Climate Change.

As human-induced climate change warms the planet, its health impacts will affect all populations, but certain groups will be more vulnerable to its impacts. Given its role as a health care safety net, emergency medicine will play a crucial role in addressing these health conditions. Additionally, with its expertise in disaster medicine, interdisciplinary collaboration, and health care systems knowledge, emergency medicine has the potential to lead the health care sector's response to climate change.

Priorities for research promoting mental health in the south and east of Asia.

Progress in promoting mental health, preventing mental illness, and improving care for people affected by mental illness is unlikely to occur if efforts remain separated from existing public health programs and the principles of public health action. Experts met recently to discuss integrating public health and mental health strategies in the south and east of Asia, especially in low- and middle-income countries. Areas of research identified as high priority were: 1) integrating mental health into perinatal care; 2) providing culturally-adjusted support for carers of people with mental and physical disorders; 3) using digital health technologies for mental health care in areas with limited resources and 4) building local research capacity. Selection of these areas was informed by their relative novelty in the region, ease of implementation, likely widespread benefit, and potential low costs. In this article, we summarise available evidence, highlight gaps and call for collaborations with research centres, leaders and persons with lived experience within and beyond the region.

Diversifying the functions of heme proteins with non-porphyrin cofactors.

Heme proteins perform diverse biochemical functions using a single iron porphyrin cofactor. This versatility makes them attractive platforms for the development of new functional proteins. While directed evolution and metal substitution have expanded the properties, reactivity, and applications of heme proteins, the incorporation of porphyrin analogs remains an underexplored approach. This review discusses the replacement of heme with non-porphyrin cofactors, such as porphycene, corrole, tetradehydrocorrin, phthalocyanine, and salophen, and the attendant properties of these conjugates. While structurally similar, each ligand exhibits distinct optical and redox properties, as well as unique chemical reactivity. These hybrids serve as model systems to elucidate the effects of the protein environment on the electronic structure, redox potentials, optical properties, or other features of the porphyrin analog. Protein encapsulation can confer distinct chemical reactivity or selectivity of artificial metalloenzymes that cannot be achieved with the small molecule catalyst alone. Additionally, these conjugates can interfere with heme acquisition and uptake in pathogenic bacteria, providing an inroad to innovative antibiotic strategies. Together, these examples illustrate the diverse functionality that can be achieved by cofactor substitution. The further expansion of this approach will access unexplored chemical space, enabling the development of superior catalysts and the creation of heme proteins with emergent properties.

Ag(III)···Ag(III) Argentophilic Interaction in a Cofacial Corrole Dyad.

Metallophilic interactions between closed-shell metal centers are exemplified by d10 ions, with Au(I) aurophilic interactions as the archetype. Such an interaction extends to d8 species, and examples involving Au(III) are prevalent. Conversely, Ag(III) argentophilic interactions are uncommon. Here, we identify argentophilic interactions in silver corroles, which are authentic Ag(III) species. The crystal structure of a monomeric silver corrole is a dimer in the solid state, and the macrocycle exhibits an atypical domed conformation. In order to evaluate whether this represents an authentic metallophilic interaction or a crystal-packing artifact, the analogous cofacial or "pacman" corrole was prepared. The conformation of the monomer was recapitulated in the silver pacman corrole, exhibiting a short 3.67 Å distance between metal centers and a significant compression of the xanthene backbone. Theoretical calculations support the presence of a rare Ag(III)···Ag(III) argentophilic interaction in the pacman complex.

Solvent-Induced Spin-State Change in Copper Corroles.

The electronic structure of copper corroles has been a topic of debate and revision since the advent of corrole chemistry. The ground state of these compounds is best described as an antiferromagnetically coupled Cu(II) corrole radical cation. In coordinating solvents, these molecules become paramagnetic, and this is often accompanied by a color change. The underlying chemistry of these solvent-induced properties is currently unknown. Here, we show that a coordinating solvent, such as pyridine, induces a change in the ground spin state from an antiferromagnetically coupled Cu(II) corrole radical cation to a ferromagnetically coupled triplet. Over time, the triplet reacts to produce a species with spectral signatures that are characteristic of the one-electron-reduced Cu(II) corrole. These observations account for the solvent-induced paramagnetism and the associated color changes that have been observed for copper corroles in coordinating solvents.

Corrole-protein interactions in H-NOX and HasA.

