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Akram Ghobadi,1 Pegah Ahmadi Sarbarzeh,2 Milad Jalilian,2 Alireza Abdi,1 Sara Manouchehri3 1Nursing Department, Nursing and Midwifery School, Kermanshah University of Medical Sciences, Kermanshah, Iran; 2Nursing Department, Nursing and Midwifery School, Student Research Committee, Kermanshah University of Medical Sciences, Kermanshah, Iran; 3Biostatistics Department, Kermanshah University of Medical Sciences, Kermanshah, IranCorrespondence: Pegah Ahmadi SarbarzehNursing Department, Nursing and Midwifery School, Student Research Committee, Kermanshah University of Medical Sciences, Kermanshah, IranTel +98 930 1946547Email Ahmadi.pegah554@yahoo.comIntroduction: Diabetes mellitus is a metabolic disease characterized by high blood sugar (BS) levels and the change in the metabolism of lipids, carbohydrates, and insulin resistance, and is one of the main causes of disability and mortality worldwide. Among the different types of complications, which have many negative effects on personal and social life, diabetic foot ulcer (DFU) is very important. This study aims to investigate the factors affecting the severity of DFU among patients with diabetes.Methods: The study participants included 190 diabetic patients with a diagnosis of DFU. Data were collected using a two-part questionnaire for self-care awareness and functions in diabetic patients and Wagner’s scale. The questionnaire was answered in cooperation with patients and the Wagner’s score was estimated by a wound supervisor in the diabetes center.Results: There was 109 women (57.4%). Twenty-six patients had other diabetic complications as well as DFU. The average score of awareness in patients was 6.99± 2.76 and the function was 62.22± 9.92. The results found a direct relation between the age and the duration of illness with the score of the patient’s awareness (P=0.008, P=0.000). There was also a direct relation between the level of education with score of awareness and the score of function in self-care (P=0.000, P=0.000), but the statistical results did not find any relation between awareness and the function in self-care of patients with the severity of DFU (P> 0.05).Discussion: There was no relation between the self-care awareness and function with severity of DFU (P> 0.05) that can be due to the more relation between DFU severity with hygiene and physical factors after the disease and the effect of awareness and function would be only in the incidence of the DFU.Conclusion: Awareness and function of patients in self-care is less than average. Increasing awareness of patients and empowering them through appropriate training can be effective in preventing diabetic foot ulcers.Keywords: diabetes, diabetic foot ulcer, diabetes complications

Abstract: Cobalt–zinc ferrite (Co0.8Zn0.2Fe2O4) was prepared by combustion method, using cobalt, zinc and iron nitrates. The crystallinity of the as-burnt powder was developed by annealing at 700°C. Crystalline phase was investigated by XRD. Using Williamson–Hall method, the average crystallite sizes for nanoparticles were determined to be about 27nm before and 37nm after annealing, and residual stresses for annealed particles were omitted. The morphology of the annealed sample was investigated by TEM and the mean particle size was determined to be about 30nm. The final stoichiometry of the sample after annealing showed good agreement with the initial stoichiometry using atomic absorption spectrometry. Magnetic properties of the annealed sample such as saturation magnetization, remanence magnetization, and coercivity measured at room temperature were 70emu/g, 14emu/g, and 270Oe, respectively. The Curie temperature of the sample was determined to be 350°C using AC-susceptibility technique. [ABSTRACT FROM AUTHOR]

Pulmonary delivery of protein therapeutics poses significant challenges that have not been well addressed in the research literature or practice. In fact, there is currently only one commercial protein therapeutic that is delivered through aerosolization and inhalation. In this study, we propose a drug delivery strategy that enables a high-concentration dosage for the pulmonary delivery of antibodies as an aerosolizable solid powder with desired stability. We utilized zwitterionic polymers for their promising properties as drug delivery vehicles and synthesized swellable, biodegradable poly(sulfo-betaine) (pSB) microparticles. The microparticles were loaded with Immunoglobulin G (IgG) as a model antibody. We quantified the microparticle size and morphology, and the particles were found to have an average diameter of 1.6 μm, falling within the optimal range (~1-5 μm) for pulmonary drug delivery. In addition, we quantified the impact of the crosslinker to monomer ratio on particle morphology and drug loading capacity. The results showed that there is a trade-off between desired morphology and drug loading capacity as the crosslinker density increases. In addition, the particles were aerosolized, and our data indicated that the particles remained intact and retained their initial morphology and size after aerosolization. The combination of morphology, particle size, antibody loading capacity, low cytotoxicity, and ease of aerosolization support the potential use of these particles for pulmonary delivery of protein therapeutics., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Competing Interests: None declared.

