Length-Dependent Cellular Internalization of Nanobody-Functionalized Poly(2-oxazoline) Nanorods.

The ability to target specific tissues and to be internalized by cells is critical for successful nanoparticle-based targeted drug delivery. Here, we combined "stealthy" rod-shaped poly(2-oxazoline) (POx) nanoparticles of different lengths with a cancer marker targeting nanobody and a fluorescent cell internalization sensor via a heat-induced living crystallization-driven self-assembly (CDSA) strategy. A significant increase in association and uptake driven by nanobody-receptor interactions was observed alongside nanorod-length-dependent kinetics. Importantly, the incorporation of the internalization sensor allowed for quantitative differentiation between cell surface association and internalization of the targeted nanorods, revealing unprecedented length-dependent cellular interactions of CDSA nanorods. This study highlights the modularity and versatility of the heat-induced CDSA process and further demonstrates the potential of POx nanorods as a modular nanomedicine platform.

Intrinsic Green Fluorescent Cross-Linked Poly(ester amide)s by Spontaneous Zwitterionic Copolymerization.

The spontaneous zwitterionic copolymerization (SZWIP) of 2-oxazolines and acrylic acid affords biocompatible but low molecular weight linear N-acylated poly(amino ester)s (NPAEs). Here, we present a facile one-step approach to prepare functional higher molar mass cross-linked NPAEs using 2,2'-bis(2-oxazoline)s (BOx). In the absence of solvent, insoluble free-standing gels were formed from BOx with different length n-alkyl bridging units, which when butylene-bridged BOx was used possessed an inherent green fluorescence, a behavior not previously observed for 2-oxazoline-based polymeric materials. We propose that this surprising polymerization-induced emission can be classified as nontraditional intrinsic luminescence. Solution phase and oil-in-oil emulsion approaches were investigated as means to prepare solution processable fluorescent NPAEs, with both resulting in water dispersible network polymers. The emulsion-derived system was investigated further, revealing pH-responsive intensity of emission and excellent photostability. Residual vinyl groups were shown to be available for modifications without affecting the intrinsic fluorescence. Finally, these systems were shown to be cytocompatible and to function as fluorescent bioimaging agents for in vitro imaging.

Low-dose aspirin for primary prevention of cardiovascular disease: Trends in use patterns among African American adults in Minnesota, 2015-2019.

Cardiovascular disease (CVD) disproportionately affects African Americans. Aspirin has long been recommended to reduce cardiovascular events. However, national guideline changes in 2016 limited the aspirin recommended population and several clinical trials questioning the utility of primary prevention aspirin were published in 2018. In light of the recent guidelines and study findings, we investigated primary prevention aspirin use among urban African American adults. Using three cross-sectional surveys, we collected data from self-identified African Americans with no CVD in 2015, 2017 and 2019, querying information on CVD risk factors, health behaviors and beliefs, and aspirin use. Poisson regression modeling was used to estimate age- and risk-factor adjusted aspirin prevalence, trends and associations. A total of 1491 African Americans adults, ages 45-79, were included in this analysis; 61% were women. There was no change in age- and risk factor-adjusted aspirin use over the 3 surveys for women (37%, 34% and 35% respectively) or men (27%, 25%, 30% respectively). However, fewer participants believed aspirin was helpful in 2019 compared to 2015-75% versus 84% (p < 0.001). Aspirin discussions with a health care practitioner were highly associated with aspirin use (adjusted RR 2.97, 95% CI 2.49-3.54) and aspirin use was 2.56 times higher (adjusted RR 95% CI 2.17-3.03) in respondents who agreed that people close to them thought they should take aspirin compared with those who disagreed or did not know. Despite major changes in national guidelines, overall primary prevention aspirin use did not significantly change in these African American samples from 2015 to 2019.

Extending the Scope of "Living" Crystallization-Driven Self-Assembly: Well-Defined 1D Micelles and Block Comicelles from Crystallizable Polycarbonate Block Copolymers.

