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FH through the Retrospectoscope [Thematic Reviews]

Abstract

After training as a gastroenterologist in the UK the author became interested in lipidology while he was a research fellow in the USA and switched careers after returning home. Together with Nick Myant he introduced the use of plasma exchange to treat FH homozygotes and undertook non-steady state studies of LDL kinetics, which showed that the fractional catabolic rate of LDL remained constant irrespective of pool size. Subsequent steady-state turnover studies showed that FH homozygotes had an almost complete lack of receptor-mediated LDL catabolism, providing in vivo confirmation of the Nobel Prize-winning discovery by Goldstein and Brown that LDL receptor dysfunction was the cause of FH. Further investigation of metabolic defects in FH revealed that a significant proportion of LDL in homozygotes and heterozygotes was produced directly via a VLDL-independent pathway.

Management of heterozygous FH has been greatly facilitated by statins and PCSK9 inhibitors but remains dependent upon lipoprotein apheresis in homozygotes. In a recent analysis of a large cohort treated with a combination of lipid-lowering measures survival was markedly enhanced in homozygotes in the lowest quartile of on-treatment serum cholesterol. Emerging therapies could further improve the prognosis of homozygous FH whereas in heterozygotes the current need is better detection.




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The emerging roles of the macular pigment carotenoids throughout the lifespan and in prenatal supplementation [Thematic Reviews]

Since the publication of the Age-Related Eye Disease Study (AREDS2) in 2013, the macular pigment carotenoids lutein and zeaxanthin have become well known to both the eye care community and the public. It is a fascinating aspect of evolution that primates have repurposed photoprotective pigments and binding proteins from plants and insects to protect and enhance visual acuity. Moreover, utilization of these plant-derived nutrients has been widely embraced for preventing vision loss from age-related macular degeneration (AMD). More recently, there has been growing awareness that these nutrients can also play a role in improving visual performance in adults. On the other hand, the potential benefits of lutein and zeaxanthin supplementation at very young ages have been underappreciated. In this review, we examine the biochemical mechanisms and supportive data for lutein and zeaxanthin supplementation throughout the lifespan, with particular emphasis on prenatal supplementation. We propose that prenatal nutritional recommendations may aim at improving maternal and infant carotenoid status. Prenatal supplementation with lutein and zeaxanthin might enhance infant visual development and performance and may even prevent retinopathy of prematurity, possibilities that should be examined in future clinical studies.




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Docosanoid signaling modulates corneal nerve regeneration: effect on tear secretion, wound healing, and neuropathic pain [Thematic Reviews]

The cornea is densely innervated, mainly by sensory nerves of the ophthalmic branch of the trigeminal ganglia (TG). These nerves  are important to maintain corneal homeostasis, and nerve damage can lead to a decrease in wound healing, an increase in corneal ulceration and dry eye disease (DED), and neuropathic pain. Pathologies, such as diabetes, aging, viral and bacterial infection, as well as  prolonged use of contact lenses and surgeries to correct vision can produce nerve damage. There are no effective therapies to alleviate DED (a multifunctional disease) and several clinical trials using -3 supplementation show unclear and sometimes negative results. Using animal models of corneal nerve damage, we show that treating corneas with pigment epithelium-derived factor (PEDF) plus docosahexaenoic acid (DHA) increases nerve regeneration, wound healing, and tear secretion. The mechanism involves the activation of a calcium-independent phospholipase A2 (iPLA2) that releases the incorporated DHA from phospholipids and enhances the synthesis of docosanoids neuroprotectin D1 (NPD1) and a new resolvin stereoisomer  RvD6i. NPD1 stimulates the synthesis of brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), and of semaphorin 7A (Sema7A).  RvD6i treatment of injured corneas modulates gene expression in the TG resulting in enhanced neurogenesis; decreased neuropathic pain and increased sensitivity. Taken together, these results represent a promising therapeutic option to re-establish the homeostasis of the cornea.




