Deville rebooted - practical N2O5 synthesis.

Dinitrogen pentoxide (N2O5), the anhydride of nitric acid, was synthesised by Henri Étienne Sainte-Claire Deville in Paris in 1849 using silver nitrate and chlorine gas. Herein, we revisit, optimise, and modify Deville's method using photocatalysis to enable a safe, clean, practical, and reproducible alternative for N2O5 synthesis in quantitative yields. Moreover, it is predicted that the modifications can accommodate an industrial scale-up, but the silver chloride generated must be recycled.

Scrolling in Supramolecular Gels: A Designer's Guide.

Gelation by small molecules is a topic of enormous importance in catalysis, nanomaterials, drug delivery, and pharmaceutical crystallization. The mechanism by which gelators self-organize into a fibrous gel network is poorly understood. Herein, we describe the crystal structures and gelation properties of a library of bis(urea) compounds and show, via molecular dynamics simulations, how gelator aggregation progresses from a continuous pattern of supramolecular motifs to a homogeneous fiber network. Our model suggests that lamellae with asymmetric surfaces scroll into uniform unbranched fibrils, while sheets with symmetric surfaces undergo stacking to form crystals. The self-assembly of asymmetric lamellae is associated with specific molecular features, such as the presence of narrow and flexible end groups with high packing densities, and likely represents a general mechanism for the formation of small-molecule gels.

6-hydroxydopamine affects multiple pathways to induce cytotoxicity in differentiated LUHMES dopaminergic neurons.

The debilitating effects of Parkinson's disease (PD) progress over time and are pathophysiologically characterized by the formation of Lewy bodies due to the accumulation of α-synuclein aggregates resulting in the death of dopaminergic neurons. In the present study, we determined cell death pathways activated by acute exposure to 6-hydroxydopamine (6-OHDA) in differentiated LUHMES cells empirically followed by a 24 h toxin free interval, henceforth termed as washout/recovery period. Acute 6-OHDA exposure led to morphological changes in LUHMES cells and resulted in significant loss of neurite length and neurite thickness. Generation of reactive oxygen species and loss of mitochondrial membrane potential in the neuronal processes were persistent even after the recovery period. Our results show that 6-OHDA exposure leads to significant reduction in expression of mitochondrial OXPHOS complexes I, II, and IV and activation of caspase mediated apoptotic cell death cascade as observed by enhanced protein expression of cleaved-PARP-1 and cleaved-Caspase-3. Immunofluorescence microscopy approach confirmed that cell death occurs independent of the AIF translocation to the nucleus. Our experimental model, led to a ∼5-fold lower α-synuclein monomer expression and, interestingly, resulted in loss of protein ubiquitination in whole cell lysates. Altogether, this work provides evidence of multiple pathways targeted by 6-OHDA in differentiated LUHMES cells and expands research avenues for addressing the knowledge gap regarding the effect of 6-OHDA in the ubiquitin proteasome system for PD therapies.

Periodic Environmental Disturbance Drives Repeated Ecomorphological Diversification in an Adaptive Radiation of Antarctic Fishes.

AbstractThe ecological theory of adaptive radiation has profoundly shaped our conceptualization of the rules that govern diversification. However, while many radiations follow classic early-burst patterns of diversification as they fill ecological space, the longer-term fates of these radiations depend on many factors, such as climatic stability. In systems with periodic disturbances, species-rich clades can contain nested adaptive radiations of subclades with their own distinct diversification histories, and how adaptive radiation theory applies in these cases is less clear. Here, we investigated patterns of ecological and phenotypic diversification within two iterative adaptive radiations of cryonotothenioid fishes in Antarctica's Southern Ocean: crocodile icefishes and notoperches. For both clades, we observe evidence of repeated diversification into disparate regions of trait space between closely related taxa and into overlapping regions of trait space between distantly related taxa. We additionally find little evidence that patterns of ecological divergence are correlated with evolution of morphological disparity, suggesting that these axes of divergence may not be tightly linked. Finally, we reveal evidence of repeated convergence in sympatry that suggests niche complementarity. These findings reflect the dynamic history of Antarctic marine habitats and may guide hypotheses of diversification dynamics in environments characterized by periodic disturbance.

Systematic Review of Self-Measured Blood Pressure Monitoring With Support: Intervention Effectiveness and Cost.

