| 1. |
- Sundquist, Fredrik, et al.
(författare)
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A Phase II Trial of a Personalized, Dose-Intense Administration Schedule of 177Lutetium-DOTATATE in Children With Primary Refractory or Relapsed High-Risk Neuroblastoma–LuDO-N
- 2022
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Ingår i: Frontiers in Pediatrics. - : Frontiers Media SA. - 2296-2360. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Background: Half the children with high-risk neuroblastoma die with widespread metastases. Molecular radiotherapy is an attractive systemic treatment for this relatively radiosensitive tumor. 131I-mIBG is the most widely used form in current use, but is not universally effective. Clinical trials of 177Lutetium DOTATATE have so far had disappointing results, possibly because the administered activity was too low, and the courses were spread over too long a period of time, for a rapidly proliferating tumor. We have devised an alternative administration schedule to overcome these limitations. This involves two high-activity administrations of single agent 177Lu-DOTATATE given 2 weeks apart, prescribed as a personalized whole body radiation absorbed dose, rather than a fixed administered activity. “A phase II trial of 177Lutetium-DOTATATE in children with primary refractory or relapsed high-risk neuroblastoma - LuDO-N” (EudraCT No: 2020-004445-36, ClinicalTrials.gov Identifier: NCT04903899) evaluates this new dosing schedule. Methods: The LuDO-N trial is a phase II, open label, multi-center, single arm, two stage design clinical trial. Children aged 18 months to 18 years are eligible. The trial is conducted by the Nordic Society for Pediatric Hematology and Oncology (NOPHO) and it has been endorsed by SIOPEN (https://www.siopen.net). The Karolinska University Hospital, is the sponsor of the LuDO-N trial, which is conducted in collaboration with Advanced Accelerator Applications, a Novartis company. All Scandinavian countries, Lithuania and the Netherlands participate in the trial and the UK has voiced an interest in joining in 2022. Results: The pediatric use of the Investigational Medicinal Product (IMP) 177Lu-DOTATATE, as well as non-IMPs SomaKit TOC® (68Ga-DOTATOC) and LysaKare® amino acid solution for renal protection, have been approved for pediatric use, within the LuDO-N Trial by the European Medicines Agency (EMA). The trial is currently recruiting. Recruitment is estimated to be finalized within 3–5 years. Discussion: In this paper we present the protocol of the LuDO-N Trial. The rationale and design of the trial are discussed in relation to other ongoing, or planned trials with similar objectives. Further, we discuss the rapid development of targeted radiopharmaceutical therapy and the future perspectives for developing novel therapies for high-risk neuroblastoma and other pediatric solid tumors.
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| 2. |
- Tesi, Bianca, et al.
(författare)
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Diagnostic yield and clinical impact of germline sequencing in children with CNS and extracranial solid tumors : a nationwide, prospective Swedish study
- 2024
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Ingår i: The Lancet Regional Health. - : Elsevier. - 2666-7762. ; 39
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundChildhood cancer predisposition (ChiCaP) syndromes are increasingly recognized as contributing factors to childhood cancer development. Yet, due to variable availability of germline testing, many children with ChiCaP might go undetected today. We report results from the nationwide and prospective ChiCaP study that investigated diagnostic yield and clinical impact of integrating germline whole-genome sequencing (gWGS) with tumor sequencing and systematic phenotyping in children with solid tumors.MethodsgWGS was performed in 309 children at diagnosis of CNS (n = 123, 40%) or extracranial (n = 186, 60%) solid tumors and analyzed for disease-causing variants in 189 known cancer predisposing genes. Tumor sequencing data were available for 74% (227/309) of patients. In addition, a standardized clinical assessment for underlying predisposition was performed in 95% (293/309) of patients.FindingsThe prevalence of ChiCaP diagnoses was 11% (35/309), of which 69% (24/35) were unknown at inclusion (diagnostic yield 8%, 24/298). A second-hit and/or relevant mutational signature was observed in 19/21 (90%) tumors with informative data. ChiCaP diagnoses were more prevalent among patients with retinoblastomas (50%, 6/12) and high-grade astrocytomas (37%, 6/16), and in those with non-cancer related features (23%, 20/88), and ≥2 positive ChiCaP criteria (28%, 22/79). ChiCaP diagnoses were autosomal dominant in 80% (28/35) of patients, yet confirmed de novo in 64% (18/28). The 35 ChiCaP findings resulted in tailored surveillance (86%, 30/35) and treatment recommendations (31%, 11/35).InterpretationOverall, our results demonstrate that systematic phenotyping, combined with genomics-based diagnostics of ChiCaP in children with solid tumors is feasible in large-scale clinical practice and critically guides personalized care in a sizable proportion of patients.
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| 3. |
- Tesi, Bianca, et al.
(författare)
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Diagnostic yield and clinical impact of germline sequencing in children with CNS and extracranial solid tumors : a nationwide, prospective Swedish study
- 2024
-
Ingår i: The Lancet Regional Health. - : Elsevier. - 2666-7762. ; 39
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Childhood cancer predisposition (ChiCaP) syndromes are increasingly recognized as contributing factors to childhood cancer development. Yet, due to variable availability of germline testing, many children with ChiCaP might go undetected today. We report results from the nationwide and prospective ChiCaP study that investigated diagnostic yield and clinical impact of integrating germline whole-genome sequencing (gWGS) with tumor sequencing and systematic phenotyping in children with solid tumors.Methods: gWGS was performed in 309 children at diagnosis of CNS (n = 123, 40%) or extracranial (n = 186, 60%) solid tumors and analyzed for disease-causing variants in 189 known cancer predisposing genes. Tumor sequencing data were available for 74% (227/309) of patients. In addition, a standardized clinical assessment for underlying predisposition was performed in 95% (293/309) of patients.Findings: The prevalence of ChiCaP diagnoses was 11% (35/309), of which 69% (24/35) were unknown at inclusion (diagnostic yield 8%, 24/298). A second-hit and/or relevant mutational signature was observed in 19/21 (90%) tumors with informative data. ChiCaP diagnoses were more prevalent among patients with retinoblastomas (50%, 6/12) and high-grade astrocytomas (37%, 6/16), and in those with non-cancer related features (23%, 20/88), and ≥2 positive ChiCaP criteria (28%, 22/79). ChiCaP diagnoses were autosomal dominant in 80% (28/35) of patients, yet confirmed de novo in 64% (18/28). The 35 ChiCaP findings resulted in tailored surveillance (86%, 30/35) and treatment recommendations (31%, 11/35).Interpretation: Overall, our results demonstrate that systematic phenotyping, combined with genomics-based diagnostics of ChiCaP in children with solid tumors is feasible in large-scale clinical practice and critically guides personalized care in a sizable proportion of patients.Funding: The study was supported by the Swedish Childhood Cancer Fund and the Ministry of Health and Social Affairs.
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| 4. |
- Bergenholtz, Sa Schoug, et al.
