The influence of uric acid treatments on liver glutathione system prevent oxidative damages in experimental autoimmune encephalomyelitis mice

Recently we reported that antioxidant system in brain and spinal cord in experimental autoimmune encephalomyelitis (EAE) mice is mainly affected at early stages of the disease [M. Zargari, A. Allameh, M.H. Sanati, T. Tiraihi, S.H. Lavasani, O. Emadyan, Relationship between the clinical scoring and demyelination in central nervous system with total antioxidant capacity of plasma during experimental autoimmune encephalomyelitis development in mice, Neurosci. Lett. 412 (2007), 24–28]. The aim of the present study was to investigate the role of uric acid (UA) on antioxidant system in liver and plasma of EAE mice. EAE was induced in C57/BL6 mice (n = 60), followed by i.p. administration of UA (10 mg/kg BW) in 30 mice at three distinct clinical stages (A: prior to onset, B: after onset, C: after development of EAE). Livers were removed and processed for measurement of lipid peroxidation products, reduced glutathione (GSH), and glutathione S-transferase (GST) and total antioxidant capacity of plasma (FRAP). The results showed that lipid peroxidation products in liver of EAE mice was increased significantly (∼85%) as compared to normal. UA administration to EAE mice caused a significant suppression of liver lipid peroxidation products (∼45%) at early stages (A and B). There was an inverse relationship between lipid peroxidation and cellular GSH in liver. GSH was significantly depleted in mice liver during the EAE progression, but it was recovered (∼29%) when UA was injected before the onset of the disease (groups A and B). Plasma total antioxidant capacity was significantly decreased during the development of EAE, however it was subsided in mice treated with UA as compared to the corresponding controls (21%) in groups A and B. Elevated liver GST as a result of EAE induction was reversed in mice treated with UA particularly in groups A and B. These results indicate that hepatic glutathione system, particularly GST plays a major role in modulation of oxidative damages to central nervous system (CNS) during EAE induction. The positive response of antioxidant system to UA administration in EAE mice was corroborated with improvement of clinical manifestation of the animals.     

Methamphetamine‐induced enhancement of hippocampal long‐term potentiation is modulated by NMDA and GABA receptors in the shell–accumbens

Addictive drugs modulate synaptic transmission in the meso‐corticolimbic system by hijacking normal adaptive forms of experience‐dependent synaptic plasticity. Psychostimulants such as METH have been shown to affect hippocampal synaptic plasticity, albeit with a less understood synaptic mechanism. METH is one of the most addictive drugs that elicit long‐term alterations in the synaptic plasticity in brain areas involved in reinforcement learning and reward processing. Dopamine transporter (DAT) is one of the main targets of METH. As a substrate for DAT, METH decreases dopamine uptake and increases dopamine efflux via the transporter in the target brain regions such as nucleus accumbens (NAc) and hippocampus. Due to cross talk between NAc and hippocampus, stimulation of NAc has been shown to alter hippocampal plasticity. In this study, we tested the hypothesis that manipulation of glutamatergic and GABA‐ergic systems in the shell‐NAc modulates METH‐induced enhancement of long term potentiation (LTP) in the hippocampus. Rats treated with METH (four injections of 5 mg/kg) exhibited enhanced LTP as compared to saline‐treated animals. Intra‐NAc infusion of muscimol (GABA receptor agonist) decreased METH‐induced enhancement of dentate gyrus (DG)‐LTP, while infusion of AP5 (NMDA receptor antagonist) prevented METH‐induced enhancement of LTP. These data support the interpretation that reducing NAc activity can ameliorate METH‐induced hippocampal LTP through a hippocampus‐NAc‐VTA circuit loop. Synapse 70:325–335, 2016 . © 2016 Wiley Periodicals, Inc.     

Examining the consumption of radical content on YouTube

Although it is under-studied relative to other social media platforms, YouTube is arguably the largest and most engaging online media consumption platform in the world. Recently, YouTube’s scale has fueled concerns that YouTube users are being radicalized via a combination of biased recommendations and ostensibly apolitical “anti-woke” channels, both of which have been claimed to direct attention to radical political content. Here we test this hypothesis using a representative panel of more than 300,000 Americans and their individual-level browsing behavior, on and off YouTube, from January 2016 through December 2019. Using a labeled set of political news channels, we find that news consumption on YouTube is dominated by mainstream and largely centrist sources. Consumers of far-right content, while more engaged than average, represent a small and stable percentage of news consumers. However, consumption of “anti-woke” content, defined in terms of its opposition to progressive intellectual and political agendas, grew steadily in popularity and is correlated with consumption of far-right content off-platform. We find no evidence that engagement with far-right content is caused by YouTube recommendations systematically, nor do we find clear evidence that anti-woke channels serve as a gateway to the far right. Rather, consumption of political content on YouTube appears to reflect individual preferences that extend across the web as a whole.

