Opportunities and Challenges: Hepatitis C Testing and Treatment Access Experiences Among People in Methadone and Buprenorphine Treatment During COVID-19, Arizona, 2021

Introduction: The purpose of this study was to characterize hepatitis C virus screening and treatment access experiences among people in treatment for opioid use disorder in Arizona during COVID-19. Methods: Arizonans receiving treatment for opioid use disorder from methadone clinics and buprenorphine providers during COVID-19 were interviewed about hepatitis C virus testing, curative treatment, and knowledge about screening recommendations. Interviews were conducted with 121 people from August 4, 2021 to October 10, 2021. Qualitative data were coded using the categories of hepatitis C virus testing, knowledge of screening recommendations, diagnosis, and experiences seeking curative treatment. Data were also quantitated for bivariate testing with outcome variables of last hepatitis C virus test, diagnosis, and curative treatment process. Findings were arrayed along an adapted hepatitis C virus cascade framework to inform program and policy improvements. Results: Just over half of the sample reported ever having tested for hepatitis C virus (51.2%, n=62) and of this group, 58.1% were tested in the past 12 months. Among those who were ever tested, 54.8% reported a hepatitis C virus diagnosis and 16.1% reported either being in treatment or having been declared cured of the hepatitis C virus. Among those who were diagnosed with hepatitis C, 14.7% indicated that they unsuccessfully tried to access curative treatment and would not attempt to again. Reasons cited for not accessing or receiving curative treatment included beliefs about treatment safety, barriers created by access requirements, natural resolution of the infection, and issues with healthcare coverage and authorization. Conclusions: Structural barriers continue to prevent curative hepatitis C virus treatment access. Given that methadone and buprenorphine treatment providers serve patients who are largely undiagnosed or treated for hepatitis C virus, opportunities exist for them to screen their patients regularly and provide support for and/or navigation to hepatitis C virus curative treatment

The MRN complex is transcriptionally regulated by MYCN during neural cell proliferation to control replication stress

The MRE11/RAD50/NBS1 (MRN) complex is a major sensor of DNA double strand breaks, whose role in controlling faithful DNA replication and preventing replication stress is also emerging. Inactivation of the MRN complex invariably leads to developmental and/or degenerative neuronal defects, the pathogenesis of which still remains poorly understood. In particular, NBS1 gene mutations are associated with microcephaly and strongly impaired cerebellar development, both in humans and in the mouse model. These phenotypes strikingly overlap those induced by inactivation of MYCN, an essential promoter of the expansion of neuronal stem and progenitor cells, suggesting that MYCN and the MRN complex might be connected on a unique pathway essential for the safe expansion of neuronal cells. Here, we show that MYCN transcriptionally controls the expression of each component of the MRN complex. By genetic and pharmacological inhibition of the MRN complex in a MYCN overexpression model and in the more physiological context of the Hedgehog-dependent expansion of primary cerebellar granule progenitor cells, we also show that the MRN complex is required for MYCN-dependent proliferation. Indeed, its inhibition resulted in DNA damage, activation of a DNA damage response, and cell death in a MYCN- and replication-dependent manner. Our data indicate the MRN complex is essential to restrain MYCN-induced replication stress during neural cell proliferation and support the hypothesis that replication-born DNA damage is responsible for the neuronal defects associated with MRN dysfunctions.Cell Death and Differentiation advance online publication, 12 June 2015; doi:10.1038/cdd.2015.81

Occipital gamma activation during Vipassana meditation

Long-term Vipassana meditators sat in meditation vs. a control rest (mind-wandering) state for 21 min in a counterbalanced design with spontaneous EEG recorded. Meditation state dynamics were measured with spectral decomposition of the last 6 min of the eyes-closed silent meditation compared to control state. Meditation was associated with a decrease in frontal delta (1–4 Hz) power, especially pronounced in those participants not reporting drowsiness during meditation. Relative increase in frontal theta (4–8 Hz) power was observed during meditation, as well as significantly increased parieto-occipital gamma (35–45 Hz) power, but no other state effects were found for the theta (4–8 Hz), alpha (8–12 Hz), or beta (12–25 Hz) bands. Alpha power was sensitive to condition order, and more experienced meditators exhibited no tendency toward enhanced alpha during meditation relative to the control task. All participants tended to exhibit decreased alpha in association with reported drowsiness. Cross-experimental session occipital gamma power was the greatest in meditators with a daily practice of 10+ years, and the meditation-related gamma power increase was similarly the strongest in such advanced practitioners. The findings suggest that long-term Vipassana meditation contributes to increased occipital gamma power related to long-term meditational expertise and enhanced sensory awareness

Mindful breath awareness meditation facilitates efficiency gains in brain networks: A steady-state visually evoked potentials study

The beneficial effects of mindfulness-based therapeutic interventions have stimulated a rapidly growing body of scientific research into underlying psychological processes. Resulting evidence indicates that engaging with mindfulness meditation is associated with increased performance on a range of cognitive tasks. However, the mechanisms promoting these improvements require further investigation. We studied changes in behavioural performance of 34 participants during a multiple object tracking (MOT) task that taps core cognitive processes, namely sustained selective visual attention and spatial working memory. Concurrently, we recorded the steady-state visually evoked potential (SSVEP), an EEG signal elicited by the continuously flickering moving objects, and indicator of attentional engagement. Participants were tested before and after practicing eight weeks of mindful breath awareness meditation or progressive muscle relaxation as active control condition. The meditation group improved their MOT-performance and exhibited a reduction of SSVEP amplitudes, whereas no such changes were observed in the relaxation group. Neither group changed in self-reported positive affect and mindfulness, while a marginal increase in negative affect was observed in the mindfulness group. This novel way of combining MOT and SSVEP provides the important insight that mindful breath awareness meditation may lead to refinements of attention networks, enabling more efficient use of attentional resources

