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- Alffenaar, J. W. C., et al.
(author)
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Clinical standards for the dosing and management of TB drugs
- 2022
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In: The International Journal of Tuberculosis and Lung Disease. - Paris, France : International Union Against Tuberculosis and Lung Disease. - 1027-3719 .- 1815-7920. ; 26:6, s. 483-
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Journal article (other academic/artistic)abstract
- Background: Optimal drug dosing is important to ensure adequate response to treatment, prevent development of drug resistance and reduce drug toxicity. The aim of these clinical standards is to provide guidance on 'best practice' for dosing and management of TB drugs.Methods: A panel of 57 global experts in the fields of microbiology, pharmacology and TB care were identified; 51 participated in a Delphi process. A 5-point Likert scale was used to score draft standards. The final document represents the broad consensus and was approved by all participants.Results: Six clinical standards were defined: Standard 1, defining the most appropriate initial dose for TB treatment; Standard 2, identifying patients who may be at risk of sub-optimal drug exposure; Standard 3, identifying patients at risk of developing drug-related toxicity and how best to manage this risk; Standard 4, identifying patients who can benefit from therapeutic drug monitoring (TDM); Standard 5, highlighting education and counselling that should be provided to people initiating TB treatment; and Standard 6, providing essential education for healthcare professionals. In addition, consensus research priorities were identified.Conclusion: This is the first consensus-based Clinical Standards for the dosing and management of TB drugs to guide clinicians and programme managers in planning and implementation of locally appropriate measures for optimal person-centred treatment to improve patient care.
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| 3. |
- Singh, K. P., et al.
(author)
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Clinical standards for the management of adverse effects during treatment for TB
- 2023
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In: The International Journal of Tuberculosis and Lung Disease. - : International Union Against Tuberculosis and Lung Disease. - 1027-3719 .- 1815-7920. ; 27:7, s. 506-519
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Journal article (peer-reviewed)abstract
- BACKGROUND: Adverse effects (AE) to TB treatment cause morbidity, mortality and treatment interruption. The aim of these clinical standards is to encourage best practise for the diagnosis and management of AE.METHODS: 65/81 invited experts participated in a Delphi process using a 5-point Likert scale to score draft standards.RESULTS: We identified eight clinical standards. Each person commencing treatment for TB should: Standard 1, be counselled regarding AE before and during treatment; Standard 2, be evaluated for factors that might increase AE risk with regular review to actively identify and manage these; Standard 3, when AE occur, carefully assessed and possible allergic or hypersensitiv-ity reactions considered; Standard 4, receive appropriate care to minimise morbidity and mortality associated with AE; Standard 5, be restarted on TB drugs after a serious AE according to a standardised protocol that includes active drug safety monitoring. In addition: Standard 6, healthcare workers should be trained on AE including how to counsel people undertaking TB treatment, as well as active AE monitoring and management; Standard 7, there should be active AE monitoring and reporting for all new TB drugs and regimens; and Standard 8, knowledge gaps identified from active AE monitoring should be systematically addressed through clinical research.CONCLUSION: These standards provide a person -centred, consensus-based approach to minimise the impact of AE TB treatment.
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| 6. |
- Gu, H., et al.