Replacing the native porphyrin cofactor in haem proteins has led to the development of novel designer proteins for a variety of applications. In most cases, haem analogues bind in a way that is comparable to the iron porphyrin, but this is not necessarily the case for complexes bearing non-exchangeable ligands. This study probes how a P[double bond, length as m-dash]O corrole binds to functionally disparate hemoproteins: a haem-dependent oxygen sensor (H-NOX) and a haem-scavenging protein (HasA). The results demonstrate that the protein-cofactor interactions are distinct from the native, haem-bound holoprotein. In H-NOX, the P[double bond, length as m-dash]O unit primarily hydrogen bonds with the haem-ligating histidine (H102), rather than the hydrogen-bonding network that stabilises the Fe(ii)-O2 complex in the native protein. In the absence of H102, the protein is still able to bind the corrole, albeit at reduced levels. Molecular dynamics simulations were utilised to determine the flexibility of apo H-NOX and revealed the coupled motion of key residues necessary for corrole binding. In the case of HasA, the P[double bond, length as m-dash]O unit does not primarily interact with either the haem-ligating histidine (H32) or tyrosine (Y75). Instead, histidine 83, the hydrogen-bonding partner for Y75, is critical for P[double bond, length as m-dash]O corrole binding. The conformation of HasA is interrogated by site-specifically labelling the protein and exploiting Förster resonance energy transfer (FRET) to determine the dye-cofactor distance. HasA reconstituted with the P[double bond, length as m-dash]O corrole exhibits an extended, apo-like conformation. Together, these results demonstrate that non-natural cofactors can bind to proteins in unexpected ways and highlight the need to uncover these interactions for the further development of designer haem proteins.

Ratiometric Oxygen Sensing with H-NOX Protein Conjugates.

Ratiometric sensors are self-referencing constructs that are functional in cells and tissues, and the read-out is independent of sensor concentration. One strategy for ratiometric sensing is to utilize two-color emission, where one component possesses analyte-dependent emission and the other is independent of analyte concentration, serving as an internal standard. In this way, the intensity ratio of the two components is a quantitative measure of the analyte. In this study, protein-based ratiometric oxygen sensors are prepared using the heme nitric oxide/oxygen-binding protein (H-NOX) from the thermophilic bacterium Caldanaerobacter subterraneus. The native heme cofactor is replaced with a Pd(II) or Pt(II) porphyrin as the oxygen-responsive phosphor. Mutagenesis is performed to incorporate a cysteine residue on the protein surface for thiol/maleimide coupling of the oxygen-insensitive dye, which serves as a Förster resonance energy transfer (FRET) donor for the porphyrin. While both Pd(II)- and Pt(II)-based sensors are responsive over biologically relevant ranges, the Pd sensor exhibits greater sensitivity at lower oxygen concentrations. Together, these sensors represent a new class of protein-based ratiometric oxygen sensors, and the modular platform allows the oxygen sensitivity to be tailored for a specific application. This proof-of-principle study has identified the key considerations and optimal methodologies to develop and subsequently refine protein-based ratiometric oxygen sensors.

Intermittent social stress produces different short- and long-term effects on effort-based reward-seeking behavior.

Previous studies show that intermittent social defeat (ISD) stress increases self-administration of psychostimulants, which suggests that ISD promotes reward-seeking behavior and, ultimately, increases vulnerability to develop drug abuse. The present study investigates whether ISD alters cost/benefit evaluations to promote reward-seeking behavior and whether these alterations are time-dependent. Male rats performed two different tasks that assessed their motivation to seek and consume food rewards. An effort-discounting task in which rats chose between less and more effortful options (i.e., 1 lever-press versus 2, 5, 10 or 20 lever-presses) associated with low- and high-reward (i.e., 1 sugar pellet versus 3 sugar pellets), respectively; and a progressive ratio task in which rats had to increase their effort (more lever presses) to obtain a sugar pellet. ISD consisted of exposing animals to social defeat once every three days for ten days (4 stress episodes). Rats were tested 24-48 h after stress episodes, and 1 week and 6 weeks after the last stress episode. In the effort-discounting task, stressed animals showed a decrease in their preference for high rewards associated with more effort (i.e., 10 and 20 lever-presses). These effects were transient and not maintained one week after stress. In the progressive ratio task, stressed animals showed an increase in the number of lever presses to obtain rewards that emerged six weeks after the last stress episode. These results suggest different short- and long-term effects on the motivation for rewards after ISD and indicate temporal dynamic adaptations in the function of the brain reward system.

Designer Heme Proteins: Achieving Novel Function with Abiological Heme Analogues.

