Previously, we have shown that native ambient mass spectrometry imaging allows the spatial mapping of folded proteins and their complexes in thin tissue sections. Subsequent top-down native ambient ...mass spectrometry of adjacent tissue section enables protein identification. The challenges associated with protein identification by this approach are (i) the low abundance of proteins in tissue and associated long data acquisition timescales and (ii) irregular spatial distributions which hamper targeted sampling of the relevant tissue location. Here, we demonstrate that these challenges may be overcome through integration of laser capture microdissection in the workflow. We show identification of intact protein assemblies in rat liver tissue and apply the approach to identification of proteins in the granular layer of rat cerebellum.
Integration of laser capture microdissection and top-down mass spectrometry aids protein identification in spatially-resolved native ambient mass spectrometry.
The article discusses how the lifesaving power of antimicrobial agents that have saved the lives of millions of patients as well as improved outcomes is at threat from antibiotic-resistant infections ...and must be preserved at all costs. The need to develop comprehensive, multipronged strategies towards the same is highlighted.
Introduction
Patients presenting to the emergency departments in pain often experience co‐occurring symptoms. Anticipatory anxiety in the emergency department may be currently under‐recognised. ...Clinical tools to facilitate the assessment of co‐occurring symptoms aligns with providing more patient centred care and improved outcomes and experience.
Aims
This integrative review aimed to identify and examine the psychometric properties of tools currently used for pain and anticipatory anxiety assessment in adult patients presenting to the emergency department. This study also aimed to identify the current clinical practice used to assess adult pain and anticipatory anxiety.
Methods
Whittemore and Knafl's methodology guided the review process, and it is reported according to relevant items from PRISMA checklist. Studies were included if they focused on tools for pain or anxiety assessment of adults in emergency departments in English language publications since 2010. Quality of studies was evaluated using the Mixed Methods Appraisal Tool (MMAT). The results were summarised through narrative synthesis.
Results
A total of 15 studies were identified for narrative synthesis. Six tools for pain, and four tools for anticipative anxiety were found. All currently used clinical tools assess symptoms in isolation. There was limited discussion of the clinical context of identified tools within the included studies.
Conclusion
Pain and anxiety assessment are currently performed in symptom isolation with a variety of tools with varying degrees of reliability. There exists a lack of clinical tools able to assess co‐occurring symptoms of pain and anticipatory anxiety in the clinical setting of the emergency department. No studies discussed clinical tool use in current practice.
Relevance to Clinical Practice
The reconstruction of available pain and anxiety assessment tools into one validated and holistic tool for assessment in the ED clinical setting, would provide a contextually appropriate guide to clinical assessment and treatment. Acknowledging and measuring these symptoms may facilitate future rigorous testing of experimental studies of novel methods to reduce pain and anxiety in the ED.
No Patient or Public Contribution
Patient or public contribution does not apply to this Integrative Review.
Clinical Trial Registration Number
Not applicable.
TOR kinase complex I (TORC1) is a key regulator of cell growth and metabolism in all eukaryotes. Previous studies in yeast have shown that three GTPases-Gtr1, Gtr2, and Rho1-bind to TORC1 in nitrogen ...and amino acid starvation conditions to block phosphorylation of the S6 kinase Sch9 and activate protein phosphatase 2A (PP2A). This leads to downregulation of 450 Sch9-dependent protein and ribosome synthesis genes and upregulation of 100 PP2A-dependent nitrogen assimilation and amino acid synthesis genes. Here, using bandshift assays and microarray measurements, we show that the TORC1 pathway also populates three other stress/starvation states. First, in glucose starvation conditions, the AMP-activated protein kinase (AMPK/Snf1) and at least one other factor push the TORC1 pathway into an off state, in which Sch9-branch signaling and PP2A-branch signaling are both inhibited. Remarkably, the TORC1 pathway remains in the glucose starvation (PP2A inhibited) state even when cells are simultaneously starved for nitrogen and glucose. Second, in osmotic stress, the MAPK Hog1/p38 drives the TORC1 pathway into a different state, in which Sch9 signaling and PP2A-branch signaling are inhibited, but PP2A-branch signaling can still be activated by nitrogen starvation. Third, in oxidative stress and heat stress, TORC1-Sch9 signaling is blocked while weak PP2A-branch signaling occurs. Together, our data show that the TORC1 pathway acts as an information-processing hub, activating different genes in different conditions to ensure that available energy is allocated to drive growth, amino acid synthesis, or a stress response, depending on the needs of the cell.
