Effect of morphology on interactions between nanoparticle-stabilised air bubbles and oil droplets.

High-speed video analysis has enabled the interaction between a pair of millimetre-sized air bubbles to be studied in aqueous solution. The bubbles were grown in the presence of either poly(glycerol monomethacrylate)-poly(benzyl methacrylate) (PGMA-PBzMA) diblock copolymer spheres or poly(glycerol monomethacrylate)-poly(2-hydroxypropyl methacrylate)-poly(benzyl methacrylate) (PGMA-PHPMA-PBzMA) triblock copolymer worms prepared by polymerisation-induced self-assembly (PISA). A reduction in interfacial tension relative to air bubbles grown in the absence of nanoparticles indicated the adsorption of nanoparticles at the air-water interface. A concentration of 0.01% w/v PGMA-PBzMA spheres conferred air bubble stability after just 30 s interfacial ageing with stirring, whereas 300 s ageing was required for worms to prevent coalescence at the same copolymer concentration. However, longer coalescence times with interfacial age suggested greater worm adsorption on the air bubbles during this period. In striking contrast, although stable millimetre-sized n-dodecane droplets were obtained in the presence of 0.01% w/v copolymer worms, the copolymer spheres did not prevent coalescence at this low concentration. Finally, the multiphase interaction and stability of immiscible fluids in the presence of either spheres or worms was assessed. More specifically, an n-dodecane oil droplet and an air bubble were grown separately in the presence of either the spheres or worms and then brought into contact. In the absence of any nanoparticles, aqueous film drainage resulted in the formation of a compound droplet consisting of an air lens on the oil droplet. In the presence of 0.01% w/v nanoparticles, ageing times of either 30 s or 120 s were required to prevent formation of compound droplets when using spheres and worms, respectively. Moreover, this asymmetric system required much shorter ageing times in the presence of adsorbed nanoparticles to gain stability compared to either the symmetric air bubble or oil droplet systems. This stability is attributed to a bridging nanoparticle monolayer between the oil droplet and the air bubble.

Spin-echo small-angle neutron scattering (SESANS) studies of diblock copolymer nanoparticles.

Poly(glycerol monomethacrylate)-poly(benzyl methacrylate) (PGMA-PBzMA) diblock copolymer nanoparticles were synthesized via polymerization-induced self-assembly (PISA) using reversible addition-fragmentation chain-transfer (RAFT) aqueous emulsion polymerization in D2O. Such PISA syntheses produce sterically-stabilized nanoparticles in situ and can be performed at relatively high copolymer concentrations (up to 50 wt%). This PGMA-PBzMA formulation is known to form only spherical nanoparticles in water using aqueous emulsion polymerization (Macromolecules, 2014, 47, 5613-5623), which makes it an ideal model system for exploring new characterization methods. The polymer micelles were characterized using small-angle X-ray scattering (SAXS) and a recently developed form of neutron scattering, spin-echo small-angle neutron scattering (SESANS). As far as we are aware, this is the first report of a study of polymer micelles by SESANS, and the data agree well with reciprocal-space scattering. Using this technique enables characterization of the concentrated, as synthesized dispersions directly without dilution, and this will provide a method to study self-assembled polymer systems that have concentration dependent morphologies, while still maintaining the advantages of scattering techniques.

Giant Pickering Droplets: Effect of Nanoparticle Size and Morphology on Stability.