INTRODUCTION: Self-measured blood pressure monitoring with support is an evidence-based intervention that helps patients control their blood pressure. This systematic economic review describes how certain intervention aspects contribute to effectiveness, intervention cost, and intervention cost per unit of the effectiveness of self-measured blood pressure monitoring with support. METHODS: Papers published between data inception and March 2021 were identified from a database search and manual searches. Papers were included if they focused on self-measured blood pressure monitoring with support and reported blood pressure change and intervention cost. Papers focused on preeclampsia, kidney disease, or drug efficacy were excluded. Quality of estimates was assessed for effectiveness, cost, and cost per unit of effectiveness. Patient characteristics and intervention features were analyzed in 2021 to determine how they impacted effectiveness, intervention cost, and intervention cost per unit of effectiveness. RESULTS: A total of 22 studies were included in this review from papers identified in the search. Type of support was not associated with differences in cost and cost per unit of effectiveness. Lower cost and cost per unit of effectiveness were achieved with simple technologies such as interactive phone systems, smartphones, and websites and where providers interacted with patients only as needed. DISCUSSION: Some of the included studies provided only limited information on key outcomes of interest to this review. However, the strength of this review is the systematic collection and synthesis of evidence that revealed the associations between the characteristics of implemented interventions and their patients and the interventions' effectiveness and cost, a useful contribution to the fields of both research and implementation.

Pharmacist Interventions for Medication Adherence: Community Guide Economic Reviews for Cardiovascular Disease.

INTRODUCTION: Adherence to medications for cardiovascular disease and its risk factors is less than optimal, although greater adherence to medication has been shown to reduce the risk factors for cardiovascular disease. This paper examines the economics of tailored pharmacy interventions to improve medication adherence for cardiovascular disease prevention and management. METHODS: Literature from inception of databases to May 2019 was searched, yielding 29 studies for cardiovascular disease prevention and 9 studies for cardiovascular disease management. Analyses were done from June 2019 through May 2020. All monetary values are in 2019 U.S. dollars. RESULTS: The median intervention cost per patient per year was $246 for cardiovascular disease prevention and $292 for cardiovascular disease management. The median change in healthcare cost per person per year due to the intervention was -$355 for cardiovascular disease prevention and -$2,430 for cardiovascular disease management. The median total cost per person per year was -$89 for cardiovascular disease prevention, with a median return on investment of 0.01. The median total cost per person per year for cardiovascular disease management was -$1,080, with a median return on investment of 7.52, and 6 of 7 estimates indicating reduced healthcare cost averted exceeded intervention cost. For cardiovascular disease prevention, the median cost per quality-adjusted life year gained was $11,298. There were no cost effectiveness studies for cardiovascular disease management. DISCUSSION: The evidence shows that tailored pharmacy-based interventions to improve medication adherence are cost effective for cardiovascular disease prevention. For cardiovascular disease management, healthcare cost averted exceeds the cost of implementation for a favorable return on investment from a healthcare systems perspective.

Phylogenomic Species Delimitation Dramatically Reduces Species Diversity in an Antarctic Adaptive Radiation.

Application of genetic data to species delimitation often builds confidence in delimitations previously hypothesized using morphological, ecological, and geographic data and frequently yields recognition of previously undescribed cryptic diversity. However, a recent critique of genomic data-based species delimitation approaches is that they have the potential to conflate population structure with species diversity, resulting in taxonomic oversplitting. The need for an integrative approach to species delimitation, in which molecular, morphological, ecological, and geographic lines of evidence are evaluated together, is becoming increasingly apparent. Here, we integrate phylogenetic, population genetic, and coalescent analyses of genome-wide sequence data with investigation of variation in multiple morphological traits to delimit species within the Antarctic barbeled plunderfishes (Artedidraconidae: Pogonophryne). Pogonophryne currently comprises 29 valid species, most of which are distinguished solely by variation in the ornamentation of the mental barbel that projects from the lower jaw, a structure previously shown to vary widely within a single species. However, our genomic and phenotypic analyses result in a dramatic reduction in the number of distinct species recognized within the clade, providing evidence to support the recognition of no more than six species. We propose to synonymize 24 of the currently recognized species with five species of Pogonophryne. We find genomic and phenotypic evidence for a new species of Pogonophryne from specimens collected in the Ross Sea. Our findings represent a rare example in which the application of molecular data provides evidence of taxonomic oversplitting on the basis of morphology, clearly demonstrating the utility of an integrative species delimitation framework.[ddRADseq; multispecies coalescent; Notothenioidei; SNPs; Southern Ocean.].

High-Yielding Flow Synthesis of a Macrocyclic Molecular Hinge.

