| 1. |
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| 2. |
- Sandén, Anna Maria, et al.
(author)
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Limiting factors in Escherichia coli fed-batch production of recombinant proteins
- 2003
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In: Biotechnology and Bioengineering. - : Wiley. - 0006-3592 .- 1097-0290. ; 81:2, s. 158-166
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Journal article (peer-reviewed)abstract
- Fed-batch production of recombinant beta-galactosidase in E. coli was studied with respect to the specific growth rate at induction. The cultivations were designed to induce protein production by IPTG at a glucose feed rate corresponding to high (mu = 0.5 h(-1)) or low (mu = 0.1 h(-1)) specific growth rate. Protein production rate was approximately 100% higher at the higher specific growth rate, resulting in the accumulation of beta-galactosidase up to 30% of the total cell protein. Transcription analysis showed that beta-galactosidase-specific messenger RNA was immediately formed after induction (<5 min), but the amount was the same in both cases and was thus not the initial limiting factor. The content of ribosomes, as represented by rRNA, rapidly decreased with specific growth rate from a relative level of 100%, at the high specific growth rate, to 20% at the low specific growth rate. At high specific growth rate, ribosomes were additionally degraded upon induction due to the high production level. Translation therefore seemed to be the initial limiting factor of the protein synthesis capacity. The alarmone guanosine tetraphosphate increased at both high and low feed level inductions, indicating an induction-forced starvation of charged tRNA and/or glucose. The altered physiological status was also detected by the formation of acetic acid. However, the higher production rate resulted in high-level accumulation of acetic acid, which was absent at low feed rate production. Acetic acid production is thus coupled to the high product formation rate and is proposed to be due either to a precursor drain of Krebs cycle intermediates and a time lag before induction of the glyoxalate shunt, or to single amino acid overflow, since the model product is relatively poor in glycin and alanin. In conclusion, it is proposed that production at high specific growth rate becomes precursor-limited, while production at low specific growth rate is carbon- and/or energy-limited.
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| 3. |
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| 6. |
- Artigas, J., et al.
(author)
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Towards a renewed research agenda in ecotoxicology
- 2012
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In: Environmental Pollution. - : Elsevier BV. - 0269-7491. ; 160, s. 201-206
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Journal article (peer-reviewed)abstract
- New concerns about biodiversity, ecosystem services and human health triggered several new regulations increasing the need for sound ecotoxicological risk assessment. The PEER network aims to share its view on the research issues that this challenges. PEER scientists call for an improved biologically relevant exposure assessment. They promote comprehensive effect assessment at several biological levels. Biological traits should be used for Environmental risk assessment (ERA) as promising tools to better understand relationships between structure and functioning of ecosystems. The use of modern high throughput methods could also enhance the amount of data for a better risk assessment. Improved models coping with multiple stressors or biological levels are necessary to answer for a more scientifically based risk assessment. Those methods must be embedded within life cycle analysis or economical models for efficient regulations. Joint research programmes involving humanities with ecological sciences should be developed for a sound risk management. (C) 2011 Elsevier Ltd. All rights reserved.
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| 7. |
- Piehl, F., et al.
(author)
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Efficacy and Safety of Rituximab for New-Onset Generalized Myasthenia Gravis The RINOMAX Randomized Clinical Trial
- 2022
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In: Jama Neurology. - : American Medical Association (AMA). - 2168-6149 .- 2168-6157.
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Journal article (peer-reviewed)abstract
- IMPORTANCE Rituximab is a third-line option for refractory generalized myasthenia gravis (MG) based on empirical evidence, but its effect in new-onset disease is unknown. OBJECTIVE To investigate the efficacy and safety of rituximab compared with placebo as an add-on to standard of care for MG. DESIGN, SETTING, AND PARTICIPANTS This randomized, double-blind, placebo-controlled study took place throughout 48 weeks at 7 regional clinics in Sweden. Key inclusion criteria were age older than 18 years, onset of generalized symptoms within 12 months or less, and a Quantitative Myasthenia Gravis (QMG) score of 6 or more. Patients were screened from October 20, 2016, to March 2, 2020. Key exclusion criteria included pure ocular MG, suspected thymoma, previous thymectomy, and prior noncorticosteroid immunosuppressants or high doses of corticosteroids. INTERVENTIONS Participants were randomized 1:1 without stratification to a single intravenous infusion of 500 mg of rituximab or matching placebo. MAIN OUTCOMES AND MEASURES Minimal disease manifestations at 16 weeks defined as a QMG score of 4 or less with prednisolone, 10 mg or less daily, and no rescue treatment. RESULTS Of 87 potentially eligible patients, 25 were randomized to rituximab (mean [SD] age, 67.4 [13.4] years; 7 [28%] female) and 22 to placebo (mean [SD] age, 58 [18.6] years; 7 [32%] female). Compared with placebo, a greater proportion with rituximab met the primary end point; 71% (17 of 24) in the rituximab group vs 29% (6 of 21) in the placebo group (Fisher exact test P = .007; probability ratio, 2.48 [95% CI, 1.20-5.11]). Secondary end points, comparing changes in Myasthenia Gravis Activities of Daily Living and Myasthenia Gravis Quality of Life at 16 weeks with QMG at 24 weeks did not differ between groups with censoring for rescue treatment (per-protocol analysis) but were in favor of active treatment when rescue treatment was taken into account by worst rank imputation (post hoc analysis). Rescue treatments were also more frequent in the placebo arm (rituximab: 1 [4%]; placebo, 8 [36%]). One patient in the placebo arm had a myocardial infarction with cardiac arrest and 1 patient in the active arm experienced a fatal cardiac event. CONCLUSIONS AND RELEVANCE A single dose of 500 mg of rituximab was associated with greater probability of minimal MG manifestations and reduced need of rescue medications compared with placebo. Further studies are needed to address long-term benefit-risk balance with this treatment.
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| 8. |
- Bell, Hege-Therese, et al.
(author)
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Nurses’ and pharmacists’ learning experiences from participating in interprofessional medication reviews for elderly in primary health care - a qualitative study
- 2017
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In: BMC Family Practice. - : Springer Science and Business Media LLC. - 1471-2296. ; 18
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Journal article (peer-reviewed)abstract
- Background: Traditionally, drug prescription and follow up have been the sole responsibility of physicians. However, interprofessional medication reviews (IMRs) have been developed to prevent drug discrepancies and patient harmespecially for elderly patients with polypharmacy and multimorbidity. What participating nurses and pharmacists learn from each other during IMR is poorly studied. The aim of this study was to investigate nurses’ and pharmacists’ perceived learning experience after participating in IMRs in primary health care for up to two years.Methods: A qualitative study with semi-structured focus group interviews and telephone interviews with nurses and pharmacists with experience from IMRs in nursing homes and home based services. The data was analysed thematically by using systematic text condensation.Results: Thirteen nurses and four pharmacists were interviewed. They described some challenges concerning how to ensure participation of all three professions and how to get thorough information about the patient. As expected, both professions talked of an increased awareness with time of the benefit of working as a team and the perception of contributing to better and more individual care. The nurses’ perception of the pharmacist changed from being a controller of drug management routines towards being a source of pharmacotherapy knowledge and a discussant partner of appropriate drug therapy in the elderly. The pharmacists became more aware of the nurses’ crucial role of providing clinical information about the patient to enable individual advice. Increasingly the nurses learned to link the patient’s symptoms of effect and side effect to the drugs prescribed.Conclusions: Although experiencing challenges in conducting IMRs, the nurses and pharmacists had learning experiences they said improved both their own practice and the quality of drug management. There are some challenges concerning how to ensure participation of all three professions and how to get thorough information about the patient.
