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  • 1.
    Abdulhassan, Faten
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV).
    UPPRENING OCH KARAKTÄRISERING AV HISTONER FRÅN VETEGRODDAR2023Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Histones are a family of proteins that form nucleosomes when packing DNA in the cell. The complex of histones and DNA named chromatin. In addition to histones, chromatin consists of proteins that are non-histones, which contribute to chromatin stability and gene activity. Histones, with molecular weights of 11-21 kDa, include five main classes: H1, H2A, H2B, H3, H4, forming a complex with each other by ionic bonding. The histone complex consists of (H2A-H2B) flanked with (H3-H4) tetramers. Since histones consist of basic amino acids such as arginine and lysine, they are positively charged, which facilitates binding with DNA which is negatively charged. Histones are considered antimicrobial peptides (AMPs) because they can neutralize bacterial endotoxin. The purpose of the study was to purify histones from wheat germ and characterize these, and study their effect on bacterial growth. Wheat germ was used because they are rich in chromatin. The method for isolation of histones was based on low ionic strength using three different buffers, as well as acid extraction of chromatin with sulfuric acid. To characterize histones, SDS-PAGE electrophoresis was performed and to study their bacterial inhibition, E. coli bacteria were used. The result showed a poor yield of histones, but the main classes of different histones could be separated and characterized by SDS-PAGE. Some samples showed an antibacterial effect. Optimization of the extraction is necessary to increase the yield and thus be able to better study the antibacterial effect of histones. Presumably, it is homogenization that limits the yield and possibly also modification of the acid extract to prevent aggregation.

    Keywords: Antimicrobial peptides, acid extraction, chromatin, DNA, histones, ionic strength, purification, wheat germ

  • 2.
    Ademovski, Emir
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV).
    In vitro effects of skincare ingredients on keratinocytes2023Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    The skin has several functions as the largest and one of the most complex organs of the body. One of the skin’s primary functions is to prevent water loss by retaining water to allow the skin to function in dry environments. The outermost layer, stratum corneum (SC), retains water loss as rehydration by natural moisturizing factors (NMFs). In this project, HaCaT cells were incubated with commonly used skincare ingredients such as urea, glycerol, transcutol, salicylic acid, and polyethylene glycol 4000 Da (PEG-4000) to evaluate their impact on cell viability, MTT proliferation assay and gene expression measurements by qPCR. The relationship between cell viability, gene expression, and water activity was also studied. The excipients showed a dose-dependent decrease in cell viability because osmotic pressure increased. One finding was that transcutol exhibited a protective effect against concentrations where osmotic pressure harmed the cells. PEG-4000, with a concentration of 10 % (w/v), showed an upregulation of elongation of very long chain fatty acid 4 (ELOVL-4). Gene expression of serine palmitoyltransferase (SPT) was low, with 10 mM transcutol, even though the cells had a viability of >100 %. It should have conducted an upregulation of SPT from the high metabolic activity in the cells. In conclusion, the viability and gene expression were most likely related to osmotic stress but should be further analyzed with digital holographic microscopy (DHM) and Western blot. 

  • 3.
    Agyemang, Alberta
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV).
    Investigation of vitamin K interaction and transdermal delivery at skin barriers:study using k4 model2021Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Vitamin K is a fat soluble compound which is synthesized by the gut microbiota and produced in many tissues within the body. Considering its role in the liver as a cofactor for gamma carboxylase enzymes, treatment of dark circles and pigments under the eye among others. It is clear that is some circumstances vitamin K has to cross biological barriers, particularly, when the vitamin is produced by microbiota in the intestine or applied topically on skin. Thus it is important to develop methods that allow studies of vitamin K permeability through the skin including its participation in redox reactions and transdermal permeability. Taking into account that transdermal permeability is strongly limited for high molecular weight compounds, i.e., compounds with higher than 500Da, the study was conducted with vitamin K of  lower molecular weight. Specifically vitamin K4 model, i.e., 1,4-dihydroxy-2 naphthoic acid, with molecular weight of 204g/mol. Vitamin K4 is suitable for this kind of study , because it can work as reducing (antioxidant) compound as well as has relatively beneficial physicochemical characteristics for transdermal permeability. Permeability studies were conducted with skin covered oxygen electrode and franz diffusion cell. Data from measurements were analyzed to estimate diffusion coefficients, apparent Michaelis-Menten constants and flux of a vitamin K4 model whilst contribution of different permeability pathways was determined theoretically.

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  • 4.
    Aherne, Olivia
    et al.
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces. CR Competence, Naturvetarvägen 14, 223 62, Lund, Sweden.
    Ortiz, Roberto
    CR Competence, Naturvetarvägen 14, 223 62, Lund, Sweden.
    Fazli, Magnus M
    Costerton Biofilm Center, Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark; SoftOx Solutions AS, Copenhagen, Denmark.
    Davies, Julia R
    Malmö University, Faculty of Odontology (OD). Malmö University, Biofilms Research Center for Biointerfaces.
    Effects of stabilized hypochlorous acid on oral biofilm bacteria2022In: BMC Oral Health, ISSN 1472-6831, E-ISSN 1472-6831, Vol. 22, no 1, article id 415Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Caries and periodontitis are amongst the most prevalent diseases worldwide, leading to pain and loss of oral function for those affected. Prevention relies heavily on mechanical removal of dental plaque biofilms but for populations where this is not achievable, alternative plaque control methods are required. With concerns over undesirable side-effects and potential bacterial resistance due to the use of chlorhexidine gluconate (CHX), new antimicrobial substances for oral use are greatly needed. Here we have investigated the antimicrobial effect of hypochlorous acid (HOCl), stabilized with acetic acid (HAc), on oral biofilms and compared it to that of CHX. Possible adverse effects of stabilized HOCl on hydroxyapatite surfaces were also examined.

    METHODS: Single- and mixed-species biofilms of six common oral bacteria (Streptococcus mutans, Streptococcus gordonii, Actinomyces odontolyticus, Veillonella parvula, Parvimonas micra and Porphyromonas gingivalis) within a flow-cell model were exposed to HOCl stabilized with 0.14% or 2% HAc, pH 4.6, as well as HOCl or HAc alone. Biofilm viability was assessed in situ using confocal laser scanning microscopy following LIVE/DEAD® BacLight™ staining. In-situ quartz crystal microbalance with dissipation (QCM-D) was used to study erosion of hydroxyapatite (HA) surfaces by stabilized HOCl.

    RESULTS: Low concentrations of HOCl (5 ppm), stabilized with 0.14% or 2% HAc, significantly reduced viability in multi-species biofilms representing supra- and sub-gingival oral communities, after 5 min, without causing erosion of HA surfaces. No equivalent antimicrobial effect was seen for CHX. Gram-positive and Gram-negative bacteria showed no significant differential suceptibility to stabilized HOCl.

    CONCLUSIONS: At low concentrations and with exposure times which could be achieved through oral rinsing, HOCl stabilized with HAc had a robust antimicrobial activity on oral biofilms, without causing erosion of HA surfaces or affecting viability of oral keratinocytes. This substance thus appears to offer potential for prevention and/or treatment of oral biofilm-mediated diseases.

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  • 5.
    Ahmed, Ammar
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV).
    Optimering av personalstrålskydd vid administration av fluor-18 märkt läkemedel2021Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    At the Nuclear medicine department at Skane University Hospital in Malmoe, the staff inject fluorine-18 labelled radiopharmaceuticals on a daily basis, which entails exposure of radiation dose. The Swedish Radiation Protection Ordinance prescribe dose limits, which works as requirements to prevent and minimize risks for future negative health effects to the public and workers handling ionizing radiation. The aim and purpose of the study was to study whether there is a statistically significant difference of radiation dose to the staffs fingers and body, when injecting fluorine-18 labelled radiopharmaceuticals, depending on when the removal of the peripheral venous catheter (PVK) is performed. The measurements were performed after the injection of fluorine-18 labelled radiopharmaceutical and after the imaging of the patients. In this study 44 measurements were performed, of which 22 measurements were performed after the injection of 18F-labelled radiopharmaceutical and 22 measurements after the medical imaging. The measurements were performed on 11 staff members in the Nuclear Medicine department in Malmoe. The results of 22 measurements showed a mean value of the equivalent doses to the fingers after injection showed 0,20 μSv/MBq and after the medical imaging of the patient of 0,18 μSv/MBq. The mean value of effective dose was entailed to 0,004 μSv/MBq after injection and 0,003 μSv/MBq after imaging. A Mann-Whitney U-test was performed and reported a p-value of >0,05, which indicates that there is no significant difference in radiation dose to the staff between the two different methods of removing the PVK. 

  • 6.
    Al Hadad, Nor
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV).
    Undersökning av effekten av KRAS-inhibitorn ISA-2011B på humana koloncancer cellinjer2022Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Colorectal cancer is the fourth most common cause of cancer-related deaths worldwide. In 2020, a total of 1.93 million new cases were diagnosed, of which 60% were diagnosed with colon cancer. Approximately 30–40% of patients with colon cancer have a mutation in the KRAS gene. This mutation is associated with poorer survival, increased tumour aggressiveness, and resistance to selected treatment strategies. There is currently no treatment for KRAS-mutated colon cancer. However, the discovery of the KRAS inhibitor ISA-2011B has increased the possibility of investigating the effect of ISA-2011B on colon cancer. This study aimed to analyse the effect of ISA-2011B in both single and combined treatment with Erlotinib and Docetaxel, on human colon cancer cell lines. The cancer cell lines HCT116 (KRAS-mutated) and HT29 (BRAF-mutated), were used to compare cell proliferation after the treatments. MTS-assay was used to analyse cell proliferation. The statistical significance for the effect of ISA-2011B was analysed by a two-tailed t-test. This study has shown a significant effect of ISA-2011B on the cell lines. Treatment with only ISA-2011B indicated a significant toxic effect on the cancer cell lines and reduced the proliferation. However, this effect was unchanged in combination with Docetaxel or Erlotinib. In contrast, ISA-2011B indicated the best effect on HCT116 in terms of reduced cell proliferation. Furthermore, the results of this study will contribute to an increased understanding of the ISA-2011B’s effect. More extensive research on spheroids and xenograft mice must be performed for ISA-2911B to be established as a functional drug.

  • 7.
    Al Mustafa, Oday
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV).
    Evaluation of antioxidant effect of an algae extract on skin: in vitro study2023Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Algae extracts are used as cosmetic products and used as additives in specific foods because of their antioxidant activity. Reactive oxygen species (ROS) such as hydrogen peroxide and superoxide radicals are toxic on the skin and can be scavenged by antioxidants, which are abundant in microalgae. Antioxidant substances protect the skin against external factors such as ultraviolet light (UV). Many creams that are concerned with treating the skin have antioxidant molecules. Researchers are performing many studies to achieve natural and non-chemical skin maintenance for the skin. Conducting in vivo studies to analyze the antioxidant potential of extracts on skin needs ethical permission to recruit a specific number of people. In this study, pig ear skin was used with the help of a skin-membrane-covered oxygen electrode (SCOE) to analyze the antioxidant effect of an extract from the microalgae Chlamydomonas reinhardtii. A study proved that this method was effective in measuring other antioxidants. Hydroquinone was used as a control to see if the system worked correctly. Hydroquinone showed that it could penetrate the skin and give antioxidant activity. When the algae extract was used, the same effect as for hydroquinone could not be detected. With a 2,2-diphenylpicrylhydrazyl (DPPH) assay, the algae extract was analyzed for its antioxidant capacity, and the assay revealed a positive antioxidant effect of the extract. The spectrophotometric measurement of the amount of bioactive antioxidant molecules in the extract in different solutions suggested that the one resuspended in ethanol presented a higher amount of carotenoids and chlorophylls than the extract resuspended in an aqueous buffer. Additional research will be needed to characterize the antioxidant potential of the extract from the microalgae Chlamydomonas reinhardtii.