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Sphingolipids as Critical Players in Retinal Physiology and Pathology [Thematic Reviews]

Sphingolipids have emerged as bioactive lipids involved in the regulation of many physiological and pathological processes. In the retina, they have been established to participate in numerous processes, such as neuronal survival and death, proliferation and migration of neuronal and vascular cells, inflammation, and neovascularization. Dysregulation of sphingolipids is, therefore, crucial in the onset and progression of retinal diseases. This review examines the involvement of sphingolipids in retinal physiology and diseases. Ceramide (Cer) emerges as a common mediator of inflammation and death of neuronal and retinal pigment epithelium cells in animal models of retinopathies such as glaucoma, age-related macular degeneration (AMD), and retinitis pigmentosa. Sphingosine-1-phosphate (S1P) has opposite roles, preventing photoreceptor and ganglion cell degeneration but also promoting inflammation, fibrosis, and neovascularization in AMD, glaucoma, and pro-fibrotic disorders. Alterations in Cer, S1P, and ceramide-1-phosphate may also contribute to uveitis. Notably, use of inhibitors that either prevent Cer increase or modulate S1P signaling, such as Myriocin, desipramine, and Fingolimod (FTY720), preserves neuronal viability and retinal function. These findings underscore the relevance of alterations in the sphingolipid metabolic network in the etiology of multiple retinopathies and highlight the potential of modulating their metabolism for the design of novel therapeutic approaches.




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Cholesterol homeostasis in the vertebrate retina: Biology and pathobiology [Thematic Reviews]

Cholesterol is a quantitatively and biologically significant constituent of all mammalian cell membrane, including those that comprise the retina. Retinal cholesterol homeostasis entails the interplay between de novo synthesis, uptake, intra-retinal sterol transport, metabolism and efflux. Defects in these complex processes are associated with several congenital and age-related disorders of the visual system. Herein, we provide an overview of the following topics: a) cholesterol synthesis in the neural retina; b) lipoprotein uptake and intraretinal sterol transport in the neural retina and the retinal pigment epithelium (RPE); c) cholesterol efflux from the neural retina and the RPE; and d) biology and pathobiology of defects in sterol synthesis and sterol oxidation in the neural retina and the RPE. We focus, in particular, on studies involving animal models of monogenic disorders pertinent to the above topics, as well as in vitro models using biochemical, metabolic, and omic approaches. We also identify current knowledge gaps as well as opportunities in the field that beg further research in this topic area.




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Overview of how N32 and N34 elovanoids sustain sight by protecting retinal pigment epithelial cells and photoreceptors [Thematic Reviews]

The essential fatty acid DHA (22:6, omega-3 or n-3) is enriched in and required for the membrane biogenesis and function of photoreceptor cells (PRC), synapses, mitochondria, etc. of the CNS. PRC DHA becomes an acyl chain at the sn-2 of phosphatidylcholine (PC), amounting to more than 50% of the PRC outer segment phospholipids, where phototransduction takes place. Very long chain PUFAs (VLC-PUFAs,n-3, ≥ 28 carbons) are at the sn-1 of this PC molecular species and interact with rhodopsin. PRC shed their tips (DHA-rich membrane disks) daily, which in turn are phagocytized by the retinal pigment epithelium (RPE), where DHA is recycled back to PRC inner segments to be used for the biogenesis of new photoreceptor membranes. Here, we review the structures and stereochemistry of novel elovanoid (ELV)-N32 and ELV-N34 to be ELV-N32: (14Z,17Z,20R,21E,23E,25Z,27S,29Z)-20,27-dihydroxydo-triaconta-14,17,21,23,25,29-hexaenoic acid; ELV-N34: (16Z,19Z,22R,23E,25E,27Z,29S,31Z)-22,29-dihydroxytetra-triaconta-16,19,23,25,27,31-hexaenoic acid. ELVs are low-abundance, high-potency, protective mediators. Their bioactivity includes enhancing of anti-apoptotic and pro-survival protein expression with concomitant downregulation of pro-apoptotic proteins when RPE is confronted with uncompensated oxidative stress (UOS). ELVs also target PRC/RPE senescence gene programming, the senescence secretory phenotype in the interphotoreceptor matrix (IPM), as well as inflammaging (chronic, sterile, low-grade inflammation). An important lesson on neuroprotection is highlighted by the ELV mediators that target the terminally differentiated PRC and RPE, sustaining a beautifully synchronized renewal process. The role of ELVs in PRC and RPE viability and function uncovers insights on disease mechanisms and the development of therapeutics for age-related macular degeneration (AMD), Alzheimer’s disease (AD), and other pathologies.