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| 9. |
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| 10. |
- Khonsari, Roman H., et al.
(author)
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Fronto-facial advancement and bipartition in Crouzon-Pfeiffer and Apert syndromes : Impact of fronto-facial surgery upon orbital and airway parameters in FGFR2 syndromes
- 2016
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In: Journal of Cranio-Maxillofacial Surgery. - : Elsevier BV. - 1010-5182 .- 1878-4119. ; 44:10, s. 1567-1575
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Journal article (peer-reviewed)abstract
- A major concern in FGFR2 craniofaciosynostosis is oculo-orbital disproportion, such that orbital malformation provides poor accommodation and support for the orbital contents and peri-orbita, leading to insufficient eyelid closure, corneal exposure and eventually to functional visual impairment. Fronto-facial monobloc osteotomy followed by distraction osteogenesis aims to correct midfacial growth deficiencies in Crouzon–Pfeiffer syndrome patients. Fronto-facial bipartition osteotomy followed by distraction is a procedure of choice in Apert syndrome patients. These procedures modify the shape and volume of the orbit and tend to correct oculo-orbital disproportion. Little is known about the detailed 3D shape of the orbital phenotype in CPS and AS, and about how this is modified by fronto-facial surgery.Twenty-eight patients with CMS, 13 patients with AS and 40 control patients were included. CT scans were performed before and after fronto-facial surgery. Late post-operative scans were available for the Crouzon–Pfeiffer syndrome group. Orbital morphology was investigated using conventional three-dimensional cephalometry and shape analysis after mesh-based segmentation of the orbital contents.We characterized the 3D morphology of CPS and AS orbits and showed how orbital shape is modified by surgery. We showed that monobloc-distraction in CPS and bipartition-distraction in AS specifically address the morphological characteristics of the two syndromes.
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| 11. |
- Khonsari, R H, et al.
(author)
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Shape and volume of craniofacial cavities in intentional skull deformations
- 2013
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In: American Journal of Physical Anthropology. - : Wiley. - 0002-9483 .- 1096-8644. ; 151:1, s. 110-119
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Journal article (peer-reviewed)abstract
- Intentional cranial deformations (ICD) have been observed worldwide but are especially prevalent in preColombian cultures. The purpose of this study was to assess the consequences of ICD on three cranial cavities (intracranial cavity, orbits, and maxillary sinuses) and on cranial vault thickness, in order to screen for morphological changes due to the external constraints exerted by the deformation device. We acquired CT-scans for 39 deformed and 19 control skulls. We studied the thickness of the skull vault using qualitative and quantitative methods. We computed the volumes of the orbits, of the maxillary sinuses, and of the intracranial cavity using haptic-aided semi-automatic segmentation. We finally defined 3D distances and angles within orbits and maxillary sinuses based on 27 anatomical landmarks and measured these features on the 58 skulls. Our results show specific bone thickness patterns in some types of ICD, with localized thinning in regions subjected to increased pressure and thickening in other regions. Our findings confirm that volumes of the cranial cavities are not affected by ICDs but that the shapes of the orbits and of the maxillary sinuses are modified in circumferential deformations. We conclude that ICDs can modify the shape of the cranial cavities and the thickness of their walls but conserve their volumes. These results provide new insights into the morphological effects associated with ICDs and call for similar investigations in subjects with deformational plagiocephalies and craniosynostoses.
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| 12. |
- Melin, Karin, 1964, et al.
(author)
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Treatment Gains Are Sustainable in Pediatric Obsessive-Compulsive Disorder: Three-Year Follow-Up From the NordLOTS
- 2020
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In: Journal of the American Academy of Child and Adolescent Psychiatry. - Amsterdam : Elsevier BV. - 0890-8567 .- 1527-5418. ; 59:2, s. 244-253
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Journal article (peer-reviewed)abstract
- © 2019 American Academy of Child and Adolescent Psychiatry Objective: This study evaluated the long-term outcomes of a stepped care treatment for pediatric obsessive-compulsive disorder (OCD) and investigated whether response to first-step cognitive-behavioral therapy (CBT) is an important indicator of 3-year outcomes. Method: This study is a part of the Nordic Long-term OCD Treatment Study (NordLOTS), in which 269 children and adolescents were treated with CBT. Nonresponders to CBT were randomized to extended treatment with continued CBT or pharmacotherapy with sertraline. Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) scores no higher than 15 and no higher than 10 were defined as treatment response and remission, respectively. Participants were assessed 2 and 3 years after first-step CBT. Linear mixed-effects models were used to analyze the outcomes. Results: Intent-to-treat analyses showed a significant decrease in CY-BOCS total score from baseline (24.6) to 3-year follow-up (5.0; p = .001), with a mean decrease of 5.9 from after treatment to 3-year follow-up. Three years after treatment, 90% (n = 242) of participants were rated as responders and 73% were in clinical remission. The duration of treatment did not influence the symptom level at 3-year follow-up (p = .998) and no significant difference was found (p = .169) between the extended treatment conditions. Conclusion: The results suggest that evidence-based treatment for pediatric OCD has long-term positive effects, whether a first step of manual-based CBT or extended treatment with CBT or sertraline. The improvements were maintained, and the symptoms decreased further during follow-up and were, after 3 years, similarly independent of treatment duration and form of extended treatment. Clinical trial registration information: Nordic Long-term Obsessive-Compulsive Disorder (OCD) Treatment Study; www.controlled-trials.com; ISRCTN66385119.
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| 13. |
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| 14. |
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| 15. |
- Tannock, Ian F., et al.
(author)
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Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer
- 2004
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In: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 351:15, s. 1502-12
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Journal article (other academic/artistic)abstract
- BACKGROUND: Mitoxantrone plus prednisone reduces pain and improves the quality of life in men with advanced, hormone-refractory prostate cancer, but it does not improve survival. We compared such treatment with docetaxel plus prednisone in men with this disease. METHODS: From March 2000 through June 2002, 1006 men with metastatic hormone-refractory prostate cancer received 5 mg of prednisone twice daily and were randomly assigned to receive 12 mg of mitoxantrone per square meter of body-surface area every three weeks, 75 mg of docetaxel per square meter every three weeks, or 30 mg of docetaxel per square meter weekly for five of every six weeks. The primary end point was overall survival. Secondary end points were pain, prostate-specific antigen (PSA) levels, and the quality of life. All statistical comparisons were against mitoxantrone. RESULTS: As compared with the men in the mitoxantrone group, men in the group given docetaxel every three weeks had a hazard ratio for death of 0.76 (95 percent confidence interval, 0.62 to 0.94; P=0.009 by the stratified log-rank test) and those given weekly docetaxel had a hazard ratio for death of 0.91 (95 percent confidence interval, 0.75 to 1.11; P=0.36). The median survival was 16.5 months in the mitoxantrone group, 18.9 months in the group given docetaxel every 3 weeks, and 17.4 months in the group given weekly docetaxel. Among these three groups, 32 percent, 45 percent, and 48 percent of men, respectively, had at least a 50 percent decrease in the serum PSA level (P<0.001 for both comparisons with mitoxantrone); 22 percent, 35 percent (P=0.01), and 31 percent (P=0.08) had predefined reductions in pain; and 13 percent, 22 percent (P=0.009), and 23 percent (P=0.005) had improvements in the quality of life. Adverse events were also more common in the groups that received docetaxel. CONCLUSIONS: When given with prednisone, treatment with docetaxel every three weeks led to superior survival and improved rates of response in terms of pain, serum PSA level, and quality of life, as compared with mitoxantrone plus prednisone.