The interaction between a pair of millimeter-sized nanoparticle-stabilized n-dodecane droplets was analyzed using a high-speed video camera. The droplets were grown in the presence of either poly(glycerol monomethacrylate)-poly(benzyl methacrylate) (PGMA-PBzMA) diblock copolymer spheres or poly(glycerol monomethacrylate)-poly(2-hydroxypropyl methacrylate)-poly(benzyl methacrylate) (PGMA-PHPMA-PBzMA) triblock copolymer worms prepared by polymerization-induced self-assembly. The effect of nanoparticle morphology on droplet coalescence was analyzed by comparing 22 nm spheres to highly anisotropic worms with a mean worm width of 26 nm and comparable particle contact angle. Both morphologies lowered the interfacial tension, providing direct evidence for nanoparticle adsorption at the oil-water interface. At 0.03 w/v % copolymer, an aging time of at least 90 s was required to stabilize the n-dodecane droplets in the presence of the worms, whereas no aging was required to produce stable droplets when using the spheres, suggesting faster diffusion of the latter to the surface of the oil droplets. The enhanced stability of the sphere-coated droplets is consistent with the higher capillary pressure in this system as the planar interfaces approach. However, the more strongly adsorbing worms ultimately also confer stability. At lower copolymer concentrations (≤0.01 w/v %), worm adsorption promoted droplet stability, whereas the spheres were unable to stabilize droplets even after longer aging times. The effect of mean sphere diameter on droplet stability was also assessed while maintaining an approximately constant particle contact angle. Small spheres of either 22 or 41 nm stabilized n-dodecane droplets, whereas larger spheres of either 60 or 91 nm were unable to prevent coalescence when the two droplets were brought into contact. These observations are consistent with the greater capillary pressure stabilizing the oil-water interfaces coated with the smaller spheres. Addition of an oil-soluble polymeric diisocyanate cross-linker to either the 60 or the 91 nm spheres produced highly stable colloidosomes, thus confirming adsorption of these nanoparticles.

Bordetella pertussis Strain Lacking Pertactin and Pertussis Toxin.

A Bordetella pertussis strain lacking 2 acellular vaccine immunogens, pertussis toxin and pertactin, was isolated from an unvaccinated infant in New York State in 2013. Comparison with a French strain that was pertussis toxin-deficient, pertactin wild-type showed that the strains carry the same 28-kb deletion in similar genomes.

Impact of education and clinic site champion on extragenital testing for sexually transmitted infections.

BACKGROUND: Sexually transmitted infections (STIs) are on the rise in the United States. Infections at extragenital (EG) sites (throat or rectum) may serve as an overlooked reservoir for STIs. The aims of this project were to determine the proportion of patients receiving EG testing and to observe the impact of an educational intervention. METHODS: Phase I included four urgent care clinics and baseline data for adults receiving STI testing (Chlamydia trachomatis and Neisseria gonorrhoeae). Clinics received access to an educational presentation regarding the importance of EG testing. Two of these clinics served as pilot sites for the implementation of self-collection kits. Phase II involved further expansion and utilization of clinic site champions. RESULTS: Phase I baseline data indicated that less than 1% of samples from patients receiving STI testing were from EG sites. There was an increase in EG testing after the educational intervention and implementation of self-collection kits. A larger increase in EG testing was seen after utilization of a site champion in Phase II. CONCLUSION: EG infections serve as a potential source for STI transmission which makes multi-site testing necessary. Our interventions to improve EG testing were most effective in Phase II after implementing a clinic site champion.

Emergency department use in the postpartum period: a retrospective cohort study.

Background: Visits to the emergency room (ED) by women in the postpartum period may reflect gaps in postpartum care and disparities in access to obstetric and primary care services. This study aimed to characterize the patients who visited the ED in the first year after delivery, their reasons for coming to the ED, and the care they received. Methods: The electronic health record was reviewed for all patients who delivered at University of Iowa Health Care between 2009 and 2023 and visited the ED within 365 days after delivery. Data drawn directly from the EHR included patient demographics and medical history, pregnancy and delivery information, and newborn characteristics. The charts were then reviewed manually for information regarding ED visits including time from delivery, chief complaint, diagnosis, and disposition. Results: 555 pregnancies had ED visits within one year of delivery, with a total 814 ED visits across the study sample. 46.7% of ED visits occurred in the first 30 days following delivery, and 35% of ED visits for obstetric complaints occurred in the first 2 weeks after delivery. Black patients visited the ED more often (mean=1.84 visits, SD=1.30) than white (mean=1.34, SD=0.92, p<0.001) or Hispanic patients (mean=1.35, SD=0.67, p = 0.004). The most common categories of chief complaint were obstetric (34.6%) and gastrointestinal (18.8%), while the most common categories of diagnosis were obstetric (31.8%) and immune/infectious (28.1%). Conclusions: Visits to the ED are common in the year following delivery. Almost half of these visits occur in the first 30 days after birth. The plurality of postpartum ED visits are due to obstetric complaints, especially in the first few weeks. Black women are more likely to use the ED during this period, potentially due to disparities in healthcare access. These findings suggest that some of these ED visits may be preventable, and that there is room for improvement in post-delivery follow-up, communication between patients and the obstetrics team, and access to outpatient obstetric care.