Many molecular machines are built from modular components with well-defined motile capabilities, such as axles and wheels. Hinges are particularly useful, as they provide the minimum flexibility needed for a simple and pronounced conformational change. Compounds with multiple stable conformers are common, but molecular hinges almost exclusively operate via dihedral rotations rather than truly hinge-like clamping mechanisms. An ideal molecular hinge would better reproduce the behavior of hinged devices, such as gates and tweezers, while remaining soluble, scalable, and synthetically versatile. Herein, we describe two isomeric macrocycles with clamp-like open and closed geometries, which crystallize as separate polymorphs but interconvert freely in solution. An unusual one-pot addition cyclization reaction was used to produce the macrocycles on a multigram scale from inexpensive reagents, without supramolecular templating or high-dilution conditions. Using mechanistic information from NMR kinetic studies and at-line mass spectrometry, we developed a semicontinuous flow synthesis with maximum conversions of 85-93% and over 80% selectivity for a single isomer. The macrocycles feature voids that are sterically protected from guests, including reactive species such as fluoride ions, and could therefore serve as chemically inert hinges for adaptive supramolecular receptors and flexible porous materials.

A Replicable Approach to Promoting Best Practices: Translating Cardiovascular Disease Prevention Research.

OBJECTIVE: Significant delays in translating health care-related research into public health programs and medical practice mean that people may not get the best care when they need it. Regarding cardiovascular disease, translation delays can mean lives may be unnecessarily lost each year. To facilitate the translation of knowledge to action, we created a Best Practices Guide for Cardiovascular Disease Prevention Programs. DESIGN: Using the Rapid Synthesis Translation Process and the Best Practices Framework as guiding frameworks, we collected and rated research evidence for hypertension control and cholesterol management strategies. After identifying best practices, we gathered information about programs that were implementing the practices and about resources useful for implementation. Research evidence and supplementary information were consolidated in an informational resource and published online. Web metrics were collected and analyzed to measure use and reach of the guide. RESULTS: The Best Practices Guide was released in January 2018 and included background information and resources on 8 best practice strategies. It was published as an online resource, publicly accessible from the Centers for Disease Control and Prevention Web site in 2 different formats. Web metrics show that in the first year after publication, there were 25 589 Web page views and 2467 downloads. A query of partner use of the guide indicated that it was often shared in partners' own resources, newsletters, and online material. CONCLUSION: In following a systematic approach to creating the Best Practices Guide and documenting the steps taken in its development, we offer a replicable approach for translating research on health care practices into a resource to facilitate implementation. The success of this approach is attributed to 3 key factors: using a prescribed and documented approach to evidence translation, working closely with stakeholders throughout the process, and prioritizing the content design and accessibility of the final product.

Timing of State and Territorial COVID-19 Stay-at-Home Orders and Changes in Population Movement - United States, March 1-May 31, 2020.

SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), is thought to spread from person to person primarily by the respiratory route and mainly through close contact (1). Community mitigation strategies can lower the risk for disease transmission by limiting or preventing person-to-person interactions (2). U.S. states and territories began implementing various community mitigation policies in March 2020. One widely implemented strategy was the issuance of orders requiring persons to stay home, resulting in decreased population movement in some jurisdictions (3). Each state or territory has authority to enact its own laws and policies to protect the public's health, and jurisdictions varied widely in the type and timing of orders issued related to stay-at-home requirements. To identify the broader impact of these stay-at-home orders, using publicly accessible, anonymized location data from mobile devices, CDC and the Georgia Tech Research Institute analyzed changes in population movement relative to stay-at-home orders issued during March 1-May 31, 2020, by all 50 states, the District of Columbia, and five U.S. territories.* During this period, 42 states and territories issued mandatory stay-at-home orders. When counties subject to mandatory state- and territory-issued stay-at-home orders were stratified along rural-urban categories, movement decreased significantly relative to the preorder baseline in all strata. Mandatory stay-at-home orders can help reduce activities associated with the spread of COVID-19, including population movement and close person-to-person contact outside the household.

Inducing Social Self-Sorting in Organic Cages To Tune The Shape of The Internal Cavity.

Many interesting target guest molecules have low symmetry, yet most methods for synthesising hosts result in highly symmetrical capsules. Methods of generating lower symmetry pores are thus required to maximise the binding affinity in host-guest complexes. Herein, we use mixtures of tetraaldehyde building blocks with cyclohexanediamine to access low-symmetry imine cages. Whether a low-energy cage is isolated can be correctly predicted from the thermodynamic preference observed in computational models. The stability of the observed structures depends on the geometrical match of the aldehyde building blocks. One bent aldehyde stands out as unable to assemble into high-symmetry cages-and the same aldehyde generates low-symmetry socially self-sorted cages when combined with a linear aldehyde. We exploit this finding to synthesise a family of low-symmetry cages containing heteroatoms, illustrating that pores of varying geometries and surface chemistries may be reliably accessed through computational prediction and self-sorting.