Several studies have suggested that there is a link between synaesthesia and autism but the nature of that link remains poorly characterised. The present study considers whether atypical sensory ...sensitivity may be a common link between the conditions. Sensory hypersensitivity (aversion to certain sounds, touch, etc., or increased ability to make sensory discriminations) and/or hyposensitivity (desire to stimulate the senses , or a reduced response to sensory stimuli are a recently introduced diagnostic feature of autism spectrum conditions (ASC). Synaesthesia is defined by unusual sensory experiences and has also been linked to a typical cortical hyper-excitability. The Glasgow Sensory Questionnaire (GSQ) was administered to synaesthetes and people with ASC. Both groups reported increased sensory sensitivity relative to controls with a large effect size. Both groups also reported a similar pattern of both increased hyper- and hypo-sensitivities across multiple senses. The AQ (Autism-Spectrum Quotient) scores were elevated in the synaesthetes, and one subscale of this measure (attention to detail) placed synaesthetes within the autistic range. A standard laboratory test of visual stress (the Pattern Glare Test), administered online, corroborated the findings of increased sensitivity to aversive visual stimuli in synaesthetes. We conclude that atypical sensory sensitivity is an important shared feature between autism and synaesthesia.
BACKGROUND:Self-testing may increase HIV testing and decrease the time people with HIV are unaware of their status, but there is concern that absence of counseling may result in increased HIV risk.
...SETTING:Seattle, Washington.
METHODS:We randomly assigned 230 high-risk HIV-negative men who have sex with men (MSM) to have access to oral fluid HIV self-tests at no cost versus testing as usual .for 15 months. The primary outcome was self-reported number of HIV tests during follow-up. To evaluate self-testing’s impact on sexual behavior, we compared the following between armsnon-HIV-concordant condomless anal intercourse (CAI) and number of male CAI partners in the last 3 months (measured at 9 and 15 months) and diagnosis with a bacterial sexually transmitted infection (STIearly syphilis, gonorrhea, chlamydial infection) at the final study visit (15 months). A post hoc analysis compared the number of STI tests reported during follow-up.
RESULTS:Men randomized to self-testing reported significantly more HIV tests during follow-up (mean=5.3, 95%CI=4.7-6.0) than those randomized to testing as usual (3.6, 3.2-4.0; p<.0001), representing an average increase of 1.7 tests per participant over 15 months. Men randomized to self-testing reported using an average of 3.9 self-tests. Self-testing was non-inferior with respect to all markers of HIV risk. Men in the self-testing arm reported significantly fewer STI tests during follow-up (mean=2.3, 95%CI=1.9-2.7) than men in the control arm (3.2, 2.8-3.6; p=0.0038).
CONCLUSIONS:Access to free HIV self-testing increased testing frequency among high-risk MSM and did not impact sexual behavior or STI acquisition.
The stepped wedge cluster randomized design has received increasing attention in pragmatic clinical trials and implementation science research. The key feature of the design is the unidirectional ...crossover of clusters from the control to intervention conditions on a staggered schedule, which induces confounding of the intervention effect by time. The stepped wedge design first appeared in the Gambia hepatitis study in the 1980s. However, the statistical model used for the design and analysis was not formally introduced until 2007 in an article by Hussey and Hughes. Since then, a variety of mixed-effects model extensions have been proposed for the design and analysis of these trials. In this article, we explore these extensions under a unified perspective. We provide a general model representation and regard various model extensions as alternative ways to characterize the secular trend, intervention effect, as well as sources of heterogeneity. We review the key model ingredients and clarify their implications for the design and analysis. The article serves as an entry point to the evolving statistical literatures on stepped wedge designs.
For the first time, using aqueous solution calorimetry, we clearly identify the chemisorption of an unusually strong iodine charge-transfer (CT) complex within the cages of a metal–organic framework. ...Specifically, we studied the sorption of iodine gas in zeolitic imidazolate framework-8 (ZIF-8, Zn(2-methylimidazolate)2). Two iodine-loaded ZIF-8 samples were examined. The first, before thermal treatment, contained 0.17 I2/Zn on the surface and 0.59 I2/Zn inside the cage. The second sample was thermally treated, leaving only cage-confined iodine, 0.59 I2/Zn. The energetics of iodine confinement per I2 (relative to solid I2) in ZIF-8 are ΔH ads = −41.47 ± 2.03 kJ/(mol I2) within the cage and ΔH ads = −18.06 ± 0.62 kJ/(mol I2) for surface-bound iodine. The cage-confined iodine exhibits a 3-fold increase in binding energy over CT complexes on various organic adsorbents, which show only moderate exothermic heats of binding, from −5 to −15 kJ/(mol I2). The ZIF-8 cage geometry allows each iodine atom to form two CT complexes between opposing 2-methylimidazolate linkers, creating the ideal binding site to maximize iodine retention.
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