Background: Recent studies suggest that shift work may cause liver dysfunction., Objective: This study aimed to examine the relationship between different patterns of shift work and elevated level of liver enzymes., Methods: In this cross-sectional study, 1910 workers aged 35 to 70 years were selected with simple random sampling from 9978 participants of the recruitment phase of Shahedieh PERSIAN cohort study. Level of serum liver enzymes (ALT, AST, ALP, and GGT) and ALT/AST ratio was compared between shift workers and non-shift workers, and among employees working in different patterns of shift work. Data were analyzed by SPSS (version 21.0) using Student's T test, Mann-Whitney U test, chi-square test, Kruskal Wallis test, and logistic regression., Results: Among 1347 males (71%) and 563 females (29%) with a mean age of 40.4±7.4 years, 469 were shift workers. Fixed evening type shift was the most common (30.3%) and fixed night-shift was the least common (0.9%) type of shift work. The mean blood levels of liver enzymes was not significantly different between shift workers and non-shift workers. In comparison between different patterns of shift work, the mean serum level of GGT was significantly higher in individuals with slow rotating shifts than those with fixed evening shifts, rapid rotating, split and fixed 24 hour shifts (p≤0.001). After adjusting for confounding factors only elevated AST was significantly higher in shift workers., Conclusion: There was only a significant association between shift work and elevated AST, and no relationship was found with ALT, ALP, GGT, and ALT/AST ratio.

Polylysine and materials that integrate lysine form promising drug delivery platforms. As a cationic macromolecule, a polylysine polymer electrostatically interacts with cells and is efficiently internalized, thereby enabling intracellular delivery. Although polylysine is intrinsically pH-responsive, the conjugation with different functional groups imparts smart, stimuli-responsive traits by adding pH-, temperature-, hypoxia-, redox-, and enzyme-responsive features for enhanced delivery of therapeutic agents. Because of such characteristics, polylysine has been used to deliver various cargos such as small-molecule drugs, genes, proteins, and imaging agents. Furthermore, modifying contrast agents with polylysine has been shown to improve performance, including increasing cellular uptake and stability. In this review, the use of lysine residues, peptides, and polymers in various drug delivery systems has been discussed comprehensively to provide insight into the design and robust manufacturing of lysine-based delivery platforms.

Many recent innovative treatments are based on monoclonal antibodies (mAbs) and other protein therapies. Nevertheless, sustained subcutaneous, oral or pulmonary delivery of such therapeutics is limited by the poor stability, short half-life, and non-specific interactions between the antibody (Ab) and delivery vehicle. Protein stabilizers (osmolytes) such as carboxybetaine can prevent non-specific interactions within proteins. In this work, a biodegradable zwitterionic poly(carboxybetaine), pCB, based microgel covalently crosslinked with tetra(ethylene glycol) diacrylate (TTEGDA) was synthesized for Ab encapsulation. The resulting microgels were characterized via FTIR, diffusion NMR, small-angle neutron scattering (SANS), and cell culture studies. The microgels were found to contain up to 97.5% water content and showed excellent degradability that can be tuned with crosslinking density. Cell compatibility of the microgel was studied by assessing the toxicity and immunogenicity in vitro. Cells exposed to microgel showed complete viability and no pro-inflammatory secretion of interleukin 6 (IL6) or tumor necrosis factor-alpha (TNFα). Microgel was loaded with Immunoglobulin G (as a model Ab), using a post-fabrication loading technique, and Ab sustained release from microgels of varying crosslinking densities was studied. The released Abs (especially from the high crosslinked microgels) proved to be completely active and able to bind with Ab receptors. This study opens a new horizon for scientists to use such a platform for local delivery of Abs to the desired target with minimized non-specific interactions.

