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1.	Lindstedt Ingemansson, Sandra, et al. (author) Myocardial topical negative pressure increases blood flow in hypothermic, ischemic myocardium. 2008 In: Scandinavian Cardiovascular Journal. - : Informa UK Limited. - 1651-2006 .- 1401-7431. ; 42, s. 345-353 Journal article (peer-reviewed)abstract Objectives. Hypothermia protects the myocardium from oxidative injury during ischemic stress and reperfusion. We have previously shown that topical negative pressure (TNP) of -50 mmHg significantly increases microvascular blood flow in the underlying myocardium in normal, ischemic, and reperfused porcine myocardium. The present study was designed to elucidate the effect of TNP between -50 mmHg and -150 mmHg on microvascular blood flow in ischemic myocardium during hypothermia. Design. The microvascular blood flow in the myocardium was recorded, in seven pigs, using laser Doppler velocimetry. Analyses were performed in the epicardium and in the myocardium, after 40 minutes of occlusion of the LAD followed by cooling to 31 degrees C. Results. A TNP of -50 mmHg applied to the epicardium, from 23.3+/-3.8 PU to 104.2+/-31.3 PU (p <0.05), and in the myocardium, from 35.0+/-7.2 PU to 74.2+/-21.8 PU (p <0.05). Conclusions. Only a TNP level of -50 mmHg significantly increased the microvascular blood flow in both the epicardium and in the myocardium during hypothermia.
2.	Ståhle, Alexander, et al. (author) Designguide för Smarta gator 2022 Book (other academic/artistic)abstract Designguiden för smarta gator konkretiserar hur de fyra megatrenderna urbanisering, digitalisering, samhällsförändringar och miljöförändringar leder till nya krav och utformningsprinciper för framtidens gator. Guiden är tänkt att fungera som en inspiration och ett underlag för att förnya svensk gatupolicy på nationell, regional och kommunal nivå.Guiden innehåller utöver en inledning följande kapitel: en historisk tillbakablick (gatans utveckling), gatans användning, gatans delar, gatans design, designprocessen, guidens genomförande.
3.	Abolhalaj, Milad, et al. (author) Profiling dendritic cell subsets in head and neck squamous cell tonsillar cancer and benign tonsils. 2018 In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8:8030 Journal article (peer-reviewed)abstract Dendritic cells (DCs) have a key role in orchestrating immune responses and are considered important targets for immunotherapy against cancer. In order to develop effective cancer vaccines, detailed knowledge of the micromilieu in cancer lesions is warranted. In this study, flow cytometry and human transcriptome arrays were used to characterize subsets of DCs in head and neck squamous cell tonsillar cancer and compare them to their counterparts in benign tonsils to evaluate subset-selective biomarkers associated with tonsillar cancer. We describe, for the first time, four subsets of DCs in tonsillar cancer: CD123+ plasmacytoid DCs (pDC), CD1c+, CD141+, and CD1c-CD141- myeloid DCs (mDC). An increased frequency of DCs and an elevated mDC/pDC ratio were shown in malignant compared to benign tonsillar tissue. The microarray data demonstrates characteristics specific for tonsil cancer DC subsets, including expression of immunosuppressive molecules and lower expression levels of genes involved in development of effector immune responses in DCs in malignant tonsillar tissue, compared to their counterparts in benign tonsillar tissue. Finally, we present target candidates selectively expressed by different DC subsets in malignant tonsils and confirm expression of CD206/MRC1 and CD207/Langerin on CD1c+ DCs at protein level. This study descibes DC characteristics in the context of head and neck cancer and add valuable steps towards future DC-based therapies against tonsillar cancer.
4.	Albrekt, Ann-Sofie, et al. (author) Skin sensitizers differentially regulate signaling pathways in MUTZ-3 cells in relation to their individual potency 2014 In: Bmc Pharmacology & Toxicology. - : Springer Science and Business Media LLC. - 1471-2210 .- 2050-6511. ; 15 Journal article (peer-reviewed)abstract Background: Due to the recent European legislations posing a ban of animal tests for safety assessment within the cosmetic industry, development of in vitro alternatives for assessment of skin sensitization is highly prioritized. To date, proposed in vitro assays are mainly based on single biomarkers, which so far have not been able to classify and stratify chemicals into subgroups, related to risk or potency. Methods: Recently, we presented the Genomic Allergen Rapid Detection (GARD) assay for assessment of chemical sensitizers. In this paper, we show how the genome wide readout of GARD can be expanded and used to identify differentially regulated pathways relating to individual chemical sensitizers. In this study, we investigated the mechanisms of action of a range of skin sensitizers through pathway identification, pathway classification and transcription factor analysis and related this to the reactive mechanisms and potency of the sensitizing agents. Results: By transcriptional profiling of chemically stimulated MUTZ-3 cells, 33 canonical pathways intimately involved in sensitization to chemical substances were identified. The results showed that metabolic processes, cell cycling and oxidative stress responses are the key events activated during skin sensitization, and that these functions are engaged differently depending on the reactivity mechanisms of the sensitizing agent. Furthermore, the results indicate that the chemical reactivity groups seem to gradually engage more pathways and more molecules in each pathway with increasing sensitizing potency of the chemical used for stimulation. Also, a switch in gene regulation from up to down regulation, with increasing potency, was seen both in genes involved in metabolic functions and cell cycling. These observed pathway patterns were clearly reflected in the regulatory elements identified to drive these processes, where 33 regulatory elements have been proposed for further analysis. Conclusions: This study demonstrates that functional analysis of biomarkers identified from our genomics study of human MUTZ-3 cells can be used to assess sensitizing potency of chemicals in vitro, by the identification of key cellular events, such as metabolic and cell cycling pathways.
