| 1. |
- Santangelo, James S., et al.
(författare)
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Global urban environmental change drives adaptation in white clover
- 2022
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 375
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Tidskriftsartikel (refereegranskat)abstract
- Urbanization transforms environments in ways that alter biological evolution. We examined whether urban environmental change drives parallel evolution by sampling 110,019 white clover plants from 6169 populations in 160 cities globally. Plants were assayed for a Mendelian antiherbivore defense that also affects tolerance to abiotic stressors. Urban-rural gradients were associated with the evolution of clines in defense in 47% of cities throughout the world. Variation in the strength of clines was explained by environmental changes in drought stress and vegetation cover that varied among cities. Sequencing 2074 genomes from 26 cities revealed that the evolution of urban-rural dines was best explained by adaptive evolution, but the degree of parallel adaptation varied among cities. Our results demonstrate that urbanization leads to adaptation at a global scale.
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| 3. |
- Albert, J., et al.
(författare)
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Risk of HIV transmission from patients on antiretroviral therapy: A position statement from the Public Health Agency of Sweden and the Swedish Reference Group for Antiviral Therapy
- 2014
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Ingår i: Scandinavian Journal of Infectious Diseases. - : Informa UK Limited. - 0036-5548 .- 1651-1980. ; 46:10, s. 673-677
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Tidskriftsartikel (refereegranskat)abstract
- The modern medical treatment of HIV with antiretroviral therapy (ART) has drastically reduced the morbidity and mortality in patients infected with this virus. ART has also been shown to reduce the transmission risk from individual patients as well as the spread of the infection at the population level. This position statement from the Public Health Agency of Sweden and the Swedish Reference Group for Antiviral Therapy is based on a workshop organized in the fall of 2012. It summarizes the latest research and knowledge on the risk of HIV transmission from patients on ART, with a focus on the risk of sexual transmission. The risk of transmission via shared injection equipment among intravenous drug users is also examined, as is the risk of mother-to-child transmission. Based on current knowledge, the risk of transmission through vaginal or anal intercourse involving the use of a condom has been judged to be minimal, provided that the person infected with HIV fulfils the criteria for effective ART. This probably also applies to unprotected intercourse, provided that no other sexually transmitted infections are present, although it is not currently possible to fully support this conclusion with direct scientific evidence. ART is judged to markedly reduce the risk of blood-borne transmission between people who share injection equipment. Finally, the risk of transmission from mother to child is very low, provided that ART is started well in advance of delivery.
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| 4. |
- Kasiske, Bertram L., et al.
(författare)
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KDIGO clinical practice guideline for the care of kidney transplant recipients: a summary
- 2010
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Ingår i: Kidney International. - : Elsevier BV. - 1523-1755 .- 0085-2538. ; 77:4, s. 299-311
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Tidskriftsartikel (refereegranskat)abstract
- The 2009 Kidney Disease: Improving Global Outcomes (KDIGO) clinical practice guideline on the monitoring, management, and treatment of kidney transplant recipients is intended to assist the practitioner caring for adults and children after kidney transplantation. The guideline development process followed an evidence-based approach, and management recommendations are based on systematic reviews of relevant treatment trials. Critical appraisal of the quality of the evidence and the strength of recommendations followed the Grades of Recommendation Assessment, Development, and Evaluation (GRADE) approach. The guideline makes recommendations for immunosuppression and graft monitoring, as well as prevention and treatment of infection, cardiovascular disease, malignancy, and other complications that are common in kidney transplant recipients, including hematological and bone disorders. Limitations of the evidence, especially the lack of definitive clinical outcome trials, are discussed and suggestions are provided for future research. This summary includes a brief description of methodology and the complete guideline recommendations but does not include the rationale and references for each recommendation, which are published elsewhere. Kidney International (2010) 77, 299-311; doi: 10.1038/ki.2009.377; published online 21 October 2009
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| 6. |
- Karlen, A, et al.
