2,5-Di-(tert-butyl)-1,4-benzohydroquinone mobilizes inositol 1,4,5-trisphosphate-sensitive and -insensitive Ca2+ stores

AbstractIn permcabilized rat hepatocytcs a maximal concentration (25 μM) of 2,5-di-(tert-butyl)-1,4-benzohydroquinone (tBuBHQ) mobilized 70% of sequestered Ca2+ and a half-maximal effect was produced by 1.7 μM tBuBHQ. Inositol 1,4,5-trisphosphate (Ins(1,4,5) P3) stimulated release of about 40% of the intracellular Ca2+ stores. Combined applications of a range of tBuBHQ concentrations with a maximal concentration of Ins(1,4,5)P3 demonstrated that tBuBHQ has slight selectivity for the Ca2+ transport process of the Ins(1,4,5) P3-sensitive stores. We conclude that the Ins(1,4,5) P3-sensitive stores arc a subset of those sensitive to tBuBHQ and that the latter is therefore unlikely to prove useful as a tool to discriminate Ins(1,4,5) P3-sensitive and -insensitive Ca2+ stores though it may provide opportunities to design more selective agents

Pulmonary vasospasm in systemic sclerosis: noninvasive techniques for detection

In a subgroup of patients with systemic sclerosis (SSc), vasospasm affecting the pulmonary circulation may contribute to worsening respiratory symptoms, including dyspnea. Noninvasive assessment of pulmonary blood flow (PBF), utilizing inert-gas rebreathing (IGR) and dual-energy computed-tomography pulmonary angiography (DE-CTPA), may be useful for identifying pulmonary vasospasm. Thirty-one participants (22 SSc patients and 9 healthy volunteers) underwent PBF assessment with IGR and DE-CTPA at baseline and after provocation with a cold-air inhalation challenge (CACh). Before the study investigations, participants were assigned to subgroups: group A included SSc patients who reported increased breathlessness after exposure to cold air (n = 11), group B included SSc patients without cold-air sensitivity (n = 11), and group C patients included the healthy volunteers. Median change in PBF from baseline was compared between groups A, B, and C after CACh. Compared with groups B and C, in group A there was a significant decline in median PBF from baseline at 10 minutes (−10%; range: −52.2% to 4.0%; P < 0.01), 20 minutes (−17.4%; −27.9% to 0.0%; P < 0.01), and 30 minutes (−8.5%; −34.4% to 2.0%; P < 0.01) after CACh. There was no significant difference in median PBF change between groups B or C at any time point and no change in pulmonary perfusion on DE-CTPA. Reduction in pulmonary blood flow following CACh suggests that pulmonary vasospasm may be present in a subgroup of patients with SSc and may contribute to worsening dyspnea on exposure to cold

Acceptability of Specialist Psychotherapy with Emotion for Anorexia in Kent and Sussex (SPEAKS): A novel intervention for anorexia nervosa

Investigate the acceptability of Specialist Psychotherapy with Emotion for Anorexia in Kent and Sussex (SPEAKS), a novel intervention for anorexia nervosa (AN), conducted as a feasibility trial to provide an initial test of the intervention. SPEAKS therapy lasting 9-12 months was provided to 34 people with AN or atypical AN by eight specialist eating disorder therapists trained in the model across two NHS Trusts in the UK (Kent and Sussex) during a feasibility trial. All participants were offered a post-therapy interview; sixteen patients and six therapists agreed. All patient participants were adult females. Interviews were semi-structured and asked questions around individuals' experience of SPEAKS, the acceptability of the intervention and of the research methods. Interviews were analyzed using thematic analysis. Key areas explored in line with research questions led to 5 overarching themes and 14 subthemes: (1) shift in treatment focus and experience, (2) balancing resources and treatment outcomes, (3) navigating the online treatment environment, (4) therapist adaptation and professional development, and (5) research processes. SPEAKS was found to be an acceptable intervention for treating AN from the perspective of patients and therapists. The findings provide strong support for delivery of a larger scale randomized control trial. Recommendations for future improvements, particularly pertaining to therapist understanding of the treatment model are detailed, alongside broader clinical implications. We aimed to evaluate the acceptability of a new anorexia nervosa treatment called SPEAKS. Interviews were conducted with patients and therapists involved in the pilot study and responses were analyzed. Results showed that both patients and therapists found SPEAKS to be an acceptable treatment for anorexia nervosa. The study suggests that SPEAKS meets the criteria for moving forward with a larger trial to assess its effectiveness. [Abstract copyright: © 2024 The Authors. International Journal of Eating Disorders published by Wiley Periodicals LLC.

Human limbal mesenchymal stem cells express ABCB5 and can grow on amniotic membrane

Aim: To isolate and characterize limbal mesenchymal stem cells (LMSCs) from human corneoscleral rings. Materials & methods: Cells were isolated from corneoscleral rings and cultured in a mesenchymal stem cell (MSC)-selective media and examined for differentiation, phenotyping and characterization. Results: LMSCs were capable of trilineage differentiation, adhered to tissue culture plastic, expressed HLA class I and cell surface antigens associated with human MSC while having no/low expression of HLA class II and negative hematopoietic lineage markers. They were capable for CXCL12-mediated cellular migration. LMSCs adhered, proliferated on amniotic membrane and expressed the common putative limbal stem cell markers. Conclusion: Limbal-derived MSC exhibited plasticity, could maintain limbal markers expression and demonstrated viable growth on amniotic membrane

Replacement of the Trabecular Meshwork Cells—A Way Ahead in IOP Control?

