| 1. |
- Thalén, Niklas, 1985-, et al.
(författare)
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Systems biology greatly improve activity of secreted therapeutic sulfatase in CHO bioprocess
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Rare diseases are, despite their name, collectively common and millions of people are affected daily of conditions where treatment often is unavailable. Sulfatases are a large family of activating enzymes related to several of these diseases. Heritable genetic variations in sulfatases may lead to impaired activity and a reduced macromolecular breakdown within the lysosome, with several severe and lethal conditions as a consequence. While therapeutic options are scarce, treatment for some sulfatase deficiencies by recombinant enzyme replacement are available. However, such recombinant production of sulfatases suffers greatly from low product activity and yield, further limiting accessibility for patient groups. Here, we have addressed this problem by defining key-proteins necessary for active sulfatase secretion by comparison of CHO clones with different levels of production of active sulfatase. Quantitative transcriptomic analysis highlighted 14 key genes associated with sulfatase production, and experimental validation by co-expression improved the sulfatase enzyme activity by up to 150-fold. Furthermore, a correlation between product mRNA levels and sulfatase activity were observed and expression with lower activity promoters showed an increased in sulfatase activity. The workflow devised is general and we propose it to be useful for resolving bottlenecks in cellular machineries for improvement of cell factories for other biologics as well.
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| 2. |
- Westin, Johan, et al.
(författare)
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Management of influenza–updated Swedish guidelines for antiviral treatment
- 2023
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Ingår i: Infectious Diseases. - : Taylor & Francis Group. - 2374-4235 .- 2374-4243. ; 55:10, s. 725-737
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Tidskriftsartikel (refereegranskat)abstract
- Influenza causes seasonal epidemics of respiratory infection in all parts of the world. Manifestations of influenza range from mild upper to severe lower respiratory tract infection. Medical risk groups are defined by factors predisposing for development of severe disease and are recommended annual vaccination as a protective measure. The previous Swedish treatment guidelines for influenza were issued in 2011, and a review of current evidence was deemed relevant. An important reason to revisit the guidelines is the recent approval of a novel drug for influenza treatment, baloxavir. Updated Swedish evidence-based guidelines created by a group of experts from various research areas, for the management of influenza are presented here. The work has been made in collaboration with the Public Health Agency of Sweden and the Swedish Reference Group for AntiViral therapy (RAV). The updated guidelines include guidelines for diagnostics, treatment and prophylaxis in special groups, including management of pregnant women and children with influenza. A new section about infection control has been added. Pharmacological treatment is covered in detail with regards to indication and dosage. Additionally, drug resistance and environmental aspects are discussed.
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| 3. |
- Nordenholm, Anna, et al.
(författare)
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Disappointment and frustration, but long-term satisfaction: patient experiences undergoing treatment for a chronic Achilles tendon rupture-a qualitative study.
- 2022
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Ingår i: Journal of orthopaedic surgery and research. - : Springer Science and Business Media LLC. - 1749-799X. ; 17:1
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Tidskriftsartikel (refereegranskat)abstract
- Delayed treatment of Achilles tendon ruptures is generally due to either misdiagnosis or patient delay. When the treatment is delayed more than 4weeks, the rupture is defined as "chronic", and almost always requires more invasive surgery and longer rehabilitation time compared with acute Achilles tendon ruptures. There is insufficient knowledge of patient experiences of sustaining and recovering from a chronic Achilles tendon rupture.To evaluate patients' experiences of suffering a chronic Achilles tendon rupture, semi-structured group interviews were conducted 4-6years after surgical treatment using a semi-structured interview guide. The data were analyzed using qualitative content analysis described by Graneheim and Lundman.The experiences of ten patients (65±14years, 7 males and 3 females) were summarized into four main categories: (1) "The injury", where the patients described immediate functional impairments, following either traumatic or non-traumatic injury mechanisms that were misinterpreted by themselves or the health-care system; (2) "The diagnosis", where the patients expressed relief in receiving the diagnosis, but also disappointment and/or frustration related to the prior misdiagnosis and delay; (3) "The treatment", where the patients expressed high expectations, consistent satisfaction with the surgical treatment, and addressed the importance of the physical therapist having the right expertise; and (4) "The outcomes", where the patients expressed an overall satisfaction with the long-term outcome and no obvious limitations in physical activity, although some fear of re-injury emerged.An Achilles tendon rupture can occur during both major and minor trauma and be misinterpreted by both the assessing health-care professional as well as the patient themselves. Surgical treatment and postoperative rehabilitation for chronic Achilles tendon rupture results in overall patient satisfaction in terms of the long-term outcomes. We emphasize the need for increased awareness of the occurrence of Achilles tendon rupture in patients with an atypical patient history.
