Antineuroinflammatory drugs in HIV-associated neurocognitive disorders as potential therapy.

Today, HIV-infected (HIV+) patients can be treated efficiently with combined antiretroviral therapy (cART), leading to long-term suppression of viral load, in turn increasing life expectancy. While cART reduced the occurrence of HIV-associated dementia, the prevalence of subtle forms of HIV-associated neurocognitive disorders (HAND) is unchanged. This is related to persistent immune activation within the CNS, which is not addressed by cART. Pathologic processes leading to HAND consist of the release of proinflammatory cytokines, chemokines, reactive oxygen metabolites and glutamate, and the release of HIV proteins. Some of those processes can be targeted using medications with immunomodulatory and neuroprotective properties such as dimethyl fumarate, teriflunomide, or minocycline. In this review, we will summarize the knowledge about key pathogenic processes involved in HAND and potential therapeutic avenues to target HAND

On the universality of the xx and AA dependence of the EMC effect and its relation to parton distributions in nuclei

It is shown that the latest results from the NMC (CERN) and E665 (Fermilab) groups on $F_2^A(x)/F_2^D(x)$ obtained in the shadowing region bring new evidence of the universal $A$ dependence of distortions made in a free-nucleon structure function by a nuclear medium. The observed universality implies that one can consider separately hard ($A\leq$ 4) and soft ($A>$ 4) parton distribution distortions. Soft distortions, which result in differencies between the deep-inelastic scattering cross-sections for nuclei with masses $A_1$, $A_2 \geq$ 4, can be explained as a consequence of the nuclear density variation, independent of $x$ in the range 0.001 $\leq x \leq$ 0.7. It is found that nuclear shadowing begins at $x_{\rm I}$ = 0.0615 $\pm$ 0.0024, independent of $A$, which is consistent with models that allow for three-parton recombination processes.Comment: 11 pages (LaTeX) and 4 Postscript figures in uuencoded compressed fil

Analisis Faktor-Faktor yang Memengaruhi Tingkat Kepatuhan Wajib Pajak Orang Pribadi di Lingkungan Kantor Pelayanan Pajak Pratama, Tigaraksa Tangerang

Tax collection is not an easy matter. Active participation from the tax authorities also requires the willingness of the taxpayer. A public reaction can be seen from the taxpayer\u27s willingness to pay taxes. Willingness and awareness to pay taxes represent a value contributed by someone (which has been determined by regulation). Tax is used to finance public expenditures without any direct benefit. Taxpayer\u27s awareness about taxation functions as state funding is needed to improve tax compliance and to determine the level of tax compliance in implementing their tax obligations. Limitation of the scope of this study is the effect of the level of awareness of paying taxes, taxpayer\u27s understanding about tax benefits, tax penalties, and understanding of service quality to the tax authorities of individual taxpayer compliance in the fulfillment of tax obligations, as well as restricted to data obtained through questionnaires received and filled by the individual taxpayer of Tigaraksa Pratama Tax Office area. Data were obtained through questionnaire and processed and analyzed using parametric statistical tests and multiple linear regression with 4 independent variables and one dependent variable resulted in the conclusion that the factors that most influence taxpayer compliance in carrying out its tax liability is the use of sanctions against taxpayers who do not carry out its obligations under applicable legislation

Autologous haematopoietic stem cell transplantation for multiple sclerosis: a position paper and registry outline

Background: While substantial progress has been made in the development of disease-modifying medications for multiple sclerosis (MS), a high percentage of treated patients still show progression and persistent inflammatory activity. Autologous haematopoietic stem cell transplantation (AHSCT) aims at eliminating a pathogenic immune repertoire through intense short-term immunosuppression that enables subsequent regeneration of a new and healthy immune system to re-establish immune tolerance for a long period of time. A number of mostly open-label, uncontrolled studies conducted over the past 20 years collected about 4000 cases. They uniformly reported high efficacy of AHSCT in controlling MS inflammatory disease activity, more markedly beneficial in relapsing-remitting MS. Immunological studies provided evidence for qualitative immune resetting following AHSCT. These data and improved safety profiles of transplantation procedures spurred interest in using AHSCT as a treatment option for MS. Objective: To develop expert consensus recommendations on AHSCT in Germany and outline a registry study project. Methods: An open call among MS neurologists as well as among experts in stem cell transplantation in Germany started in December 2021 to join a series of virtual meetings. Results: We provide a consensus-based opinion paper authored by 25 experts on the up-to-date optimal use of AHSCT in managing MS based on the Swiss criteria. Current data indicate that patients who are most likely to benefit from AHSCT have relapsing-remitting MS and are young, ambulatory and have high disease activity. Treatment data with AHSCT will be collected within the German REgistry Cohort of autologous haematopoietic stem CeLl trAnsplantation In MS (RECLAIM). Conclusion: Further clinical trials, including registry-based analyses, are urgently needed to better define the patient characteristics, efficacy and safety profile of AHSCT compared with other high-efficacy therapies and to optimally position it as a treatment option in different MS disease stages. Keywords: Autologous haematopoietic stem cell transplantation (AHSCT), multiple sclerosis, registry study, treatment recommendation

CMS physics technical design report : Addendum on high density QCD with heavy ions