Rapid clearance of thrombolytics from blood following intravenous injection is a major clinical challenge in cardiovascular medicine. To overcome this barrier, nanoparticle (NP) based drug delivery systems have been reported. Although superior than conventional therapy, a large proportion of the injected NP is still cleared by the reticuloendothelial system. Previously, we and others showed that ex vivo attachment of bioscavengers, thrombolytics, and nanoparticles (NPs) to glycophorin A receptors on red blood cells (RBCs) improved the blood half-life. This is promising, but ex-vivo approaches are cumbersome and challenging to translate clinically. Here, we developed a novel Ter119-polymeric NP containing tissue plasminogen activator for on-demand targeting of GPA receptors in vivo. Upon intravenous injection, the Ter119-NPs achieved remarkable RBC labeling efficiencies (>95%), resulting in marked enhancement of blood residence time of tPA from minutes to several days without any morphological, hematological, and histological complications. Our approach of RBC labeling with the NPs also prevented reticuloendothelial detections and the activations of innate and adaptive immune system. Data suggest that real-time targeting of therapeutics to RBC with NPs can potentially improve outcomes and reduce complications against a variety chronic disease., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Tissue engineering and regenerative medicine follow a multidisciplinary attitude to the expansion and application of new materials for the treatment of different tissue defects. Typically, proper tissue regeneration is accomplished through concurrent biocompatibility and positive cellular activity. This can be resulted by the smart selection of platforms among bewildering arrays of structural possibilities with various porosity properties (ie, pore size, pore connectivity, etc). Among diverse porous structures, zeolite is known as a microporous tectosilicate that can potentially provide a biological microenvironment in tissue engineering applications. In addition, zeolite has been particularly appeared promising in wound dressing and bone- and tooth-oriented scaffolds. The wide range of composition and hierarchical pore structure renders the zeolitic materials a unique character, particularly, for tissue engineering purposes. Despite such unique features, research on zeolitic platforms for tissue engineering has not been classically presented. In this review, we overview, classify, and categorize zeolitic platforms employed in biological and tissue engineering applications., Competing Interests: The authors declare no conflict of interest., (© 2020 The Authors. MedComm published by Sichuan International Medical Exchange & Promotion Association (SCIMEA) and John Wiley & Sons Australia, Ltd.)

Postoperative inflammation and the formation of fibrotic tissue around the intracochlear electrode array are often held responsible for negative outcomes in cochlear implant recipients. Here we test the effectiveness of intracochlear delivery of dexamethasone via a drug-eluting electrode array in reducing fibrotic tissue formation, assessed via measurement of both monopolar and four-point electrode impedance. Adult guinea pigs were bilaterally implanted with a dexamethasone-eluting array (left ear) and a standard non-eluting array (right ear). Arrays were electrically stimulated daily for 4 weeks, commencing 1 week after implantation, and impedance measured both before and after stimulation. Histological assessment of the tissue was made at the end of the 5-week period. The dexamethasone-eluting array did not reduce monopolar (MP1 + 2) electrode impedance over the course of 5 weeks, and no significant difference was observed in fibrotic tissue, new bone growth, or spiral ganglion neuron density between array types. However, four-point impedance, which provides an indication of the local environment at the neural-tissue interface, was significantly lower in the presence of dexamethasone. A strong relationship was seen between four-point and monopolar impedance for individual electrode arrays, with the exception of the standard array after daily electrical stimulation. This group instead showed a significant correlation between the final four-point impedance measure and percentage of fibrous tissue and new bone growth. In conclusion, this study demonstrated that dexamethasone influences four-point electrode impedance as well as the relationship between fibrotic tissue and impedance, and that both outcomes are shaped by daily electrical stimulation. These results suggest a change occurs at the local tissue-electrode interface in the presence of sustained, intracochlear release of dexamethasone.

Microporous and mesoporous minerals are key elements of advanced technological cycles nowadays. Nature-driven microporous materials are known for biocompatibility and renewability. Zeolite is known as an eminent microporous hydrated aluminosilicate mineral containing alkali metals. It is commercially available as adsorbent and catalyst. However, the large quantity of water uptake occupies active sites of zeolite making it less efficient. The widely-used chitosan polysaccharide has also been used in miscellaneous applications, particularly in medicine. However, inferior mechanical properties hampered its usage. Chitosan-modified zeolite composites exhibit superior properties compared to parent materials for innumerable requests. The alliance between a microporous and a biocompatible material with the accompaniment of negative and positive charges, micro/nanopores and proper mechanical properties proposes promising platforms for different uses. In this review, chitosan-modified zeolite composites and their applications have been overviewed., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: To test the hypothesis that in profile smiling view, for ideal aesthetics, a tangent to the labial face of the maxillary central incisor crowns should be approximately parallel to the true vertical line and thereby perpendicular to the true horizontal line., Methods: An idealized female image was created with computer software and manipulated using the same software to construct an "ideal" female profile image with proportions, and linear and angular soft tissue measurements, based on currently accepted criteria for idealized Caucasian profiles. The maxillary incisor labial face tangent was altered in 5° increments from 70 to 120°, creating a range of images, shown in random order to 70 observers (56 lay people and 14 clinicians), who ranked the images from the most to the least attractive. The main outcome was the preference ranks of image attractiveness given by the observers., Results: The most attractive inclination of a tangent to the labial face of the maxillary incisor crowns in profile view in relation to the true horizontal line was 85°, i.e. 5° retroclined from a perpendicular 90° inclination. The most attractive range appears to be between 80 and 90°. Excessive proclination appeared to be less desirable than retroclination. Beyond 105° most observers recommend treatment., Conclusion: In natural head position, the ideal inclination of the maxillary incisor crown labial face tangent in profile view will be approximately parallel to the true vertical line and thereby approximately perpendicular to the true horizontal line., Competing Interests: Competing interestsThe authors declare that they have no competing interests.

