| 1. |
- Andrén, Oliver C. J., et al.
(författare)
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Antibiotic-Free Cationic Dendritic Hydrogels as Surgical-Site-Infection-Inhibiting Coatings
- 2019
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Ingår i: Advanced Healthcare Materials. - : Wiley. - 2192-2640 .- 2192-2659.
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Tidskriftsartikel (refereegranskat)abstract
- A non-toxic hydrolytically fast-degradable antibacterial hydrogel is herein presented to preemptively treat surgical site infections during the first crucial 24 h period without relying on conventional antibiotics. The approach capitalizes on a two-component system that form antibacterial hydrogels within 1 min and consist of i) an amine functional linear-dendritic hybrid based on linear poly(ethylene glycol) and dendritic 2,2-bis(hydroxymethyl)propionic acid, and ii) a di-N-hydroxysuccinimide functional poly(ethylene glycol) cross-linker. Broad spectrum antibacterial effect is achieved by multivalent representation of catatonically charged β-alanine on the dendritic periphery of the linear dendritic component. The hydrogels can be applied readily in an in vivo setting using a two-component syringe delivery system and the mechanical properties can accurately be tuned in the range equivalent to fat tissue and cartilage (G' = 0.5-8 kPa). The antibacterial effect is demonstrated both in vitro toward a range of relevant bacterial strains and in an in vivo mouse model of surgical site infection.
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| 2. |
- Andrén, Oliver, 1987-
(författare)
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Exploring bis-MPA Based Dendritic Structures in Biomedicine
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In the last decades there has been significant advances in polymer chemistry. New coupling chemistries, polymerization techniques and accelerated approaches enable researches to push the limits of structural control. One outcome of such development is the field of linear dendritic (LD) and dendritic linear dendritic (DLD) hybrid materials, drawing benefit from both linear and dendritic material properties. LD-hybrids with their high density of functional groups and customizability offer much promise for use in biological applications. This thesis deals with the potential use of sophisticated LD-hybrid materials focusing on the field of biomedicine and biomedical applications. The linear component is manly poly(ethylene glycol) (PEG) while the dendritic part consists of 2,2-Bis(hydroxymethyl)propionic (bis-MPA) building blocks.Initially a family of unsymmetrical LD amphiphiles was constructed and evaluated as carriers for drug delivery of chemotherapeutics. Through self-assembly driven by their amphiphilic nature nanocarriers (NC) were constructed with a hydrophobic core and hydrophilic corona. NC were found to enhance the effect of conventional therapeutics by relocating the drug from just the nucleus to the mitochondria among other organelles. Their versatile nature allowed for dual loading of a combination of chemotherapeutics and circumvented the resistance mechanism of resistant cancer cells.Dendrimers containing a disulfide in the backbone were also constructed, these enabled the selective fragmentation of the dendrimer by reduction to small molecular thiols. The fragments were also envisioned to disrupt the delicate thiol-disulfide balance intracellularly causing reactive oxygen species (ROS). Dendrimers were elaborated by conjugation to linear PEG creating LD-hybrids and evaluated in vitro and where found to cause high degree of ROS in cancerous cells.Thiol functional polymers were created, including linear polymers, dendrimers and DLD-hybrids. The DLD-hybrids were utilized as hydrogels through two efficient chemistries relying on the versatility of the thiol. By varying the generation of the LD-hybrid and the cross-linking chemistry the modulus could be tuned.Amine functional LD-hybrids were constructed utilizing the amino acid alanine. Scaffolds were utilized as antimicrobial hydrogels for prophylaxis during surgical intervention. LD-hybrids were initially evaluated in planktonic mode, and were found to have broad spectrum effect and were highly effective against resistant bacteria. Gelation was studied relying on N-hydroxysuccinimide (NHS) esters as cross-linkers, enabling instantaneous gelation under biological conditions. The gels moduli could be varied to match various tissues including stromal and muscle. The effect of the antimicrobial coatings was investigated with promising results both in vitro and in vivo.Finally, more industrially applicable hyperbranched LD-hybrids were constructed. The synthetic strategy relied on a convenient pseudo one-pot approach using Fisher esterification along with sequential monomer addition. Materials were found to have properties and characteristics similar to those of perfect dendritic LD-hybrids. And the scaffolds were evaluated in a range of applications such as hydrogels and isopourous films with promising results.
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| 3. |
- Brådvik, Louise, et al.