5.	Altunbulakli, Can, et al. (author) Targeted spatial proteomic analysis of CD8+ T- and myeloid cells in tonsillar cancer 2023 In: Frontiers in Oncology. - 2234-943X. ; 13 Journal article (peer-reviewed)abstract Background: Tonsillar cancer is caused by high-risk human papillomavirus (HPV), tobacco smoking, and alcohol abuse. Aspects of the patient’s immune response to this disease have arisen as prognostic factors and treatment targets, reflecting differences in the type and protein expression profile of immune cells. Because tonsillar cancers are heterogenous lesions such data need to be spatially resolved. Methods: In this study, we aim to explore inter-patient and intra-tumoral sources of variation in tonsillar cancer using immunofluorescence and targeted spatial proteomics to interrogate a cohort of 105 patients. Furthermore, we assess prognostic factors and elucidate molecular targets. We have used CD8, CD11c, and Pan-cytokeratin (PanCK) to quantify and locate immune cells driving antigen-specific cellular immunity. Guided by immunofluorescence information, we selected 355 CD8+, CD11c+, or PanCK+ areas inside and outside (i.e., stroma) cancer-cell islets, to quantify 43 immune-related proteins using digital spatial profiling. Results: Quantitative analysis of immunofluorescence in combination with clinical data revealed that the abundance of total CD8+ cells and CD8+ cells infiltrating cancer-cell islets, respectively, were associated with higher 5-year disease-free survival and overall survival, independently of HPV-status and clinical stage. Comparison of CD8+ cells inside and outside cancer-cell islets revealed an upregulation of effector CD8+ T-cell and immune checkpoint molecules in the former. Among these, the expression of PD-L1 by CD8+ T-cells was associated with lower all-cause mortality in a univariate proportional hazards model. Similarly, a comparison of tumor boundary and stroma CD11c+ cells showed upregulation of both co-stimulatory and immune checkpoint molecules with proximity to tumor cell islets. Conclusion: Our findings highlight the relevance of analyzing aspects of tumor micro-architecture in the search of prognostic markers and molecular targets for tonsillar cancer. The abundance of intra-tumoral CD8+ T-cells can be considered a positive predictive marker for tonsillar cancer, while the significance of PD-L1 expression by intra-tumoral CD8+ T-cells warrants further evaluation. Location-based differences in CD8+ and CD11c+ cells suggest an immune cell-altering effect on the tumor microenvironment, and grant new insight into which cells that can be targeted by novel therapeutic agents.
6.	Andersson, Hampus, et al. (author) Early Pharmacodynamic Changes Measured Using RNA Sequencing of Peripheral Blood from Patients in a Phase I Study with Mitazalimab, a Potent CD40 Agonistic Monoclonal Antibody 2023 In: Cells. - 2073-4409. ; 12:19 Journal article (peer-reviewed)abstract CD40-targeting therapies can enhance the dendritic cell priming of tumor-specific T cells and repolarize intratumoral macrophages to alleviate the tumoral immunosuppressive environment and remodel the extracellular matrix. Mitazalimab is a potent agonistic CD40 monoclonal IgG1 antibody currently under clinical development. This study used RNA sequencing of blood samples from a subset of patients from a Phase I trial with mitazalimab (NCT02829099) to assess peripheral pharmacodynamic activity. We found that mitazalimab induced transient peripheral transcriptomic alterations (at 600 µg/kg and 900 µg/kg dose administered intravenously), which mainly were attributed to immune activation. In particular, the transcriptomic alterations showed a reduction in effector cells (e.g., CD8+ T cells and natural killer cells) and B cells peripherally with the remaining cells (e.g., dendritic cells, monocytes, B cells, and natural killer cells) showing transcription profiles consistent with activation. Lastly, distinct patient subgroups based on the pattern of transcriptomic alterations could be identified. In summary, the data presented herein reinforce the anticipated mode of action of mitazalimab and support its ongoing clinical development.
