A long-acting C-natriuretic peptide for achondroplasia.

The C-natriuretic peptide (CNP) analog vosoritide has recently been approved for treatment of achondroplasia in children. However, the regimen requires daily subcutaneous injections in pediatric patients over multiple years. The present work sought to develop a long-acting CNP that would provide efficacy equal to or greater than that of vosoritide but require less frequent injections. We used a technology for half-life extension, whereby a drug is attached to tetra-polyethylene glycol hydrogels (tetra-PEG) by ß-eliminative linkers that cleave at predetermined rates. These hydrogels-fabricated as uniform ∼60-µm microspheres-are injected subcutaneously, where they serve as a stationary depot to slowly release the drug into the systemic circulation. We prepared a highly active, stable CNP analog-[Gln6,14]CNP-38-composed of the 38 C-terminal amino acids of human CNP-53 containing Asn to Gln substitutions to preclude degradative deamidation. Two microsphere [Gln6,14]CNP-38 conjugates were prepared, with release rates designed to allow once-weekly and once-monthly administration. After subcutaneous injection of the conjugates in mice, [Gln6,14]CNP-38 was slowly released into the systemic circulation and showed biphasic elimination pharmacokinetics with terminal half-lives of ∼200 and ∼600 h. Both preparations increased growth of mice comparable to or exceeding that produced by daily vosoritide. Simulations of the pharmacokinetics in humans indicated that plasma [Gln6,14]CNP-38 levels should be maintained within a therapeutic window over weekly, biweekly, and likely, monthly dosing intervals. Compared with vosoritide, which requires ∼30 injections per month, microsphere [Gln6,14]CNP-38 conjugates-especially the biweekly and monthly dosing-could provide an alternative that would be well accepted by physicians, patients, and patient caregivers.

A Cross-Sectional Analysis of Pediatric Necrotizing Soft Tissue Infection Cases and Racial Disparities From the 2016 to 2020 National Inpatient Sample.

INTRODUCTION: The incidence, treatment, and outcomes of necrotizing soft tissue infections (NSTIs) and associated racial disparities have been described in adults, but research in the pediatric population is limited. The purpose of this study is to provide a nationally representative characterization of pediatric NSTI and determine the presence of any racial disparities. METHODS: The National Inpatient Sample was analyzed from 2016 through 2020. Patients aged less than 20 y with a diagnosis of necrotizing fasciitis, Fournier's gangrene, or gas gangrene (based on International Classification of Diseases, Tenth Revision, Clinical Modification codes) were included for analysis. RESULTS: A total of 355 patients were identified. Black and Hispanic patients accounted for the most admissions in 2016 and 2018, respectively (P = 0.024). Compared to White patients, more Black patients were insured by Medicaid (P = 0.037) and were in the first zip code-based income quartile (P = 0.005). The leading infection overall was necrotizing fasciitis and most patients (81.7%) underwent a surgical procedure by the first calendar day after admission. Although the proportion of Black patients undergoing subcutaneous tissue and fascia excisions was more than that of White patients (P = 0.005), there were no significant differences by race in the time to first procedure, the total number of procedures, or number of postoperative complications. Our amputation and mortality rates were low and unreportable, but there were no differences by race. CONCLUSIONS: NSTI is rare in the pediatric population and mortality is low. Black patients are disproportionately diagnosed, but these disparities do not extend to disease treatment or outcomes.

On the dual behaviour of water in octanol-rich aqueous n-octanol mixtures: an X-ray scattering and computer simulation study.

