| 1. |
- Asif, Sana, M.D, PhD student, et al.
(författare)
-
Severe obstetric lacerations associated with postpartum depression among women with low resilience : a Swedish birth cohort study
- 2020
-
Ingår i: British Journal of Obstetrics and Gynecology. - : Wiley. - 1470-0328 .- 1471-0528. ; 127:11, s. 1382-1390
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Women's levels of resilience and attitudes towards perineal lacerations vary greatly. Some women see them as part of the birthing process, while others react with anger, depressed mood or even self-harm thoughts. A previous study has reported increased risk of postpartum depressive (PPD) symptoms in women with severe perineal lacerations. The aim of this study was to assess the association between severe obstetric perineal lacerations and PPD. A secondary objective was to assess this association among women with low resilience.DESIGN: Nested cohort study.SETTING: Uppsala, Sweden.SAMPLE: Vaginally delivered women with singleton pregnancies (n = 2,990).METHODS: The main exposure was obstetric perineal lacerations. Resilience was assessed in gestational week 32 using the Swedish version of the Sense of Coherence Scale (SOC-29). A digital acyclic graph (DAG) was used to identify possible confounders and mediators. Logistic regression was used to estimate odds ratios and 95% confidence intervals. A sub-analysis was run after excluding women with normal or high resilience.MAIN OUTCOME MEASURES: Postpartum depression, assessed with the Depression Self-Reporting Scale (DSRS), completed at six weeks postpartum.RESULTS: There was no significant association between severe obstetric perineal lacerations and PPD at six weeks postpartum. However, a significant association was found between severe lacerations and PPD in women with low resilience (OR =4.8 95% CI = 1.2-20), persisting even after adjusting for confounding factors.CONCLUSION: Health care professionals might need to identify women with low resilience, as they are at increased risk for PPD after a severe perineal laceration.
|
|
| 2. |
- Welander, Nike Zoe, et al.
(författare)
-
Migraine as a risk factor for mixed symptoms of peripartum depression and anxiety in late pregnancy : A prospective cohort study.
- 2021
-
Ingår i: Journal of Affective Disorders. - : Elsevier. - 0165-0327 .- 1573-2517. ; 295, s. 733-739
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Migraine has been identified as a risk factor for peripartum depression. However, little is known about the contribution of anxiety to this association or potential changes throughout the peripartum period.METHODS: In a sample of 4,831 women from the Biology, Affect, Stress, Imaging and Cognition cohort in Sweden, participants were asked about history of migraine prior to pregnancy. The participants completed the Edinburgh Postnatal Depression Scale (EPDS) at gestational weeks 17 and 32 and postpartum week 6. Multinomial logistic regression analyses were used to assess associations between migraine and symptoms of depression, anxiety or mixed depression and anxiety, while adjusting for potential confounders.RESULTS: In crude estimates, migraine was associated with separate and mixed symptoms of depression and anxiety at most time points. After adjustments, migraine was associated with anxiety at week 17 (adjusted odds ratio: 1.69; 95% confidence interval: 1.11-2.54) and with mixed depression and anxiety at week 32 (adjusted odds ratio: 1.45; 95% confidence interval: 1.06-1.99). None of the other associations remained statistically significant after adjustments.LIMITATIONS: Migraine history was self-reported. Symptoms of depression and anxiety were based on the screening tool EPDS and not on clinical diagnoses.CONCLUSIONS: The results demonstrate that migraine may be a risk factor for anxiety in mid- pregnancy and mixed symptoms of peripartum depression and anxiety in late pregnancy. Inflammatory and hormonal factors may underlie the association between migraine, depression and anxiety across the peripartum period.
|
|
| 3. |
- Asif, Sana, M.D, PhD student, et al.