7.	Andersson, Hampus, et al. (author) Next-generation CD40 agonists for cancer immunotherapy 2024 In: Expert Opinion on Biological Therapy. - : TAYLOR & FRANCIS LTD. - 1471-2598 .- 1744-7682. ; 24:5, s. 351-363 Research review (peer-reviewed)abstract Introduction: There is a need for new therapies that can enhance response rates and broaden the number of cancer indications where immunotherapies provide clinical benefit. CD40 targeting therapies provide an opportunity to meet this need by promoting priming of tumor-specific T cells and reverting the suppressive tumor microenvironment. This is supported by emerging clinical evidence demonstrating the benefits of immunotherapy with CD40 antibodies in combination with standard of care chemotherapy. Areas covered: This review is focused on the coming wave of next-generation CD40 agonists aiming to improve efficacy and safety, using new approaches and formats beyond monospecific antibodies. Further, the current understanding of the role of different CD40 expressing immune cell populations in the tumor microenvironment is reviewed. Expert opinion: There are multiple promising next-generation approaches beyond monospecific antibodies targeting CD40 in immuno-oncology. Enhancing efficacy is the most important driver for this development, and approaches that maximize the ability of CD40 to both remodel the tumor microenvironment and boost the anti-tumor T cell response provide great opportunities to benefit cancer patients. Enhanced understanding of the role of different CD40 expressing immune cells in the tumor microenvironment may facilitate more efficient clinical development of these compounds.
8.	Andreasson, Jesper, et al. (author) Exhaled phospholipid transfer protein and hepatocyte growth factor receptor in lung adenocarcinoma 2022 In: Respiratory Research. - : Springer Science and Business Media LLC. - 1465-9921 .- 1465-993X. ; 23:1, s. 1-10 Journal article (peer-reviewed)abstract BACKGROUND: Screening decreases mortality among lung cancer patients but is not widely implemented, thus there is an unmet need for an easily accessible non-invasive method to enable early diagnosis. Particles in exhaled air offer a promising such diagnostic tool. We investigated the validity of a particles in exhaled air device (PExA) to measure the particle flow rate (PFR) and collect exhaled breath particles (EBP) to diagnose primary lung adenocarcinoma (LUAD).METHODS: Seventeen patients listed for resection of LUAD stages IA-IIIA and 18 non-cancer surgical control patients were enrolled. EBP were collected before and after surgery for LUAD, and once for controls. Proteomic analysis was carried out using a proximity extension assay technology. Results were validated in both plasma from the same cohort and with microarray data from healthy lung tissue and LUAD tissue in the GSE10072 dataset.RESULTS: Of the 92 proteins analyzed, levels of five proteins in EBP were significantly higher in the LUAD patients compared to controls. Levels of phospholipid transfer protein (PLTP) and hepatocyte growth factor receptor (MET) decreased in LUAD patients after surgery compared to control patients. PFR was significantly higher in the LUAD cohort at all timepoints compared to the control group. MET in plasma correlated significantly with MET in EBP.CONCLUSION: Collection of EBP and measuring of PFR has never been performed in patients with LUAD. In the present study PFR alone could distinguish between LUAD and patients without LUAD. PLTP and MET were identified as potential biomarkers to evaluate successful tumor excision.
9.	Andreasson, Ulrika, et al. (author) The human IgE-encoding transcriptome to assess antibody repertoires and repertoire evolution 2006 In: Journal of Molecular Biology. - : Elsevier BV. - 1089-8638 .- 0022-2836. ; 362:2, s. 212-227 Journal article (peer-reviewed)abstract Upon encounter with antigen, the B lymphocyte population responds by producing a diverse set of antigen-specific antibodies of various isotypes. The vast size of the responding populations makes it very difficult to study clonal evolution and repertoire composition occurring during these processes in humans. Here, we have explored an approach utilizing the H-EPSILON-encoding transcriptome to investigate aspects of repertoire diversity during the season of antigen exposure. We show through sequencing of randomly picked transcripts that the sizes of patients' repertoires are relatively small. This specific aspect of the transcriptome allows us to construct evolutionary trees pinpointing features of somatic hypermutation as it occurs in humans. Despite the small size of the repertoires, they are highly diverse with respect to VDJ gene usage, suggesting that the H-EPSILON-encoding transcriptome is a faithful mimic of other class-switched isotypes. Importantly, it is possible to use antibody library and selection technologies to define the specificity of clonotypes identified by random sequencing. The small size of the H-EPSILON-encoding transcriptome of peripheral blood B cells, the simple identification of clonally related sets of genes in this population, and the power of library and selection technologies ensure that this approach will allow us to investigate antibody evolution in human B lymphocytes of known specificity. As H-EPSILON repertoires show many of the hallmarks of repertoires encoding other isotypes, we suggest that studies of this type will have an impact on our understanding of human antibody evolution even beyond that occurring in the IgE-producing B cell population.
