Orthogonal Covalent Entrapment of Cargo into Biodegradable Polymeric Micelles via Native Chemical Ligation.

Polymeric micelles (PMs) are promising platforms for enhanced tissue targeting of entrapped therapeutic agents. Strategies to circumvent premature release of entrapped drugs include cross-linking of the micellar core as well as covalent attachment of the drug cargo. The chemistry employed to obtain cross-linked micelles needs to be mild to also allow entrapment of fragile molecules, such as certain peptides, proteins, oligonucleotides, and fluorescent dyes. Native chemical ligation (NCL) is a mild bio-orthogonal reaction between a N-terminal cysteine residue and a thioester that proceeds under physiological conditions. Here, we designed a trifunctional cross-linker containing two cysteine residues for the micelle core-cross-linking reaction and an azide residue for ring-strained alkyne conjugation of fluorescent dyes. We applied this approach to thermosensitive methoxypolyethylene glycol-b-N-(2-hydroxypropyl)methacrylamide-lactate (mPEG-b-HPMAmLacn) based block copolymers of a core-cross-linked polymeric micelle (CCPM) system by attaching thioester residues (using ethyl thioglycolate-succinic anhydride, ETSA) for NCL cross-linking with the trifunctional cross-linker under physiological conditions. By use of mild copper-free click chemistry, we coupled fluorescent dyes, Sulfo.Cy5 and BODIPY, to the core via the azide residue present on the cross-linker by triazole ring formation. In addition, we employed a recently developed cycloheptyne strain promoted click reagent (TMTHSI, CliCr) in comparison to the frequently employed cyclooctyne derivative (DBCO), both achieving successful dye entrapment. The size of the resulting CCPMs could be tuned between 50 and 100 nm by varying the molecular weight of the thermosensitive block and ETSA content. In vitro cell experiments showed successful internalization of the dye entrapped CCPMs, which did not affect cell viability up to a polymer concentration of 2 mg/mL in PC3 cells. These fluorescent dye entrapped CCPMs can be applied in diagnostic imaging and the chemistry developed in this study serves as a steppingstone toward covalently entrapped fragile drug compounds with tunable release in CCPMs.

Hydrazone linked doxorubicin-PLA prodrug nanoparticles with high drug loading.

An optimal drug delivery system should be characterized by biocompatibility, biodegradability, high drug loading and favorable drug release profile. To achieve this goal a hydrazone linked doxorubicin-poly(lactic acid) prodrug (PLA-DOX) was synthesized by the functionalization of a short polymer chain produced by ring opening polymerization. The hydrophobic prodrug generated in this way was nanoprecipitated using a block copolymer to form polymeric nanoparticles (NPs) with a quantitative loading efficiency and a high and tunable drug loading. The effects of the concentration of the PLA-DOX prodrug and surfactant were studied by dynamic light scattering showing a range of NP size between 50 and 90 nm and monodispersed size distributions with polydispersity indexes lower then 0.27 up to a maximum DOX concentration of 27% w/w. The release profile of DOX from these NPs, tested at different pH conditions, showed a higher release rate in acidic conditions, consistent with the nature of the hydrazone bond which was used to conjugate the drug to the polymer. In vitro cytotoxicity studies performed on BV2 microglia-like cell line highlighted a specific cytotoxic effect of these NPs suggesting the maintenance of the drug efficacy and a modified release profile upon encapsulation of DOX in the NPs.

PEGylated Nanoparticles Obtained through Emulsion Polymerization as Paclitaxel Carriers.

Polymer nanoparticles (NPs) represent a promising way to deliver poorly water-soluble anticancer drugs without the use of unwanted excipients, whose presence can be the cause of severe side effects. In this work, a Cremophor-free formulation for paclitaxel (PTX) has been developed by employing PEGylated polymer nanoparticles (NPs) as drug delivery carriers based on modified poly(ε-caprolactone) macromonomers and synthesized through free radical emulsion polymerization. Paclitaxel was loaded in the NPs in a postsynthesis process which allowed to obtain a drug concentration suitable for in vivo use. In vivo experiments on drug biodistribution and therapeutic efficacy show comparable behavior between the NPs and the Cremophor formulation, also showing good tolerability of the new formulation proposed.