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| 16. |
- Undeland, I, et al.
(author)
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Preventing lipid oxidation during recovery of functional proteins from herring (Clupea harengus) fillets by an acid solubilization process
- 2005
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In: Journal of Agricultural and Food Chemistry. - 0021-8561 .- 1520-5118. ; 53:14, s. 5625-5634
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Journal article (peer-reviewed)abstract
- It has previously been found that a process based on solubilization at pH 2.7 gives high yields of herring muscle proteins with good functionality. In this study, the development of lipid oxidation during acid processing of herring mince was studied. It was tested how modifications of the process conditions and/or additions of antioxidants could prevent lipid oxidation during the actual process and then during ice storage of the protein isolates. Processing parameters evaluated were prewash of the mince, exposure time to pH 2.7, inclusion or exclusion of a high-speed centrifugation, and addition of antioxidants. Antioxidants tested were erythorbate (0.2%, 9.3 mM), sodium tripolyphosphate (STPP; 0.2%, 5.4 mM), ethylenediaminetetraacetic acid (EDTA; 0.044%, 1.5 mM), and milk proteins (4%). The first three antioxidants were added in the prewash or during the homogenization step, whereas milk proteins were added to the final precipitate. At time 0, all isolates were analyzed for pH, moisture content, and thiobarbituric reactive substances (TBARS). Selected isolates were also analyzed for lipid and protein content. Stability during ice storage was followed in terms of odor, TBARS, and color (a*/b* values). Extensive lipid oxidation took place using the "control" process without high-speed centrifugation. This was not significantly (p <= 0.05) affected by a prewash or varied exposure time to pH 2.7. Including high-speed centrifugation (20 min, 10000g) significantly (p <= 0.05) reduced TBARS values, total lipids, a* values and b* values. Erythorbate alone, or in combination with STPP/EDTA, significantly (p <= 0.05) reduced lipid oxidation during processing if added in the prewash or homogenization step. During ice storage, better stability was gained when antioxidants were added in both of these steps and when EDTA was used instead of STPP.
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| 17. |
- Van Dam, K.K., et al.
(author)
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Velo and REXAN – Integrated Data Management and High Speed Analysis for Experimental Facilities
- 2012
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In: <em>Proceeding IEEE International Conference on E-Science</em> 2012. - 9781467344678 ; , s. 1-9
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Conference paper (other academic/artistic)abstract
- The Chemical Imaging Initiative at the Pacific Northwest National Laboratory (PNNL) is creating a `Rapid Experimental Analysis' (REXAN) Framework, based on the concept of reusable component libraries. REXAN allows developers to quickly compose and customize high throughput analysis pipelines for a range of experiments, as well as supporting the creation of multi-modal analysis pipelines. In addition, PNNL has coupled REXAN with its collaborative data management and analysis environment Velo to create an easy to use data management and analysis environments for experimental facilities. This paper will discuss the benefits of Velo and REXAN in the context of three examples: PNNL High Resolution Mass Spectrometry - reducing analysis times from hours to seconds, and enabling the analysis of much larger data samples (100KB to 40GB) at the same time. · ALS X-Ray Tomography - reducing analysis times of combined STXM and EM data collected at the ALS from weeks to minutes, decreasing manual work and increasing data volumes that can be analysed in a single step. · Multi-modal nano-scale analysis of STXM and TEM data - providing a semi automated process for particle detection. The creation of REXAN has significantly shortened the development time for these analysis pipelines. The integration of Velo and REXAN has significantly increased the scientific productivity of the instruments and their users by creating easy to use data management and analysis environments with greatly reduced analysis times and improved analysis capabilities.
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| 18. |
- Wiklund, Ingela, et al.
(author)
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A comparative study in Stockholm, Sweden of labour outcome and women's perceptions of being referred in labour
- 2002
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In: Midwifery. - : Churchill Livingstone. - 0266-6138 .- 1532-3099. ; 18:3, s. 193-199
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Journal article (peer-reviewed)abstract
- Objective: to study the outcome of labour and women's perceptions of being referred after onset of labour. Design: a comparative study carried out between October 1998 and April 1999. Setting: prospective parents in Stockholm, Sweden are offered a choice of which of the five hospitals in which they want to give birth. In reality, there is a lack of maternity beds in Stockholm to implement this policy and therefore nearly 10% of labouring women are being referred during labour. Participants: the study population was selected from one of the five hospitals. Included in the study were 266 labouring women, with a 37-42 weeks uncomplicated pregnancy, fetus presenting by the vertex and spontaneous onset of labour. During pregnancy, all the women had chosen the same labour ward where they planned to deliver. However, at the onset of labour half of the women, case group I (n = 133) were referred to another maternity unit due to lack of space in the labour ward. For every referred woman a control woman matched for age, parity and date of delivery was selected, with the same inclusion criteria, except being referred, control group II (n = 133). Methods: a questionnaire with closed and open questions was posted to the women after birth and used to collect quantitative and qualitative data on the outcome of labour and the women's perceptions of referral during labour. Findings: routines such as epidural analgesia (EDA) (p < 0.002), episiotomies (p < 0.015) and morphine/pethidine during labour (p < 0.023) were more common in the referred group. The women in the referred group considered to a higher extent that referral during labour had affected their emotional state (p < 0.001). Women in both groups had been worried during pregnancy by the thought of having to be referred when labour had started and the referral had caused practical problems, stress and a feeling of not being welcome in the referral labour ward. Key conclusion and implications for practice: referral during established normal labour may affect labour outcome, and the possibility that they may be referred worries women during pregnancy. Maternity policies and practices should be organised so that caring goals, such as continuity of care and women's' participation in birth planning, can be met. © 2002 Elsevier Science Ltd. All rights reserved.
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| 19. |
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| 20. |
- Ali, Ahmed, et al.
(author)
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Single cell metabolism : current and future trends
- 2022
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In: Metabolomics. - : Springer. - 1573-3882 .- 1573-3890. ; 18:10
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Research review (peer-reviewed)abstract
- Single cell metabolomics is an emerging and rapidly developing field that complements developments in single cell analysis by genomics and proteomics. Major goals include mapping and quantifying the metabolome in sufficient detail to provide useful information about cellular function in highly heterogeneous systems such as tissue, ultimately with spatial resolution at the individual cell level. The chemical diversity and dynamic range of metabolites poses particular challenges for detection, identification and quantification. In this review we discuss both significant technical issues of measurement and interpretation, and progress toward addressing them, with recent examples from diverse biological systems. We provide a framework for further directions aimed at improving workflow and robustness so that such analyses may become commonly applied, especially in combination with metabolic imaging and single cell transcriptomics and proteomics.
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| 21. |
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| 22. |
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| 23. |
- Bannatyne, B Anne, et al.