(författare)
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Nogo receptor 1 regulates formation of lasting memories
- 2009
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490. ; 106:48, s. 20476-20481
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Tidskriftsartikel (refereegranskat)abstract
- Formation of lasting memories is believed to rely on structural alterations at the synaptic level. We had found that increased neuronal activity down-regulates Nogo receptor-1 (NgR1) in brain regions linked to memory formation and storage, and postulated this to be required for formation of lasting memories. We now show that mice with inducible overexpression of NgR1 in forebrain neurons have normal long-term potentiation and normal 24-h memory, but severely impaired month-long memory in both passive avoidance and swim maze tests. Blocking transgene expression normalizes these memory impairments. Nogo, Lingo-1, Troy, endogenous NgR1, and BDNF mRNA expression levels were not altered by transgene expression, suggesting that the impaired ability to form lasting memories is directly coupled to inability to down-regulate NgR1. Regulation of NgR1 may therefore serve as a key regulator of memory consolidation. Understanding the molecular underpinnings of synaptic rearrangements that carry lasting memories may facilitate development of treatments for memory dysfunction.
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| 8. |
- Ng, Bobby G., et al.
(författare)
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DPAGT1 deficiency with encephalopathy (DPAGT1-CDG) : Clinical and genetic description of 11 new patients
- 2018
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Ingår i: JIMD Reports. - Berlin, Heidelberg : Springer Berlin Heidelberg. - 2192-8312 .- 2192-8304. ; 44, s. 85-92
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Bokkapitel (refereegranskat)abstract
- Pathogenic mutations in DPAGT1 cause a rare type of a congenital disorder of glycosylation termed DPAGT1-CDG or, alternatively, a milder version with only myasthenia known as DPAGT1-CMS. Fourteen disease-causing mutations in 28 patients from 10 families have previously been reported to cause the systemic form, DPAGT1-CDG. We here report on another 11 patients from 8 families and add 10 new mutations. Most patients have a very severe disease course, where common findings are pronounced muscular hypotonia, intractable epilepsy, global developmental delay/intellectual disability, and early death. We also present data on three affected females that are young adults and have a somewhat milder, stable disease. Our findings expand both the molecular and clinical knowledge of previously published data but also widen the phenotypic spectrum of DPAGT1-CDG.
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| 17. |
- Katritsis, Demosthenes G, et al.
(författare)
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Executive Summary : European Heart Rhythm Association Consensus Document on the Management of Supraventricular Arrhythmias
- 2016
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Ingår i: Arrhythmia & electrophysiology review. - 2050-3369. ; 5:3, s. 210-224
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Tidskriftsartikel (refereegranskat)abstract
- This paper is an executive summary of the full European Heart Rhythm Association (EHRA) consensus document on the management of supraventricular arrhythmias, published in Europace. It summarises developments in the field and provides recommendations for patient management, with particular emphasis on new advances since the previous European Society of Cardiology guidelines. The EHRA consensus document is available to read in full at http://europace.oxfordjournals.org.
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| 28. |
- Chen, Zhen, et al.
(författare)
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Design, Synthesis, and Evaluation of Reversible and Irreversible Monoacylglycerol Lipase Positron Emission Tomography (PET) Tracers Using a "Tail Switching" Strategy on a Piperazinyl Azetidine Skeleton
- 2019
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Ingår i: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 62:7, s. 3336-3353
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Tidskriftsartikel (refereegranskat)abstract
- Monoacylglycerol lipase (MAGL) is a senile hydrolase that degrades 2-arachidonoylglycerol (2-AG) in the endocannabinoid system (eCB). Selective inhibition of MAGL has emerged as a potential therapeutic approach for the treatment of diverse pathological conditions, including chronic pain, inflammation, cancer, and neurodegeneration. Herein, we disclose a novel array of reversible and irreversible MAGL inhibitors by means of "tail switching" on a piperazinyl azetidine scaffold. We developed a lead irreversible-binding MAGL inhibitor 8 and reversible-binding compounds 17 and 37, which are amenable for radiolabeling with C-11 or F-18. [C-11]8 ([C-11]MAGL-2-11) exhibited high brain uptake and excellent binding specificity in the brain toward MAGL. Reversible radioligands [C-11]17 ([C-11]PAD) and [F-18]37 ([F-18]MAGL-4-11) also demonstrated excellent in vivo binding specificity toward MAGL in peripheral organs. This work may pave the way for the development of MAGL-targeted positron emission tomography tracers with tunability in reversible and irreversible binding mechanisms.