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Lipid metabolism dysregulation in diabetic retinopathy [Thematic Reviews]

Lipid metabolic abnormalities have emerged as potential risk factors for the development and progression of diabetic complications, including diabetic retinopathy (DR).  This review article provides an overview of the results of clinical trials evaluating the potential benefits of lipid lowering drugs, such as fibrates, omega 3 fatty acids, and statins, for the prevention and treatment of DR. Although several clinical trials demonstrated that treatment with fibrates leads to improvement of DR, there is a dissociation between the protective effects of fibrates in the retina, and the intended blood lipid classes, including plasma triglycerides, total cholesterol or HDL/LDL cholesterol ratio. Guided by these findings, plasma lipid and lipoprotein-independent mechanisms are addressed based on clinical, cell culture and animal model studies. Potential retinal-specific effects of fatty acids oxidation products, cholesterol, and ceramide, as well as lipid independent effects of PPAR alpha activation are summarized based on current literature. Overall, this review highlights promising potential of lipid-based treatment strategies further enhanced by the new knowledge of intra-retinal lipids and lipoproteins in DR.




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Chylomicronemia from GPIHBP1 autoantibodies [Reviews]

Some cases of chylomicronemia are caused by autoantibodies against glycosylphosphatidylinositol-anchored HDL binding protein 1 (GPIHBP1), an endothelial cell protein that shuttles LPL to the capillary lumen. GPIHBP1 autoantibodies prevent binding and transport of LPL by GPIHBP1, thereby disrupting the lipolytic processing of triglyceride-rich lipoproteins. Here, we review the "GPIHBP1 autoantibody syndrome" and summarize clinical and laboratory findings in 22 patients. All patients had GPIHBP1 autoantibodies and chylomicronemia, but we did not find a correlation between triglyceride levels and autoantibody levels. Many of the patients had a history of pancreatitis, and most had clinical and/or serological evidence of autoimmune disease. IgA autoantibodies were present in all patients, and IgG4 autoantibodies were present in 19 of 22 patients. Patients with GPIHBP1 autoantibodies had low plasma LPL levels, consistent with impaired delivery of LPL into capillaries. Plasma levels of GPIHBP1, measured with a monoclonal antibody–based ELISA, were very low in 17 patients, reflecting the inability of the ELISA to detect GPIHBP1 in the presence of autoantibodies (immunoassay interference). However, GPIHBP1 levels were very high in five patients, indicating little capacity of their autoantibodies to interfere with the ELISA. Recently, several GPIHBP1 autoantibody syndrome patients were treated successfully with rituximab, resulting in the disappearance of GPIHBP1 autoantibodies and normalization of both plasma triglyceride and LPL levels. The GPIHBP1 autoantibody syndrome should be considered in any patient with newly acquired and unexplained chylomicronemia.




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A review of phosphatidate phosphatase assays [Reviews]

Phosphatidate phosphatase (PAP) catalyzes the penultimate step in the synthesis of triacylglycerol and regulates the synthesis of membrane phospholipids. There is much interest in this enzyme because it controls the cellular levels of its substrate, phosphatidate (PA), and product, DAG; defects in the metabolism of these lipid intermediates are the basis for lipid-based diseases such as obesity, lipodystrophy, and inflammation. The measurement of PAP activity is required for studies aimed at understanding its mechanisms of action, how it is regulated, and for screening its activators and/or inhibitors. Enzyme activity is determined through the use of radioactive and nonradioactive assays that measure the product, DAG, or Pi. However, sensitivity and ease of use are variable across these methods. This review summarizes approaches to synthesize radioactive PA, to analyze radioactive and nonradioactive products, DAG and Pi, and discusses the advantages and disadvantages of each PAP assay.