(author)
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Differential projections of excitatory and inhibitory dorsal horn interneurons relaying information from group II muscle afferents in the cat spinal cord.
- 2006
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In: The Journal of neuroscience : the official journal of the Society for Neuroscience. - 1529-2401. ; 26:11, s. 2871-80
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Journal article (peer-reviewed)abstract
- Dorsal horn interneurons with input from group II muscle spindle afferents are components of networks involved in motor control. Thirteen dorsal horn interneurons with monosynaptic group II input were characterized electrophysiologically and labeled intracellularly with Neurobiotin. Their axonal projections were traced, and neurotransmitter content was established by using immunocytochemistry. Two subpopulations were identified: five interneurons had axons that contained vesicular glutamate transporter 2 and hence were glutamatergic and excitatory. Terminals of the remaining eight interneurons were immunoreactive for the glycine transporter 2 or were apposed to gephyrin but did not contain the GABA-synthesizing enzyme glutamic acid decarboxylase and were therefore glycinergic and inhibitory. Excitatory cells were located mainly in the central region of lamina IV and had relatively small somata and restricted dendritic trees. In contrast, inhibitory interneurons were located more ventrally, in lamina V and had relatively larger somata and more extensive dendritic trees. Axonal projections of the two subpopulations differed considerably. Excitatory interneurons predominantly projected ipsilaterally, whereas most inhibitory interneurons projected both ipsilaterally and contralaterally. Three inhibitory axons formed contacts with large cholinergic cells in motor nuclei, thus revealing a novel direct coupling between inhibitory dorsal horn interneurons and motoneurons. The organization of the excitatory interneurons is consistent with current knowledge of reflex pathways to motoneurons, but the existence and connections of the inhibitory subpopulation could not be predicted from previous data. Our results indicate that these latter interneurons exercise widespread inhibitory control over a variety of cell types located on both sides of the spinal cord.
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| 24. |
- Bannatyne, B A, et al.
(author)
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Excitatory and inhibitory intermediate zone interneurons in pathways from feline group I and II afferents: differences in axonal projections and input.
- 2009
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In: The Journal of physiology. - : Wiley. - 1469-7793 .- 0022-3751. ; 587:Pt 2, s. 379-99
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Journal article (peer-reviewed)abstract
- The aim of the present study was to compare properties of excitatory and inhibitory spinal intermediate zone interneurons in pathways from group I and II muscle afferents in the cat. Interneurons were labelled intracellularly and their transmitter phenotypes were defined by using immunocytochemistry. In total 14 glutamatergic, 22 glycinergic and 2 GABAergic/glycinergic interneurons were retrieved. All interneurons were located in laminae V-VII of the L3-L7 segments. No consistent differences were found in the location, the soma sizes or the extent of the dendritic trees of excitatory and inhibitory interneurons. However, major differences were found in their axonal projections; excitatory interneurons projected either ipsilaterally, bilaterally or contralaterally, while inhibitory interneurons projected exclusively ipsilaterally. Terminal projections of glycinergic and glutamatergic cells were found within motor nuclei as well as other regions of the grey matter which include the intermediate region, laminae VII and VIII. Cells containing GABA/glycine had more restricted projections, principally within the intermediate zone where they formed appositions with glutamatergic axon terminals and unidentified cells and therefore are likely to be involved in presynaptic as well as postsynaptic inhibition. The majority of excitatory and inhibitory interneurons were found to be coexcited by group I and II afferents (monosynaptically) and by reticulospinal neurons (mono- or disynaptically) and to integrate information from several muscles. Taken together the morphological and electrophysiological data show that individual excitatory and inhibitory intermediate zone interneurons may operate in a highly differentiated way and thereby contribute to a variety of motor synergies.
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| 25. |
- Bannatyne, B A, et al.
(author)
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Inhibitory inputs to four types of spinocerebellar tract neurons in the cat spinal cord.
- 2012
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In: Neuroscience. - : Elsevier BV. - 1873-7544 .- 0306-4522. ; 226, s. 253-69
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Journal article (peer-reviewed)abstract
- Spinocerebellar tract neurons are inhibited by various sources of input via pathways activated by descending tracts as well as peripheral afferents. Inhibition may be used to modulate transmission of excitatory information forwarded to the cerebellum. However it may also provide information on the degree of inhibition of motoneurons and on the operation of inhibitory premotor neurons. Our aim was to extend previous comparisons of morphological substrates of excitation of spinocerebellar neurons to inhibitory input. Contacts formed by inhibitory axon terminals were characterised as either GABAergic, glycinergic or both GABAergic/glycinergic by using antibodies against vesicular GABA transporter, glutamic acid decarboxylase and gephyrin. Quantitative analysis revealed the presence of much higher proportions of inhibitory contacts when compared with excitatory contacts on spinal border (SB) neurons. However similar proportions of inhibitory and excitatory contacts were associated with ventral spinocerebellar tract (VSCT) and dorsal spinocerebellar tract neurons located in Clarke's column (ccDSCT) and the dorsal horn (dhDSCT). In all of the cells, the majority of inhibitory terminals were glycinergic. The density of contacts was higher on somata and proximal versus distal dendrites of SB and VSCT neurons but more evenly distributed in ccDSCT and dhDSCT neurons. Variations in the density and distribution of inhibitory contacts found in this study may reflect differences in information on inhibitory processes forwarded by subtypes of spinocerebellar tract neurons to the cerebellum.
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| 26. |
- Bannatyne, B Anne, et al.
(author)
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Networks of inhibitory and excitatory commissural interneurons mediating crossed reticulospinal actions.
- 2003
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In: The European journal of neuroscience. - 0953-816X. ; 18:8, s. 2273-84
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Journal article (peer-reviewed)abstract
- Axonal projections and neurotransmitters used by commissural interneurons mediating crossed actions of reticulospinal neurons were investigated in adult cats. Eighteen interneurons, located in or close to lamina VIII in midlumbar segments, that were monosynaptically excited by reticulospinal tract fibres and projected to contralateral motor nuclei were labelled by intracellular injection of tetramethylrhodamine-dextran and Neurobiotin. The nine most completely labelled interneurons were analysed with combined confocal and light microscopy. None of the stem axons gave off ipsilateral axon collaterals. Seven cells had axon collaterals that arborized in the contralateral grey matter in the ventral horn of the same segments. Transmitters were identified by using antibodies raised against vesicular glutamate transporters 1 and 2, glutamic acid decarboxylase and the glycine transporter 2. The axons of two cells were immunoreactive for the glycine transporter 2 and hence were glycinergic. Three cells were immunoreactive for the vesicular glutamate transporter 2 and hence were glutamatergic. None of the axons displayed immunoreactivity for glutamic acid decarboxylase. Electron microscopy of two cells revealed direct synaptic connections with motoneurons and other neurons. Axonal swellings of one neuron formed synapses with profiles in motor nuclei whereas those of the other formed synapses with other structures, including cell bodies in lamina VII. The results show that this population of commissural interneurons includes both excitatory and inhibitory cells that may excite or inhibit contralateral motoneurons directly. They may also influence the activity of motoneurons indirectly by acting through interneurons located outside motor nuclei in the contralateral grey matter but are unlikely to have direct actions on interneurons in the ipsilateral grey matter.
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| 31. |
- Beckmann, K., et al.
