A Structural Study on Absorption of Lysozyme in Amorphous Starch Microspheres.

The potential of using proteins as drugs is held back by their low stability in the human body and challenge of delivering them to the site of function. Extensive research is focused on drug delivery systems that can protect, carry, and release proteins in a controlled manner. Of high potential are cross-linked degradable starch microspheres (DSMs), as production of these is low-cost and environmentally friendly, and the products are degradable by the human body. Here, we demonstrate that DSMs can absorb the model protein lysozyme from an aqueous solution. At low amounts of lysozyme, its concentration in starch microspheres strongly exceeds the bulk concentration in water. However, at higher protein contents, the difference between concentrations in the two phases becomes small. This indicates that, at lower lysozyme contents, the absorption is driven by protein-starch interactions, which are counteracted by protein-protein electrostatic repulsion at high concentrations. By applying small-angle X-ray scattering (SAXS) to the DSM-lysozyme system, we show that lysozyme molecules are largely unaltered by the absorption in DSM. In the same process, the starch network is slightly perturbed, as demonstrated by a decrease in the characteristic chain to chain distance. The SAXS data modeling suggests an uneven distribution of the protein within the DSM particles, which can be dependent on the internal DSM structure and on the physical interactions between the components. The results presented here show that lysozyme can be incorporated into degradable starch microspheres without any dependence on electrostatic or specific interactions, suggesting that similar absorption would be possible for pharmaceutical proteins.

Obesity Predisposes Anthracycline-Treated Survivors of Childhood and Adolescent Cancers to Subclinical Cardiac Dysfunction.

Anthracyclines are effective chemotherapeutics used in approximately 60% of pediatric cancer cases but have a well-documented risk of cardiotoxicity. Existing cardiotoxicity risk calculators do not include cardiovascular risk factors present at the time of diagnosis. The goal of this study is to leverage the advanced sensitivity of strain echocardiography to identify pre-existing risk factors for early subclinical cardiac dysfunction among anthracycline-exposed pediatric patients. We identified 115 pediatric patients with cancer who were treated with an anthracycline between 2013 and 2019. Peak longitudinal left ventricular strain was retroactively calculated on 495 surveillance echocardiograms via the TOMTEC AutoSTRAIN software. Cox proportional hazards models were employed to identify risk factors for abnormal longitudinal strain (> - 16%) following anthracycline treatment. High anthracycline dose (≥ 250 mg/m2 doxorubicin equivalents) and obesity at the time of diagnosis (BMI > 95th percentile-for-age) were both significant predictors of abnormal strain with hazard ratios of 2.79, 95% CI (1.07-7.25), and 3.85, 95% CI (1.42-10.48), respectively. Among pediatric cancer survivors, patients who are obese at the time of diagnosis are at an increased risk of sub-clinical cardiac dysfunction following anthracycline exposure. Future studies should explore the incidence of symptomatic cardiomyopathy 10-15 years post-treatment among patients with early subclinical cardiac dysfunction.

QCM-D Investigation of Swelling Behavior of Layer-by-Layer Thin Films upon Exposure to Monovalent Ions.

Polyelectrolyte multilayers and layer-by-layer assemblies are susceptible to structural changes in response to ionic environment. By altering the salt type and ionic strength, structural changes can be induced by disruption of intrinsically bound ion pairs within the multilayer network via electrostatic screening. Notably, high salt concentrations have been used for the purposes of salt-annealing and self-healing of LbL assemblies with KBr, in particular, yielding a remarkably rapid response. However, to date, the structural and swelling effects of various monovalent ion species on the behavior of LbL assemblies remain unclear, including a quantitative view of ion content in the LbL assembly and thickness changes over a wide concentration window. Here, we investigate the effects of various concentrations of KBr (0 to 1.6 M) on the swelling and de-swelling of LbL assemblies formed from poly(diallyldimethylammonium) polycation (PDADMA) and poly(styrene sulfonate) polyanion (PSS) in 0.5 M NaCl using quartz-crystal microbalance with dissipation (QCM-D) monitoring as compared to KCl, NaBr, and NaCl. The ion content after salt exchange is quantified using neutron activation analysis (NAA). Our results demonstrate that Br- ions have a much greater effect on the structure of as-prepared thin films than Cl- at ionic strengths above assembly conditions, which is possibly caused by the more chaotropic nature of Br-. It is also found that the anion in general dominates the swelling response as compared to the cation because of the excess PDADMA in the multilayer. Four response regimes are identified that delineate swelling due to electrostatic repulsion, slight contraction, swelling due to doping, and film destruction as ionic strength increases. This understanding is critical if such materials are to be used in applications requiring submersion in chemically dynamic environments such as sensors, coatings on biomedical implants, and filtration membranes.

