The Goldfish as a Model for Studying Neuroestrogen Synthesis, Localization, and Action in the Brain and Visual System

Organizational and activational effects of estrogen (E) in the central nervous system (CNS) are exerted directly by circulating E and indirectly after aromatization of circulating androgen to E in the brain itself. Understanding an environmental chemical's ability to disrupt E-dependent neural processes, therefore, requires attention to both pathways. Because aromatase (Aro) is highly expressed in teleost brain, when compared to mammals and other vertebrates, fish are technically advantageous for localization and regulation studies and may also provide a model in which the functional consequences of brain-derived (neuro-)E synthesis are exaggerated. Recently, Aro was immunolocalized in cell bodies and fiber projections of second- and third-order neurons of the goldfish retina and in central visual processing areas. Authentic Aro enzyme activity was verified biochemically, suggesting a heretofore unrecognized role of sex steroids in the visual system. Initial studies show that in vivo treatment with aromatizable androgen or E increases calmodulin synthesis and calmodulin protein in retina and also affects retinal protein and DNA. Whether there are related changes in the processing of visual information that is essential for seasonal reproduction or in the generative and regenerative capacity of the goldfish visual system requires further investigation. IMAGES.National Science Foundation (DCB8916809

CD40 is constitutively expressed on platelets and provides a novel mechanism for platelet activation

CD40 is a 48-kDa phosphorylated transmembrane glycoprotein belonging to the TNF receptor superfamily. CD40 has been demonstrated on a range of cell types, and it has an important role in adaptive immunity and inflammation. CD40 has recently been described on platelets but platelet activation by CD40 has not been described. In the present study, we use flow cytometry and immunoblotting to confirm that platelets constitutively express surface CD40. CD40 mRNA was undetectable, suggesting that the protein is synthesized early in platelet differentiation by megakaryocytes. Ligation of platelet CD40 with recombinant soluble CD40L trimer (sCD40LT) caused increased platelet CD62P expression, -granule and dense granule release, and the classical morphological changes associated with platelet activation. CD40 ligation also caused ß3 integrin activation, although this was not accompanied by platelet aggregation. These actions were abrogated by the CD40L blocking antibody TRAP-1 and the CD40 blocking antibodies M2 and M3, showing that activation was mediated by CD40L binding to platelet CD40. ß3 integrin blockade with eptifibatide had no effect, indicating that outside-in signaling via IIbß3 was not contributing to these CD40-mediated effects. CD40 ligation led to enhanced platelet-leukocyte adhesion, which is important in the recruitment of leukocytes to sites of thrombosis or inflammation. Our results support a role for CD40-mediated platelet activation in thrombosis, inflammation, and atherosclerosis

Near-field and far-field analysis of an azimuthally polarized slow Bloch mode microlaser

We report on the near- and far-field investigation of the slow Bloch modes associated with the G point of the Brillouin zone, for a honeycomb lattice photonic crystal, using near-field scanning optical microscopy (NSOM) and infra-red CCD camera. The array of doughnut-shaped monopolar mode (mode M) inside each unit cell, predicted previously by numerical simulation, is experimentally observed in the near-field by means of a metal-coated NSOM tip. In far-field, we detect the azimuthal polarization of the doughnut laser beam due to destructive and constructive interference of the mode radiating from the surface (mode TEM01*). A divergence of 2° for the laser beam and a mode size of (12.8 ± 1) μm for the slow Bloch mode at the surface of the crystal are also estimated. © 2010 Optical Society of America