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| 29. |
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| 30. |
- Edman, K A Paul, et al.
(författare)
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Determinants of force rise time during isometric contraction of frog muscle fibres
- 2007
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Ingår i: Journal of Physiology. - : Wiley. - 1469-7793 .- 0022-3751. ; 580:3, s. 1007-1019
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Tidskriftsartikel (refereegranskat)abstract
- Force-velocity (F-V) relationships were determined for single frog muscle fibres during the rise of tetanic contraction. F-V curves obtained using isotonic shortening early in a tetanic contraction were different from those obtained at equivalent times with isovelocity shortening, apparently because changing activation early in the contraction leads, in isovelocity experiments, to changing force and changing series elastic extension. F-V curves obtained with isotonic and with isovelocity shortening are similar if the shortening velocity in the isovelocity trials is corrected for series elastic extension. There is a progressive shift in the scaling of force-velocity curves along the force axis during the course of the tetanic rise, reflecting increasing fibre activation. The time taken for F-V curves to reach the steady-state position was quite variable, ranging from about 50 ms after the onset of contraction (1-3 degrees C) to well over 100 ms in different fibres. The muscle force at a fixed, moderately high shortening velocity relative to the force at this velocity during the tetanic plateau was taken as a measure of muscle activation. The reference velocity used was 60% of the maximum shortening velocity (V-max) at the tetanic plateau. The estimated value of the fractional activation at 40 ms after the onset of contraction was used as a measure of the rate of activation. The rate of rise of isometric tension in different fibres was correlated with the rate of fibre activation and with V-max during the plateau of the tetanus. Together differences in rate of activation and in V-max accounted for 60-80% of the fibre-to-fibre variability in the rate of rise of isometric tension, depending on the measure of the force rise time used. There was not a significant correlation between the rate of fibre activation and Vmax. The steady-state F-V characteristics and the rate at which these characteristics are achieved early in contraction are seemingly independent. A simulation study based on F-V properties and series compliance in frog muscle fibres indicates that if muscle activation were instantaneous, the time taken for force to rise to 50% of the plateau value would be about 60% shorter than that actually measured from living fibres. Thus about 60% of the force rise time is a consequence of the time course of activation processes and about 40% represents time taken to stretch series compliance by activated contractile material.
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| 31. |
- Fochsen, G, et al.
(författare)
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Predictors of leaving nursing care: a longitudinal study among Swedish nursing personnel.
- 2006
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Ingår i: Occupational and environmental medicine. - : BMJ. - 1470-7926 .- 1351-0711. ; 63:3, s. 198-201
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Despite extensive research on turnover among nursing personnel very little is known about the impact of physical workload and health on leaving. The aim of this study was to find predictors for leaving nursing care with special reference to physical working conditions and musculoskeletal problems. METHODS: This study is based on longitudinal data from a survey of nursing personnel who were employed at various county hospitals in Sweden from 1992-95. A self administrated follow up questionnaire was used to identify their present position in the labour market. The response rate was 73% (n = 1095). RESULTS: The results showed that nursing personnel reporting musculoskeletal problems of the neck/shoulder or knees and those who had limited use of transfer devices were more likely to leave nursing care. CONCLUSIONS: The study highlights the importance of taking musculoskeletal problems and use of transfer devices into consideration in order to retain nursing personnel.
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| 33. |
- Guruprasad, Puneeth, et al.