(författare)
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A case study on stress preconditioning of a Lactobacillus strain prior to freeze-drying
- 2012
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Ingår i: Cryobiology. - : Elsevier BV. - 0011-2240 .- 1090-2392. ; 64:3, s. 152-159
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Tidskriftsartikel (refereegranskat)abstract
- Freeze-drying of bacterial cells with retained viability and activity after storage requires appropriate formulation, i.e. mixing of physiologically adapted cell populations with suitable protective agents, and control of the freeze-drying process. Product manufacturing may alter the clinical effects of probiotics and it is essential to identify and understand possible factor co-dependencies during manufacturing. The physical solid-state behavior of the formulation and the freeze-drying parameters are critical for bacterial survival and thus process optimization is important, independent of strain. However, the maximum yield achievable is also strain-specific and strain survival is governed by e.g. medium, cell type, physiological state, excipients used, and process. The use of preferred compatible solutes for cross-protection of Lactobacilli during industrial manufacturing may be a natural step to introduce robustness, but knowledge is lacking on how compatible solutes, such as betaine, influence formulation properties and cell survival. This study characterized betaine formulations, with and without sucrose, and tested these with the model lactic acid bacteria Lactobacillus coryniformis Si3. Betaine alone did not act as a lyo-protectant and thus betaine import prior to freeze-drying should be avoided. Differences in protective agents were analyzed by calorimetry, which proved to be a suitable tool for evaluating the characteristics of the freeze-dried end products.
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| 5. |
- Dekker Nitert, Marloes, et al.
(författare)
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Impact of an Exercise Intervention on DNA Methylation in Skeletal Muscle From First-Degree Relatives of Patients With Type 2 Diabetes.
- 2012
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Ingår i: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797.
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Tidskriftsartikel (refereegranskat)abstract
- To identify epigenetic patterns, which may predispose to type 2 diabetes (T2D) due to a family history (FH) of the disease, we analyzed DNA methylation genome-wide in skeletal muscle from individuals with (FH(+)) or without (FH(-)) an FH of T2D. We found differential DNA methylation of genes in biological pathways including mitogen-activated protein kinase (MAPK), insulin, and calcium signaling (P ≤ 0.007) and of individual genes with known function in muscle, including MAPK1, MYO18B, HOXC6, and the AMP-activated protein kinase subunit PRKAB1 in skeletal muscle of FH(+) compared with FH(-) men. We further validated our findings from FH(+) men in monozygotic twin pairs discordant for T2D, and 40% of 65 analyzed genes exhibited differential DNA methylation in muscle of both FH(+) men and diabetic twins. We further examined if a 6-month exercise intervention modifies the genome-wide DNA methylation pattern in skeletal muscle of the FH(+) and FH(-) individuals. DNA methylation of genes in retinol metabolism and calcium signaling pathways (P < 3 × 10(-6)) and with known functions in muscle and T2D including MEF2A, RUNX1, NDUFC2, and THADA decreased after exercise. Methylation of these human promoter regions suppressed reporter gene expression in vitro. In addition, both expression and methylation of several genes, i.e., ADIPOR1, BDKRB2, and TRIB1, changed after exercise. These findings provide new insights into how genetic background and environment can alter the human epigenome.
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| 6. |
- Dural-Erem, Aysin, et al.
(författare)
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Biocontrol of solid surfaces in hospitals using microbial-based wipes
- 2019
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Ingår i: Textile research journal. - : SAGE Publications. - 0040-5175 .- 1746-7748. ; 89:2, s. 216-222
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Tidskriftsartikel (refereegranskat)abstract
- Hospital-acquired infections have become a major challenge which threaten the hospitalized patients’ safety. The presence of nosocomial pathogens is generally reported in connection with solid surfaces near patient environments. These surfaces become significant sources of transmission and lead most often to the contamination and cross-contamination of nosocomial pathogens to the patients and staff. This paper investigates strategies to apply beneficial bacteria on viscose-based nonwoven wipes and the viability of these beneficial bacteria on the wipes along with characterization of the physical properties of the wipes. Major findings include that it is possible to produce dry wipes which contain an adequate number of beneficial bacteria or spores. After these wipes are wetted, they can release a certain number of bacteria from the wetted wipes. These released beneficial bacteria can inhibit pathogens by growing and colonizing on the wiped surfaces.
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| 7. |
- Eriksson, Hanna M., et al.
(författare)
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Massive formation of intracellular membrane vesicles in Escherichia coli by a monotopic membrane-bound lipid glycosyltransferase
- 2009
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Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 284:49, s. 33904-33914
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Tidskriftsartikel (refereegranskat)abstract
- The morphology and curvature of biological bilayers are determined by the packing shapes and interactions of their participant molecules. Bacteria, except photosynthetic groups, usually lack intracellular membrane organelles. Strong overexpression in Escherichia coli of a foreign monotopic glycosyltransferase (named monoglycosyldiacylglycerol synthase), synthesizing a nonbilayer-prone glucolipid, induced massive formation of membrane vesicles in the cytoplasm. Vesicle assemblies were visualized in cytoplasmic zones by fluorescence microscopy. These have a very low buoyant density, substantially different from inner membranes, with a lipid content of > or = 60% (w/w). Cryo-transmission electron microscopy revealed cells to be filled with membrane vesicles of various sizes and shapes, which when released were mostly spherical (diameter approximately 100 nm). The protein repertoire was similar in vesicle and inner membranes and dominated by the glycosyltransferase. Membrane polar lipid composition was similar too, including the foreign glucolipid. A related glycosyltransferase and an inactive monoglycosyldiacylglycerol synthase mutant also yielded membrane vesicles, but without glucolipid synthesis, strongly indicating that vesiculation is induced by the protein itself. The high capacity for membrane vesicle formation seems inherent in the glycosyltransferase structure, and it depends on the following: (i) lateral expansion of the inner monolayer by interface binding of many molecules; (ii) membrane expansion through stimulation of phospholipid synthesis, by electrostatic binding and sequestration of anionic lipids; (iii) bilayer bending by the packing shape of excess nonbilayer-prone phospholipid or glucolipid; and (iv) potentially also the shape or penetration profile of the glycosyltransferase binding surface. These features seem to apply to several other proteins able to achieve an analogous membrane expansion.
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| 8. |
- Guan, Jikui, et al.
(författare)
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Clinical response of the novel activating ALK-I1171T mutation in neuroblastoma to the ALK inhibitor ceritinib.
- 2018
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Ingår i: Cold Spring Harbor molecular case studies. - : Cold Spring Harbor Laboratory. - 2373-2873. ; 4:4
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Tidskriftsartikel (refereegranskat)abstract
- Tumors with Anaplastic Lymphoma Kinase (ALK) fusion rearrangements, including non-small cell lung cancer and anaplastic large cell lymphoma, are highly sensitive to ALK tyrosine kinase inhibitors (TKIs), underscoring the notion that such cancers are addicted to ALK activity. While mutations in ALK are heavily implicated in childhood neuroblastoma, response to the ALK TKI crizotinib has been disappointing. Embryonal tumors in patients with DNA repair defects such as Fanconi anemia (FA) often have a poor prognosis, due to lack of therapeutic options. Here we report a child with underlying FA and ALK mutant high-risk neuroblastoma responding strongly to precision therapy with the ALK TKI ceritinib. Conventional chemotherapy treatment caused severe, life-threatening toxicity. Genomic analysis of the initial biopsy identified germ-line FANCA mutations as well as a novel ALK-I1171T variant. ALK-I1171T generates a potent gain-of-function mutant, as measured in PC12 cell neurite outgrowth and NIH3T3 transformation. Pharmacological inhibition profiling of ALK-I1171T in response to various ALK TKIs identified an 11-fold improved inhibition of ALK-I1171T with ceritinib when compared with crizotinib. Immunoaffinity-coupled LC-MS/MS phosphoproteomics analysis indicated a decrease in ALK signaling in response to ceritinib. Ceritinib was therefore selected for treatment in this child. Mono-therapy with ceritinib was well tolerated and resulted in normalized catecholamine markers and tumor shrinkage. After 7.5 months treatment, residual primary tumor was surgically removed and exhibited hallmarks of differentiation together with reduced Ki67 levels. Clinical follow-up after 21 months treatment revealed complete clinical remission including all metastatic sites. Therefore, ceritinib presents a viable therapeutic option for ALK-positive neuroblastoma.