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Belarusians’ views on the political crisis - April 2021

Belarusians’ views on the political crisis - April 2021 Other resource NCapeling 11 June 2021

Results of a public opinion poll conducted between 20 and 30 April 2021.

Chatham House surveyed a total of 937 respondents between 20 and 30 April 2021. Our survey sample corresponds to the general structure of Belarus’s urban population and is corrected and weighted by gender, age, size of respondents’ town of residence and education level.

Summary

  • After Lukashenka, the most known political figures in Belarus are pro-protest politicians: Tsikhanouskaya, Babaryka, Tsikhanouski, Kalesnikava, Tsapkala and Latushka. Viktar Babaryka is the most popular presidential candidate among Belarusian urban citizens, and Lukashenka comes second to him.
  • State organizations and bodies are still mistrusted by more than half the population, while the army is slightly more popular than other bodies. Independent media, labour unions and human rights organizations are trusted far more than state ones.
  • Russia leads when it comes to positive attitudes to foreign states: one in three Belarusians feel very positive about their neighbour and 79 per cent feel positive in general. 71 per cent Belarusians feel positive about China, which is the next highest indicator. Despite propaganda efforts, Ukraine, Lithuania, Poland and EU states in general are still perceived positively by more than 60 per cent of Belarusians, with fewer than 20 per cent feeling negative about them.
  • The position on Russian interference in the Belarusian political crisis is consolidated enough: 58 per cent think that Russia should remain neutral. The rest are almost equally divided between those who think Russia should support the protest movement (19 per cent) and those who think Russia should support Lukashenka (23 per cent).
  • 40 per cent have changed their attitude to the Russian government since it supported Lukashenka in the crisis, and 73 per cent are sure that Russia is his sole support.
  • While 32 per cent of Belarusians see union with Russia as the most appropriate foreign policy, 46 per cent would like to be in a union with both Russia and the EU simultaneously.
  • Almost half the population thinks that Belarusian foreign policy in the event of a pro-protest government coming to power would be oriented toward friendship and cooperation with both Russia and the West, which correlates with how the majority thinks it should be. Although 42 per cent expect foreign policy would lean toward the EU in that situation, which is less acceptable: only 25 per cent think it ‘should’.
  • The proportion of respondents who think Belarus should remain in the Collective Security Treaty Organization is 58 per cent, while 35 per cent would like to see Belarus not belonging to any military bloc and a small share (seven per cent) would prefer Belarus to join NATO.
  • Almost half of the population considers Lukashenka to be the major obstacle for political stability and economic development and is sure he does not care about, and in fact is a threat to, independence.
  • In general, most Belarusians have a consolidated opinion that the authorities should start negotiating with opponents and free all political prisoners.
  • More than half of Belarusians think that Lukashenka must leave immediately or before the end of 2021, while 27 per cent think he should leave when his term ends in 2025. The opinion that Lukashenka should rule for another term beginning in 2025 is marginal – only ten per cent support this.
  • Expectations are not so optimistic though: only 26 per cent believe he will leave office this year. One in three thinks he will leave in 2025; a further 19 per cent say that he will stay on for further terms in office.
  • If Lukashenka doesn’t leave, people expect an increase in emigration and unemployment, the continuation of repression in all areas of life, falling exchange rates and the tightening of dependency on Russia.
  • Opinion on abortions is still consolidated, with only 19 per cent thinking they should be banned in most or all cases. The same applies to Lukashenka’s infamous statement that society in Belarus is not ready to have a female president: only 20 per cent agree with the opinion.
  • 52 per cent don’t think there is a problem of wage inequality between men and women in Belarus, while 37 per cent do see an issue.

Download a presentation of the survey’s main findings




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Belarusians’ views on the political crisis - Nov 2021

Belarusians’ views on the political crisis - Nov 2021 Other resource NCapeling 20 January 2022

Results of a public opinion poll conducted between 1 and 10 November 2021.

Chatham House surveyed a total of 767 respondents between 1 and 10 November 2021. Our survey sample corresponds to the general structure of Belarus’s urban population and is adjusted by gender, age, education level and the size of respondents’ place of residence.