Heme proteins have proven to be a convenient platform for the development of designer proteins with novel functionalities. This is achieved by substituting the native iron porphyrin cofactor with a heme analogue that possesses the desired properties. Replacing the iron center of the porphyrin with another metal provides one inroad to novel protein function. A less explored approach is substitution of the porphyrin cofactor with an alternative tetrapyrrole macrocycle or a related ligand. In general, these ligands exhibit chemical properties and reactivity that are distinct from those of porphyrins. While these techniques have most prominently been utilized to develop artificial metalloenzymes, there are many other applications of this methodology to problems in biochemistry, health, and medicine. Incorporation of synthetic cofactors into protein environments represents a facile way to impart water solubility and biocompatibility. It circumvents the laborious synthesis of water-soluble cofactors, which often introduces substantial charge that leads to undesired bioaccumulation. To this end, the incorporation of unnatural cofactors in heme proteins has enabled the development of designer proteins as optical oxygen sensors, MRI contrast agents, spectroscopic probes, tools to interrogate protein function, antibiotics, and fluorescent proteins.Incorporation of an artificial cofactor is frequently accomplished by denaturing the holoprotein with removal of the heme; the refolded apoprotein is then reconstituted with the artificial cofactor. This process often results in substantial protein loss and does not necessarily guarantee that the refolded protein adopts the native structure. To circumvent these issues, our laboratory has pioneered the use of the RP523 strain of E. coli to incorporate artificial cofactors into heme proteins using expression-based methods. This strain lacks the ability to biosynthesize heme, and the bacterial cell wall is permeable to heme and related molecules. In this way, heme analogues supplemented in the growth medium are incorporated into heme proteins. This approach can also be leveraged for the direct expression of the apoprotein for subsequent reconstitution.These methodologies have been exploited to incorporate non-native cofactors into heme proteins that are resistant to harsh environmental conditions: the heme nitric oxide/oxygen binding protein (H-NOX) from Caldanaerobacter subterraneus (Cs) and the heme acquisition system protein A (HasA) from Pseudomonas aeruginosa (Pa). The exceptional stability of these proteins makes them ideal scaffolds for biomedical applications. Optical oxygen sensing has been accomplished using a phosphorescent ruthenium porphyrin as the artificial heme cofactor. Paramagnetic manganese and gadolinium porphyrins yield high-relaxivity, protein-based MRI contrast agents. A fluorescent phosphorus corrole serves as a heme analogue to produce fluorescent proteins. Iron complexes of nonporphyrin cofactors bound to HasA inhibit the growth of pathogenic bacteria. Moreover, HasA can deliver a gallium phthalocyanine into the bacterial cytosol to serve as a sensitizer for photochemical sterilization. Together, these examples illustrate the potential for designer heme proteins to address burgeoning problems in the areas of health and medicine. The concepts and methodologies presented in this Account can be extended to the development of next-generation biomedical sensing and imaging agents to identify and quantify clinically relevant metabolites and other key disease biomarkers.

Lung Health in the Solomon Islands: A Mixed Methods Study.

BACKGROUND AND OBJECTIVES: Despite a population of 600,000 people from 900 islands, there is little published data on the prevalence of lung disease in the Solomon Islands. We sought to 1) estimate the prevalence of obstructive lung disease (OLD) in Gizo, Solomon Islands, 2) identify risk factors for respiratory disease in this population and 3) review current management practices for respiratory disease through an audit of local emergency department (ED) presentations. METHODS: A two-part mixed methods study was performed between March and May 2019; the first was a population-based, cross-sectional study conducted in Gizo, Solomon Islands, with a random sample undergoing questionnaires and spirometry. The second was an audit of Gizo Hospital ED records to assess presentation numbers, diagnoses and outcomes. RESULTS: A total of 104 patients were randomly selected for spirometry. The mean age was 46.9 years. Current smoking rates were high (24.0% overall, 43.3% age < 40, 16.2% age ≥ 40) as was regular (>10h/week) exposure to indoor/enclosed wood fire ovens (51.5%). The prevalence of COPD was 3.2% overall. A further 9.7% of participants demonstrated significant bronchodilator responsiveness suggestive of possible asthma. Most patients seen in ED presented with a respiratory condition or fever/viral illness, but spirometry was not available. Only four outpatients were prescribed salbutamol and two patients inhaled corticosteroid. CONCLUSION: There appears to be a high burden of obstructive lung disease in the Solomon Islands with high smoking rates, indoor smoke exposure and bronchodilator responsiveness. Respiratory symptoms are common amongst hospital ED presentations; however, inhaled asthma treatments are infrequently prescribed to outpatients.

Corrole-Substituted Fluorescent Heme Proteins.