Fiber-like block copolymer (BCP) micelles offer considerable potential for a variety of applications; however, uniform samples of controlled length and with spatially tailored chemistry have not been accessible. Recently, a seeded growth method, termed "living" crystallization-driven self-assembly (CDSA), has been developed to allow the formation of 1D micelles and block comicelles of precisely controlled dimensions from BCPs with a crystallizable segment. An expansion of the range of core-forming blocks that participate in living CDSA is necessary for this technique to be compatible with a broad range of applications. Few examples currently exist of well-defined, water-dispersible BCP micelles prepared using this approach, especially from biocompatible and biodegradable polymers. Herein, we demonstrate that BCPs containing a crystallizable polycarbonate, poly(spiro[fluorene-9,5'-[1,3]-dioxan]-2'-one) (PFTMC), can readily undergo living CDSA processes. PFTMC- b-poly(ethylene glycol) (PEG) BCPs with PFTMC:PEG block ratios of 1:11 and 1:25 were shown to undergo living CDSA to form near monodisperse fiber-like micelles of precisely controlled lengths of up to ∼1.6 µm. Detailed structural characterization of these micelles by TEM, AFM, SAXS, and WAXS revealed that they comprise a crystalline, chain-folded PFTMC core with a rectangular cross-section that is surrounded by a solvent swollen PEG corona. PFTMC- b-PEG fiber-like micelles were shown to be dispersible in water to give colloidally stable solutions. This allowed an assessment of the toxicity of these structures toward WI-38 and HeLa cells. From these experiments, we observed no discernible cytotoxicity from a sample of 119 nm fiber-like micelles to either healthy (WI-38) or cancerous (HeLa) cell types. The living CDSA process was extended to PFTMC- b-poly(2-vinylpyridine) (P2VP), and addition of this BCP to PFTMC- b-PEG seed micelles led to the formation of well-defined segmented fibers with spatially localized coronal chemistries.

Enabling Heterogeneous Gold Catalysis with Patchy Micelles.

Patch works! Patchy block copolymer micelles with a corona consisting of two chemically different patches have been designed for the selective binding of catalytically active nanoparticles. The fabrication of nonwoven supports by electrospinning was combined with crystallization-driven self-assembly for precise control over micelle formation to prepare a new recyclable catalyst platform.

In Situ Visualization of Block Copolymer Self-Assembly in Organic Media by Super-Resolution Fluorescence Microscopy.

Analytical methods that enable visualization of nanomaterials derived from solution self-assembly processes in organic solvents are highly desirable. Herein, we demonstrate the use of stimulated emission depletion microscopy (STED) and single molecule localization microscopy (SMLM) to map living crystallization-driven block copolymer (BCP) self-assembly in organic media at the sub-diffraction scale. Four different dyes were successfully used for single-colour super-resolution imaging of the BCP nanostructures allowing micelle length distributions to be determined in situ. Dual-colour SMLM imaging was used to measure and compare the rate of addition of red fluorescent BCP to the termini of green fluorescent seed micelles to generate block comicelles. Although well-established for aqueous systems, the results highlight the potential of super-resolution microscopy techniques for the interrogation of self-assembly processes in organic media.

Anticipating change, sparking innovation: framing the future.

As the 100th anniversary of the 1915 Welch-Rose report approaches, the Association of Schools and Programs of Public Health (ASPPH) has been pursuing two initiatives to spark innovation in academic partnerships for enhancing population health: (1) Framing the Future: The Second 100 Years of Education for Public Health and (2) Reconnecting Public Health and Care Delivery to Improve the Health of Populations. We describe how ASPPH-member schools and programs accredited by the Council on Education for Public Health, along with their extraordinarily diverse array of partners, are working to improve education that better prepares health professionals to meet 21st-century population health needs.

Legitimising fatigue after breast-cancer treatment.

This study aimed to explore the experience of women living with fatigue following chemotherapy for breast cancer. Six focus groups were conducted (n=40); all participants had taken part in a multi-site acupuncture trial. There were three to seven people per focus group. Additionally, two people attended one-to-one interviews and four people provided written responses to the trigger questions. The audiotapes from these sessions were transcribed and analysed using a thematic approach. Participants raised concerns about fatigue possibly being a symptom of the cancer coming back or a sign of senility. Respondents described the effects of fatigue on relationships, sexuality, social life, home life and returning to work. The Coping with Fatigue booklet ( Macmillan Cancer Support, 2011 ) was discussed in terms of legitimising the experience of cancer-related fatigue and explaining symptoms to family and work colleagues. More research work is required to evaluate non-pharmaceutical interventions and advice to support women living with fatigue after chemotherapy for breast cancer.

