| 11. |
- Sundvall, Pär-Daniel, et al.
(author)
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Antimicrobial resistance in urinary pathogens among Swedish nursing home residents remains low: a cross-sectional study comparing antimicrobial resistance from 2003 to 2012
- 2014
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In: BMC Geriatrics. - : Springer Science and Business Media LLC. - 1471-2318. ; 14
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Journal article (peer-reviewed)abstract
- Background: There are several risk factors for the colonisation, infection and spreading of antibiotic resistant bacteria among elderly residents of nursing homes. An updated estimate of the native prevalence of antimicrobial resistance in uropathogens among Swedish nursing home residents is needed. Methods: Urine specimens were collected for culture and antimicrobial susceptibility testing against mecillinam, ampicillin, cefadroxil, trimethoprim, nitrofurantoin and quinolones from the residents of 32 and 22 nursing homes, respectively. The residents were capable of providing a voided urine sample in 2003 and 2012. In 2012 urine specimens were also collected from residents with urinary catheters. Any antibiotic treatment during the previous month was registered in 2003 as well as hospitalisation and any antibiotic treatment during the previous six months in 2012. Results: The proportion of positive urine cultures was 32% (207/651) in voided urine specimens in 2003, 35% (147/421) in 2012, and 46% (27/59) in urine samples from catheters in 2012. Escherichia coli (E. coli) was the most commonly occurring bacteria. Resistance rates in E. coli (voided urine specimens) in 2012 were; ampicillin 21%, trimethoprim 12%, mecillinam 7.7%, ciprofloxacin 3.4%, cefadroxil 2.6% and nitrofurantoin 0.85%. There were no significant changes in the average resistance rates in E. coli for antibiotics tested 2003-2012. In 2012, two isolates of E. coli produced extended spectrum beta-lactamase enzymes (ESBL) and one with plasmid mediated AmpC production. Any antibiotic treatment during the previous month increased the risk for resistance in E. coli, adjusted for age and gender; for mecillinam with an odds ratio (OR) of 7.1 (2.4-21; p = 0.00049), ampicillin OR 5.2 (2.4-11; p = 0.000036), nalidixic acid OR 4.6 (1.4-16; p = 0.014) and trimethoprim OR 3.9 (1.6-9.2; p = 0.0023). Hospitalisation during the previous six months increased the risk for antibiotic resistance in E. coli to ampicillin, ciprofloxacin and any antimicrobial tested, adjusted for age, gender and antibiotic treatments during the previous six months. Conclusions: The average rates of antimicrobial resistance were low and did not increase between 2003 and 2012 in E. coli urinary isolates among Swedish nursing home residents. Antibiotic treatment during the previous month and hospitalisation during the previous six months predicted higher resistance rates.
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| 12. |
- Sundvall, Pär-Daniel, et al.
(author)
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Interleukin-6 concentrations in the urine and dipstick analyses were related to bacteriuria but not symptoms in the elderly: a cross sectional study of 421 nursing home residents
- 2014
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In: BMC Geriatrics. - : Springer Science and Business Media LLC. - 1471-2318. ; 14
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Journal article (peer-reviewed)abstract
- Background: Up to half the residents of nursing homes for the elderly have asymptomatic bacteriuria (ABU), which should not be treated with antibiotics. A complementary test to discriminate between symptomatic urinary tract infections (UTI) and ABU is needed, as diagnostic uncertainty is likely to generate significant antibiotic overtreatment. Previous studies indicate that Interleukin-6 (IL-6) in the urine might be suitable as such a test. The aim of this study was to investigate the association between laboratory findings of bacteriuria, IL-6 in the urine, dipstick urinalysis and newly onset symptoms among residents of nursing homes. Methods: In this cross sectional study, voided urine specimens for culture, urine dipstick and IL-6 analyses were collected from all residents capable of providing a voided urine sample, regardless of the presence of symptoms. Urine specimens and symptom forms were provided from 421 residents of 22 nursing homes. The following new or increased nonspecific symptoms occurring during the previous month were registered; fatigue, restlessness, confusion, aggressiveness, loss of appetite, frequent falls and not being herself/himself, as well as symptoms from the urinary tract; dysuria, urinary urgency and frequency. Results: Recent onset of nonspecific symptoms was common among elderly residents of nursing homes (85/421). Urine cultures were positive in 32% (135/421), Escherichia coli was by far the most common bacterial finding. Residents without nonspecific symptoms had positive urine cultures as often as those with nonspecific symptoms with a duration of up to one month. Residents with positive urine cultures had higher concentrations of IL-6 in the urine (p < 0.001). However, among residents with positive urine cultures there were no differences in IL-6 concentrations or dipstick findings between those with or without nonspecific symptoms. Conclusions: Nonspecific symptoms among elderly residents of nursing homes are unlikely to be caused by bacteria in the urine. This study could not establish any clinical value of using dipstick urinalysis or IL-6 in the urine to verify if bacteriuria was linked to nonspecific symptoms.
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| 13. |
- Svensen, Christer H, et al.