Fate of PLA and PCL-Based Polymeric Nanocarriers in Cellular and Animal Models of Triple-Negative Breast Cancer.

An integrated platform to assess the interaction between nanocarriers and biological matrices has been developed by our group using poly methyl-methacrylate nanoparticles. In this study, we exploited this platform to evaluate the behavior of two biodegradable formulations, poly-ε-caprolactone (PCL3) and poly lactic-acid (PLA8), respectively, in cellular and animal models of triple-negative breast cancer (TNBC). Both NPs shared the main physicochemical parameters (size, shape, ζ-potential) and exclusively differentiated on the material on which they are composed. Our results showed that (1) PLA8 NPs, systemically injected in mice, underwent rapid degradation without penetration into tumors; (2) PLA8 NPs were not internalized in the human TNBC cell line (MDA-MB-231); (3) PCL3 NPs had a longer bioavailability, reached the tumor parenchyma, and efficiently penetrated in MDA-MB-231 cells. Our data highlight the relevance of the material selection to both improve bioavailability and target tropism, and make PCL3 NPs an interesting tool for the development of nanodrugs against TNBC.

Comparison of ATR-FTIR and NIR spectroscopy for identification of microplastics in biosolids.

Biosolids are considered a potentially major input of microplastics (MPs) to agricultural soils. Our study aims to identify the polymeric origin of MPs extracted from biosolid samples by comparing their Attenuated Total Reflection (ATR) - Fourier-transform infrared (FTIR) spectra with the corresponding near-infrared (NIR) spectra. The reflectance spectra were preprocessed by Savitzky-Golay (SG), first derivative (FD) and compared with analogous spectra acquired on a set of fifty-two selected commercial plastic (SCP) materials collected from readily available products. According to the results portrayed in radar chart and built from both ATR-FTIR and NIR spectral datasets, the MPs showed high correlations with polymers such as polyethylene (LDPE, HDPE), polyethylene terephthalate (PET), polystyrene (PS), polypropylene (PP) and polyamide (PA), determined in SCP samples. Each unknown MP sample had on average three or more links to several types of SCP, according to the correlation coefficients for each polymer ranging from 0.7 up to 1. The comparison analysis classified the majority of MPs as composed mainly by LDPE/HDPE, according to the top correlation coefficients (r > 0.90). PP and PET were better identified with NIR than ATR-FTIR. In contrast to ATR-FTIR analysis, NIR was unable to identify PS. Based on these results, the primary sources of MPs in the biosolids could be identified as discarded consumer packaging (containers, bags, bottles) and fibers from laundry, disposable glove, and cleaning cloth. SYNOPSIS: Microplastics (MPs) are considered contaminants of emerging concern. This study compares two simple and fast spectroscopy techniques to identify microplastics in the biosolid matrix.

Anthropic impact on soil heavy metal contamination in riparian ecosystems of northern Algeria.

The aim of this research was to highlight the impact of urbanization and agriculture on soil quality, mainly by focusing on heavy metal accumulation (Cd, Cu, Fe, Mn, Ni, Pb and Zn) in the fragile riparian ecosystems of the Medjerda river (Souk-Ahras, Algeria). This study was performed in three cultivated soils (0-10, 10-20, 20-60 cm depth) along an increasing gradient of anthropogenic pressure in non-urban (NU), peri-urban (PU) and urban areas (U). Geo-accumulation index (Igeo), Enrichment factor (EF), Pollution load index (PLI) and Potential ecological risk index (RI) were calculated, as well as the potential non-carcinogenic risk for humans (HI). Additionally, to corroborate the role of Bufo spinosus D. as biosentinel, a skin biopsy was performed to quantify the concentration of heavy metals in both terrestrial and aquatic ecosystems. The results showed that when compared to NU, U and PU areas were richer in heavy metals. In particular, Igeo-Cd displayed strongly contaminated soil in U (>3), EF showed high enrichment of heavy metals (>2) for all the soils except for Ni, PLI presented no contamination for all (<1) while RI was significantly higher in U (>300), denoting a strong impact of heavy metals on soil quality. However, HI was below 1 for all the studied areas, although the highest values were related to U and PU. The skin biopsy showed the highest values for Cu, Fe and Pb in PU (0.328, 0.713 and 0.524 mg kg-1, respectively) similarly to trends observed in the soil of that area. This study shed light on the rising pollution of heavy metals due to urbanization and agricultural input in these fragile ecosystems where Bufo spinosus D. plays the role of potential bio-indicator for environmental pollution.