Rhesus macaque MHC class I molecules show differential subcellular localizations

The MHC class I gene family of rhesus macaques is characterised by considerable gene duplications. While a HLA-C-orthologous gene is absent, the Mamu-A and in particular the Mamu-B genes have expanded, giving rise to plastic haplotypes with differential gene content. Although some of the rhesus macaque MHC class I genes are known to be associated with susceptibility/resistance to infectious diseases, the functional significance of duplicated Mamu-A and Mamu-B genes and the expression pattern of their encoded proteins are largely unknown. Here, we present data of the subcellular localization of AcGFP-tagged Mamu-A and Mamu-B molecules. We found strong cell surface and low intracellular expression for Mamu-A1, Mamu-A2 and Mamu-A3-encoded molecules as well as for Mamu-B*01704, Mamu-B*02101, Mamu-B*04801, Mamu-B*06002 and Mamu-B*13401. In contrast, weak cell surface and strong intracellular expression was seen for Mamu-A4*1403, Mamu-B*01202, Mamu-B*02804, Mamu-B*03002, Mamu-B*05704, Mamu-I*010201 and Mamu-I*0121. The different expression patterns were assigned to the antigen-binding α1 and α2 domains, suggesting failure of peptide binding is responsible for retaining ‘intracellular’ Mamu class I molecules in the endoplasmic reticulum. These findings indicate a diverse functional role of the duplicated rhesus macaque MHC class I genes

Challenges for global ocean observation: the need for increased human capacity

Sustained global ocean observations are needed to recognise, understand, and manage changes in marine biodiversity, resources and habitats, and to implement wise conservation and sustainable development strategies. To meet this need, the Global Ocean Observing System (GOOS), a network of observing systems distributed around the world and coordinated by the Intergovernmental Oceanographic Commission (IOC) has proposed Essential Ocean Variables (EOVs) that are relevant to both the scientific and the broader community, including resource managers. Building a network that is truly global requires expanding participation beyond scientists from well-resourced countries to a far broader representation of the global community. New approaches are required to provide appropriate training, and resources and technology should follow to enable the application of this training to engage meaningfully in global observing networks and in the use of the data. Investments in technical capacity fulfil international reporting obligations under the UN Sustainable Development Goal 14A. Important opportunities are emerging now for countries to develop research partnerships with the IOC and GOOS to address these obligations. Implementing these partnerships requires new funding models and initiatives that support a sustained research capacity and marine technology transfer

S100A7 (psoriasin) expression is associated with aggressive features and alteration of Jab1 in ductal carcinoma in situ of the breast

INTRODUCTION: The S100A7 (psoriasin) gene is highly expressed in ductal carcinoma in situ (DCIS) of the breast and can be downregulated in invasive carcinoma. Persistent S100A7 expression in invasive carcinoma is associated with a worse prognosis, and this effect may be mediated in part through interaction with the multifunctional cell signaling protein Jab1. METHODS: In order to investigate the relationship between S100A7 and progression from DCIS to invasive carcinoma, we studied S100A7 expression in 136 patients with DCIS (including 46 patients with associated invasive carcinoma) by immunohistochemistry. RESULTS: S100A7 expression was present in 63 out of 136 (46%) of DCIS lesions and was associated with estrogen receptor negative status (P = 0.0002), higher nuclear grade (P < 0.0001), necrosis (P < 0.0001) and inflammation (P < 0.0001). S100A7 status was no different between DCIS with and DCIS without an invasive component, but higher levels of S100A7 were present in DCIS associated with invasive carcinoma (P < 0.004). Analysis of a subset of cases showed that S100A7 expression was also associated with an increase in nuclear Jab1 (n = 43; P = 0.0019) and reduced p27(kip1 )(n = 47; P = 0.0168). In cases of DCIS associated with invasive carcinoma, there was also a significant reduction in S100A7 between in situ and invasive components (n = 46; P < 0.0001). In pure DCIS cases treated by local excision, there was no difference in frequency of S100A7 expression between patients with recurrence of DCIS (n = 9) and those without (n = 36). CONCLUSION: The findings reported here suggest that, although S100A7 may not be a marker for recurrence of DCIS, it is associated with poor prognostic markers in DCIS and may influence progression of breast carcinoma through its interaction with and influence on Jab1

Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV

The performance of muon reconstruction, identification, and triggering in CMS has been studied using 40 inverse picobarns of data collected in pp collisions at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection criteria covering a wide range of physics analysis needs have been examined. For all considered selections, the efficiency to reconstruct and identify a muon with a transverse momentum pT larger than a few GeV is above 95% over the whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4, while the probability to misidentify a hadron as a muon is well below 1%. The efficiency to trigger on single muons with pT above a few GeV is higher than 90% over the full eta range, and typically substantially better. The overall momentum scale is measured to a precision of 0.2% with muons from Z decays. The transverse momentum resolution varies from 1% to 6% depending on pseudorapidity for muons with pT below 100 GeV and, using cosmic rays, it is shown to be better than 10% in the central region up to pT = 1 TeV. Observed distributions of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO