Exposure assessment of plastics, phthalate plasticizers and their transformation products in diverse bio-based fertilizers.

Bio-based fertilizers (BBFs) produced from organic waste have the potential to reduce societal dependence on limited and energy-intensive mineral fertilizers. BBFs, thereby, contribute to a circular economy for fertilizers. However, BBFs can contain plastic fragments and hazardous additives such as phthalate plasticizers, which could constitute a risk for agricultural soils and the environment. This study assessed the exposure associated with plastic and phthalates in BBFs from three types of organic wastes: agricultural and food industry waste (AgriFoodInduWaste), sewage sludge (SewSludge), and biowaste (i.e., garden, park, food and kitchen waste). The wastes were associated with various treatments like drying, anaerobic digestion, and vermicomposting. The number of microplastics (0.045-5 mm) increased from AgriFoodInduWaste-BBFs (15-258 particles g-1), to SewSludge-BBFs (59-1456 particles g-1) and then to Biowaste-BBFs (828-2912 particles g-1). Biowaste-BBFs mostly contained packaging plastics (e.g., polyethylene terephthalate), with the mass of plastic (>10 g kg-1) exceeding the EU threshold (3 g kg-1, plastics >2 mm). Other BBFs mostly contained small (< 1 mm) non-packaging plastics in amounts below the EU limit. The calculated numbers of microplastics entering agricultural soils via BBF application was high (107-1010 microplastics ha-1y-1), but the mass of plastic released from AgriFoodInduWaste-BBFs and SewSludge-BBFs was limited (< 1 and <7 kg ha-1y-1) compared to Biowaste-BBFs (95-156 kg ha-1y-1). The concentrations of di(2-ethylhexyl)phthalate (DEHP; < 2.5 mg kg-1) and phthalate transformation products (< 8 mg kg-1) were low (< benchmark of 50 mg kg-1 for DEHP), attributable to both the current phase-out of DEHP as well as phthalate degradation during waste treatment. The Biowaste-BBF exposed to vermicomposting indicated that worms accumulated phthalate transformation products (4 mg kg-1). These results are overall positive for the implementation of the studied AgriFoodInduWaste-BBFs and SewSludge-BBFs. However, the safe use of the studied Biowaste-BBFs requires reducing plastic use and improving sorting methods to minimize plastic contamination, in order to protect agricultural soils and reduce the environmental impact of Biowaste-BBFs.

Midkine characterization in human ovaries: potential new variants in follicles.

OBJECTIVE: To characterize the growth factor midkine (MDK) in the human ovary to determine whether MDK is produced locally within the ovary, examine whether different ovarian cell types are more likely to produce MDK, and determine whether there are any stage-specific variations during follicle growth. Previous studies have revealed that MDK potentially affects human follicle growth and oocyte maturation. Proteomic analyses in follicular fluid (FF) have identified MDK to functionally cluster together and follow a similar expression profile to that of well-known proteins involved in ovarian follicle development. Midkine has not yet been characterized in the human ovary. DESIGN: Descriptive study. SETTING: University Hospital. PATIENTS: The study included samples from 121 patients: 71 patients (aged 17-37 years) who underwent ovarian tissue cryopreservation provided granulosa cells (GC), cumulus cells, ovarian cortex, medulla tissue, and FF from small antral follicles (SAF); and 50 patients (aged 20-35 years) receiving in vitro fertilization treatment provided FF from preovulatory follicles before and after induction of final follicle maturation. INTERVENTIONS: None. MAIN OUTCOME MEASURES: MDK relative gene expression was quantified using a real-time quantitative polymerase chain reaction in cumulus cells, GC, and medulla tissue. Additionally, immunostaining and western blotting assays were used to detect MDK protein in the ovarian cortex, which contains preantral follicles, SAF, and medulla tissue. Furthermore, enzyme-linked immunosorbent assay analyses were performed to measure the concentration of MDK in FF aspirated from SAF and preovulatory follicles both before and 36 hours after inducing the final maturation of follicles. RESULTS: Immunostaining and reverse transcription-quantitative polymerase chain reaction revealed a more prominent expression of MDK in GC compared with other ovarian cell types. Intrafollicular MDK concentration was significantly higher in SAF compared with preovulatory follicles. In addition, different molecular weight species of MDK were detected using western blotting in various ovarian sample types: GC and FF samples presented primarily one band of approximately 15 kDa and an additional band of approximately 13 kDa, although other bands with higher molecular weight (between 30 and 38 kDa) were detected in medulla tissue. CONCLUSIONS: This is the first time that MDK has been immunolocalized in human ovarian cells at the protein level and that potentially different MDK variants have been detected in human FF, GC, and ovarian medulla tissue. Future studies are needed to sequence and identify the different potential MDK variants found to determine their functional importance for ovary and oocyte competence.