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| 9. |
- Lahermo, P, et al.
(författare)
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A quality assessment survey of SNP genotyping laboratories
- 2006
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Ingår i: Human Mutation. - : Hindawi Limited. - 1059-7794 .- 1098-1004. ; 27:7, s. 711-714
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- To survey the quality of SNP genotyping, a joint Nordic quality assessment (QA) round was organized between 11 laboratories in the Nordic and Baltic countries. The QA round involved blinded genotyping of 47 DNA samples for 18 or six randomly selected SNPs. The methods used by the participating laboratories included all major platforms for small- to medium-size SNP genotyping. The laboratories used their standard procedures for SNP assay design, genotyping, and quality control. Based on the joint results from all laboratories, a consensus genotype for each DNA sample and SNP was determined by the coordinator of the survey, and the results from each laboratory were compared to this genotype. The overall genotyping accuracy achieved in the survey was excellent. Six laboratories delivered genotype data that were in full agreement with the consensus genotype. The average accuracy per SNP varied from 99.1 to 100% between the laboratories, and it was frequently 100% for the majority of the assays for which SNP genotypes were reported. Lessons from the survey are that special attention should be given to the quality of the DNA samples prior to genotyping, and that a conservative approach for calling the genotypes should be used to achieve a high accuracy.
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| 10. |
- Liedberg, Fredrik, et al.
(författare)
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Long-term follow-up after radical cystectomy with emphasis on complications and reoperations: A Swedish population-based survey
- 2012
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Ingår i: Scandinavian Journal of Urology and Nephrology. - : Informa Healthcare. - 0036-5599 .- 1651-2065. ; 46:1, s. 14-18
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Tidskriftsartikel (refereegranskat)abstract
- Objective. To evaluate outcome after radical cystectomy for primary bladder cancer in a large population-based material. Material and methods. Between 1997 and 2002 all patients treated with radical cystectomy within 3 months after diagnosis of primary bladder cancer without distant metastasis were retrieved through the Swedish Bladder Cancer Registry. A follow-up questionnaire was distributed to all units where the primary registration of patients was performed. Follow-up data on recurrence date were retrieved from the patient charts and causes of death were obtained from the Swedish Cause of Death Registry until 2003. Results. During the study period radical cystectomy was performed in 39 units in Sweden, of which only five units were considered high-volume hospitals performing 10 or more procedures annually. Mean blood loss was 2300 ml (median 2000 ml) and the 90-day mortality rate was 5.7%. Blood loss was higher in high-volume units than in hospitals with lower hospital volumes, but the 90-day mortality rates were similar. During a median follow-up of 3.5 years, 24% of the patients were submitted to a reoperation. Reoperation rates were significantly higher in patients who received a continent urinary diversion (29%) compared with an ileal conduit (22%, p andlt; 0.015). Conclusions. Radical cystectomy was associated with a reoperation rate of 24% in Sweden during the study period. The reoperation rates were higher in patients receiving a continent cutaneous diversion or bladder substitution. Blood loss was higher in high-volume units; otherwise, surgical volume did not affect mortality rates, cancer-specific survival or reoperation rates.
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| 11. |
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| 12. |
- Lundquist, Anna, et al.
(författare)
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Melittin–Lipid interaction : A comparative study using liposomes, micelles and bilayer disks
- 2008
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Ingår i: Biochimica et Biophysica Acta - Biomembranes. - : Elsevier BV. - 0005-2736 .- 1879-2642. ; 1778:10, s. 2210-2216
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Tidskriftsartikel (refereegranskat)abstract
- Comparison of melittin interaction with liposomes, bilayer disks and micelles showed that melittin binding to lipid aggregates is largely dictated by the amount of highly curved areas in the aggregates. The PEG-stabilised bilayer disks were characterised by a combination of small angle neutron scattering, cryo-transmission electron microscopy and dynamic light scattering. Importantly, the theoretically foreseen partial segregation of the lipid components, important for maintaining the structure of the bilayer disk, was confirmed. Steady state fluorescence spectroscopy indicated that melittin mainly resides at the rim of the bilayer disks. Results of the present study help increase the understanding of the mechanisms behind, and the physico-chemical factors affecting, melittin–lipid interaction. We suggest that bilayer disks, due to their stable structure, constitute interesting vehicles for transport of peptides that have high propensity to associate with lipid surfaces of high curvature.
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| 13. |
- Milberg, Per, et al.
(författare)
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Do differences in plasticity during early growth lead to differing success in competition? A test using four co-occurring annual Papaver
- 2014
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Ingår i: Plant Species Biology. - : Wiley-Blackwell: No OnlineOpen. - 0913-557X .- 1442-1984. ; 29:1, s. 92-100
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Tidskriftsartikel (refereegranskat)abstract
- Plant species differ in their ability to transform available resources to biomass and to respond in a plastic way to environmental circumstances; we hypothesized that such differences among four weed taxa of Papaver would explain differences in their competitive response. We first compared two populations each of Papaver rhoeasL., P.dubiumL. ssp. dubium, P.dubiumL. ssp. lecoqii (Lamotte) Syme and P.argemoneL., grown in a greenhouse for 6 weeks in a nutrient gradient combined with two light treatments to elucidate possible differences in responses. As there were clear differences, a second experiment evaluated whether these differences also meant differences in competitive response, during early growth, when tested against two crops (wheat, rape). The assumption that competitive response was linked to the ability to transform nutrient and light to biomass was not supported: even though differences in extent of plasticity existed, the effect of competition was similar for the taxa. Thus, higher plasticity and ability to transform available recourses to biomass did not lead to stronger competitiveness for Papaver during early growth.
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| 14. |
- Möllsten, Anna, et al.
(författare)
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A functional polymorphism in the manganese superoxide dismutase gene and diabetic nephropathy.