Although fluorescent proteins have been utilized for a variety of biological applications, they have several optical limitations, namely weak red and near-infrared emission and exceptionally broad (>200 nm) emission profiles. The photophysical properties of fluorescent proteins can be enhanced through the incorporation of novel cofactors with the desired properties into a stable protein scaffold. To this end, a fluorescent phosphorus corrole that is structurally similar to the native heme cofactor is incorporated into two exceptionally stable heme proteins: H-NOX from Caldanaerobacter subterraneus and heme acquisition system protein A (HasA) from Pseudomonas aeruginosa. These yellow-orange emitting protein conjugates are examined by steady-state and time-resolved optical spectroscopy. The HasA conjugate exhibits enhanced fluorescence, whereas emission from the H-NOX conjugate is quenched relative to the free corrole. Despite the low fluorescence quantum yields, these corrole-substituted proteins exhibit more intense fluorescence in a narrower spectral profile than traditional fluorescent proteins that emit in the same spectral window. This study demonstrates that fluorescent corrole complexes are readily incorporated into heme proteins and provides an inroad for the development of novel fluorescent proteins.

Here's something I prepared earlier: a review of the time to publication of cross-sectional reviews of smartphone health apps.

OBJECTIVES: Across a range of health conditions, apps are increasingly valued as tools for supporting the delivery and coordination of healthcare. Research-led cross-sectional reviews of apps are a potential resource to inform app selection in face of uncertainties around content quality, safety and privacy. However, these peer-reviewed publications only capture a snapshot of highly dynamic app stores and marketplaces. To determine the extent to which marketplace dynamics might impact the interpretation of app reviews, the current study sought to quantify the lag between the reported time of app assessment and publication of the results of these studies. DESIGN: Searches were conducted on MEDLINE, Embase and PsycINFO to identify published cross-sectional reviews of health, fitness or wellness apps. Publication timeline metadata were extracted, allowing the primary outcome measure, the delay between app store search and manuscript publication, to be calculated. A secondary measure, the time between search and manuscript submission, was also calculated where possible. RESULTS: After screening, 136 relevant cross-sectional app review studies were analysed. The median time to publication was 431 days (approximately 14 months, range: 42-1054 days). The median time to submission was 269 days (approximately 9 months, range: 5-874 days). Studies which downloaded apps typically took longer to publish (p=0.010), however the number of apps reviewed did not impact the time to publication (p=0.964). Studies which recommended specific apps were not published more rapidly (p=0.998). CONCLUSIONS: Most health app reviews present data that are at least a year out-of-date at the time of publication. Given the high rate of turnover of health apps in public marketplaces, it may not be appropriate, therefore, for these reviews to be presented as a resource concerning specific products for commissioners, clinicians and the public. Alternative sources of information may be better calibrated to the dynamics of the app marketplace.

Multielectron C-H photoactivation with an Sb(v) oxo corrole.

Pnictogen complexes are ideal for mediating multi-electron chemical reactions in two-electron steps. We report an Sb(v) bis-µ-oxo corrole that photochemically oxidises the C-H bonds of organic substrates. In the case of toluene, the substrate is oxidised to benzaldehyde, a rare example of a four-electron photoreaction.

A Narrative Review of Methods for Applying User Experience in the Design and Assessment of Mental Health Smartphone Interventions.

OBJECTIVES: User experience (UX) plays a key role in uptake and usage of mental health smartphone interventions, yet remains underinvestigated. This review aimed to characterize and compare UX evaluation approaches that have been applied in this specific context, and to identify implications for research and practice. METHODS: A narrative review was conducted of UX-themed studies published in PubMed, PsycINFO, and Scopus up to February 2019. Eligible studies reported on data reflecting users' interactions with a smartphone intervention for any mental health condition. Studies were categorized into "situated" versus "construct-based" methods according to whether or not an established UX construct was used to acquire and analyze data. RESULTS: Situated approaches used bespoke UX metrics, including quantitative measures of usage and performance, as well as grounded interview data. Construct-based approaches such as assessments of usability and acceptability were based on conceptual frameworks, with methodologically stronger versions featuring construct definitions, validated measurement tools, and an ability to compare data across studies. Constructs and measures were sometimes combined to form bespoke construct-based approaches. CONCLUSIONS: Both situated and construct-based UX data may provide benefits during design and implementation of a mental health smartphone intervention by helping to clarify the needs of users and the impact of new features. Notable however was the omission of UX methods, such as split testing. Future research should consider these unaddressed methods, aim to improve the rigor of UX assessment, integrate their use alongside clinical outcomes, and explore UX assessment of more complex, adaptive interventions.