Comparison of KBr and NaCl effects on the glass transition temperature of hydrated layer-by-layer assemblies.

The influence of assembly and post-assembly conditions on the glass transition temperature of free-standing poly(diallyldimethyl ammonium) (PDADMA)/poly(4-styrene sulfonate) (PSS) layer-by-layer (LbL) films assembled in 0.5M NaCl and 0.5M KBr are explored using modulated differential scanning calorimetry. Upon completion, PDADMA/PSS LbL assemblies are hydrated using solutions containing various concentrations of KBr. The data indicate that water provides the primary driving force for changes in the glass transition temperature of completed films rather than the post-assembly salt type. However, upon changing the assembly salt conditions from NaCl to KBr, the glass transition temperature shows a decrease of nearly 20 °C. Additionally, the composition of the films upon analysis with 1H NMR spectroscopy and neutron activation analysis indicates an elevated number of extrinsic binding sites within the film structure when KBr is the assembly salt. This shows a clear link between the assembly conditions and the internal structure and, therefore, the thermal properties of PDADMA/PSS LbL assemblies.

High-throughput screening of respiratory hazards: Exploring lung surfactant inhibition with 20 benchmark chemicals.

As environmental air quality worsens and respiratory health injuries and diseases increase, it is essential to enhance our ability to develop better methods to identify potential hazards. One promising approach in emerging toxicology involves the utilization of lung surfactant as a model that addresses the limitations of conventional in vitro toxicology methods by incorporating the biophysical aspect of inhalation. This study employed a constrained drop surfactometer to assess 20 chemicals for potential surfactant inhibition. Of these, eight were identified as inhibiting lung surfactant function: 1-aminoethanol, bovine serum albumin, maleic anhydride, propylene glycol, sodium glycocholate, sodium taurocholate, sodium taurodeoxycholate, and Triton X-100. These results are consistent with previously reported chemical-induced acute lung dysfunction in vivo. The study provides information on each chemical's minimum and maximum surface tension conditions and corresponding relative area and contact angle values. Isotherms and box plots are reported for selected chemicals across doses, and vector plots are used to summarize and compare the results concisely. This lung surfactant bioassay is a promising non-animal model for hazard identification, with broader implications for developing predictive modeling and decision-making tools.

WellNest: A Medical Student-Run Housing Support Program.

PROBLEM: Being unhoused and facing housing insecurity contribute to poor health outcomes. Medical school curricula may include social determinants of health (SDOH) topics. However, experiential learning opportunities allow students to better contextualize how SDOH impact patients. The WellNest Housing Support Program (WellNest) was conceived and developed by Duke University medical students to learn from and support community members with a history of housing insecurity. APPROACH: Under the supervision of community organizations providing housing assistance services, WellNest was created in April 2020. Medical student-volunteers (MSVs) call clients, who are referred to WellNest by the community organizations, to plan move-ins. Local experts provide trainings on topics relevant to health care for individuals experiencing loss of housing. MSVs source and move furniture and clients' belongings into the new homes. Following move-in, MSVs are paired with clients to provide longitudinal tenancy support for at least one year. Student-volunteers contemplate their experiences and learning takeaways through debriefing sessions and an optional online survey. OUTCOMES: From fall 2021 to spring 2023, 83 student-volunteers from across the university participated in WellNest. Student-volunteers were generally medical students (37, 45%), and 16 MSVs served on the leadership team. WellNest facilitated 29 move-ins, and 26 clients requested to be paired with MSVs for longitudinal tenancy support. Following participation in WellNest, student-volunteers reported increased comfort, awareness, knowledge, and motivation related to caring for, discussing, and advocating for individuals experiencing housing insecurity. NEXT STEPS: As students from other programs are also interested in WellNest, there is potential for interprofessional education. Student-volunteers will be encouraged to participate in additional opportunities for reflection and advocacy activities. The impact of WellNest on clients will be explored through a questionnaire and narrative interviews. Long-term financial support was secured from community donations and partnering community organizations.

Development of a curricular thread to foster medical students' critical reflection and promote action on climate change, health, and equity.