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  • 8.
    Aleksejeva, Olga
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV).
    Blue copper proteins as bioelements for bioelectronic devices2019Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    This thesis is focused on bioelements for biological electric power sources,specifically, on blue copper proteins with and without an intrinsic biocatalyticactivity, i.e. ability to reduce oxygen directly to water. These proteins, viz. differentlaccases, ceruloplasmin, and rusticyanin, were characterised in detailand employed for the construction of both self-charging and conventional biosupercapacitors.First, similarities and particularities of oxygen electroreductionvs. bioelectroreduction were reviewed. Moreover, being a promising candidatefor the construction of autotolerant implantable biocathodes, the electrochemistryof human ceruloplasmin was revisited. For the first time, a clearbioelectrocatalytic reduction of oxygen on ceruloplasmin modified electrodeswas shown. Second, computational design combined with directed evolutionresulted in a high redox potential mutated laccase, GreeDo, with increased redoxpotential of the T1 site, increased activity towards high redox potentialmediators, as well as enhanced stability. Third, GreeDo was electrochemicallycharacterised in detail. The mutant exhibited higher open circuit potentialvalues and onset potentials for oxygen bioelectroreduction compared to the parental laccase, OB-1. Moreover, the operational stability of GreeDo modifiedgraphite electrodes was found to be more than 2 h in a decidedly acidicelectrolyte, in agreement with the extended operational and storage stabilitiesof the enzyme in acidic solutions. Fourth, multi-cell single-electrolyte glucose/oxygen biodevices with adjustable open-circuit and operating voltages,which are independent on the difference in equilibrium redox potentials of thetwo redox couples, gluconolactone/glucose and oxygen/water, viz. 1.18 V, butdependent on the number of half-cells in the biodevice construction, were designedand tested. The biodevices were made from tubular graphite electrodeswith electropolymerised poly(3,4-ethylenedioxythiophene) modified withTrametes hirsuta laccase and Neurospora crassa cellobiose dehydrogenase as the cathodic and anodic biocatalysts, respectively. Due to the interplay betweenfaradaic and non-faradaic electrochemical processes, as well as betweenionic and electronic conductivities, the open-circuit voltage of the self-chargedbiodevice is extraordinarily high, reaching 3 V, when seven biosupercapacitorsoperating in a common electrolyte were connected in series. Moreover,glucose/oxygen biodevices could be externally discharged at an operatingvoltage exceeding the maximal limiting open-circuit value of 1.24 V for thecomplete glucose oxidation. Last but not least, a conventional biosupercapacitor,i.e. a biodevice lacking self-charging ability, was composed of Acidithiobacillusferrooxidans rusticyanin modified gold electrodes. The complete biodevicesas well as separate electrodes were thoroughly characterised electrochemically.The symmetrical biosupercapacitor based on two identical goldelectrodes modified with rusticyanin is able to capacitively store electricityand deliver electric power, accumulated mostly in the form of biopseudocapacitance,when charged and discharged externally.

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  • 9.
    Aleksejeva, Olga
    et al.
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV).
    Gonzalez-Arribas, Elena
    Di Bari, Chiara
    De Lacey, Antonio L.
    Pita, Marcos
    Ludwig, Roland
    Andoralov, Victor
    Blum, Zoltan
    Shleev, Sergey
    Membrane-free and mediator-less high voltage glucose/oxygenelectric power biodevices2019Manuscript (preprint) (Other academic)
  • 10.
    Aleksejeva, Olga
    et al.
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV).
    Mateljak, Ivan
    Ludwig, Roland
    Alcalde, Miguel
    Shleev, Sergey
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV).
    Electrochemistry of a high redox potential laccase obtained by computer-guided mutagenesis combined with directed evolution2019In: Electrochemistry communications, ISSN 1388-2481, E-ISSN 1873-1902, Vol. 106, article id UNSP 106511Article in journal (Refereed)
    Abstract [en]

    Electrochemical characterization of the GreeDo variant of a high redox potential fungal laccase obtained by laboratory evolution together with computer-guided mutagenesis, in comparison to its parental variety (the OB-1 mutant), is presented. Both laccases, when immobilized on graphite electrodes either by direct physical adsorption or covalently attached via gold nanoparticles, were capable of both non-mediated and mediator-based bioelectroreduction of molecular oxygen at low overpotentials. GreeDo exhibited higher open circuit potential values and onset potentials for oxygen bioelectroreduction compared to OB-1. However, even though in homogeneous catalysis GreeDo outperforms OB-1 in terms of turnover numbers and catalytic efficiency, when exposed to high redox potential substrates, direct electron transfer based bioelectrocatalytic currents of GreeDo and OB-1 modified electrodes were similar. High operational stability of freely diffusing GreeDo and also the immobilized enzyme in the acidic electrolyte was registered, in agreement with high storage stability of GreeDo in acidic solutions.

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  • 11.
    Aleksejeva, Olga
    et al.
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV).
    Nilsson, N.
    Obducat Technol AB, S-22363 Lund, Sweden..
    Genevskiy, Vladislav
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV).
    Thulin, K.
    Obducat Technol AB, S-22363 Lund, Sweden..
    Shleev, Sergey
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV).
    Dual-feature photobioanodes based on nanoimprint lithography for photoelectric biosupercapacitors2022In: Journal of Power Sources, ISSN 0378-7753, E-ISSN 1873-2755, Vol. 517, article id 230677Article in journal (Refereed)
    Abstract [en]

    Direct transformation of solar energy into electrical energy by means of biological photosynthesis is considered as an attractive option for sustainable electrical energy production. Thylakoid membranes, the site of photosynthesis, are regarded as a promising biological material for the development of photoelectric biodevices, which produce electrical power consuming only light energy as oxygen evolves at photobioanode upon irradiation and biocathode converts it back to water. Therefore, in this work dual-feature photobioanode based on nanoimprinted gold substrates modified with thylakoids in combination with a capacitive part made of a planar gold substrate coated with a conductive polymer was designed and evaluated, providing open-circuit potential of -0.21 V vs. Ag vertical bar AgCl vertical bar KClsat and a capacitance of ca. 60 F m(-2) both at ambient light and artificial illumination of 400 W m(-2). Combination of thylakoid based dual-feature photobioanode with bilirubin oxidase modified transparent and capacitive indium tin oxide biocathode resulted in a photoelectric biosupercapacitor with remarkable characteristics at ambient light, viz. an open-circuit voltage as high as 0.74 V, which was stable upon charge-discharge cycles during ca. 2 h.

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  • 12.
    Aleksejeva, Olga
    et al.
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV).
    Nilsson, Nicklas
    Obducat Technol AB, S-22363 Lund, Sweden..
    Genevskiy, Vladislav
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV).
    Thulin, Kristian
    Obducat Technol AB, S-22363 Lund, Sweden..
    Shleev, Sergey
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV).
    Photobioanodes Based on Nanoimprinted Electrodes and Immobilized Chloroplasts2022In: ChemElectroChem, E-ISSN 2196-0216, Vol. 9, no 2, p. 37-42Article in journal (Refereed)
    Abstract [en]

    As the global energy demand continues to increase, the interest in photosynthetic energy conversion is growing accordingly. Chloroplasts, photosynthetic organelles present in plants and algae, are attractive candidates for construction of bio solar cells; however, they have been less studied because of their complex membrane system, which restricts electrochemical communication with an electrode surface. Nevertheless, in this work photobioanodes based on planar and nanoimprinted gold substrates modified with chloroplasts were designed and evaluated. Apparently, nanoimprint lithography contributed to higher photocurrent densities, not only owing to the enlarged real surface area, but also due to boosting electrochemical communication between the photosynthetic organelles and the electrode. Combining chloroplast-modified nanoimprinted gold electrodes with a capacitive part made of a planar gold substrate, coated with a conductive polymer, resulted in a dual-feature photobioanode providing a lower open-circuit potential, i. e., -0.11 V vs. Ag|AgCl|KClsat, and an enhanced capacitance of ca. 37 F m(-2) upon illumination of 400 W m(-2).

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  • 13.
    Aleksejeva, Olga
    et al.
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV).
    Sokolov, A. V.
    Russia Saint-Petersburg State University, Russia.
    Marquez, I.
    University of Seville, Spain.
    Gustafsson, Anna
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV).
    Bushnev, S.
    Russian Academy of Sciences, Russia.
    Eriksson, Håkan
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV).
    Ljunggren, Lennart
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV).
    Shleev, Sergey
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Russian Academy of Sciences, Russia.
    Autotolerant ceruloplasmin based biocathodes for implanted biological power sources2021In: Bioelectrochemistry, ISSN 1567-5394, E-ISSN 1878-562X, Vol. 140Article in journal (Refereed)
    Abstract [en]

    High-performance autotolerant bioelectrodes should be ideally suited to design implantable bioelectronic devices. Because of its high redox potential and ability to reduce oxygen directly to water, human ceruloplasmin, HCp, the only blue multicopper oxidase present in human plasma, appears to be the ultimate biocatalyst for oxygen biosensors and also biocathodes in biological power sources. In comparison to fungal and plant blue multicopper oxidases, e.g. Myrothecium verrucaria bilirubin oxidase and Rhus vernicifera laccase, respectively, the inflammatory response to HCp in human blood is significantly reduced. Partial purification of HCp allowed to preserve the native conformation of the enzyme and its biocatalytic activity. Therefore, electrochemical studies were carried out with the partially purified enzyme immobilised on nanostructured graphite electrodes at physiological pH and temperature. Amperometric investigations revealed low reductive current densities, i.e. about 1.65 µA cm−2 in oxygenated electrolyte and in the absence of any mediator, demonstrating nevertheless direct electron transfer based O2 bioelectroreduction by HCp for the first time. The reductive current density obtained in the mediated system was about 12 µA cm−2. Even though the inflammatory response of HCp is diminished in human blood, inadequate bioelectrocatalytic performance hinders its use as a cathodic bioelement in a biofuel cell.