(author)
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Radical radiotherapy for prostate cancer: patterns of care in Sweden 1998-2016
- 2020
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In: Acta Oncologica. - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 59:5, s. 549-557
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Journal article (peer-reviewed)abstract
- Introduction: Radiotherapy is an established treatment option for prostate cancer (PCa), both as primary treatment and secondary treatment after radical prostatectomy (RP). Since 1998, detailed data on radiotherapy delivered to Swedish men with PCa (e.g. treatment modalities, absorbed doses, fractionation) have been collated within PCa data Base Sweden (PCBaSe). This study reports patterns of radical radiotherapy for PCa in Sweden over the past two decades. Materials and methods: All men with non-metastatic PCa (1998-2016) who received external beam radiotherapy (EBRT) or high or low dose-rate brachytherapy (HDR-BT/LDR-BT) were identified in PCBaSe. Analyses included: trends in radiation techniques, fractionation patterns and total doses over time; PCa-specific survival comparing treatment in 2007-2017 with 1998-2006; and regional variation in type of primary radiotherapy. Results: About 20,876 men underwent primary radiotherapy. The main treatment modalities include conventionally fractionated (2.0 Gy/fraction) EBRT (51%), EBRT with HDR-BT boost (27%) and hypofractionated (>2.4 Gy/fraction) EBRT (11%). EBRT with photon or proton boost and HDR-BT and LDR-BT monotherapies were each used minimally. Use of dose-escalated EBRT (>74 Gy) and moderate hypofractionation increased over time, while use of HDR-BT declined. Considerable regional variation in treatment modalities was apparent. Risk of PCa death following primary radiotherapy had declined for intermediate-risk (HR: 0.60; 95%CI 0.47-0.87) and high-risk PCa (HR: 0.72; 95%CI 0.61-0.86). Discussion: Increased use of dose escalation and hypofractionated EBRT has occurred in Sweden over the past two decades, reflecting current evidence and practice guidelines. Disease-specific outcomes have also improved. Data collected in PCBaSe provide an excellent resource for further research into RT use in PCa management.
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| 32. |
- Bemis, Kylie A., et al.
(author)
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Statistical detection of differentially abundant ions in mass spectrometry-based imaging experiments with complex designs
- 2019
-
In: International Journal of Mass Spectrometry. - : ELSEVIER SCIENCE BV. - 1387-3806 .- 1873-2798. ; 437, s. 49-57
-
Journal article (peer-reviewed)abstract
- Mass Spectrometry Imaging (MSI) characterizes changes in chemical composition between regions of biological samples such as tissues. One goal of statistical analysis of MSI experiments is class comparison, i.e. determining analytes that change in abundance between conditions more systematically than as expected by random variation. To reach accurate and reproducible conclusions, statistical analysis must appropriately reflect the initial research question, the design of the MSI experiment, and all the associated sources of variation. This manuscript highlights the importance of following these general statistical principles. Using the example of two case studies with complex experimental designs, and with different strategies of data acquisition, we demonstrate the extent to which choices made at key points of this workflow impact the results, and provide suggestions for appropriate design and analysis of MSI experiments that aim at detecting differentially abundant analytes. (C) 2018 Elsevier B.V. All rights reserved.
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| 33. |
- Berg, Marie, 1955, et al.
(author)
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Evidence-based care and childbearing - A critical approach
- 2008
-
In: International Journal of Qualitative Studies on Health and Well-being. - : Informa UK Limited. - 1748-2623 .- 1748-2631. ; :3, s. 239-247
-
Journal article (peer-reviewed)abstract
- Developing the best care for clients and patients is a paramount aim of all health care practices, which therefore, should be based on best evidence. This is also crucial for care during the childbearing period here defined as pregnancy, childbirth, and infancy. However, due to dominance of the evidence-based medicine (EBM) model, health care practice has encountered problems especially regarding its relationship to qualitative research. In this article, we analyze and discuss how research based on a lifeworld perspective fits with evidence-based care (EBC), and how a circular model instead of a hierarchy is suitable when attributing value to knowledge for EBC. The article focuses on the history of EBM and EBC, the power of the evidence concept, and EBC from a narrow to a broad view. Further qualitative research and its use for developing EBC is discussed and examples are presented from the authors’ own lifeworld research in the Nordic childbearing context. Finally, an alternative circular model of knowledge for EBC is presented. In order to develop evidence-based care, there is need for multiple types of scientific knowledge with equal strength of evidence, integrated with clinical experience, setting, circumstances and health care resources, and incorporating the experiences and clinical state of the childbearing woman and her family.
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| 34. |
- Bjurhager, Ingela, et al.
(author)
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Mechanical characterization of juvenile European aspen (Populus tremula) and hybrid aspen (Populus tremula × Populus tremuloides) using full-field strain measurements
- 2008
-
In: Journal of Wood Science. - : Springer Science and Business Media LLC. - 1435-0211 .- 1611-4663. ; 54:5, s. 349-355
-
Journal article (peer-reviewed)abstract
- Functional analysis of genes and proteins involved in wood formation and fiber properties often involves phenotyping saplings of transgenic trees. The objective of the present study was to develop a tensile test method for small green samples from saplings, and to compare mechanical properties of juvenile European aspen (Populus tremula) and hybrid aspen (Populus tremula × tremuloides). Small microtomed sections were manufactured and successfully tested in tension parallel to fiber orientation. Strain was determined by digital speckle photography. Results showed significantly lower values for juvenile hybrid aspen in both Young's modulus and tensile strength parallel to the grain. Average Young's moduli spanned the ranges of 5.9-6.6 and 4.8-6.0 GPa for European aspen and hybrid aspen, respectively. Tensile strength was in the range of 45-49 MPa for European aspen and 32-45 MPa for hybrid aspen. The average density (oven-dry) was 284 kg/m3 for European aspen and 221 kg/m3 for hybrid aspen. Differences in mechanical properties correlated with differences in density.
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| 35. |
- Bjurhager, Ingela, et al.
(author)
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Mechanical performance of yew (Taxus baccata L.) from a longbow perspective
- 2013
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In: Holzforschung. - : Walter de Gruyter GmbH. - 0018-3830 .- 1437-434X. ; 67:7, s. 763-770
-
Journal article (peer-reviewed)abstract
- Yew (Taxus baccata L.) longbow was the preferred weapon in the Middle Ages until the emergence of guns. In this study, the tensile, compression, and bending properties of yew were investigated. The advantage of yew over the other species in the study was also confirmed by a simple beam model. The superior toughness of yew has the effect that a yew longbow has a higher range compared with bows made from other species. Unexpectedly, the mechanical performance of a bow made from yew is influenced by the juvenile-to-mature wood ratio rather than by the heartwood-to-sapwood ratio. A yew bow is predicted to have maximized performance at a juvenile wood content of 30-50%, and located at the concave side (the compressive side facing the bowyer). Here, the stiffness and yield stress in compression should be as high as possible.
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| 36. |
- Bjurhager, Ingela, et al.