INTRODUCTION: Due to the health consequences arising from climate change, medical students will inevitably interact with affected patients during their training and careers. Accordingly, medical schools must incorporate education on the impacts of climate change on health and equity into their curricula. We created a curricular thread called "Climate Change, Health, and Equity" in the first-year preclinical medical program to teach foundational concepts and foster self-reflection and critical consciousness. METHODS: The authors developed a continuum of practice including administrators, educators and faculty members, students, and community partners to plan and design curricular activities. First-year medical students at Duke University School of Medicine participated in seven mandatory foundational lectures and two experiential learning opportunities in the local community. Following completion of activities, students wrote a critical reflection essay and completed a self-directed learning exercise. Essays were evaluated using the REFLECT rubric to assess if students achieved critical reflection and for thematic analysis by Bloom's Taxonomy. RESULTS: All students (118) submitted essays. A random sample of 30 (25%) essays underwent analysis. Evaluation by the REFLECT rubric underscored that all students were reflecting or critically reflecting on thread content. Thematic analysis highlighted that all students (30/30, 100%) were adept at identifying new areas of medical knowledge and connecting concepts to individual experiences, institutional practices, and public health and policy. Most students (27/30; 90%) used emotionally laden words, expressing negative feelings like frustration and fear but also positive sentiments of solidarity and hope regarding climate change and effects on health. Many students (24/30; 80%) expressed actionable items at every level including continuing self-directed learning and conversing with patients, minimizing healthcare waste, and advocating for climate-friendly policies. CONCLUSION: After participating in the curricular thread, most medical students reflected on cognitive, affective, and actionable aspects relating to climate change, health, and equity.

Stereoselective synthesis of an advanced trans-decalin intermediate towards the total synthesis of anthracimycin.

Progress towards the total synthesis of the macrolide natural product anthracimycin is described. This new approach utilises an intermolecular Diels-Alder strategy followed by epimeirsation to form the key trans-decalin framework. The route culminates in the stereoselective synthesis of an advanced tricyclic lactone intermediate, containing five contiguous sterogenic centres with the correct relative and absolute stereochemistry required for the anthracimycin core motif.

Men calling healthline.

OBJECTIVE: To compare data for men who call Healthline for themselves with data from women callers and to use those pilot data to inform strategies to encourage men to use Healthline. SUBJECTS AND METHODS: This was a study examining retrospective data for people calling Healthline in a week in October 2010. Calls from 487 men were compared with those from 487 women. Geocoded data provided deprivation levels. RESULTS: There were fewer men calling than women in all age groups, although younger men were overrepresented. Young men were more acutely unwell than young women or older men. Men called at all times of the day, and call duration was similar to that of women callers. Most men callers were European; men of other ethnic groups were underrepresented compared with women and compared with their representation in the New Zealand population. Men from higher deprivation areas were more likely to call than those from lower deprivation areas. CONCLUSIONS: Compared with women, men underuse Healthline as they do other primary care services. Overall, men are more symptomatic than women; of interest is our observation that among men, the users are likely to be younger, of lower socioeconomic status, and European. Healthline may be an acceptable source of health advice for these men, and it should be considered central in any future initiative addressing men's health.

Metaboverse enables automated discovery and visualization of diverse metabolic regulatory patterns.

Metabolism is intertwined with various cellular processes, including controlling cell fate, influencing tumorigenesis, participating in stress responses and more. Metabolism is a complex, interdependent network, and local perturbations can have indirect effects that are pervasive across the metabolic network. Current analytical and technical limitations have long created a bottleneck in metabolic data interpretation. To address these shortcomings, we developed Metaboverse, a user-friendly tool to facilitate data exploration and hypothesis generation. Here we introduce algorithms that leverage the metabolic network to extract complex reaction patterns from data. To minimize the impact of missing measurements within the network, we introduce methods that enable pattern recognition across multiple reactions. Using Metaboverse, we identify a previously undescribed metabolite signature that correlated with survival outcomes in early stage lung adenocarcinoma patients. Using a yeast model, we identify metabolic responses suggesting an adaptive role of citrate homeostasis during mitochondrial dysfunction facilitated by the citrate transporter, Ctp1. We demonstrate that Metaboverse augments the user's ability to extract meaningful patterns from multi-omics datasets to develop actionable hypotheses.

Differential host responses within the upper respiratory tract and peripheral blood of children and adults with SARS-CoV-2 infection.