10.	Anesater, Erik, et al. (author) A Rigid Disc for Protection of Exposed Blood Vessels During Negative Pressure Wound Therapy 2013 In: Surgical Innovation. - : SAGE Publications. - 1553-3506 .- 1553-3514. ; 20:1, s. 74-80 Journal article (peer-reviewed)abstract Background. There are increasing reports of serious complications and deaths associated with negative pressure wound therapy (NPWT). Bleeding may occur when NPWT is applied to a wound with exposed blood vessels. Inserting a rigid disc in the wound may protect these structures. The authors examined the effects of rigid discs on wound bed tissue pressure and blood flow through a large blood vessel in the wound bed during NPWT. Methods. Wounds were created over the femoral artery in the groin of 8 pigs. Rigid discs were inserted. Wound bed pressures and arterial blood flow were measured during NPWT. Results. Pressure transduction to the wound bed was similar for control wounds and wounds with discs. Blood flow through the femoral artery decreased in control wounds. When a disc was inserted, the blood flow was restored. Conclusions. NPWT causes hypoperfusion in the wound bed tissue, presumably as a result of mechanical deformation. The insertion of a rigid barrier alleviates this effect and restores blood flow.
11.	Anesäter, Erik, et al. (author) The influence on wound contraction and fluid evacuation of a rigid disc inserted to protect exposed organs during negative pressure wound therapy. 2011 In: International Wound Journal. - 1742-481X. ; 8, s. 393-399 Journal article (peer-reviewed)abstract The use of a rigid disc as a barrier between the wound bed and the wound filler during negative pressure wound therapy (NPWT) has been suggested to prevent damage to exposed organs. However, it is important to determine that the effects of NPWT, such as wound contraction and fluid removal, are maintained during treatment despite the use of a barrier. This study was performed to examine the effect of NPWT on wound contraction and fluid evacuation in the presence of a rigid disc. Peripheral wounds were created on the backs of eight pigs. The wounds were filled with foam, and rigid discs of different designs were inserted between the wound bed and the foam. Wound contraction and fluid evacuation were measured after application of continuous NPWT at -80 mmHg. Wound contraction was similar in the presence and the absence of a rigid disc (84 ± 4% and 83 ± 3%, respectively, compared with baseline). Furthermore, the rigid disc did not affect wound fluid removal compared with ordinary NPWT (e.g. after 120 seconds, 71 ± 4 ml was removed in the presence and 73 ± 3 ml was removed in the absence of a disc). This study shows that a rigid barrier may be placed under the wound filler to protect exposed structures during NPWT without affecting wound contraction and fluid removal, which are two crucial features of NPWT.
12.	Anesäter, Erik, et al. (author) The use of a rigid disc to protect exposed structures in wounds treated with negative pressure wound therapy: Effects on wound bed pressure and microvascular blood flow. 2012 In: Wound Repair and Regeneration. - 1524-475X. ; 20:4, s. 611-616 Journal article (peer-reviewed)abstract There are increasing reports of deaths and serious complications associated with the use of negative pressure wound therapy (NPWT). Bleeding may occur in patients when NPWT is applied to a wound with exposed blood vessels or vascular grafts, possibly due to mechanical deformation and hypoperfusion of the vessel walls. Recent evidence suggests that using a rigid barrier disc to protect underlying tissue can prevent this mechanical deformation. The aim of this study was to examine the effect of rigid discs on the tissue exposed to negative pressure with regard to tissue pressure and microvascular blood flow. Peripheral wounds were created on the backs of eight pigs. The pressure and microvascular blood flow in the wound bed were measured when NPWT was applied. The wound was filled with foam, and rigid discs of different designs were inserted between the wound bed and the foam. The discs were created with or without channels (to accommodate exposed sensitive structures such as blood vessels and nerves), perforations, or a porous dressing that covered the underside of the discs (to facilitate pressure transduction and fluid evacuation). When comparing the results for pressure transduction to the wound bed, no significant differences were found using different discs covered with dressing, whereas pressure transduction was lower with bare discs. Microvascular blood flow in the wound bed decreased by 49 ± 7% when NPWT was applied to control wounds. The reduction in blood flow was less in the presence of a protective disc (e.g., -6 ± 5% for a dressing-covered, perforated disc, p = 0.006). In conclusion, NPWT causes hypoperfusion of superficial tissue in the wound bed. The insertion of a rigid barrier counteracts this effect. The placement of a rigid disc over exposed blood vessels or nerves may protect these structures from rupture and damage.