Summary

  • After Aliaksandr Lukashenka, the most well-known political figures in Belarus are the protest leaders: Sviatlana Tsikhanouskaya, Viktar Babaryka, Siarhei Tsikhanouski, Valery Tsapkala, Marya Kalesnikava and Pavel Latushka.
  • Lukashenka and Babaryka have the highest popularity ratings among Belarus’s urban population. At the same time, Lukashenka has a high negative rating: half of the city residents surveyed say that they would never vote for him. Babaryka has one of the lowest negative ratings in the country.
  • The popularity ratings of pro-government politicians are low, and their negative ratings remain extremely high, although the latter have decreased slightly in comparison with July 2021. The popularity ratings of protest leaders are significantly higher than those of politicians who support the current government.
  • Trust in state and independent organizations is polarized along political lines. Thus, respondents classed as hardcore protesters do not trust state structures and do trust independent ones, while Lukashenka’s supporters hold the opposite positions.
  • Belarusians’ geopolitical orientations remain stable. The most widely preferred option for a geopolitical union is simultaneous integration with the EU and Russia.
  • Belarusians have become increasingly negative about the possibility that Russian airbases could be established on Belarusian territory (48 per cent in November 2021, compared to 39 per cent in July 2021).
  • Belarusians are now feeling more strongly that the situation concerning the COVID-19 pandemic has worsened: in November, more than half were beginning to respond that Belarus is unable to cope with the spread of coronavirus.
  • Sanctions against Lukashenka and those around him are supported more widely than sanctions against state enterprises.
  • Belarusians feel there is acute social tension in their country: almost everyone surveyed states that social tension exists, while one in every five respondents considers the situation catastrophic. A perception that there is social tension is closely related to many factors, with the strongest of all being a sense of a lack of personal safety.
  • Only one-third of Belarusians are prepared to call the state built under Lukashenka their own. Most of the survey respondents do not trust this state to some degree, and do not believe that the state protects the interests of Belarusian citizens.

Download a presentation of the survey’s main findings

Belarusians’ views on the political crisis (PDF)

Взгляды белорусов на политический кризис (PDF)




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Rediscovering School Quality Reviews

Resurrecting an old idea about assessing school quality could allow schools to examine a broad range of data on performance and practices and lead to improvement.





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NASA’s Juno Probe Captures Stunning Views of Jupiter’s Storms and Moon Amalthea

NASA’s Juno probe captured vibrant, high-contrast images of Jupiter’s stormy atmosphere and an up-close view of its moon, Amalthea, during the spacecraft’s 66th flyby on October 23. The images were processed by citizen scientists, enhancing the colours to showcase Jupiter’s unique cloud formations and highlighting details of Amalthea against the backdrop of space. Launched in 2016, Juno’s mission is set to conclude in 2025 with a final dive into Jupiter’s atmosphere.




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Irreconcilable Views of Reconciliation (Voddie Baucham) (Ephesians 2:11-22)

Check here each week to keep up with the latest from John MacArthur's pulpit at Grace Community Church.




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Japan and South Korea: Two "Like-Minded" States Have Mixed Views on Conflicts in the South China Sea

Japan and South Korea: Two "Like-Minded" States Have Mixed Views on Conflicts in the South China Sea Japan and South Korea: Two "Like-Minded" States Have Mixed Views on Conflicts in the South China Sea
Anonymous (not verified) Fri, 04/24/2020 - 11:40

East-West Wire

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News, Commentary, and Analysis
East-West Wire

The East-West Wire is a news, commentary, and analysis service provided by the East-West Center in Honolulu. Any part or all of the Wire content may be used by media with attribution to the East-West Center or the person quoted. To receive East-West Center Wire media releases via email, subscribe here.

For links to all East-West Center media programs, fellowships and services, see www.eastwestcenter.org/journalists.

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East-West Wire

Tagline
News, Commentary, and Analysis
East-West Wire

The East-West Wire is a news, commentary, and analysis service provided by the East-West Center in Honolulu. Any part or all of the Wire content may be used by media with attribution to the East-West Center or the person quoted. To receive East-West Center Wire media releases via email, subscribe here.

