| 1. |
|
|
| 2. |
- Blach, S., et al.
(författare)
-
Global change in hepatitis C virus prevalence and cascade of care between 2015 and 2020: a modelling study
- 2022
-
Ingår i: Lancet Gastroenterology & Hepatology. - : Elsevier BV. - 2468-1253. ; 7:5, s. 396-415
-
Tidskriftsartikel (refereegranskat)abstract
- Background Since the release of the first global hepatitis elimination targets in 2016, and until the COVID-19 pandemic started in early 2020, many countries and territories were making progress toward hepatitis C virus (HCV) elimination. This study aims to evaluate HCV burden in 2020, and forecast HCV burden by 2030 given current trends. Methods This analysis includes a literature review, Delphi process, and mathematical modelling to estimate HCV prevalence (viraemic infection, defined as HCV RNA-positive cases) and the cascade of care among people of all ages (age =0 years from birth) for the period between Jan 1, 2015, and Dec 31, 2030. Epidemiological data were collected from published sources and grey literature (including government reports and personal communications) and were validated among country and territory experts. A Markov model was used to forecast disease burden and cascade of care from 1950 to 2050 for countries and territories with data. Model outcomes were extracted from 2015 to 2030 to calculate population-weighted regional averages, which were used for countries or territories without data. Regional and global estimates of HCV prevalence, cascade of care, and disease burden were calculated based on 235 countries and territories. Findings Models were built for 110 countries or territories: 83 were approved by local experts and 27 were based on published data alone. Using data from these models, plus population-weighted regional averages for countries and territories without models (n=125), we estimated a global prevalence of viraemic HCV infection of 0.7% (95% UI 0.7-0.9), corresponding to 56.8 million (95% UI 55.2-67.8) infections, on Jan 1, 2020. This number represents a decrease of 6.8 million viraemic infections from a 2015 (beginning of year) prevalence estimate of 63.6 million (61.8-75.8) infections (0.9% [0.8-1.0] prevalence). By the end of 2020, an estimated 12.9 million (12.5-15.4) people were living with a diagnosed viraemic infection. In 2020, an estimated 641 000 (623 000-765 000) patients initiated treatment. Interpretation At the beginning of 2020, there were an estimated 56.8 million viraemic HCV infections globally. Although this number represents a decrease from 2015, our forecasts suggest we are not currently on track to achieve global elimination targets by 2030. As countries recover from COVID-19, these findings can help refocus efforts aimed at HCV elimination. Copyright (C) 2022 Elsevier Ltd. All rights reserved.
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
- Surendran, Praveen, et al.
(författare)
-
Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension
- 2016
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 48:10, s. 1151-1161
-
Tidskriftsartikel (refereegranskat)abstract
- High blood pressure is a major risk factor for cardiovascular disease and premature death. However, there is limited knowledge on specific causal genes and pathways. To better understand the genetics of blood pressure, we genotyped 242,296 rare, low-frequency and common genetic variants in up to 192,763 individuals and used -1/4155,063 samples for independent replication. We identified 30 new blood pressure- or hypertension-associated genetic regions in the general population, including 3 rare missense variants in RBM47, COL21A1 and RRAS with larger effects (>1.5 mm Hg/allele) than common variants. Multiple rare nonsense and missense variant associations were found in A2ML1, and a low-frequency nonsense variant in ENPEP was identified. Our data extend the spectrum of allelic variation underlying blood pressure traits and hypertension, provide new insights into the pathophysiology of hypertension and indicate new targets for clinical intervention.
|
|
| 7. |
- Zumla, A, et al.
(författare)
-
Towards host-directed therapies for tuberculosis
- 2015
-
Ingår i: Nature reviews. Drug discovery. - : Springer Science and Business Media LLC. - 1474-1784 .- 1474-1776. ; 14:8, s. 511-
-
Tidskriftsartikel (refereegranskat)
|
|
| 8. |
- Surendran, Praveen, et al.