(author)
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State of degradation in archeological oak from the 17th century vasa ship : Substantial strength loss correlates with reduction in (holo)cellulose molecular weight
- 2012
-
In: Biomacromolecules. - : American Chemical Society (ACS). - 1525-7797 .- 1526-4602. ; :8, s. 2521-2527
-
Journal article (peer-reviewed)abstract
- In 1628, the Swedish warship Vasa capsized on her maiden voyage and sank in the Stockholm harbor. The ship was recovered in 1961 and, after polyethylene glycol (PEG) impregnation, it was displayed in the Vasa museum. Chemical investigations of the Vasa were undertaken in 2000, and extensive holocellulose degradation was reported at numerous locations in the hull. We have now studied the longitudinal tensile strength of Vasa oak as a function of distance from the surface. The PEG-content, wood density, and cellulose microfibril angle were determined. The molar mass distribution of holocellulose was determined as well as the acid and iron content. A good correlation was found between the tensile strength of the Vasa oak and the average molecular weight of the holocellulose, where the load-bearing cellulose microfibril is the critical constituent. The mean tensile strength is reduced by approximately 40%, and the most affected areas show a reduction of up to 80%. A methodology is developed where variations in density, cellulose microfibril angle, and PEG content are taken into account, so that cell wall effects can be evaluated in wood samples with different rate of impregnation and morphologies.
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| 37. |
- Bjurhager, Ingela, et al.
(author)
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Towards improved understanding of PEG-impregnated waterlogged archaeological wood : A model study on recent oak
- 2010
-
In: Holzforschung. - 0018-3830 .- 1437-434X. ; 64:2, s. 243-250
-
Journal article (peer-reviewed)abstract
- To prevent deformation and cracking of waterlogged archaeological wood, polyethylene glycol (PEG) as a bulk impregnation agent is commonly applied. PEG maintains the wood in a swollen state during drying. However, swelling of wood can reduce its mechanical properties. In this study, the cellular structure of oak and cell wall swelling was characterized by scanning electron microscopy (SEM) of transverse cross-sections, and the microfibril angle of oak fibers was determined by wide angle X-ray scattering (WAXS). Samples of recent European oak (Quercus robur L) impregnated with PEG (molecular weight of 600) were tested in axial tension and radial compression. Mechanical tests showed that axial tensile modulus and strength were only slightly affected by PEG, whereas radial compressive modulus and yield strength were reduced by up to 50%. This behavior can be explained by the microstructure and deformation mechanisms of the material. Microfibril angles in tensile test samples were close to zero. This implies tensile loading of cellulose microfibrils within the fiber cell walls without almost any shear in the adjacent amorphous matrix. These results are important because they can help separate the impact of PEG on mechanical properties from that of chemical degradation in archaeological artifacts, which display only small to moderate biological degradation.
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| 38. |
- Bjurhager, Ingela, et al.
(author)
-
Ultrastructure and Mechanical Properties of Populus Wood with Reduced Lignin Content Caused by Transgenic Down-Regulation of Cinnamate 4-Hydroxylase
- 2010
-
In: Biomacromolecules. - : American Chemical Society (ACS). - 1525-7797 .- 1526-4602. ; 11:9, s. 2359-2365
-
Journal article (peer-reviewed)abstract
- Several key enzymes in lignin biosynthesis of Populus have been down-regulated by transgenie approaches to investigate their role in wood lignification and to explore their potential for lignin modification. Cinnamate 4-hydroxylase is an enzyme in the early phenylpropanoid pathway that has not yet been functionally analyzed in Populus. This study shows that down-regulation of cinnamate 4-hydroxylase reduced Klason lignin content by 30% with no significant change in syringyl to guaiacyl ratio. The lignin reduction resulted in ultrastructural differences of the wood and a 10% decrease in wood density. Mechanical properties investigated by tensile tests and dynamic mechanical analysis showed a decrease in stiffness, which could be explained by the lower density. The study demonstrates that a large modification in lignin content only has minor influences on tensile properties of wood in its axial direction and highlights the usefulness of wood modified beyond its natural variation by transgene technology in exploring the impact of wood biopolymer composition and ultrastructure on its material properties.
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| 39. |
- Carlander, A. -KK., et al.
(author)
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Contact between mother, child and partner and attitudes towards breastfeeding in relation to mode of delivery
- 2010
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In: Sexual & Reproductive HealthCare. - : Elsevier BV. - 1877-5756 .- 1877-5764. ; 1:1, s. 27-34
-
Journal article (peer-reviewed)abstract
- Objective: To investigate contact between mothers and their newborn child and study if there are differences between those who requested an elective caesarean section compared to women who had a vaginal birth and those who underwent an elective caesarean section due to obstetrical indication. The psychometric properties of a scale that measure the contact between mother and child were also investigated. Design: A prospective cohort study. Setting: Danderyd Hospital, Stockholm, Sweden. Sample: 510 primiparas from three groups: women undergoing caesarean section on maternal request (n = 96), women undergoing caesarean section on obstetrical indication (n = 116) and women planning a vaginal delivery (n = 198). The later were further divided into subgroups; women who underwent assisted vaginal delivery (n = 35) and women who had an emergency caesarean section (n = 65). Methods: The instrument used was the Alliance Scale. Main outcome measure: The contact between mother and child in relation to mode of delivery. Results: The contact with the child was rated as positive on all occasions: there were no significant differences between the groups. The relation to the partner was rated as positive at all occasions. Mothers with a vaginal delivery experienced breastfeeding less stressful than the mothers with a caesarean delivery. Three and nine months after delivery the mothers with a caesarean delivery on request reported more breastfeeding problems than mothers in the other groups. Mothers with a vaginal delivery rated less sadness at every occasion. Conclusion: Mode of delivery does not seem to affect how mothers experience their contact towards the newborn child. © 2009 Elsevier B.V. All rights reserved.
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| 40. |
- Carlander, A. K. K., et al.
(author)
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Health-related quality of life five years after birth of the first child
- 2015
-
In: Sexual & Reproductive HealthCare. - : Elsevier. - 1877-5756 .- 1877-5764. ; 6:2, s. 101-107
-
Journal article (peer-reviewed)abstract
- Objectives: The aim of this study was to describe the overall health-related quality of life (HRQoL) in women five years after the birth of their first child as well as the HRQoL in relation to mode of delivery. Methods: 545 first-time pregnant women, drawn from a hospital situated in Sweden, consented to be included in a cohort. Five years after the birth of the first child, 372 (68%) women agreed to participate in a follow-up study. HRQoL was measured using the Swedish Health-Related Quality of Life Survey (SWED-QUAL) questionnaire. Socio-demographic background and variables related to pregnancy and childbirth were collected using a self-report questionnaire. Results: Overall, the HRQoL was perceived to be good. Suboptimal scores were obtained for the three variables: Sleeping problems, Emotional well-being - negative affect and Family functioning - sexual functioning. Women having a vaginal birth, an instrumental vaginal birth or women who underwent caesarean section on maternal request were more likely to report better perceived HRQoL than women who had undergone an emergency caesarean section or caesarean section due to medical indication. Conclusion: This study demonstrates that the overall HRQoL of the women in the cohort was reported as good. Mode of delivery was associated with differences in HRQoL five years after birth of the first child. Our result suggests that some differences in perceived HRQoL persist in the long term. © 2015 Elsevier B.V.
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| 41. |
- Cazzaniga, W., et al.