13.	Ansson, Cu, et al. (author) Blood perfusion in Hewes tarsoconjunctival flaps in pigs measured by laser speckle contrast imaging 2018 In: JPRAS Open. - : Elsevier BV. - 2352-5878. ; 18, s. 98-103 Journal article (peer-reviewed)abstract BackgroundHewes flap is a tarsoconjunctival eyelid flap, based at the lateral canthal tendon, and rotated and stretched to repair lateral defects in the lower eyelid commonly following tumor surgery. The aim of the present study was to monitor perfusion in a Hewes flap during reconstruction, which to the best of our knowledge, has not previously been done.MethodsA Hewes tarsoconjunctival eyelid flap was raised and the effects on blood perfusion of rotating the flaps by 90° and 180°, stretching the flaps with a force of 5 or 10 N, and repeated diathermic coagulation was monitored with laser speckle contrast imaging.ResultsRotating the flaps by 90° did not significantly affect perfusion, while further rotation to 180° reduced blood perfusion to 75% of the baseline value. When the tarsoconjunctival flaps were both rotated 90° and stretched with 5 N, the perfusion was reduced even further, to 63%. A further reduction in perfusion, to 36%, was seen when the higher force of 10 N was applied. Diathermy decreased blood perfusion to 56% after being applied once. Successive applications led to further decreases: 43%, 31%, and 15%, after the second, third and fourth applications.ConclusionsPerfusion in Hewes tarsoconjunctival flaps is affected by both rotation and stretching, but some perfusion is maintained despite these manipulations. Diathermy, however, has detrimental effects and should be avoided.
14.	Ansson, Cu Dybelius, et al. (author) Perfusion in Upper Eyelid Flaps : Effects of Rotation and Stretching Measured With Laser Speckle Contrast Imaging in Patients 2020 In: Ophthalmic Plastic and Reconstructive Surgery. - 1537-2677. ; 36:5, s. 481-484 Journal article (peer-reviewed)abstract PURPOSE: The aim of this study was to investigate how the blood perfusion in human upper eyelid skin flaps is affected by the length of the flap and the degree of stretching and rotation of the flap.METHODS: Twenty-nine upper eyelids were dissected as part of a blepharoplastic procedure in patients. The 1-cm wide proximal end of the flap remains attached, to mimic a random pattern skin flap (hereafter called a "skin flap"). Blood perfusion was measured with laser speckle contrast imaging before and after the flap was stretched with forces of 0.5, 1, and 2 N. The flap was then rotated 90°, and the same tensions were applied.RESULTS: Blood perfusion decreased gradually from the base to the tip of the flap. The flap was only well perfused in the proximal 1 cm (60% at 0.5 cm and 37% at 1.0 cm) and was minimally perfused beyond 2 cm (22% at 2.0 cm). Stretching the nonrotated flaps affected perfusion slightly (decreased to 43% at 0.5 cm). Simply rotating the flaps by 90° had no significant effect on the perfusion. The combination of rotation (90°) and stretching reduced the perfusion to 22% at 2 N, when measured 0.5 cm from the base.CONCLUSIONS: Blood perfusion in upper eyelid skin flaps decreases rapidly with distance from the base of the flap. Rotating and stretching the skin flap reduces blood perfusion even further, leading to minimal perfusion in this kind of flap at distances greater than 1.5 cm from the base.
15.	Askmyr, David, et al. (author) Pattern recognition receptor expression and maturation profile of dendritic cell subtypes in human tonsils and lymph nodes 2021 In: Human Immunology. - : Elsevier BV. - 0198-8859. ; 82:12, s. 976-981 Journal article (peer-reviewed)abstract Dendritic cells (DCs) with capacity of antigen cross-presentation are of key interest for immunotherapy against cancer as they can induce antigen-specific cytotoxic T lymphocyte (CTL) responses. This study describes frequencies of DC subtypes in human tonsils and lymph nodes, and phenotypic aspects that may be targeted by adjuvant measures. From human tonsils and neck lymph nodes, DCs were identified through flow cytometry, and subsets of plasmacytoid DCs (pDCs) and myeloid DCs (mDCs) were investigated. Maturity status was assessed and surface receptors with CTL-promoting potentials were studied. CD123+ pDCs as well as CD1c+, CD141+, and CD1c-CD141- mDCs were detected in tonsils and lymph nodes. Both sites featured a similar presence of DC subsets, with CD123+ pDC being dominant and CD141+ mDCs least frequent. Based on CD80/CD86 expression, all DC subtypes featured a low degree of maturation. Expression of pattern recognition receptors (PRRs) CD206, CD207, DC-SIGN, TLR2, and TLR4, as well as the chemokine receptor XCR1, indicated DC subset-specific receptor profiles. We conclude that tonsils and lymph nodes share common features in terms of DC subset frequency and maturation as well as PRR and XCR1 expression pattern. Our work suggests that both sites may be considered for vaccine deposition in DC-mediated immunotherapy.