(författare)
-
Immuno-Modulatory Effects of Dexamethasone in Severe COVID-19 : A Swedish Cohort Study
- 2023
-
Ingår i: Biomedicines. - : MDPI. - 2227-9059. ; 11:1
-
Tidskriftsartikel (refereegranskat)abstract
- Dexamethasone (Dex) has been shown to decrease mortality in severe coronavirus disease 2019 (COVID-19), but the mechanism is not fully elucidated. We aimed to investigate the physiological and immunological effects associated with Dex administration in patients admitted to intensive care with severe COVID-19. A total of 216 adult COVID-19 patients were included-102 (47%) received Dex, 6 mg/day for 10 days, and 114 (53%) did not. Standard laboratory parameters, plasma expression of cytokines, endothelial markers, immunoglobulin (Ig) IgA, IgM, and IgG against SARS-CoV-2 were analyzed post-admission to intensive care. Patients treated with Dex had higher blood glucose but lower blood lactate, plasma cortisol, IgA, IgM, IgG, D-dimer, cytokines, syndecan-1, and E-selectin and received less organ support than those who did not receive Dex (Without-Dex). There was an association between Dex treatment and IL-17A, macrophage inflammatory protein 1 alpha, syndecan-1 as well as E-selectin in predicting 30-day mortality. Among a subgroup of patients who received Dex early, within 14 days of COVID-19 debut, the adjusted mortality risk was 0.4 (95% CI 0.2-0.8), i.e., 40% compared with Without-Dex. Dex administration in a cohort of critically ill COVID-19 patients resulted in altered immunological and physiologic responses, some of which were associated with mortality.
|
|
| 4. |
- Asif, Sana, M.D, PhD student, et al.
(författare)
-
Plasma endostatin correlates with hypoxia and mortality in COVID-19-associated acute respiratory failure
- 2021
-
Ingår i: Biomarkers in Medicine. - : Future Medicine. - 1752-0363 .- 1752-0371. ; 15:16, s. 1509-1517
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The contribution of endothelial injury in the pathogenesis of COVID-19-associated acute respiratory distress syndrome (ARDS) and resulting respiratory failure remains unclear. Plasma endostatin, an endogenous inhibitor of angiogenesis and endothelial dysfunction is upregulated during hypoxia, inflammation and progress of pulmonary disease.Aim: To investigate if plasma endostatin is associated to hypoxia, inflammation and 30-day mortality in patients with severe COVID-19 infection.Method: Samples for blood analysis and plasma endostatin quantification were collected from adult patients with ongoing COVID-19 (n = 109) on admission to intensive care unit (day 1). Demographic characteristics and 30-day mortality data were extracted from medical records. The ability of endostatin to predict mortality was analyzed using receiving operating characteristics and Kaplan-Meier analysis with a cutoff at 46.2 ng/ml was used to analyze the association to survival.Results: Plasma endostatin levels correlated with; PaO2/FiO2 (r = -0.3, p < 0.001), arterial oxygen tension (r = -0.2, p = 0.01), lactate (r = 0.2, p = 0.04), C-reactive protein (r = 0.2, p = 0.04), ferritin (r = 0.2, p = 0.09), D-dimer (r = 0.2, p = 0.08) and IL-6 (r = 0.4, p < 0.001). Nonsurvivors at 30 days had higher plasma endostatin levels than survivors (72 ± 26 vs 56 ± 16 ng/ml, p = 0.01). Receiving operating characteristic curve (area under the curve 0.7) showed that plasma endostatin >46.2 ng/ml predicts mortality with a sensitivity of 92% and specificity of 71%. In patients with plasma endostatin >46.2 ng/ml probability of survival was lower (p = 0.02) in comparison to those with endostatin <46.2 ng/ml.Conclusion: Our results suggest that plasma endostatin is an early biomarker for disease severity in COVID-19.