- 2007
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 56:1, s. 265-269
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Tidskriftsartikel (refereegranskat)abstract
- Oxidative stress has been suggested to contribute to the development of diabetic nephropathy. Manganese superoxide dismutase (MnSOD) protects the cells from oxidative damage by scavenging free radicals. The demand for antioxidants is increased by smoking, which could disturb the balance between antioxidants and radicals. The present study aimed to determine whether a valine/alanine polymorphism in MnSOD (V16A, rs4880), alone or in combination with smoking, can contribute to development of diabetic nephropathy in 1,510 Finnish and Swedish patients with type 1 diabetes. Overt diabetic nephropathy (n = 619) was defined as having an albumin excretion rate (AER) >200 microg/min or renal replacement therapy; incipient diabetic nephropathy was defined as having an AER of 20-200 microg/min (n = 336). The control subjects had diabetes duration of >or=20 years, without albuminuria (AER <20 microg/min) and without antihypertensive treatment (n = 555). In addition to male sex and elevated A1C, smoking was significantly associated with diabetic nephropathy (overt plus incipient), odds ratio (OR) 2.00 (95% CI 1.60-2.50). When controlling for age at onset, diabetes duration, A1C, smoking, and sex, the Val/Val genotype was associated with an increase in risk of diabetic nephropathy (1.32 [1.00-1.74], P = 0.049). When evaluating the combined effect of genotype and smoking, we used logistic regression with stratification according to smoking status and genotype. The high-risk group (ever smoking plus Val/Val genotype) had 2.52 times increased risk of diabetic nephropathy (95% CI 1.73-3.69) compared with the low-risk group, but no departure from additivity was found. Our results indicate that smoking and homozygosity for the MnSOD Val allele is associated with an increased risk of diabetic nephropathy, which supports the hypothesis that oxidative stress contributes to the development of diabetic nephropathy.
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| 15. |
- Rivas-Franco, Frederico, et al.
(författare)
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Effect of coating maize seed with entomopathogenic fungi on plant growth and resistance against Fusarium graminearum and Costelytra giveni
- 2019
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Ingår i: Biocontrol science and technology (Print). - : Taylor and Francis Ltd.. - 0958-3157 .- 1360-0478. ; 29:9, s. 877-900
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Tidskriftsartikel (refereegranskat)abstract
- Some entomopathogenic fungi such as Metarhizium and Beauveria not only have the ability to infect and kill insects but also the capability to associate with plant roots. The potential benefits from this plant-fungus association include nutrient acquisition, plant growth promotion and protection against stressors. The objective of this study was to evaluate the delivery of entomopathogenic fungi in seed coating to determine whether the fungal presence affected maize performance. Additionally, fungal biocontrol ability was assessed in terms of plant resistance to the larvae of Costelytra giveni (Coleoptera: Scarabaeidae) and to the fungus Fusarium graminearum (Nectriaceae). Maize seeds were coated with conidia from Metarhizium spp. or Beauveria bassiana and plant performance was evaluated as seed germination and plant dry weight. Larval mortality and the presence of Fusarium root rot symptoms were also determined. The entomopathogenic fungal persistence on the maize rhizosphere was demonstrated with a M. anisopliae isolate expressing the green fluorescent protein. Presence of both challengers was detrimental to maize performance with 33% reduction in root dry weight in control plants while no variation was observed when the entomopathogenic fungi were used to coat seeds. Some seed coatings resulted in up to 67% mycosis of C. giveni larvae and a reduction in Fusarium rot root symptoms between 24–44%. This study showed that seed coating with conidia of Metarhizium or Beauveria can be used as a delivery system for pests and plant pathogen control, while at the same time hyphae formed a close association with plant roots after conidial germination.
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| 16. |
- Rivas-Franco, Frederico, et al.
(författare)
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Effects of a maize root pest and fungal pathogen on entomopathogenic fungal rhizosphere colonization, endophytism and induction of plant hormones
- 2020
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Ingår i: Biological control (Print). - : Academic Press Inc.. - 1049-9644 .- 1090-2112. ; 150
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Tidskriftsartikel (refereegranskat)abstract
- Some entomopathogenic fungi, such as Metarhizium spp. and Beauveria spp., closely interact with plants by colonizing the rhizosphere or growing endophytically inside root tissues. These characteristics increase the potential for endophytic entomopathogenic fungi to persist in the root system when used as biological control agents. The mechanism by which endophytic entomopathogenic fungi are capable to colonize the internal plant tissues is also influenced by plants and can be regarded as an adaptive protection acquired by plants against herbivorous insects. The mutual benefits obtained by plants and fungi through this peculiar endophytic association supports the bodyguard hypothesis. The objectives of this study were to evaluate the ability of different isolates of Metarhizium spp. and a single isolate of Beauveria bassiana, coated onto seeds, to colonize the rhizosphere and root tissues of maize (Zea mays) and to assess whether the presence of an insect pest and fungal root pathogen influenced this interaction. All the entomopathogenic fungal isolates tested were able to colonize the rhizosphere to some extent, but one isolate of M. anisopliae and the one of M. robertsii performed best. Overall, the presence of Costelytra giveni (Scarabaeidae) larvae significantly decreased rhizosphere colonization by the entomopathogens, while the phytopathogenic fungus Fusarium graminearum (Nectriaceae: Hypocreales) did not. Similarly, the presence of C. giveni decreased endophytic growth in root tissues by around 75% when considering all entomopathogens together. In contrast, a 112% increase in overall root endophytic colonization occurred in the presence of F. graminearum. Salicylic acid (SA) and jasmonic acid (JA) content in maize plants changed depending on the isolate of M. anisopliae incorporated through seed coating and root herbivory by larval presence. In the absence of C. giveni, plants treated with M. anisopliae A1080 had higher SA and JA root content than control plants. Conversely, when larvae were present, maize plants treated with M. anisopliae F672 had increased levels of both phytohormones, indicating a potentially primed state. The observed decrease in root colonization by some entomopathogenic fungal isolates in the presence of larvae of C. giveni and the increase in endophytic colonization in the presence of F. graminearum are in accordance with the bodyguard hypothesis. Additionally, the changes observed in the SA and JA content in Metarhizium treated plants corresponded to plant responses related to systemic acquired resistance and to induced systemic resistance. Our results demonstrate that biotic soil factors can shape the outcome of endophytic entomopathogenic fungi-plant interaction, as well as affecting the plant physiology.
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| 17. |
- Rivas-Franco, Frederico, et al.
(författare)
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Production of Microsclerotia From Entomopathogenic Fungi and Use in Maize Seed Coating as Delivery for Biocontrol Against Fusarium graminearum
- 2020
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Ingår i: Frontiers in Sustainable Food Systems. - : Frontiers Media S.A.. - 2571-581X. ; 4
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Tidskriftsartikel (refereegranskat)abstract
- The commercial use of the entomopathogenic fungi Metarhizium spp. in biopesticides has gained more interest since the discovery that several species of this genus are able to colonize roots. In general, commercial products with Metarhizium are formulated based on conidia for insect pest control. The process of mass production, harvesting, and formulation of infective conidia can be detrimental for conidial viability. Entomopathogenic fungi such as Metarhizium spp. are able to produce high concentrations of resistant structures, known as microsclerotia, when grown in liquid media. Microsclerotia are desiccation tolerant, with excellent storage stability, and are capable of producing high quantities of infective conidia after rehydration. The aim of this study was to evaluate microsclerotia production by different isolates of Metarhizium spp. and determine the effect of microsclerotia coated onto maize seeds on plant growth in the presence of soil-borne pathogen Fusarium graminearum. On average, ~1 × 105 microsclerotia/mL were produced by selected isolates of M. anisopliae (A1080 and F672) and Metarhizium robertsii (F447). Microsclerotia were formulated as granules with diatomaceous earth and used for seed coating, after which propagules produced around 5 × 106 CFU/g of seeds. In the presence of the plant pathogen, maize plants grown from untreated seeds had the lowest growth, while plants treated with the Metarhizium microsclerotia had significantly greater growth than the control plants. Hyphae were observed growing on and in root tissues in all the Metarhizium spp. treatments but not in samples from control plants. Metarhizium hyphal penetration points' on roots were observed 1 month after sowing, indicating the fungi were colonizing roots as endophytes. The results obtained indicate that microsclerotia can be coated onto seeds, providing plant protection against soil plant pathogens and a method to establish Metarhizium in the ecto- and endo-rhizosphere of maize roots, allowing the persistence of this biocontrol agent.