Gradient crystallization-driven self-assembly: cylindrical micelles with "patchy" segmented coronas via the coassembly of linear and brush block copolymers.

Block copolymers (BCPs) with a short crystallizable poly(ferrocenyldimethylsilane) (PFS) core-forming block self-assemble in selective solvents to afford cylindrical micelles, the ends of which are active to further growth via a process termed living crystallization-driven self-assembly (CDSA). We now report studies of the CDSA of a series of crystalline-brush BCPs with C6 (BCP(6)), C12 (BCP(12)), and C18 (BCP(18)) n-alkyl branches that were prepared by the thiol-ene functionalization of PFS-b-PMVS (PMVS = poly(methylvinylsiloxane)). Although the increased n-alkyl brush length of BCP(12) and BCP(18) hindered micelle growth, the increased intercoronal chain repulsion could be alleviated by their coassembly with linear PFS-b-PMVS. When the coassembly was initiated by short cylindrical seed micelles, monodisperse block comicelles of controllable length with "patchy" coronal nanodomains were accessible. TEM and AFM analysis of micelles prepared from BCP(18) and PFS-b-PMVS were found to provide complementary characterization in that the OsO4-stained PMVS coronal domains were observed by TEM, whereas the brush block domains of BCP(18) (which displayed greater height) were detected by tapping mode AFM. The results showed that the coassembly afforded a gradient structure, with an initial bias for the growth of the linear BCP over that of the more sterically demanding brush BCP, which was gradually reversed as the linear material was consumed. This represents the first example of living gradient CDSA, a process reminiscent of a living covalent gradient copolymerization of two different monomers. Although other possible explanations exist, simulations based on a statistical model indicated that the coronal nanodomains detected likely result from a segmented, gradient comicelle architecture that arises as a consequence of: (i) different rates of addition of BCP unimer to the micelle termini, and (ii) a cumulative effect resulting from steric hindrance associated with the brush block.

Socioeconomic differences in the risk profiles of susceptibility and ever use of tobacco among Indian urban youth: a latent class approach.

PURPOSE: To empirically determine the socioeconomic differences in risk profiles of susceptibility and ever use of tobacco among adolescents in India and to investigate the association between the risk profiles and the psychosocial factors for tobacco use. METHODS: Students in 16 private (higher socioeconomic status [SES]; n = 4,489) and 16 government (lower SES; n = 7,153) schools in two large cities in India were surveyed about their tobacco use and related psychosocial factors in 2004. Latent class analysis was used to identify homogenous, mutually exclusive typologies existing within the data. RESULTS: Overall, 3 and 4 latent classes of susceptibility and ever use of tobacco best described students in higher- and lower- SES schools, respectively. Profiles with various combinations of susceptibility and ever use of tobacco were differentially related to psychosocial factors, with lower- SES students being more vulnerable to increased levels of tobacco use than higher- SES students. CONCLUSIONS: Acknowledging the multiple dimensions of tobacco use behaviors and identifying constellations of risk behaviors will enable more accurate understanding of etiological processes and will provide information for refining and targeting preventive interventions. Additionally, identifying the socioeconomic differences in susceptibility and ever use risk profiles and their psychosocial correlates will enable policy makers to address these inequities through improved allocation of resources.

"No decision about me without me" in the context of cancer multidisciplinary team meetings: a qualitative interview study.

BACKGROUND: Cancer care is commonly managed by multidisciplinary teams (MDTs) who meet to discuss and agree treatment for individual patients. Patients do not attend MDT meetings but recommendations for treatments made in the meetings directly influence the decision-making process between patients and their responsible clinician. No research to-date has considered patient perspectives (or understanding) regarding MDTs or MDT meetings, though research has shown that failure to consider patient-based information can lead to recommendations that are inappropriate or unacceptable, and can consequently delay treatment. METHODS: Semi-structured interviews were conducted with current cancer patients from one cancer centre who had either upper gastrointestinal or gynaecological cancer (n = 9) and with MDT members (n = 12) from the teams managing their care. Interview transcripts were analysed thematically using Framework approach. Key themes were identified and commonalities and discrepancies within and between individual transcripts and within and between patient and team member samples were identified and examined using the constant comparative method. RESULTS: Patients had limited opportunities to input to or influence the decision-making process in MDT meetings. Key explanatory factors included that patients were given limited and inconsistent information about MDTs and MDT meetings, and that MDT members had variable definitions of patient-centredness in the context of MDTs and MDT meetings. Patients that had knowledge of medicine (through current/previous employment themselves or that of a close family member) appeared to have greater understanding and access to the MDT. Reassurance emerged as a 'benefit' of informing patients about MDTs and MDT meetings. CONCLUSIONS: There is a need to ensure MDT processes are both efficient and patient-centred. The operationalization of "No decision about me without me" in the context of MDT models of care - where patients are not present when recommendations for treatment are discussed - requires further consideration. Methods for ensuring that patients are actively integrated into the MDT processes are required to ensure patients have an informed choice regarding engagement, and to ensure recommendations are based on the best available patient-based and clinical evidence.