Environmental implications of interaction between humic substances and iron oxide nanoparticles: A review.

Goethite, hematite, ferrihydrite, and other iron oxides bind through various sorption reactions with humic substances (HS) in soils creating nano-, micro-, and macro-aggregates with a specific nature and stability. Long residence times of soil organic matter (SOM) have been attributed to iron-humic substance (Fe-HS) complexes due to physical protection and chemical stabilization at the organic-mineral interface. Humic acids (HA) and fulvic acids (FA) contain many acidic functional groups that interact with Fe oxides through different mechanisms. Due to the numerous interactions between mineral Fe and natural SOM, much research has led into a better identification and definition of HS. In this review, we first focus on the surface colloidal properties of Fe oxides and their reactivity toward HS. These minerals can be efficiently identified by usual techniques, such as XRD, FTIR spectroscopy, XAS, Mössbauer, diffuse reflectance spectroscopies (DRS), HRTEM, ATM, NanoSIMS. Second, we present the recent state of art regarding the adsorption/precipitation of HS onto iron mineral surfaces and their effects on binding metalloid and trace elements. Finally, we consider future research directions based on recent scientific literature, with particular focus on the ability of Fe nano-particles to increase Fe bioavailability, improve carbon sequestration, reduce greenhouse gas emissions, and decrease the impact of persistent organic and inorganic pollutants. The methodology in this field has rapidly developed over the last decade. However, new procedures to estimate the nature of Fe-HA bonds will be important contributions in clarifying the role of natural iron oxides in soil for carbon stabilization.

Prediction of bioaccessible lead in urban and suburban soils with Vis-NIR diffuse reflectance spectroscopy.

The successful use of visible and near-infrared (Vis-NIR) reflectance spectroscopy analysis requires selecting an optimal procedure of data acquisition and an accurate modeling approach. In this study, Vis-NIR with 350-2500 nm wavelengths were applied to detect different forms of lead (Pb) through the spectrally active soil constituents combining principal component regression (PCR) and Partial least-square regression (PLSR) for the Vis-NIR model calibration. Three clouds with different soil spectral properties were divided by the Linear discriminant analysis (LDA) in categories of Pb contamination risks: "low," "health," "ecological," ranging from 200 to 750 mg kg-1. Farm soils were used for calibration (n = 26), and more polluted garden soils (n = 36) from New York City were used for validation. Total and bioaccessible Pb concentrations were examined with PLSR models and compared with Support Vector Machine (SVM) Regression and Boosting Regression Tree (BRT) models. Performances of all models' predictions were qualitatively evaluated by the Root Mean Square Error (RMSE), Residual Prediction Deviation (RPD), and coefficient of determination (R2). For total Pb, the best predictive models were obtained with BRT (R2 = 0.82 and RMSE 341.80 mg kg-1) followed by SVM (validation, R2 = 0.77 and RMSE 337.96 mg kg-1), and lastly by PLSR (validation, R2 = 0.74 and RMSE 499.04 mg kg-1). The PLSR technique is the most accurate calibration model for bioaccessible Pb with an R2 value of 0.91 and RMSE of 68.27 mg kg-1. The regression analysis indicated that bioaccessible Pb is strongly influenced by organic content, and to a lesser extent, by Fe concentrations. Although PLSR obtained lower accuracy, the model selected many characteristic bands and, thus, provided accurate approach for Pb pollution monitoring.