Aqueous n-octanol (n = 1, 2, 3, and 4) mixtures from the octanol rich side are studied by X-ray scattering and computer simulation, with a focus on structural changes, particularly in what concerns the hydration of the hydroxyl-group aggregated chain-like structures, under the influence of various branching of the alkyl tails. Previous studies have indicated that hydroxyl-group chain-cluster formation is hindered in proportion to the branching number. Here, water mole fractions up to x = 0.2 are examined, i.e. up to the miscibility limit. It is found that water molecules within the hydroxyl-chain domains participate in the chain formations in a different manner for 1-octanol and the branched octanols. The hydration of the octanol hydroxyl chains is confirmed by the shifting of the scattering pre-peak position kPP to smaller values, both from measured and simulated X-ray scattering intensities, which corresponds to an increased size of the clusters. Experimental pre-peak amplitudes are seen to increase with increasing water content for 1-octanol, while this trend is reversed in all branched octanols, with the amplitudes decreasing with the increase of the branching number. Conjecturing that the amplitudes of pre-peaks are related to the density of the corresponding aggregates, these results are interpreted as water breaking large OH hydroxyl chains in 1-octanol, hence increasing the density of aggregates, while enhancing hydroxyl aggregates in branched alcohols by inserting itself into the OH chains. The analysis of the cluster distributions from computer simulations provide more details on the role of water. For cluster sizes smaller than dc = 2π/kPP, water is found to always play the role of a structure enforcer for all n-octanols, while for clusters of size dc water is always a destructor. For cluster sizes larger than dc, the role of water differs from 1-octanol and the branched ones: it acts as a structure maker or breaker in inverse proportion to the hindering of OH hydroxyl chain structures arising from the topology of the alkyl tails (branched or not).

Expanding records of occurrence of the whale shark (Rhincodon typus) in The Bahamas and a call for sustainable tourism practices.

This report updates our understanding of whale shark occurrences in The Bahamas by drawing upon a variety of data sources. Our findings reveal previously unreported sighting locations, often associated with tourism activities, underscoring the pivotal role played by nontraditional data sources in addressing knowledge gaps. These revelations emphasize the ongoing necessity for monitoring efforts. Additionally, we have found cases that raise concerns related to unregulated human-shark interactions in the region, highlighting the pressing need for sustainable tourism practices within Bahamian waters.

Colonization, diversity, and seasonality of fishes at pelagic fish aggregating devices.

The pelagic zone of the ocean can be a challenging environment in which to conduct research and as a result we lack the robust baseline abundance and diversity data, compared to what is available in more accessible coastal habitats, to be able to track changes or stressors to the biota in this environment. Many large-scale fisheries target pelagic fish, and much of the information available on these species is based on fisheries-dependent data that may be biased towards hotspots and commercially valuable fishes. Here, a long-term video and visual fish survey was conducted on two subsurface moored fish aggregating devices (FADs) in the pelagic waters of the central Bahamas to determine the feasibility of using moored pelagic FADs as tools for collecting fish abundance and diversity data. A wide range of species was documented, including large migratory fish that are the focus of commercial and recreational fisheries, and smaller often overlooked species on which little abundance or seasonality information exists. We found that FADs colonize quickly and reach a peak stable (albeit seasonally cyclical) abundance and diversity within the first several months after deployment. Species richness was higher in video surveys, but abundance was higher in visual surveys, except for sharks. Our results highlight the need to tailor survey methods to fit the context and study objective, and provide further evidence for the importance of fisheries-independent data in monitoring pelagic species.

Host genetic identity determines parasite community structure across time and space in oyster restoration.

Intraspecific variation in host susceptibility to individual parasite species is common, yet how these effects scale to mediate the structure of diverse parasite communities in nature is less well understood. To address this knowledge gap, we tested how host genetic identity affects parasite communities on restored reefs seeded with juvenile oysters from different sources-a regional commercial hatchery or one of two wild progenitor lines. We assessed prevalence and intensity of three micro- and two macroparasite species for 4 years following restoration. Despite the spatial proximity of restored reefs, oyster source identity strongly predicted parasite community prevalence across all years, with sources varying in their relative susceptibility to different parasites. Oyster seed source also predicted reef-level parasite intensities across space and through time. Our results highlight that host intraspecific variation can shape parasite community structure in natural systems, and reinforce the importance of considering source identity and diversity in restoration design.

Energetic connectivity of diverse elasmobranch populations - implications for ecological resilience.