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| 18. |
- Strömstedt, Adam A., et al.
(författare)
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Effect of lipid headgroup composition on the interaction between melittin and lipid bilayers
- 2007
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Ingår i: Journal of Colloid and Interface Science. - : Elsevier BV. - 0021-9797 .- 1095-7103. ; 311:1, s. 59-69
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Tidskriftsartikel (refereegranskat)abstract
- The effect of the lipid polar headgroup on melittin-phospholipid interaction was investigated by cryo-TEM, fluorescence spectroscopy, ellipsometry, CD, electrophoresis and photon correlation spectroscopy. In particular, focus was placed on the effect of the lipid polar headgroup on peptide adsorption to, and penetration into, the lipid bilayer, as well as on resulting colloidal stability effects for large unilamellar liposomes. The effect of phospholipid headgroup properties on melittin-bilayer interaction was addressed by comparing liposomes contg. phosphatidylcholine, -acid, and -inositol at varying ionic strength. Increasing the bilayer neg. charge leads to an increased liposome tolerance toward melittin which is due to an electrostatic arrest of melittin at the membrane interface. Balancing the electrostatic attraction between the melittin pos. charges and the phospholipid neg. charges through a hydration repulsion, caused by inositol, reduced this surface arrest and increased liposome susceptibility to the disruptive actions of melittin. Furthermore, melittin was demonstrated to induce liposome structural destabilization on a colloidal scale which coincided with leakage induction for both anionic and zwitterionic systems. The latter findings thus clearly show that coalescence, aggregation, and fragmentation contribute to melittin-induced liposome leakage, and that detailed mol. analyses of melittin pore formation are incomplete without considering also these colloidal aspects.
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| 19. |
- Wadensten, Elisabeth, et al.
(författare)
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Diagnostic Yield From a Nationwide Implementation of Precision Medicine for all Children With Cancer.
- 2023
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Ingår i: JCO Precision Oncology (JCO PO). - : American Society of Clinical Oncology. - 2473-4284. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Several studies have indicated that broad genomic characterization of childhood cancer provides diagnostically and/or therapeutically relevant information in selected high-risk cases. However, the extent to which such characterization offers clinically actionable data in a prospective broadly inclusive setting remains largely unexplored.We implemented prospective whole-genome sequencing (WGS) of tumor and germline, complemented by whole-transcriptome sequencing (RNA-Seq) for all children diagnosed with a primary or relapsed solid malignancy in Sweden. Multidisciplinary molecular tumor boards were set up to integrate genomic data in the clinical decision process along with a medicolegal framework enabling secondary use of sequencing data for research purposes.During the study's first 14 months, 118 solid tumors from 117 patients were subjected to WGS, with complementary RNA-Seq for fusion gene detection in 52 tumors. There was no significant geographic bias in patient enrollment, and the included tumor types reflected the annual national incidence of pediatric solid tumor types. Of the 112 tumors with somatic mutations, 106 (95%) exhibited alterations with a clear clinical correlation. In 46 of 118 tumors (39%), sequencing only corroborated histopathological diagnoses, while in 59 cases (50%), it contributed to additional subclassification or detection of prognostic markers. Potential treatment targets were found in 31 patients (26%), most commonly ALK mutations/fusions (n = 4), RAS/RAF/MEK/ERK pathway mutations (n = 14), FGFR1 mutations/fusions (n = 5), IDH1 mutations (n = 2), and NTRK2 gene fusions (n = 2). In one patient, the tumor diagnosis was revised based on sequencing. Clinically relevant germline variants were detected in 8 of 94 patients (8.5%).Up-front, large-scale genomic characterization of pediatric solid malignancies provides diagnostically valuable data in the majority of patients also in a largely unselected cohort.
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| 20. |
- Wadensten, Elisabeth, et al.
(författare)
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Diagnostic Yield From a Nationwide Implementation of Precision Medicine for all Children With Cancer
- 2023
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Ingår i: JCO Precision Oncology. - : American Society of Clinical Oncology. - 2473-4284. ; :7
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Several studies have indicated that broad genomic characterization of childhood cancer provides diagnostically and/or therapeutically relevant information in selected high-risk cases. However, the extent to which such characterization offers clinically actionable data in a prospective broadly inclusive setting remains largely unexplored.Methods: We implemented prospective whole-genome sequencing (WGS) of tumor and germline, complemented by whole-transcriptome sequencing (RNA-Seq) for all children diagnosed with a primary or relapsed solid malignancy in Sweden. Multidisciplinary molecular tumor boards were set up to integrate genomic data in the clinical decision process along with a medicolegal framework enabling secondary use of sequencing data for research purposes.Results: During the study's first 14 months, 118 solid tumors from 117 patients were subjected to WGS, with complementary RNA-Seq for fusion gene detection in 52 tumors. There was no significant geographic bias in patient enrollment, and the included tumor types reflected the annual national incidence of pediatric solid tumor types. Of the 112 tumors with somatic mutations, 106 (95%) exhibited alterations with a clear clinical correlation. In 46 of 118 tumors (39%), sequencing only corroborated histopathological diagnoses, while in 59 cases (50%), it contributed to additional subclassification or detection of prognostic markers. Potential treatment targets were found in 31 patients (26%), most commonly ALK mutations/fusions (n = 4), RAS/RAF/MEK/ERK pathway mutations (n = 14), FGFR1 mutations/fusions (n = 5), IDH1 mutations (n = 2), and NTRK2 gene fusions (n = 2). In one patient, the tumor diagnosis was revised based on sequencing. Clinically relevant germline variants were detected in 8 of 94 patients (8.5%).Conclusion: Up-front, large-scale genomic characterization of pediatric solid malignancies provides diagnostically valuable data in the majority of patients also in a largely unselected cohort.
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| 21. |
- Wessman, Per, et al.
(författare)
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Effect of α-helical peptides on liposome structure : A comparative study of melittin and alamethicin
- 2010
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Ingår i: Journal of Colloid and Interface Science. - : Elsevier. - 0021-9797 .- 1095-7103. ; 346:1, s. 127-135
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Tidskriftsartikel (refereegranskat)abstract
- Cryo-transmission electron microscopy was used in combination with turbidity and leakage measurements to explore and compare the membrane perturbing effects of melittin and alamethicin on POPC-based liposomes of varying composition. The results show that the two peptides, despite their differences in physico-chemical properties and proposed mode of action, induce similar structural effects on the liposomes. Importantly, whereas low peptide concentrations leave pure POPC liposomes intact and seemingly unperturbed, POPC liposomes supplemented with 40 mol.% cholesterol change their shape, rupture and fuse in response to the addition of both melittin and alamethicin. In the case of alamethicin, but not melittin, fusion is effectively prevented by inclusion of 10 mol.% POPG in the liposome membranes. By means of a competitive binding assay we furthermore show that alamethicin, in line with earlier findings for melittin, possess high affinity for positively curved lipid surfaces. Moreover, results from the present study show that magainin 2 has a similar preference for curved surfaces.