(author)
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Arteriovenous differences in plasma dilution and the distribution kinetics of lactated ringer's solution
- 2009
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In: Anesthesia and Analgesia. - : Lippincott Williams & Wilkins. - 0003-2999 .- 1526-7598. ; 108:1, s. 128-133
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Journal article (peer-reviewed)abstract
- BACKGROUND: Conventional concept suggests that infused crystalloid fluid is first distributed in the plasma volume and then, since the capillary permeability for fluid is very high, almost instantly equilibrates with the extracellular fluid space. We challenge whether this view is consistent with findings based on volume kinetic analysis.METHODS: Fifteen volunteers received an IV infusion of 15 mL/kg of lactated Ringer's solution during 10 min. Simultaneous arterial and venous blood hemoglobin (Hgb) samples were obtained and Hgb concentrations measured. The arteriovenous (AV) difference in Hgb dilution in the forearm was determined and a volume kinetic model was fitted to the series of Hgb concentrations in arterial and venous blood.RESULTS: The AV difference in plasma dilution was only positive during the infusion and for 2.5 min thereafter, which represents the period of net flow of fluid from plasma to tissue. Kinetic analysis showed that volume expansion of the peripheral fluid space began to decrease 14 min (arterial blood) and 20 min (venous blood) after the infusion ended. Distribution of lactated Ringer's solution apparently occurs much faster in the forearm than in the body as a whole. Therefore, the AV difference in the arm does not accurately reflect the distribution of Ringer's solutions or whole-body changes in plasma volume.CONCLUSIONS: The relatively slow whole-body distribution of lactated Ringer's solution, which boosts the plasma volume expansion during and for up to 30 min after an infusion, is probably governed by a joint effect of capillary permeability and differences in tissue perfusion between body regions.
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| 14. |
- Thalén, Niklas, 1985-, et al.
(author)
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Systems biology greatly improve activity of secreted therapeutic sulfatase in CHO bioprocess
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Other publication (other academic/artistic)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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| 15. |
- Thalén, Niklas, et al.
(author)
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Tuning of CHO secretional machinery improve activity of secreted therapeutic sulfatase 150-fold
- 2024
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In: Metabolic engineering. - : Elsevier BV. - 1096-7176 .- 1096-7184. ; 81, s. 157-166
-
Journal article (peer-reviewed)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. The recombinant production of such sulfatases suffers greatly from both low product activity and yield, further limiting accessibility for patient groups. To mitigate the low product activity, we have investigated cellular properties through computational evaluation of cultures with varying media conditions and comparison of two CHO clones with different levels of one active sulfatase variant. Transcriptome analysis identified 18 genes in secretory pathways correlating with increased sulfatase production. Experimental validation by upregulation of a set of three key genes improved the specific enzymatic activity at varying degree up to 150-fold in another sulfatase variant, broadcasting general production benefits. We also identified a correlation between product mRNA levels and sulfatase activity that generated an increase in sulfatase activity when expressed with a weaker promoter. Furthermore, we suggest that our proposed workflow for resolving bottlenecks in cellular machineries, to be useful for improvements of cell factories for other biologics as well.
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| 16. |
- van der Velde, Ype, et al.
(author)
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Consequences of mixing assumptions for time-variable travel time distributions
- 2015
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In: Hydrological Processes. - : Wiley. - 0885-6087 .- 1099-1085. ; 29:16, s. 3460-3474
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Journal article (peer-reviewed)abstract
- The current generation of catchment travel time distribution (TTD) research, integrating nearly three decades of work since publication of Water's Journey from Rain to Stream, seeks to represent the full distribution in catchment travel times and its temporal variability. Here, we compare conceptualizations of increasing complexity with regards to mixing of water storages and evaluate how these assumptions influence time-variable TTD estimates for two catchments with contrasting climates: the Gardsjon catchment in Sweden and the Marshall Gulch catchment in Arizona, USA. Our results highlight that, as long as catchment TTDs cannot be measured directly but need to be inferred from input-output signals of catchments, the inferred catchment TTDs depend strongly on the underlying assumptions of mixing within a catchment. Furthermore, we found that the conceptualization of the evapotranspiration flux strongly influences the inferred travel times of stream discharge. For the wet and forested Gardsjon catchment in Sweden, we inferred that evapotranspiration most likely resembles a completely mixed sample of the water stored in the catchment; however, for the drier Marshall Gulch catchment in Arizona, evapotranspiration predominantly contained the younger water stored in the catchment. For the Marshall Gulch catchment, this higher probability for young water in evapotranspiration resulted in older water in the stream compared to travel times inferred with assumptions of complete mixing. New observations that focus on the TTD of the evapotranspiration flux and the actual travel time of water through a catchment are necessary to improve identification of mixing and consequently travel times of stream water. Copyright (c) 2014 John Wiley & Sons, Ltd.
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| 17. |
- Webb, Jim, et al.
(author)
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An Assessment of the Variation of Manure Nitrogen Efficiency throughout Europe and an Appraisal of Means to Increase Manure-N Efficiency
- 2013
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In: Advances in Agronomy. ; 119, s. 371-442
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Journal article (peer-reviewed)abstract
- Using the nitrogen (N) in organic manures more effectively reduces losses to the environment. A requirement to take allowance of the N conserved by reduced ammonia (NH3)-emission techniques would increase manure-N efficiency by up to 15%. Covering manure stores and land application of slurry by injection beneath the soil surface and by rapid incorporation of both slurries and solid manures into uncropped soil reduce NH3 emissions. Injection of cattle slurry also reduces N immobilization compared with application methods, which mix the slurry with soil and increases manure-N efficiency by ca 10-15%. In growing cereals, NH3 emissions can be reduced by band spreading within the canopy. Anaerobic digestion of slurry may also increase manure-N availability in the season of application by 10-20%, compared with undigested slurry. Slurry acidification may increase manure-N efficiency by 35-65% by reducing total NH3 losses by 70% compared with unacidified slurry stored without cover and not incorporated after spreading. To fully utilize the fertilizer value of manure-N, uptake over more than 1 year needs to be accounted for. This is particularly important for solid manures which provide less-available N in the season after application than slurries but release more N to crops in subsequent years. Using manure-N as a sole N source may limit overall manure-N efficiency. Applying manures at reduced rates over a larger crop area, using N fertilizer at times when crop recovery of manure-N may be limited, may give the greatest overall manure-N efficiency.
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| 18. |
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