Translating Workforce Development Policy Interventions for Community Health Workers: Application of a Policy Research Continuum.

CONTEXT: There is a need for knowledge translation to advance health equity in the prevention and control of cardiovascular disease and type 2 diabetes. One recommended strategy is engaging community health workers (CHWs) to have a central role in related interventions. Despite strong evidence of effectiveness for CHWs, there is limited information examining the impact of state CHW policy interventions. This article describes the application of a policy research continuum to enhance knowledge translation of CHW workforce development policy in the United States. METHODS: During 2016-2019, a team of public health researchers and practitioners applied the policy research continuum, a multiphased systematic assessment approach that incorporates legal epidemiology to enhance knowledge translation of CHW workforce development policy interventions in the United States. The continuum consists of 5 discrete, yet interconnected, phases including early evidence assessments, policy surveillance, implementation studies, policy ratings, and impact studies. RESULTS: Application of the first 3 phases of the continuum demonstrated (1) how CHW workforce development policy interventions are linked to strong evidence bases, (2) whether existing state CHW laws are evidence-informed, and (3) how different state approaches were implemented. DISCUSSION: As a knowledge translation tool, the continuum enhances dissemination of timely, useful information to inform decision making and supports the effective implementation and scale-up of science-based policy interventions. When fully implemented, it assists public health practitioners in examining the utility of different policy intervention approaches, the effects of adaptation, and the linkages between policy interventions and more distal public health outcomes.

Meta-analysis on the comparative efficacy of drains, progressive tension sutures and subscarpal fat preservation in reducing complications of abdominoplasty.

INTRODUCTION: Abdominoplasty is a popular aesthetic operation. Complication rates vary from 4-80%. To date, there is a lack of evidence for complication-reducing techniques. The aim of this meta-analysis was to summarise and quantify the effects of these techniques on complication rates and determine the safest combination. METHODS: A literature search was undertaken from MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials databases. Two authors assessed the abstracts and evaluated their suitability for inclusion in the review. For each complication (including overall), a random effects meta-analysis was conducted to investigate the average number of complications. The log rate and associated variance is calculated in R using the "escalc" function from the metafor R package. For the forest plots the model output is back-transformed to the original scale. RESULTS: 4295 patients were included in the meta-analysis. Overall complication rates ranged from 9.3-33.8%. Revision rates were 3-21.9%. Forest plots of data extracted from observational studies demonstrated summary measures favouring the sub-scarpal fat preservation and drains, and drains only groups for overall complications. There were no significant differences between groups for seroma, haematoma, infection/abscess, skin/fat necrosis, dehiscence, surgical revision rate and VTE rate. CONCLUSIONS: The rates of individual complications are no different with or without the use of PTS, drain or sub-Scarpal fat preservation in different combinations.

Lilypad aggregation: localised self-assembly and metal sequestration at a liquid-vapour interface.

Spatially resolved soft materials, such as vesicles and microgels, have shown promise as selective adsorbents and microscale reaction vessels. However, spatiotemporal control of aggregation can be difficult to achieve. In this study, nickel(ii) chloride and a dipyridyl oligo(urea) ligand were combined in a vapour-diffusion setup to produce a localised spheroidal aggregate at the liquid-vapour interface. This aggregate forms via the self-assembly and fusion of monodisperse colloids and grows until its weight is no longer counterbalanced by surface tension. A simple physical model reveals that this process, termed lilypad aggregation, is possible only for surface energies that favour neither bulk aggregation nor the growth of an interfacial film. These surface energies dictate the final size and shape of the aggregate and may be estimated through visual monitoring of its changing morphology. Lilypad aggregates sequester metal from the surrounding sol and can be collected manually from the surface of the liquid.

Bromelain-based enzymatic debridement of e-cigarette burns: a single unit experience.

OBJECTIVE: It is widely accepted that the early debridement of burns improves outcome. There is increasing evidence that enzymatic debridement is an effective technique for removal of full-thickness and deep-dermal burns, reducing blood loss and often the need for autologous skin grafting by avoiding over excision of the burn. We aim to highlight the potential use of this form of debridement as an alternative to surgical management in patients with electronic cigarette (e-cigarette)-associated flame burn injuries. METHODS: This case series presents the use of Nexobrid (MediWound Ltd, Israel), a non-surgical, bromelain-based enzymatic debridement technique, in patients with deep partial-thickness burns (range: 1-3% total body surface area), avoiding the need for autologous skin grafting. RESULTS: Burn wounds in two patients healed within 14 days without complications or the need for further surgical intervention. Another patient required further dressings after discharge but failed to attend follow-up appointments. These results are comparable with those reported by others using conservative management of e-cigarette burns. CONCLUSION: The authors wish to raise awareness of the potential for a combination of thermal and chemical burns related to e-cigarette explosions. Chemical burns should be excluded by pH testing of the burn wound. From our experience, small e-cigarette-associated flame burns can be considered for management with enzymatic debridement.