(författare)
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Integrated automated particle tracking microfluidic enables high-throughput cell deformability cytometry for red cell disorders
- 2019
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Ingår i: American Journal of Hematology. - : Wiley-Blackwell. - 0361-8609 .- 1096-8652. ; 94:2, s. 189-199
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Tidskriftsartikel (refereegranskat)abstract
- Investigating individual red blood cells (RBCs) is critical to understanding hematologic diseases, as pathology often originates at the single-cell level. Many RBC disorders manifest in altered biophysical properties, such as deformability of RBCs. Due to limitations in current biophysical assays, there exists a need for high-throughput analysis of RBC deformability with single-cell resolution. To that end, we present a method that pairs a simple in vitro artificial microvasculature network system with an innovative MATLAB-based automated particle tracking program, allowing for high-throughput, single-cell deformability index (sDI) measurements of entire RBC populations. We apply our technology to quantify the sDI of RBCs from healthy volunteers, Sickle cell disease (SCD) patients, a transfusion-dependent beta thalassemia major patient, and in stored packed RBCs (pRBCs) that undergo storage lesion over 4 weeks. Moreover, our system can also measure cell size for each RBC, thereby enabling 2D analysis of cell deformability vs cell size with single cell resolution akin to flow cytometry. Our results demonstrate the clear existence of distinct biophysical RBC subpopulations with high interpatient variability in SCD as indicated by large magnitude skewness and kurtosis values of distribution, the "shifting" of sDI vs RBC size curves over transfusion cycles in beta thalassemia, and the appearance of low sDI RBC subpopulations within 4 days of pRBC storage. Overall, our system offers an inexpensive, convenient, and high-throughput method to gauge single RBC deformability and size for any RBC population and has the potential to aid in disease monitoring and transfusion guidelines for various RBC disorders.
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| 36. |
- Jehi, L., et al.
(författare)
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Timing of referral to evaluate for epilepsy surgery: Expert Consensus Recommendations from the Surgical Therapies Commission of the International League Against Epilepsy
- 2022
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Ingår i: Epilepsia. - : Wiley. - 0013-9580 .- 1528-1167. ; 63:10, s. 2491-2506
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Tidskriftsartikel (refereegranskat)abstract
- Epilepsy surgery is the treatment of choice for patients with drug-resistant seizures. A timely evaluation for surgical candidacy can be life-saving for patients who are identified as appropriate surgical candidates, and may also enhance the care of nonsurgical candidates through improvement in diagnosis, optimization of therapy, and treatment of comorbidities. Yet, referral for surgical evaluations is often delayed while palliative options are pursued, with significant adverse consequences due to increased morbidity and mortality associated with intractable epilepsy. The Surgical Therapies Commission of the International League Against Epilepsy (ILAE) sought to address these clinical gaps and clarify when to initiate a surgical evaluation. We conducted a Delphi consensus process with 61 epileptologists, epilepsy neurosurgeons, neurologists, neuropsychiatrists, and neuropsychologists with a median of 22 years in practice, from 28 countries in all six ILAE world regions. After three rounds of Delphi surveys, evaluating 51 unique scenarios, we reached the following Expert Consensus Recommendations: (1) Referral for a surgical evaluation should be offered to every patient with drug-resistant epilepsy (up to 70 years of age), as soon as drug resistance is ascertained, regardless of epilepsy duration, sex, socioeconomic status, seizure type, epilepsy type (including epileptic encephalopathies), localization, and comorbidities (including severe psychiatric comorbidity like psychogenic nonepileptic seizures [PNES] or substance abuse) if patients are cooperative with management; (2) A surgical referral should be considered for older patients with drug-resistant epilepsy who have no surgical contraindication, and for patients (adults and children) who are seizure-free on 1-2 antiseizure medications (ASMs) but have a brain lesion in noneloquent cortex; and (3) referral for surgery should not be offered to patients with active substance abuse who are noncooperative with management. We present the Delphi consensus results leading up to these Expert Consensus Recommendations and discuss the data supporting our conclusions. High level evidence will be required to permit creation of clinical practice guidelines.
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| 38. |
- Josephson, A
(författare)
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Forum play
- 2011
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Rapport (övrigt vetenskapligt/konstnärligt)
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| 40. |
- Josephson, C. B., et al.