Understanding the factors shaping patterns of ecological resilience is critical for mitigating the loss of global biodiversity. Throughout aquatic environments, highly mobile predators are thought to serve as important vectors of energy between ecosystems thereby promoting stability and resilience. However, the role these predators play in connecting food webs and promoting energy flow remains poorly understood in most contexts. Using carbon and nitrogen isotopes, we quantified the use of several prey resource pools (small oceanic forage, large oceanics, coral reef, and seagrass) by 17 species of elasmobranch fishes (n = 351 individuals) in The Bahamas to determine their functional diversity and roles as ecosystem links. We observed remarkable functional diversity across species and identified four major groups responsible for connecting discrete regions of the seascape. Elasmobranchs were responsible for promoting energetic connectivity between neritic, oceanic and deep-sea ecosystems. Our findings illustrate how mobile predators promote ecosystem connectivity, underscoring their functional significance and role in supporting ecological resilience. More broadly, strong predator conservation efforts in developing island nations, such as The Bahamas, are likely to yield ecological benefits that enhance the resilience of marine ecosystems to combat imminent threats such as habitat degradation and climate change.

Popular to a Point: The Enduring Political Challenges of the Public Option.

Policy Points A decade after failing to make it into the Affordable Care Act, the public option reemerged as a health reform goal at both the national and state levels, with polls reporting strong, bipartisan support. A 2020 poll that probed both support for one public option approach (Medicare "buy-in") and attitudes toward government suggests that differences in these attitudes could plague reform advocates' efforts. Although the COVID-19 pandemic viscerally highlighted the need for a more coherent health care system-including universal coverage-other recent evolutions in the broader US political context could undermine reform.

Diverticulitis in Older Adults: Is Cognitive Impairment Associated With Outcomes?

INTRODUCTION: Older age is associated with increased prevalence of both diverticulitis and cognitive impairment. The association between cognitive impairment and outcomes among older adults presenting to the emergency department (ED) for diverticulitis is unknown. METHODS: Adults aged ≥65 y presenting to an ED with a primary diagnosis of colonic diverticulitis were identified using the Nationwide Emergency Department Sample (2016-2019) and stratified by cognitive impairment status in this retrospective cohort study. Multivariable Poisson regression models adjusted for patient age, sex, Elixhauser Comorbidity Index, primary payer status, and presence of complicated diverticulitis quantified relative risk of a) inpatient admission, b) operative intervention, and c) in-hospital mortality comparing patients with or without a diagnosis code suggestive of cognitive impairment. RESULTS: Among 683,444 older adults with an ED encounter for diverticulitis from 2016 to 2019, there were 468,226 patients with isolated colonic diverticulitis and 26,388 (5.6%) with comorbid cognitive impairment. After adjustment, the risk of inpatient admission for those with cognitive impairment was 18% higher than for those without cognitive impairment (adjusted relative risks [aRR]: 1.18, 95% confidence interval [CI]: 1.17-1.20). Those with cognitive impairment were 34% more likely to undergo colectomy than those without cognitive impairment (aRR: 1.34, 95% CI: 1.24-1.44). Older adults with cognitive impairment had a 32% greater mortality than those without cognitive impairment (aRR: 1.32, 95% CI: 1.05-1.67). CONCLUSIONS: Among older adults presenting for ED care with a primary diagnosis of colonic diverticulitis, individuals with cognitive impairment had higher rates of hospitalization, operative intervention, and in-hospital mortality than those without cognitive impairment.

Association of Postoperative Delirium and Parkinson Disease After Common United States Surgical Procedures.

INTRODUCTION: To determine the association of Parkinson disease (PD) and postoperative delirium following common surgical procedures. METHODS: We performed a retrospective database analysis of the National Inpatient Sample. We used a matched sample of patients with and without PD who underwent any of ten common surgical procedures in the US, 2005-2014. Primary outcome measure was postoperative delirium for patients with and without PD. Secondary measures included disposition, length of stay, and hospital costs. RESULTS: There were 3,235,866 patients receiving any of the ten most common operative procedures, 2005-2014. There were 35,743 patients with and without PD matched based on age, sex, elective admission status, Charlson Comorbidity index, and presence of dementia. Median age was 77 y (interquartile range 72-82), median Charlson Comorbidity index was 1 (standard deviation 0-2), 46.6% were female, and 46.8% were admitted electively. The three most common operative procedures were hip arthroplasty (28.5%), knee arthroplasty (16.1%), and percutaneous coronary angioplasty (14.9%). Postoperative delirium was present in 1519 patients with PD compared to 828 matched patients without PD (4.2% versus 2.3%; P < 0.001). The adjusted odds ratio of postoperative delirium for PD compared to the matched cohort without PD was 1.88 (95% confidence interval 1.73-2.05). Those undergoing spinal fusion (adjusted odds ratio 2.99, 95% confidence interval 2.06-4.38) had the greatest odds of delirium. For patients with PD, adjusted length of stay, adjusted hospital costs, and adjusted odds of postacute care facility discharge were greater compared to the matched cohort without PD. CONCLUSIONS: Patients with PD are more likely to develop postoperative delirium and have a more complicated postoperative course with longer length of stay and greater hospitalization costs.