Age is among the strongest risk factors for severe outcomes from SARS-CoV-2 infection. We sought to evaluate associations between age and both mucosal and systemic host responses to SARS-CoV-2 infection. We profiled the upper respiratory tract (URT) and peripheral blood transcriptomes of 201 participants (age range of 1 week to 83 years), including 137 non-hospitalized individuals with mild SARS-CoV-2 infection and 64 uninfected individuals. Among uninfected children and adolescents, young age was associated with upregulation of innate and adaptive immune pathways within the URT, suggesting that young children are primed to mount robust mucosal immune responses to exogeneous respiratory pathogens. SARS-CoV-2 infection was associated with broad induction of innate and adaptive immune responses within the URT of children and adolescents. Peripheral blood responses among SARS-CoV-2-infected children and adolescents were dominated by interferon pathways, while upregulation of myeloid activation, inflammatory, and coagulation pathways was observed only in adults. Systemic symptoms among SARS-CoV-2-infected subjects were associated with blunted innate and adaptive immune responses in the URT and upregulation of many of these same pathways within peripheral blood. Finally, within individuals, robust URT immune responses were correlated with decreased peripheral immune activation, suggesting that effective immune responses in the URT may promote local viral control and limit systemic immune activation and symptoms. These findings demonstrate that there are differences in immune responses to SARS-CoV-2 across the lifespan, including between young children and adolescents, and suggest that these varied host responses contribute to observed differences in the clinical presentation of SARS-CoV-2 infection by age. One Sentence Summary: Age is associated with distinct upper respiratory and peripheral blood transcriptional responses among children and adults with SARS-CoV-2 infection.

A Unifying Bioinspired Synthesis of (-)-Asperaculin A and (-)-Penifulvin D.

The first syntheses of the isomeric dioxafenestrene natural products (-)-asperaculin A and (-)-penifulvin D are reported. Each target is formed selectively by choice of oxidant in a final divergent bioinspired Baeyer-Villiger (BV) reaction. Density functional theory calculations reveal that electrostatic interactions between the oxidant leaving group and the lactone motif accounts for a reversal of selectivity with H2O2/H3O+ compared to peracids. Synthetic features include forging the polycyclic carbon framework with a diastereoselective meta-photocycloaddition biased by an ether substituent at the aryl α-position. The encumbered tertiary alcohol was installed by cyanation of a ketone intermediate followed by nonaqueous hydrolysis of the resulting delicate cyanohydrin.

Interface-exfoliated graphene-based conductive screen-printing inks: low-loading, low-cost, and additive-free.

Paper diagnostics are of growing interest due to their low cost and easy accessibility. Conductive inks, necessary for manufacturing the next generation diagnostic devices, currently face challenges such as high cost, high sintering temperatures, or harsh conditions required to remove stabilizers. Here we report an effective, inexpensive, and environmentally friendly approach to graphene ink that is suitable for screen printing onto paper substrates. The ink formulation contains only pristine graphite, water, and non-toxic alkanes formed by an interfacial trapping method in which graphite spontaneously exfoliates to graphene. The result is a viscous graphene stabilized water-in-oil emulsion-based ink. This ink does not require sintering, but drying at 90 °C or brief microwaving can improve the conductivity. The production requires only 40 s of shaking to form the emulsion. The sheet resistance of the ink is approximately 600 Ω/sq at a thickness of less than 6 µm, and the ink can be stabilized by as little as 1 wt% graphite.

High Modulus, Thermally Stable, and Self-Extinguishing Aramid Nanofiber Separators.

Mechanically and thermally robust separators offer an alternative approach for preventing battery failure under extreme conditions such as high loads and temperatures. However, the trade-off between electrochemical performance and mechanical and thermal stability remains an ongoing challenge. Here, we investigate aramid nanofiber (ANF) separators that possess high moduli and self-extinguishing characteristics. The ANF separators are formed from the dissolution of bulk Kevlar fibers and their subsequent vacuum-assisted self-assembly. Thermogravimetric analysis shows a high 5 wt % decomposition temperature of 447 °C, which is over ∼175 °C higher than commercial Celgard separators. The ANF separator also possesses a high Young's modulus of 8.8 GPa, which is ∼1000% higher than commercial separators. Even when dry or when soaked in battery electrolyte, the ANF separators self-extinguish upon exposure to flame, whereas commercial separators melt or drip. We show that these features, although adventitious, present a trade-off with electrochemical performance in which a lithium nickel manganse cobalt (NMC) oxide-based battery possessed a reduced capacity of 123.4 mA h g-1. Considering the separator holistically, we propose that the ANF separator shows an excellent balance of the combined properties of high modulus, flame-resistance, thermal stability, and electrochemical stability and might be suitable for extreme environment applications with further testing.

How safe is telenursing from home?