Peer reviewe

Letter to the editor regarding Gholamzad et al., “A comprehensive review on the treatment approaches of multiple sclerosis: currently and in the future”

Background!#!Endovascular treatment can be a fast and safe option in the case of acute, internal bleeding - but it requires special knowledge and technical skills. Interventionalists must consider the anatomy and potential complications. As in this case report, the anterior spinal artery, for example, can be a crucial vessel that must always be considered when embolizing intercostal or lumbar arteries. The risk of spinal ischemia has to be taken into account and should be minimized by choosing the appropriate treatment option.!##!Case presentation!#!We report about a 77 year old, male patient with upper gastrointestinal bleeding after esophagectomy and gastric conduit reconstruction. A CT scan identified a pseudoaneurysm of an intercostal artery penetrating the gastric conduit as the bleeding source. In the DSA, a direct connection between the intercostal artery and the anterior spinal artery appeared to be likely. Due to the associated risk of spinal ischemia, an embolization of the intercostal artery was not an option. We decided to implant a stentgraft that would stop the perfusion of the pseudoaneurysm, but preserve the perfusion of the intercostal artery. Due to the small diameter of the vessel, we could not implant our commonly used stentgrafts in this case. Therefore, we chose an uncommon solution and used a stentgraft that is designed primarily for coronary arteries.!##!Conclusions!#!Whenever intercostal or lumbar arteries need to be embolized, a possible connection to the anterior spinal artery must be considered and interventionalists have to be aware of possible ischemic complications. In this case, a stentgraft designed primarily for coronary arteries offered a good endovascular treatment option for the pseudoaneurysm of an intercostal artery. The risk of spinal ischemia could be minimized by using this stentgraft

Die Pathogenese der HIV-Demenz

Trotz hoch aktiver antiretroviraler Therapie ist die Prävalenz von HIV-assoziierten neurokognitiven Störungen hoch. Die "Bystander Hypothese" postuliert mikroglial vermittelte Neurotoxizität unabhängig von viraler Replikation und Viruslast im Zentralnervensystem. Um dies zu untersuchen wurde ein Zellkulturmodell basierend auf primärer humaner Mikroglia und HIV-Partikel infizierten monozytären Zellen entwickelt. Als virale Determinanten mikroglialer Aktivierung wurden die frühen Schritte der Infektion und die Anwesenheit von viraler RNA im monozytären Zytosol identifiziert. Die Expression weiterer HIV-kodierter Gene hatte keinen verstärkenden Einfluss auf mikrogliale Aktivierung. Die funktionelle Relevanz entsprechender Zytokine wurde durch eine positive Korrelation mit Neurofilament H in Liquor cerebrospinalis von neurokognitiv asymptomatischen HIV-positiven Patienten bestätigt. Dies trägt zu einem tieferen Verständnis der inflammatorischen Vorgänge von Mikroglia in diesem Kontext bei

Positive effect of immunomodulatory therapies on disease progression in Huntington’s disease? Data from a real-world cohort

Background: The role of neuroinflammation and autoimmune processes in neurodegenerative diseases is not fully understood. Activation of microglia with expression of proinflammatory cytokines supports the hypothesis that immune processes may play an important role in the pathophysiology of Huntington’s disease (HD) and thus, immunomodulating therapies might have potential neuroprotective properties. Until now, no disease-modifying therapy (DMT) is available for HD. Objective: The aim of this research was to characterize a cohort of patients suffering from both HD and autoimmune demyelinating diseases of the central nervous system (classified as G35-37 in ICD-10; ADD-CNS) in comparison to HD cases without ADD-CNS. In particular, we were interested to investigate potential modulating effects on disease manifestation and progression of HD over time of prescribed immunomodulating medications (DMT). Methods: We analyzed the course of HD regarding motoric, functional, and cognitive aspects, using longitudinal data of up to 2 years from the worldwide registry study ENROLL-HD. Additional cross-sectional data in the largest cohort worldwide of HD patients was analyzed using demographic and molecular genetic parameters. Data were analyzed using analysis of variance (ANOVA) for cross-sectional and repeated-measures ANOVA for longitudinal parameters in IBM SPSS Statistics V.27. Results: Within the ENROLL-HD database, we investigated N =  21,116 participants and identified n  = 60 participants suffering from ADD-CNS. Molecular, genetic, and demographic data did not differ between groups. The subgroup of n =  32 participants with motor-manifest HD revealed better cognitive performance in five out of eight cognitive tests at baseline with less progression over time in two tests (all p <  0.05). Differentiation between DMT-treated and untreated patients revealed better cognitive and motor performance in the DMT group; those patients, however, tended to be younger. Pre-manifest HD patients simultaneously diagnosed with ADD-CNS ( n =  12) showed lower functional scores and more decline over time when compared with other pre-manifest HD ( p <  0.05). Conclusion: Patients suffering from motor-manifest HD and simultaneously from ADD-CNS have better cognitive capacities compared with other motor-manifest HD patients. Moreover, DMTs might have beneficial effects on progression of neurodegeneration including the motor phenotype. However, this effect might have been biased by younger age in DMT-treated patients. Pre-manifest HD patients showed more functional impairment as expected due to their additional ADD-CNS disease