An Evaluation of Sex-Based Differences in Surrogate Consent for Older Adults Undergoing Surgical Intervention.

INTRODUCTION: Differences between female and male patients have been identified in many facets of medicine. We sought to understand whether differences in frequency of surrogate consent for operation exist between older female and male patients. MATERIALS AND METHODS: A descriptive study was designed using data from the hospitals participating in the American College of Surgeons National Surgical Quality Improvement Program. Patients age 65 y and older who underwent operation between 2014 and 2018 were included. RESULTS: Of 51,618 patients identified, 3405 (6.6%) had surrogate consent for surgery. Overall, 7.7% of females had surrogate consent compared to 5.3% of males (P < 0.001). Stratified analysis based on age categories showed no difference in surrogate consent between female and male patients aged 65-74 yy (2.3% versus 2.6%, P = 0.16), but higher rates of surrogate consent in females than males among patients aged 75-84 y old (7.3% versus 5.6%, P < 0.001) and age ≥85 y (29.7% versus 20.8%, P < 0.001). A similar relationship was seen between sex and preoperative cognitive status. There was no difference in preoperative cognitive impairment in female and male patients age 65-74 y (4.4% versus 4.6%, P = 0.58), but higher rates of preoperative cognitive impairment were seen in females than males for those age 75-84 (9.5% versus 7.4%, P < 0.001) and aged ≥85 y (29.4% versus 21.3%, P < 0.001). Matching for age and cognitive impairment, there was no significant difference between rate of surrogate consent in males and females. CONCLUSIONS: Female patients are more likely than males to undergo surgery with surrogate consent. This difference is not based on patient sex alone - females undergoing operation are older than their male counterparts and more likely to be cognitively impaired.

Indoor Versus Outdoor: Does Occupational Sunlight Exposure Increase Melanoma Risk? A Systematic Review.

INTRODUCTION: Melanoma is the fifth most common cancer diagnosed in the United States, representing 5.6% of all new cancer cases. There are conflicting reports correlating a relationship between primarily outdoor occupations, associated with increased exposure to direct sunlight, and the incidence of cutaneous melanoma. Our objective was to outline and critically evaluate the relevant literature related to chronic occupational exposure to sunlight and risk of developing cutaneous melanoma. METHODS: The study protocol for this systematic review was submitted to the International Prospective Register of Systematic Reviews and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. For each relevant study included, the following information was extracted: author names, publication year, study name, study design, age, exposure assessment, outcome, comparison, number of cases, case ascertainment, and descriptive and adjusted statistics. Study quality and evidence certainty was assessed using the Grading of Recommendations, Assessment, Development and Evaluations model. RESULTS: The initial database search yielded 1629 articles for review and following full-text screening, a total of 14 articles were included for final analysis. Of the studies included, seven articles were retrospective case control and seven were cohort studies. The studies did not report any differences in the likelihood of cutaneous melanoma development based upon membership in the outdoor versus indoor occupation groups included in each study. CONCLUSIONS: Overall, the articles included in this systematic review did not report an increased risk of developing cutaneous melanoma among individuals with outdoor occupations. Further investigation is required to determine if other occupational or life-style-related risk factors exist, to help support the development of individualized skin screening recommendations and improve the early detection of melanoma in all populations.

Humic-like Substances (HULIS) in Ship Engine Emissions: Molecular Composition Effected by Fuel Type, Engine Mode, and Wet Scrubber Usage.