As affective political polarization rises in the United States (1) and trust in traditional sources of authority declines (2, 3), concerns have arisen regarding the presence, prevalence, and impact of false, hyperpartisan, or conspiratorial content on social media platforms. Most research on the potentially polarizing and misleading effects of social media has focused on Facebook and Twitter (4–12), reflecting a common view that these platforms are the most “news-oriented” social media platforms. However, roughly 23 million Americans rely on YouTube as a source of news (13, 14), a number comparable to the corresponding Twitter audience (13, 15), and it is growing in both size and engagement. YouTube news content spans the political spectrum, and includes content producers of all sizes. Recent work (16) has identified a large number of YouTube channels, mostly operated by individuals or small organizations, that promote a collection of “far-right” ideologies (e.g., white identitarian) and conspiracy theories (e.g., QAnon). The popularity of some of these channels, along with salient popular anecdotes, has prompted claims that YouTube’s recommendation engine systematically drives users to this content, and effectively radicalizes its users (17–20). For example, it has been reported that, starting from factual videos about the flu vaccine, the recommender system can lead users to antivaccination conspiracy videos (18).Recent qualitative work (21) has identified a separate collection of channels labeled variously as “reactionary,” “anti-woke” (AW), “anti-social justice warriors” (ASJW), “intellectual dark web” (IDW), or simply “antiestablishment.” Although these channels do not identify themselves as politically conservative, and often position themselves as nonideological or even liberal “free thinkers,” in practice, their positions are largely defined in opposition to progressive social justice movements, especially those concerning identity and race, as well as critiquing institutions such as academia and mainstream media for their “left-wing bias” (21, 22). Concurrently, “anti-woke” rhetoric has increasingly been adopted by mainstream Republican politicians (23), undermining claims that it is intrinsically apolitical. While anti-woke YouTube channels typically do not explicitly endorse far-right ideologies, some channel owners invite guests who are affiliated with the far right onto their shows and allow them to air their views relatively unchallenged, thereby effectively broadcasting and legitimizing far-right ideologies (21). If these channels act as a kind of gateway to the far right, they would constitute a related yet distinct radicalization mechanism from the recommendation system per se (17, 24). Based on these considerations, and recognizing that any label for this loose collection of channels is likely to be inaccurate for at least some members, we refer to them hereafter as anti-woke (AW).Although reports of various mechanisms driving people to politically radical content have received great attention, quantitative evidence to support them has proven elusive. On a platform with almost 2 billion users (25), it is possible to find examples of almost any type of behavior; hence anecdotes of radicalized individuals (17), however vivid, do not, on their own, indicate systematic problems. Thus, the observation that a particular mechanism (e.g., recommendation systems steering users to extreme content; far-right personalities appearing on anti-woke channels acting as gateways to the far right) might plausibly have a large and measurable effect on audiences does not substitute for measuring the effect. Finally, the few empirical studies (24, 26–29) that have examined the question of YouTube radicalization have reached conflicting conclusions, with some finding evidence for it (24, 26) and others finding the opposite (27, 28). These disagreements may arise from methodological differences that make results difficult to fairly compare—for example, ref. 28 examines potential biases in the recommender by simulating logged-out users, whereas ref. 24 reconstructs user histories from scraped comments. The disagreement may also reflect limitations in the available data, which is intrinsically ill suited to measuring either individual or aggregate consumption of different types of content over extended time intervals, such as user sessions or “lifetimes.” Absent such data for a large, representative sample of real YouTube users, it is difficult to evaluate how much far-right content is, in fact, being consumed (vs. produced), how it is changing over time, and to what extent it is being driven by YouTube’s own recommendations, spillovers from anti-woke channels, or other entry points.Here we investigate the consumption of radical political news content on YouTube using a unique dataset comprising a large (N=309,813) representative sample of the US population, and their online browsing histories, both on and off the YouTube platform, spanning 4 years from January 2016 to December 2019. To summarize, we present five main findings. 1) Consistent with previous estimates (30), we find that the total consumption of any news-related content on YouTube accounts for 11% of overall consumption and is dominated by mainstream, and generally centrist or left-leaning, sources. 2) The consumption of far-right content is small in terms of both number of viewers and total watch time, where the former decreased slightly and the latter increased slightly over the observation period. 3) In contrast, the consumption of anti-woke content, while also small relative to mainstream or left-leaning content, grew in both numbers of users and total watch time. 4) The pathways by which users reach far-right videos are diverse, and only a fraction can plausibly be attributed to platform recommendations. Within sessions of consecutive video viewership, we find no trend toward more extreme content, either left or right, indicating that consumption of this content is determined more by user preferences than by recommendation. 5) Consumers of anti-woke, right, and far-right content also consume a meaningful amount of far-right content elsewhere online, indicating that, rather than the platform (either the recommendation engine or consumption of anti-woke content) pushing them toward far-right content, it is a complement to their larger news diet.These results indicate little evidence for the popular claim that YouTube drives users to consume more radical political content, either left or right. Instead, we find strong evidence that, while somewhat unique with its growing and dedicated anti-woke channels, YouTube should otherwise be viewed as part of a larger information ecosystem in which conspiracy theories, misinformation, and hyperpartisan content are widely available, easily discovered, and actively sought out (27, 31).     