|
|
| 5. |
- Asif, Sana, M.D, PhD student
(författare)
-
Regulation of thromboinflammation in therapeutic medicine : Special focus on surface coating strategies
- 2019
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Biomaterials are an integral part of modern health care and offer potential treatment modalities to diseases and conditions otherwise intractable. However, the critical issue herein is incompatibility reactions.Our innate immune system is fundamental in protection against pathogens and foreign intruders and controls the discrimination between self and non-self. Biomaterials come in contact with blood upon implantation where they are sensed by innate immune mediators which through a cascade of complex, multifaceted reactions induce inflammation as well as thrombosis which may induce biomaterial dysfunction and rejection. This explains why patients undergoing haemodialysis therapy exhibit an increased incidence of whole-body inflammation and other thrombotic events. Similarly, therapeutic cells such as hepatocytes upon implantation initiate an instant blood mediated inflammatory reaction, responsible for cell damage and death via apoptosis.In order to achieve safer and more efficient therapeutic interventions, engineering of materials and cells that can avoid these adverse reactions is essential. Fabrication of biomaterials consisting of coating of bioinert polymers to avoid immune recognition and activation is a promising approach to modulate immune reactions.In this thesis, we have employed a PEG-lipid polymer coating, which intercalates in to biomembranes via hydrophobic interactions and thus shields from immune rejection. Treatment with PEG-lipid not only makes the surface “invisible” to immune cells but it also acts as a filter which prevents entry of immune cells without inducing cytotoxicity. Results from this thesis illustrate that fabrication of bio-surfaces by bio-inert PEG-lipid polymer is a harmless procedure which not only attenuates thrombo-inflammation but also assist in design of self-tailored materials for a wide range of biomedical applications.
|
|
| 6. |
- Asif, Sana, M.D, PhD student, et al.
(författare)
-
Validation of an MPC polymer coating to attenuate surface- induced cross-talk between the complement and coagulation systems in whole blood in in vitro and in vivo models
- 2019
-
Ingår i: Macromolecular Bioscience. - : Wiley-VCH Verlagsgesellschaft. - 1616-5187 .- 1616-5195. ; 19:5
-
Tidskriftsartikel (refereegranskat)abstract
- Artificial surfaces that come into contact with blood induce an immediate activation of the cascade systems of the blood, leading to a thrombotic and/or inflammatory response that can eventually cause damage to the biomaterial or the patient, or to both. Heparin coating has been used to improve hemocompatibility, and another approach is 2-methacryloyloxyethyl phosphorylcholine (MPC)-based polymer coatings. Here, the aim is to evaluate the hemocompatibility of MPC polymer coating by studying the interactions with coagulation and complement systems using human blood in vitro model and pig in vivo model. The stability of the coatings is investigated in vitro and MPC polymer-coated catheters are tested in vivo by insertion into the external jugular vein of pigs to monitor the catheters' antithrombotic properties. There is no significant activation of platelets or of the coagulation and complement systems in the MPC polymer-coated one, which was superior in hemocompatibility to non-coated matrix surfaces. The protective effect of the MPC polymer coat does not decline after incubation in human plasma for up to 2 weeks. With MPC polymer-coated catheters, it is possible to easily draw blood from pig for 4 days in contrast to the case for non-coated catheters, in which substantial clotting is seen.
|
|
| 7. |
- Asif, Sana, M.D, PhD student, et al.
(författare)
-
Validation of an MPC polymer coating to reduce surface-induced cascade system activation in whole blood in in vitroand in vivo models
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- ABSTRACTBackground: Artificial surfaces that come into contact with blood (e.g., when used in various forms of biomedical device) induce an immediate activation of the cascade systems of the blood, the coagulation and complement systems. These reactions may lead to a thrombotic and/or inflammatory response that can eventually cause damage to the biomaterial or the patient, or to both. Multiple strategies to dampen these reactions have been employed, with heparin conjugation to the material surface being the most successfulthus far. Another approach to improving hemocompatibility is to use 2-methacryloyloxyethyl phosphorylcholine (MPC)-based polymer coatings.Experimental: In the present study, we evaluated the effectiveness of MPC polymer coating and compared it to a commercially available heparin coating in various in vitromodels using fresh human blood with the aim to replace the costly heparin-coated equipment with the more economic MPC. We then investigated the stability of the various coatings in human plasma in vitrofor 2 weeks. Finally, we inserted MPC polymer-coated catheters into the external jugular vein of pigs and monitored the catheters’ antithrombotic properties for 4 days.Results: 1) There was no significant activation of platelets and of the coagulation and complement systems on the MPC polymer-coated or the commercially available heparin surface. 2) Both coats were superior in hemocompatibility to non-coated matrix surfaces. 3) The protective effect of the MPC polymer coat did not decline after incubation in plasma for up to 2 weeks. 4) With MPC polymer-coated catheters, it was possible to easily draw blood from experimental animals for 4 days, in contrast to the case for heparin-flushed commercially available non-coated catheters, in which substantial clotting was seen.
|
|
| 8. |
|
|
| 9. |
- Brandhorst, Heide, 1962-, et al.