16.	Berggren, Johanna, et al. (author) Reperfusion of Free Full-Thickness Skin Grafts in Periocular Reconstructive Surgery Monitored Using Laser Speckle Contrast Imaging 2021 In: Ophthalmic Plastic and Reconstructive Surgery. - 1537-2677. ; 37:4, s. 324-328 Journal article (peer-reviewed)abstract PURPOSE: Free skin grafts are frequently used in reconstructive surgery. However, little is known about the course of reperfusion due to the previous lack of reliable perfusion monitoring techniques. The aim of this study was to use state-of-the-art laser speckle contrast imaging to monitor free skin grafts in the periocular area.METHODS: Seven patients needing surgery due to tumor removal or cicatricial ectropion in the periocular region underwent reconstructive surgery using free skin grafts from either the contralateral upper eyelid or the upper inner arm. The free skin grafts measured 10-30 mm horizontally and 9-30 mm vertically. Blood perfusion was monitored using laser speckle contrast imaging immediately postoperatively (0 weeks) and at follow-up after 1, 3, and 7 weeks.RESULTS: All grafts were reperfused gradually during healing, the median value being 46% in the central part of the graft after 1 week and 79% after 3 weeks. The grafts were completely reperfused after 7 weeks. No difference was observed in the rate of reperfusion between the center and periphery of the grafts (p = not significant). The cosmetic and functional outcome was excellent in all but 1 patient, who developed ectropion that had to be surgically corrected.CONCLUSIONS: Skin grafts in the periorbital area are fully reperfused after 7 weeks. The periocular area is known to be well-vascularized and thus forgiving to reconstructive surgery. Future investigations of the reperfusion of free skin grafts in other parts of the body or in higher-risk populations should be carried out.
17.	Berggren, Johanna, et al. (author) Revascularization After H-plasty Reconstructive Surgery in the Periorbital Region Monitored With Laser Speckle Contrast Imaging 2021 In: Ophthalmic Plastic and Reconstructive Surgery. - 1537-2677. ; 37:3, s. 269-273 Journal article (peer-reviewed)abstract BACKGROUND: H-plasty reconstructive surgery is commonly used to close defects after tumor excision in the periorbital region. Revascularization of the bipedicle skin flaps is essential for healing. However, it has not previously been possible to study this revascularization in humans due to the lack of noninvasive perfusion monitoring techniques. The aim was to monitor perfusion in H-plasty flaps during surgery and during postoperative follow-up, using laser speckle contrast imaging.METHOD: H-plasty, i.e., bipedicle random advancement skin flaps, was used for reconstruction of the eyelids after tumor removal in 7 patients. The median length and width of the skin flaps were 13 mm (range, 8-20 mm) and 10 mm (range, 5-11 mm), respectively. Blood perfusion was measured using laser speckle contrast imaging during surgery and at follow up 1, 3, and 6 weeks postoperatively, to monitor revascularization.RESULTS: Immediately postoperatively, the perfusion in the distal end of the flaps had fallen to 54% (95% CI, 38%-67%). The perfusion then quickly increased during the healing process, being 104% (86%-124%) after 1 week, 115% (94%-129%) after 3 weeks, and 112% (96%-137%) after 6 weeks. There was no clinically observable ischemia or tissue necrosis.CONCLUSIONS: Revascularization of the H-plasty procedure flaps occurs quickly, within a week postoperatively, presumably due to the existing vascular network of the flap pedicle, and was not dependent on significant angiogenesis. This perfusion study confirms the general opinion that H-plasty is a good reconstructive technique, especially in the periorbital region with its rich vascular supply.
18.	Berggren, Johanna, et al. (author) Revascularization of Free Skin Grafts Overlying Modified Hughes Tarsoconjunctival Flaps Monitored Using Laser-Based Techniques 2019 In: Ophthalmic Plastic and Reconstructive Surgery. - 1537-2677. ; 35:4, s. 378-382 Journal article (peer-reviewed)abstract Purpose: It has recently been shown that the flap pedicle does not supply blood to a tarsoconjunctival graft in the modified Hughes procedure in patients. This raises questions concerning the rate of revascularization of the free skin graft commonly used to reconstruct the anterior lamella. The aim of this study was, thus, to monitor the course of revascularization in free skin grafts overlying modified Hughes tarsoconjunctival flaps, using laser-based techniques.Methods: Free skin grafts from the upper eyelid or upper arm in 9 patients were used to cover a tarsoconjunctival flap according to the modified Hughes procedure. Blood perfusion was monitored using laser speckle contrast imaging, and vascular reactivity was studied with laser Doppler velocimetry after heating the tissue to 44°C. Measurements were made at the time of surgery (baseline) and at 1, 3, 8, and 16 weeks postoperatively.Results: The gradual increase in perfusion of the free skin grafts during the healing process indicates revascularization. A slight increase in perfusion was seen already after 1 week. Perfusion reached 50% of the baseline after 3 weeks, and complete restoration of perfusion was seen after 8 weeks. The vascular function monitored with heat-induced hyperemia increased in a similar fashion.Conclusions: Full-thickness skin grafts revascularize within 3 to 8 weeks, despite overlying a tarsoconjunctival flap, which has recently been reported to be avascular. This provides further evidence that it should be possible to repair large eyelid defects using free full-thickness eyelid grafts.