Humic-like substances (HULIS), known for their substantial impact on the atmosphere, are identified in marine diesel engine emissions obtained from five different fuels at two engine loads simulating real world scenarios as well as the application of wet sulfur scrubbers. The HULIS chemical composition is characterized by electrospray ionization (ESI) ultrahigh resolution mass spectrometry and shown to contain partially oxidized alkylated polycyclic aromatic compounds as well as partially oxidized aliphatic compounds, both including abundant nitrogen- and sulfur-containing species, and clearly different to HULIS emitted from biomass burning. Fuel properties such as sulfur content and aromaticity as well as the fuel combustion efficiency and engine mode are reflected in the observed HULIS composition. When the marine diesel engine is operated below the optimum engine settings, e.g., during maneuvering in harbors, HULIS-C emission factors are increased (262-893 mg kg-1), and a higher number of HULIS with a shift toward lower degree of oxidation and higher aromaticity is detected. Additionally, more aromatic and aliphatic CHOS compounds in HULIS were detected, especially for high-sulfur fuel combustion. The application of wet sulfur scrubbers decreased the HULIS-C emission factors by 4-49% but also led to the formation of new HULIS compounds. Overall, our results suggest the consideration of marine diesel engines as a relevant regional source of HULIS emissions.

Arterial Diameter and Percentage of Monocytes are Sex-Dependent Predictors of Early Arteriovenous Fistula Maturation.

BACKGROUND: Arteriovenous fistulae mature less frequently in women than in men, leading to inferior patency and decreased fistula utilization in women. We hypothesized that both anatomic and physiologic sex differences explain reduced maturation. METHODS: The electronic medical records of patients who had a primary arteriovenous fistula created from 2016 to 2021 at a single center were reviewed; sample size was determined using a power calculation. Postoperative ultrasound and laboratory tests were obtained at least 4 weeks after fistula creation. Primary unassisted fistula maturation was determined up to 4 years postprocedure. RESULTS: A total of 28 women and 28 men with a brachial-cephalic fistula were analyzed. The inflow brachial artery diameter was smaller in women than in men, both preoperatively (4.2 ± 0.9 vs. 4.9 ± 1.0 mm, P = 0.008) and postoperatively (4.8 ± 0.8 vs. 5.3 ± 0.9 mm, P = 0.039). Despite similar preoperative brachial artery peak systolic velocity, women had significantly lower postoperative arterial velocity (P = 0.027). Fistula flow was reduced in women, particularly in the midhumerus (747.0 ± 570.4 vs. 1,117.1 ± 471.3 cc/min, P = 0.003). Percentages of neutrophils and lymphocytes were similar among women and men 6 weeks after fistula creation. However, women had reduced monocytes (8.5 ± 2.0 vs. 10.0 ± 2.6%, P = 0.0168). Among 28 men, 24 of 28 (85.7%) achieved unassisted maturation, whereas only 15 of 28 (53.6%) women had fistulae that matured without intervention. Secondary analysis using logistic regression suggested that postoperative arterial diameter was associated with maturation in men, while postoperative monocyte percentage was associated with maturation in women. CONCLUSIONS: Sex differences during arteriovenous fistula maturation are present in arterial diameter and velocity, suggesting that both anatomic and physiologic differences in arterial inflow contribute to sex differences in fistula maturation. In men, postoperative arterial diameter is correlated with maturation, whereas in women, the significantly lower proportion of circulating monocytes suggests a role for the immune response in fistula maturation.

SUSTAINED BIWEEKLY AFLIBERCEPT FOR REFRACTORY NEOVASCULAR AGE-RELATED MACULAR DEGENERATION: The Prospective TRISTAR Study.