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| 22. |
- Wessman, Per, et al.
(författare)
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Formulations for freeze-drying of bacteria and their influence on cell survival
- 2013
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Ingår i: Journal of Visualized Experiments. - : MyJove Corporation. - 1940-087X. ; :78
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Tidskriftsartikel (refereegranskat)abstract
- Cellular water can be removed to reversibly inactivate microorganisms to facilitate storage. One such method of removal is freeze-drying, which is considered a gentle dehydration method. To facilitate cell survival during drying, the cells are often formulated beforehand. The formulation forms a matrix that embeds the cells and protects them from various harmful stresses imposed on the cells during freezing and drying. We present here a general method to evaluate the survival rate of cells after freeze-drying and we illustrate it by comparing the results obtained with four different formulations: the disaccharide sucrose, the sucrose derived polymer Ficoll PM400, and the respective polysaccharides hydroxyethyl cellulose (HEC) and hydroxypropyl methyl cellulose (HPMC), on two strains of bacteria, P. putida KT2440 and A. chlorophenolicus A6. In this work we illustrate how to prepare formulations for freeze-drying and how to investigate the mechanisms of cell survival after rehydration by characterizing the formulation using of differential scanning calorimetry (DSC), surface tension measurements, X-ray analysis, and electron microscopy and relating those data to survival rates. The polymers were chosen to get a monomeric structure of the respective polysaccharide resembling sucrose to a varying degrees. Using this method setup we showed that polymers can support cell survival as effectively as disaccharides if certain physical properties of the formulation are controlled.
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| 23. |
- Wessman, Per, et al.
(författare)
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Impact of matrix properties on survival of freeze-dried bacteria
- 2011
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Ingår i: Journal of the Science of Food and Agriculture. - : Wiley. - 0022-5142 .- 1097-0010. ; 91:14, s. 2518-2528
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Tidskriftsartikel (refereegranskat)abstract
- Background: Disaccharides are in general first choice as formulation compounds when freezedrying microorganisms. Although polysaccharides and other biopolymers are considered too large to stabilize and interact with cell components in the same beneficial way as disaccharides, polymers have been reported to support cell survival. In the present study we compare the efficiency of sucrose, the polymers Ficoll, hydroxyethylcellulose, hydroxypropylmethylcellulose and polyvinylalcohol to support survival of three bacterial strains during freeze-drying. The initial osmotic conditions were adjusted to be similar for all formulations. Formulation characterization was used to interpret the impact that different compound properties had on cell survival. Results: Despite differences in molecular size, both sucrose and the sucrose based polymer Ficoll supported cell survival after freeze-drying equally well. All formulations became amorphous upon dehydration. Scanning electron microscopy and X-ray diffraction data showed that the discerned differences in structure of the dry formulations had little impact on the survival rates. The capability of the polymers to support cell survival correlated with the surface activity of the polymers in a similar way for all investigated bacterial strains. Conclusion: Polymer-based formulations can support cell survival as effectively as disaccharides if formulation properties of importance for maintaining cell viability are identified and controlled.
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| 24. |
- Wessman, Per, et al.
(författare)
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Melittin-lipid bilayer interactions and the role of cholesterol
- 2008
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Ingår i: Biophysical Journal. - : Elsevier BV. - 0006-3495 .- 1542-0086. ; 95:9, s. 4324-4336
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Tidskriftsartikel (refereegranskat)abstract
- The membrane-destabilizing effect of the peptide melittin on phosphatidylcholine membranes is modulated by the presence of cholesterol. This investigation shows that inclusion of 40 mol % cholesterol in 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine or 1,2-dioleoyl-sn-glycero-3-phosphocholine liposomes reduces melittin's affinity for the membrane. It is significant that the presence of cholesterol does not increase the amount of membrane-associated melittin needed to cause maximum leakage from, or major structural rearrangements of, the liposomes. Furthermore, comparison of microscopy and leakage data suggests that melittin-induced leakage occurs via different mechanisms in the cholesterol-free and cholesterol-supplemented systems. In the absence of cholesterol, leakage of carboxyfluorescein takes place from intact liposomes in a manner compatible with the presence of small melittin-induced pores. In the presence of cholesterol, on the other hand, adsorption of the peptide causes complete membrane disruption and the formation of long-lived open-bilayer structures. Moreover, in the case of cholesterol-supplemented systems, melittin induces pronounced liposome aggregation. Cryotransmission electron microscopy was used, together with ellipsometry, circular dichroism, turbidity, and leakage measurements, to investigate the effects of melittin on phosphatidylcholine membranes in the absence and presence of cholesterol. The melittin partitioning behavior in the membrane systems was estimated by means of steady-state fluorescence spectroscopy measurements.
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| 25. |
- Wessman, Per, et al.
(författare)
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Minor Components and Oxidative Stability as Determined by DSC of Fractionated and Lipase-catalyzed Structured Rapeseed Oil
- 2013
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Ingår i: Grasas y Aceites. - : Editorial CSIC. - 0017-3495 .- 1988-4214. ; 64, s. 264-271
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Tidskriftsartikel (refereegranskat)abstract
- Natural fats and oils can be modified by various methods to prepare products with desired physical, chemical and nutritional properties. The enrichment and retention of the minor lipid components, the incorporation of capric acid and oxidative stability in low temperature fractionated rapeseed oil (RSO) in acetone were assessed in this study. The fractionated liquid part (L-RSO), the solid part (S-RSO) and the RSO were transesterified with capric acid (CA) at different mole ratios using lipase. The yields of L-RSO and S-RSO were 30 and 70 g per 100 g, respectively. The L-RSO contained higher levels of linoleic acid and linolenic acid, and a lower level of oleic acid compared to the S-RSO. The S-RSO contained a higher amount of total sterols than the RSO and the L-RSO. In contrast, the L-RSO contained a higher amount of total tocopherols than the RSO and the S-RSO. The incorporation of CA was ideal at a mole ratio of 1:3. The content of sterols and tocopherols gradually decreased with an increased mole ratio for the CA incorporation. The oxidative stability shown as onset temperature, determined by DSC, of the S-RSO was higher compared to those of the L-RSO and RSO.