A 16-month community-based intervention to increase aspirin use for primary prevention of cardiovascular disease.

INTRODUCTION: Cardiovascular diseases are the leading causes of disability and death in the United States. Primary prevention of these events may be achieved through aspirin use. The ability of a community-based intervention to increase aspirin use has not been evaluated. The objective of this study was to evaluate an educational intervention implemented to increase aspirin use for primary prevention of cardiovascular disease in a small city in Minnesota. METHODS: A community-based intervention was implemented during 16 months in a medium-sized community in Minnesota. Messages for aspirin use were disseminated to individuals, health care professionals, and the general population. Independent cross-sectional samples of residents (men aged 45-79, women aged 55-79) were surveyed by telephone to identify candidates for primary prevention aspirin use, examine their characteristics, and determine regular aspirin use at baseline and after the campaign at 4 months and 16 months. RESULTS: In primary prevention candidates, regular aspirin use rates increased from 36% at baseline to 54% at 4 months (odds ratio = 2.05; 95% confidence interval, 1.09-3.88); the increase was sustained at 52% at 16 months (odds ratio = 1.89; 95% confidence interval, 1.02-3.49). The difference in aspirin use rates at 4 months and 16 months was not significant (P = .77). CONCLUSION: Aspirin use rates for primary prevention remain low. A combined public health and primary care approach can increase and sustain primary prevention aspirin use in a community setting.

A technique to retrieve an internalised embedded central venous catheter.

BACKGROUND: Central venous catheters may become embedded due to the formation of adhesions between the indwelling catheter and the vein wall. CASE PRESENTATION: A 49-year-old patient with bacteraemia was referred for retrieval of an embedded internalised central venous dialysis catheter. Recently the catheter had been surgically ligated at the venotomy site internalising the intravascular catheter component, which precluded antegrade ballooning through the catheter hub. Seldinger technique was used to access the catheter lumen within the left internal jugular vein and through and through access was established across the catheter. Retrograde endoluminal balloon dilation was performed to disrupt adhesions and free the catheter. The catheter was snared over the wire and removed from the right femoral vein. CONCLUSION: This case report outlines an effective, minimally invasive retrieval method in a rare case of an embedded internalised central venous catheter.

CT guided sharp recanalization to restore dialysis access in patients with central venous obstruction: A single centre experience and review of alternative techniques.

Central venous obstructions that impedes catheter placement or results in catheter dysfunction is a significant problem for haemodialysis patients. Recanalization can be performed with an intent to restore central venous access, improve outflow from arteriovenous fistula or to relieve symptomatic venous obstructions. Sharp recanalization encompasses various interventional techniques using a sharp instrument to puncture through or bypass around a venous obstruction. In this paper we outline our experience performing CT guided sharp recanalization and review alternative sharp recanalization techniques that are specifically used to restore haemodialysis access in patients with thoracic central venous obstruction.

Impact of Drug Conjugation Site and Corona Chemistry on the Therapeutic Activity of Polymer Nanorod - Drug Conjugates.