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| 4. |
- Viklund, Emilia, et al.
(författare)
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Severe acute respiratory syndrome coronavirus 2 can be detected in exhaled aerosol sampled during a few minutes of breathing or coughing
- 2022
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Ingår i: Influenza and other Respiratory Viruses. - : Wiley. - 1750-2640 .- 1750-2659. ; 16:3, s. 402-10
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Tidskriftsartikel (refereegranskat)abstract
- Background: The knowledge on the concentration of viral particles in exhaled breath is limited. The aim of this study was to explore if severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can be detected in aerosol from subjects with the coronavirus disease 2019 (COVID-19) during various types of breathing and coughing and how infection with SARS-CoV-2 may influence the number and size of exhaled aerosol particles. Methods: We counted and collected endogenous particles in exhaled breath in subjects with COVID-19 disease by two different impaction-based methods, during 20 normal breaths, 10 airway opening breaths, and three coughs, respectively. Breath samples were analyzed with reverse transcription real-time polymerase chain reaction (RT-PCR). Results: Detection of RNA in aerosol was possible in 10 out of 25 subjects. Presence of virus RNA in aerosol was mainly found in cough samples (n = 8), but also in airway opening breaths (n = 3) and in normal breaths (n = 4), with no overlap between the methods. No association between viral load in aerosol and number exhaled particles <5μm was found. Subjects with COVID-19 exhaled less particles than healthy controls during normal breathing and airway opening breaths (all P < 0.05), but not during cough. Conclusion: SARS-CoV-2 RNA can be detected in exhaled aerosol, sampled during a limited number of breathing and coughing procedures. Detection in aerosol seemed independent of viral load in the upper airway swab as well as of the exhaled number of particles. The infectious potential of the amount of virus detected in aerosol needs to be further explored.
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| 5. |
- Nordén, Rickard, 1977, et al.
(författare)
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Quantification of torque teno virus and Epstein-Barr virus is of limited value for predicting the net state of immunosuppression after lung transplantation
- 2018
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Ingår i: Open Forum Infectious Diseases. - : Oxford University Press (OUP). - 2328-8957. ; 5:4
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Tidskriftsartikel (refereegranskat)abstract
- Background. Major hurdles for survival after lung transplantation are rejections and infectious complications. Adequate methods for monitoring immune suppression status are lacking. Here, we evaluated quantification of torque teno virus (TTV) and Epstein-Barr virus (EBV) as biomarkers for defining the net state of immunosuppression in lung-transplanted patients. Methods. This prospective single-center study included 98 patients followed for 2 years after transplantation. Bacterial infections, fungal infections, viral respiratory infections (VRTI), cytomegalovirus (CMV) viremia, and acute rejections, as well as TTV and EBV levels, were monitored. Results. The levels of torque teno virus DNA increased rapidly after transplantation, likely due to immunosuppressive treatment. A modest increase in levels of Epstein-Barr virus DNA was also observed after transplantation. There were no associations between either TTV or EBV and infectious events or acute rejection, respectively, during follow-up. When Tacrolimus was the main immunosuppressive treatment, TTV DNA levels were significantly elevated 6-24 months after transplantation as compared with Cyclosporine treatment. Conclusions. Although replication of TTV, but not EBV, appears to reflect the functionality of the immune system, depending on the type of immunosuppressive treatment, quantification of TTV or EBV as biomarkers has limited potential for defining the net state of immune suppression.
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| 7. |
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| 8. |
- Jerkeman, Anna, et al.
(författare)
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Chronic hepatitis C in Swedish subjects receiving opiate substitution therapy-Factors associated with advanced fibrosis
- 2014
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Ingår i: Scandinavian Journal of Infectious Diseases. - : Informa Healthcare. - 0036-5548 .- 1651-1980. ; 46, s. 340-347
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Tidskriftsartikel (refereegranskat)abstract
- Background: Opiate substitution therapy (OST) reduces the risk of death from directly drug-related causes in heroin users, allowing other chronic health problems to emerge. People who inject drugs (PWID) are exposed to hepatitis C virus (HCV), with an associated risk of chronic liver disease. We investigated HCV prevalence and liver-related morbidity in a cohort of OST recipients, and analyzed factors associated with significant hepatic fibrosis. Methods: All patients registered on 1 April 2008 in 4 clinics providing OST in the 3 largest cities in Sweden were eligible for inclusion. HCV viremic subjects were evaluated for fibrosis stage by liver biopsy, transient elastometry (TE), and/or a biochemical fibrosis index (Göteborg University Cirrhosis Index; GUCI). Factors associated with severity of fibrosis were determined by logistic regression analysis. Results: Out of 524 eligible patients, 277 consented to enrolment. Two hundred and thirty-six subjects (88%) were anti-HCV-positive, and 162 of these were viremic (69%). Significant liver fibrosis (defined as Ishak stages F3-F6, TE value ≥ 8.85 kPa, or GUCI > 0.33) was found in 69 out of 103 (67%) tested viremic patients, and was associated with alcohol intake (p = 0.03), higher body mass index (BMI; p = 0.04), and the presence of anti-HBc antibodies (indicating exposure to hepatitis B virus (HBV); p = 0.02). Conclusions: Significant liver fibrosis was detected in two-thirds of HCV viremic OST recipients in this cohort, and was associated with alcohol use, high BMI, and exposure to HBV. These findings indicate that the management of HCV and associated risk factors should be emphasized in Swedish OST programs. © 2014 Informa Healthcare.