Glaucoma is one of the leading causes of vision loss worldwide, characterised with irreversible optic nerve damage and progressive vision loss. Primary open-angle glaucoma (POAG) is a subset of glaucoma, characterised by normal anterior chamber angle and raised intraocular pressure (IOP). Reducing IOP is the main modifiable factor in the treatment of POAG, and the trabecular meshwork (TM) is the primary site of aqueous humour outflow (AH) and the resistance to outflow. The structure and the composition of the TM are key to its function in regulating AH outflow. Dysfunction and loss of the TM cells found in the natural ageing process and more so in POAG can cause abnormal extracellular matrix (ECM) accumulation, increased TM stiffness, and increased IOP. Therefore, repair or regeneration of TM’s structure and function is considered as a potential treatment for POAG. Cell transplantation is an attractive option to repopulate the TM cells in POAG, but to develop a cell replacement approach, various challenges are still to be addressed. The choice of cell replacement covers autologous or allogenic approaches, which led to investigations into TM progenitor cells, induced pluripotent stem cells (iPSCs), and mesenchymal stem cells (MSCs) as potential stem cell source candidates. However, the potential plasticity and the lack of definitive cell markers for the progenitor and the TM cell population compound the biological challenge. Morphological and differential gene expression of TM cells located within different regions of the TM may give rise to different cell replacement or regenerative approaches. As such, this review describes the different approaches taken to date investigating different cell sources and their differing cell isolation and differentiation methodologies. In addition, we highlighted how these approaches were evaluated in different animal and ex vivo model systems and the potential of these methods in future POAG treatment

The diagnostic accuracy of clinical tests for anterior cruciate ligament tears are comparable but the Lachman test has been previously overestimated: a systematic review and meta-analysis

Abstract Purpose The diagnostic accuracy of clinical tests for anterior cruciate ligament injury has been reported in previous systematic reviews. Numerous studies in these reviews include subjects with additional knee ligament injury, which could affect the sensitivity of the tests. Meta-analyses have also been performed using methods that do not account for the non-independence of sensitivity and specificity, potentially overestimating diagnostic accuracy. The aim of this study was to report the diagnostic accuracy of clinical tests for anterior cruciate ligament tears (partial and complete) without concomitant knee ligament injury. Methods A systematic review with meta-analysis was performed according to the PRISMA guidelines. Meta-analyses included studies reporting the specificity and/or sensitivity of tests with or without concomitant meniscal injury. Where possible, pooled diagnostic estimates were calculated with bivariate random-effects modelling to determine the most accurate effect sizes. Diagnostic accuracy values are presented for the anterior drawer, Lachman, Lever sign and pivot shift tests overall and in acute or post-acute presentations. Results Pooled estimates using a bivariate model for overall sensitivity and specificity respectively were as follows: anterior drawer test 83% [95% CI, 77–88] and 85% [95% CI, 64–95]; Lachman test 81% [95% CI, 73–87] and 85% [95% CI, 73–92]; pivot shift test 55% [95% CI, 47–62] and 94% [95% CI, 88–97]; Lever sign test 83% [95% CI, 68–92] and 91% [95% CI, 83–95]. For specific presentations, the sensitivity and specificity of the Lachman test, respectively, were: complete tears 68% [95% CI, 54–79] and 79% [95% CI, 51–93]; post-acute injuries 70% [95% CI, 57–80] and 77% [95% CI, 53–91]. Conclusions The pivot shift and Lever sign were the best tests overall for ruling in or ruling out an anterior cruciate ligament tear, respectively. The diagnostic accuracy of the Lachman test, particularly in post-acute presentations and for complete tears, is lower than previously reported. Further research is required to establish more accurate estimates for the Lachman test in acute presentations and partial ligament tears using bivariate analysis. Level of evidence III. </jats:sec

A Molecular–Structure Hypothesis

The self-similar symmetry that occurs between atomic nuclei, biological growth structures, the solar system, globular clusters and spiral galaxies suggests that a similar pattern should characterize atomic and molecular structures. This possibility is explored in terms of the current molecular structure-hypothesis and its extension into four-dimensional space-time. It is concluded that a quantum molecule only has structure in four dimensions and that classical (Newtonian) structure, which occurs in three dimensions, cannot be simulated by quantum-chemical computation

Sub-Planckian black holes and the Generalized Uncertainty Principle

The Black Hole Uncertainty Principle correspondence suggests that there could exist black holes with mass beneath the Planck scale but radius of order the Compton scale rather than Schwarzschild scale. We present a modified, self-dual Schwarzschild-like metric that reproduces desirable aspects of a variety of disparate models in the sub-Planckian limit, while remaining Schwarzschild in the large mass limit. The self-dual nature of this solution under $M \leftrightarrow M^{-1}$ naturally implies a Generalized Uncertainty Principle with the linear form $\Delta x \sim \frac{1}{\Delta p} + \Delta p$. We also demonstrate a natural dimensional reduction feature, in that the gravitational radius and thermodynamics of sub-Planckian objects resemble that of $(1+1)$-D gravity. The temperature of sub-Planckian black holes scales as $M$ rather than $M^{-1}$ but the evaporation of those smaller than $10^{-36}$g is suppressed by the cosmic background radiation. This suggests that relics of this mass could provide the dark matter.Comment: 12 pages, 9 figures, version published in J. High En. Phy