Agarose is a natural polysaccharide polymer having unique characteristics that give reason to consider it for tissue engineering applications. Special characteristics of agarose such as its excellent biocompatibility, thermo-reversible gelation behavior and physiochemical features support its use as a biomaterial for cell growth and/or controlled/localized drug delivery. The resemblance of this natural carbohydrate polymer to the extracellular matrix results in attractive features that bring about a strong interest in its usage in the field. The scope of this review is to summarize the extensive researches addressing agarose-based biomaterials in order to provide an in-depth understanding of its tissue engineering-related applications., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Skin is the outermost covering of the human body and at the same time the largest organ comprising 15% of body weight and 2 m 2 surface area. Skin plays a key role as a barrier against the outer environment depending on its thickness, color and structure, which differ from one site to another. The four major types of problematic wounds include ulcers (diabetic, venous, pressure) and burn wounds. Developing novel dressings helps us to improve the wound healing process in difficult patients. Recent advances in regenerative medicine and nanotechnology are revolutionizing the field of wound healing. Antimicrobial activity, exogenous cell therapy, growth factor delivery, biodegradable and biocompatible matrix construction, all play a role in hi-tech dressing design. In the present review, we discuss how the principles of regenerative medicine and nanotechnology can be combined in innovative wound dressings.

Exosomes found in the circulation are a primary source of important cancer-related RNA and protein biomarkers that are expected to lead to early detection, liquid biopsy, and point-of-care diagnostic applications. Unfortunately, due to their small size (50-150 nm) and low density, exosomes are extremely difficult to isolate from plasma. Current isolation methods are time-consuming multistep procedures that are unlikely to translate into diagnostic applications. To address this issue, we demonstrate the ability of an alternating current electrokinetic (ACE) microarray chip device to rapidly isolate and recover glioblastoma exosomes from undiluted human plasma samples. The ACE device requires a small plasma sample (30-50 μL) and is able to concentrate the exosomes into high-field regions around the ACE microelectrodes within 15 min. A simple buffer wash removes bulk plasma materials, leaving the exosomes concentrated on the microelectrodes. The entire isolation process and on-chip fluorescence analysis is completed in less than 30 min which enables subsequent on-chip immunofluorescence detection of exosomal proteins, and provides viable mRNA for RT-PCR analysis. These results demonstrate the ability of the ACE device to streamline the process for isolation and recovery of exosomes, significantly reducing the number of processing steps and time required.

Aim: Circulating cell free (ccf) DNA contains information about mutations affecting chronic lymphocytic leukemia (CLL). The complexity of isolating DNA from plasma inhibits the development of point-of-care diagnostics. Here, we introduce an electrokinetic method that enables rapid recovery of DNA from plasma., Materials & Methods: ccf-DNA was isolated from 25 µl of CLL plasma using dielectrophoresis. The DNA was used for PCR amplification, sequencing and analysis., Results: The ccf-DNA collected from plasma of 5 CLL patients revealed identical mutations to those previously identified by extracting DNA from CLL cells from the same patients., Conclusion: Rapid dielectrophoresis isolation of ccf-DNA directly from plasma provides sufficient amounts of DNA to use for identification of point mutations in genes associated with CLL progression., Competing Interests: Financial & competing interests disclosure The DEP technology used in the study was the result of original research carried out by the MJ Heller laboratory at the UCSD Moores Cancer Center under NIH NCI NanoTumor Center Grant (U54-CA119335). The work was also funded in part by NIH SBIR grant 1R43CA183414-01. Other than MJ Heller who is on the Scientific Advisory Board of Biological Dynamics (La Jolla, CA), no other authors have any relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. No writing assistance was utilized in the production of this manuscript.