Lyophilization stabilizes clinical-stage core-crosslinked polymeric micelles to overcome cold chain supply challenges.

BACKGROUND: CriPec technology enables the generation of drug-entrapped biodegradable core-crosslinked polymeric micelles (CCPM) with high drug loading capacity, tailorable size, and drug release kinetics. Docetaxel (DTX)-entrapped CCPM, also referred to as CPC634, have demonstrated favorable pharmacokinetics, tolerability, and enhanced tumor uptake in patients. Clinical efficacy evaluation is ongoing. CPC634 is currently stored (shelf life > 5 years) and shipped as a frozen aqueous dispersion at temperatures below -60°C, in order to prevent premature release of DTX and hydrolysis of the core-crosslinks. Consequently, like other aqueous nanomedicine formulations, CPC634 relies on cold chain supply, which is unfavorable for commercialization. Lyophilization can help to bypass this issue. METHODS AND RESULTS: Freeze-drying methodology for CCPM was developed by employing CPC634 as a model formulation, and sucrose and trehalose as cryoprotectants. We studied the residual moisture content and reconstitution behavior of the CPC634 freeze-dried cake, as well as the size, polydispersity index, morphology, drug retention, and release kinetics of reconstituted CPC634. Subsequently, the freeze-drying methodology was validated in an industrial setting, yielding a CPC634 freeze-dried cake with a moisture content of less than 0.1 wt%. It was found that trehalose-cryoprotected CPC634 could be rapidly reconstituted in less than 5 min at room temperature. Critical quality attributes such as size, morphology, drug retention, and release kinetics of trehalose-cryoprotected freeze-dried CPC634 upon reconstitution were identical to those of non-freeze-dried CPC634. CONCLUSION: Our findings provide proof-of-concept for the lyophilization of drug-containing CCPM and our methodology is readily translatable to large-scale manufacturing for future commercialization.

Traction Therapy for Cervical Radicular Syndrome is Statistically Significant but not Clinically Relevant for Pain Relief. A Systematic Literature Review with Meta-Analysis and Trial Sequential Analysis.

AIM: We aimed to investigate the effectiveness of traction therapy in reducing pain by performing a systematic review with meta-analysis. We also explore the best modality for administering traction to patients with cervical radicular syndrome (CRS). METHODS: We searched the Medline, Physiotherapy Evidence Database (PEDro), Cochrane Central Register of Controlled Trials, and Cumulative Index to Nursing and Allied Health Literature (CINAHL) electronic databases. Two reviewers independently selected randomized controlled trials (RCTs) that compared traction in addition to other treatments versus the effectiveness of other treatments alone for pain outcome. We calculated the mean differences (MDs) and 95% confidence intervals (CIs). We used Cochrane's tool to assess risk of bias and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to evaluate the quality of evidence and summarize the study conclusions. RESULTS: A total of seven studies (589 patients), one with low risk of bias, were evaluated. An overall estimate of treatment modalities showed low evidence that adding traction to other treatments is statistically significant (MD -5.93 [95% CI, -11.81 to -0.04] P = 0.05 and I2 = 57%) compared to other treatments alone. The subgroup analyses were still statistically significant only for mechanical and continuous modalities. CONCLUSIONS: Overall analysis showed that, compared to controls, reduction in pain intensity after traction therapy was achieved in patients with cervical radiculopathy. However, the quality of evidence was generally low and none of these effects were clinically meaningful.

Recovery of Mineral Oil from Underground Electrical Cables.

To remove the mineral oil impregnating the insulating paper present in old, disconnected, underground electrical cables, which represents a threat to the environment, two approaches are investigated at laboratory (1 m) and pilot (10 m) scales. The first one involves in situ polymerization to clog the inner channel of the cables and to enable the washing of the outer paper region impregnated by the oil by axial flow of a displacing fluid (water). The second approach leaves the inner channel open and employs repeated cycles of pressurization and rest to displace the oil contained in the paper by radially pushing the water from the inner channel into the outer layers. The pressurization and rest times were optimized to obtain the highest oil extraction rate. While the first approach showed limitations in terms of required pressures and operating time, which increase with the length of the cables, the second one was effective at removing 97% of the oil impregnating the paper layers within 25 cycles. Even more relevant, this second solution, in contrast to the first one, can be easily scaled up as it does not depend on the length of the cable, and was successfully tested on a 10 m cable, showing 98% oil recovery.

