| 21. |
- Blalock, Zachary N., et al.
(författare)
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Circulating cell-free mitochondrial DNA levels and glucocorticoid sensitivity in a cohort of male veterans with and without combat-related PTSD
- 2024
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Ingår i: Translational Psychiatry. - 2158-3188. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Circulating cell-free mitochondrial DNA (ccf-mtDNA) is a biomarker of cellular injury or cellular stress and is a potential novel biomarker of psychological stress and of various brain, somatic, and psychiatric disorders. No studies have yet analyzed ccf-mtDNA levels in post-traumatic stress disorder (PTSD), despite evidence of mitochondrial dysfunction in this condition. In the current study, we compared plasma ccf-mtDNA levels in combat trauma-exposed male veterans with PTSD (n = 111) with those who did not develop PTSD (n = 121) and also investigated the relationship between ccf mt-DNA levels and glucocorticoid sensitivity. In unadjusted analyses, ccf-mtDNA levels did not differ significantly between the PTSD and non-PTSD groups (t = 1.312, p = 0.191, Cohen’s d = 0.172). In a sensitivity analysis excluding participants with diabetes and those using antidepressant medication and controlling for age, the PTSD group had lower ccf-mtDNA levels than did the non-PTSD group (F(1, 179) = 5.971, p = 0.016, partial η 2 = 0.033). Across the entire sample, ccf-mtDNA levels were negatively correlated with post-dexamethasone adrenocorticotropic hormone (ACTH) decline (r = −0.171, p = 0.020) and cortisol decline (r = −0.149, p = 0.034) (viz., greater ACTH and cortisol suppression was associated with lower ccf-mtDNA levels) both with and without controlling for age, antidepressant status and diabetes status. Ccf-mtDNA levels were also significantly positively associated with IC50-DEX (the concentration of dexamethasone at which 50% of lysozyme activity is inhibited), a measure of lymphocyte glucocorticoid sensitivity, after controlling for age, antidepressant status, and diabetes status (β = 0.142, p = 0.038), suggesting that increased lymphocyte glucocorticoid sensitivity is associated with lower ccf-mtDNA levels. Although no overall group differences were found in unadjusted analyses, excluding subjects with diabetes and those taking antidepressants, which may affect ccf-mtDNA levels, as well as controlling for age, revealed decreased ccf-mtDNA levels in PTSD. In both adjusted and unadjusted analyses, low ccf-mtDNA levels were associated with relatively increased glucocorticoid sensitivity, often reported in PTSD, suggesting a link between mitochondrial and glucocorticoid-related abnormalities in PTSD.
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| 22. |
- Boyages, John, et al.
(författare)
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Liposuction for Advanced Lymphedema: A Multidisciplinary Approach for Complete Reduction of Arm and Leg Swelling
- 2015
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Ingår i: Annals of Surgical Oncology. - : Springer Science and Business Media LLC. - 1534-4681 .- 1068-9265. ; 22, s. 1263-1270
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Tidskriftsartikel (refereegranskat)abstract
- Purpose. This research describes and evaluates a liposuction surgery and multidisciplinary rehabilitation approach for advanced lymphedema of the upper and lower extremties. Methods. A prospective clinical study was conducted at an Advanced Lymphedema Assessment Clinic (ALAC) comprised of specialists in plastic surgery, rehabilitation, imaging, oncology, and allied health, at Macquarie University, Australia. Between May 2012 and 31 May 2014, a total of 104 patients attended the ALAC. Eligibility criteria for liposuction included (i) unilateral, non-pitting, International Society of Lymphology stage II/III lymphedema; (ii) limb volume difference greater than 25 %; and (iii) previously ineffective conservative therapies. Of 55 eligible patients, 21 underwent liposuction (15 arm, 6 leg) and had at least 3 months postsurgical follow-up (85.7 % cancer-related lymphedema). Liposuction was performed under general anesthesia using a published technique, and compression garments were applied intraoperatively and advised to be worn continuously thereafter. Limb volume differences, bioimpedance spectroscopy (L-Dex), and symptom and functional measurements (using the Patient-Specific Functional Scale) were taken presurgery and 4 weeks postsurgery, and then at 3, 6, 9, and 12 months postsurgery. Results. Mean presurgical limb volume difference was 45.1 % (arm 44.2 %; leg 47.3 %). This difference reduced to 3.8 % (arm 3.6 %; leg 4.3 %) by 6 months postsurgery, a mean percentage volume reduction of 89.6 % (arm 90.2 %; leg 88.2 %) [p < 0.001]. All patients had improved symptoms and function. Bioimpedance spectroscopy showed reduced but ongoing extracellular fluid, consistent with the underlying lymphatic pathology. Conclusions. Liposuction is a safe and effective option for carefully selected patients with advanced lymphedema. Assessment, treatment, and follow-up by a multidisciplinary team is essential.