(author)
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Ultra-high static magnetic fields cause immunosuppression through disrupting B-cell peripheral differentiation and negatively regulating BCR signaling
- 2023
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In: Medcomm. ; 4:5
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Journal article (peer-reviewed)abstract
- To increase the imaging resolution and detection capability, the field strength of static magnetic fields (SMFs) in magnetic resonance imaging (MRI) has significantly increased in the past few decades. However, research on the side effects of high magnetic field is still very inadequate and the effects of SMF above 1 T (Tesla) on B cells have never been reported. Here, we show that 33.0 T ultra-high SMF exposure causes immunosuppression and disrupts B cell differentiation and signaling. 33.0 T SMF treatment resulted in disturbance of B cell peripheral differentiation and antibody secretion and reduced the expression of IgM on B cell membrane, and these might be intensity dependent. In addition, mice exposed to 33.0 T SMF showed inhibition on early activation of B cells, including B cell spreading, B cell receptor clustering and signalosome recruitment, and depression of both positive and negative molecules in the proximal BCR signaling, as well as impaired actin reorganization. Sequencing and gene enrichment analysis showed that SMF stimulation also affects splenic B cells' transcriptome and metabolic pathways. Therefore, in the clinical application of MRI, we should consider the influence of SMF on the immune system and choose the optimal intensity for treatment. 33.0 T SMF treatment resulted in disturbance of B cell peripheral differentiation and antibody secretion, but lower magnetic fields, including 28.7, 17.8, or the 11.2 T SMFs had much less or no such effects. 33.0 T SMF treatment induced downregulate BCR proximal signaling and impaired F-actin remodeling related BCR clustering. SMF stimulation affected the transcriptome and metabolic pathways of B cells.image.
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- Kozlov, Mikhail, V, et al.
(author)
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Climate shapes the spatiotemporal variation in color morph diversity and composition across the distribution range of Chrysomela lapponica leaf beetle
- 2022
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In: Insect Science. - : John Wiley & Sons. - 1672-9609 .- 1744-7917. ; 29:3, s. 942-955
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Journal article (peer-reviewed)abstract
- Color polymorphism offers rich opportunities for studying the eco-evolutionary mechanisms that drive the adaptations of local populations to heterogeneous and changing environments. We explored the color morph diversity and composition in a Chrysomela lapponica leaf beetle across its entire distribution range to test the hypothesis that environmental and climatic variables shape spatiotemporal variation in the phenotypic structure of a polymorphic species. We obtained information on 13 617 specimens of this beetle from museums, private collections, and websites. These specimens (collected from 1830-2020) originated from 959 localities spanning 33 degrees latitude, 178 degrees longitude, and 4200 m altitude. We classified the beetles into five color morphs and searched for environmental factors that could explain the variation in the level of polymorphism (quantified by the Shannon diversity index) and in the relative frequencies of individual color morphs. The highest level of polymorphism was found at high latitudes and altitudes. The color morphs differed in their climatic requirements; composition of colour morphs was independent of the geographic distance that separated populations but changed with collection year, longitude, mean July temperature and between-year temperature fluctuations. The proportion of melanic beetles, in line with the thermal melanism hypothesis, increased with increasing latitude and altitude and decreased with increasing climate seasonality. Melanic morph frequencies also declined during the past century, but only at high latitudes and altitudes where recent climate warming was especially strong. The observed patterns suggest that color polymorphism is especially advantageous for populations inhabiting unpredictable environments, presumably due to the different climatic requirements of coexisting color morphs.
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| 8. |
- Lind, C. M., et al.
(author)
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Effectiveness and usability of real-time vibrotactile feedback training to reduce postural exposure in real manual sorting work
- 2023
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In: Ergonomics. - : Informa UK Limited. - 0014-0139 .- 1366-5847. ; 66:2, s. 198-216
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Journal article (peer-reviewed)abstract
- Vibrotactile feedback training may be used as a complementary strategy to reduce time in demanding postures in manual handling. This study evaluated the short- and medium-term effects of concurrent posture-correction vibrotactile feedback training on trunk inclination exposure in real manual sorting work. Fifteen warehouse workers completed the training and the follow-up sessions. Trunk inclination angles were recorded using the ambulatory Smart Workwear System. Questionnaires were used for assessing system usability, perceived physical exertion, and work ability. The results showed reduced time in trunk inclination >30°, >45°, and >60°, and reductions in the 90th, 95th, and 99th percentile trunk inclination angles, when receiving feedback and immediately after feedback withdrawal. No significant reduction was retained after one and three weeks. The wearer's comfort was scored high, and the feedback did not increase the perceived cognitive demands. No significant effects attributed to changed trunk inclination exposure were observed for perceived physical exertion or work ability. The training program has the potential of contributing to reduced trunk inclination exposure in the short term. Future studies are needed to evaluate if improvements in the feedback training can transfer the short-term results to retained median- and long-term effects. Practitioner summary: A two-day training program with concurrent posture-correction vibrotactile feedback can contribute to reduced exposure of trunk inclination in real manual sorting work in the short term. More research is needed on how to design the feedback training programs in order to be effective in the long term.