Management and outcomes after neoadjuvant treatment for locally advanced breast cancer in older versus younger women.

AIM: This study examined treatment and survival among women with locally advanced breast cancer (LABC) through comparative analyses of women ≥70 years and those <70 years. The primary endpoint was surgery with curative intention following neoadjuvant therapy. Secondary endpoints were 3-year disease free survival (DFS), overall survival (OS), response rates, and adherence to treatment guidelines. METHODS: Patients diagnosed and treated for LABC between 2010 and 2019 at Odense University Hospital, Denmark, were eligible. Surgical information was dichotomized into surgery and no surgery for patients ≥70 years and <70 years, and treatment response was extracted from scan and pathology reports. Adherence to treatment guidelines was registered for the initiated neoadjuvant treatment, and 3-year OS and DFS were estimated using Kaplan-Meier and Log-rank-test. RESULTS: Of 210 women, 57/102 (55.9%) of those ≥70 years received surgery with curative intent compared with 103/108 (95.4%) of those <70 years. The main reason for omitting surgery was the patient's request. Fewer women ≥70 years received neoadjuvant therapy according to guidelines compared with their younger counterparts (63.7% versus 98.1%, p < 0.001), but treatment response for women who underwent surgery was similar in both groups. A non-significant difference in 3-year DFS and OS was observed between the groups. Three-year DFS was 80.5% and 73.3%, whereas 3-year OS was 89.6% and 88.7% for patients ≥70 years and <70 years, respectively. CONCLUSION: Among women with LABC, women ≥70 years were less likely to receive neoadjuvant therapy according to guidelines. Only half of the patients ≥70 years reached the goal of surgery with curative intent, with no difference in 3-year OS and DFS between age groups.

Improving hemocompatibility of artificial lungs by click conjugation of glycoengineered endothelial cells onto blood-contacting surfaces.

Artificial lungs, also known as oxygenators, allow adequate oxygenation of the blood in patients with severe respiratory failure and enable patient survival. However, the insufficient hemocompatibility of the current of artificial lungs hampers their long-term use. Therefore, in this study, a novel strategy was developed to efficiently endothelialize blood-contacting surfaces to improve their hemocompatibility. Hollow fiber membranes (HFMs) were functionalized with dibenzylcyclooctyne (DBCO), and endothelial cells were glycoengineered for covalent conjugation to DBCO by a copper-free click reaction. Metabolic glycoengineering using azidoacetylmannosamine-tetraacylated (Ac4ManNAz) resulted in highly efficient functionalization of endothelial cells with azide (N3) molecules on the cell surface without negative impact on cell viability. After 48 h, significantly improved endothelialization was detected on the HFM surfaces functionalized with DBCO compared to unmodified HFMs. Endothelial cells were responsive to inflammatory stimulus and expressed adhesion-promoting molecules (E-selectin, VCAM-1, and ICAM-1). Furthermore, the hemocompatibility of HFMs was analyzed by dynamic incubation with fresh human blood. DBCO-coated and uncoated HFMs showed a comparable hemocompatibility, but the endothelialization of HFMs significantly reduced the activation of blood coagulation and platelets. Interestingly, the incubation of endothelialized HFMs with human blood further reduced the expression of E-selectin and VCAM-1 in endothelial cells. In this study, a highly efficient, cell-compatible method for endothelialization of artificial lungs was established. This click chemistry-based method can be also applied for the endothelialization of other artificial surfaces for tissue engineering and regenerative medicine applications.

Stabilization of PFAS-contaminated soil with activated biochar.