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  • 14. Al-Hashar, Amna
    et al.
    Al-Zakwani, Ibrahim
    Eriksson, Tommy
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV).
    Sarakbi, Alaa
    Al-Zadjali, Badriya
    Al Mubaihsi, Saif
    Al Za'abi, Mohammed
    Impact of medication reconciliation and review and counselling, on adverse drug events and healthcare resource use2018In: International Journal of Clinical Pharmacy, ISSN 2210-7703, E-ISSN 2210-7711, Vol. 40, no 5, p. 1154-1164Article in journal (Refereed)
    Abstract [en]

    Background Adverse drug events from preventable medication errors can result in patient morbidity and mortality, and in cost to the healthcare system. Medication reconciliation can improve communication and reduce medication errors at transitions in care. Objective Evaluate the impact of medication reconciliation and counselling intervention delivered by a pharmacist for medical patients on clinical outcomes 30 days after discharge. Setting Sultan Qaboos University Hospital, Muscat, Oman. Methods A randomized controlled study comparing standard care with an intervention delivered by a pharmacist and comprising medication reconciliation on admission and discharge, a medication review, a bedside medication counselling, and a take-home medication list. Medication discrepancies during hospitalization were identified and reconciled. Clinical outcomes were evaluated by reviewing electronic health records and telephone interviews. Main outcome measures Rates of preventable adverse drug events as primary outcome and healthcare resource utilization as secondary outcome at 30 days post discharge. Results A total of 587 patients were recruited (56 ± 17 years, 57% female); 286 randomized to intervention; 301 in the standard care group. In intervention arm, 74 (26%) patients had at least one discrepancy on admission and 100 (35%) on discharge. Rates of preventable adverse drug events were significantly lower in intervention arm compared to standard care arm (9.1 vs. 16%, p = 0.009). No significant difference was found in healthcare resource use. Conclusion The implementation of an intervention comprising medication reconciliation and counselling by a pharmacist has significantly reduced the rate of preventable ADEs 30 days post discharge, compared to the standard care. The effect of the intervention on healthcare resource use was insignificant. Pharmacists should be included in decentralized, patient-centred roles. The findings should be interpreted in the context of the study's limitations.

  • 15.
    Ali, Abdullah
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV).
    Topical formulations, design and drug delivery: "A dive into water"2021Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Water is a vital component regulating the properties of topical formulations and their interaction with biological barriers, such as skin and mucosa. Changing the watercontent within the frame of the pharmaceutical triangle will have a huge impact on which type of formulation, such as a cream, ointment, gel, or lotion, is formed, as well as the physical properties of the formulation. The composition of a formulation, and the subsequent reformulation after application, will govern the features of the residual film. This will in turn affect the barrier properties of the underlying tissue and consequently the penetration of various substances across skin or mucosa.The primary aim of this thesis has been to provide further understanding on differences between traditional surfactant-based formulations and particle-stabilized, Pickering, formulations and how specific excipients, like alcohols, emollients, and thickeners can affect their physical and/or sensorial properties. The secondary aim has been to gain more knowledge on the role of water in topical formulations and how it affects the properties of the underlaying tissue on application.

    By combining a portfolio of physicochemical techniques combined with sensory science, we have been able to identify differences between Pickering and surfactantstabilized formulations. Starch-based Pickering emulsions were perceived as less greasy and sticky than traditional creams, even at high oil content. Moreover, we were able develop a novel type of alcohol-based Pickering emulsion with combined moisturizing and antiseptic properties. We have also been able to link sensory attributes, evaluated by human volunteers, with physicochemical characterizations. Furthermore, the in vitro ForceBoard™ method was developed further and we evaluated its potential to be used as an ex vivo method using excised skin. In addition, we have shown that that the water gradient over a biological barrier has a general relevance with respect to drug absorption and should be considered not only in dermaldrug delivery but also for buccal and nasal drug delivery.

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  • 16.
    Ali, Abdullah
    et al.
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces. Speximo AB, Medicon Village, Lund.
    Ringstad, Lovisa
    RISE Research Institutes of Sweden, Bioeconomy and Health, Stockholm.
    Skedung, Lisa
    RISE Research Institutes of Sweden, Bioeconomy and Health, Stockholm.
    Falkman, Peter
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Wahlgren, Marie
    Food Technology, Engineering and Nutrition, Lund University.
    Engblom, Johan
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Tactile friction of topical creams and emulsions: Friction measurements on excised skin and VitroSkin® using ForceBoard™.2022In: International Journal of Pharmaceutics, ISSN 0378-5173, E-ISSN 1873-3476, Vol. 615, article id 121502Article in journal (Refereed)
    Abstract [en]

    Tactile perception can be investigated through ex vivo friction measurements using a so-called ForceBoard™, providing objective assessments and savings in time and money, compared to a subjective human panel. In this work we aim to compare excised skin versus VitroSkin® as model substrates for tactile friction measurements. A further aim is to detect possible differences between traditional surfactant-based creams, and a particle-stabilized (Pickering) cream and investigate how the different substrates affect the results obtained. It was found that the difference in tactile friction between excised skin and VitroSkin® was small on untreated substrates. When topical creams were applied, the same trends were observed for both substrates, although the frictional variation over time relates to the difference in surface structure between the two substrates. The results also confirmed that there is a difference between starch-based Pickering formulations and surfactant-based creams after application, indicating that the latter is greasier than Pickering cream. It was also shown that the tactile friction of Pickering emulsions was consistently high even with high amounts of oil, indicating a non-greasy, and non-sticky formulation. The characteristics of starch-stabilized Pickering formulations make them promising candidates in the development of surfactant-free topical formulations with unique tactile properties.

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  • 17.
    Ali, Abdullah
    et al.
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV).
    Skedung, L
    RISE Research Institutes of Sweden, Bioeconomy and Health, Perception and Design, Stockholm, Sweden.
    Burleigh, S
    Food Technology, Engineering and Nutrition, Lund University, Lund, Sweden.
    Lavant, Eva
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Ringstad, L
    RISE Research Institutes of Sweden, Bioeconomy and Health, Perception and Design, Stockholm, Sweden.
    Andersson, CD
    Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.
    Wahlgren, M
    Food Technology, Engineering and Nutrition, Lund University, Lund, Sweden.
    Engblom, Johan
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Relationship between sensorial and physical characteristics of topical creams: a comparative study of effects of excipients2022In: International Journal of Pharmaceutics, ISSN 0378-5173, E-ISSN 1873-3476, Vol. 613, p. 1-12, article id 121370Article in journal (Refereed)
    Abstract [en]

    Rising consumer demands for safer, more natural, and sustainable topical products have led to increased interest in finding alternative excipients, while retaining functionality and cosmetic appeal. Particle-stabilized Pickering creams have emerged as possible alternatives to replace traditional surfactant-stabilized creams and are thus one of the focuses in this study. The aim of this paper was to study relationships between sensorial characteristics and physical properties to understand how different excipients affect these aspects, comparing one starch particle–stabilized and three surfactant-stabilized formulations. A human panel was used to evaluate sensorial perception, while physical properties were deduced by rheology and tactile friction, together with in vivo and ex vivo skin hydration measurements.

    The results show that sensorial attributes related to the application phase can be predicted with rheology, while afterfeel attributes can be predicted with tactile friction studies. Differences in rheological and sensory properties among surfactant-based creams could mainly be attributed to the type of emollients used, presence of thickeners and surfactant composition. Differences between surfactant-based creams and a Pickering cream were more evident in relation to the afterfeel perception. Presence of starch particles in the residual film on skin results in high tactile friction and low perception of residual coating, stickiness, greasiness, and slipperiness in sensorial afterfeel.

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  • 18.
    Ali, Abdullah
    et al.
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV).
    Thuresson, S
    Anderson, C D
    Falkman, P
    Kocherbitov, V
    Ringstad, L
    Sjöö, M
    Skenderska, A
    Wahlgren, M
    Engblom, J
    Alcohol-based Pickering emulsions as moisturizing topical handsanitizers2021Manuscript (preprint) (Other academic)
  • 19.
    Ali, Abdullah
    et al.
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Wahlgren, Marie
    Food Technology, Engineering and Nutrition, Lund University, P.O. Box 124, SE-221 00, Lund, Sweden.
    Pedersen, Lina
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Engblom, Johan
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Will a water gradient in oral mucosa affect transbuccal drug absorption?2018In: Journal of Drug Delivery Science and Technology, ISSN 1773-2247, Vol. 48, p. 338-345Article in journal (Refereed)
    Abstract [en]

    Formulations for buccal drug delivery often comprise polymers to facilitate mucoadhesion based on water sorption. The main objective of the current study was therefore to evaluate the effect of dehydration on drug uptake through oral mucosa. We have used diffusion cells with excised porcine mucosa to study uptake of three alternative drugs (i.e., Metronidazole, Benzydamine and Xylometazoline) together with polyethylene glycol (PEG) as the model polymer for adjusting water activity in the test solutions. Taking drug activity into account, we can conclude that addition of PEG results in a drug flux through mucosa that is about two times lower for Metronidazole and more than 40 times lower for Xylometazoline compared to that from a pure PBS-solution. However, for Benzydamine the uptake through mucosa was more or less the same, which could possibly be due to the high PEG-concentration (65 wt%) affecting the dissociation constant and thus the permeability. These results indicate that an increased water gradient may have the same limiting effect on permeability through oral mucosa as previously seen for skin. Thus, water gradient effects should be a factor to consider when developing buccal adhesive formulations.

  • 20.
    Ali, Abdullah
    et al.
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Wahlgren, Marie
    Food Technology, Engineering and Nutrition, Lund University, Lund, Sweden.
    Rembratt-Svensson, Birgitta
    Bioglan AB, Malmö, Sweden.
    Daftani, Ameena
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Falkman, Peter
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Wollmer, Per
    Department of Translational Medicine, Faculty of Medicine, Lund University, Malmö, Sweden.
    Engblom, Johan
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Dehydration affects drug transport over nasal mucosa2019In: Drug Delivery, ISSN 1071-7544, E-ISSN 1521-0464, Vol. 26, no 1, p. 831-840Article in journal (Refereed)
    Abstract [en]

    Formulations for nasal drug delivery often rely on water sorption to adhere to the mucosa, which also causes a higher water gradient over the tissue and subsequent dehydration. The primary aim of this study was therefore to evaluate mucosal response to dehydration and resolve the hypothesis that mucoadhesion achieved through water sorption could also be a constraint for drug absorption via the nasal route. The effect of altering water activity of the vehicle on Xylometazoline HCl and Cr-EDTA uptake was studied separately using flow through diffusion cells and excised porcine mucosa. We have shown that a modest increase in the water gradient over mucosa induces a substantial decrease in drug uptake for both Xylometazoline HCl and Cr-EDTA. A similar result was obtained when comparing two different vehicles on the market; Nasoferm (Nordic Drugs, Sweden) and BLOX4 (Bioglan, Sweden). Mucoadhesion based on water sorption can slow down drug uptake in the nasal cavity. However, a clinical study is required to determine whether prolonged duration of the vehicle or preventing dehydration of the mucosa is the most important factor for improving bioavailability.