(author)
-
Mini Review on the Use of Clinical Cancer Registers for Prostate Cancer: The National Prostate Cancer Register (NPCR) of Sweden
- 2019
-
In: Frontiers in Medicine. - : Frontiers Media SA. - 2296-858X. ; 6
-
Journal article (peer-reviewed)abstract
- Given the increasing prevalence of cancer, it is vital to systematically collect data in order to monitor disease trends and quality of cancer care. For this purpose, clinical cancer registries have been developed in some countries. These registers are intended to be used as a basis for quality assurance and quality improvement, but they also constitute a rich resource of real world data for research. The aim of thismini-review was to describe the structure and the organization of the National Prostate Cancer Register (NPCR) with some examples on how data in NPCR have affected prostate cancer care in Sweden.
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| 42. |
- Devik A., Siri, et al.
(author)
-
Variations in drug-related problems detected by multidisciplinary teams in Norwegian nursing homes and home nursing care
- 2018
-
In: Scandinavian Journal of Primary Health Care. - : Taylor & Francis Group. - 0281-3432 .- 1502-7724. ; 36:3, s. 291-299
-
Journal article (peer-reviewed)abstract
- OBJECTIVE:Traditionally, nursing homes have been associated with suboptimal drug therapy and drug-related problems (DRPs). In contrast, less is known about drug safety in homecare. The aim of this study was to describe and compare DRPs in older persons across two care settings: nursing homes and home nursing care.DESIGN:Cross-sectional study using descriptive and inferential statistics.SETTING:Nursing homes (n = 5) and home nursing care units (n = 8) across nine municipalities in the middle of Norway.PARTICIPANTS:Multidisciplinary medication reviews for 61 nursing home residents and 93 patients receiving home nursing care performed over the 2013-2014 period, were mapped and examined (N = 154).MAIN OUTCOME MEASURES:DRPs classified by a Norwegian Classification Tool.RESULTS:In all, 740 DRPs were detected in the total sample, 227 in nursing homes and 513 in home nursing care. DRPs were significantly higher among patients receiving home-based care (Mean =5.5) compared to patients in nursing homes (Mean =3.7, p = 0.002). Among the problem categories, the need for additional drug was most frequent in nursing homes (p = 0.001), while documentation discrepancies reached the highest numbers in patients receiving home nursing care (p = 0.000). Additionally, patients in home nursing care had more problems concerning adverse reactions (p = 0.060); however, this was not statistically significant. Differences in DRP categories leading to changes in the patients' medication lists were also discovered.CONCLUSIONS:The frequency of unclear documentation and adverse reactions found in the homecare setting is alarming. This is an important issue given the trend in aged care towards caring people in their own homes. Further research is warranted to explore how different care settings may influence the safety of pharmacotherapy for older persons.Key PointsDrug related problems are a significant cause of concern among patients receiving home nursing care as well as for patients living in nursing homes. The findings of this study showed that:Significantly more DRPs were detected among patients receiving home nursing care than patients living in nursing homes.While patients living in nursing homes were often undermedicated, documentation discrepancies were more frequent in home nursing care.DRP categories leading to changes on the medication lists differed between the settings.
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| 43. |
- Djupedal, Ingela, et al.
(author)
-
Analysis of small RNA in fission yeast; centromeric siRNAs are potentially generated through a structured RNA
- 2009
-
In: EMBO Journal. - : Wiley. - 0261-4189 .- 1460-2075. ; 28:24, s. 3832-3844
-
Journal article (peer-reviewed)abstract
- The formation of heterochromatin at the centromeres in fission yeast depends on transcription of the outer repeats. These transcripts are processed into siRNAs that target homologous loci for heterochromatin formation. Here, high throughput sequencing of small RNA provides a comprehensive analysis of centromere-derived small RNAs. We found that the centromeric small RNAs are Dcr1 dependent, carry 50-monophosphates and are associated with Ago1. The majority of centromeric small RNAs originate from two remarkably well-conserved sequences that are present in all centromeres. The high degree of similarity suggests that this non-coding sequence in itself may be of importance. Consistent with this, secondary structure-probing experiments indicate that this centromeric RNA is partially double-stranded and is processed by Dicer in vitro. We further demonstrate the existence of small centromeric RNA in rdp1D cells. Our data suggest a pathway for siRNA generation that is distinct from the well-documented model involving RITS/RDRC. We propose that primary transcripts fold into hairpin-like structures that may be processed by Dcr1 into siRNAs, and that these siRNAs may initiate heterochromatin formation independent of RDRC activity. The EMBO Journal (2009) 28, 3832-3844. doi: 10.1038/emboj.2009.351; Published online 26 November 2009
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| 44. |
- Duncan, Kyle D., et al.
(author)
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Membrane Sampling Separates Naphthenic Acids from Biogenic Dissolved Organic Matter for Direct Analysis by Mass Spectrometry
- 2022
-
In: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 56:5, s. 3096-3105
-
Journal article (peer-reviewed)abstract
- Oil sands process waters can release toxic naphthenic acids (NAs) into aquatic environments. Analytical techniques for NAs are challenged by sample complexity and interference from naturally occurring dissolved organic matter (DOM). Herein, we report the use of a poly(dimethylsiloxane) (PDMS) polymer membrane for the on-line separation of NAs from DOM and use direct infusion electrospray ionization mass spectrometry to yield meaningful qualitative and quantitative information with minimal sample cleanup. We compare the composition of membrane-permeable species from natural waters fortified with a commercial NA mixture to those derived from weak anion exchange solid-phase extraction (SPE) using high-resolution mass spectrometry. The results show that SPE retains a wide range of carboxylic acids, including biogenic DOM, while permeation through PDMS was selective for petrogenic classically defined NAs (CnH2n+zO2). A series of model compounds (log K-ow similar to 1-7) were used to characterize the perm-selectivity and reveal the separation is based on hydrophobicity. This convenient sample cleanup method is selective for the O-2 class of NAs and can be used prior to conventional analysis or as an on-line analytical strategy when coupled directly to mass spectrometry.
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| 45. |
- Edgley, S A, et al.
(author)
-
Both dorsal horn and lamina VIII interneurones contribute to crossed reflexes from feline group II muscle afferents.
- 2003
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In: The Journal of physiology. - : Wiley. - 0022-3751 .- 1469-7793. ; 552:Pt 3, s. 961-74
-
Journal article (peer-reviewed)abstract
- Previous studies have demonstrated that group II muscle afferents exert powerful actions on contralateral motoneurones and that these actions are mediated primarily via lamina VIII commissural interneurones. We examined whether dorsal horn interneurones also contribute to these actions, as they have been shown to contribute to the actions of group II afferents on ipsilateral motoneurones. We tested the susceptibility of IPSPs and EPSPs evoked from group II afferents in contralateral motoneurones to presynaptic inhibition as an indicator of the relative contribution of dorsal horn interneurones to these PSPs, since the monosynaptic activation of dorsal horn interneurones is more weakly and more briefly depressed by presynaptic inhibition than is the monosynaptic activation of lamina VIII and other intermediate zone and ventral horn interneurones. While the earliest components of IPSPs and EPSPs evoked by group II afferents were abolished by conditioning stimulation of group II afferents, consistent with them being evoked disynaptically by commissural interneurones, trisynaptic components of these PSPs were only partly reduced and are therefore attributed to dorsal horn interneurones. The same conditioning stimuli depressed the disynaptic excitation of lamina VIII commissural interneurones by group II afferents much less effectively than they depressed monosynaptic excitation, indicating that dorsal horn interneurones contribute to this disynaptic excitation. On the basis of these observations we conclude that that dorsal horn interneurones contribute to the late actions of group II muscle afferents on contralateral motoneurones through their disynaptic actions on commissural interneurones.