Biochars are considered potential sustainable sorbents to reduce the leaching of per- and polyfluoroalkyl substances (PFAS) from contaminated soils. However, biochar characteristics must probably be optimized to achieve useful sorption capacity. In the present work, eight waste timber biochars were produced, including biochars activated to different degrees, at different temperatures, and using both steam and CO2. In laboratory batch experiments, the eight biochars were amended to soil samples from two different horizons, with low and high total organic carbon (TOC, 1.6% and 34.2%, respectively), of a heavily PFAS-contaminated soil (1200-3800 µg kg-1 PFAStot), at varying doses (0, 0.1, 0.5, 1.0 and 5.0%). With a 5% amendment to the low-TOC soil, all eight biochars resulted in strongly reduced leachate PFAS concentrations (by 98-100%). At the same amendment dose in the high-TOC soil, leachate concentration reductions were more modest (23-100%). This was likely due to a strong PFAS-sorption to the high-TOC soil itself, as well as biochar pore clogging in the presence of abundant organic matter, resulting in fewer sorption sites available to PFAS. Reduction in PFAS leaching was proportional to the degree of activation and activation temperature. Thus, lower amendment doses of activated biochars were needed to reduce PFAS leaching to the same level as with the non-activated biochar. Activation however, came at a tradeoff with biochar yield. Furthermore, the adsorption ability of these biochars increased proportionally with PFAS-fluorocarbon chain length, demonstrating the role of hydrophobic interactions in reduction of PFAS leaching. Development of internal surface area and porosity was proposed as the main factor causing the improved performance of activated biochars. This study shows that woody residues such as waste timber can be used to produce effective sorbents for the remediation of PFAS-contaminated soil. It also highlights the desirability of sorbate and matrix-specific optimization of biochar production.

Does GP empathy influence patient enablement and success in lifestyle change among high risk patients?

BACKGROUND: Chronic lifestyle-related-diseases can be prevented by healthy lifestyle. Patients at high risk of disease may benefit from targeted health checks in general practice. However, general-practice-based-studies have shown that patient outcome, enablement, and well-being may be influenced by general practitioner (GP) empathy. The aim of this study is to investigate 1) how high risk patients evaluate their GPs' empathy during a health check consultation, 2) whether the perceived GP empathy is associated with the patient's enablement in immediate continuation of the health check consultation and 3) the patient's subsequent lifestyle changes. METHODS: This study is part of a population based non-randomized feasibility study testing a complex intervention that systematically identifies citizens at high risk of lifestyle-related disease and with health-risk behavior and offers targeted preventive services in the Danish primary care sector. The ultimate aim of the intervention is to improve lifestyle and thereby reduce the risk of lifestyle-related disease. In the feasibility study a random sample of patients aged 30 to 59 years were invited to participate, and to fill in a questionnaire on lifestyle-risk factors. Participants deemed to be at high risk of disease were offered a focused clinical examination and a subsequent health check consultation at the GP. Following each health check consultation GP empathy and patient enablement were assessed using The Care Measure (CARE) and Patient Enablement Instrument (PEI). Patient's perceived healthy-lifestyle change (y/n) was assessed after three months. The study has been approved by the Danish Data Protection Agency (J.nr 2015-57-0008) and registered at ClinicalTrial. Gov on June 13, 2016. RESULTS: Twenty-six GP's participated in the study. Among 93 patients receiving a health check consultation 60 rated the GPs empathy. The median CARE-score was 40. The PEI median was 5.5 and 44.9% achieved a healthier lifestyle. No association was observed between GP empathy and patient enablement or a perceived healthier lifestyle. CONCLUSION: No statistical significant association between the CARE-score and patient enablement or a perceived healthier lifestyle was observed. Our results contrast previous findings and may to some extent be explained by a small sample size and the selected high-risk group. TRIAL REGISTRATION NUMBER: NCT02797392 .

Getting a good view: in vitro imaging of platelets under flow.

As the anucleate cells responsible for hemostasis and thrombosis, platelets are exposed to a myriad of biophysical and biochemical stimuli within vasculature and heterogeneous blood clots. Highly controlled, reductionist in vitro imaging studies have been instrumental in providing a detailed and quantitative understanding of platelet biology and behavior, and have helped elucidate some surprising functions of platelets. In this review, we highlight the tools and approaches that enable visualization of platelets in conjunction with precise control over the local biofluidic and biochemical microenvironment. We also discuss next generation tools that add further control over microenvironment cell stiffness or enable visualization of the interactions between platelets and endothelial cells. Throughout the review, we include pragmatic knowledge on imaging systems, experimental conditions, and approaches that have proved to be useful to our in vitro imaging studies of platelets under flow.