The effect of complex biological fluids on the surface and structure of nanoparticles is a rapidly expanding field of study. One of the challenges holding back this research is the difficulty of recovering therapeutic nanoparticles from biological samples due to their small size, low density, and stealth surface coatings. Here, the first demonstration of the recovery and analysis of drug delivery nanoparticles from undiluted human plasma samples through the use of a new electrokinetic platform technology is presented. The particles are recovered from plasma through a dielectrophoresis separation force that is created by innate differences in the dielectric properties between the unaltered nanoparticles and the surrounding plasma. It is shown that this can be applied to a wide range of drug delivery nanoparticles of different morphologies and materials, including low-density nanoliposomes. These recovered particles can then be analyzed using different methods including scanning electron microscopy to monitor surface and structural changes that result from plasma exposure. This new recovery technique can be broadly applied to the recovery of nanoparticles from high conductance fluids in a wide range of applications., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: Magnetic Nanoparticles (MNP) have been used for contrast enhancement in Magnetic Resonance Imaging (MRI). In recent years, research on the use of ferrite nanoparticles in T2 contrast agents has shown a great potential application in MR imaging. In this work, Co0.5Zn0.5Fe2O4 and Co0.5Zn0.5Fe2O4-DMSA magnetic nanoparticles, CZF-MNPs and CZF-MNPs-DMSA, were investigated as MR imaging contrast agents., Methods: Cobalt zinc ferrite nanoparticles and their suitable coating, DMSA, were investigated under in vitro condition. Human prostate cancer cell lines (DU145 and PC3) with bare (uncoated) and coated magnetic nanoparticles were investigated as nano-contrast MR imaging agents., Results: Using T2-weighted MR images identified that signal intensity of bare and coated MNPs was enhanced with increasing concentration of MNPs in water. The values of 1/T2 relaxivity (r2) for bare and coated MNPs were found to be 88.46 and 28.80 (mM (-1) s(-1)), respectively., Conclusion: The results show that bare and coated MNPs are suitable as T2-weighted MR imaging contrast agents. Also, the obtained r2/r1 values (59.3 and 50) for bare and coated MNPs were in agreement with the results of other previous relevant works.

Conventional methods for the isolation of cancer-related circulating cell-free (ccf) DNA from patient blood (plasma) are time consuming and laborious. A DEP approach utilizing a microarray device now allows rapid isolation of ccf-DNA directly from a small volume of unprocessed blood. In this study, the DEP device is used to compare the ccf-DNA isolated directly from whole blood and plasma from 11 chronic lymphocytic leukemia (CLL) patients and one normal individual. Ccf-DNA from both blood and plasma samples was separated into DEP high-field regions, after which cells (blood), proteins, and other biomolecules were removed by a fluidic wash. The concentrated ccf-DNA was detected on-chip by fluorescence, and then eluted for PCR and DNA sequencing. The complete process from blood to PCR required less than 10 min; an additional 15 min was required to obtain plasma from whole blood. Ccf-DNA from the equivalent of 5 μL of CLL blood and 5 μL of plasma was amplified by PCR using Ig heavy-chain variable (IGHV) specific primers to identify the unique IGHV gene expressed by the leukemic B-cell clone. The PCR and DNA sequencing results obtained by DEP from all 11 CLL blood samples and from 8 of the 11 CLL plasma samples were exactly comparable to the DNA sequencing results obtained from genomic DNA isolated from CLL patient leukemic B cells (gold standard)., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: Circulating cell-free DNA (ccf-DNA) is becoming an important biomarker for cancer diagnostics and therapy monitoring. The isolation of ccf-DNA from plasma as a "liquid biopsy" may begin to replace more invasive tissue biopsies for the detection and analysis of cancer-related mutations. Conventional methods for the isolation of ccf-DNA from plasma are costly, time-consuming, and complex, preventing the use of ccf-DNA biomarkers for point-of-care diagnostics and limiting other biomedical research applications., Methods: We used an AC electrokinetic device to rapidly isolate ccf-DNA from 25 μL unprocessed blood. ccf-DNA from 15 chronic lymphocytic leukemia (CLL) patients and 3 healthy individuals was separated into dielectrophoretic (DEP) high-field regions, after which other blood components were removed by a fluidic wash. Concentrated ccf-DNA was detected by fluorescence and eluted for quantification, PCR, and DNA sequencing. The complete process, blood to PCR, required <10 min. ccf-DNA was amplified by PCR with immunoglobulin heavy chain variable region (IGHV)-specific primers to identify the unique IGHV gene expressed by the leukemic B-cell clone, and then sequenced., Results: PCR and DNA sequencing results obtained by DEP from 25 μL CLL blood matched results obtained by use of conventional methods for ccf-DNA isolation from 1 mL plasma and for genomic DNA isolation from CLL patient leukemic B cells isolated from 15-20 mL blood., Conclusions: Rapid isolation of ccf-DNA directly from a drop of blood will advance disease-related biomarker research, accelerate the transition from tissue to liquid biopsies, and enable point-of-care diagnostic systems for patient monitoring.