19.	Berggren, Johanna V, et al. (author) Blood Perfusion of Human Upper Eyelid Skin Flaps Is Better in Myocutaneous than in Cutaneous Flaps 2022 In: Ophthalmic Plastic and Reconstructive Surgery. - 1537-2677. ; 38:2, s. 166-169 Journal article (peer-reviewed)abstract BACKGROUND: The aim of this study was to monitor blood perfusion in human upper eyelid skin flaps and examine how the perfusion is affected by the thickness of the flap.METHODS: Twenty upper eyelids were dissected as part of a blepharoplasty procedure in patients. The medial end of the blepharoplasty flap remained attached to mimic a flap design often used in reconstruction in the periocular area, a myocutaneous flap in which the blood supply follows the fibers of the orbicularis muscle and is thus parallel to the long axis of the flap. The muscle was thereafter dissected from the flap to create a cutaneous flap. Blood perfusion in the 2 types of flaps was compared using laser speckle contrast imaging.RESULTS: Blood perfusion decreased gradually from the base to the tip of all the flaps. Perfusion was significantly higher in the myocutaneous flaps than in the cutaneous flaps (p < 0.0004): 69% in the myocutaneous flaps and 43% in the cutaneous flaps, measured 5 mm from the base. Blood perfusion was preserved to a greater extent distally in the myocutaneous flaps (minimum value seen at 25 mm) than in the cutaneous flaps (minimum seen at 11 mm).CONCLUSIONS: Blood perfusion was better preserved in myocutaneous flaps, including both skin and the orbicularis oculi muscle, than in cutaneous flaps. This may be of clinical interest in patients with poor microcirculation in which a long flap is required for reconstructive surgery.
20.	Berggren, Johanna V, et al. (author) Laser Speckle Contrast Imaging of the Blood Perfusion in Glabellar Flaps Used to Repair Medial Canthal Defects 2022 In: Ophthalmic Plastic and Reconstructive Surgery. - 1537-2677. ; 38:3, s. 274-279 Journal article (peer-reviewed)abstract BACKGROUND: The glabellar flap is a common technique for surgical repair after tumor excision in the medial canthal area. However, the outcome may be affected by partial flap necrosis. Little is known about the impact of surgery on blood perfusion and the postoperative course of reperfusion due to the absence of reliable and noninvasive perfusion monitoring techniques. The aim of this study was to use a modern imaging technique to assess blood perfusion in glabellar flaps.METHODS: Glabellar flaps were used to repair medial canthal defects following tumor excision in 7 patients. Blood perfusion was monitored using laser speckle contrast imaging: during surgery, immediately postoperatively (0 weeks), and at follow-up, 1, 3, and 6 weeks after surgery.RESULTS: Perfusion decreased gradually along the length of the flap, and reached a minimum 15 mm from the flap base. Perfusion in the proximal 20 mm of the flap was completely restored after 1 week, while the distal part of the flap was gradually reperfused over 6 weeks. Both the functional and esthetic surgical outcomes were excellent.CONCLUSIONS: The rapid reperfusion of the glabellar flap may be explained by its connection to the vascular network via the flap pedicle. In flaps longer than 20 mm, the distal part can be considered a free skin transplant, and a combination of a glabellar flap and a free skin graft could then be considered.
21.	Berggren, Johanna V, et al. (author) The Effect of Canthotomy on Blood Perfusion During the Repair of Lower Eyelid Defects 2020 In: Ophthalmic Plastic and Reconstructive Surgery. - 1537-2677. ; 36:2, s. 135-138 Journal article (peer-reviewed)abstract PURPOSE: Canthotomy is frequently used to mobilize extra tissue when repairing larger lower eyelid defects. The aim of this study was to explore the effect of canthotomy on blood perfusion and oxygen tension.METHODS: Eight pigs underwent a wedge resection of the lower eyelid and canthotomy (with cantholysis involving the lateral palpebral artery). The wedge resection was performed 8, 6, and 4 mm from the canthotomy. Perfusion and oxygen tension were monitored in the eyelid between the wedge resection and canthotomy using laser Doppler velocimetry and a Clark electrode. Verapamil was administered, and measurements were also performed 12 hours after surgery, to investigate the possible effects of vasospasm RESULTS:: The wedge resection alone did not affect perfusion. Canthotomy led to a reduction in perfusion; being 60% when the length of remaining eyelid was 8 mm, 32% when it was 6 mm, and 24% when it was 4 mm. Similar results were observed for oxygen tension. Vasospasm did not affect the results.CONCLUSIONS: Canthotomy in combination with a wedge resection of the lower eyelid affects blood perfusion. A smaller length of remaining eyelid tissue will have less perfusion. This may not have any implications in cases of direct closure, but may play a role when the eyelid is to provide oxygen and nutrients to avascular grafts.