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| 26. |
- Wessman, Per, 1976-
(författare)
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Physico-Chemical Investigations of, and Characterization of Model Membranes for, Lipid-Peptide Interactions
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The main focus of this thesis is on the effects caused by α-helical peptides on liposome structure, the impact of cholesterol on the peptide-membrane interactions, and the effect of aggregate curvature on the peptide affinity. Results of the studies show that the membrane destabilizing effect of the cationic α-helical peptide melittin is modulated by cholesterol. Melittin induces leakage from pure phospholipid liposomes in a manner that is compatible with the presence of small pores. In the case of cholesterol-supplemented liposomes leakage coincides, however, with major structural transformations and rupture of the liposomes. Cholesterol decreases the affinity of melittin for phospholipid bilayers, but once the peptide has adsorbed to the membrane the presence of cholesterol does not offer any resistance against melittin-induced membrane destabilization. Our investigations indicate that cholesterol affects the alamethicin-lipid bilayer interactions in a similar way. PEG-stabilized bilayer disks are formed upon addition of polyethylene glycol (PEG)-lipids to lipid mixtures with high bending rigidity. The partial segregation of components within the bilayer disk, suggested by theoretical calculations and experimental observations, was verified by small angle neutron scattering. By means of a novel competitive binding assay it was shown that the three α-helical peptides melittin, alamethicin, and magainin have high affinity for the curved rim of PEG-stabilized bilayer disks. The bilayer disks have structural, and other properties, that make them interesting for the formulation of peptides and membrane-associated proteins. For stability reasons dry formulations are often preferred. The PEG-stabilized bilayer disks were shown to retain their structure in rehydrated samples that had been freeze- or spray-dried in the presence of lactose.
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| 27. |
- Wessman, Per, et al.
(författare)
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Structural effects caused by spray- and freeze-drying of liposomes and bilayer disks
- 2010
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Ingår i: Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0022-3549 .- 1520-6017. ; 99:4, s. 2032-2048
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Tidskriftsartikel (refereegranskat)abstract
- Cryo-TEM and dynamic light scattering was used to investigate morphological changes induced by spray- and freeze-drying of liposomes and nanosized bilayer disks composed of 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), cholesterol, and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-5000] (DSPE-PEG) from lactose solution. Particular focus was put on the identification of structural alterations that risk influencing the performance of liposomes and bilayer disks as carriers for protein and peptide drugs. Significant changes in the lipid aggregate structure and/or size was noted upon dehydration. Uni-lamellar liposomes tended to shrink in size and become bi-lamellar as a consequence of the drying process. The same transformation was observed upon deliberate establishment of a lactose gradient over the membranes of liposomes in solution. A mechanism based on an osmotically driven invagination of the liposomes is proposed to explain the change from uni- to bi-lamellar structures. PEGylation promoted formation of larger liposomes during spray-drying, and had a similar, but less pronounced, effect also during freeze-drying. The observed structural changes may have important consequences for the bioavailability of protein/peptide drugs bound to, or embedded in, the liposome membranes. The radius of bilayer disks increased upon both spray- and freeze-drying, but the drying procedure did not change the open single-bilayer structure of the disks.
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| 28. |
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| 29. |
- Wessman, T., et al.
(författare)
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Myocardial injury defined as elevated high-sensitivity cardiac troponin T is associated with higher mortality in patients seeking care at emergency departments with acute dyspnea
- 2023
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Ingår i: BMC Emergency Medicine. - 1471-227X. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Elevated levels of cardiac troponin T has been observed in patients seeking care at the emergency department (ED) presenting with chest pain but without myocardial infarction (MI). The clinical importance of this observation remains, however, still unclear. Our main aim was to study the role of cardiac troponin T in patients admitted to the emergency department with acute dyspnea, a group of patients with a high cardiovascular comorbidity, but no primary acute MI. Population and methods: Patients from the age of 18 seeking care at the ED for dyspnea, without an acute cardiac syndrome, and with a recorded assessment of high-sensitivity cardiac troponin T (hs-cTnT), were included (n = 1001). Patients were categorized into 3 groups by hs-cTnT level, i.e. <15, 15–100 and > 100 µg/l. Cox regression with Hazard Ratios (HRs) and 95% Confidence Intervals (CI) for 3-months mortality was performed, with adjustment for sex, age, respiratory frequency, saturation, CHF, renal disease, and BMI. Results: Fully adjusted HRs (95% CI) for 3-month mortality, with hs-cTnT < 15 µg/l as reference level, showed for hs-cTnT 15–100 a HR of 3.682 (1.729–7.844), and for hs-cTnT > 100 a HR of 10.523 (4.465–24.803). Conclusion: Elevated hs-cTnT seems to be a relevant marker of poor prognosis in patients with acute dyspnea without MI and warrants further validation and clinical testing.
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| 30. |
- Wessman, Torgny, et al.
(författare)
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Relationships Between Charlson Comorbidity Index Associated Biomarkers and Outcomes Among Participants in the Malmö Diet and Cancer Study
- 2024
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Ingår i: Biomarkers. - 1366-5804. ; 28:8, s. 722-730
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: The aim was to evaluate two biomarker scores trained to identify comorbidity burden in the prediction of specified chronic morbidities, and mortality in the general population. Methods: Cardiovascular biomarkers were measured in the cardiovascular cohort of the Malmö Diet and Cancer Study. A score of 19 biomarkers associated with Charlson Comorbidity Index (CCI) was created (BSMDC). Individuals with CCI diagnoses and other major comorbidities were excluded. Another score of 11 biomarkers associated with comorbidity burden from a previous study of acute dyspnea was also created (BSADYS). The scores were prospectively evaluated for prediction of mortality, and some chronic diseases, using Cox Proportional Hazards Modell.Results: Fully adjusted models showed that BSMDC was significantly associated per 1 SD increment of the score with incident COPD, 55%, and congestive heart failure, 32%; and with mortality, 33% cardiovascular, 91% respiratory, 30% cancer, and 45% with all-cause mortality. The BSADYS showed no association with these outcomes, after simultaneous inclusion of both biomarker scores to all the clinical covariates.Conclusion: BSMDC shows strong prediction of morbidity and mortality in individuals free from comorbidities at baseline, and the results suggest that healthy individuals with high level of BSMDC would benefit from intense preventive actions.
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| 31. |
- Wessman, Torgny, et al.
(författare)
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The association between length of stay in the emergency department and short-term mortality
- 2022
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Ingår i: Internal and Emergency Medicine. - : Springer Science and Business Media LLC. - 1828-0447 .- 1970-9366. ; 17:1, s. 233-240
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Tidskriftsartikel (refereegranskat)abstract
- The detrimental effects of increased length of stay at the emergency department (ED-LOS) for patient outcome have been sparsely studied in the Swedish setting. Our aim was to further explore the association between ED-LOS and short-term mortality in patients admitted to the EDs of two large University hospitals in Sweden. All adult patients (> 18 years) visiting the ED at the Karolinska University Hospital, Sweden, from 1/1/2010 to 1/1/2015 (n = 639,385) were retrospectively included. Logistic regression analysis was used to determine association between ED-LOS and 7- and 30-day mortality rates. All patients were triaged according to the RETTS-A into different levels of medical urgency and subsequently separated into five quintiles of ED-LOS. Mortality rate was highest in highest triage priority level (7-day mortality 5.24%, and 30-day mortality 9.44%), and decreased by lower triage priority group. For patients with triage priority levels 2–4, prolonged ED-LOS was associated with increased mortality, especially for lowest priority level, OR for priority level 4 and highest quintile of ED-LOS 30-day mortality 1.49 (CI 95% 1.20–1.85). For patients with highest triage priority level the opposite was at hand, with decreasing mortality risk with increasing quintile of ED-LOS for 7-day mortality, and lower mortality for the two highest quintile of ED-LOS for 30-day mortality. In patients not admitted to in-hospital care higher ED-LOS was associated with higher mortality. Our data suggest that increased ED-LOS could be associated with slightly increased short-term mortality in patients with lower clinical urgency and dismissed from the ED.
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| 32. |
- Wollmer, Martin, et al.
(författare)
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Plasma calprotectin in the emergency department : a potential clinical biomarker for patients with infectious diseases
- 2021
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Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation. - : Taylor & Francis. - 0036-5513 .- 1502-7686. ; 81:7, s. 593-597
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Tidskriftsartikel (refereegranskat)abstract
- Increased levels of plasma calprotectin are reported in patients with infectious diseases. However, the clinical usefulness of calprotectin as a biomarker to identify patients with infectious diseases in the emergency department (ED) setting has not been investigated. To study the ability of calprotectin to discriminate patients with acute infectious diseases and dyspnea from patients with other causes of acute dyspnea in the ED setting. Patients aged ≥18 years seeking ED during daytime on weekdays between March 2013 and July 2018, with acute dyspnea, were included. Participants (n = 1287) were triaged according to Medical Emergency Triage and Treatment System-Adult score (METTS-A) or Rapid Emergency Triage and Treatment System (RETTS), and blood samples were collected. The association between calprotectin and other markers of infectious diseases, i.e. biomarkers (CRP, leucocytes) and body temperature, was studied. The predictive value of calprotectin for the outcome of acute infection was evaluated with receiver operating characteristic (ROC) analysis. Univariate cross-sectional regression showed significant associations between calprotectin and leucocytes, CRP and body temperature. Patients with severe infections including pneumonia (n = 119) had significantly higher concentrations of calprotectin compared to patients with heart failure (n = 162) or chronic obstructive pulmonary disease (n = 183). When tested for the outcome of acute infection (n = 109), the area under the ROC curve (AUROC) was for CRP 0.83 and for calprotectin 0.78. Plasma calprotectin identifies infectious diseases in ED patients with acute dyspnea, and the clinical usefulness of Calprotectin in the ED has to be further studied.
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| 33. |
- Wright, David A., et al.
(författare)
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Surface coating aids survival of Serratia entomophila (Enterobacteriaceae) in granules for surface application
- 2017
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Ingår i: Biocontrol science and technology (Print). - : Informa UK Limited. - 0958-3157 .- 1360-0478. ; 27:12, s. 1383-1399
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Tidskriftsartikel (refereegranskat)abstract
- The nonspore-forming bacterium Serratia entomophila may be used to control the New Zealand grass grub (Costelytra giveni) but is sensitive to environmental stress and must be formulated to improve survival. Existing formulations require subsurface application limiting the area that can be treated. Formulations that allow delivery by broadcast methods are desirable to reduce application costs and increase the potential for aerial application to inaccessible areas. Two formulations were prepared for use in experiments examining the persistence and movement of inoculum through soil. When granules were applied to the soil surface, bacterial survival was negligible in uncoated core, but improved with increasing thickness of the coating. Both survival of bacteria and release into the soil were influenced by soil moisture content. Granules at <12% soil moisture showed high bacterial mortality and reduced delivery to the soil, while at 28% soil moisture most bacteria were released to the soil. There was a high level of survival of the applied bacteria within granules at 20% and 28% soil moisture. The formulations maintained viability of S. entomophila in granules stored under ambient conditions for more than 6 months. In laboratory and field tests, the application of granules caused disease in the target grass grub larvae, whether application was applied to the surface or subsurface. In field trials, broadcast applied granules could produce equivalent disease to thin-coat granules drilled into the soil, but these levels of disease were associated with the occurrence of precipitation shortly after application.
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| 34. |
- Wändell, Per, et al.
(författare)
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The association between BMI and 90-day mortality in patients with and without diabetes seeking care at the emergency department.
- 2021
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Ingår i: Upsala Journal of Medical Sciences. - : Uppsala Medical Society. - 0300-9734 .- 2000-1967. ; 126
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Tidskriftsartikel (refereegranskat)abstract
- Background: The impact of body mass index (BMI) on mortality varies with age and disease states. The aim of this research study was to analyse the associations between BMI categories and short- and long-term mortality in patients with or without diabetes seeking care at the emergency department (ED) with acute dyspnoea.Population and methods: Patients aged ≥18 years at ED during daytime on weekdays from March 2013 to July 2018 were included. Participants were triaged according to the Medical Emergency Triage and Treatment System-Adult score (METTS-A), and blood samples were collected. Totally, 1,710 patients were enrolled, with missing values in 113, leaving 1,597 patients, 291 with diabetes and 1,306 without diabetes. The association between BMI and short-term (90-day) and long-term (mean follow-up time 2.1 years) mortality was estimated by Cox regression with normal BMI (18.5-24.9) as referent category, with adjustment for age, sex, METTS-A scoring, glomerular filtration rate, smoking habits and cardiovascular comorbidity in a fully adjusted model. The Bonferroni correction was also used.Results: Regarding long-term mortality, patients with diabetes and BMI category ≥30 kg/m2 had a fully adjusted Hazard Ratio (HR) of 0.40 (95% confidence interval [CI]: 0.23-0.69), significant after the Bonferroni correction. Amongst patients without diabetes, those with underweight had an increased risk but only of borderline significance, whilst risks in those with overweight or obesity did not differ from reference.Regarding short-term mortality, risks did not differ from reference amongst patients with or without diabetes.Conclusions: We found divergent long-term mortality risks in patients with and without diabetes, with lower risk in obese patients (BMI ≥ 30 kg/m2) with diabetes, but no increased risk for patients without diabetes and overweight (BMI: 25-29.9 kg/m2) and obesity.
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| 35. |
- Önneby, Karin, et al.
(författare)
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Effects of di- and polysaccharide formulations and storage conditions on survival of freeze-dried Sphingobium sp.
- 2013
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Ingår i: World Journal of Microbiology & Biotechnology. - : Springer Science and Business Media LLC. - 0959-3993 .- 1573-0972. ; 29:8, s. 1399-1408
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Tidskriftsartikel (refereegranskat)abstract
- In this study we have compared the ability of the organic polymers Ficoll and hydroxyethylcellulose (HEC) and the disaccharides sucrose and trehalose to support cell survival during freeze-drying and subsequent storage of a gram-negative Sphingobium sp. In addition to determination of viability rates, cell integrity was evaluated using lipid peroxidation and RNA quality assays for the different storage conditions and formulation compositions. All formulations resulted in high initial cell survival rates after freeze-drying. However, the disaccharide formulations were superior to the polymer-based formulations in supporting cell survival during storage with the exception of Ficoll that upon storage under vacuum yielded bacterial survival rates equal to that of sucrose. Storage in the presence of both oxygen and moisture was detrimental for bacterial survival in all formulations tested, however, lipid peroxidation or RNA damages were not the controlling mechanisms for cell death in this system. The ability of Ficoll and HEC to support cell survival during freeze-drying show that organic polymers, expected to lack the water replacing capability of e.g. disaccharides, can successfully be used as lyoprotectants. For storage under vacuum conditions we suggest that the intracellular amount of sugars (i.e. trehalose), or other protective native cell components, is sufficient for a basic protection inside the bacteria cell and that the amorphous state is the most important aspect of the formulation excipient. However, when exposed to oxygen and moisture during storage this protection is not sufficient to prevent cell degeneration.
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