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- Mårtensson, Jonas, et al.
(author)
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The Two Formyl Peptide Receptors Differently Regulate GPR84-Mediated Neutrophil NADPH Oxidase Activity
- 2021
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In: Journal of Innate Immunity. - : S. Karger AG. - 1662-811X .- 1662-8128. ; 13:4, s. 242-256
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Journal article (peer-reviewed)abstract
- Neutrophils express the two formyl peptide receptors (FPR1 and FPR2) and the medium-chain fatty acid receptor GPR84. The FPRs are known to define a hierarchy among neutrophil G protein-coupled receptors (GPCRs), that is, the activated FPRs can either suppress or amplify GPCR responses. In this study, we investigated the position of GPR84 in the FPR-defined hierarchy regarding the activation of neutrophil nicotine adenine dinucleotide phosphate (NADPH) oxidase, an enzyme system designed to generate reactive oxygen species (ROS), which are important regulators in cell signaling and immune regulation. When resting neutrophils were activated by GPR84 agonists, a modest ROS release was induced. However, vast amounts of ROS were induced by these GPR84 agonists in FPR2-desensitized neutrophils, and the response was inhibited not only by a GPR84-specific antagonist but also by an FPR2-specific antagonist. This suggests that the amplified GPR84 agonist response is achieved through a reactivation of desensitized FPR2s. In addition, the GPR84-mediated FPR2 reactivation was independent of beta-arrestin recruitment and sensitive to a protein phosphatase inhibitor. In contrast to FPR2-desensitized cells, FPR1 desensitization primarily resulted in a suppressed GPR84 agonist-induced ROS response, indicating a receptor hierarchical desensitization of GPR84 by FPR1-generated signals. In summary, our data show that the two FPRs in human neutrophils control the NADPH oxidase activity with concomitant ROS production by communicating with GPR84 through different mechanisms. While FPR1 desensitizes GPR84 and by that suppresses the release of ROS induced by GPR84 agonists, amplified ROS release is achieved by GPR84 agonists through reactivation of the desensitized FPR2.
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| 10. |
- Abed, Ayman, 1976, et al.
(author)
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3D simulations of deep mixed columns under road embankment
- 2021
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In: Rakenteiden Mekaniikka. - 0783-6104 .- 1797-5301. ; 54:1, s. 1-20
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Journal article (peer-reviewed)abstract
- When column stabilisation is meant to function as a ground improvement under an embankment, the design cases to be considered consist of overall stability, compression resistance of the column heads, arching of the embankment on the columns and settlements. This paper focuses on the compression resistance of the columns. The proper geotechnical design of deep mixed (deep stabilised) columns under road embankment requires good estimation of the stress-strain behaviour of the columns and the surrounding soil under the embankment and traffic loading. Earlier Finnish design approaches relied on an even traffic load of 10 kN/m2 on the road surface. The dimensioning methods for column stabilised soil are also based on the idea of an even traffic load. Due to Eurocode recommendations a more realistic scenario is introduced, which remarkably increases the magnitude of the traffic loading. After deriving suitable material properties and stiffness parameters for static and dynamic traffic loading, three-dimensional finite element calculations are performed to achieve better understanding of the mechanical interaction between the embankment, columns and soil under the new loading configuration. Even though more investigations are needed before delivering a final statement, the calculations show that, for the considered case in this paper, the new loading scenario has no relevant consequences on the design compared to the earlier design approach.
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