Oil-in-oil pickering emulsions stabilized by diblock copolymer nanoparticles.

HYPOTHESIS: Diblock copolymer nanoparticles have been shown to be Pickering emulsifiers for both oil-in-water and water-in-oil emulsions. Recently, we reported the preparation of sterically-stabilized diblock copolymer spheres in a low-viscosity silicone oil (Macromolecules 53 (2020) 1785-1794). We hypothesized that such spheres could be used as a Pickering emulsifier for a range of oil-in-oil emulsions comprising droplets of a bio-sourced oil dispersed in silicone oil. EXPERIMENTS: Diblock copolymer spheres were prepared via reversible addition-fragmentation chain transfer (RAFT) dispersion polymerization of benzyl methacrylate in silicone oil and characterized by dynamic light scattering and transmission electron microscopy. These spheres were evaluated as Pickering emulsifiers for a series of oil-in-oil Pickering emulsions. The influence of both sphere size and core-forming block composition was investigated. FINDINGS: Optimization of the nanoparticle size and core-forming block composition enabled stable bio-sourced oil-in-silicone emulsions to be obtained for nine out of the ten bio-sourced oils investigated. These emulsions were characterized in terms of their mean droplet size by optical microscopy.

Synthesis of High Molecular Weight Poly(glycerol monomethacrylate) via RAFT Emulsion Polymerization of Isopropylideneglycerol Methacrylate.

High molecular weight water-soluble polymers are widely used as flocculants or thickeners. However, synthesis of such polymers via solution polymerization invariably results in highly viscous fluids, which makes subsequent processing somewhat problematic. Alternatively, such polymers can be prepared as colloidal dispersions; in principle, this is advantageous because the particulate nature of the polymer chains ensures a much lower fluid viscosity. Herein we exemplify the latter approach by reporting the convenient one-pot synthesis of high molecular weight poly(glycerol monomethacrylate) (PGMA) via the reversible addition-fragmentation chain transfer (RAFT) aqueous emulsion polymerization of a water-immiscible protected monomer precursor, isopropylideneglycerol methacrylate (IPGMA) at 70 °C, using a water-soluble poly(glycerol monomethacrylate) (PGMA) chain transfer agent as a steric stabilizer. This formulation produces a low-viscosity aqueous dispersion of PGMA-PIPGMA diblock copolymer nanoparticles at 20% solids. Subsequent acid deprotection of the hydrophobic core-forming PIPGMA block leads to particle dissolution and affords a viscous aqueous solution comprising high molecular weight PGMA homopolymer chains with a relatively narrow molecular weight distribution. Moreover, it is shown that this latex precursor route offers an important advantage compared to the RAFT aqueous solution polymerization of glycerol monomethacrylate since it provides a significantly faster rate of polymerization (and hence higher monomer conversion) under comparable conditions.

Stimulus-responsive block copolymer nano-objects and hydrogels via dynamic covalent chemistry.

Herein we demonstrate that dynamic covalent chemistry can be used to induce reversible morphological transitions in block copolymer nano-objects and hydrogels. Poly(glycerol monomethacrylate)-poly(2-hydroxypropyl methacrylate) (PGMA-PHPMA) diblock copolymer nano-objects (vesicles or worms) were prepared via polymerization-induced self-assembly. Addition of 4-carboxyphenylboronic acid (CPBA) leads to the formation of phenylboronate ester bonds with the 1,2-diol pendent groups on the hydrophilic PGMA stabilizer chains; such binding causes a subtle reduction in the packing parameter, which in turn induces either vesicle-to-worm or worm-to-sphere transitions. Moreover, CPBA binding is pH-dependent, so reversible transitions can be achieved by switching the solution pH, with relatively high copolymer concentrations leading to associated (de)gelation. This distinguishes these new physical hydrogels from the covalently cross-linked gels prepared using dynamic covalent chemistry reported in the literature.