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  • 21.
    Allavi, Marzieh
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV).
    ALUMINIUM-BASERADE ADJUVANTERS PÅVERKAN PÅ MAKROFAGERS METABOLISM2022Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Ever since the first vaccine was discovered during the smallpox pandemic in the late 19th century, the vaccine has become an essential tool for protection against various diseases. A vaccine needs an adjuvant that has an enhancing effect; today, aluminum-based adjuvants (ABA) are most commonly used. The development of ABA has been empirical, with no understanding of its mechanism and impact on the immune system. Scientists worldwide are unanimous that the uptake of ABA through phagocytosis of phagocytic cells leads to immunoactivity; however, the causes are still unknown. The purpose of the study was to investigate whether ABA influences the metabolism in macrophages. The final product of glycolysis is pyruvate that undergoes a chain of reactions and converts to lactate. Therefore, was the analysis based on the lactate production of the cells before and after incubation with different concentrations of the ABA Alhydrogel. The study was conducted on a human monocytic cell line THP-1 and a human periphery monocyte. The differentiation of the two cell lines into M1, M2, and M0 macrophages was performed with stimulating factors such as LPS and cytokines such as IL-4, IL-13 and INF-γ. After completed incubations with ABA, the medium of the cells was collected for analysis of lactate and simultaneously measuring the viability of the cells. To quantify lactate, Lactate-GloTM Assay was used, and the measurement of viability was performed with CellTiterFluorTM Cell Viability Assay. The results showed a noticeable increase in the lactate production of the cells when incubated with low levels of ABA, particularly in the M1 macrophages. On the contrary, higher levels of ABA showed a noticeable reduction in lactate and the viability of the cells. The results showed that phagocytosis of ABA influences the metabolism in macrophages, but high levels of ABA lead to possible cell death. However, additional research needs to be done to attain significant statistical data.

  • 22.
    Always Alzubedy, Lina
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV).
    Dendritiska cellers intracellulära koncentrationer av laktat efter exponering för aluminium adjuvant.2023Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Dendritic cells (DCs) are a type of phagocytic and antigen-presenting cells that play a crucial role in bridging the innate and adaptive immune responses. DCs have the primary function of phagocytizing foreign substances and presenting antigens to naive T cells. Over the past decades, antigen-presenting cells (APCs) have played a significant role in vaccine development. The advancement of vaccines has greatly focused on enhancing safety and reducing side effects. Previous studies have shown that macrophages exposed to aluminum adjuvants, and thereby phagocytizing the adjuvant, experience an increased intracellular lactate content. Lactate concentration was measured to assess potential changes in metabolism after phagocytosis of Al adjuvants. The measurement of lactate concentration was performed using Lactate-Glo™ Assay kits, based on a luminescence-based method. The aim of the study was to investigate the intracellular lactate concentration in in vitro-differentiated monocyte-derived dendritic cells (MoDCs) incubated with and without lipopolysaccharides (LPS). The results of this study have indicated a potential alteration in lactate production in non-activated MoDCs after incubation with two different concentrations of aluminum adjuvants (Al 2.5 µg/ml and Al 5 µg/ml). Regarding LPS-activated MoDCs, the study showed no significant impact of the aluminum adjuvant on cell lactate production. To draw conclusions, several additional experiments were required to determine whether there is a significant effect on the lactate concentration in dendritic cells after exposure to Al adjuvant.

  • 23.
    Ambaw, Y. A.
    et al.
    Precision Medicine Translational Research Programme and Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119077, Singapore; SLING, Singapore Lipidomics Incubator, Life Sciences Institute, National University of Singapore, Singapore 119077, Singapore; Department of Molecular Metabolism, Harvard T.H. Chan School of Public Health, Harvard University, Cambridge, MA 02138, USA.
    Dahl, S. R.
    Department of Chemistry, University of Oslo, 0315 Oslo, Norway; Hormone Laboratory, Department of Medical Biochemistry, Oslo University Hospital, 0424 Oslo, Norway.
    Chen, Y.
    Department of Chemistry, University of Oslo, 0315 Oslo, Norway.
    Greibrokk, T.
    Department of Chemistry, University of Oslo, 0315 Oslo, Norway.
    Lundanes, E.
    Department of Chemistry, University of Oslo, 0315 Oslo, Norway.
    Lazraq, Issam
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Shinde, Sudhirkumar
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces. School of Consciousness, Dr Vishwanath Karad Maharashtra Institute of Technology–World Peace University, Kothrud, Pune 411038, Maharashtra, India.
    Selvalatchmanan, J.
    Precision Medicine Translational Research Programme and Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119077, Singapore; SLING, Singapore Lipidomics Incubator, Life Sciences Institute, National University of Singapore, Singapore 119077, Singapore.
    Wenk, M. R.
    Precision Medicine Translational Research Programme and Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119077, Singapore; SLING, Singapore Lipidomics Incubator, Life Sciences Institute, National University of Singapore, Singapore 119077, Singapore.
    Sellergren, Börje
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Torta, F.
    Precision Medicine Translational Research Programme and Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119077, Singapore; SLING, Singapore Lipidomics Incubator, Life Sciences Institute, National University of Singapore, Singapore 119077, Singapore.
    Tailored polymer-based selective extraction of lipid mediators from biological samples2021In: Metabolites, ISSN 2218-1989, E-ISSN 2218-1989, Vol. 11, no 8, article id 539Article in journal (Refereed)
    Abstract [en]

    Lipid mediators, small molecules involved in regulating inflammation and its resolution, are a class of lipids of wide interest as their levels in blood and tissues may be used to monitor health and disease states or the effect of new treatments. These molecules are present at low levels in biological samples, and an enrichment step is often needed for their detection. We describe a rapid and selective method that uses new low-cost molecularly imprinted (MIP) and non-imprinted (NIP) polymeric sorbents for the extraction of lipid mediators from plasma and tissue samples. The extraction process was carried out in solid-phase extraction (SPE) cartridges, manually packed with the sorbents. After extraction, lipid mediators were quantified by liquid chromatography–tandem mass spectrometry (LC–MSMS). Various parameters affecting the extraction efficiency were evaluated to achieve optimal recovery and to reduce non-specific interactions. Preliminary tests showed that MIPs, designed using the prostaglandin biosynthetic precursor arachidonic acid, could effectively enrich prostaglandins and structurally related molecules. However, for other lipid mediators, MIP and NIP displayed comparable recoveries. Under optimized conditions, the recoveries of synthetic standards ranged from 62% to 100%. This new extraction method was applied to the determination of the lipid mediators concentration in human plasma and mouse tissues and compared to other methods based on commercially available cartridges. In general, the methods showed comparable performances. In terms of structural specificity, our newly synthesized materials accomplished better retention of prostaglandins (PGs), hydroxydocosahexaenoic acid (HDoHE), HEPE, hydroxyeicosatetraenoic acids (HETE), hydroxyeicosatrienoic acid (HETrE), and PUFA compounds, while the commercially available Strata-X showed a higher recovery for dihydroxyeicosatetraenoic acid (diHETrEs). In summary, our results suggest that this new material can be successfully implemented for the extraction of lipid mediators from biological samples. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

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  • 24.
    Andersson, Anni
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV).
    Utvärdering av biomarkörerna PD-L1 och calretinin i parade histologiska och cytologiska provmaterial från patienter med mesoteliom2023Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Malignant mesothelioma is a rare and aggressive cancer. It is most common in the pleura, called pleural mesothelioma. The most common reason for developing pleural mesothelioma is exposure to asbestosis. Patients that get sick have a poor prognosis and limited treatment options. X-ray can in a first stadium give diagnose of the disease. A biopsy is often necessary to confirm the diagnosis. Even sampling of pleural fluid can give valuable diagnostic information. Immunohistochemistry is a common additional analysis for diagnosis with biopsy and cell block. Immunohistochemistry implies staining with antibodies. For example, for pleural mesothelioma the antibodies PD-L1 and calretinin can be used for diagnosis. In this study 10 paired pleural biopsies and cell blocks from pleural fluid from patients with malign mesothelioma were immunostained. The study aimed to evaluate expression of PD-L1 and calretinin. All the stained glasses were evaluated by a light microscope. For PD-L1, only membranous staining was considered positive and for calretinin cytoplasmic and/or nuclear staining was considered positive. Percentage number of positive tumor cells were evaluated at two cutoff values, ≥1 % and ≥10 %. Percentage number <1 % at cutoff ≥1 % and percentage number <10 % at cutoff ≥10 % were considered negative. The same criteria were applied for both antibodies. The number of positive and negative biopsies as well as cell blocks and the concordance were reported. Overall percentage agreement (OPA), Cohen’s kappa (κ) and confidence interval (CI) was also calculated. Result showed lower number of positive staining for the cell blocks than for the biopsies for both antibodies. The concordance was shown to be equal for PD-L1 and calretinin at cutoff ≥1 % but higher for PD-L1 than for calretinin at cutoff ≥10 %.

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  • 25.
    Andoralov, Victor
    et al.
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV).
    Shleev, Sergey
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces. Research Centre of Biotechnology, Russian Academy of Sciences, 119071 Moscow, Russia.
    Dergousova, Natalia
    Research Centre of Biotechnology, Russian Academy of Sciences, 119071 Moscow, Russia.
    Kulikova, Olga
    Research Centre of Biotechnology, Russian Academy of Sciences, 119071 Moscow, Russia.
    Popov, Vladimir
    Research Centre of Biotechnology, Russian Academy of Sciences, 119071 Moscow, Russia; Kurchatov NBIC Centre, National Research Centre “Kurchatov Institute”, 123182 Moscow, Russia.
    Tikhonova, Tamara
    Research Centre of Biotechnology, Russian Academy of Sciences, 119071 Moscow, Russia.
    Octaheme nitrite reductase: The mechanism of intramolecular electron transfer and kinetics of nitrite bioelectroreduction.2021In: Bioelectrochemistry, ISSN 1567-5394, E-ISSN 1878-562X, Vol. 138, article id 107699Article in journal (Refereed)
    Abstract [en]

    Detailed impedance and voltammetric studies of hexameric octaheme nitrite reductase immobilized on carbon-based nanomaterials, specifically nanotubes and nanoparticles, were performed. Well-pronounced bioelectrocatalytic reduction of nitrite on enzyme-modified electrodes was obtained. Analysis of the impedance data indicated the absence of long-lived intermediates involved in the nitrite reduction. Cyclic voltammograms of biomodified electrodes had a bi-sigmoidal shape, which pointed to the presence of two enzyme orientations on carbon supports. The maximum (limiting) catalytic currents were determined and, by applying the correction by the mixed kinetics equation, the Tafel dependences were plotted for each catalytic wave/each enzyme orientation. Finally, two schemes for the rate-limiting processes during bioelectrocatalysis were proposed, viz. for low- and high-potential orientations.

  • 26. Angiolini, Lorenzo
    et al.
    Valetti, Sabrina
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Cohen, Boiko
    Feiler, Adam
    Douhal, Abderrazzak
    Fluorescence imaging of antibiotic clofazimine encapsulated within mesoporous silica particle carriers: relevance to drug delivery and the effect on its release kinetics2018In: Physical Chemistry, Chemical Physics - PCCP, ISSN 1463-9076, E-ISSN 1463-9084, Vol. 20, no 17, p. 11899-11911Article in journal (Refereed)
    Abstract [en]

    We report on the encapsulation of the antibiotic clofazimine (CLZ) within the pores of mesoporous silica particles having hydrophilic (CBET value of 137) and more hydrophobic (CBET value of 94 after calcination at 600 °C) surfaces. We studied the effect of pH on the released amount of CLZ in aqueous solutions and observed a maximum at pH 4.1 in correlation with the solubility of the drug. Less release of the drug was observed from the more hydrophobic particles which was attributed to a difference in the affinity of the drug to the carrier particles. Fluorescence lifetime imaging microscopy, emission spectra, and fluorescence lifetimes of single drug loaded particles provided detailed understanding and new knowledge of the physical form of the encapsulated drug and the distribution within the particles. The distribution of CLZ within the particles was independent of the surface chemistry of the particles. The confirmation of CLZ molecules as monomers or aggregates was revealed by controlled removal of the drug with solvent. Additionally, the observed optical "halo effect" in the fluorescent images was interpreted in terms of specific quenching of high concentration of molecules. The emission lifetime experiments suggest stronger interaction of CLZ with the more hydrophobic particles, which is relevant to its release. The results reported in this work demonstrate that tuning the hydrophilicity/hydrophobicity of mesoporous silica particles can be used as a tool to control the release without impacting their loading ability.