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| 9. |
- Klevebro, Susanna, et al.
(författare)
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Early energy and protein intakes and associations with growth, BPD and ROP in extremely preterm infants
- 2019
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Ingår i: Clinical Nutrition. - : Elsevier. - 0261-5614 .- 1532-1983. ; 38:3, s. 1289-1295
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Tidskriftsartikel (refereegranskat)abstract
- Background & aim: Extremely preterm infants face substantial neonatal morbidity. Nutrition is important to promote optimal growth and organ development in order to reduce late neonatal complications. The aim of this study was to examine the associations of early nutritional intakes on growth and risks of bronchopulmonary dysplasia (BPD) and retinopathy of prematurity (ROP) in a high-risk population.Methods: This population-based cohort study includes infants born before 27 0/7 weeks of gestational age without severe malformations and surviving ≥10 days. Intake of energy and protein on postnatal days 4–6 and association with weight standard deviation score (WSDS) from birth to day 7, as well as intakes of energy and protein on postnatal days 4–6 and 7 to 27, respectively, and association with composite outcome of death and BPD and separate outcomes of BPD and ROP were examined, and adjusted for potential confounders.Results: The cohort comprised 296 infants with a median gestational age of 25 3/7 weeks. Expressed as daily intakes, every additional 10 kcal/kg/d of energy during days 4–6 was associated with 0.08 higher WSDS on day 7 (95% CI 0.06–0.11; p < 0.001). Between days 7 and 27, every 10 kcal/kg/d increase in energy intake was associated with a reduced risk of BPD of 9% (95% CI 1–16; p = 0.029) and any grade of ROP with a reduced risk of 6% (95% CI 2–9; p = 0.005) in multivariable models. This association was statistically significant in infants with ≤10 days of mechanical ventilation. In infants with >10 days of mechanical ventilation, a combined higher intake of energy and protein was associated with a reduced risk of BPD.Conclusion: Early provision of energy and protein may reduce postnatal weight loss and risk of morbidity in extremely preterm infants.
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| 10. |
- Nilsson, Niklas, et al.
(författare)
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The economic cost and patient-reported outcomes of chronic Achilles tendon ruptures.
- 2020
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Ingår i: Journal of experimental orthopaedics. - : Springer Science and Business Media LLC. - 2197-1153. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- While most Achilles tendon ruptures are dramatic and diagnosed quickly, some are missed, with a risk of becoming chronic. A chronic Achilles tendon rupture is defined as a rupture that has been left untreated for more than 4 weeks. By mapping the health economic cost of chronic Achilles tendon ruptures the health-care system might be able to better distribute resources to detect these ruptures at an earlier time.All patients with a chronic Achilles tendon rupture who were treated surgically at Sahlgrenska University Hospital or Kungsbacka Hospital between 2013 and 2018 were invited to participate in the study. The patients were evaluated postoperatively using the validated Achilles tendon Total Rupture Score (ATRS). The health-care costs were assessed using clinical records. The production-loss costs were extracted from the Swedish Social Insurance Agency. The cost of chronic Achilles tendon ruptures was then compared with the cost of acute ruptures in a previous study by Westin et.al.Forty patients with a median (range) age of 66 (28-86) were included in the study. The mean total cost (± SD) for the patients with a chronic Achilles tendon rupture was 6494 EUR±6508, which is 1276 EUR higher than the mean total cost of acute ruptures. Patients with chronic Achilles tendon ruptures reported a mean (min-max) postoperative ATRS of 73 (14-100).Missing an Achilles tendon rupture will entail higher health-care costs compared with acute ruptures. Health-care resources can be saved if Achilles tendon ruptures are detected at an early stage.
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