Bioactive food packaging based on starch, citric pectin and functionalized with Acca sellowiana waste by-product: Characterization and application in the postharvest conservation of apple.

Innovative biodegradable packaging with antimicrobial and antioxidant properties was developed, and functionalized with Acca sellowiana waste by-product (feijoa peel flour, FPF). Physicochemical, morphological, antioxidant, antimicrobial properties, and in situ application in the postharvest conservation of apple were conducted with the packaging produced. The results obtained demonstrate that FPF addition had a positive influence on the packaging characteristics, for all the parameters tested. The high concentration of antioxidant compounds in the films with FPF promoted antimicrobial activity against Escherichia coli, Salmonella typhimurium, and Pseudomonas aeruginosa. The packaging produced maintained the quality of apples during storage, with constant weight after 5 days of storage. Based on our results, the bioactive, antioxidant and antimicrobial packaging functionalized with Acca sellowiana waste by-product may be considered as a new alternative to packaging in food systems.

Microvasculature-on-a-chip for the long-term study of endothelial barrier dysfunction and microvascular obstruction in disease.

Alterations in the mechanical properties of erythrocytes occurring in inflammatory and hematologic disorders such as sickle cell disease (SCD) and malaria often lead to increased endothelial permeability, haemolysis, and microvascular obstruction. However, the associations among these pathological phenomena remain unknown. Here, we report a perfusable, endothelialized microvasculature-on-a-chip featuring an interpenetrating-polymer-network hydrogel that recapitulates the stiffness of blood-vessel intima, basement membrane self-deposition and self-healing endothelial barrier function for longer than 1 month. The microsystem enables the real-time visualization, with high spatiotemporal resolution, of microvascular obstruction and endothelial permeability under physiological flow conditions. We found how extracellular heme, a hemolytic byproduct, induces delayed but reversible endothelial permeability in a dose-dependent manner, and demonstrate that endothelial interactions with SCD or malaria-infected erythrocytes cause reversible microchannel occlusion and increased in situ endothelial permeability. The microvasculature-on-a-chip enables mechanistic insight into the endothelial barrier dysfunction associated with SCD, malaria and other inflammatory and haematological diseases.

Platelet Mechanotransduction.

The vasculature is a dynamic environment in which blood platelets constantly survey the endothelium for sites of vessel damage. The formation of a mechanically coherent hemostatic plug to prevent blood loss relies on a coordinated series of ligand-receptor interactions governing the recruitment, activation, and aggregation of platelets. The physical biology of each step is distinct in that the recruitment of platelets depends on the mechanosensing of the platelet receptor glycoprotein Ib for the adhesive protein von Willebrand factor, whereas platelet activation and aggregation are responsive to the mechanical forces sensed at adhesive junctions between platelets and at the platelet-matrix interface. Herein we take a biophysical perspective to discuss the current understanding of platelet mechanotransduction as well as the measurement techniques used to quantify the physical biology of platelets in the context of thrombus formation under flow.

Extracellular fluid tonicity impacts sickle red blood cell deformability and adhesion.

Abnormal sickle red blood cell (sRBC) biomechanics, including pathological deformability and adhesion, correlate with clinical severity in sickle cell disease (SCD). Clinical intravenous fluids (IVFs) of various tonicities are often used during treatment of vaso-occlusive pain episodes (VOE), the major cause of morbidity in SCD. However, evidence-based guidelines are lacking, and there is no consensus regarding which IVFs to use during VOE. Further, it is unknown how altering extracellular fluid tonicity with IVFs affects sRBC biomechanics in the microcirculation, where vaso-occlusion takes place. Here, we report how altering extracellular fluid tonicity with admixtures of clinical IVFs affects sRBC biomechanical properties by leveraging novel in vitro microfluidic models of the microcirculation, including 1 capable of deoxygenating the sRBC environment to monitor changes in microchannel occlusion risk and an "endothelialized" microvascular model that measures alterations in sRBC/endothelium adhesion under postcapillary venular conditions. Admixtures with higher tonicities (sodium = 141 mEq/L) affected sRBC biomechanics by decreasing sRBC deformability, increasing sRBC occlusion under normoxic and hypoxic conditions, and increasing sRBC adhesion in our microfluidic human microvasculature models. Admixtures with excessive hypotonicity (sodium = 103 mEq/L), in contrast, decreased sRBC adhesion, but overswelling prolonged sRBC transit times in capillary-sized microchannels. Admixtures with intermediate tonicities (sodium = 111-122 mEq/L) resulted in optimal changes in sRBC biomechanics, thereby reducing the risk for vaso-occlusion in our models. These results have significant translational implications for patients with SCD and warrant a large-scale prospective clinical study addressing optimal IVF management during VOE in SCD.