22.	Bodén, Embla, et al. (author) Quantitative Proteomics Indicate Radical Removal of Non-Small Cell Lung Cancer and Predict Outcome 2022 In: Biomedicines. - : MDPI AG. - 2227-9059. ; 10:11 Journal article (peer-reviewed)abstract Non-small cell lung cancer (NSCLC) is associated with low survival rates, often due to late diagnosis and lack of personalized medicine. Diagnosing and monitoring NSCLC using blood samples has lately gained interest due to its less invasive nature. In the present study, plasma was collected at three timepoints and analyzed using proximity extension assay technology and quantitative real-time polymerase chain reaction in patients with primary NSCLC stages IA–IIIA undergoing surgery. Results were adjusted for patient demographics, tumor, node, metastasis (TNM) stage, and multiple testing. Major histocompatibility (MHC) class 1 polypeptide-related sequence A/B (MIC-A/B) and tumor necrosis factor ligand superfamily member 6 (FASLG) were significantly increased post-surgery, suggesting radical removal of cancerous cells. Levels of hepatocyte growth factor (HGF) initially increased postoperatively but were later lowered, potentially indicating radical removal of malignant cells. The levels of FASLG in patients who later died or had a relapse of NSCLC were lower at all three timepoints compared to surviving patients without relapse, indicating that FASLG may be used as a prognostic biomarker. The biomarkers were confirmed using microarray data. In conclusion, quantitative proteomics could be used for NSCLC identification but may also provide information on radical surgical removal of NSCLC and post-surgical prognosis.
23.	Borgquist, Ola, et al. (author) Undertrycksbehandling av sår: Kunskap om verkningsmekanismer och komplikationer ger nya möjligheter. 2011 In: Läkartidningen. - 0023-7205. ; 108:46, s. 2372-2375 Research review (peer-reviewed)
24.	Broberg, Ellen, et al. (author) Releasing high positive end-expiratory pressure to a low level generates a pronounced increase in particle flow from the airways 2023 In: Intensive Care Medicine Experimental. - : Springer Science and Business Media LLC. - 2197-425X. ; 11:1 Journal article (peer-reviewed)abstract Objectives: Detecting particle flow from the airways by a non-invasive analyzing technique might serve as an additional tool to monitor mechanical ventilation. In the present study, we used a customized particles in exhaled air (PExA) technique, which is an optical particle counter for the monitoring of particle flow in exhaled air. We studied particle flow while increasing and releasing positive end-expiratory pressure (PEEP). The aim of this study was to investigate the impact of different levels of PEEP on particle flow in exhaled air in an experimental setting. We hypothesized that gradually increasing PEEP will reduce the particle flow from the airways and releasing PEEP from a high level to a low level will result in increased particle flow. Methods: Five fully anesthetized domestic pigs received a gradual increase of PEEP from 5 cmH2O to a maximum of 25 cmH2O during volume-controlled ventilation. The particle count along with vital parameters and ventilator settings were collected continuously and measurements were taken after every increase in PEEP. The particle sizes measured were between 0.41 µm and 4.55 µm. Results: A significant increase in particle count was seen going from all levels of PEEP to release of PEEP. At a PEEP level of 15 cmH2O, there was a median particle count of 282 (154–710) compared to release of PEEP to a level of 5 cmH2O which led to a median particle count of 3754 (2437–10,606) (p < 0.009). A decrease in blood pressure was seen from baseline to all levels of PEEP and significantly so at a PEEP level of 20 cmH2O. Conclusions: In the present study, a significant increase in particle count was seen on releasing PEEP back to baseline compared to all levels of PEEP, while no changes were seen when gradually increasing PEEP. These findings further explore the significance of changes in particle flow and their part in pathophysiological processes within the lung.
25.	Broos, Sissela, et al. (author) Immunomodulatory nanoparticles as adjuvants and allergen-delivery system to human dendritic cells: Implications for specific immunotherapy. 2010 In: Vaccine. - : Elsevier BV. - 1873-2518 .- 0264-410X. ; 28, s. 5075-5085 Journal article (peer-reviewed)abstract Novel adjuvants and antigen-delivery systems with immunomodulatory properties that shift the allergenic Th2 response towards a Th1 or regulatory T cell response are desired for allergen-specific immunotherapy. This study demonstrates that 200-nm sized biodegradable poly(gamma-glutamic acid) (gamma-PGA) nanoparticles (NPs) are activators of human monocyte-derived dendritic cells (MoDCs). gamma-PGA NPs are efficiently internalized by immature MoDCs and strongly stimulate production of chemokines and inflammatory cytokines as well as up-regulation of co-stimulatory molecules and immunomodulatory mediators involved in efficient T cell priming. Furthermore, MoDCs from allergic subjects stimulated in vitro with a mixture of gamma-PGA NPs and extract of grass pollen allergen Phleum pratense (Phl p) augment allergen-specific IL-10 production and proliferation of autologous CD4(+) memory T cells. Thus, gamma-PGA NPs are promising as sophisticated adjuvants and allergen-delivery systems in allergen-specific immunotherapy.

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