(författare)
-
A new oxygen carrier for improved long-term storage of human pancreata before islet isolation
- 2010
-
Ingår i: Transplantation. - 0041-1337 .- 1534-6080. ; 89:2, s. 155-60
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Pancreas oxygenation during cold storage has been established in islet isolation and transplantation to prevent ischemic tissue damage using perfluorodecalin (PFD) as hyperoxygen carrier. However, studies in humans and pigs provided conflicting results about the efficiency of PFD for pancreas oxygenation. The aim of this study was to compare PFD with a newly developed oxygen carrier composed of perfluorohexyloctane and polydimethylsiloxane 5 (F6H8S5) for long-term storage of human pancreata.METHODS: After 24-hr storage in preoxygenated PFD or F6H8S5, pancreata were processed using Liberase HI for pancreas dissociation and a Ficoll gradient for islet purification. Islet quality assessment was performed measuring glucose-stimulated insulin release, viability, islet ATP content, and posttransplant function in diabetic nude mice.RESULTS: Compared with PFD, F6H8S5 significantly increased the intrapancreatic partial oxygen pressure and islet ATP content. This corresponded to an increase of islet yield, recovery after culture, glucose stimulation index, viability, and improved graft function in diabetic nude mice.CONCLUSIONS: The present findings indicate clearly that F6H8S5 improves isolation outcome after prolonged ischemia compared with PFD. This observation seems to be related to the significant lipophilicity and almost pancreas-specific density of F6H8S5. Moreover, these characteristics facilitate pancreas shipment without using custom-made transport vessels as required for PFD.
|
|
| 10. |
|
|
| 11. |
|
|
| 12. |
|
|
| 13. |
- Nilsson Ekdahl, Kristina, et al.
(författare)
-
Dangerous liaisons : complement, coagulation, and kallikrein/kinin cross-talk act as a linchpin in the events leading to thromboinflammation
- 2016
-
Ingår i: Immunological Reviews. - : Wiley. - 0105-2896 .- 1600-065X. ; 274:1, s. 245-269
-
Forskningsöversikt (refereegranskat)abstract
- Innate immunity is fundamental to our defense against microorganisms. Physiologically, the intravascular innate immune system acts as a purging system that identifies and removes foreign substances leading to thromboinflammatory responses, tissue remodeling, and repair. It is also a key contributor to the adverse effects observed in many diseases and therapies involving biomaterials and therapeutic cells/organs. The intravascular innate immune system consists of the cascade systems of the blood (the complement, contact, coagulation, and fibrinolytic systems), the blood cells (polymorphonuclear cells, monocytes, platelets), and the endothelial cell lining of the vessels. Activation of the intravascular innate immune system in vivo leads to thromboinflammation that can be activated by several of the system's pathways and that initiates repair after tissue damage and leads to adverse reactions in several disorders and treatment modalities. In this review, we summarize the current knowledge in the field and discuss the obstacles that exist in order to study the cross-talk between the components of the intravascular innate immune system. These include the use of purified in vitro systems, animal models and various types of anticoagulants. In order to avoid some of these obstacles we have developed specialized human whole blood models that allow investigation of the cross-talk between the various cascade systems and the blood cells. We in particular stress that platelets are involved in these interactions and that the lectin pathway of the complement system is an emerging part of innate immunity that interacts with the contact/coagulation system. Understanding the resulting thromboinflammation will allow development of new therapeutic modalities.
|
|
| 14. |
- Nilsson Ekdahl, Kristina, et al.
