Skeletal muscle glucose uptake during treadmill exercise in neuronal nitric oxide synthase-μ knockout mice

Nitric oxide influences intramuscular signaling that affects skeletal muscle glucose uptake during exercise. The role of the main NO-producing enzyme isoform activated during skeletal muscle contraction, neuronal nitric oxide synthase-μ (nNOSμ), in modulating glucose uptake has not been investigated in a physiological exercise model. In this study, conscious and unrestrained chronically catheterized nNOSμ+/+ and nNOSμ−/− mice either remained at rest or ran on a treadmill at 17 m/min for 30 min. Both groups of mice demonstrated similar exercise capacity during a maximal exercise test to exhaustion (17.7 ± 0.6 vs. 15.9 ± 0.9 min for nNOSμ+/+ and nNOSμ−/−, respectively, P &gt; 0.05). Resting and exercise blood glucose levels were comparable between the genotypes. Very low levels of NOS activity were detected in skeletal muscle from nNOSμ−/− mice, and exercise increased NOS activity only in nNOSμ+/+ mice (4.4 ± 0.3 to 5.2 ± 0.4 pmol·mg−1·min−1, P &lt; 0.05). Exercise significantly increased glucose uptake in gastrocnemius muscle (5- to 7-fold) and, surprisingly, more so in nNOSμ−/− than in nNOSμ+/+ mice ( P &lt; 0.05). This is in parallel with a greater increase in AMPK phosphorylation during exercise in nNOSμ−/− mice. In conclusion, nNOSμ is not essential for skeletal muscle glucose uptake during exercise, and the higher skeletal muscle glucose uptake during exercise in nNOSμ−/− mice may be due to compensatory increases in AMPK activation. </jats:p

Navigating 'ethics in practice': An ethnographic case study with young women living with HIV in Zambia.

While 'procedural ethics' provides essential frameworks for governing global health research, reflecting on 'ethics in practice' offers important insights into addressing ethically important moments that arise in everyday research. Particularly for ethnographic research, renowned for it's fluid and spontaneous nature, engaging with 'ethics in practice' has the potential to enhance research practice within global health. We provide a case study for such reflexivity, exploring 'ethics in practice' of ethnographic research with middle-income young women living with HIV in Lusaka, Zambia. We explore the ethical issues arising from the layered interaction of the population (young women), the disease under investigation (HIV), the method of study (ethnographic), and the setting (Zambia, a lower middle income country). We describe how we navigated five key practical ethical tensions that arose, namely the psycho-emotional benefits of the research, the negotiated researcher-participant relationship, protecting participants' HIV status, confidentiality and data ownership, and researcher obligations after the end of the research. We exemplify reflexive engagement with 'ethics in practice' and suggest that engaging with ethics in this way can make important contributions towards developing more adequate ethical guidelines and research practice in global public health

Coming of age with HIV: a temporal understanding of young women's experiences in Zambia.

Young perinatally-infected women living with HIV in Zambia grew up alongside antiretroviral therapy (ART) roll-out and expanding prevention programmes. We used Bonnington's temporal framework to understand how HIV impacted the experiences of these women over time. Data were drawn from two sequential studies with a cohort of young women living with HIV: a qualitative study in 2014-16 and an ethnographic study in 2017-18. Data from workshops, in-depth interviews, participant observation and diaries were analysed thematically, guided by three temporalities within the framework: everyday, biographical and epochal time. In everyday time, repetitive daily treatment-taking reminded young women of their HIV status, affecting relationships and leading to secrecy with ART. In biographical time, past events including HIV disclosure, experiences of illness, and loss shaped present experiences and future aspirations. Lastly, in epochal time, the women's HIV infection and their survival were intimately interlinked with the history of ART availability. The epochal temporal understanding leads us to extend Reynolds Whyte's notion of "biogeneration" to conceptualise these women, whose experiences of living with HIV are enmeshed with their biosocial environment. Support groups for young women living with HIV should help them to process biographical events, as well as supporting their everyday needs