Biocompatible rod-shaped nanoparticles of controlled length can be produced through the heat-induced "living" seeded crystallization-driven self-assembly (CDSA) of poly(2-isopropyl-2-oxazoline)-containing block copolymers. With a hydrophilic poly(2-methyl-2-oxazine) or poly(2-methyl-2-oxazoline) corona, these nanorods have proven non-cytotoxic, non-hemolytic, and ideal for use as a polymer-based drug delivery system. This study demonstrates a facile, one-pot method for the synthesis of mycophenolic acid (MPA)-conjugated block copolymer "unimers" for use in seeded CDSA. Through altering block order during sequential monomer addition cationic ring-opening polymerization (CROP), MPA is conjugated to either the chain end of the core-forming or corona-forming block. This allows bioactive polymer nanorods to be prepared with MPA positioned at either the periphery of the corona, or at the core-corona interface of the nanorod formed during seeded CDSA. In vitro, these nanorods arrest growth in human T and B lymphocytes, with reduced effect in "off-target" monocytes when compared with unconjugated MPA. Furthermore, the conjugation of MPA to the core-corona interface of the nanorods leads to a slower release and reduced cytostatic effect. This study offers a robust investigation into the effect of steric hindrance and corona chemistry on the therapeutic potential of drug-conjugated CDSA nanorods and demonstrates the potential of poly(2-oxazoline)/poly(2-oxazine)-based CDSA nanomaterials as effective drug delivery platforms.

A randomized, controlled trial of acupuncture self-needling as maintenance therapy for cancer-related fatigue after therapist-delivered acupuncture.

BACKGROUND: Maintenance acupuncture is advocated by clinicians after successful clinic-based acupuncture. We aimed to assess the effectiveness of maintenance acupuncture in the management of cancer-related fatigue (CRF); treatment delivered by therapists or self-acupuncture/self-needling was compared with no maintenance treatment. METHODS: Breast cancer patients who participated in a randomized trial of acupuncture for CRF management (reported elsewhere) were re-randomized to receive an additional four acupuncturist-delivered weekly sessions; four self-administered weekly acupuncture sessions (self-needling); or no acupuncture. Primary outcome was general fatigue (Multidimensional Fatigue Inventory). Mood, quality of life and safety were also assessed. RESULTS: In total, 197 patients were re-randomized, with 65 to therapist-delivered sessions, 67 to self-acupuncture/self-needling and 65 to no further acupuncture. Primary outcome scores were equivalent between the therapist-delivered acupuncture and self-acupuncture (P > 0.05). A non-significant trend in improving fatigue was observed at the end of 4 weeks in the combined acupuncture arms (P = 0.07). There was no impact on mood or quality of life of the further acupuncture sessions at 18 weeks beyond the improvement observed in initial trial. CONCLUSION: Self-acupuncture is an acceptable, feasible and safe maintenance treatment for patients with CRF. However, overall, maintenance acupuncture did not yield important improvements beyond those observed after an initial clinic-based course of acupuncture. TRIAL REGISTRATION NUMBER: NCT00957112.

Individual and neighborhood socioeconomic status effects on adolescent smoking: a multilevel cohort-sequential latent growth analysis.

OBJECTIVES: We examined the prospective effects of parental education (as a proxy for individual socioeconomic status [SES]) and neighborhood SES on adolescent smoking trajectories and whether the prospective effects of individual SES varied across neighborhood SES. METHODS: The study included 3635 randomly recruited adolescents from 5 age cohorts (12-16 years) assessed semiannually for 3 years in the Minnesota Adolescent Community Cohort study. We employed a cohort-sequential latent growth model to examine smoking from age 12 to 18 years with predictors. RESULTS: Lower individual SES predicted increased levels of smoking over time. Whereas neighborhood SES had no direct effect, the interaction between individual and neighborhood SES was significant. Among higher and lower neighborhood SES, lower individual SES predicted increased levels of smoking; however, the magnitude of association between lower individual SES and higher smoking levels was significantly greater for higher neighborhood SES. CONCLUSIONS: We found evidence for differential effects of individual SES on adolescent smoking for higher and lower neighborhood SES. The group differences underscore social conditions as fundamental causes of disease and development of interventions and policies to address inequality in the resources.

Public health as a distinct profession: has it arrived?

