Paroxetine suppresses recombinant human P2X7 responses

P2X7 receptor (P2X7) activity may link inflammation to depressive disorders. Genetic variants of human P2X7 have been linked with major depression and bipolar disorders, and the P2X7 knockout mouse has been shown to exhibit anti-depressive-like behaviour. P2X7 is an ATP-gated ion channel and is a major regulator of the pro-inflammatory cytokine interleukin 1β (IL-1β) secretion from monocytes and microglia. We hypothesised that antidepressants may elicit their mood enhancing effects in part via modulating P2X7 activity and reducing inflammatory responses. In this study, we determined whether common psychoactive drugs could affect recombinant and native human P2X7 responses in vitro. Common antidepressants demonstrated opposing effects on human P2X7-mediated responses; paroxetine inhibited while fluoxetine and clomipramine mildly potentiated ATP-induced dye uptake in HEK-293 cells stably expressing recombinant human P2X7. Paroxetine inhibited dye uptake mediated by human P2X7 in a concentration-dependent manner with an IC50 of 24 μM and significantly reduces ATP-induced inward currents. We confirmed that trifluoperazine hydrochloride suppressed human P2X7 responses (IC50 of 6.4 μM). Both paroxetine and trifluoperazine did not inhibit rodent P2X7 responses, and mutation of a known residue (F 95L) did not alter the effect of either drug, suggesting neither drug binds at this site. Finally, we demonstrate that P2X7-induced IL-1β secretion from lipopolysaccharide (LPS)-primed human CD14+ monocytes was suppressed with trifluoperazine and paroxetine

Insights from Amphioxus into the Evolution of Vertebrate Cartilage

Central to the story of vertebrate evolution is the origin of the vertebrate head, a problem difficult to approach using paleontology and comparative morphology due to a lack of unambiguous intermediate forms. Embryologically, much of the vertebrate head is derived from two ectodermal tissues, the neural crest and cranial placodes. Recent work in protochordates suggests the first chordates possessed migratory neural tube cells with some features of neural crest cells. However, it is unclear how and when these cells acquired the ability to form cellular cartilage, a cell type unique to vertebrates. It has been variously proposed that the neural crest acquired chondrogenic ability by recruiting proto-chondrogenic gene programs deployed in the neural tube, pharynx, and notochord. To test these hypotheses we examined the expression of 11 amphioxus orthologs of genes involved in neural crest chondrogenesis. Consistent with cellular cartilage as a vertebrate novelty, we find that no single amphioxus tissue co-expresses all or most of these genes. However, most are variously co-expressed in mesodermal derivatives. Our results suggest that neural crest-derived cartilage evolved by serial cooption of genes which functioned primitively in mesoderm

Polarimetric Multi-View Inverse Rendering

A polarization camera has great potential for 3D reconstruction since the angle of polarization (AoP) of reflected light is related to an object's surface normal. In this paper, we propose a novel 3D reconstruction method called Polarimetric Multi-View Inverse Rendering (Polarimetric MVIR) that effectively exploits geometric, photometric, and polarimetric cues extracted from input multi-view color polarization images. We first estimate camera poses and an initial 3D model by geometric reconstruction with a standard structure-from-motion and multi-view stereo pipeline. We then refine the initial model by optimizing photometric and polarimetric rendering errors using multi-view RGB and AoP images, where we propose a novel polarimetric rendering cost function that enables us to effectively constrain each estimated surface vertex's normal while considering four possible ambiguous azimuth angles revealed from the AoP measurement. Experimental results using both synthetic and real data demonstrate that our Polarimetric MVIR can reconstruct a detailed 3D shape without assuming a specific polarized reflection depending on the material.Comment: Paper accepted in ECCV 202

Recommendations for surveillance of pulmonary dysfunction among childhood, adolescent, and young adult cancer survivors: a report from the International Late Effects of Childhood Cancer Guideline Harmonization Group