(författare)
-
Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals
- 2020
-
Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 52:12, s. 1314-1332
-
Tidskriftsartikel (refereegranskat)abstract
- Genetic studies of blood pressure (BP) to date have mainly analyzed common variants (minor allele frequency > 0.05). In a meta-analysis of up to similar to 1.3 million participants, we discovered 106 new BP-associated genomic regions and 87 rare (minor allele frequency <= 0.01) variant BP associations (P < 5 x 10(-8)), of which 32 were in new BP-associated loci and 55 were independent BP-associated single-nucleotide variants within known BP-associated regions. Average effects of rare variants (44% coding) were similar to 8 times larger than common variant effects and indicate potential candidate causal genes at new and known loci (for example, GATA5 and PLCB3). BP-associated variants (including rare and common) were enriched in regions of active chromatin in fetal tissues, potentially linking fetal development with BP regulation in later life. Multivariable Mendelian randomization suggested possible inverse effects of elevated systolic and diastolic BP on large artery stroke. Our study demonstrates the utility of rare-variant analyses for identifying candidate genes and the results highlight potential therapeutic targets.
|
|
| 9. |
|
|
| 10. |
|
|
| 11. |
|
|
| 12. |
- van Rheenen, Wouter, et al.
(författare)
-
Genome-wide association analyses identify new risk variants and the genetic architecture of amyotrophic lateral sclerosis
- 2016
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 48:9, s. 1043-1048
-
Tidskriftsartikel (refereegranskat)abstract
- To elucidate the genetic architecture of amyotrophic lateral sclerosis (ALS) and find associated loci, we assembled a custom imputation reference panel from whole-genome-sequenced patients with ALS and matched controls (n = 1,861). Through imputation and mixed-model association analysis in 12,577 cases and 23,475 controls, combined with 2,579 cases and 2,767 controls in an independent replication cohort, we fine-mapped a new risk locus on chromosome 21 and identified C21orf2 as a gene associated with ALS risk. In addition, we identified MOBP and SCFD1 as new associated risk loci. We established evidence of ALS being a complex genetic trait with a polygenic architecture. Furthermore, we estimated the SNP-based heritability at 8.5%, with a distinct and important role for low-frequency variants (frequency 1-10%). This study motivates the interrogation of larger samples with full genome coverage to identify rare causal variants that underpin ALS risk.
|
|
| 13. |
|
|
| 14. |
- Mantz, A. B., et al.
(författare)
-
The XXL Survey. V. Detection of the Sunyaev-Zel'Dovich Effect of the Redshift 1.9 Galaxy Cluster XLSSU J021744.1-034536 With Carma
- 2014
-
Ingår i: Astrophysical Journal. - : American Astronomical Society. - 1538-4357 .- 0004-637X. ; 794:2
-
Tidskriftsartikel (refereegranskat)abstract
- We report the detection of the Sunyaev-Zel'dovich (SZ) effect of galaxy cluster XLSSU J021744.1-034536, using 30 GHz Combined Array for Research in Millimeter-wave Astronomy (CARMA) data. This cluster was discovered via its extended X-ray emission in the XMM-Newton Large Scale Structure survey, the precursor to the XXL survey. It has a photometrically determined redshift z = 1.91(-0.21)(+0.19), making it among the most distant clusters known, and nominally the most distant for which the SZ effect has been measured. The spherically integrated Comptonization is Y-500 = (3.0 +/- 0.4) x 10(-12), a measurement that is relatively insensitive to assumptions regarding the size and redshift of the cluster, as well as the background cosmology. Using a variety of locally calibrated cluster scaling relations extrapolated to z similar to 2, we estimate a mass M-500 similar to (1-2) x 10(14) M-circle dot from the X-ray flux and SZ signal. The measured properties of this cluster are in good agreement with the extrapolation of an X-ray luminosity-SZ effect scaling relation calibrated from clusters discovered by the South Pole Telescope at higher masses and lower redshifts. The full XXL-CARMA sample will provide a more complete, multi-wavelength census of distant clusters in order to robustly extend the calibration of cluster scaling relations to these high redshifts.
|
|
| 15. |
- Abdulla, Salim, et al.