  • 27.
    Argatov, Ivan
    et al.
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces. Institut für Mechanik, Technische Universität Berlin, 10623 Berlin, Germany.
    Engblom, Johan
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Kocherbitov, Vitaly
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Modeling of composite sorption isotherm for stratum corneum2022In: Biochimica et Biophysica Acta - Biomembranes, ISSN 0005-2736, E-ISSN 1879-2642, Vol. 1864, no 7, p. 1-8, article id 183910Article in journal (Refereed)
    Abstract [en]

    Equilibrium water sorption in stratum corneum (SC) is considered by treating it as a biocomposite with two main phases, namely, corneocytes and lipids. To validate the rule of mixtures for the individual phase sorption isotherms, a new flexible fitting model is introduced by accounting for characteristic features observed in the variations of the thermodynamic correction factors corresponding to the individual sorption isotherms. The comparison of the model fitting performance with that of the five-parameter Park's model shows a remarkably good ability to fit experimental data for different types of sorption isotherms. The effect of the lipids content on the variance of the composite sorption isotherm of stratum corneum is highlighted. The sensitivity analysis reveals that for the typical water content 20-30 wt%, which corresponds to the SC in a stable condition, the sensitivity of the composite sorption isotherm to the variation of the lipids content on dry basis is predominantly positive and sufficiently small. The good agreement observed between the experimental sorption isotherm for SC and the composite isotherm, which is based on the rule of mixtures for the individual phase sorption isotherms, yields a plausible conclusion (hypothesis) that the corneocytes-lipids mechanical interaction during unconstrained swelling of the SC membrane in the in vitro laboratory experiment is negligible.

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  • 28.
    Argatov, Ivan
    et al.
    Malmö University, Biofilms Research Center for Biointerfaces. Malmö University, Faculty of Technology and Society (TS), Department of Materials Science and Applied Mathematics (MTM).
    Kocherbitov, Vitaly
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    A note on artificial neural network modeling of vapor-liquid equilibrium in multicomponent mixtures2019In: Fluid Phase Equilibria, ISSN 0378-3812, E-ISSN 1879-0224, Vol. 502, article id 112282Article in journal (Refereed)
    Abstract [en]

    Application of artificial neural networks (ANNs) for modeling of vapor-liquid equilibrium in multicomponent mixtures is considered. Two novel ANN-based models are introduced, which can be seen as generalizations of the Wilson model and the NRTL model. A unique feature of the proposed approach is that an ANN approximation for the molar excess Gibbs energy generates approximations for the activity coefficients. A special case of the ternary acetic acid-n-propyl alcohol-water system (at 313.15 K) is used to illustrate the efficiency of the different models, including Wilson's model, Focke's model, and the introduced generalized degree-1 homogeneous neural network model. Also, the latter one-level NN model is compared to the Wilson model on 10 binary systems. The efficiency of the two-level NN model is assessed by a comparison with the NRTL model. (C) 2019 Elsevier B.V. All rights reserved.

  • 29.
    Argatov, Ivan
    et al.
    Malmö University, Biofilms Research Center for Biointerfaces. Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Chongqing University, China.
    Kocherbitov, Vitaly
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    An empirical model for sorption by glassy polymers: An assessment of thermodynamic parameters2021In: Polymer testing, ISSN 0142-9418, E-ISSN 1873-2348, Vol. 99Article in journal (Refereed)
    Abstract [en]

    A new fitting model for sorption by glassy polymers is suggested based on the Flory–Huggins (FH) equation with a composite formula for the FH interaction parameter, χ, which is applicable if sorption experimental data shows a single-maximum variation of the FH parameter. Namely, a power-like and a linear approximation is assumed for χ(φ1), as a function of solvent volume fraction φ1, before and after the point of its maximum. After determining the maximum point from a direct inspection of the sorption data, the three fitting parameters are evaluated by solving two independent least-square minimization problems. Several sorption studies of biopolymers taken from the literature show that the endset of the glass transition region is correlated with the position of the maximum of the FH interaction parameter. Based on this hypothesis and the Vrentas–Vrentas model for sorption of glassy polymers, a theoretical framework for the glass transition analysis is developed. In particular, the solvent-induced glass transition temperature variation can be estimated from the sorption isotherm as a function of the solvent content corresponding to temperatures above the temperature of sorption.

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  • 30.
    Argatov, Ivan
    et al.
    Malmö University, Biofilms Research Center for Biointerfaces. Malmö University, Faculty of Technology and Society (TS), Department of Materials Science and Applied Mathematics (MTM). Tech Univ Berlin, Inst Mech, Berlin, Germany.
    Kocherbitov, Vitaly
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Analysis of the minimal model for the enthalpy relaxation and recovery in glass transition: application to constant-rate differential scanning calorimetry2021In: Continuum Mechanics and Thermodynamics, ISSN 0935-1175, E-ISSN 1432-0959, Vol. 33, p. 107-123Article in journal (Refereed)
    Abstract [en]

    The so-called minimal model is formulated for describing the enthalpy relaxation and recovery in glass transition. The model is based on the Arrhenius law for the enthalpy relaxation, which uses two-dimensional parameters, namely the activation energy and the so-called pre-factor (relaxation time at relatively high temperature). A numerically effective exact analytical solution is obtained for the case of constant-rate differential scanning calorimetry. The developed model is analyzed according to the logic of the model itself without introducing additional simplifying assumptions of thermodynamic nature. For typical range of the model parameters, the resulting differential equation contains a large parameter, which offers an opportunity for the application of asymptotic and approximate techniques. A number of simple approximations have been provided for some thermodynamic quantities of interest.

  • 31.
    Argatov, Ivan
    et al.
    Tech Univ Berlin, Inst Mech, D-10623 Berlin, Germany..
    Krcic, Nedim
    Magle Chemoswed, Agneslundsvagen 27, SE-21215 Malmö, Sweden..
    Kocherbitov, Vitaly
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Sedimentation of a starch microsphere: What is usually missed and why?2023In: Heliyon, E-ISSN 2405-8440, Vol. 9, no 10, article id e20257Article in journal (Refereed)
    Abstract [en]

    Gravimetric sedimentation is known as a relatively simple method of determining density of spherical particles. When the method is applied to water-swollen starch microparticles of about submillimeter sizes, it becomes evident that a careful selection of the experimental setup parameters is needed for producing accurate testing results. The main reason for this is that the mean particle density is very close to the density of water, and therefore, a dynamic model accounting for the so-called Bassett history force should be employed for describing the unsteady accelerating particle settling. A main novelty of this study consists in deriving a priori estimates for the settling time and distance.

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  • 32.
    Argatov, Ivan
    et al.
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Tech Univ Berlin, Inst Mech, D-10623 Berlin, Germany..
    Roosen-Runge, Felix
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Kocherbitov, Vitaly
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Dynamics of post-occlusion water diffusion in stratum corneum2022In: Scientific Reports, E-ISSN 2045-2322, Vol. 12, no 1, article id 17957Article in journal (Refereed)
    Abstract [en]

    Diffusion of water through membranes presents a considerable challenge, as the diffusivity often depends on the local concentration of water. One particular example with strong biological relevance is the stratum corneum (SC) as the primary permeability barrier for the skin. A simple alternative for the constant diffusivity model is provided by the Fujita's two-parameter rational approximation, which captures the experimentally observed fact that the SC diffusion constant for water increases with increasing the water concentration. Based on Fick's law of diffusion, a one-dimensional concentration-dependent diffusion model is developed and applied for the analysis of both the steady-state transepidermal water loss (TEWL) and the non-steady-state so-called skin surface water loss (SSWL) occurred after removal of an occlusion patch from the SC surface. It is shown that some of the age-related changes in the SSWL can be qualitatively explained by the variation of the dimensionless Fujita concentration-dependence parameter.

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  • 33.
    Aria, Danish
    et al.
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV).
    Eriksson, Tommy
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV).
    Westerlund, Tommy
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV).
    Use of an electronic expert support system in a Swedish community pharmacy to identify and resolve drug-related problems2020Manuscript (preprint) (Other academic)
    Abstract [en]

    Background The Lund Integrated MedicinesManagement model offers a systematic approach forindividualising and optimising patient drug treatment.Clinical, economical and humanistic outcomes havebeen shown as well as results from the medicationreconciliation process. There is a need also to describethe medication review process.Objective To describe the frequency and types of drug-relatedproblems (DRPs) identified during medicationreviews and to evaluate the actions of the pharmacistsand the physicians regarding the identified DRPs.Method Structured medication reviews were conductedby a multi-professionalteam on top of standard care for719 patients in two internal medicine wards in a SwedishUniversity Hospital. The medication reviews were studiedretrospectively to classify DRPs and actions taken.Results A total of 573 (80%) of patients had at leastone actual DRP; an average of three DRPs per patientand in total 2164. Wrong drug and adverse drug reactionwere the most common types of DRPs. The most frequentmedication groups involved in DRPs were drugs forthe cardiovascular system and the nervous system andthe most frequent substances were warfarin, digoxin,furosemide and paracetamol. The 10 most commonmedications accounted for 27% of the actual DRPs. Ofthe identified DRPs, a total of 1740 (80%) were actedon. The three most common types of adjustments madewere withdrawal of drug therapy, change of drug therapyand initiation of drug therapy. When the pharmacistsuggested an adjustment, the physician implemented88% (1037/1174) of the recommendations.Conclusion DRPs are common among elderly patientswho are admitted to hospital. Systematic identificationof high-riskmedications and common DRP types enablestargeting of prioritised patients for medication reviews.

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  • 34.
    Awad, Eman
    et al.
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV).
    Ramji, Rathi
    Malmö University, Faculty of Health and Society (HS), Department of Care Science (VV).
    Cirovic, Stefan
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV).
    Rämgård, Margareta
    Malmö University, Faculty of Health and Society (HS), Department of Care Science (VV).
    Kottorp, Anders
    Malmö University, Faculty of Health and Society (HS), Department of Care Science (VV).
    Shleev, Sergey
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University.
    Developing and evaluating non-invasive healthcare technologies for a group of female participants from a socioeconomically disadvantaged area2021In: Scientific Reports, E-ISSN 2045-2322, Vol. 11, no 1, article id 23896Article in journal (Refereed)
    Abstract [en]

    When compared to the general population, socioeconomically disadvantaged communitiesfrequently experience compromised health. Monitoring the divide is challenging since standardizedbiomedical tests are linguistically and culturally inappropriate. The aim of this study was to developand test a unique mobile biomedical testbed based on non-invasive analysis, as well as to explorethe relationships between the objective health measures and subjective health outcomes, asevaluated with the World Health Organization Quality of Life survey. The testbed was evaluated in asocioeconomically disadvantaged neighborhood in Malmö, which has been listed as one of the twelvemost vulnerable districts in Sweden. The study revealed that compared to conventional protocolsthe less intrusive biomedical approach was highly appreciated by the participants. Surprisingly, thecollected biomedical data illustrated that the apparent health of the participants from the ethnicallydiverse low-income neighborhood was comparable to the general Swedish population. Statisticallysignificant correlations between perceived health and biomedical data were disclosed, even thoughthe dependences found were complex, and recognition of the manifest complexity needs to beincluded in further research. Our results validate the potential of non-invasive technologies incombination with advanced statistical analysis, especially when combined with linguistically andculturally appropriate healthcare methodologies, allowing participants to appreciate the significanceof the different parameters to evaluate and monitor aspects of health.