Experiences of hearing voices: analysis of a novel phenomenological survey

Background: Auditory hallucinations—or voices—are a common feature of many psychiatric disorders and are also experienced by individuals with no psychiatric history. Understanding of the variation in subjective experiences of hallucination is central to psychiatry, yet systematic empirical research on the phenomenology of auditory hallucinations remains scarce. We aimed to record a detailed and diverse collection of experiences, in the words of the people who hear voices themselves. Methods: We made a 13 item questionnaire available online for 3 months. To elicit phenomenologically rich data, we designed a combination of open-ended and closed-ended questions, which drew on service-user perspectives and approaches from phenomenological psychiatry, psychology, and medical humanities. We invited people aged 16–84 years with experience of voice-hearing to take part via an advertisement circulated through clinical networks, hearing voices groups, and other mental health forums. We combined qualitative and quantitative methods, and used inductive thematic analysis to code the data and χ2 tests to test additional associations of selected codes. Findings: Between Sept 9 and Nov 29, 2013, 153 participants completed the study. Most participants described hearing multiple voices (124 [81%] of 153 individuals) with characterful qualities (106 [69%] individuals). Less than half of the participants reported hearing literally auditory voices—70 (46%) individuals reported either thought-like or mixed experiences. 101 (66%) participants reported bodily sensations while they heard voices, and these sensations were significantly associated with experiences of abusive or violent voices (p=0·024). Although fear, anxiety, depression, and stress were often associated with voices, 48 (31%) participants reported positive emotions and 49 (32%) reported neutral emotions. Our statistical analysis showed that mixed voices were more likely to have changed over time (p=0·030), be internally located (p=0·010), and be conversational in nature (p=0·010). Interpretation: This study is, to our knowledge, the largest mixed-methods investigation of auditory hallucination phenomenology so far. Our survey was completed by a diverse sample of people who hear voices with various diagnoses and clinical histories. Our findings both overlap with past large-sample investigations of auditory hallucination and suggest potentially important new findings about the association between acoustic perception and thought, somatic and multisensorial features of auditory hallucinations, and the link between auditory hallucinations and characterological entities

Why the Patient-Made Term 'Long Covid' is needed

The patient-made term ‘Long Covid’ is, we argue, a helpful and capacious term that is needed to address key medical, epidemiological and socio-political challenges posed by diverse symptoms persisting beyond four weeks after symptom onset suggestive of coronavirus disease 2019 (COVID-19). An international movement of patients (which includes all six authors) brought the persistence and heterogeneity of long-term symptoms to widespread visibility. The same grassroots movement introduced the term ‘Long Covid’ (and the cognate term ‘long-haulers’) to intervene in relation to widespread assumptions about disease severity and duration. Persistent symptoms following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are now one of the most pressing clinical and public health phenomena to address: their cause(s) is/are unknown, their effects can be debilitating, and the percentage of patients affected is unclear, though likely significant. The term ‘Long Covid’ is now used in scientific literature, the media, and in interactions with the WHO. Uncertainty regarding its value and meaning, however, remains. In this Open Letter, we explain the advantages of the term ‘Long Covid’ and bring clarity to some pressing issues of use and definition. We also point to the importance of centring patient experience and expertise in relation to ‘Long Covid’ research, as well as the provision of care and rehabilitation.</ns4:p

Thymic output and CD4 T-cell reconstitution in HIV-infected children on early and interrupted antiretroviral treatment: evidence from the CHER trial.

Objectives: Early treatment of HIV-infected children and adults is important for optimal immune reconstitution. Infants’ immune systems are more plastic and dynamic than older children’s or adults’, and deserve particular attention. This study aimed to understand the response of the HIV-infected infant immune system to early antiretroviral therapy (ART) and planned ART interruption and re-start. Design: We used linear and nonlinear regression and mixed-effects models to describe children’s CD4 trajectories and to identify predictors of CD4 count during early and interrupted ART. Methods: Data from HIV-infected children enrolled CHER trial, starting ART aged between 6 and 12 weeks, was used to explore the effect of ART on immune reconstitution. Results: Early treatment arrested the decline in CD4 count but did not fully restore it to the levels observed in HIV-uninfected children. Treatment interruption at 40 or 96 weeks resulted in a rapid decline in CD4 T-cells, which on retreatment returned to levels observed before interruption. Naïve CD4 T-cell count was an important determinant of overall CD4 levels. A strong correlation was observed between thymic output and the stable CD4 count both before and after treatment interruption. Conclusions: Early identification and treatment of HIV-infected infants is important to stabilize CD4 counts at the highest levels possible. Once stabilized, children’s CD4 counts appear resilient, with good potential for recovery following treatment interruption. The naïve T-cell pool and thymic production of naive cells are key determinants of children’s CD4 levels

