Allosteric Modulation of NMDARs Reverses Patients' Autoantibody Effects in Mice

Background and ObjectivesTo demonstrate that an analog (SGE-301) of a brain-derived cholesterol metabolite, 24(S)-hydroxycholesterol, which is a selective positive allosteric modulator (PAM) of NMDA receptors (NMDARs), is able to reverse the memory and synaptic alterations caused by CSF from patients with anti-NMDAR encephalitis in an animal model of passive transfer of antibodies.MethodsFour groups of mice received (days 1–14) patients' or controls' CSF via osmotic pumps connected to the cerebroventricular system and from day 11 were treated with daily subcutaneous injections of SGE-301 or vehicle (no drug). Visuospatial memory, locomotor activity (LA), synaptic NMDAR cluster density, hippocampal long-term potentiation (LTP), and paired-pulse facilitation (PPF) were assessed on days 10, 13, 18, and 26 using reported techniques.ResultsOn day 10, mice infused with patients' CSF, but not controls' CSF, presented a significant visuospatial memory deficit, reduction of NMDAR clusters, and impairment of LTP, whereas LA and PPF were unaffected. These alterations persisted until day 18, the time of maximal deficits in this model. In contrast, mice that received patients' CSF but from day 11 were treated with SGE-301 showed memory recovery (day 13), and on day 18, all paradigms (memory, NMDAR clusters, and LTP) had reversed to values similar to those of controls. On day 26, no differences were observed among experimental groups.DiscussionAn oxysterol biology-based PAM of NMDARs is able to reverse the synaptic and memory deficits caused by CSF from patients with anti-NMDAR encephalitis. These findings suggest a novel adjuvant treatment approach that deserves future clinical evaluation.

Habitability and Hygrothermal Comfort Analysis of Social Housing in Ecuador, Temperate Continental Climatic Zone

Housing sector plays an essential role in the sustainable development of the countries; however, there are significant problems in terms of its ability to access which promotes the occurrence of solutions that guide the housing deficit reduction as well as economic savings and natural resources preservation. One key strategic would be the use of social housing as a mechanism to ensure a decent house accessed by vulnerable population. The general housing design requires satisfying characteristics of indoor environmental comfort, arising the need outlook technical solutions. This research aims to propose functional and hygrothermal improvements for social housing located in a temperate continental climate zone in The Sierra region of Ecuador. The methodology was focused on energy simulations using Design Builder software and comparing the results with the application of passive bioclimatic recommendations. In addition, based on the quantitative housing deficit this research achieves qualitative contributions in order to improve the living conditions of low-income population whose get access to social housing in Ecuador. An experimental case study, located in Azogues a canton of the province of Cañar, has been selected for the simulation analysis which belongs to a housing governmental program named Manuela Espejo promoted by the Ministry of Urban Development and Housing and special designed for people with disabilities. The research has an applicative nature approach, with a sectional scope and explanatory depth, based on primary and secondary information sources; data collection techniques were social perception surveys used to determine comfort levels of the social housing users. The results show, based on the energy simulations carried out, improvements in terms of habitability conditions and an architectural proposal compiles passive bioclimatic recommendations focused on the design of social housing in Ecuador. Therefore, this research contributes to the implementation of new social housing plans that not only would help to reduce the housing deficit, but also contribute to improving the housing indoor environmental comfort perceived by the users.

South Africa finance ministry faces competing pressure

Significance This occurs in a context of market concerns over the recent exits of five senior National Treasury (finance ministry) officials and serious social and economic challenges manifested in high unemployment, inequality and poverty. Impacts Godongwana will resist efforts to create a basic income grant. Higher commodity prices may increase expected revenues, temporarily allowing both increased spending and deficit reduction. Weak results in the November 1 municipal elections may spur greater pressure for more spending.

Effectiveness of neurotropic therapy in the treatment of non-psychotic mental disorders in patients who have suffered a cerebral stroke

The purpose of the study: to clarify the prevalence of non-psychotic mental disorders in the population of patients suffered a cerebral stroke, and to assess the potential use of neurotropic drugs for the correction of certain types of psychopathological syndromes. Materials and methods: 180 patients were examined in the recovery period of brain stroke (the average duration of stroke was 20.7±6.6 months): 78 men and 102 women aged 39 to 90 years (the average age was 64.8±11.2). All patients underwent neuroimaging, experimental psychological research and a psychiatrist’s examination. Results: as a result of the survey, almost all patients in the recovery period of a brain stroke (90.5%) were found non-psychotic mental disorders with a predominance of psychoasthenic syndrome and mnestic-intellectual disorders that develop because of the predomimamt lesion of the brain frontal lobes. As a result of isolated neurotropic therapy, several therapeutic tasks were solved: treatment of focal neurological deficit, reduction of asthenia and the severity of mnestico-intellectual disorders, reduced drug load on the patient. Conclusion: the majority of patients in the recovery period of stroke have various psychopathological disorders, but due to somatic burden can not always receive psychotropic therapy. In this case, it is important to use new approaches to the correction of psychopathological disorders. The use of isolated neurotropic therapy has shown high efficiency in correcting the psychopathological component of stroke, which allows solving several rehabilitation tasks. Research on various aspects of post-stroke mental disorders can help identify additional opportunities for personalized and safe treatment of patients who have suffered acute stroke.

THE EFFECT OF PIR-20 COMPOUND ON COGNITIVE DEFICIT REDUCTION IN EXPERIMENTAL GLOBAL CEREBRAL ISCHEMIA IN RATS

A study was conducted to assess the effect of a new pyrimidine derivative PIR-20 (50 mg/kg) on the development of cognitive deficits in the conditions of global cerebral ischemia in rats. The study was performed on 40 male Wistar rats weighing 200–220 g, divided into 4 groups of 10 individuals. False-operated rats and negative control animals were injected with a suspension of purified water and tween-80, the third group of animals received Cavinton (3,2 mg/kg), the fourth — PIR-20 (50 mg/kg). All test subjects were injected intraperitoneally for ten days prior to surgery. The number of dives increased to 100%, while the decision-making time decreased by 55,2% (p<0,05) in the extrapolation escape test against the background of the PIR-20 compound administration. 75% of the animals treated with PIR-20 did not re-visit the dark compartment, and the time of entering the dark chamber increased by 172,9% (p<0,05) as compared to the group of negative control rats in the test of passive avoidance of the avesir environment. It was confirmed that the studied compound PIR-20 contributes to the improvement of cognitive and mnestic functions, which is confirmed by the results of tests of passive and active aversive environment avoidance. The obtained effect exceeded the results of the control group and the reference drug Cavinton.

Deficits Pro forma and Substantive: Multilevel Policy Implementation in China’s Administrative Approval Intermediaries Reform

Policy implementation deficits tend to emerge and expand as implementation moves downward through multilevel administration. This article uses China as an example and examines its policy implementation at both its provincial and prefectural levels under the administrative intermediaries reform policy. By analyzing data from 225 prefectures in China and their component provinces, we identify two types of implementation deficits: deficits pro forma and substantive deficits. We highlight three factors mitigating both types of deficits and their exacerbation from the provincial level to the prefectural level: self-imposed requirements, top-down pressure, and demonstration effects from upper levels. We find that while self-imposed requirements have no binding effect, rigid executive directives from upper levels have the strongest effect on deficits mitigation while demonstration effects also play an important role in deficit reduction. Our research contributes to the implementation literature by distinguishing between pro forma and substantive deficits and by focusing on the middle layer of government as well as the phenomenon of deficit exacerbation across layers.

Adrenergic Alpha-2 Receptor Antagonists Regulate Noise–induced Metabolic and Cognitive Changes in Rats

Background: Noise is a modern life wide-spread stressor produced by urban traffic and the industrial environment. The noise stress causes central nervous system’s dysfunction and neurotransmission impairment in the brain, as well as changes the hormones levels resulting in psychological and behavioral problems. Underscoring the chronic stress implications, this investigation was to study the level of inositol triphosphate (IP3) in the mitochondrial fraction of the brain (MFB), and α-Tocopherol (α-T) and malondialdehyde (MDA) in the plasma and erythrocytes’ membrane (EM). At the same time, the behavioral characteristics of experimental animals, and the influence of α2-adrenoblockers to evident their modulating effect during noise exposure were studied. Results: The obtained results imply increase of plasma and erythrocytes’ membrane MDA content and decrease in IP3 and α-T and impacted cognitive functions. Conclusion: The use of α2-adrenoblockers to the noise-exposed animals by the specific tests revealed a regulatory effect on the noise time-dependent delay in behavioral activity manifested by disorientation, and the spatial memory deficit. Reduction of the noise impact by α2-adrenoblockers was expressed by less level of MDA and increased level of IP3 and α-T in the plasma and EM, in the 3rd and the 4th groups.

Second COVID wave could stall Macron’s relaunch

Significance However, the second lockdown in October and November, coupled with persistent uncertainty about the pandemic’s trajectory, threatens to undermine the effectiveness of Relaunching France ahead of the 2022 presidential election. Impacts A bleak employment picture would seriously affect Macron’s re-election prospects. Debt and deficit reduction will likely not be reprioritised this side of the 2022 presidential election. Effective and consistent government communication over the COVID-19 vaccine is essential in order to encourage sufficient uptake. A prolonged economic downturn could reignite the Yellow Vest movement and trigger social unrest.

relationship between international trade and immigration policies

This paper concerned is how the Trump administration treats Mexico as Testing Ground in term of trade and immigration two major subjects on which the US president promised a radical policy shift. The main objective of this paper is to demonstrate that the announcement of the new immigration law known as the Reforming American Immigration for Strong Employment (RAISE) and the immigration policy as a whole are the reflection of racism and white supremacy of the Trump administration. the current account deficit between Mexico and the United States has been used as an anchor for the immigration policy. We will also analyze the realistic theory of international relations, according to which, power is at the center of all types of freed trade agreements. We point to these following structural problems (i); the racism and white-nationalism in the Trump administration, (ii) the causes and consequences of power and the degree of exploitation in the trade relationship between Unites States and Mexico, (iii); the Trade deficit reduction of US with NAFTA partners is not a reflect of Fair Play in a World Trade and therefore is unsustainable in the long term, and (iv); The Gross Domestic Product (GDP) growth in the first quarter of 2019 (3.2 percent) of the United States is not the measure of the economy or import tariff, it is a result of a big corporate tax cut which necessarily mean a higher corporate benefits.