Biostimulant Potential of Humic Acids Extracted From an Amendment Obtained via Combination of Olive Mill Wastewaters (OMW) and a Pre-treated Organic Material Derived From Municipal Solid Waste (MSW).

Olive mill wastewaters (OMW) contain significant levels of phenolic compounds with antimicrobial/phytotoxic activity and high amounts of undecomposed organic matter that may exert negative effects on soil biology. Among OMW detoxification techniques, those focusing on oxidative degradation of phenolic compounds are relevant. The composting (bio-oxidation) process in particular, exploits exothermic oxidation reactions by microorganisms to transform the organic matrix of OMW into an amendment biologically stable and feasible to use in agriculture. This process consists of an active phase during which organic compounds are rapidly decomposed, and a curing phase characterized by a slow breakdown of the remaining materials with the formation of humic substances (HS) as by-products. In this study, bio-oxidation of OMW was performed using a pre-treated organic material derived from municipal solid waste (MSW). The obtained amendment (OMWF) was stable and in accordance with the legislative parameters of mixed organic amendments. HS were then extracted from OMWF and MSW (control amendment, Amd-C), and differences in structural properties of their humic acid (HA) fraction were highlighted via spectroscopy (Fourier Transform Infrared) and Dynamic Light Scattering. To assay a potential use of HA as biostimulants for crops, 12-day old Zea Mays L. plants were supplied with HA at 0.5 mg and 1 mg C L-1 for 2 days. HA from both amendments increased plant growth, but HA from OMWF was more effective at both dosages (plus 35-37%). Also, HA from OMWF enhanced both nitrogen assimilation and glycolysis by increasing the activity of nitrate reductase (∼1.8-1.9 fold), phosphoglucose isomerase (PGI) (∼1.8-2 fold) and pyruvate kinase (PK) (∼1.5-1.8 fold), while HA from Amd-C targeted glycolysis preferentially. HA from OMWF, however, significantly stimulated plant nutrition only at lower dosage, perhaps because certain undetermined compounds from detoxified OMW and incorporated in HA altered the root membrane permeability, thus preventing the increase of nutrient uptake. Conversely, HA from Amd-C increased nutrient accumulation in maize at both dosages. In conclusion, our results indicate that the amendment obtained via OMW composting using MSW had a reduced pollution load in terms of phenolic compounds, and HA extracted from OMWF could be used as valuable biostimulants during maize cultivation.

Cadmium removal from simulated groundwater using alumina nanoparticles: behaviors and mechanisms.

Cadmium (Cd), one of the most toxic contaminants in groundwater, can cause a severe threat to human health and ecological systems. In this study, alumina nanoparticles were synthesized and tested for high-efficiency Cd removal from simulated groundwater. Furthermore, the synthesized alumina nanoparticles were successfully modified using negatively charged glycerol, to alleviate the challenge of its low mobility in groundwater for the Cd removal. The maximum removal efficiency of both synthesized and glycerol-modified alumina nanoparticles were more than 99%. The sorption isotherm and kinetic data of both synthesized and glycerol-modified alumina nanoparticles were best fitted to the Freundlich model and the pseudo-second-order model, respectively, indicating that the sorption of Cd ions occurs on heterogeneous surfaces of both alumina nanoparticles via the chemisorption mechanism. X-ray photoelectron spectroscopy and energy dispersive X-ray analysis revealed the presence of Cd peak in both sorbents after contact with Cd. In addition, the FTIR analyses demonstrated that hydroxyl group participated in the sorption of Cd on both synthesized and glycerol-modified alumina nanoparticles, while other glycerol associated groups contributed to the removal of Cd ions by the glycerol-modified alumina nanoparticles. It was concluded that Cd removal by synthesized and glycerol-modified alumina nanoparticles were mainly due to ion exchange and electrostatic attraction, respectively. Desorption experiment suggested that both alumina nanoparticles are effective and practically significant sorbents to remediate Cd from contaminated groundwater. However, the stronger bond between Cd and glycerol-modified alumina, plus its potential of higher mobility due to the negative charge on the surface, warrant glycerol-modified alumina nanoparticles a better performance in remediating Cd contaminated groundwater than that of the synthesized alumina nanoparticles.