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  • 35. Badell, Maria Valldeperas
    et al.
    Dabkowska, Aleksandra
    Naidjonoka, Polina
    Welbourn, Rebecca
    Palsson, Gunnar K.
    Barauskas, Justas
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV).
    Nylander, Tommy
    Lipid Sponge-Phase Nanoparticles as Carriers for Enzymes2018In: Biophysical Journal, ISSN 0006-3495, E-ISSN 1542-0086, Vol. 114, no 3, suppl 1, p. 15A-15AArticle in journal (Other academic)
    Abstract [en]

    Immobilization of enzymes into different support materials has been widely studied as means to control their activity and stability. Here we will consider lipid liquid crystalline phases as enzyme carriers, as they have been demonstrated to have a high potential in a range of applications such as drug delivery, protein encapsulation or crystallization thanks to the wide range of self-assembly structures they can form, which have cavities of nano-scale dimensions. Furthermore, such structures have also been observed in a range of living organisms. Although, reverse cubic or hexagonal lipid aqueous phase can be used to entrap smaller biomolecules, it is still challenging to encapsulate bioactive macromolecules, such as proteins. Here, we will present a novel lipid system able to form highly swollen sponge phases (L3), with aqueous pores up to 13 nm of diameter. We will show that this structure is preserved even in excess aqueous solution, where they form sponge-like nanoparticles (L3 NPs) in which two enzymes of different sizes, Aspartic protease and beta-galactosidase (34 KDa and 460 KDa, respectively), could be included. To reveal the nature of the interaction between the enzymes and the lipid matrix, we studied the adsorption of both proteins on the lipid layers formed by the L3 NPs. The results will be discussed in terms of the ability of these nanoparticles to encapsulate and release of the proteins in the lipid matrix.

  • 36. Bahmanzadeh, Safiyeh
    et al.
    Ruzgas, Tautgirdas
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Sotres, Javier
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Proteolytic degradation of gelatin-tannic acid multilayers2018In: Journal of Colloid and Interface Science, ISSN 0021-9797, E-ISSN 1095-7103, Vol. 526, p. 244-252Article in journal (Refereed)
    Abstract [en]

    Hypothesis Gelatin is one of the most popular constituents of biodegradable/edible films. Because of its poor mechanical properties, it typically needs to be cross-linked. In this regard, the use of tannic acid has attracted significant interest. Whereas the biodegradability of gelatin is well established, little is known on how different crosslinking methods affect biodegradability. In most cases, the ionic strength at which protein films are grown has a drastic effect on their structure. Thus, it is expected that by controlling the ionic strength during the growth of cross-linked gelatin films it should be possible to tune the access to relevant cleavage sites by proteases and, therefore, their biodegradability. Experiments Gelatin-tannic acid were grown at different ionic strengths by means of the layer-by-layer self-assembly method. The growth of these multilayers and their response to the presence of different proteases were monitored by means of Electrochemical Impedance Spectroscopy and Quartz Crystal Microbalance with Dissipation. Findings Gelatin-tannic acid multilayers grown at low ionic strength exhibited a swollen structure that allowed easy access to their cleavage sites by proteases. Multilayers formed at physiological ionic strength exhibited a compacter structure, which limited their proteolytic degradation.

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  • 37. Bakkour, Rani
    et al.
    Bolotin, Jakov
    Sellergren, Börje
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV).
    Hofstetter, Thomas B.
    Molecularly Imprinted Polymers for Compound-Specific Isotope Analysis of Polar Organic Micropollutants in Aquatic Environments2018In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 90, no 12, p. 7292-7301Article in journal (Refereed)
    Abstract [en]

    Compound-specific isotope analysis (CSIA) of polar organic micropollutants in environmental waters requires a processing of large sample volumes to obtain the required analyte masses for analysis by gas chromatography/isotoperatio mass spectrometry (GC/IRMS). However, the accumulation of organic matter of unknown isotopic composition in standard enrichment procedures currently compromises the accurate determination of isotope ratios. We explored the use of molecularly imprinted polymers (MIPs) for selective analyte enrichment for C-13/C-12 and N-15/N-14 ratio measurements by GC/IRMS using 1H-benzotriazole, a typical corrosion inhibitor in dishwashing detergents, as example of a widely detected polar organic micropollutant. We developed procedures for the treatment of >10 L of water samples, in which custom-made MIPs enabled the selective cleanup of enriched analytes in organic solvents obtained through conventional solid-phase extractions. Hydrogen bonding interactions between the triazole moiety of 1H-benzotriazole, and the MIP were responsible for selective interactions through an assessment of interaction enthalpies and N-15 isotope effects. The procedure was applied successfully without causing isotope fractionation to river water samples, as well as in- and effluents of wastewater treatment plants containing mu g/L concentrations of 1H-benzotriazole and dissolved organic carbon (DOC) loads of up to 28 mg C/L. MIP-based treatments offer new perspectives for CSIA of organic micropollutants through the reduction of the DOC-to-micropollutant ratios.

  • 38.
    Banan, Kamran
    et al.
    Shahid Beheshti Univ Med Sci, Sch Pharm, Dept Pharmaceut, Tehran, Iran..
    Ghorbani-Bidkorbeh, Fatemeh
    Shahid Beheshti Univ Med Sci, Sch Pharm, Dept Pharmaceut, Tehran, Iran..
    Afsharara, Hanif
    Shahid Beheshti Univ Med Sci, Sch Pharm, Dept Med Chem, Tehran, Iran..
    Hatamabadi, Dara
    Shahid Beheshti Univ Med Sci, Sch Pharm, Dept Med Chem, Tehran, Iran..
    Landi, Behnaz
    Shahid Beheshti Univ Med Sci, Sch Pharm, Dept Pharmaceut, Tehran, Iran..
    Kecili, Rustem
    Anadolu Univ, Yunus Emre Vocat Sch Hlth Serv, Dept Med Serv & Tech, Eskisehir, Turkey..
    Sellergren, Börje
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV).
    Nano-sized magnetic core-shell and bulk molecularly imprinted polymers for selective extraction of amiodarone from human plasma2022In: Analytica Chimica Acta, ISSN 0003-2670, E-ISSN 1873-4324, Vol. 1198, article id 339548Article in journal (Refereed)
    Abstract [en]

    Bulk and magnetic core-shell Molecularly Imprinted Polymers (MMIPs) have been introduced and compared to extract and determine amiodarone from a complex matrix, i.e., plasma, due to the importance of Therapeutic Drug Monitoring (TDM). Polymer synthesis was confirmed by FTIR, AFM, TGA, DLS, VSM, TEM, and the adsorption studies such as capacity, isothermal models, selectivity, and regeneration were performed to evaluate and compare polymer efficiency in extraction and separation of amiodarone from sample solutions and human plasma. Both nano-sized and bulk polymers successfully extracted the target molecule at the low therapeutic ranges and the overdose concentrations (recoveries of 98.38%-102.70%). The maximum adsorption capacity of the MMIPs was 42.5 mu g/mg compared with 2.6 mu g/mg for bulk polymers. The imprinting factors of the polymers were 15.12 and 6.84 for MMIPs and bulk, respectively. MMIPs and bulk polymers presented 4.68 and 1.66 selectivity factors, respectively, towards amiodarone compared with lidocaine. LOD, LOQ and enrichment factor in human plasma were 0.09, 0.28 mu g mL(-1), and 10 respectively. Recoveries of therapeutic concentration from plasma were 91.38 and 97.33% for bulk and MMIPs, respectively. MMIPs as an adsorbent in amiodarone extraction from plasma offered reduced necessary sample amount, less adsorbent consumption, reduced pretreatment time, and reduced elution solvent waste while yielding higher extraction recovery and more specificity for the target compared with the bulk polymer. Bulk polymers have a more straightforward synthesis procedure due to fewer synthesis steps and fewer variables, and Molecularly Imprinted Polymer Solid-phase Extraction (MIP-SPE) has already been introduced commercially. MMIPs prevail on a small scale, and in the context of a simple extraction, separation, or concentration in large-scale bioanalysis, efforts towards optimization and development of MMIPs can unearth tremendous opportunities for green chemistry principles. 

  • 39.
    Barriga, Hanna
    et al.
    Department of Medical Biochemistry and Biophysics, Karolinska Institutet Stockholm, Sweden.
    Cárdenas, Marité
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Hall, Stephen
    Division of Solid Mechanics, Lund University, and Lund Institute of Advanced Neutron and X-ray Science, Lund, Sweden.
    Hellsing, Maja
    Division for Bioeconomy and Health, RISE Research Institutes of Sweden, Stockholm, Sweden.
    Karlsson, Maths
    Department of Chemistry and Chemical Engineering, Chalmers University of Technology, Göteborg, Sweden.
    Pavan, Adriano
    Department of Chemistry, Uppsala University, Uppsala, Sweden.
    Peng, Ru
    Department of Management and Engineering, Linköping University, Linköping, Sweden.
    Strandqvist, Nanny
    Department of Physics and Astronomy, Uppsala University, Uppsala, Sweden.
    Wolff, Max
    Department of Physics and Astronomy, Uppsala University, Uppsala, Sweden.
    A Bibliometric Study on Swedish Neutron Users for the Period 2006–20202021In: Neutron News, ISSN 1044-8632, E-ISSN 1931-7352, Vol. 32, no 4, p. 28-33Article in journal (Refereed)
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  • 40.
    Beck, Christian
    et al.
    Univ Tubingen, Inst Angew Phys, Morgenstelle 10, D-72076 Tubingen, Germany.;Inst Max von Laue Paul Langevin, 71 Ave Martyrs, F-38042 Grenoble, France..
    Grimaldo, Marco
    Inst Max von Laue Paul Langevin, 71 Ave Martyrs, F-38042 Grenoble, France..
    Braun, Michal K.
    Univ Tubingen, Inst Angew Phys, Morgenstelle 10, D-72076 Tubingen, Germany..
    Buhl, Lena
    Univ Tubingen, Inst Angew Phys, Morgenstelle 10, D-72076 Tubingen, Germany..
    Matsarskaia, Olga
    Inst Max von Laue Paul Langevin, 71 Ave Martyrs, F-38042 Grenoble, France..
    Jalarvo, Niina H.
    Forschungszentrum Julich, Julich Ctr Neutron Sci JCNS, D-52425 Julich, Germany.;Oak Ridge Natl Lab, Chem & Engn Mat Div, Neutron Sci Directorate, POB 2008, Oak Ridge, TN 37831 USA.;Oak Ridge Natl Lab, JCNS Outstn Spallat Neutron Source SNS, POB 2008, Oak Ridge, TN 37831 USA..
    Zhang, Fajun
    Univ Tubingen, Inst Angew Phys, Morgenstelle 10, D-72076 Tubingen, Germany..
    Roosen-Runge, Felix
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces. Lund Univ, Div Phys Chem, Nat Vetarvagen 14, S-22100 Lund, Sweden..
    Schreiber, Frank
    Univ Tubingen, Inst Angew Phys, Morgenstelle 10, D-72076 Tubingen, Germany..
    Seydel, Tilo
    Inst Max von Laue Paul Langevin, 71 Ave Martyrs, F-38042 Grenoble, France..
    Temperature and salt controlled tuning of protein clusters2021In: Soft Matter, ISSN 1744-683X, E-ISSN 1744-6848, no 37, p. 8506-8516Article in journal (Refereed)
    Abstract [en]