Englacial Architecture of Lambert Glacier, East Antarctica

The analysis of englacial layers using radio-echo sounding data enables the characterisation and reconstruction of current and past ice-sheet flow. Despite the Lambert Glacier catchment being one of the largest in Antarctica, discharging ~16 % of East Antarctica&rsquo;s ice, its englacial architecture has been little analysed. Here, we present a comprehensive analysis of Lambert Glacier&rsquo;s englacial architecture using radio-echo sounding data collected by the Antarctica's Gamburtsev Province Project (AGAP) North survey. We used an &ldquo;internal-layering continuity index&rdquo; (ILCI) to characterise the internal architecture of the ice and identify four macro-scale ILCI zones with distinct glaciological contexts. Whilst the catchment is dominated by continuous englacial layering, disrupted or discontinuous layering is highlighted by the ILCI at both the onset of enhanced ice flow (defined here as &gt;15 ma&minus;1) and along the shear margin, revealing the transition from internal-deformation-controlled to basal-sliding-dominated ice flow. These zones are characterised by buckled and folded englacial layers which align with the current ice-flow regime, and which we interpret as evidence that the flow direction of the Lambert Glacier trunk has changed little, if at all, during the Holocene. However, disturbed englacial layers along a deep subglacial channel that does not correspond to modern ice-flow routing suggest that ice-flow change has occurred in a former tributary which fed Lambert Glacier from grid north. As large outlet systems such as Lambert Glacier are likely to play a vital role in the future drainage of the East Antarctic Ice Sheet, constraining their englacial architecture to reconstruct their past ice flow and assess basal conditions is important.</p

Unravelling subjectivity, embodied experience and (taking) psychotropic medication

This paper explores how distinctions between ‘intended’ and ‘side’ effects are troubled in personal narratives of taking psychotropic medications. Grounded in interviews with 29 participants diagnosed with mental illness in Victoria, Australia between February and December 2014, we consider how people interpret pharmaceutical compounds beyond their desired or intended effects, and how such effects shape and transform subjectivity and their relationship with their bodies. This paper contributes to recent discussions of mental illness and medication effects, informed by feminist science studies. It emphasises the co-constitution of social, affective and material relations in the context of ‘taking’ psychotropic medication. This paper discusses three key themes as important to the phenomenology of the nexus of illness and psychotropic medication: movement, ambivalence, and sociality. Our analysis demonstrates how psychotropic drugs are productive of subjectivity through their promises and potential, their unexpected harms and the institutions from which they are inseparable

Naive B cell output in HIV-infected and HIV-uninfected children.

In this study, we aimed to quantify KREC (kappa-deleting recombination excision circle) levels and naive B cell output in healthy HIV-uninfected children, compared with HIV-infected South African children, before and after starting ART (antiretroviral therapy). Samples were acquired from a Child Wellness Clinic (n = 288 HIV-uninfected South African children, 2 weeks-12 years) and the Children with HIV Early Antiretroviral Therapy (CHER) trial (n = 153 HIV-infected South African children, 7 weeks-8 years). Naive B cell output was estimated using a mathematical model combining KREC levels to reflect B cell emigration into the circulation, flow cytometry measures of naive unswitched B cells to quantify total body naive B cells, and their rates of proliferation using the intracellular marker Ki67. Naive B cell output increases from birth to 1 year, followed by a decline and plateau into late childhood. HIV-infected children on or off ART had higher naive B cell outputs than their uninfected counterparts (p = .01 and p = .04). This is the first study to present reference ranges for measurements of KRECs and naive B cell output in healthy and HIV-infected children. Comparison between HIV-uninfected healthy children and HIV-infected children suggests that HIV may increase naive B cell output. Further work is required to fully understand the mechanisms involved and clinical value of measuring naive B cell output in children