(författare)
-
Thromboinflammation in Therapeutic Medicine
- 2015
-
Ingår i: Advances in Experimental Medicine and Biology. - Cham : Springer International Publishing. - 0065-2598 .- 2214-8019. - 9783319186023 - 9783319186030 ; 865, s. 3-17
-
Forskningsöversikt (refereegranskat)abstract
- Thromboinflammation is primarily triggered by the humoral innate immune system, which mainly consists of the cascade systems of the blood, i.e., the complement, contact/coagulation and fibrinolytic systems. Activation of these systems subsequently induces activation of endothelial cells, leukocytes and platelets, finally resulting in thrombotic and inflammatory reactions. Such reactions are triggered by a number of medical procedures, e.g., treatment with biomaterials or drug delivery devices as well as in transplantation with cells, cell clusters or whole vascularized organs. Here, we (1) describe basic mechanisms for thromboinflammation; (2) review thromboinflammatory reactions in therapeutic medicine; and (3) discuss emerging strategies to dampen thromboinflammation.
|
|
| 15. |
- Teramura, Yuji, et al.
(författare)
-
Cell Adhesion Induced Using Surface Modification with Cell-Penetrating Peptide-Conjugated Poly(ethylene glycol)-Lipid : A New Cell Glue for 3D Cell-Based Structures
- 2017
-
Ingår i: ACS Applied Materials and Interfaces. - : American Chemical Society (ACS). - 1944-8244 .- 1944-8252. ; 9:1, s. 244-254
-
Tidskriftsartikel (refereegranskat)abstract
- We synthesized a novel material, cell-penetrating peptide conjugated poly(ethylene glycol)-lipid (CPP-PEG-lipid), that can induce the adhesion of floating cells. Firm cell adhesion with spreading could be induced by cell surface modification with the CPP-PEG-lipids. Cell adhesion was induced by CPPs but not by any other cationic short peptides we tested. Here, we demonstrated adherence using the floating cell line CCRF-CEM as well as primary human T cells, B cells, erythrocytes, and hepatocytes. As compared to cells grown in suspension, adherent cells were more rapidly induced to attach to substrates with the cell-surface modification. The critical factor for attachment was localization of CPPs at the cell membrane by PEG-lipids with PEG > 20 kDa. These cationic CPPs on PEG chains were able to interact with substrate surfaces such as polystyrene (PS) surfaces, glass surfaces, and PS microfibers that are negatively charged, inducing firm cell adhesion and cell spreading. Also, as opposed to normal cationic peptides that interact strongly with cell membranes, CPPs were less interactive with the cell surfaces because of their cell-penetrating property, making them more available for adhering cells to the substrate surface. No effects on cell viability or cell proliferation were observed after the induction of cell adhesion. With this technique, cells could be easily immobilized onto PS microfibers, an important step in fabricating 3D cell-based structures. Cells immobilized onto 3D PS microfibers were alive, and human hepatocytes showed normal production of urea and albumin on the microfibers. This method is novel in inducing firm cell adhesion-via a one-step treatment.
|
|
| 16. |
- Teramura, Yuji, et al.
(författare)
-
Cell surface engineering for regulation of immune reactions in cell therapy
- 2015
-
Ingår i: Advances in Experimental Medicine and Biology. - Cham : Springer. - 0065-2598 .- 2214-8019. - 9783319186023 - 9783319186030 ; 865, s. 189-209
-
Tidskriftsartikel (refereegranskat)abstract
- Transplantation of the pancreatic islets of Langerhans (islets) is a promising cell therapy for treating insulin-dependent type 1 diabetes mellitus. Islet transplantation is a minimally-invasive technique involving relatively simple surgery. However, after intraportal transplantation, the transplanted islets are attacked by the recipient’s immune system, because they activate a number of systems, including coagulation, complement response, inflammation, immune rejection, and recurrence of autoimmune disease. We have developed a surface modification and microencapsulation technique that protects cells and islets with biomaterials and bioactive substances, which may be useful in clinical settings. This approach employs amphiphilic polymers, which can interact with lipid bilayer membranes, without increasing cell volume. Molecules attached to these polymers can protect transplanted cells and islets from attack by the host immune system. We expect that this surface modification technique will improve graft survival in clinical islet transplantation.
|
|