    The formation of molecular assemblies in protein solutions is of strong interest both from a fundamental viewpoint and for biomedical applications. While ordered and desired protein assemblies are indispensable for some biological functions, undesired protein condensation can induce serious diseases. As a common cofactor, the presence of salt ions is essential for some biological processes involving proteins, and in aqueous suspensions of proteins can also give rise to complex phase diagrams including homogeneous solutions, large aggregates, and dissolution regimes. Here, we systematically study the cluster formation approaching the phase separation in aqueous solutions of the globular protein BSA as a function of temperature (T), the protein concentration (c(p)) and the concentrations of the trivalent salts YCl3 and LaCl3 (c(s)). As an important complement to structural, i.e. time-averaged, techniques we employ a dynamical technique that can detect clusters even when they are transient on the order of a few nanoseconds. By employing incoherent neutron spectroscopy, we unambiguously determine the short-time self-diffusion of the protein clusters depending on c(p), c(s) and T. We determine the cluster size in terms of effective hydrodynamic radii as manifested by the cluster center-of-mass diffusion coefficients D. For both salts, we find a simple functional form D(c(p), c(s), T) in the parameter range explored. The calculated inter-particle attraction strength, determined from the microscopic and short-time diffusive properties of the samples, increases with salt concentration and temperature in the regime investigated and can be linked to the macroscopic behavior of the samples.

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  • 41.
    Beck, Christian
    et al.
    Institut für Angewandte Physik, Universität Tübingen, Auf der Morgenstelle 10, 72076 Tübingen, Germany; Institut Max von Laue─Paul Langevin (ILL), CS 20156, F-38042 Grenoble Cedex 9, France.
    Grimaldo, Marco
    Institut Max von Laue─Paul Langevin (ILL), CS 20156, F-38042 Grenoble Cedex 9, France.
    Lopez, Hender
    School of Physics and Optometric & Clinical Sciences, Technological University Dublin, D07 XT95 Grangegorman, Ireland.
    Da Vela, Stefano
    Institut für Angewandte Physik, Universität Tübingen, Auf der Morgenstelle 10, 72076 Tübingen, Germany.
    Sohmen, Benedikt
    Institut für Angewandte Physik, Universität Tübingen, 72076 Tübingen, Germany.
    Zhang, Fajun
    Institut für Angewandte Physik, Universität Tübingen, Auf der Morgenstelle 10, 72076 Tübingen, Germany.
    Oettel, Martin
    Institut für Angewandte Physik, Universität Tübingen, Auf der Morgenstelle 10, 72076 Tübingen, Germany.
    Barrat, Jean-Louis
    Univ. Grenoble Alpes, CNRS, LiPhy, 38000 Grenoble, France.
    Roosen-Runge, Felix
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Schreiber, Frank
    Institut für Angewandte Physik, Universität Tübingen, Auf der Morgenstelle 10, 72076 Tübingen, Germany.
    Seydel, Tilo
    Institut Max von Laue─Paul Langevin (ILL), CS 20156, F-38042 Grenoble Cedex 9, France.
    Short-Time Transport Properties of Bidisperse Suspensions of Immunoglobulins and Serum Albumins Consistent with a Colloid Physics Picture.2022In: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207, Vol. 126, no 38, p. 7400-7408Article in journal (Refereed)
    Abstract [en]

    The crowded environment of biological systems such as the interior of living cells is occupied by macromolecules with a broad size distribution. This situation of polydispersity might influence the dependence of the diffusive dynamics of a given tracer macromolecule in a monodisperse solution on its hydrodynamic size and on the volume fraction. The resulting size dependence of diffusive transport crucially influences the function of a living cell. Here, we investigate a simplified model system consisting of two constituents in aqueous solution, namely, of the proteins bovine serum albumin (BSA) and bovine polyclonal gamma-globulin (Ig), systematically depending on the total volume fraction and ratio of these constituents. From high-resolution quasi-elastic neutron spectroscopy, the separate apparent short-time diffusion coefficients for BSA and Ig in the mixture are extracted, which show substantial deviations from the diffusion coefficients measured in monodisperse solutions at the same total volume fraction. These deviations can be modeled quantitatively using results from the short-time rotational and translational diffusion in a two-component hard sphere system with two distinct, effective hydrodynamic radii. Thus, we find that a simple colloid picture well describes short-time diffusion in binary mixtures as a function of the mixing ratio and the total volume fraction. Notably, the self-diffusion of the smaller protein BSA in the mixture is faster than the diffusion in a pure BSA solution, whereas the self-diffusion of Ig in the mixture is slower than in the pure Ig solution.

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  • 42.
    Beck, Christian
    et al.
    Institut für Angewandte Physik, Universität Tübingen, Auf der Morgenstelle 10, 72076 Tübingen, Germany; Institut Max von Laue Paul Langevin (ILL), CS 20156, F-38042 Grenoble Cedex 9, France..
    Pounot, Kevin
    Institut für Angewandte Physik, Universität Tübingen, Auf der Morgenstelle 10, 72076 Tübingen, Germany; Institut Max von Laue Paul Langevin (ILL), CS 20156, F-38042 Grenoble Cedex 9, France..
    Mosca, Ilaria
    Institut für Angewandte Physik, Universität Tübingen, Auf der Morgenstelle 10, 72076 Tübingen, Germany; Institut Max von Laue Paul Langevin (ILL), CS 20156, F-38042 Grenoble Cedex 9, France..
    H Jalarvo, Niina
    Jülich Centre for Neutron Science (JCNS), Forschungszentrum Jülich GmbH, D-52425 Jülich, Germany; Chemical and Engineering Materials Division, Neutron Sciences Directorate, and JCNS Outstation at the Spallation Neutron Source (SNS), Oak Ridge National Laboratory, P.O. Box 2008, Oak Ridge, Tennessee 37831, USA.
    Roosen-Runge, Felix
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Schreiber, Frank
    Institut für Angewandte Physik, Universität Tübingen, Auf der Morgenstelle 10, 72076 Tübingen, Germany.
    Seydel, Tilo
    Institut Max von Laue Paul Langevin (ILL), CS 20156, F-38042 Grenoble Cedex 9, France.
    Notes on Fitting and Analysis Frameworks for QENS Spectra of (Soft) Colloid Suspensions2022In: EPJ Web of Conferences, E-ISSN 2100-014X, Vol. 272, p. 01004-01004Article in journal (Refereed)
    Abstract [en]

    With continuously improving signal-to-noise ratios, a statistically sound analysis of quasi-elasticneutron scattering (QENS) spectra requires to fit increasingly complex models which poses several challenges.Simultaneous fits of the spectra for all recorded values of the momentum transfer become a standard approach.Spectrometers at spallation sources can have a complicated non-Gaussian resolution function which has to bedescribed most accurately. At the same time, to speed up the fitting, an analytical convolution with this resolutionfunction is of interest. Here, we discuss basic concepts to efficient approaches for fits of QENS spectra basedon standard MATLAB and Python fit algorithms. We illustrate the fits with example data from IN16B, BASIS,and BATS.

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  • 43. Bergdahl, Gizem Ertürk
    et al.
    Akhoundian, Maedeh
    Lueg-Althoff, Kyra
    Yeung, Sing Yee
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Hedström, Martin
    Schrader, Thomas
    Matiasson, Bo
    Sellergren, Börje
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Shinde, Sudhirkumar
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Bisphosphonate Ligand Mediated Ultrasensitive Capacitive Protein Sensor: Complementary Match of Supramolecular and Dynamic Chemistry2019In: New Journal of Chemistry, ISSN 1144-0546, E-ISSN 1369-9261, Vol. 43, no 2, p. 847-852Article in journal (Refereed)
    Abstract [en]

    Modern healthcare demands rapid and accurate detection of proteins/enzymes at the ultratrace level. Herein we present a molecularly imprinted capacitive sensor for Trypsin, developed by microcontact imprinting. High affinity and selectivity was achieved by doping the prepolymerization mixture with a stoichiometric amount of methacrylamide-based bisphosphonate (BP) monomer. Taking advantage of the strong interaction of bisphosphonate with lysine/arginine residues on the surface of Trypsin, we have constructed a powerful polymeric sensor. The BP based sensor has the ability to recognize trypsin over other arginine-rich proteins, even in high ionic strength buffers with a sub-picomolar detection limit (pM). We believe that the combination of supramolecular chemistry, molecular imprinting and advanced instrumentation has a potential for future drug development and diagnostics that extends beyond biomolecular recognition.

  • 44.
    Bertelsen, Sissel Asser
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV).
    Hormonal and stress-related effects in men aged 25-35, from daily intake of Lactobacillus probiotic dietary supplements2021Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Background: There is a bidirectional communication system between the gut-microbiota and the brain. Probiotics are live microorganisms that should have health benefits on the host. Modulations of the gut-microbiota using probiotics to target inflammation, stress and depression have shown promising results in rodent studies and are now to be proven in human subjects. 

    Method: 20 male participants aged 25-35, were aliquoted into three groups. All groups consumed placebo tablets for two weeks. For additionally six weeks, two of the groups were administered different commercially available probiotic tablets containing Lactobacillus reuteri and the last group continued the placebo tablets. Venous blood samples and a questionnaire about general wellbeing were collected at baseline, after two weeks, and at the end of the eight weeks study. Cortisol was analysed by electrochemiluminescence immunoassay (ECLIA). An enzymatic colorimetric test was used to determine glucose concentrations (GOD-PAP). Soluble urokinase plasminogen activator receptor (suPAR) concentrations determined with ELISA. Oxidative stress was carried out using Free Oxygen Radicals Testing (FORT).

    Results: For all biomarkers no significant differences were found (p>0.05). For the questionnaires, a significant difference was found in the placebo group. Here, a general wellbeing improved throughout the study. 

    Conclusion: The present study was affected by the COVID-19 pandemic, which led to a decrease in number of participants, change of environment and sampling at different times of the day which could have had an impact on diurnal variation. Although none of the biomarkers showed statistically significant results, further investigations of Lactobacillus reuteri in human subjects are necessary. In addition, this study highlights the importance of developing a robust model for translating findings in rodent studies to healthy human subjects.