PURPOSE: To assess the safety and efficacy of biweekly (every 2 weeks) intravitreal aflibercept injections (IAI) 2 mg in eyes with refractory neovascular age-related macular degeneration (NVAMD). METHODS: A prospective, single-arm, interventional study was conducted. Eyes with refractory NVAMD received six biweekly IAIs through week 12, followed by a 4-week treatment pause until week 16. Eyes with residual subretinal fluid (SRF) at week 16 were randomized 1:1 to either four additional biweekly IAIs or to 4-week (q4W) IAI dosing through week 24. All eyes were subsequently treated q4W through week 52. RESULTS: Enrolled eyes (n = 22) had persistent SRF despite a mean of 11.8 injections over the prior 12 months. One patient developed endophthalmitis at week 12. There were no additional drug/procedure-related adverse events. Best-corrected visual acuity (BCVA) improved significantly from baseline to week 14 (2.52 letters, P < 0.001). The mean central subfield thickness (CST) was also significantly improved at week 14 (-31.9 µ m, P < 0.001) with eight of 22 eyes achieving complete SRF resolution. Only two of eight eyes remained free of SRF at week 16, with a corresponding increase in mean CST of 26.7 µ m compared with week 14. By week 52, improvements in BCVA and CST were lost. CONCLUSION: In patients with refractory NVAMD-related SRF, sustained biweekly IAIs resulted in significant functional and anatomical improvements during biweekly dosing. These gains, however, were lost on return to monthly dosing. These findings suggest that efforts to reduce refractory SRF in NVAMD with biweekly dosing may provide added benefit compared with standard of care treatment if biweekly dosing is sustained.

Aerobic response to thermal stress across ontogeny and habitats in a teleost fish.

Near-future climate change projections predict an increase in sea surface temperature that is expected to have significant and rapid effects on marine ectotherms, potentially affecting a number of critical life processes. Some habitats also undergo more thermal variability than others, and the inhabitants therefore must be more tolerant to acute periods of extreme temperatures. Mitigation of these outcomes may occur through acclimation, plasticity or adaptation, although the rate and extent of a species' ability to adjust to warmer temperatures is largely unknown, specifically as it pertains to effects on various performance metrics in fishes that inhabit multiple habitats throughout ontogenetic stages. Here, the thermal tolerance and aerobic performance of schoolmaster snapper (Lutjanus apodus Walbaum, 1792) collected from two different habitats were experimentally assessed under different warming scenarios (temperature treatments = 30, 33, 35, 36°C) to assess vulnerability to an imminently changing thermal habitat. Larger subadult and adult fish collected from a 12 m deep coral reef exhibited a lower critical thermal maximum (CTmax ) compared to smaller juvenile fish collected from a 1 m deep mangrove creek. However, the CTmax of the creek-sampled fish was only 2°C above the maximum water temperature measured in the habitat from which they were collected, compared to a CTmax that was 8°C higher in the reef-sampled fish, resulting in a wider thermal safety margin at the reef site. A generalized linear model showed a marginally significant effect of temperature treatment on resting metabolic rate (RMR), but there were no effects of any of the tested factors on maximum metabolic rate or absolute aerobic scope. Post hoc tests revealed that RMR was significantly higher for creek-collected fish at the 36°C treatment and significantly higher for reef-collected fish at 35°C. Swimming performance [measured by critical swimming speed] was significantly lower at the highest temperature treatment for creek-collected fish and trended down with each successive increase in temperature treatment for reef-collected fish. These results show that metabolic rate and swimming performance responses to thermal challenges are somewhat consistent across collection habitats, and this species may be susceptible to unique types of thermal risk depending on its habitat. We show the importance of intraspecific studies that couple habitat profiles and performance metrics to better understand possible outcomes under thermal stress.

The interaction of viral fusion peptides with lipid membranes.

In this paper, we studied fusogenic peptides of class I-III fusion proteins, which are relevant to membrane fusion for certain enveloped viruses, in contact with model lipid membranes. We resolved the vertical structure and examined the adsorption or penetration behavior of the fusogenic peptides at phospholipid Langmuir monolayers with different initial surface pressures with x-ray reflectometry. We show that the fusion loops of tick-borne encephalitis virus (TBEV) glycoprotein E and vesicular stomatitis virus (VSV) G-protein are not able to insert deeply into model lipid membranes, as they adsorbed mainly underneath the headgroups with only limited penetration depths into the lipid films. In contrast, we observed that the hemagglutinin 2 fusion peptide (HA2-FP) and the VSV-transmembrane domain (VSV-TMD) can penetrate deeply into the membranes. However, in the case of VSV-TMD, the penetration was suppressed already at low surface pressures, whereas HA2-FP was able to insert even into highly compressed films. Membrane fusion is accompanied by drastic changes of the membrane curvature. To investigate how the peptides affect the curvature of model lipid membranes, we examined the effect of the fusogenic peptides on the equilibration of cubic monoolein structures after a phase transition from a lamellar state induced by an abrupt hydrostatic pressure reduction. We monitored this process in presence and absence of the peptides with small-angle x-ray scattering and found that HA2-FP and VSV-TMD drastically accelerate the equilibration, while the fusion loops of TBEV and VSV stabilize the swollen state of the lipid structures. In this work, we show that the class I fusion peptide of HA2 penetrates deeply into the hydrophobic region of membranes and is able to promote and accelerate the formation of negative curvature. In contrast, we found that the class II and III fusion loops of TBEV and VSV tend to counteract negative membrane curvature.