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| 23. |
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| 24. |
- Chirikian, Orlando, et al.
(författare)
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The effects of xeno-free cryopreservation on the contractile properties of human iPSC derived cardiomyocytes
- 2022
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Ingår i: Journal of Molecular and Cellular Cardiology. - : Elsevier. - 0022-2828 .- 1095-8584. ; 168, s. 107-114
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Tidskriftsartikel (refereegranskat)abstract
- Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have advanced our ability to study the basic function of the heart and model cardiac diseases. Due to the complexities in stem cell culture and differentiation protocols, many researchers source their hiPSC-CMs from collaborators or commercial biobanks. Generally, the field has assumed the health of frozen cardiomyocytes is unchanged if the cells adhere to the substrate and commence beating. However, very few have investigated the effects of cryopreservation on hiPSCCM's functional and transcriptional health at the cellular and molecular level. Here we review methods and challenges associated with cryopreservation, and examine the effects of cryopreservation on the functionality (contractility and calcium handling) and transcriptome of hiPSC-CMs from six healthy stem cell lines. Utilizing protein patterning methods to template physiological cell aspect ratios (7:1, length:width) in conjunction with polyacrylamide (PA) hydrogels, we measured changes in force generation and calcium handling of single hiPSCCMs. We observed that cryopreservation altered the functionality and transcriptome of hiPSC-CMs towards larger sizes and contractile force as assessed by increased spread area and volume, single cell traction force microscopy and delayed calcium dynamics. hiPSC-CMs are broadly used for basic science research, regenerative medicine, and testing biological therapeutics. This study informs the design of experiments utilizing hiPSC-CMs to avoid confounding functional changes due to cryopreservation with other treatments.
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| 25. |
- Coulman, Karen D., et al.
(författare)
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Development of a Bariatric Surgery Core Data Set for an International Registry
- 2023
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Ingår i: Obesity Surgery. - : Springer. - 0960-8923 .- 1708-0428. ; 33:5, s. 1463-1475
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Bariatric and metabolic surgery is an effective treatment for severe and complex obesity; however, robust long-term data comparing operations is lacking. Clinical registries complement clinical trials in contributing to this evidence base. Agreement on standard data for bariatric registries is needed to facilitate comparisons. This study developed a Core Registry Set (CRS) - core data to include in bariatric surgery registries globally.MATERIALS AND METHODS: Relevant items were identified from a bariatric surgery research core outcome set, a registry data dictionary project, systematic literature searches, and a patient advisory group. This comprehensive list informed a questionnaire for a two-round Delphi survey with international health professionals. Participants rated each item's importance and received anonymized feedback in round 2. Using pre-defined criteria, items were then categorized for voting at a consensus meeting to agree the CRS.RESULTS: Items identified from all sources were grouped into 97 questionnaire items. Professionals (n = 272) from 56 countries participated in the round 1 survey of which 45% responded to round 2. Twenty-four professionals from 13 countries participated in the consensus meeting. Twelve items were voted into the CRS including demographic and bariatric procedure information, effectiveness, and safety outcomes.CONCLUSION: This CRS is the first step towards unifying bariatric surgery registries internationally. We recommend the CRS is included as a minimum dataset in all bariatric registries worldwide. Adoption of the CRS will enable meaningful international comparisons of bariatric operations. Future work will agree definitions and measures for the CRS including incorporating quality-of-life measures defined in a parallel project.
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| 26. |
- Duncan, Kyle D., et al.