Characterization of an umbilical cord blood sourced product suitable for allogeneic applications.

Aim: Umbilical cord blood (UCB) sourced allografts are promising interventions for tissue regeneration. As applications of these allografts and regulations governing them continue to evolve, we were prompted to identify parameters determining their quality, safety and regenerative potential. Materials & methods: Flow-cytometry, mass-spectrometry, protein multiplexing, nanoparticle tracking analysis and standard biological techniques were employed. Results: Quality attributes of a uniquely processed UCB-allograft (UCBr) were enumerated based on identity (cell viability, immunophenotyping, proteomic profiling, and quantification of relevant cytokines); safety (bioburden and microbiological screening), purity (endotoxin levels) and potency (effect of UCBr on chondrocytes and mesenchymal stem cells derived exosomes). These attributes were stable up to 24 months in cryopreserved UCBr. Conclusion: We identified a comprehensive panel of tests to establish the clinical efficacy and quality control attributes of a UCB-sourced allograft.

Pre-nucleation aggregation based on solvent microheterogeneity.

Investigation into pre-nucleation aggregates indicating hydrate formation of caffeine and theophylline in aqueous acetonitrile showed hydrate crystallisation at much lower water fraction than significant solute self-association. Molecular dynamics simulations indicate that the solvent separates on the molecular scale and that solute molecules preferentially localise on the phase interface.

Braiding, branching and chiral amplification of nanofibres in supramolecular gels.

Helical nanofibres play key roles in many biological processes. Entanglements between helices can aid gelation by producing thick, interconnected fibres, but the details of this process are poorly understood. Here, we describe the assembly of an achiral oligo(urea) peptidomimetic compound into supramolecular helices. Aggregation of adjacent helices leads to the formation of fibrils, which further intertwine to produce high-fidelity braids with periodic crossing patterns. A braid theory analysis suggests that braiding is governed by rigid topological constraints, and that branching occurs due to crossing defects in the developing braids. Mixed-chirality helices assemble into relatively complex, odd-stranded braids, but can also form helical bundles by undergoing inversions of chirality. The oligo(urea) assemblies are also highly sensitive to chiral amplification, proposed to occur through a majority-rules mechanism, whereby trace chiral materials can promote the formation of gels containing only homochiral helices.

Economics of Community Health Workers for Chronic Disease: Findings From Community Guide Systematic Reviews.

CONTEXT: Cardiovascular disease in the U.S. accounted for healthcare cost and productivity losses of $330 billion in 2013-2014 and diabetes accounted for $327 billion in 2017. The impact is disproportionate on minority and low-SES populations. This paper examines the available evidence on cost, economic benefit, and cost effectiveness of interventions that engage community health workers to prevent cardiovascular disease, prevent type 2 diabetes, and manage type 2 diabetes. EVIDENCE ACQUISITION: Literature from the inception of databases through July 2016 was searched for studies with economic information, yielding nine studies in cardiovascular disease prevention, seven studies in type 2 diabetes prevention, and 13 studies in type 2 diabetes management. Analyses were done in 2017. Monetary values are reported in 2016 U.S. dollars. EVIDENCE SYNTHESIS: The median intervention cost per patient per year was $329 for cardiovascular disease prevention, $600 for type 2 diabetes prevention, and $571 for type 2 diabetes management. The median change in healthcare cost per patient per year was -$82 for cardiovascular disease prevention and -$72 for type 2 diabetes management. For type 2 diabetes prevention, one study saw no change and another reported -$1,242 for healthcare cost. One study reported a favorable 1.8 return on investment from engaging community health workers for cardiovascular disease prevention. Median cost per quality-adjusted life year gained was $17,670 for cardiovascular disease prevention, $17,138 (mean) for type 2 diabetes prevention, and $35,837 for type 2 diabetes management. CONCLUSIONS: Interventions engaging community health workers are cost effective for cardiovascular disease prevention and type 2 diabetes management, based on a conservative $50,000 benchmark for cost per quality-adjusted life year gained. Two cost per quality-adjusted life year estimates for type 2 diabetes prevention were far below the $50,000 benchmark.