A pressure-jump study on the interaction of osmolytes and crowders with cubic monoolein structures.

Many vital processes that take place in biological cells involve remodeling of lipid membranes. These processes take place in a milieu that is packed with various solutes, ranging from ions and small organic osmolytes to proteins and other macromolecules, occupying about 30% of the available volume. In this work, we investigated how molecular crowding, simulated with the polymer polyethylene glycol (PEG), and the osmolytes urea and trimethylamine-N-oxide (TMAO) affect the equilibration of cubic monoolein structures after a phase transition from a lamellar state induced by an abrupt pressure reduction. In absence of additives, swollen cubic crystallites form after the transition, releasing excess water over several hours. This process is reflected in a decreasing lattice constant and was monitored with small angle X-ray scattering. We found that the osmotic pressure exerted by PEG and TMAO, which are displaced from narrow inter-bilayer spaces, accelerates the equilibration. When the radius of gyration of the added PEG was smaller than the radius of the water channels of the cubic phase, the effect became more pronounced with increasing molecular weight of the polymers. As the release of hydration water from the cubic structures is accompanied by an increasing membrane curvature and a reduction of the interface between lipids and aqueous phase, urea, which has a slight affinity to reside near membrane surfaces, stabilized the swollen crystallites and slowed down the equilibration dynamics. Our results support the view that cellular solutes are important contributors to dynamic membrane processes, as they can accelerate dehydration of inter-bilayer spaces and promote or counteract membrane curvature.

Innovation Centers in Health Care Delivery Systems: Structures for Success.

The need to support innovation in health care delivery was prompted by payment reforms and access to digital tools and has been accelerated by the shift to virtual care as part of the COVID-19 pandemic response. Prior to the pandemic, a growing number of health systems set up innovation centers to focus on creating new services and exploring new business models relevant to value-based care. This is distinct from process improvement or implementation science, and often needs a different set of incentives to succeed within a large organization. We used a national survey to identify a diverse sample of innovation centers, and interviewed leaders to describe their aims, organizational structures, and activities. They all aim to improve patient outcomes and experience while reducing costs, but their strategic focus may differ. The centers also vary in their reporting structure, how they build internal capacity, and how they measure success. We highlight the range of strategies through examples of projects that improve quality, reduce costs, and generate new revenue. While the optimal forms and impact of innovation centers are still emerging, the fiscal pressures and the rapid uptake of digital technologies present opportunities for the redesign of health services in the postpandemic era. The experiences of these centers illustrate a set of approaches to increase any organization's capacity for innovation.

The collaborative research and service delivery partnership between the United States healthcare system and the U.S. Military Health System during the COVID-19 pandemic.

OBJECTIVES: To examine the military-civilian collaborative efforts which addressed the unprecedented challenges of the COVID-19 pandemic, particularly in areas including provision of supplies, patient and provider support, and development and dissemination of new vaccine and drug candidates. METHODS: We examined peer reviewed and grey literature from September 2020 to June 2021 to describe the relationship between the U.S. healthcare system and Military Health System (MHS). For analysis, we applied the World Health Organization framework for health systems, which consists of six building blocks. RESULTS: The strongest collaborative efforts occurred in areas of medicine and technology, human resources, and healthcare delivery, most notably in the MHS supplying providers, setting up treatment venues, and participating in development of vaccines and therapeutics. Highlighting that the MHS, with its centralized structure and ability to deploy assets rapidly, is an important contributor to the nation's ability to provide a coordinated, large-scale response to health emergencies. CONCLUSIONS: Continuing the relationship between the two health systems is vital to maintaining the nation's capability to meet future health challenges.