  • 45.
    Beyer, Sarah
    et al.
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV).
    Kimani, Martha
    Chemical and Optical Sensing Division, Bundesanstalt für Materialforschung und -prüfung (BAM), Richard-Willstätter Straße 11, 12489 Berlin, Germany.
    Zhang, Yuecheng
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Verhassel, Alejandra
    Institute of Biomedicine, University of Turku, 20520 Turku, Finland; FICAN West Cancer Centre, Turku University Hospital, 20520 Turku, Finland.
    Sternbæk, Louise
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces. Phase Holographic Imaging AB, SE-223 63 Lund, Sweden.
    Wang, Tianyan
    Department of Molecular Biology, Umeå University, SE-901 87 Umeå, Sweden.
    Persson, Jenny L.
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces. Department of Molecular Biology, Umeå University, SE-901 87 Umeå, Sweden.
    Härkönen, Pirkko
    Institute of Biomedicine, University of Turku, 20520 Turku, Finland; FICAN West Cancer Centre, Turku University Hospital, 20520 Turku, Finland.
    Johansson, Emil
    Department of Chemistry, Umeå University, SE-901 87 Umeå, Sweden; Umeå Centre for Microbial Research, Umeå University, SE-901 87 Umeå, Sweden.
    Caraballo, Remi
    Department of Chemistry, Umeå University, SE-901 87 Umeå, Sweden; Umeå Centre for Microbial Research, Umeå University, SE-901 87 Umeå, Sweden.
    Elofsson, Mikael
    Department of Chemistry, Umeå University, SE-901 87 Umeå, Sweden; Umeå Centre for Microbial Research, Umeå University, SE-901 87 Umeå, Sweden.
    Gawlitza, Kornelia
    Chemical and Optical Sensing Division, Bundesanstalt für Materialforschung und -prüfung (BAM), Richard-Willstätter Straße 11, 12489 Berlin, Germany.
    Rurack, Knut
    Chemical and Optical Sensing Division, Bundesanstalt für Materialforschung und -prüfung (BAM), Richard-Willstätter Straße 11, 12489 Berlin, Germany.
    Ohlsson, Lars
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    El-Schich, Zahra
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Gjörloff Wingren, Anette
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Stollenwerk, Maria M
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Fluorescent Molecularly Imprinted Polymer Layers against Sialic Acid on Silica-Coated Polystyrene Cores-Assessment of the Binding Behavior to Cancer Cells.2022In: Cancers, ISSN 2072-6694, Vol. 14, no 8, article id 1875Article in journal (Refereed)
    Abstract [en]

    Sialic acid (SA) is a monosaccharide usually linked to the terminus of glycan chains on the cell surface. It plays a crucial role in many biological processes, and hypersialylation is a common feature in cancer. Lectins are widely used to analyze the cell surface expression of SA. However, these protein molecules are usually expensive and easily denatured, which calls for the development of alternative glycan-specific receptors and cell imaging technologies. In this study, SA-imprinted fluorescent core-shell molecularly imprinted polymer particles (SA-MIPs) were employed to recognize SA on the cell surface of cancer cell lines. The SA-MIPs improved suspensibility and scattering properties compared with previously used core-shell SA-MIPs. Although SA-imprinting was performed using SA without preference for the α2,3- and α2,6-SA forms, we screened the cancer cell lines analyzed using the lectins Maackia Amurensis Lectin I (MAL I, α2,3-SA) and Sambucus Nigra Lectin (SNA, α2,6-SA). Our results show that the selected cancer cell lines in this study presented a varied binding behavior with the SA-MIPs. The binding pattern of the lectins was also demonstrated. Moreover, two different pentavalent SA conjugates were used to inhibit the binding of the SA-MIPs to breast, skin, and lung cancer cell lines, demonstrating the specificity of the SA-MIPs in both flow cytometry and confocal fluorescence microscopy. We concluded that the synthesized SA-MIPs might be a powerful future tool in the diagnostic analysis of various cancer cells.

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  • 46.
    Björk, Emmielina
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV).
    Skillnader i bilirubinkoncentrationer vid diagnostik av neonatal hyperbilirubinemi: En metodjämförelse mellan Siemens Atellica och blodgasinstrument2021Independent thesis Basic level (university diploma), 180 HE creditsStudent thesis
  • 47.
    Björklund, Sebastian
    et al.
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Kocherbitov, Vitaly
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Water vapor sorption-desorption hysteresis in glassy surface films of mucins investigated by humidity scanning QCM-D2019In: Journal of Colloid and Interface Science, ISSN 0021-9797, E-ISSN 1095-7103, Vol. 545, p. 289-300Article in journal (Refereed)
    Abstract [en]

    Hypothesis: Investigating the origin of water sorption-desorption hysteresis in glassy biopolymers is important for understanding the properties of biological barriers, such as the mucus epithelium. In general, hysteresis is a result of a complex interplay between diffusion of water and relaxation of the polymer matrix. Our hypothesis is that for thin films, typical for quartz crystal microbalance with dissipation monitoring (QCM-D) experiments performed in gas phase with defined relative humidity, the diffusion limitation is eliminated and hysteresis results only from relaxation of the polymer matrix. Experiments: We use a recently developed humidity scanning (HS) QCM-D method to obtain water sorption-desorption isotherms of mucin films under controlled conditions where water diffusion is not the limiting factor, neither in the vapor phase nor in the glassy mucin film. Findings: We present new results on the water sorption-desorption behavior of glassy mucin films with nanoscale thicknesses. Despite the fact that water diffusion is not the limiting factor, the sorption-desorption branches show clear hysteresis effects that are similar to those typically observed in bulk samples. The hydration-induced glass transition, resolved from monitoring the rheological behavior of the films, is shown to be in excellent agreement with the onset of the sorption-desorption hysteresis. We suggest that the hysteresis effect is related to a difference in dynamical and structural properties of the glassy materials depending on the hydration history of the films.

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  • 48. Bobrowski, Tim
    et al.
    Arribas, Elena Gonzalez
    Ludwig, Roland
    Toscano, Miguel D.
    Shleev, Sergey
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV).
    Schuhmann, Wolfgang
    Rechargeable, flexible and mediator-free biosupercapacitor based on transparent ITO nanoparticle modified electrodes acting in mu M glucose containing buffers2018In: Biosensors & bioelectronics, ISSN 0956-5663, E-ISSN 1873-4235, Vol. 101, p. 84-89Article in journal (Refereed)
    Abstract [en]

    We present a transparent and flexible self-charging biosupercapacitor based on an optimised mediator- and membrane-free enzymatic glucose/oxygen biofuel cell. Indium tin oxide (ITO) nanoparticles were spray-coated on transparent conducting ITO supports resulting in a flocculent, porous and nanostructured electrode surface. By this, high capacitive currents caused by an increased electrochemical double layer as well as enhanced catalytic currents due to a higher number of immobilised enzyme molecules were obtained. After a chemical pretreatment with a silane derivative, bilirubin oxidase from Myrothecium verrucaria was immobilized onto the ITO nanostructured electrode surface under formation of a biocathode, while bioanodes were obtained by either immobilisation of cellobiose dehydrogenase from Corynascus thermophilus or soluble PQQ-dependent glucose dehydrogenase from Acinetobacter calcoaceticus. The latter showed a lower apparent K-M value for glucose conversion and higher catalytic currents at mu M glucose concentrations. Applying the optimised device as a biosupercapacitor in a discontinuous charge/discharge mode led to a generated power output of 0.030 mW/cm(2) at 50 mu M glucose, simulating the glucose concentration in human tears. This represents an enhancement by a factor of 350 compared to the power density obtained from the continuously operating biofuel cell with a maximum power output of 0.086 mu W/cm(2) under the same conditions. After 17 h of charging/discharging cycles a remarkable current enhancement was still measured. The entire device was transferred to flexible materials and applied for powering a flexible display showing its potential applicability as an intermittent power source in smart contact lenses.

  • 49.
    Bogdanova, Ekaterina
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV).
    Effect of water on the glass transition and properties of solid-state pharmaceutical formulations2022Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The aim of this thesis was to increase our knowledge of the glassy state and the glass transition phenomenon and to evaluate the effect of water on the glassy state. To accomplish this, investigations were focused on the amorphous sucrose-water (paper I, II, III), trehalose-water (paper I), maltodextrin-water (paper I), and lysozyme-sucrose-water (paper IV) systems.

    We studied temperature-induced and isothermal glass transition (I, II, III, IV), as well as the impact of water on the activation energy of the relaxation process (II). It has been shown that water undergoes glass transition with disaccharides, but in polysaccharides water dynamics is uncoupled from the polymer matrix. This results in differences in the water diffusion coefficient: water moves several orders of magnitude faster in the polymers than in disaccharides (I). Water reduces the activation energy of the relaxation process in the sucrose-water system (II). Attenuated water diffusion at sub-zero temperatures leads to a delay in water crystallization/melting in the sucrose-water system, which does not happen in a polysaccharide - water system (III). 

    The Tg of the lysozyme-sucrose system increases with increasing lysozyme concentration, i.e., the DCp of the mixtures does not follow the prediction based on the properties of the pure components. Consequently, lysozyme does not modulate the glass transition of the sucrose matrix and the increase of the Tg of the mixtures is a result of the confinement of amorphous sucrose in the space between lysozyme molecules. The amorphous structure and unfolding of lysozyme in the presence of sucrose was investigated by DSC and SAXS. These data revealed an increase of the protein-protein distance upon addition of sucrose and upon heating, as a result of lysozyme unfolding (IV).

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  • 50.
    Bogdanova, Ekaterina
    et al.
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces. NextBioForm Competence Centre, Stockholm, Sweden.
    Fureby, Anna Millqvist
    RISE Research Institutes of Sweden, Stockholm, Sweden; NextBioForm Competence Centre, Stockholm, Sweden.
    Kocherbitov, Vitaly
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces. NextBioForm Competence Centre, Stockholm, Sweden.
    Influence of cooling rate on ice crystallization and melting in sucrose-water system2022In: Journal of Pharmaceutical Sciences, ISSN 0022-3549, E-ISSN 1520-6017, Vol. 111, no 7, p. 2030-2037, article id S0022-3549(22)00035-1Article in journal (Refereed)
    Abstract [en]

    The ice crystallization and melting in systems where the equilibrium state is difficult to reach is one of the growing areas in pharmaceutical freeze-drying research. The quality of the final freeze-dried product depends on the parameters of the cooling step, which affect the ice nucleation and growth. In this paper, we present a DSC study of ice crystallization and melting in a sucrose-water system. Using two different types of thermal cycles, we examine the influence of cooling and heating rates on the thermal behavior of sucrose-water solutions with water contents between 50 and 100 wt%.

    The DSC results show that low cooling rates provide crystallization at higher temperatures and lead to lower amount of nonfreezing water. Consequently, the glass transition and ice melting properties observed upon heating depend on the cooling conditions in the preceding step. Based on the experimental results, we investigate the reasons for the existence of the two steps on DSC heating curves in sucrose-water systems: the glass transition step and the onset of ice melting. We show that diffusion of water can be the limiting factor for ice growth and melting in the sucrose-water system when the amorphous phase is in a liquid state. In particular, when the diffusion coefficient drops below 10−14 m2/sec, the ice crystals growth or melting becomes strongly suppressed even above the glass transition temperature. Understanding the diffusion limitations in the sucrose-water system can be used for the optimization of the freeze-drying protocols for proteins and probiotics.

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