Clinical Implications of Single-Cell Microfluidic Devices for Hematological Disorders.

Single-cell microfluidic devices are poised to substantially impact the hematology field by providing a high-throughput and rapid device to analyze disease-mediated biophysical cellular changes in the clinical setting in order to diagnose patients and monitor disease prognosis. In this Feature, we cover recent advances of single-cell microfluidic devices for studying and diagnosing hematological dysfunctions and the clinical impact made possible by these advances.

Platelet-Microcapsule Hybrids Leverage Contractile Force for Targeted Delivery of Hemostatic Agents.

We report a cell-mediated, targeted drug delivery system utilizing polyelectrolyte multilayer capsules that hybridize with the patient's own platelets upon intravenous administration. The hybridized platelets function as the sensor and actuator for targeted drug delivery and controlled release in our system. These capsules are biochemically and mechanically tuned to enable platelet adhesion and capsule rupture upon platelet activation and contraction, enabling the targeted and controlled "burst" release of an encapsulated biotherapeutic. As platelets are the "first responders" in the blood clot formation process, this platelet-hybridized system is ideal for the targeted delivery of clot-augmenting biotherapeutics wherein immediate therapeutic efficacy is required. As proof-of-concept, we tailored this system to deliver the pro-clotting biotherapeutic factor VIII for hemophilia A patients that have developed inhibitory antifactor VIII antibodies. The polyelectrolyte multilayer capsules physically shield the encapsulated factor VIII from the patient's inhibitors during circulation, preserving its bioactivity until it is delivered at the target site via platelet contractile force. Using an in vitro microfluidic vascular injury model with factor VIII-inhibited blood, we demonstrate a 3.8× increase in induced fibrin formation using capsules loaded with factor VIII at a concentration an order of magnitude lower than that used in systemic delivery. We further demonstrate that clot formation occurs 18 min faster when factor VIII loaded capsules are used compared to systemic delivery at the same concentration. Because platelets are integral in the pathophysiology of thrombotic disorders, cancer, and innate immunity, this paradigm-shifting smart drug delivery system can be similarly applied to these diseases.

Video consultations as add-on to standard care among patients with type 2 diabetes not responding to standard regimens: a randomized controlled trial.

OBJECTIVE: To examine whether video consultations preceded by measurements of blood glucose, weight and blood pressure as add-on to standard care could contribute to achieving and maintaining good diabetes control among patients with poorly regulated type 2 diabetes (T2D). DESIGN: Randomized controlled trial. METHODS: 165 patients with T2D were randomized 1:1 to telemedicine intervention as add-on to clinic-based care or control (clinic-based care). The intervention consisted of monthly video conferences with a nurse via a tablet computer and lasted for 32 weeks. Regularly self-monitored measurements of blood sugar, blood pressure and weight were uploaded and visible to patient and nurse. Both groups were followed up six months after the end of the intervention period. PRIMARY ENDPOINT: HbA1c after eight months. RESULTS: Video conferences preceded by uploads of measurements as add-on to clinic-based care led to a significant reduction of HbA1c compared to that in standard care (0.69% vs 0.18%, P = 0.022). However, at six-month follow-up, the inter-group difference in HbA1c-reduction was no longer significant. Non-completers had higher HbA1c levels at baseline and a lower degree of education. CONCLUSION: Video consultations preceded by uploading relevant measurements can lead to clinically and statistically significant improvements in glycemic control among patients who have not responded to standard regimens. However, continuing effort and attention are essential as the effect does not persist when intervention ends. Furthermore, future studies should focus on differentiation as the most vulnerable patients are at greater risk of non-adherence.

