension, albuminuria, and early mortality, but this delay did not reach statistical significance. Ac-SDKP prevented glomerulosclerosis, but not interstitial fibrosis in SLE-Hyp mice. SLE-Hyp mice showed a decrease in helper and cytotoxic T cells as well as an increase in double negative lymphocytes and T helper 17 cells, but these cells were unaffected by Ac-SDKP In conclusion, Ac-SDKP prevents kidney damage, without affecting blood pressure in an SLE animal model. However, during the acute relapse of SLE, Ac-SDKP might also delay the manifestation of an acute and severe form of hypertension leading to early mortality. Ac-SDKP is a potential tool to treat renal damage in SLE-Hyp mice

The modulating effect of education on semantic interference during healthy aging

Aging has traditionally been related to impairments in name retrieval. These impairments have usually been explained by a phonological transmission deficit hypothesis or by an inhibitory deficit hypothesis. This decline can, however, be modulated by the educational level of the sample. This study analyzed the possible role of these approaches in explaining both object and face naming impairments during aging. Older adults with low and high educational level and young adults with high educational level were asked to repeatedly name objects or famous people using the semantic-blocking paradigm. We compared naming when exemplars were presented in a semantically homogeneous or in a semantically heterogeneous context. Results revealed significantly slower rates of both face and object naming in the homogeneous context (i.e., semantic interference), with a stronger effect for face naming. Interestingly, the group of older adults with a lower educational level showed an increased semantic interference effect during face naming. These findings suggest the joint work of the two mechanisms proposed to explain age-related naming difficulties, i.e., the inhibitory deficit and the transmission deficit hypothesis. Therefore, the stronger vulnerability to semantic interference in the lower educated older adult sample would possibly point to a failure in the inhibitory mechanisms in charge of interference resolution, as proposed by the inhibitory deficit hypothesis. In addition, the fact that this interference effect was mainly restricted to face naming and not to object naming would be consistent with the increased age-related difficulties during proper name retrieval, as suggested by the transmission deficit hypothesis.This research was supported by grants PSI2013-46033-P to A.M., PSI2015-65502-C2-1-P to M.T.B., PCIN-2015-165-C02-01 to D.P., PSI2017-89324-C2-1-P to DP from the Spanish Ministry of Economy and Competitiveness (http://www.mineco.gob.es/)

Reclaiming the local in EU peacebuilding: Effectiveness, ownership, and resistance

Since the early 2000s, the "local turn" has thoroughly transformed the field of peacebuilding. The European Union (EU) policy discourse on peacebuilding has also aligned with this trend, with an increasing number of EU policy statements insisting on the importance of "the local." However, most studies on EU peacebuilding still adopt a top-down approach and focus on institutions, capabilities, and decision-making at the EU level. This special issue contributes to the literature by focusing on bottom-up and local dynamics of EU peacebuilding. After outlining the rationale and the scope of the special issue, this article discusses the local turn in international peacebuilding and identifies several interrelated concepts relevant to theorizing the role of the local, specifically those of effectiveness, ownership, and resistance. In the conclusion, we summarize the key contributions of this special issue and suggest some avenues for further research

The Father, the Son and the Holy Ghost:A Grounded Theory approach to the comparative study of decision-making in the NAC and PSC

Studies of the relationship between the EU and NATO often focus on the limitations of cooperation, be it at the political or the operational level. However, little is known about the functioning of the political institutional linkages between the EU and NATO. This article therefore studies the main decision-making bodies of the two organisations at the political, ambassadorial level, namely the Political and Security Committee (PSC) of the EU and the North Atlantic Council (NAC) in NATO, as well as their joint meetings. The article employs an inductive Grounded Theory approach, drawing on open-ended interviews with PSC and NAC ambassadors, which reveal direct insights from the objects of analysis. The findings emphasise the impact of both structural and more agency-related categories on decision-making in these three fora. The article thus addresses both the paucity of study on these bodies more broadly and the complete lacuna on joint PSC–NAC meetings specifically, warranting the inductive approach this article endorses

Genome-wide association study of corticobasal degeneration identifies risk variants shared with progressive supranuclear palsy

Corticobasal degeneration (CBD) is a neurodegenerative disorder affecting movement and cognition, definitively diagnosed only at autopsy. Here, we conduct a genome-wide association study (GWAS) in CBD cases (n = 152) and 3, 311 controls, and 67 CBD cases and 439 controls in a replication stage. Associations with meta-analysis were 17q21 at MAPT (P = 1.42 x 10(-12)),8p12 at lnc-KIF13B-1, a long non-coding RNA (rs643472;P = 3.41 x 10(-8)),and 2p22 at SOS1 (rs963731;P = 1.76 x 10(-7)). Testing for association of CBD with top progressive supranuclear palsy (PSP) GWAS single-nucleotide polymorphisms (SNPs) identified associations at MOBP (3p22;rs1768208;P = 2.07 x 10(-7)) and MAPT H1c (17q21;rs242557;P = 7.91 x 10(-6)). We previously reported SNP/transcript level associations with rs8070723/MAPT, rs242557/MAPT, and rs1768208/MOBP and herein identified association with rs963731/SOS1. We identify new CBD susceptibility loci and show that CBD and PSP share a genetic risk factor other than MAPT at 3p22 MOBP (myelin-associated oligodendrocyte basic protein)