H2O2 Enables Convenient Removal of RAFT End-Groups from Block Copolymer Nano-Objects Prepared via Polymerization-Induced Self-Assembly in Water.

RAFT-synthesized polymers are typically colored and malodorous due to the presence of the sulfur-based RAFT end-group(s). In principle, RAFT end-groups can be removed by treating molecularly dissolved copolymer chains with excess free radical initiators, amines, or oxidants. Herein we report a convenient method for the removal of RAFT end-groups from aqueous dispersions of diblock copolymer nano-objects using H2O2. This oxidant is relatively cheap, has minimal impact on the copolymer morphology, and produces benign side products that can be readily removed via dialysis. We investigate the efficiency of end-group removal for various diblock copolymer nano-objects prepared with either dithiobenzoate- or trithiocarbonate-based RAFT chain transfer agents. The advantage of using UV GPC rather than UV spectroscopy is demonstrated for assessing both the kinetics and extent of end-group removal.

Evidence-based medicine: discrepancy between perceived competence and actual performance among graduating medical students.

Since at the time of graduation from medical school physicians are expected to demonstrate adequate professional competence including mastery of critical appraisal skills, we conducted a preliminary, cross-sectional, web-based study to examine the extent to which fourth year medical students in the US are competent in core areas of evidence-based medicine (EBM). Using self-assessment instruments, subjects (n = 150) were asked to demonstrate their ability to understand the practical meaning of key methodological and data analysis constructs as they relate to patient care, to rate their perceived competence in core areas of EBM and to disclose their attitudes toward critical appraisal of the literature and EBM. The mean score in our cohort was 55% suggesting that students may have knowledge gaps that interfere with their ability to critically appraise the medical literature. There was an apparent chasm between subjects' perceived competence and their actual performance on the assessment instrument. These findings, if corroborated in larger studies, (1) suggest that better education in EBM is needed so as to avoid the possibility that patient care may inadvertently be jeopardized; and (2) cast doubt on the use of self-assessed knowledge as a proxy for actual skills with respect to EBM and medical decision-making.

RAFT Aqueous Dispersion Polymerization of N-(2-(Methacryloyloxy)ethyl)pyrrolidone: A Convenient Low Viscosity Route to High Molecular Weight Water-Soluble Copolymers.

RAFT solution polymerization of N-(2-(methacryoyloxy)ethyl)pyrrolidone (NMEP) in ethanol at 70 °C was conducted to produce a series of PNMEP homopolymers with mean degrees of polymerization (DP) varying from 31 to 467. Turbidimetry was used to assess their inverse temperature solubility behavior in dilute aqueous solution, with an LCST of approximately 55 °C being observed in the high molecular weight limit. Then a poly(glycerol monomethacylate) (PGMA) macro-CTA with a mean DP of 63 was chain-extended with NMEP using a RAFT aqueous dispersion polymerization formulation at 70 °C. The target PNMEP DP was systematically varied from 100 up to 6000 to generate a series of PGMA63-PNMEP x diblock copolymers. High conversions (≥92%) could be achieved when targeting up to x = 5000. GPC analysis confirmed high blocking efficiencies and a linear evolution in Mn with increasing PNMEP DP. A gradual increase in Mw/Mn was also observed when targeting higher DPs. However, this problem could be minimized (Mw/Mn < 1.50) by utilizing a higher purity grade of NMEP (98% vs 96%). This suggests that the broader molecular weight distributions observed at higher DPs are simply the result of a dimethacrylate impurity causing light branching, rather than an intrinsic side reaction such as chain transfer to polymer. Kinetic studies confirmed that the RAFT aqueous dispersion polymerization of NMEP was approximately four times faster than the RAFT solution polymerization of NMEP in ethanol when targeting the same DP in each case. This is perhaps surprising because both 1H NMR and SAXS studies indicate that the core-forming PNMEP chains remain relatively solvated at 70 °C in the latter formulation. Moreover, dissolution of the initial PGMA63-PNMEP x particles occurs on cooling from 70 to 20 °C as the PNMEP block passes through its LCST. Hence this RAFT aqueous dispersion polymerization formulation offers an efficient route to a high molecular weight water-soluble polymer in a rather convenient low-viscosity form. Finally, the relatively expensive PGMA macro-CTA was replaced with a poly(methacrylic acid) (PMAA) macro-CTA. High conversions were also achieved for PMAA85-PNMEP x diblock copolymers prepared via RAFT aqueous dispersion polymerization for x ≤ 4000. Again, better control was achieved when using the 98% purity NMEP monomer in such syntheses.