Statin-induced increases in atrophy gene expression occur independently of changes in PGC1α protein and mitochondrial content

One serious side effect of statin drugs is skeletal muscle myopathy. Although the mechanism(s) responsible for statin myopathy remains to be fully determined, an increase in muscle atrophy gene expression and changes in mitochondrial content and/or function have been proposed to play a role. In this study, we examined the relationship between statin-induced expression of muscle atrophy genes, regulators of mitochondrial biogenesis, and markers of mitochondrial content in slow- (ST) and fast-twitch (FT) rat skeletal muscles. Male Sprague Dawley rats were treated with simvastatin (60 or 80 mg&middot;kg(-1)&middot;day(-1)) or vehicle control via oral gavage for 14 days. In the absence of overt muscle damage, simvastatin treatment induced an increase in atrogin-1, MuRF1 and myostatin mRNA expression; however, these were not associated with changes in peroxisome proliferator gamma co-activator 1 alpha (PGC-1&alpha;) protein or markers of mitochondrial content. Simvastatin did, however, increase neuronal nitric oxide synthase (nNOS), endothelial NOS (eNOS) and AMPK &alpha;-subunit protein expression, and tended to increase total NOS activity, in FT but not ST muscles. Furthermore, simvastatin induced a decrease in &beta;-hydroxyacyl CoA dehydrogenase (&beta;-HAD) activity only in FT muscles. These findings suggest that the statin-induced activation of muscle atrophy genes occurs independent of changes in PGC-1&alpha; protein and mitochondrial content. Moreover, muscle-specific increases in NOS expression and possibly NO production, and decreases in fatty acid oxidation, could contribute to the previously reported development of overt statin-induced muscle damage in FT muscles

Secrets and Silence: Agency of Young Women Managing HIV Disclosure.

Drawing on a 12-month ethnography with young women living with HIV in Zambia, we explore their everyday strategies to avoid unintentional disclosure of their HIV status. Young women practiced secrecy with sexual partners, through hiding their antiretroviral therapy and using veiled language around HIV. Whilst remaining silent about their HIV status enabled them to maintain identities beyond HIV, this secrecy triggered feelings of guilt and anxiety, suggesting that their agency was "bounded" by the context of persistent stigma. These strategies to hide their HIV status question public health narratives urging disclosure, and support disclosure-counseling approaches that champions choice

Lilia, A Showcase for Fast Bootstrap of Conversation-Like Dialogues Based on a Goal-Oriented System

International audienceRecently many works have proposed to cast human-machine interaction in a sentence generation scheme. Neural networks models can learn how to generate a probable sentence based on the user's statement along with a partial view of the dialogue history. While appealing to some extent, these approaches require huge training sets of general-purpose data and lack a principled way to intertwine language generation with information retrieval from back-end resources to fuel the dialogue with actualised and precise knowledge. As a practical alternative, in this paper, we present Lilia, a showcase for fast bootstrap of conversation-like dialogues based on a goal-oriented system. First, a comparison of goal-oriented and conversational system features is led, then a conversion process is described for the fast bootstrap of a new system, finalised with an on-line training of the system's main components. Lilia is dedicated to a chitchat task, where speakers exchange viewpoints on a displayed image while trying collaboratively to derive its author's intention. Evaluations with user trials showed its efficiency in a realistic setup

"My mother told me that I should not": a qualitative study exploring the restrictions placed on adolescent girls living with HIV in Zambia.

