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- Davegårdh, Cajsa, et al.
(författare)
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VPS39-deficiency observed in type 2 diabetes impairs muscle stem cell differentiation via altered autophagy and epigenetics
- 2021
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Insulin resistance and lower muscle quality (strength divided by mass) are hallmarks of type 2 diabetes (T2D). Here, we explore whether alterations in muscle stem cells (myoblasts) from individuals with T2D contribute to these phenotypes. We identify VPS39 as an important regulator of myoblast differentiation and muscle glucose uptake, and VPS39 is downregulated in myoblasts and myotubes from individuals with T2D. We discover a pathway connecting VPS39-deficiency in human myoblasts to impaired autophagy, abnormal epigenetic reprogramming, dysregulation of myogenic regulators, and perturbed differentiation. VPS39 knockdown in human myoblasts has profound effects on autophagic flux, insulin signaling, epigenetic enzymes, DNA methylation and expression of myogenic regulators, and gene sets related to the cell cycle, muscle structure and apoptosis. These data mimic what is observed in myoblasts from individuals with T2D. Furthermore, the muscle of Vps39(+/-) mice display reduced glucose uptake and altered expression of genes regulating autophagy, epigenetic programming, and myogenesis. Overall, VPS39-deficiency contributes to impaired muscle differentiation and reduced glucose uptake. VPS39 thereby offers a therapeutic target for T2D. Insulin resistance and lower muscle strength in relation to mass are hallmarks of type 2 diabetes. Here, the authors report alterations in muscle stem cells from individuals with type 2 diabetes that may contribute to these phenotypes through VPS39 mediated effects on autophagy and epigenetics.
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| 3. |
- Erichsen Andersson, Annette, 1966, et al.
(författare)
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The application of evidence-based measures to reduce surgical site infections during orthopedic surgery - report of a single-center experience in Sweden.
- 2012
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Ingår i: Patient safety in surgery. - : Springer Science and Business Media LLC. - 1754-9493. ; 6:11
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Tidskriftsartikel (refereegranskat)abstract
- ABSTRACT: BACKGROUND: Current knowledge suggests that, by applying evidence-based measures relating to the correct use of prophylactic antibiotics, perioperative normothermia, urinary tract catheterization and hand hygiene, important contributions can be made to reducing the risk of postoperative infections and device-related infections. The aim of this study was to explore and describe the application of intraoperative evidence-based measures, designed to reduce the risk of infection. In addition, we aimed to investigate whether the type of surgery, i.e. total joint arthroplasty compared with tibia and femur/hip fracture surgery, affected the use of protective measures. METHOD: Data on the clinical application of evidence-based measures were collected structurally on site during 69 consecutively included operations involving fracture surgery (n = 35) and total joint arthroplasties (n = 34) using a pre-tested observation form. For observations in relation to hand disinfection, a modified version of the World Health Organization hand hygiene observation method was used. RESULTS: In all, only 29 patients (49%) of 59 received prophylaxis within the recommended time span. The differences in the timing of prophylactic antibiotics between total joint arthroplasty and fracture surgery were significant, i.e. a more accurate timing was implemented in patients undergoing total joint arthroplasty (p = 0.02). Eighteen (53%) of the patients undergoing total joint arthroplasty were actively treated with a forced-air warming system. The corresponding number for fracture surgery was 12 (34%) (p = 0.04).Observations of 254 opportunities for hand hygiene revealed an overall adherence rate of 10.3% to hand disinfection guidelines. CONCLUSIONS: The results showed that the utilization of evidence-based measures to reduce infections in clinical practice is not sufficient and there are unjustifiable differences in care depending on the type of surgery. The poor adherence to hand hygiene precautions in the operating room is a serious problem for patient safety and further studies should focus on resolving this problem. The WHO Safe Surgery checklist "time out" worked as an important reminder, but is not per se a guarantee of safety; it is the way we act in response to mistakes or lapses that finally matters.
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- Erichsen Andersson, Annette, 1966, et al.