(författare)
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Direct analysis of naphthenic acids in constructed wetland samples by condensed phase membrane introduction mass spectrometry
- 2020
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Ingår i: Science of the Total Environment. - : ELSEVIER. - 0048-9697 .- 1879-1026. ; 716
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Tidskriftsartikel (refereegranskat)abstract
- The application of direct mass spectrometry techniques to the analysis of complex samples has a number of advantages including reduced sample handling, higher sample throughput, in situ process monitoring, and the potential for adaptation to on-site analysis. We report the application of a semi-permeable capillary hollow fibre membrane probe (immersed directly into an aqueous sample) coupled to a triple quadrupole mass spectrometer by a continuously flowing methanol acceptor phase for the rapid analysis of naphthenic adds with unit mass resolution. The intensity of the naphthenic add-associated peaks in the mass spectrum are normalized to an internal standard in the acceptor phase for quantitation and the relative abundance of the peaks in the mass spectrum are employed to monitor compositional changes in the naphthenic add mixture using principle component analysis. We demonstrate the direct analysis of a synthetic oil sands process-affected water for classical (CnH2n+zO2) as they are attenuated through constructed wetlands containing sedge (Carex aquatilis), cattail (Typha latifolia), or bulrush (Schoenoplectus acutus). Quantitative results for on-line membrane sampling compare favourably to those obtained by solid-phase extraction high-resolution mass spectrometry. Additionally. chemometric analysis of the mass spectra indicates a clear discrimination between naphthenic acid-influenced and natural background waters. Furthermore, the compositional changes within complex naphthenic acid mixtures track closely with the degree of attenuation. Overall, the technique is successful in following changes in both the concentration and composition of naphthenic acids from synthetic oil sands process-affected waters. with the potential for high throughput screening and environmental forensics.
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| 27. |
- Engdahl, Elin, et al.
(författare)
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Bisphenol A Inhibits the Transporter Function of the Blood-Brain Barrier by Directly Interacting with the ABC Transporter Breast Cancer Resistance Protein (BCRP)
- 2021
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Ingår i: International Journal of Molecular Sciences. - : MDPI. - 1661-6596 .- 1422-0067. ; 22:11
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Tidskriftsartikel (refereegranskat)abstract
- The breast cancer resistance protein (BCRP) is an important efflux transporter in the blood-brain barrier (BBB), protecting the brain from a wide range of substances. In this study, we investigated if BCRP function is affected by bisphenol A (BPA), a high production volume chemical used in common consumer products, as well as by bisphenol F (BPF) and bisphenol S (BPS), which are used to substitute BPA. We employed a transwell-based in vitro cell model of iPSC-derived brain microvascular endothelial cells, where BCRP function was assessed by measuring the intracellular accumulation of its substrate Hoechst 33342. Additionally, we used in silico modelling to predict if the bisphenols could directly interact with BCRP. Our results showed that BPA significantly inhibits the transport function of BCRP. Additionally, BPA was predicted to bind to the cavity that is targeted by known BCRP inhibitors. Taken together, our findings demonstrate that BPA inhibits BCRP function in vitro, probably by direct interaction with the transporter. This effect might contribute to BPA's known impact on neurodevelopment.
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| 28. |
- Fazey, Ioan, et al.
(författare)
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Transforming knowledge systems for life on Earth : Visions of future systems and how to get there
- 2020
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Ingår i: Energy Research & Social Science. - : Elsevier. - 2214-6296 .- 2214-6326. ; 70
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Tidskriftsartikel (refereegranskat)abstract
- Formalised knowledge systems, including universities and research institutes, are important for contemporary societies. They are, however, also arguably failing humanity when their impact is measured against the level of progress being made in stimulating the societal changes needed to address challenges like climate change. In this research we used a novel futures-oriented and participatory approach that asked what future envisioned knowledge systems might need to look like and how we might get there. Findings suggest that envisioned future systems will need to be much more collaborative, open, diverse, egalitarian, and able to work with values and systemic issues. They will also need to go beyond producing knowledge about our world to generating wisdom about how to act within it. To get to envisioned systems we will need to rapidly scale methodological innovations, connect innovators, and creatively accelerate learning about working with intractable challenges. We will also need to create new funding schemes, a global knowledge commons, and challenge deeply held assumptions. To genuinely be a creative force in supporting longevity of human and non-human life on our planet, the shift in knowledge systems will probably need to be at the scale of the enlightenment and speed of the scientific and technological revolution accompanying the second World War. This will require bold and strategic action from governments, scientists, civic society and sustained transformational intent.