For links to all East-West Center media programs, fellowships and services, see www.eastwestcenter.org/journalists.

Explore




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Special Investment Facilitation Council Reviews Progress and Strategies for Economic Stability in Pakistan

The Apex Committee of the Special Investment Facilitation Council (SIFC) met to evaluate advancements in fostering investments in Pakistan. Chaired by the caretaker prime minister, discussions encompassed strategies such as the privatization of financially struggling government institutions. In a separate interaction, the Army Chief reiterated the armed forces’ dedication to supporting the nation’s economic stability. ... Read more

The post Special Investment Facilitation Council Reviews Progress and Strategies for Economic Stability in Pakistan appeared first on Pakistan Tribune.




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Education Cannot Wait Interviews Matthias Schmale, UN Resident and Humanitarian Coordinator in Ukraine

  Matthias Schmale is the Assistant Secretary-General, UN Resident and Humanitarian Coordinator in Ukraine. Schmale brings more than 30 years of experience in humanitarian and development work. He previously served as Senior Adviser to the UN Development Coordination Office’s regional team for Africa, as Resident and Humanitarian Coordinator (a.i) in Nigeria, and in several high-level […]



  • Education
  • Education Cannot Wait. Future of Education is here
  • Human Rights
  • Education Cannot Wait (ECW)
  • IPS UN Bureau

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Decoding biology with massively parallel reporter assays and machine learning [Reviews]

Massively parallel reporter assays (MPRAs) are powerful tools for quantifying the impacts of sequence variation on gene expression. Reading out molecular phenotypes with sequencing enables interrogating the impact of sequence variation beyond genome scale. Machine learning models integrate and codify information learned from MPRAs and enable generalization by predicting sequences outside the training data set. Models can provide a quantitative understanding of cis-regulatory codes controlling gene expression, enable variant stratification, and guide the design of synthetic regulatory elements for applications from synthetic biology to mRNA and gene therapy. This review focuses on cis-regulatory MPRAs, particularly those that interrogate cotranscriptional and post-transcriptional processes: alternative splicing, cleavage and polyadenylation, translation, and mRNA decay.




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A cellular identity crisis? Plasticity changes during aging and rejuvenation [Reviews]

Cellular plasticity in adult multicellular organisms is a protective mechanism that allows certain tissues to regenerate in response to injury. Considering that aging involves exposure to repeated injuries over a lifetime, it is conceivable that cell identity itself is more malleable—and potentially erroneous—with age. In this review, we summarize and critically discuss the available evidence that cells undergo age-related shifts in identity, with an emphasis on those that contribute to age-associated pathologies, including neurodegeneration and cancer. Specifically, we focus on reported instances of programs associated with dedifferentiation, biased differentiation, acquisition of features from alternative lineages, and entry into a preneoplastic state. As some of the most promising approaches to rejuvenate cells reportedly also elicit transient changes to cell identity, we further discuss whether cell state change and rejuvenation can be uncoupled to yield more tractable therapeutic strategies.




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Seventy-Five Years of Interactions: The Department of Physiology and Pharmacology at Karolinska Institutet and Pharmacological Reviews [75th Anniversary Celebration Collection Special Section-Editorial]




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Summing Up Pharmacological Reviews 75th Anniversary Year and a Look to the Future [75th Anniversary Celebration Collection Special Section-Editorial]




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GPs’ views of prescribing beta- blockers for people with anxiety disorders: a qualitative study