\ua9 2024. Childhood, adolescent, and young adult (CAYA) cancer survivors are at risk of pulmonary dysfunction. Current follow-up care guidelines are discordant. Therefore, the International Late Effects of Childhood Cancer Guideline Harmonization Group established and convened a panel of 33 experts to develop evidence-based surveillance guidelines. We critically reviewed available evidence regarding risk factors for pulmonary dysfunction, types of pulmonary function testing, and timings of surveillance, then we formulated our recommendations. We recommend that CAYA cancer survivors and healthcare providers are aware of reduced pulmonary function risks and pay vigilant attention to potential symptoms of pulmonary dysfunction, especially among survivors treated with allogeneic haematopoietic stem cell transplantation, thoracic radiotherapy, and thoracic surgery. Based on existing limited evidence and current lack of interventions, our panel recommends pulmonary function testing only for symptomatic survivors. Since scarce existing evidence informs our recommendation, we highlight the need for prospective collaborative studies to address pulmonary function knowledge gaps among CAYA cancer survivors

Feasibility and acceptability of point of care HIV testing in community outreach and GUM drop-in services in the North West of England: A programmatic evaluation

Background: In Liverpool, injecting drug users (IDUs), men-who-have-sex-with-men (MSM) and UK Africans experience a disproportionate burden of HIV, yet services do not reach out to these groups and late presentations continue. We set out to: increase testing uptake in targeted marginalized groups through a community and genitourinary medicine (GUM)-based point of care testing (POCT) programme; and conduct a process evaluation to examine service provider inputs and document service user perceptions of the programme. Methods: Mixed quantitative, qualitative and process evaluation methods were used. Service providers were trained to use fourth generation rapid antibody/antigen HIV tests. Existing outreach services incorporated POCT into routine practice. Clients completed a semi-structured questionnaire and focus group discussions (FGDs) were held with service providers. Results: Between September 2009 and June 2010, 953 individuals underwent POCT (GUM: 556 [59%]; communitybased sites: 397 [42%]). Participants in the community were more likely to be male (p = 0.028), older (p < 0.001), of UK African origin (p < 0.001) and IDUs (p < 0.001) than participants from the GUM clinic. Seventeen new HIV diagnoses were confirmed (prevalence = 1.8%), 16 of whom were in risk exposure categories (prevalence: 16/517, 3.1%). Questionnaires and FGDs showed that clients and service providers were supportive of POCT, highlighting benefits of reaching out to marginalised communities and incorporating HIV prevention messages. Conclusions: Community and GUM clinic-based POCT for HIV was feasible and acceptable to clients and service providers in a low prevalence setting. It successfully reached target groups, many of whom would not have otherwise tested. We recommend POCT be considered among strategies to increase the uptake of HIV testing among groups who are currently underserved

Gain-through-filtering enables tuneable frequency comb generation in passive optical resonators

Optical frequency combs (OFCs), consisting of a set of phase-locked, equally spaced laser frequency lines, have enabled a great leap in precision spectroscopy and metrology since seminal works of Hänsch et al. Nowadays, OFCs are cornerstones of a wealth of further applications ranging from chemistry and biology to astrophysics and including molecular fingerprinting and light detection and ranging (LIDAR) systems, among others. Driven passive optical resonators constitute the ideal platform for OFC generation in terms of compactness and low energy footprint. We propose here a technique for the generation of OFCs with a tuneable repetition rate in externally driven optical resonators based on the gain-through-filtering process, a simple and elegant method, due to asymmetric spectral filtering on one side of the pump wave. We demonstrate a proof-of-concept experimental result in a fibre resonator, pioneering a new technique that does not require specific engineering of the resonator dispersion to generate frequency-agile OFCs

Influence of social support on cognitive function in the elderly

BACKGROUND: Social support is important in daily activities of the elderly. This study tests the hypothesis that there is an association between social support and cognitive function among the elderly in a community setting. METHODS: Face-to-face interviews were conducted in a cross-sectional stratified random sample of 4,993 elderly (≥65 years) city residents. Using multiple regression analysis, we investigated the influence of social support on cognitive function. RESULTS: 12% were over 80 years old. 53.28% were men. 67.14% were married. Higher Short Portable Mental Status Questionnaire (SPMSQ) scores (higher score means better cognitive function) were associated with strong social support, as measured by marital status and perceived positive support from friends. Lower cognitive function was associated with older and with female respondents. Only instrumental activities of daily living (IADL) were statistically and negatively related to SPMSQ. Lower functional status was associated with lower cognitive function. Elders with grade school educations had lower SPMSQ scores than did elders with high school educations. CONCLUSIONS: In Taiwan, higher cognitive function in community-living elderly was associated with increased social support. Life-style management should provide social activities for the elderly to promote a better quality of life