(författare)
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Clinical prediction of suicide and undetermined death : A pseudo-prospective clinical and medico-legal study of substance abusers
- 2017
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Ingår i: International Journal of Environmental Research and Public Health. - : MDPI AG. - 1661-7827 .- 1660-4601. ; 14:3
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Tidskriftsartikel (refereegranskat)abstract
- This study examines aspects of prediction of suicide and death of undetermined intent. We investigated all consecutive, autopsied patients between 1993 and 1997 who had been in contact with the Addiction Centre in Malmö from 1968 onwards. The staff was asked, shortly after autopsy but before they knew of the manner of death, if they thought the patient had committed suicide. The case records were blindly evaluated, and toxicological autopsy findings for alcohol in blood samples investigated. The specificity of prediction was 83% and significantly more often correct than the sensitivity, which was only 45% for suicide and for suicide/death of undetermined intent (93% versus 39%). Suicidal communication was more often considered non-serious before death of undetermined intent than before suicide. The former could be predicted by ideation but not by suicide attempt reported in case records, unlike suicide, which was predicted by both. The undetermined group also showed higher levels of alcohol in the blood at autopsy. We concluded that more serious clinical investigation of suicidal feelings, which may be hidden and not taken seriously, and treatment of alcohol use disorders with active follow-up appear urgent in the efforts to prevent suicide.
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| 4. |
- Brådvik, Louise, et al.
(författare)
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From Substance Use Disorders in Life to Autopsy Findings : A Combined Case-Record and Medico-Legal Study
- 2019
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Ingår i: International Journal of Environmental Research and Public Health. - : MDPI AG. - 1660-4601. ; 16:5
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Several studies have shown mortality and suicide risk in substance use disorders, and autopsy findings with respect to the used substances. However, there seems to be a gap in the knowledge about substances misused in life and at death at the within-person level. Methods: All consecutive, autopsied patients during 1993 to 1997, who had been in contact with the Addiction Centre in Malmö from 1968, were investigated (365 subjects). Drug misuse in the long-term course noted in case records was related to autopsy findings. Self-inflicted death (suicide/undetermined suicide/accidental overdose) was compared with natural death. Results: Benzodiazepine misuse was associated with a high risk of autopsy findings of the substance in suicide and death of undetermined intent. It was also associated among non-misusers, but less so. An alcohol level above 1‰ was found more often in self-inflicted death. Prescription opioids at autopsy were mainly found in self-inflicted death among non-misusers. Heroin misuse was related to overdose. Central nervous system stimulants (CNS-S) and cannabis were rarely found in self-inflicted death among previous misusers. The overlap between depression in life and antidepressants at death was low. Conclusions: Benzodiazepines and alcohol seem to disinhibit suicidal tendencies. Suicide risk among users of cannabis and CNS-S may be related to other risk factors than acute use. Implications for suicide prevention are discussed.
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| 5. |
- von Vogelsang, A. -C, et al.
(författare)
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Effect of mobile laminar airflow units on airborne bacterial contamination during neurosurgical procedures
- 2018
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Ingår i: Journal of Hospital Infection. - : Elsevier BV. - 0195-6701 .- 1532-2939. ; 99:3, s. 271-278
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Tidskriftsartikel (refereegranskat)abstract
- Background: Surgical site infections (SSIs) after neurosurgery are potentially life-threatening and entail great costs. SSIs may occur from airborne bacteria in the operating room, and ultraclean air is desired during infection-prone cleaning procedures. Door openings and the number of persons present in the operating room affect the air quality. Mobile laminar airflow (MLAF) units, with horizontal laminar airflow, have previously been shown to reduce airborne bacterial contamination. Aim: To assess the effect of MLAF units on airborne bacterial contamination during neurosurgical procedures. Methods: In a quasi-experimental design, bacteria-carrying particles (colony-forming units: cfu) during neurosurgical procedures were measured with active air-sampling in operating rooms with conventional turbulent ventilation, and with additional MLAF units. The MLAF units were shifted between operating rooms monthly. Colony-forming unit count and bacterial species detection were conducted after incubation. Data was collected for a period of 18 months. Findings: A total of 233 samples were collected during 45 neurosurgical procedures. The use of MLAF units significantly reduced the numbers of cfu in the surgical site area (P < 0.001) and above the instrument table (P < 0.001). Logistic regression showed that the only significant predictor affecting cfu count was the use of MLAF units (odds ratio: 41.6; 95% confidence interval: 11.3–152.8; P < 0.001). The most frequently detected bacteria were coagulase-negative staphylococci. Conclusion: MLAF successfully reduces cfu during neurosurgery to ultraclean air levels. MLAF units are valuable when the main operating room ventilation system is unable to produce ultraclean air in infection-prone clean neurosurgery.
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