BackgroundBetween 2003 and 2018, incident prescriptions of beta-blockers for anxiety increased substantially, particularly for young adults. National Institute for Health and Care Excellence guidance for anxiety does not recommend beta-blockers, probably due to a lack of evidence to support such use. Recent reports have highlighted the potential risks of beta-blockers.AimTo understand when and why GPs prescribe beta-blockers for people with anxiety.Design and settingIn-depth interviews with 17 GPs in Bristol and the surrounding areas.MethodInterviews were held by telephone or video call. A topic guide was used to ensure consistency across interviews. Interviews were audio-recorded, transcribed verbatim, and analysed thematically.ResultsMany GPs viewed beta-blockers as ‘low risk’, particularly for young adults. Some GPs viewed beta-blockers as an alternative to benzodiazepines, acting quickly and not leading to dependence. GPs reflected that some patients appeared to want an ‘immediate fix’ to their symptoms, which GPs thought beta-blockers could potentially offer. This is salient in light of substantial waiting lists for talking therapies and delays in antidepressants taking effect. GPs described how some patients seemed more willing to try beta-blockers than antidepressants, as patients did not perceive them as ‘mental health drugs’ and therefore viewed them as potentially more acceptable and less stigmatising. Further, GPs viewed beta-blockers as ‘patient-led’, with patients managing their own dose and frequency, without GP input.ConclusionMany GPs believe that beta-blockers have a role to play in the management of anxiety. Given recent increases in the prescribing of these drugs in primary care, there is a need to assess their safety and effectiveness as a treatment for people with anxiety disorders.




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Stellar views of some of the most spectacular sights in the universe

These dazzling images taken by NASA's Hubble Space Telescope are from the upcoming book Cosmos: Explore the wonders of the universe, which has a foreword by astrophysicist Becky Smethurst




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First Day First Show | Reviews of ‘Here’ and ‘Vijay 69’

The Hindu’s First Day First Show newsletter brings you news and reviews from the world of cinema and streaming





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SwitchArcade Round-Up: Reviews Featuring ‘Sam & Max: The Devil’s Playhouse’, Plus the Latest Releases and Sales

Hello gentle readers, and welcome to the SwitchArcade Round-Up for August 20th, 2024. In today’s article, I’ve got a couple …




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Steam Deck Weekly: Gamescom 2024 Steam Deck News, Reviews Including Bakeru and SCHiM, New Verified Games, Discounts, and More

Welcome to this week’s edition of the Steam Deck Weekly. I delayed publishing this because Gamescom 2024 is on right …




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Steam Deck Weekly: Visions of Mana and More Reviews, Reynatis Preview, Age of Mythology Retold Steam Deck Impressions, News, and More

Welcome to this week’s edition of the Steam Deck Weekly. If you missed my Gundam Breaker 4 Steam Deck review, …




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SwitchArcade Round-Up: Reviews Featuring ‘Bakeru’ & ‘Peglin’, Plus Highlights From Nintendo’s Blockbuster Sale

Hello gentle readers, and welcome to the SwitchArcade Round-Up for September 2nd, 2024. I think it’s a holiday today in …







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Steam Deck Weekly: NBA 2K25, ARCO, ODDADA, DATE a LIVE Ren Dystopia, Star Trucker, Skull and Bones, & More Reviews With New Verified Games

Welcome to this week’s edition of the Steam Deck Weekly. If you missed my Warhammer 40000: Space Marine 2 Steam …




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SwitchArcade Round-Up: Reviews Featuring ‘Fitness Boxing feat. Hatsune Miku’, Plus New Releases, Sales, and Good-Byes

Hello gentle readers, and welcome to the SwitchArcade Round-Up for September 6th, 2024. Well, this is the last one. You’ll …




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FTC Announces Final Rule to Prohibit Deceptive Online Reviews and Testimonials

Effective on October 21st of this year, the Federal Trade Commission (FTC) issued a new final rule that is intended to better combat ​“fake” reviews and testimonials by prohibiting the sale or purchase of “fake reviews” as well as granting the agency the opportunity to seek civil penalties against ​willful violators. The FTC made only […]




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Hardware Reviews! HyperX Mouse, Keyboards, Headphones, and Mousepad

The Alloy Origins Core is a tenkeyless mechanical keyboard made of airplane-grade aluminum, which prompts the question: Why don't they make the whole plane out of keyboard?




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Steam Reviews For America

Pay to win garbage. Not even a chance for anyone who got f****d over by RNG. Total scam!