Determining the Effective Density and Stabilizer Layer Thickness of Sterically Stabilized Nanoparticles.

A series of model sterically stabilized diblock copolymer nanoparticles has been designed to aid the development of analytical protocols in order to determine two key parameters: the effective particle density and the steric stabilizer layer thickness. The former parameter is essential for high resolution particle size analysis based on analytical (ultra)centrifugation techniques (e.g., disk centrifuge photosedimentometry, DCP), whereas the latter parameter is of fundamental importance in determining the effectiveness of steric stabilization as a colloid stability mechanism. The diblock copolymer nanoparticles were prepared via polymerization-induced self-assembly (PISA) using RAFT aqueous emulsion polymerization: this approach affords relatively narrow particle size distributions and enables the mean particle diameter and the stabilizer layer thickness to be adjusted independently via systematic variation of the mean degree of polymerization of the hydrophobic and hydrophilic blocks, respectively. The hydrophobic core-forming block was poly(2,2,2-trifluoroethyl methacrylate) [PTFEMA], which was selected for its relatively high density. The hydrophilic stabilizer block was poly(glycerol monomethacrylate) [PGMA], which is a well-known non-ionic polymer that remains water-soluble over a wide range of temperatures. Four series of PGMA x -PTFEMA y nanoparticles were prepared (x = 28, 43, 63, and 98, y = 100-1400) and characterized via transmission electron microscopy (TEM), dynamic light scattering (DLS), and small-angle X-ray scattering (SAXS). It was found that the degree of polymerization of both the PGMA stabilizer and core-forming PTFEMA had a strong influence on the mean particle diameter, which ranged from 20 to 250 nm. Furthermore, SAXS was used to determine radii of gyration of 1.46 to 2.69 nm for the solvated PGMA stabilizer blocks. Thus, the mean effective density of these sterically stabilized particles was calculated and determined to lie between 1.19 g cm-3 for the smaller particles and 1.41 g cm-3 for the larger particles; these values are significantly lower than the solid-state density of PTFEMA (1.47 g cm-3). Since analytical centrifugation requires the density difference between the particles and the aqueous phase, determining the effective particle density is clearly vital for obtaining reliable particle size distributions. Furthermore, selected DCP data were recalculated by taking into account the inherent density distribution superimposed on the particle size distribution. Consequently, the true particle size distributions were found to be somewhat narrower than those calculated using an erroneous single density value, with smaller particles being particularly sensitive to this artifact.

Reliability and validity of the DCP among hispanic veterans.

The Diabetes Care Profile (DCP) was designed to measure psychosocial factors related to diabetes and its treatment. This study sought to determine the reliability and validity of the DCP in Hispanic veterans with Type 2 diabetes. Hispanic (n=81) and non-Hispanic White (n=238) patients were recruited at three southwestern VA hospitals. Scale reliabilities calculated by Cronbach's coefficient alpha revealed reliabilities ranging from .54 to .97 in Hispanics and .63 to .95 in non-Hispanic Whites. Only one scale, Monitoring Barriers, differed significantly between the two patient groups. Mean values on the DCP scales were consistent within and across ethnicities lending support for construct validity of the DCP in Hispanics. Convergent validity was also supported for DCP scales within the Hispanic patients as evidenced by correlations in expected directions with external measures.