Do Electronic Medical Records Improve Advance Directive Documentation? A Systematic Review.

BACKGROUND: Documentation rates of advance directives (ADs) remain low. Using electronic medical records (EMRs) could help, but a synthesis of evidence is currently lacking. OBJECTIVES: To evaluate the evidence for using EMRs in documenting ADs and its implications for overcoming challenges associated with their use. DESIGN: Systematic review of articles in English, published from inception of databases to December 2017. DATA SOURCES: PubMed, PsycINFO, EMBASE, and CINAHL. METHODS/MEASUREMENTS: Four databases were searched from inception to December 2017. Randomized and nonrandomized quantitative studies examining the effects of EMRs on creation, storage, or use of ADs were included. All featured an advance care planning process. Evidence was evaluated using the Cochrane Collaboration's risk assessment tool. RESULTS: Fifteen studies were included: 1 randomized controlled trial, 1 randomized pilot, 4 pre-post studies, 4 cross-sectional studies, 1 retrospective cohort study, 1 historical control study, 1 retrospective observational study, 1 retrospective review, and 1 evaluation of an EMR feature. Seven studies showed that EMR-based reminders, AD templates, and decision aids can improve AD documentation rates. Three demonstrated that EMR search functions, decision aids, and automatic identification software can help identify patients who have or need ADs according to certain criteria. Five showed EMRs can create documentation challenges, including locating ADs, and making some patients more likely than others to have an AD. Most studies had an unclear or high risk of bias. CONCLUSIONS: Limited evidence suggests EMRs could be used to help address AD documentation challenges but may also create additional problems. Stronger evidence is needed to more conclusively determine how EMR may assist in population approaches to improving AD documentation.

Halogen Photoelimination from SbV Dihalide Corroles.

Main-group p-block metals are ideally suited for mediating two-electron reactions because they cycle between M n and M n+2 redox states, as the one-electron state is thermodynamically unstable. Here, we report the synthesis and structure of an SbIII corrole and its SbVX2 (X = Cl, Br) congeners. SbIII sits above the corrole ring, whereas SbV resides in the corrole centroid. Electrochemistry suggests interconversion between the SbIII and SbVX2 species. TD-DFT calculations indicate a HOMO → LUMO+2 parentage for excited states in the Soret spectral region that have significant antibonding character with respect to the Sb-X fragment. The photochemistry of 2 and 3 in THF is consistent with the computational results, as steady-state photolysis at wavelengths coincident with the Soret absorption of SbVX2 corrole lead to its clean conversion to the SbIII corrole. This ability to photoactivate the Sb-X bond reflects the proclivity of the pnictogens to rely on the PnIII/V couple to drive the two-electron photochemistry of M-X bond activation, an essential transformation needed to develop HX-splitting cycles.

Changes in User Perceptions of a Telemedicine System Over Time: From Initial Implementation to Everyday Use.

BACKGROUND: Benefits associated with telemedicine are contingent upon positive user perceptions. Despite this, research on user perceptions of telemedicine remains limited. INTRODUCTION: Usability approaches offer a robust way to assess user perceptions, but have rarely been applied in telemedicine. In this study, a usability approach was employed to examine how user perceptions toward a telemedicine system changed over the course of everyday use. MATERIALS AND METHODS: A telemedicine system was introduced to a hospital in the home service. Ten mobile nurses completed the System Usability Scale (SUS) after initial use, then again after 18 months of everyday use. Results were compared. Analysis included Bangor et al.'s (2009) adjective rating scale. RESULTS: The initial SUS mean was 83 (standard deviation [SD] = 7.98), indicating "excellent" usability. After 18 months, the SUS mean was 64.38, indicating "OK" usability (SD = 14.25, p < 0.05, 95% confidence interval [CI]). Over time, users had lower desire to use the system frequently (p < 0.05, 95% CI), found it more complex (p < 0.05, 95% CI), and perceived greater inconsistency in its design (p < 0.05, 95% CI). DISCUSSION: Considered with existing evidence, our usability findings indicate that a temporary period of positive user perceptions occurs when new telemedicine systems are used for the first few months. This fades with everyday use, with design inconsistency and perceived complexity becoming more noticeable. Although other factors such as user satisfaction and efficiency may also contribute, further studies are needed for confirmation. CONCLUSIONS: User perceptions of telemedicine vary with time. To help maximize the benefits and longevity of telemedicine systems, responding to intermittent user appraisal is desirable.