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Arcane Season 2 Act 2 Trailer Previews What’s Next for Jinx & Vi

Following its return last Saturday, Netflix has finally shared the Arcane Season 2 Act 2 trailer for the next three episodes of the hit action fantasy series, based on Riot Games’ League of Legends video game. The second half of the final season will be available for streaming this Saturday, November 16. “The aftermath of […]

The post Arcane Season 2 Act 2 Trailer Previews What’s Next for Jinx & Vi appeared first on ComingSoon.net - Movie Trailers, TV & Streaming News, and More.




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Bleach: Rebirth of Souls Game's Character Trailer Previews Nel

3D arena fighting game slated for PS5, PS4, Xbox Series X|S, PC in early 2025




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Witchy Precure!!: MIRAI DAYS Anime's Trailer Previews Opening Song, Saori Hayami's 2nd Role

Saori Hayami plays mysterious girl Hisui, performs ending song 'Kisekiralink' with Rie Takahashi, Yui Horie




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638. Smart Bitches After Dark – Tara interviews Sarah & Amanda

Tara Scott, staff writer at SBTB and co-host of the Queerly Recommended podcast, is in the interviewer’s chair, asking Amanda and me questions about Smart Bitches After Dark, our new community support wing. We talk about what After Dark is, and also about the larger enshittification of different parts of the internet, and how we navigate that as a 20 year old blog. Yay blogs! I was really nervous about being interviewed, and I hope … Continue reading 638. Smart Bitches After Dark – Tara interviews Sarah & Amanda




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639. RT Rewind: November 2015 Reviews

It’s time to take a look at the new books in November 2015 inside Romantic Times! We’ve got spanking and small towns, and a magazine that seems more targeted toward aspiring writers than readers. That yielded a mixed bag! But we have some books to talk about so let’s get to it! So many small town contemporaries, so many historicals, so many Four Star reviews with word salad. And some cat poo. TW/CW: very brief … Continue reading 639. RT Rewind: November 2015 Reviews



  • Romantic Times Rewind

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'[It] is just really tacky': Job candidate interviews with glowing recommendation, picky manager spots one flaw and refuses to hire her

This manager is being totally ridiculous, and he doesn't even realize the full scope of what he did. 

Sticking your neck out for a friend can be risky. In this person's case, they recommended their friend for an interview at their coffee shop job. They figured this friend would be a shoo-in for the role. To be a great barista, you need to be upbeat and positive when interacting with customers, be able to put drinks together quickly, and work well under pressure. U/BAAAUGH was completely exasperated by the way her boss treated that friend she recommended for the job

The only person who should be embarrassed by the way things went down is the boss. It almost seems like he's worried that his staffers will steal coffee or something. First of all, most baristas do drink coffee at their workplaces, but it's a cheap item, just let them have it! And secondly, if that's the boss's biggest concern about a potential employee, maybe he should spend some more time behind the counter, preparing orders, and learning what it actually takes to thrive in a cafe environment. 

Up next, read about this scorned ex who yanked a $600 gift card back from an ex just to get back at her. 




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Amazon's rating trickery: How products are being swapped without changing reviews

The malpractice has been brought to light by tech-influencer who explains how the products listed on the site and the products rated can be two completely different items to begin with.




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Carlos Santana's Hillside Home Provides San Francisco Bay Views

Once inside, the house's modern style flows across an open floor plan marked by clean lines and quality craftsmanship from the kitchen and dining areas to the living room. Hardwood flooring and walls of windows frame the picturesque views from nearly every room.




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Sip Or Skip : Meet The Boss Who Swears By The Coffee Cup Test In Interviews!

Can a coffee cup determine your success at an interview? Well, we've all been there; nervously sitting in a job interview, knowing that our future hangs in the balance. Some interviews are tough, while others might feel surprisingly straightforward. Here an




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White torture [Electronic book] : interviews with Iranian women prisoners / Narges Mohammadi ; translated by Amir Rezanezhad ; [foreword by Shirin Ebadi].

New York : Oneworld Publications, 2022.




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Dissenting words : interviews with Jacques Rancière [Electronic book] / edited and translated by Emiliano Battista.

London; New York : Bloomsbury Academic, 2017.




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Claude Chabrol : interviews [Electronic book] / edited by Christopher Beach.

Jackson : University Press of Mississippi, 2020.