INTRODUCTION: Adolescent girls in sub-Saharan Africa are disproportionately affected by HIV due to a range of social and structural factors. As they transition to adulthood, they are recipients of increasing blame for HIV infection and 'improper' sex, as well as increasing scrutiny, restrictions and surveillance. This study used a qualitative and participatory approach to explore the messaging and restrictions imposed on adolescent girls living with HIV in Zambia. METHODS: Thirty-four in-depth interviews and four participatory workshops were carried out with 24 adolescent girls aged 15 to 19 years old living with HIV in Lusaka, Zambia. Key themes explored included experiences living with HIV, finding out about HIV status, disclosure, experiences with antiretroviral treatment, and support needs. Data were organized, coded and analysed using a grounded theory approach to thematic analysis. This analysis uses data on participants' experiences of living with HIV and their interactions with their parents, guardians and healthcare providers. RESULTS: Family and healthcare providers, partly in a quest to protect both the health of adolescent girls living with HIV and also to protect them from blaming discourse, imposed restrictions on their behaviour around three main topics: don't disclose your HIV status, don't have sex, and don't miss your medicines. These restrictions were often delivered using tactics of fear, and usually disconnected from other options. Participants responded to these messages in several ways, including internalizing the messages, changing their behaviour either to comply with or resist the restrictions, by remaining silent and anxious when restrictions were broken, and developing concerns around their own health and sexual and reproductive aspirations. Participants also sometimes experiencing stigma when restrictions could not be maintained. CONCLUSIONS: Restrictive messages were delivered to adolescent girls living with HIV through the broader social discourses of stigma, religion, and global and local narratives about HIV. Programmes aiming to support adolescent girls living with HIV need to work together with parents and healthcare providers to reflect on the impact of sanctioning messages, and to encourage more enabling and empowering messaging for adolescent girls living with HIV

Scintillator-based ion beam profiler for diagnosing laser-accelerated ion beams

Next generation intense, short-pulse laser facilities require new high repetition rate diagnostics for the detection of ionizing radiation. We have designed a new scintillator-based ion beam profiler capable of measuring the ion beam transverse profile for a number of discrete energy ranges. The optical response and emission characteristics of four common plastic scintillators has been investigated for a range of proton energies and fluxes. The scintillator light output (for 1 MeV > Ep < 28 MeV) was found to have a non-linear scaling with proton energy but a linear response to incident flux. Initial measurements with a prototype diagnostic have been successful, although further calibration work is required to characterize the total system response and limitations under the high flux, short pulse duration conditions of a typical high intensity laser-plasma interaction

Role of domain walls in the abnormal photovoltaic effect in BiFeO3

Recently, the anomalous photovoltaic (PV) effect in BiFeO3 (BFO) thin films, which resulted in open circuit voltages (V-oc) considerably larger than the band gap of the material, has generated a revival of the entire field of photoferroelectrics. Here, via temperature-dependent PV studies, we prove that the bulk photovoltaic (BPV) effect, which has been studied in the past for many non-centrosymmetric materials, is at the origin of the anomalous PV effect in BFO films. Moreover, we show that irrespective of the measurement geometry, V-oc as high as 50V can be achieved by controlling the conductivity of domain walls (DW). We also show that photoconductivity of the DW is markedly higher than in the bulk of BFO

Between division and connection: a qualitative study of the impact of COVID-19 restrictions on social relationships in the United Kingdom.

Background: The first national COVID-19 lockdown in the United Kingdom between March to July 2020 resulted in sudden and unprecedented disruptions to daily life. This study sought to understand the impact of COVID-19 non-pharmaceutical interventions (NPIs), such as social distancing and quarantine, on people's lived experiences, focusing on social connections and relationships. Methods: Data were generated through 20 in-depth online and telephone interviews, conducted between May and July 2020, and analysed using thematic analysis informed by an ecological framework. Results: Findings show that the use of NPIs impacted social relationships and sociality at every level, disrupting participant's sense of self; relationships with their partners, household members, neighbours, and communities; and polarising social and political views. However, experiences of personal meaning-making and reflection, and greater social connectedness, solidarity, and compassion - despite physical distance - were also common. Conclusions: Participant's lived experiences of the first UK lockdown underscore the interconnectedness of relationships at the individual, community and societal level and point towards the important role of trust, social cohesion, and connectedness in coping with pandemic stress and adversity. Where infectious disease prevention measures rupture sociality, support for social connection at every relational level is likely to help build resilience in light of ongoing COVID-19 restrictions