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| 46. |
- Edgley, S A, et al.
(author)
-
Ipsilateral actions of feline corticospinal tract neurons on limb motoneurons.
- 2004
-
In: The Journal of neuroscience : the official journal of the Society for Neuroscience. - 1529-2401. ; 24:36, s. 7804-13
-
Journal article (peer-reviewed)abstract
- Contralateral pyramidal tract (PT) neurons arising in the primary motor cortex are the major route through which volitional limb movements are controlled. However, the contralateral hemiparesis that follows PT neuron injury on one side may be counteracted by ipsilateral of actions of PT neurons from the undamaged side. To investigate the spinal relays through which PT neurons may influence ipsilateral motoneurons, we analyzed the synaptic actions evoked by stimulation of the ipsilateral pyramid on hindlimb motoneurons after transecting the descending fibers of the contralateral PT at a low thoracic level. The results show that ipsilateral PT neurons can affect limb motoneurons trisynaptically by activating contralaterally descending reticulospinal neurons, which in turn activate spinal commissural interneurons that project back across to motoneurons ipsilateral to the stimulated pyramidal tract. Stimulation of the pyramids alone did not evoke synaptic actions in motoneurons but potently facilitated disynaptic EPSPs and IPSPs evoked by stimulation of reticulospinal tract fibers in the medial longitudinal fascicle. In parallel with this double-crossed pathway, corticospinal neurons could also evoke ipsilateral actions via ipsilateral descending reticulospinal tract fibers, acting through ipsilaterally located spinal interneurons. Because the actions mediated by commissural interneurons were found to be stronger than those of ipsilateral premotor interneurons, the study leads to the conclusion that ipsilateral actions of corticospinal neurons via commissural interneurons may provide a better opportunity for recovery of function in hemiparesis produced by corticospinal tract injury.
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| 47. |
- Engström, Patrik, 1982-, et al.
(author)
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Mutations in hemG Mediate Resistance to Salicylidene Acylhydrazides, Demonstrating a Novel Link between Protoporphyrinogen Oxidase (HemG) and Chlamydia trachomatis Infectivity
- 2013
-
In: Journal of Bacteriology. - Washington DC, USA : American Society for Microbiology. - 0021-9193 .- 1098-5530. ; 195:18, s. 4221-4230
-
Journal article (peer-reviewed)abstract
- Salicylidene acylhydrazides (SAHs) inhibit the type III secretion system (T3S) of Yersinia and other Gram-negative bacteria. In addition, SAHs restrict the growth and development of Chlamydia species. However, since the inhibition of Chlamydia growth by SAH is suppressed by the addition of excess iron and since SAHs have an iron-chelating capacity, their role as specific T3S inhibitors is unclear. We investigated here whether SAHs exhibit a function on C. trachomatis that goes beyond iron chelation. We found that the iron-saturated SAH INP0341 (IS-INP0341) specifically affects C. trachomatis infectivity with reduced generation of infectious elementary body (EB) progeny. Selection and isolation of spontaneous SAH-resistant mutant strains revealed that mutations in hemG suppressed the reduced infectivity caused by IS-INP0341 treatment. Structural modeling of C. trachomatis HemG predicts that the acquired mutations are located in the active site of the enzyme, suggesting that IS-INP0341 inhibits this domain of HemG and that protoporphyrinogen oxidase (HemG) and heme metabolism are important for C. trachomatis infectivity.
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| 48. |
- Fotin-Mleczek, Mariola, et al.
(author)
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Apoptotic crosstalk of TNF receptors : TNF-R2-induces depletion of TRAF2 and IAP proteins and accelerates TNF-R1-dependent activation of caspase-8
- 2002
-
In: Journal of Cell Science. - 0021-9533 .- 1477-9137. ; 115:Pt 13, s. 2757-70
-
Journal article (peer-reviewed)abstract
- We have recently shown that stimulation of TNF-R2 selectively enhances apoptosis induction by the death receptor TNF-R1. Here, we demonstrate that stimulation of CD30 or CD40 also leads to selective enhancement of TNF-R1-induced cell death. Enhancement of apoptosis was correlated with the depletion of endogenous TRAF2 within 1 to 6 hours. Selective prestimulation of TNF-R2 for several hours inhibited TNF-R2-induced activation of the anti-apoptotic NF-kappaB pathway up to 90% and dramatically enhanced apoptosis induction by this receptor. When both TNF-receptors were stimulated simultaneously, TNF-R1-induced NF-kappaB activation remained unaffected but TNF-R1-induced apoptosis was still significantly enhanced. Compared with FasL-induced cell death TNF-R1-induced activation of caspase-8 was significantly weaker and delayed. Costimulation or prestimulation of TNF-R2 enhanced caspase-8 processing. Life cell imaging and confocal microscopy revealed that both TNF-R1 and TNF-R2 recruited the anti-apoptotic factor cIAP1 in a TRAF2-dependent manner. Thus, TNF-R2 may compete with TNF-R1 for the recruitment of newly synthesized TRAF2-bound anti-apoptotic factors, thereby promoting the formation of a caspase-8-activating TNF-R1 complex. Hence, TNF-R2 triggering can interfere with TNF-R1-induced apoptosis by inhibition of NF-kappaB-dependent production of anti-apoptotic factors and by blocking the action of anti-apoptotic factors at the post-transcriptional level.
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| 49. |
- Franck-Lissbrant, Ingela, 1969, et al.
(author)
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Population-based study on use of chemotherapy in men with castration resistant prostate cancer
- 2013
-
In: Acta Oncologica. - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 52:8, s. 1593-1601
-
Journal article (peer-reviewed)abstract
- Background. Chemotherapy prolongs life and relieves symptoms in men with castration resistant prostate cancer (CRPC). There is limited information on a population level on the use of chemotherapy for CRPC. Material and methods. To assess the use of chemotherapy in men with CRPC we conducted a register-based nationwide population-based study in Prostate Cancer data Base Sweden (PCBaSe) and a nationwide in-patient drug register (SALT database) between May 2009 and December 2010. We assumed that men who died of prostate cancer (PCa) underwent a period of CRPC before they died. Results. Among the 2677 men who died from PCa during the study inclusion period, 556 (21%) had received chemotherapy (intravenous or per oral) detectable within the observation period in SALT database. Specifically, 239 (61%) of men <70 years had received chemotherapy, 246 (30%) of men between 70 and 79 years and 71 (5%) men older than 80 years. The majority of men 465/556 (84%) had received a docetaxel-containing regimen. Among chemotherapy treated men, 283/556 (51%) received their last dose of chemotherapy during the last six months prior to death. Treatment with chemotherapy was more common among men with little comorbidity and high educational level, as well as in men who had received curatively intended primary treatment. Conclusion. A majority of men younger than 70 years with CRPC were treated with chemotherapy in contrast to men between 70 and 79 years of whom half as many received chemotherapy. Chemotherapy treatment was often administered shortly prior to death. The low uptake of chemotherapy in older men with CRPC may be caused by concerns about tolerability of treatment, as well as treatment decisions based on chronological age rather than global health status.
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| 50. |
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