Effects and Side Effects of Using Sorafenib and Sunitinib in the Treatment of Metastatic Renal Cell Carcinoma.

In recent years, targeted therapies have proven beneficial in terms of progression-free survival (PFS) and overall survival (OS) in the treatment of metastatic renal cell carcinoma (mRCC). The tyrosine kinase inhibitors (TKIs) sorafenib and sunitinib are included in international clinical guidelines as first-line and second-line therapy in mRCC. Hypertension is an adverse effect of these drugs and the degree of hypertension associates with the anti-tumour effect. Studies have compared newer targeted drugs to sorafenib and sunitinib in terms of PFS, OS, quality of life and safety profiles. Phase III studies presented promising response rates and acceptable safety profiles of axitinib and tivozanib compared to sorafenib, and a phase II study reported greater efficacy using a combination of bevacizumab and IFN-α compared to sunitinib. Treatment with nintedanib exhibited a notably low prevalence of hypertension compared to sunitinib. The use of sorafenib and sunitinib are challenged by new drugs, but do not appear likely to be substituted in the near future. To clarify whether newer targeted drugs should replace sorafenib and sunitinib, more research is needed. This manuscript reviews the current utility and adverse effects of sorafenib and sunitinib and newer targeted therapies in the treatment of mRCC.

Factor XIIIa-dependent retention of red blood cells in clots is mediated by fibrin α-chain crosslinking.

Factor XIII(a) [FXIII(a)] stabilizes clots and increases resistance to fibrinolysis and mechanical disruption. FXIIIa also mediates red blood cell (RBC) retention in contracting clots and determines venous thrombus size, suggesting FXIII(a) is a potential target for reducing thrombosis. However, the mechanism by which FXIIIa retains RBCs in clots is unknown. We determined the effect of FXIII(a) on human and murine clot weight and composition. Real-time microscopy revealed extensive RBC loss from clots formed in the absence of FXIIIa activity, and RBCs exhibited transient deformation as they exited the clots. Fibrin band-shift assays and flow cytometry did not reveal crosslinking of fibrin or FXIIIa substrates to RBCs, suggesting FXIIIa does not crosslink RBCs directly to the clot. RBCs were retained in clots from mice deficient in α2-antiplasmin, thrombin-activatable fibrinolysis inhibitor, or fibronectin, indicating RBC retention does not depend on these FXIIIa substrates. RBC retention in clots was positively correlated with fibrin network density; however, FXIIIa inhibition reduced RBC retention at all network densities. FXIIIa inhibition reduced RBC retention in clots formed with fibrinogen that lacks γ-chain crosslinking sites, but not in clots that lack α-chain crosslinking sites. Moreover, FXIIIa inhibitor concentrations that primarily block α-, but not γ-, chain crosslinking decreased RBC retention in clots. These data indicate FXIIIa-dependent retention of RBCs in clots is mediated by fibrin α-chain crosslinking. These findings expose a newly recognized, essential role for fibrin crosslinking during whole blood clot formation and consolidation and establish FXIIIa activity as a key determinant of thrombus composition and size.

Ultrasoft, highly deformable microgels.

Microgels are colloidally stable, hydrogel microparticles that have previously been used in a range of (soft) material applications due to their tunable mechanical and chemical properties. Most commonly, thermo and pH-responsive poly(N-isopropylacrylamide) (pNIPAm) microgels can be fabricated by precipitation polymerization in the presence of the co-monomer acrylic acid (AAc). Traditionally pNIPAm microgels are synthesized in the presence of a crosslinking agent, such as N,N'-methylenebisacrylamide (BIS), however, microgels can also be synthesized under 'crosslinker free' conditions. The resulting particles have extremely low (<0.5%), core-localized crosslinking resulting from rare chain transfer reactions. AFM nanoindentation of these ultralow crosslinked (ULC) particles indicate that they are soft relative to crosslinked microgels, with a Young's modulus of ∼10 kPa. Furthermore, ULC microgels are highly deformable as indicated by a high degree of spreading on glass surfaces and the ability to translocate through nanopores significantly smaller than the hydrodynamic diameter of the particles. The size and charge of ULCs can be easily modulated by altering reaction conditions, such as temperature, monomer, surfactant and initiator concentrations, and through the addition of co-monomers. Microgels based on the widely utilized, biocompatible polymer polyethylene glycol (PEG) can also be synthesized under crosslinker free conditions. Due to their softness and deformability, ULC microgels are a unique base material for a wide variety of biomedical applications including biomaterials for drug delivery and regenerative medicine.