(författare)
-
Baseline data of parasite clearance in patients with falciparum malaria treated with an artemisinin derivative : an individual patient data meta-analysis
- 2015
-
Ingår i: Malaria Journal. - : Springer Science and Business Media LLC. - 1475-2875 .- 1475-2875. ; 14
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Artemisinin resistance in Plasmodium falciparum manifests as slow parasite clearance but this measure is also influenced by host immunity, initial parasite biomass and partner drug efficacy. This study collated data from clinical trials of artemisinin derivatives in falciparum malaria with frequent parasite counts to provide reference parasite clearance estimates stratified by location, treatment and time, to examine host factors affecting parasite clearance, and to assess the relationships between parasite clearance and risk of recrudescence during follow-up. Methods: Data from 24 studies, conducted from 1996 to 2013, with frequent parasite counts were pooled. Parasite clearance half-life (PC1/2) was estimated using the WWARN Parasite Clearance Estimator. Random effects regression models accounting for study and site heterogeneity were used to explore factors affecting PC1/2 and risk of recrudescence within areas with reported delayed parasite clearance (western Cambodia, western Thailand after 2000, southern Vietnam, southern Myanmar) and in all other areas where parasite populations are artemisinin sensitive. Results: PC1/2 was estimated in 6975 patients, 3288 of whom also had treatment outcomes evaluate d during 28-63 days follow-up, with 93 (2.8 %) PCR-confirmed recrudescences. In areas with artemisinin-sensitive parasites, the median PC1/2 following three-day artesunate treatment (4 mg/kg/day) ranged from 1.8 to 3.0 h and the proportion of patients with PC1/2 > 5 h from 0 to 10 %. Artesunate doses of 4 mg/kg/day decreased PC1/2 by 8.1 % (95 % CI 3.2-12.6) compared to 2 mg/kg/day, except in populations with delayed parasite clearance. PC1/2 was longer in children and in patients with fever or anaemia at enrolment. Long PC1/2 (HR = 2.91, 95 % CI 1.95-4.34 for twofold increase, p < 0.001) and high initial parasitaemia (HR = 2.23, 95 % CI 1.44-3.45 for tenfold increase, p < 0.001) were associated independently with an increased risk of recrudescence. In western Cambodia, the region with the highest prevalence of artemisinin resistance, there was no evidence for increasing PC1/2 since 2007. Conclusions: Several factors affect PC1/2. As substantial heterogeneity in parasite clearance exists between locations, early detection of artemisinin resistance requires reference PC1/2 data. Studies with frequent parasite count measurements to characterize PC1/2 should be encouraged. In western Cambodia, where PC1/2 values are longest, there is no evidence for recent emergence of higher levels of artemisinin resistance.
|
|
| 16. |
- Aguiar-Pulido, Vanessa, et al.
(författare)
-
Systems biology analysis of human genomes points to key pathways conferring spina bifida risk
- 2021
-
Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490. ; 118:51
-
Tidskriftsartikel (refereegranskat)abstract
- Spina bifida (SB) is a debilitating birth defect caused by multiple gene and environment interactions. Though SB shows non-Mendelian inheritance, genetic factors contribute to an estimated 70% of cases. Nevertheless, identifying human mutations conferring SB risk is challenging due to its relative rarity, genetic heterogeneity, incomplete penetrance, and environmental influences that hamper genome-wide association studies approaches to untargeted discovery. Thus, SB genetic studies may suffer from population substructure and/or selection bias introduced by typical candidate gene searches. We report a population based, ancestry-matched whole-genome sequence analysis of SB genetic predisposition using a systems biology strategy to interrogate 298 case-control subject genomes (149 pairs). Genes that were enriched in likely gene disrupting (LGD), rare protein-coding variants were subjected to machine learning analysis to identify genes in which LGD variants occur with a different frequency in cases versus controls and so discriminate between these groups. Those genes with high discriminatory potential for SB significantly enriched pathways pertaining to carbon metabolism, inflammation, innate immunity, cytoskeletal regulation, and essential transcriptional regulation consistent with their having impact on the pathogenesis of human SB. Additionally, an interrogation of conserved noncoding sequences identified robust variant enrichment in regulatory regions of several transcription factors critical to embryonic development. This genome-wide perspective offers an effective approach to the interrogation of coding and noncoding sequence variant contributions to rare complex genetic disorders.
|
|
| 17. |
- Brook, M. S., et al.
