Antiretroviral neurotoxicity

Combination antiretroviral therapy (CART) has proven to effectively suppress systemic HIV burden, however, poor penetration into the central nervous system (CNS) provides incomplete protection. Although the severity of HIV-associated neurocognitive disorders (HAND) has been reduced, neurological disease is expected to exert an increasing burden as HIV-infected patients live longer. Strategies to enhance penetration of antiretroviral compounds into the CNS could help to control HIV replication in this reservoir but also carries an increased risk of neurotoxicity. Efforts to target antiretroviral compounds to the CNS will have to balance these risks against the potential gain. Unfortunately, little information is available on the actions of antiretroviral compounds in the CNS, particularly at concentrations that provide effective virus suppression. The current studies evaluated the direct effects of 15 anti-retroviral compounds on neurons to begin to provide basic neurotoxicity data that will serve as a foundation for the development of dosing and drug selection guidelines. Using sensitive indices of neural damage, we found a wide range of toxicities, with median toxic concentrations ranging from 2 to 10,000 ng/ml. Some toxic concentrations overlapped concentrations currently seen in the CSF but the level of toxicity was generally modest at clinically relevant concentrations. Highest neurotoxicities were associated with abacavir, efavarenz, etravirine, nevaripine, and atazanavir, while the lowest were with darunavir, emtracitabine, tenofovir, and maraviroc. No additive effects were seen with combinations used clinically. These data provide initial evidence useful for the development of treatment strategies that might reduce the risk of antiretroviral neurotoxicity

Acclimatization of micropropagated Heliconia bihai (Heliconiaceae) plants

A cultura da helicônia é a que apresenta maior crescimento entre o cultivo de flores tropicais para a exportação. Avaliou-se o comportamento de mudas de helicônias micropropagadas no processo de aclimatização, em diferentes substratos e níveis de sombreamento. Foram plantadas mudas de H. bihai (Lobster Claw I) em bandejas plásticas contendo os diferentes substratos: areia lavada, vermiculita (textura média) e PlantMax® Horticultura. Na avaliação de níveis de sombreamento foi utilizado o telado (sombrite), com ordem de sombreamento 0% (pleno sol), 30%, 40%, 50%, 60%, 70% e 80%. O desempenho foi superior nos substratos areia lavada e PlantMax® Horticultura e nas condições de sombreamento a partir de 50 %, em especial 70% e 80%. As raízes pré-existentes, oriundas do enraizamento in vitro, mostraram-se não funcionais, sem a emissão de raízes secundárias e apresentando necrose do tecido radicular. As mudas aclimatizadas desenvolveram novas raízes, o que sugere que esta cultura pode ser aclimatizada sem que as plântulas passem pela fase de enraizamento em laboratório.To evaluate the behavior of micropropagated heliconia seedlings during the acclimatization process using different substrates and shade levels, seedlings of H. bihai (Lobster Claw I) were planted in plastic trays using the substrates: washed sand, vermiculite (medium texture), and PlantMax® Horticultura, and shade cloths with percentages of 0% (full sun), 30%, 40%, 50%, 60%, 70%, and 80% of shade in relation to full sun. Best results were obtained for washed sand and PlantMax substrates at shade conditions starting from 50%, especially at 70% and 80%. Pre-existing roots from in vitro rootings were not functional, not presenting secondary roots, and showing root tissue necrosis. Acclimatized seedlings developed new roots. This finding suggests that this plant can be acclimatized without going through a laboratory rooting stage

Aclimatização de mudas micropropagadas de Heliconia bihai (Heliconiaceae)

To evaluate the behavior of micropropagated heliconia seedlings during the acclimatization process using different substrates and shade levels, seedlings of H. bihai (Lobster Claw I) were planted in plastic trays using the substrates: washed sand, vermiculite (medium texture), and PlantMax® Horticultura, and shade cloths with percentages of 0% (full sun), 30%, 40%, 50%, 60%, 70%, and 80% of shade in relation to full sun. Best results were obtained for washed sand and PlantMax substrates at shade conditions starting from 50%, especially at 70% and 80%. Pre-existing roots from in vitro rootings were not functional, not presenting secondary roots, and showing root tissue necrosis. Acclimatized seedlings developed new roots. This finding suggests that this plant can be acclimatized without going through a laboratory rooting stage.A cultura da helicônia é a que apresenta maior crescimento entre o cultivo de flores tropicais para a exportação. Avaliou-se o comportamento de mudas de helicônias micropropagadas no processo de aclimatização, em diferentes substratos e níveis de sombreamento. Foram plantadas mudas de H. bihai (Lobster Claw I) em bandejas plásticas contendo os diferentes substratos: areia lavada, vermiculita (textura média) e PlantMax® Horticultura. Na avaliação de níveis de sombreamento foi utilizado o telado (sombrite), com ordem de sombreamento 0% (pleno sol), 30%, 40%, 50%, 60%, 70% e 80%. O desempenho foi superior nos substratos areia lavada e PlantMax® Horticultura e nas condições de sombreamento a partir de 50 %, em especial 70% e 80%. As raízes pré-existentes, oriundas do enraizamento in vitro, mostraram-se não funcionais, sem a emissão de raízes secundárias e apresentando necrose do tecido radicular. As mudas aclimatizadas desenvolveram novas raízes, o que sugere que esta cultura pode ser aclimatizada sem que as plântulas passem pela fase de enraizamento em laboratório.299301Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