This article reviews the elements consistent with the definition of a "profession" in the contemporary United States and argues that public health should be considered a distinct profession, recognizing that it has a unique knowledge base and career paths independent of any other occupation or profession. The Welch-Rose Report of 1915 prescribed education for public health professionals and assumed that, although at first the majority of students would be drawn from other professions, such as medicine, nursing, and sanitary engineering, public health was on its way to becoming "a new profession." Nearly a century later, the field of public health has evolved dramatically in the direction predicted. It clearly meets the criteria for being a "profession" in that it has (1) a distinct body of knowledge, (2) an educational credential offered by schools and programs accredited by a specialized accrediting body, (3) career paths that include autonomous practice, and (4) a separate credential, Certified in Public Health (CPH), indicative of self-regulation based on the newly launched examination of the National Board of Public Health Examiners. Barriers remain that challenge independent professional status, including the breadth of the field, more than one accrediting body, wide variation in graduate school curricula, and the newness of the CPH. Nonetheless, the benefits of recognizing public health as a distinct profession are considerable, particularly to the practice and policy communities. These include independence in practice, the ability to recruit the next generation, increased influence on health policy, and infrastructure based on a workforce of strong capacity and leadership capabilities.

Visible Light-Accelerated Photoiniferter Polymerization in Ionic Liquid.

The effect of ionic liquids on the reversible addition-fragmentation chain transfer (RAFT) polymerization mediated by a visible-light-induced photoiniferter mechanism was investigated. N,N-Dimethyl acrylamide was polymerized by photoiniferter polymerization in 1-ethyl-3-methylimidazolium ethylsulfate [EMIM][EtSO4] ionic liquid. We observed a considerable increase in the polymerization rate constants in ionic liquids (ILs), as well as in the mixed solvent of water and the IL, compared to those observed with water alone as the solvent. To demonstrate the robustness of the process, block copolymers with varying block ratios were synthesized with precise control over their molecular weight and mass dispersity (D). The very high chain-end fidelity provided by the photoiniferter polymerization in IL was described by using MALDI-ToF MS analysis.

Obesity, Sarcopenia and Myosteatosis: Impact on Clinical Outcomes in the Operative Management of Crohn's Disease.

BACKGROUND: Obesity, sarcopenia, and myosteatosis in inflammatory bowel disease may confer negative outcomes, but their prevalence and impact among patients with Crohn's disease (CD) have not been systematically studied. The aim of this study was to assess nutritional status and body composition among patients undergoing resectional surgery for CD and determine impact on operative outcomes. METHODS: Consecutive patients with CD undergoing resection from 2000 to 2018 were studied. Total, subcutaneous, and visceral fat areas and lean tissue area (LTA) and intramuscular adipose tissue (IMAT) were determined preoperatively by computed tomography at L3 using SliceOmatic (Tomovision, Canada). Univariable and multivariable linear, logistic, and Cox proportional hazards regression were performed. RESULTS: One hundred twenty-four consecutive patients were studied (ileocolonic disease 53%, n = 62, biologic therapy 34.4% n = 43). Mean fat mass was 22.7 kg, with visceral obesity evident in 23.9% (n = 27). Increased fat stores were associated with reduced risk of emergency presentation but increased corticosteroid use (ß 9.09, standard error 3.49; P = .011). Mean LBM was 9.9 kg. Sarcopenia and myosteatosis were associated with impaired baseline nutritional markers. Myosteatosis markers IMAT (P = .002) and muscle attenuation (P = .0003) were associated with increased grade of complication. On multivariable analysis, IMAT was independently associated with increased postoperative morbidity (odds ratio [OR], 1.08; 95% confidence interval (CI), 1.01-1.16; P = .037) and comprehensive complications index (P = .029). Measures of adiposity were not associated with overall morbidity; however, increased visceral fat area independently predicted venous thromboembolism (OR, 1.02; 95% CI, 1.00-1.05; P = .028), and TFA was associated with increased wound infection (OR, 1.00; 95% CI, 1.00-1.01; P = .042) on multivariable analysis. CONCLUSION: Myosteatosis is associated with nutritional impairment and predicts increased overall postoperative morbidity following resection for CD. Despite its association with specific increased postoperative risks, increased adiposity does not increase overall morbidity, reflecting preservation of nutritional status and relatively more quiescent disease phenotype. Impaired muscle mass and function represent an appealing target for patient optimization to improve outcomes in the surgical management of CD.

Myosteatosis was predictive of postoperative morbidity following surgery for Crohn's Disease. Increased adiposity does not increase overall morbidity, reflecting a more quiescent disease phenotype. Obesity, myosteatosis, and sarcopenia represent appealing targets for patient optimization to improve outcomes surgical outcomes in Crohn's Disease.