OBJECTIVE: To compare the work of telenurses working from home with that of their colleagues working in a health call centre. DESIGN: A retrospective review of existing clinical and other data. SETTING: NURSE-ON-CALL, the telephone triage and advice line operated for the Department of Human Services, Victoria by McKesson Asia Pacific. SUBJECTS: Nurses employed by McKesson Asia Pacific, Victoria, Australia working in their call centre and from home. MAIN OUTCOME MEASURES: Comparison between nurses working from home with those working in the centre: demographics and dispositions of callers, management of mystery callers, frequency of risk incidents, productivity, and satisfaction. RESULTS: Callers sought triage for the same range of symptoms and were triaged to similar dispositions; mystery callers were managed similarly; there were a similar number of risk incidents. Nurses working from home were more productive, took fewer days sick leave and had a lower attrition rate. Nurses working from home identified more flexible hours and less travel as advantages. No disadvantages were identified. CONCLUSIONS: Nurses who worked from home were provided with adequate education for their role, full technological facilities, decision support software, ready access to supervision and continuing education. They managed a similar range of cases as nurses working in a health call centre, did so as safety, were more productive and expressed high levels of satisfaction.

Universal telenursing triage in Australia and New Zealand - a new primary health service.

BACKGROUND: Most Australian and all New Zealand residents now have 24 hour access to free telephone advice and symptom triage. Australasia is following an international trend triggered by a perceived need for standardised advice, demand management (primary care and emergency department), and equity of access. A growing literature describes the impact of this new service on existing primary health services. OBJECTIVE: This article summarises the results of telephone triage projects in Australia and New Zealand to acquaint Australian general practitioners with nurse led telephone triage services that have health call centre technology. DISCUSSION: Australian and New Zealand services are similar with respect to the demographics of callers, when they call, and the issues on which they seek advice. Further study is needed in order to understand how telenursing can best be integrated with general practice and other primary care services.

A pressure-tuned Fabry Pérot interferometer for laser frequency stabilization and tuning.

We present a simple, inexpensive pressure-tuned Fabry Pérot interferometer which can be used to frequency stabilize and tune a laser when no suitable atomic reference is available. Our design, made largely from off-the-shelf parts, yields a tuning range of about 4 GHz and offers an absolute tuning accuracy of better than 1 MHz. The interferometer, which uses air as its working medium, is characterized by a low thermal drift rate of order 1 MHz per hour.

Professional isolation and performance assessment in New Zealand.

INTRODUCTION: Solo and nonurban practice, nonmembership of a professional group, and aging are all associated with underperformance and may be indicators of professional isolation. Although it may lead to underperformance in physicians, there are no clear measures to assess professional isolation. METHODS: By mailed questionnaire, experienced performance assessors were asked to list markers of professional isolation. RESULTS: A set of criteria and descriptors for professional isolation was generated, and included personality; solo practice; poor colleague relationships; outlier practice; MOPS or CPD failure; specialist in only private practice; stress, no relief, complaints, job dissatisfaction; locum, itinerant or part-time practice; cultural barriers; male gender. DISCUSSION: The identification of physicians at risk for professional isolation may enable the prevention of poor performance.

Death certification and doctors' dilemmas: a qualitative study of GPs' perspectives.

BACKGROUND: Death certificate inaccuracies have implications for funding and planning public health services, health research and family settlements. Improved training has been identified as a way of reducing inaccuracies. Understanding the influences on certifying doctors should inform that training. AIM: To explore what factors influence GPs as they complete death certificates. DESIGN: Focus groups held by teleconference with 16 GPs. SETTING: New Zealand general practice. METHOD: Four teleconferenced focus groups were taped and transcribed. Transcripts were examined for emerging themes. Credibility, transferability and confirmability were underwritten by a clear audit trail. RESULTS: Participants identified two factors that influenced death certification: clinical uncertainty and the family. Other themes provided an understanding of the personal and professional concerns for GPs. CONCLUSION: Improving death certification accuracy is a complex issue and needs to take into consideration factors that influence certifiers.

Assessing the competence of practicing physicians in New Zealand, Canada, and the United Kingdom: progress and problems.

Members of the public expect practicing physicians to be competent. They expect poorly performing physicians to be identified and either helped or removed from practice. "Maintenance of professional standards" by continuing education does not identify the poorly performing physician; assessment of clinical performance is necessary for that. Assessment may be responsive-ie, following a complaint- or periodic, either for all physicians or for an identified high-risk group. A thorough review using a range of tools is appropriate for a responsive assessment but is not practical for periodic assessment for all. A single, valid, reliable, and practical screening tool has yet to be devised to identify physicians whose practice is suboptimal. Further, articulate commentators are concerned about the harm that too-intensive scrutiny of professional performance may cause. We conclude that high performance by all physicians throughout their careers cannot be fully ensured, but it is nonetheless the responsibility of licensing bodies to use reasonable methods to determine whether performance remains acceptable. Such methods should be shown scientifically to be accurate, valid, and reliable for practicing physicians. Such an approach is likely to encourage the agreement and cooperation of the profession. To do less risks losing the trust of the public.