Microgel mechanics in biomaterial design.

The field of polymeric biomaterials has received much attention in recent years due to its potential for enhancing the biocompatibility of systems and devices applied to drug delivery and tissue engineering. Such applications continually push the definition of biocompatibility from relatively straightforward issues such as cytotoxicity to significantly more complex processes such as reducing foreign body responses or even promoting/recapitulating natural body functions. Hydrogels and their colloidal analogues, microgels, have been and continue to be heavily investigated as viable materials for biological applications because they offer numerous, facile avenues in tailoring chemical and physical properties to approach biologically harmonious integration. Mechanical properties in particular are recently coming into focus as an important manner in which biological responses can be altered. In this Account, we trace how mechanical properties of microgels have moved into the spotlight of research efforts with the realization of their potential impact in biologically integrative systems. We discuss early experiments in our lab and in others focused on synthetic modulation of particle structure at a rudimentary level for fundamental drug delivery studies. These experiments elucidated that microgel mechanics are a consequence of polymer network distribution, which can be controlled by chemical composition or particle architecture. The degree of deformability designed into the microgel allows for a defined response to an imposed external force. We have studied deformation in packed colloidal phases and in translocation events through confined pores; in all circumstances, microgels exhibit impressive deformability in response to their environmental constraints. Microgels further translate their mechanical properties when assembled in films to the properties of the bulk material. In particular, microgel films have been a large focus in our lab as building blocks for self-healing materials. We have shown that their ability to heal after damage arises from polymer mobility during hydration. Furthermore, we have shown film mobility dictates cell adhesion and spreading in a manner that is fundamentally different from previous work on mechanotransduction. In total, we hope that this Account presents a broad introduction to microgel research that intersects polymer chemistry, physics, and regenerative medicine. We expect that research intersection will continue to expand as we fill the knowledge gaps associated with soft materials in biological milieu.

Effects of telemedicine in the treatment of patients with type 2 diabetes--a study protocol.

INTRODUCTION: Despite rehabilitation programmes offered to all patients with newly diagnosed type 2 diabetes in Denmark, a number of patients either never accomplish good diabetes regulation or the regulation deteriorates with time. Therefore, new approaches are needed. The aim of the present study is to examine whether telemedicine conferences with a nurse can contribute to achieving good diabetes control among patients with poorly regulated type 2 diabetes. MATERIAL AND METHODS: A total of 165 patients with type 2 diabetes who have formerly undergone a rehabilitation programme are randomized to either telemedicine intervention or usual care. The intervention lasts for 32 weeks and consists of monthly videoconferences with a nurse from a health-care centre as an add-on to usual care. Blood sugar, blood pressure and weight are regularly self-monitored and measurements are automatically transferred to a database. Glycaemic control (HbA1c level) is examined at baseline, 16 weeks, 32 weeks and 58 weeks (six months post intervention). Blood pressure, weight, waist/hip ratio, quality of life, physical activity, lipids, creatinine and haemoglobin are examined at baseline and after 32 weeks. CONCLUSION: The study will examine whether telemedicine technology can contribute to achieving good diabetes regulation. FUNDING: The City of Copenhagen and the Prevention Fund of the Capital Region of Denmark funded the project. Also "Smedemester Niels Hansen og Hustru Johanne F. Frederiksens Legat" has supported the study. TRIAL REGISTRATION: ClinicalTrials.gov registration number: NCT01688778.

[The prevalence of type 2-diabetes in ethnic minorities]. / Type 2-diabetes hos etniske minoriteter.

In general, type 2 diabetes is more common among immigrants than among the inhabitants with a Western background. The higher prevalence among ethnic minorities is probably due to a complex correlation between genetic factors, diet, exercise, linguistic and cultural obstacles, low birthweight and high catch up weight as well as socio-economic factors. Ethnic minorities are heterogeneous, and individual initiatives within the different groups are needed. The evidence regarding the effect of initiatives targeted at ethnic minorities in Denmark is sparse. In future, clinically controlled studies in this field should be carried out.