Double-blind, placebo-controlled trial comparing effects of supplementation of two micronutrient sprinkles on fatty acid status in Cambodian infants.

BACKGROUND: Infants in developing countries require early dietary interventions to prevent nutritional deficiencies, above all protein, energy, iron and zinc. To what extent these interventions may affect the fatty acid (FA) status is still unknown. OBJECTIVES: To examine and compare the effects of 2 micronutrient "sprinkles" supplementations (iron 12.5 mg + folic acid 150 microg, iron/folate and iron 12.5 mg + folic acid 150 microg + zinc 5 mg + vitamins A, C and D3, mineral/micronutrient [MMN]) versus placebo on the FA status of Cambodian infants. METHODS: A total of 204 infants age 6 mo and living in Kompong Chhnang Province, Cambodia, were randomly assigned to receive daily supplementation of MMN (n = 68) and iron/folate (n = 68) or placebo (n = 68) for a 12-mo period in powder form as sprinkles. At the end of the intervention period, FAs in the range of 16 to 24 C were determined in blood drops absorbed on a strip collected from 182 subjects, and values among the 3 intervention subgroups and those of 21 Italian 18-mo-old, normal-growing infants as the reference group were compared. RESULTS: At the end of the supplementation trial, higher levels of the 2 essential FAs (EFAs) (linoleic acid, 18:2n-6, and alpha-linolenic acid, 18:3n-3) were found in the MMN group. No differences occurred for the major longer chain derivatives of both EFAs arachidonic acid (20:4n-6) and docosahexaenoic acid (22:6n-3). In MMN supplemented Cambodians, blood levels of linoleic acid approached those of Italian infants, and in addition their alpha-linolenic acid levels were improved. Cambodian infants, mostly still breast-fed through the second year of life, showed significantly higher levels of long-chain derivatives of both the n-6 and the n-3 series compared with Italians. CONCLUSIONS: Supplementation with iron, folic acid, zinc and vitamins was associated with an increase of linoleic acid and alpha-linolenic acid levels in Cambodian infants versus placebo, without significant changes in the concentrations of their longer chain derivatives, resulting in a FA status closer to Italian counterparts for the essential polyunsaturated FA levels. The iron/folate-treated infants showed no differences compared with the other 2 groups. Studies are needed to differentiate the potential effects of the supplemented micronutrients on the FA status.

Levels of the n-3 fatty acid eicosapentaenoic acid in addition to those of alpha linolenic acid are significantly raised in blood lipids by the intake of four walnuts a day in humans.

BACKGROUND AND AIMS: Ingestion of alpha linolenic acid (ALA), with the richest source among dry fruits such as walnuts, is associated with cardiovascular prevention. The aim of this study was to selectively evaluate the effects of moderate walnut consumption on the levels of ALA and its metabolic derivatives in human blood. METHODS AND RESULTS: After a 2-week run-in period, 10 volunteers consumed 4 walnuts per day (in addition to their habitual diet) for 3 weeks. Fatty acid profiles, with special attention to levels of ALA and long chain polyunsaturated fatty acids (LC-PUFA), were assessed in blood drops collected from fingertips. The data indicate that the administration of a few walnuts a day for 3 weeks significantly increases blood levels, not only of ALA (from 0.23+/-0.07 SD to 0.47+/-0.13 SD), but also of its longer chain derivative eicosapentaenoic acids (EPA) (from 0.23+/-0.37 to 0.82+/-0.41) with levels remaining elevated over basal values after washout. CONCLUSION: The findings of this pilot study indicate that plant ALA in appropriate food items favourably affects the n-3 LC-PUFA status.