(författare)
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Predicting postoperative epilepsy surgery satisfaction in adults using the 19-item Epilepsy Surgery Satisfaction Questionnaire and machine learning
- 2021
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Ingår i: Epilepsia. - : Wiley. - 0013-9580 .- 1528-1167. ; 62:9, s. 2103-2112
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The 19-item Epilepsy Surgery Satisfaction Questionnaire (ESSQ-19) is a validated and reliable post hoc means of assessing patient satisfaction with epilepsy surgery. Prediction models building on these data can be used to counsel patients. Methods: The ESSQ-19 was derived and validated on 229 patients recruited from Canada and Sweden. We isolated 201 (88%) patients with complete clinical data for this analysis. These patients were adults (≥18years old) who underwent epilepsy surgery 1year or more prior to answering the questionnaire. We extracted each patient’s ESSQ-19 score (scale is 0–100; 100 represents complete satisfaction) and relevant clinical variables that were standardized prior to the analysis. We used machine learning (linear kernel support vector regression [SVR]) to predict satisfaction and assessed performance using the R2 calculated following threefold cross-validation. Model parameters were ranked to infer the importance of each clinical variable to overall satisfaction with epilepsy surgery. Results: Median age was 41 years (interquartile range [IQR] = 32–53), and 116 (57%) were female. Median ESSQ-19 global score was 68 (IQR = 59–75), and median time from surgery was 5.4years (IQR = 2.0–8.9). Linear kernel SVR performed well following threefold cross-validation, with an R2 of.44 (95% confidence interval =.36–.52). Increasing satisfaction was associated with postoperative self-perceived quality of life, seizure freedom, and reductions in antiseizure medications. Self-perceived epilepsy disability, age, and increasing frequency of seizures that impair awareness were associated with reduced satisfaction. Significance: Machine learning applied postoperatively to the ESSQ-19 can be used to predict surgical satisfaction. This algorithm, once externally validated, can be used in clinical settings by fixing immutable clinical characteristics and adjusting hypothesized postoperative variables, to counsel patients at an individual level on how satisfied they will be with differing surgical outcomes. © 2021 International League Against Epilepsy
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| 41. |
- Josephson, F., et al.
(författare)
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CYP3A induction and inhibition by different antiretroviral regimens reflected by changes in plasma 4beta-hydroxycholesterol levels
- 2008
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Ingår i: European Journal of Clinical Pharmacology. - : Springer Science and Business Media LLC. - 0031-6970 .- 1432-1041. ; 64:8, s. 775-81
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE AND METHODS: A member of the major human cytochrome P450 superfamily of hemoproteins, CYP3A4/5, converts cholesterol into 4beta-hydroxycholesterol. We studied plasma 4beta-hydroxycholesterol levels prior to and 4 weeks after initiating antiretroviral therapy that included efavirenz, ritonavir-boosted atazanavir or ritonavir-boosted lopinavir with the aim of exploring the usefulness of plasma 4beta-hydroxycholesterol levels as an endogenous biomarker of CYP3A activity. Efavirenz is an inducer of CYP3A, whereas the ritonavir-boosted regimens are net inhibitors of CYP3A. RESULTS: In patients treated with efavirenz, the median plasma 4beta-hydroxycholesterol level increased by 46 ng/mL (p = 0.004; n = 11). In contrast, patients given ritonavir-boosted atazanavir showed a median decrease in plasma 4beta-hydroxycholesterol of -9.4 ng/mL (p = 0.0003; n = 22), and those given ritonavir-boosted lopinavir showed a median change from baseline of -5.8 ng/mL (p = 0.38; n = 19). There were significant between-group differences in the effects of antiretroviral treatment on plasma 4beta-hydroxycholesterol levels (p < 0.0001). CONCLUSION: Changes in plasma 4beta-hydroxycholesterol following the initiation of efavirenz- or atazanavir/ritonavir-based antiretroviral therapy reflected the respective net increase and decrease of CYP3A activity of these regimens. The plasma 4beta-hydroxycholesterol level did not indicate a net CYP3A inhibition in the lopinavir/ritonavir arm, possibly because of concomitant enzyme induction.
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