Rules versus Discretion in Committee Decision Making: An Application to the 2001 RAE for UK Economics Departments

The question of rules versus discretion has generated a great deal of debate in many areas of the social sciences. Recently, much of the discussion among academics and stakeholders about the assessment of research in UK higher education institutions has focused on the means that should be used to determine research quality. We present a model of committee decision-making when both rules and discretion are available. Some of the predictions of the model are tested empirically using the UK RAE 2001 results

Activation and discovery of earth-abundant metal catalysts using sodium tert-butoxide

First-row, earth-abundant metals offer an inexpensive and sustainable alternative to precious-metal catalysts. As such, iron and cobalt catalysts have garnered interest as replacements for alkene and alkyne hydrofunctionalization reactions. However, these have required the use of air- and moisture-sensitive catalysts and reagents, limiting both adoption by the non-expert as well as applicability, particularly in industrial settings. Here, we report a simple method for the use of earth-abundant metal catalysts by general activation with sodium tert-butoxide. Using only robust air- and moisture-stable reagents and pre-catalysts, both known and, significantly, novel catalytic activities have been successfully achieved, covering hydrosilylation, hydroboration, hydrovinylation, hydrogenation and [2π+2π] alkene cycloaddition. This activation method allows for the easy use of earth-abundant metals, including iron, cobalt, nickel and manganese, and represents a generic platform for the discovery and application of non-precious metal catalysis

Soy Isoflavones Genistein and Daidzein Exert Anti-Apoptotic Actions via a Selective ER-mediated Mechanism in Neurons following HIV-1 Tat1–86 Exposure

HIV-1 viral protein Tat partially mediates the neural dysfunction and neuronal cell death associated with HIV-1 induced neurodegeneration and neurocognitive disorders. Soy isoflavones provide protection against various neurotoxic insults to maintain neuronal function and thus help preserve neurocognitive capacity.We demonstrate in primary cortical cell cultures that 17β-estradiol or isoflavones (genistein or daidzein) attenuate Tat(1-86)-induced expression of apoptotic proteins and subsequent cell death. Exposure of cultured neurons to the estrogen receptor antagonist ICI 182,780 abolished the anti-apoptotic actions of isoflavones. Use of ERα or ERβ specific antagonists determined the involvement of both ER isoforms in genistein and daidzein inhibition of caspase activity; ERβ selectively mediated downregulation of mitochondrial pro-apoptotic protein Bax. The findings suggest soy isoflavones effectively diminished HIV-1 Tat-induced apoptotic signaling.Collectively, our results suggest that soy isoflavones represent an adjunctive therapeutic option with combination anti-retroviral therapy (cART) to preserve neuronal functioning and sustain neurocognitive abilities of HIV-1 infected persons

An Exploratory Study of Honors College Students’ Conceptualizations About Social Justice on and Off Campus

An Exploratory Study of Honors College Students’ Conceptualizations About Social Justice on and Off Campus. Quakish Beatrice Williams Liner, 2023. Applied Dissertation, Nova Southeastern University, Abraham S. Fischler College of Education and School of Criminal Justice. Keywords: honors, social justice, 2-year college, intersectionality This applied dissertation explored how honor students perceived social justice and how those perceptions shaped actions on-or off-campus to show what experiences influenced how social justice perceptions develop. This study was a basic qualitative research design generic study because the inquiry centered on students’ perceptions of social justice. Twenty college honors students discussed accounts of their subjective beliefs related to their experiences to describe an external social phenomenon: social justice conceptualizations. Participants participated in semistructured interviews. The results of the qualitative data analysis revealed seven themes used to answer the research questions. College honors students believed that social justice entailed equality, manifesting in equal rights, opportunities, and treatments regardless of sex, gender identity, race, citizenship, and other social statuses. Participants developed social justice from their college experiences, privileges, and personal attributes and experiences. Some perceived social justice differently after experiences with peers and mentors in college, resulting in actively joining organizations in and out of school to advocate for people with less privileges and more struggles than them. Participants emphasized respecting the rights of others as central in social justice. The participants believed that their South Florida college could improve student awareness and engagement in activities to help them better understand social justice. Despite the findings, the literature gap behind the research remains: It is unknown how college honors students perceive social justice. One reason is that participants varied significantly in their views of social justice. Due to the remaining gap and limitations, several recommendations for future research were provided. The information from this study was used to develop several policy and practice recommendations