Mechanistic Origin of the Combined Effect of Surfaces and Mechanical Agitation on Amyloid Formation.

Interactions between proteins and surfaces in combination with hydrodynamic flow and mechanical agitation can often trigger the conversion of soluble peptides and proteins into aggregates, including amyloid fibrils. Despite the extensive literature on the empirical effects of surfaces and mechanical forces on the formation of amyloids, the molecular details of the mechanisms underlying this behavior are still elusive. This limitation is, in part, due to the complex reaction network underlying the formation of amyloids, where several microscopic reactions of nucleation and growth can occur both at the interfaces and in bulk. In this work, we design a high-throughput assay based on nanoparticles and we apply a chemical kinetic platform to analyze the mechanisms underlying the effect of surfaces and mechanical forces on the formation of amyloid fibrils from human insulin under physiological conditions. By considering a variety of polymeric nanoparticles with different surface properties we explore a broad range of repulsive and attractive interactions between insulin and surfaces. Our analysis shows that hydrophobic interfaces induce the formation of amyloid fibrils by specifically promoting the primary heterogeneous nucleation rate. In contrast, mechanical forces accelerate the formation of amyloid fibrils by favoring mass transport and further amplify the number of fibrils by promoting fragmentation events. Thus, surfaces and agitation have a combined effect on the kinetics of protein aggregation observed at the macroscopic level but, individually, they each affect distinct microscopic reaction steps: the presence of interfaces generates primary nucleation events of fibril formation, which is then amplified by mechanical forces. These results suggest that the inhibition of surface-induced heterogeneous nucleation should be considered a primary target to suppress aggregation and explain why in many systems the simultaneous presence of surfaces and hydrodynamic flow enhances protein aggregation.

The effects of kinesio taping on the color intensity of superficial skin hematomas: A pilot study.

OBJECTIVES: To analyze the effects of kinesio taping (KT) -applied with three different strains that induced or not the formation of skin creases (called convolutions)- on color intensity of post-surgical superficial hematomas. DESIGN: Single-blind paired study. SETTING: Rehabilitation clinic. PARTICIPANTS: A convenience sample of 13 inpatients with post-surgical superficial hematomas. INTERVENTIONS: The tape was applied for 24 consecutive hours. Three tails of KT were randomly applied with different degrees of strain: none (SN); light (SL); and full longitudinal stretch (SF). We expected to obtain correct formation of convolutions with SL, some convolutions with SN, and no convolutions with SF. MAIN OUTCOME MEASURES: The change in color intensity of hematomas, measured by means of polar coordinates CIE L*a*b* using a validated and standardized digital images system. RESULTS: Applying KT to hematomas did not significantly change the color intensity in the central area under the tape (p > 0.05). There was a significant treatment effect (p < 0.05) under the edges of the tape, independently of the formation of convolutions (p > 0.05). CONCLUSIONS: The changes observed along the edges of the tape could be related to the formation of a pressure gradient between the KT and the adjacent area, but were not dependent on the formation of skin convolutions.

Polymer Nanoparticle Engineering for Podocyte Repair: From in Vitro Models to New Nanotherapeutics in Kidney Diseases.

Specific therapeutic targeting of kidney podocytes, the highly differentiated ramified glomerular cells involved in the onset and/or progression of proteinuric diseases, could become the optimal strategy for preventing chronic kidney disease. With this aim, we developed a library of engineered polymeric nanoparticles (NPs) of tuneable size and surface properties and evaluated their interaction with podocytes. NP cytotoxicity, uptake, and cytoskeletal effects on podocytes were first assessed. On the basis of these data, nanodelivery of dexamethasone loaded into selected biocompatible NPs was successful in repairing damaged podocytes. Finally, a three-dimensional in vitro system of co-culture of endothelial cells and podocytes was exploited as a new tool for mimicking the mechanisms of NP interaction with glomerular cells and the repair of the kidney filtration barrier.