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| 29. |
- Fisher, Rebecca E., et al.
(författare)
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Measurement of the C-13 isotopic signature of methane emissions from northern European wetlands
- 2017
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Ingår i: Global Biogeochemical Cycles. - 0886-6236 .- 1944-9224. ; 31:3, s. 605-623
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Tidskriftsartikel (refereegranskat)abstract
- Isotopic data provide powerful constraints on regional and global methane emissions and their source profiles. However, inverse modeling of spatially resolved methane flux is currently constrained by a lack of information on the variability of source isotopic signatures. In this study, isotopic signatures of emissions in the Fennoscandian Arctic have been determined in chambers over wetland, in the air 0.3 to 3m above the wetland surface and by aircraft sampling from 100m above wetlands up to the stratosphere. Overall, the methane flux to atmosphere has a coherent delta C-13 isotopic signature of -71 +/- 1%, measured in situ on the ground in wetlands. This is in close agreement with delta C-13 isotopic signatures of local and regional methane increments measured by aircraft campaigns flying through air masses containing elevated methane mole fractions. In contrast, results from wetlands in Canadian boreal forest farther south gave isotopic signatures of -67 +/- 1%. Wetland emissions dominate the local methane source measured over the European Arctic in summer. Chamber measurements demonstrate a highly variable methane flux and isotopic signature, but the results from air sampling within wetland areas show that emissions mix rapidly immediately above the wetland surface and methane emissions reaching the wider atmosphere do indeed have strongly coherent C isotope signatures. The study suggests that for boreal wetlands (>60 degrees N) global and regional modeling can use an isotopic signature of -71 parts per thousand to apportion sources more accurately, but there is much need for further measurements over other wetlands regions to verify this.
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| 30. |
- Hazlett, Karsten RO, et al.
(författare)
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Adaptation of Francisella tularensis to the mammalian environment is governed by cues which can be mimicked in vitro
- 2008
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Ingår i: Infection and Immunity. - 0019-9567 .- 1098-5522. ; 76:10, s. 4479-4488
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Tidskriftsartikel (refereegranskat)abstract
- The intracellular bacterium Francisella tularensis survives in mammals, arthropods, and freshwater amoeba. It was previously established that the conventional media used for in vitro propagation of this microbe do not yield bacteria that mimic those harvested from infected mammals; whether these in vitro-cultivated bacteria resemble arthropod- or amoeba-adapted Francisella is unknown. As a foundation for our goal of identifying F. tularensis outer membrane proteins which are expressed during mammalian infection, we first sought to identify in vitro cultivation conditions that induce the bacterium's infection-derived phenotype. We compared Francisella LVS grown in brain heart infusion broth (BHI; a standard microbiological medium rarely used in Francisella research) to that grown in Mueller-Hinton broth (MHB; the most widely used F. tularensis medium, used here as a negative control) and macrophages (a natural host cell, used here as a positive control). BHI- and macrophage-grown F. tularensis cells showed similar expression of MglA-dependent and MglA-independent proteins; expression of the MglA-dependent proteins was repressed by the supraphysiological levels of free amino acids present in MHB. We observed that during macrophage infection, protein expression by intracellular bacteria differed from that by extracellular bacteria; BHI-grown bacteria mirrored the latter, while MHB-grown bacteria resembled neither. Naïve macrophages responding to BHI- and macrophage-grown bacteria produced markedly lower levels of proinflammatory mediators than those in cells exposed to MHB-grown bacteria. In contrast to MHB-grown bacteria, BHI-grown bacteria showed minimal delay during intracellular replication. Cumulatively, our findings provide compelling evidence that growth in BHI yields bacteria which recapitulate the phenotype of Francisella organisms that have emerged from macrophages.
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