The Investigation of Drug Resistance Substitutions in NS3 Protease Sequence of Hepatitis C Virus from Non-Responder Patients

Background: Even with the fantastic successes of direct-acting antivirals (DAA) in the treatment of Hepatitis CVirus (HCV) infection, natural drug resistance remains a challenging obstacle for their impacts. The data regardingprotease inhibitors (PIs) resistance in Iran population are limited. The aim of this study was to investigate the variationsin NS3 protease of HCV from non-responder patients. Methods: In this cross-sectional study, 14 HCV infected patientswith genotype 1(N=5) and 3(N=9) who have not responded to Interferon-related regime were enrolled from LiverClinic, Shiraz. The NS3 protease region was amplified by Nested-PCR followed by product gel extraction. Besides,some amplified protease regions were cloned into a cloning vector to improve the sensitivity of mutation detection.Both crude and cloned sequences were then introduced into sequencing. The obtained sequences were compared withthe NS3 reference sequences and analyzed by Geno2pheno available software to find possible substitutions. In theend, the phylogenetic tree was constructed. Results: Among variations responsible for PIs resistance, only one out of14 (7%) sample who was infected with genotype 1a, harbored R117C+N174S double mutation, which causes reducedsusceptibility to Telaprevir. Any another resistance mutation was not found among the studied population. The mostfrequent substitutions were determined as I52M(N=9), S102A(N=9), S166A(8) and V170I(8) for genotype 3a, andF147S/A(4) for genotype 1. However, some uncharacterized substitutions on scored position, including I132L(N=1),I170V(N=3) and N174S(N=2) were also determined among sequences. Phylogenetic analysis demonstrated that theprotease region has enough power to correctly classify enrolled samples into relevant clusters on the tree. There were 2,3 and 9 cases of sub-genotypes 1a, 1b, and 3a, respectively. Conclusion: A low frequency of PIs resistance mutationsin our HCV infected population is a hopeful point of starting these drugs in HCV infected patients.     

Successful treatment of severe conjunctivitis and blepharitis caused by Escherichia coli in an ostrich (Struthio camelus)

The aim of the present report was to describe the clinical features and antibiotic susceptibility of severe conjunctivitis and blepharitis caused by Escherichia coli in an ostrich. A 2-month-old ostrich chick was presented with a 5-day history of left periocular swellings and severe conjunctivitis and blepharitis. There were no other abnormalities. The bacteria cultured from the pus aspirated from the periocular swellings were identified to be E. coli. Sensitivities were determined by a modified disc diffusion method, and isolates were fully susceptible to ciprofloxacin, co-trimoxazole, gentamicin, amikacin and chloramphenicol. The ostrich was treated by intramuscular ceftriaxone (10 mg/kg) BID for 1 week. The eye was treated with topical 0.3% ciprofloxacin HCl ophthalmic solution for 2 weeks.     

Evaluating the factors associated with pregnancy loss in pregnant women undergoing assisted reproductive techniques

Introduction

Whenever assisted reproductive techniques (ART) leading to successful pregnancy (with live birth), they can be considered useful .This study is aimed at assessing the effect of risk factors associated with the pregnancy loss on pregnancy outcomes in pregnant women undergoing ART.

Successful management of refractory psychomotor seizures with gabapentin and phenobarbital in a Doberman pinscher dog

Gabapentin is a new antiepileptic drug which is used in humans with complex partial epilepsy. Recently, two published studies described the efficacy of gabapentin in dogs with refractory epilepsy. However, clinical application of gabapentin in dogs with refractory psychomotor seizure has not been documented. The present report describes a 2-year-old male Doberman pinscher dog with a history of recurrent bizarre behaviors such as aggression, circling, and flank-biting. Initial oral administration of phenobarbital resulted in resolution of psychomotor seizures, but 3 months after the initial presentation, the dog became refractory to the selected treatment. The treatment was changed to a combination therapy with phenobarbital and gabapentin. Two days after starting the combination therapy, the dog became seizure-free, and there were no detectable signs of previous abnormal behaviors during the 14-month follow-up period.     

Non-alcoholic steatohepatitis and influence of age and gender on histopathologic findings

AIM:To characterize the histopathologic specifications of non-alcoholic steatohepatitis(NASH)according to age and gender.METHODS:An analytical cross-sectional study was conducted in two private gastroenterology clinics on biopsy proven patients suffering from NASH.Biopsy histopathologic findings as well as demographic and laboratory data of the patients at the time of biopsy were gathered retrospectively from clinical records.The grading and staging of histopathologic findings were performed according to th...