Development and validation of a new global well-being outcomes rating scale for integrative medicine research.

BACKGROUND: Researchers are finding limitations of currently available disease-focused questionnaire tools for outcome studies in complementary and alternative medicine/integrative medicine (CAM/IM). METHODS: Three substudies investigated the new one-item visual analogue Arizona Integrative Outcomes Scale (AIOS), which assesses self-rated global sense of spiritual, social, mental, emotional, and physical well-being over the past 24 hours and the past month. The first study tested the scale's ability to discriminate unhealthy individuals (n = 50) from healthy individuals (n = 50) in a rehabilitation outpatient clinic sample. The second study examined the concurrent validity of the AIOS by comparing ratings of global well-being to degree of psychological distress as measured by the Brief Symptom Inventory (BSI) in undergraduate college students (N = 458). The third study evaluated the relationships between the AIOS and positively- and negatively-valenced tools (Positive and Negative Affect Scale and the Positive States of Mind Scale) in a different sample of undergraduate students (N = 62). RESULTS: Substudy (i) Rehabilitation patients scored significantly lower than the healthy controls on both forms of the AIOS and a current global health rating. The AIOS 24-hours correlated moderately and significantly with global health (patients r = 0.50; controls r = 0.45). AIOS 1-month correlations with global health were stronger within the controls (patients r = 0.36; controls r = 0.50). Controls (r = 0.64) had a higher correlation between the AIOS 24-hour and 1-month forms than did the patients (r = 0.33), which is consistent with the presumptive improvement in the patients' condition over the previous 30 days in rehabilitation. Substudy (ii) In undergraduate students, AIOS scores were inversely related to distress ratings, as measured by the global severity index on the BSI (rAIOS24h = -0.42, rAIOS1month = -0.40). Substudy (iii) AIOS scores were significantly correlated with positive affect (rAIOS24h = 0.56, rAIOS1month = 0.57) and positive states of mind (rAIOS24h = 0.42, rAIOS1month = 0.45), and inversely correlated with negative affect (rAIOS24h = -0.41, rAIOS1month = -0.59). CONCLUSIONS: The AIOS is able to distinguish relatively sicker from relatively healthier individuals; and correlates in expected directions with a measure of distress and indicators of positive and negative affect and positive states of mind. The AIOS offers a tool for CAM/IM research that extends beyond a disease emphasis.

Individual differences in response to randomly assigned active individualized homeopathic and placebo treatment in fibromyalgia: implications of a double-blinded optional crossover design.

OBJECTIVE: To assess individual difference characteristics of subgroups of patients with fibromyalgia (FM) patients with respect to the decision to stay in or switch from randomly-assigned verum or placebo treatment during an optional crossover phase of a double-blinded homeopathy study. DESIGN: Double-blinded, randomized, placebo-controlled, optional crossover clinical trial. PARTICIPANTS: Fifty-three (53) community-recruited patients with FM entered the optional crossover phase. INTERVENTION: Two homeopaths jointly selected an individualized homeopathic remedy for all patients. The pharmacy dispensed either verum LM remedy or indistinguishable placebo in accord with randomized assignment for 4 months and the patient's optional crossover decision for an additional 2 months. OUTCOME MEASURES: Patients completed a battery of baseline state/trait questionnaires, including mood, childhood neglect and abuse, and trait absorption. They rated global health (whole person-centered) and tender point pain on physical examination (disease-specific) at baseline, 3 months, and 6 months. RESULTS: Rates of optional crossover from verum to placebo or placebo to verum were comparable (p = 0.6; 31%, and 41%, respectively). The switch subgroups had greater baseline psychologic issues (emotional neglect in placebo-switch; depression and anger in verum-switch). The verum-stay subgroup scored highest on treatment helpfulness and included all six exceptional responders who fell, prior to crossover, into the top terciles for improvement in both global health and pain. Patients staying in their randomly assigned groups, active or placebo (n = 34), scored significantly higher in trait absorption than did those who switched groups (n = 19). CONCLUSION: Individual difference factors may predict better and poorer responders with FM to specific and nonspecific effects of homeopathic and placebo treatment.