(författare)
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Traffic flow in the operating room : An explorative and descriptive study on air quality during orthopedic trauma implant surgery
- 2012
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Ingår i: American Journal of Infection Control. - : Elsevier. - 0196-6553 .- 1527-3296. ; 40:8, s. 750-755
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Tidskriftsartikel (refereegranskat)abstract
- Background:Understanding the protective potential of operating room (OR) ventilation under different conditions is crucial to optimizing the surgical environment. This study investigated the air quality, expressed as colony-forming units (CFU)/m³, during orthopedic trauma surgery in a displacementventilated OR; explored how traffic flow and the number of persons present in the OR affects the air contamination rate in the vicinity of surgical wounds; and identified reasons for door openings in the OR.Methods:Data collection, consisting of active air sampling and observations, was performed during 30 orthopedic procedures.Results:In 52 of the 91 air samples collected (57%), the CFU/m³ values exceeded the recommended level of <10 CFU/m³. In addition, the data showed a strongly positive correlation between the total CFU/m³ per operation and total traffic flow per operation (r=0.74;P=.001; n=24), after controlling for duration of surgery. A weaker, yet still positive correlation between CFU/m³ and the number of persons present in the OR (r=0.22;P=.04; n=82) was also found. Traffic flow, number of persons present, and duration of surgery explained 68% of the variance in total CFU/m³ (P=.001).Conclusions:Traffic flow has a strong negative impact on the OR environment. The results of this study support interventions aimed at preventing surgical site infections by reducing traffic flow in the OR.
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| 5. |
- James, John R., et al.
(författare)
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The T Cell Receptor Triggering Apparatus Is Composed of Monovalent or Monomeric Proteins
- 2011
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Ingår i: Journal of Biological Chemistry. - : American Society for Biochemistry and Molecular Biology, Inc.. - 0021-9258 .- 1083-351X. ; 286:37, s. 31993-32001
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Tidskriftsartikel (refereegranskat)abstract
- Understanding the component stoichiometry of the T cell antigen receptor (TCR) triggering apparatus is essential for building realistic models of signal initiation. Recent studies suggesting that the TCR and other signaling-associated proteins are preclustered on resting T cells relied on measurements of the behavior of membrane proteins at interfaces with functionalized glass surfaces. Using fluorescence recovery after photo-bleaching, we show that, compared with the apical surface, the mobility of TCRs is significantly reduced at Jurkat T cell/glass interfaces, in a signaling-sensitive manner. Using two biophysical approaches that mitigate these effects, bioluminescence resonance energy transfer and two-color coincidence detection microscopy, we show that, within the uncertainty of the methods, the membrane components of the TCR triggering apparatus, i.e. the TCR complex, MHC molecules, CD4/Lck and CD45, are exclusively monovalent or monomeric in human T cell lines, implying that TCR triggering depends only on the kinetics of TCR/pMHC interactions. These analyses also showed that constraining proteins to two dimensions at the cell surface greatly enhances random interactions versus those between the membrane and the cytoplasm. Simulations of TCR-pMHC complex formation based on these findings suggest how unclustered TCR triggering-associated proteins might nevertheless be capable of generating complex signaling outputs via the differential recruitment of cytosolic effectors to the cell membrane.
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| 6. |
- Leinweber, Julia, et al.
(författare)
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Developing a woman-centered, inclusive definition of positive childbirth experiences : A discussion paper
- 2023
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Ingår i: Birth. - : John Wiley & Sons. - 0730-7659 .- 1523-536X. ; 50:2, s. 362-383
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Tidskriftsartikel (refereegranskat)abstract
- Introduction A positive childbirth experience promotes women’s health, both during and beyond the perinatal period. Understanding what constitutes a positive childbirth experience is thus critical to providing high-quality maternity care. Currently, there is no clear, inclusive, woman-centered definition of a positive childbirth experience to guide practice, education, and research.Aim To formulate an inclusive woman-centered definition of a positive childbirth experience.Methods A six-step process was undertaken: (a) Key concepts associated with a positive childbirth were derived from a rapid literature review; (b) The key concepts were used by interdisciplinary experts in the author group to create a draft definition; (c) The draft definition was presented to clinicians and researchers during a European research meeting on perinatal mental health; (d) The authors integrated the expert feedback to refine the working definition; (e) A revised definition was shared with women from consumer groups in six countries to confirm its face validity; and (f) A final definition was formulated based on the women’s feedback (n = 42).Results The following definition was formulated: “A positive childbirth experience refers to a woman’s experience of interactions and events directly related to childbirth that made her feel supported, in control, safe, and respected; a positive childbirth can make women feel joy, confident, and/or accomplished and may have short and/or long-term positive impacts on a woman’s psychosocial well-being.”Conclusions This inclusive, woman-centered definition highlights the importance of provider interactions for facilitating a positive childbirth experience. Feeling supported and having a sense of control, safety, and respect are central tenets. This definition could help to identify and validate positive childbirth experience(s), and to inform practice, education, research, advocacy, and policy-making.
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