European economic integration and migration in Romania

Considering the recent debates on the benefits of European economic integration, the purpose of this paper is to assess the impact of EU membership on the migration process in the case of Romania. The paper focussed on two directions of research: comparisons with neighbouring countries that are not member or candidates for EU and the explanation of the remittances based on the economic situation in the destination countries. The approach based on comparisons used difference-in-difference estimator as quantitative method, while the approach based on economic factors in destination countries employed mixed-effects models. The results based on these two approaches indicated that Romania did not send more migrants abroad in the period 2002–2017 compared to Ukraine and Republic of Moldova due its EU membership. On the other hand, Romania gained around 2.5 percentage points more remittances due its EU membership compared to Republic of Moldova and Ukraine. However, the unemployment and the GDP per capita in the destination countries are more important determinants of remittances rather than EU membership in the period 2010–2017. The results reveal that the remittances of Romanian migrants are conditioned by labour market issues in the destination countries, the unemployment in host country having a greater impact on remittances compared to GDP per capita and EU membership. It is expected that a future economic crisis will reduce remittances gained by Romania from other EU countries

Paradigmatic or Critical? Resilience as a New Turn in EU Governance for the Neighbourhood

Rising from the margins of EU aid documents, resilience became a centrepiece of the 2016 EU Global Security Strategy, especially in relation to the neighbourhood. While new resilience-thinking may signify another paradigmatic shift in EU modus operandi, the question that emerges is whether it is critical enough to render EU governance a new turn, to make it sustainable? This article argues that in order for resilience-framed governance to become more effective, the EU needs not just engage with ‘the local’ by way of externally enabling their communal capacity. More crucially, the EU needs to understand resilience for what it is – a self-governing project – to allow ‘the local’ an opportunity to grow their own critical infrastructures and collective agency, in their pursuit of ‘good life’. Is the EU ready for this new thinking, and not just rhetorically or even methodologically when creating new instruments and subjectivities? The bigger question is whether the EU is prepared to critically turn the corner of its neoliberal agenda to accommodate emergent collective rationalities of self-governance as a key to make its peace-building project more successful

Effect of SGLT2 inhibitors on stroke and atrial fibrillation in diabetic kidney disease: Results from the CREDENCE trial and meta-analysis

BACKGROUND AND PURPOSE: Chronic kidney disease with reduced estimated glomerular filtration rate or elevated albuminuria increases risk for ischemic and hemorrhagic stroke. This study assessed the effects of sodium glucose cotransporter 2 inhibitors (SGLT2i) on stroke and atrial fibrillation/flutter (AF/AFL) from CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation) and a meta-Analysis of large cardiovascular outcome trials (CVOTs) of SGLT2i in type 2 diabetes mellitus. METHODS: CREDENCE randomized 4401 participants with type 2 diabetes mellitus and chronic kidney disease to canagliflozin or placebo. Post hoc, we estimated effects on fatal or nonfatal stroke, stroke subtypes, and intermediate markers of stroke risk including AF/AFL. Stroke and AF/AFL data from 3 other completed large CVOTs and CREDENCE were pooled using random-effects meta-Analysis. RESULTS: In CREDENCE, 142 participants experienced a stroke during follow-up (10.9/1000 patient-years with canagliflozin, 14.2/1000 patient-years with placebo; hazard ratio [HR], 0.77 [95% CI, 0.55-1.08]). Effects by stroke subtypes were: ischemic (HR, 0.88 [95% CI, 0.61-1.28]; n=111), hemorrhagic (HR, 0.50 [95% CI, 0.19-1.32]; n=18), and undetermined (HR, 0.54 [95% CI, 0.20-1.46]; n=17). There was no clear effect on AF/AFL (HR, 0.76 [95% CI, 0.53-1.10]; n=115). The overall effects in the 4 CVOTs combined were: Total stroke (HRpooled, 0.96 [95% CI, 0.82-1.12]), ischemic stroke (HRpooled, 1.01 [95% CI, 0.89-1.14]), hemorrhagic stroke (HRpooled, 0.50 [95% CI, 0.30-0.83]), undetermined stroke (HRpooled, 0.86 [95% CI, 0.49-1.51]), and AF/AFL (HRpooled, 0.81 [95% CI, 0.71-0.93]). There was evidence that SGLT2i effects on total stroke varied by baseline estimated glomerular filtration rate (P=0.01), with protection in the lowest estimated glomerular filtration rate (45 mL/min/1.73 m2]) subgroup (HRpooled, 0.50 [95% CI, 0.31-0.79]). CONCLUSIONS: Although we found no clear effect of SGLT2i on total stroke in CREDENCE or across trials combined, there was some evidence of benefit in preventing hemorrhagic stroke and AF/AFL, as well as total stroke for those with lowest estimated glomerular filtration rate. Future research should focus on confirming these data and exploring potential mechanisms