(författare)
-
Omega-3 supplementation during unilateral resistance exercise training in older women : A within subject and double-blind placebo-controlled trial
- 2021
-
Ingår i: Clinical Nutrition ESPEN. - : Elsevier. - 2405-4577. ; 46, s. 394-404
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND & AIMS: The skeletal muscle anabolic effects of n-3 polyunsaturated fatty acids (n-3 PUFA) appear favoured towards women; a property that could be exploited in older women who typically exhibit poor muscle growth responses to resistance exercise training (RET). Here we sought to generate novel insights into the efficacy and mechanisms of n-3 PUFA alongside short-term RET in older women.METHODS: We recruited 16 healthy older women (Placebo n = 8 (PLA): 67±1y, n-3 PUFA n = 8: 64±1y) to a randomised double-blind placebo-controlled trial (n-3 PUFA; 3680 mg/day versus PLA) of 6 weeks fully-supervised progressive unilateral RET (i.e. 6 × 8 reps, 75% 1-RM, 3/wk-1). Strength was assessed by knee extensor 1-RM and isokinetic dynamometry ∼ every 10 d. Thigh fat free mass (TFFM) was measured by DXA at 0/3/6 weeks. Bilateral vastus lateralis (VL) biopsies at 0/2/4/6 weeks with deuterium oxide (D2O) dosing were used to determine MPS responses for 0-2 and 4-6 weeks. Further, fibre cross sectional area (CSA), myonuclei number and satellite cell (SC) number were assessed, alongside muscle anabolic/catabolic signalling via immunoblotting.RESULTS: RET increased 1-RM equally in the trained leg of both groups (+23 ± 5% n-3 PUFA vs. +25 ± 5% PLA (both P < 0.01)) with no significant increase in maximum voluntary contraction (MVC) (+10 ± 6% n-3 PUFA vs. +13 ± 5% PLA). Only the n-3 PUFA group increased TFFM (3774 ± 158 g to 3961 ± 151 g n-3 PUFA (P < 0.05) vs. 3406 ± 201 g to 3561 ± 170 PLA) and type II fibre CSA (3097 ± 339 μm2 to 4329 ± 264 μm2 n-3 PUFA (P < 0.05) vs. 2520 ± 316 μm2 to 3467 ± 303 μm2 in PL) with RET. Myonuclei number increased equally in n-3 PUFA and PLA in both type I and type II fibres, with no change in SC number. N-3 PUFA had no added benefit on muscle protein synthesis (MPS), however, during weeks 4-6 of RET, absolute synthesis rates (ASR) displayed a trend to increase with n-3 PUFA only (5.6 ± 0.3 g d-1 to 7.1 ± 0.5 g d-1 n-3 PUFA (P = 0.09) vs. 5.5 ± 0.5 g d-1 to 6.5 ± 0.5 g d-1 PLA). Further, the n-3 PUFA group displayed greater 4EBP1 activation after acute RE at 6 weeks.CONCLUSION: n3-PUFA enhanced RET gains in muscle mass through type II fibre hypertrophy, with data suggesting a role for MPS rather than via SC recruitment. As such, the present study adds to a literature base illustrating the apparent enhancement of muscle hypertrophy with RET in older women fed adjuvant n3-PUFA.
|
|
| 18. |
|
|
| 19. |
|
|
| 20. |
- Salama, Suzy M., et al.
(författare)
-
A Zinc Morpholine Complex Prevents HCl/Ethanol-Induced Gastric Ulcers in a Rat Model
- 2016
-
Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
-
Tidskriftsartikel (refereegranskat)abstract
- Zinc is a naturally occurring element with roles in wound healing and rescuing tissue integrity, particularly in the gastrointestinal system, where it can be detected in the mucosal and submucosal layers. Zinc chelates are known to have beneficial effects on the gastrointestinal mucosa and in cases of gastric ulcer. We synthesized complexes of zinc featuring a heterocyclic amine binding amino acids then investigated their ability to enhance the gastric self-repair. Zinc-morpholine complex, Zn(L)SCN, namely showed strong free-radical scavenging, promotion of the DNA and RNA polymerases reconstruction and suppression of cell damage. The complex's mode of action is proposed to involve hydrogen bond formation via its bis(thiocyanato-k) zinc moiety. Zn(L) SCN complex had potent effects on gastric enzymatic activity both in vitro and in vivo. The complex disrupted the ulcerative process as demonstrated by changes in the intermediate metabolites of the oxidative pathway - specifically, reduction in the MDA levels and elevation of reduced glutathione together with an attenuation of oxidative DNA damage. Additionally, Zn(L) SCN restored the gastric mucosa, inhibited the production of pro-inflammatory cytokines (IL-6, TNF and the caspases), and preserved the gastric mucous balance. Zn(L) SCN thus exhibited anti-oxidative, anti-inflammatory and anti-apoptotic activities, all of which have cytoprotective effects on the gastric lining.
|
|
| 21. |
- Schutte, Aletta E., et al.
(författare)
-
Addressing global disparities in blood pressure control : perspectives of the International Society of Hypertension
- 2023
-
Ingår i: Cardiovascular Research. - : Oxford University Press (OUP). - 0008-6363 .- 1755-3245. ; 119:2, s. 381-409
-
Forskningsöversikt (refereegranskat)abstract
- Raised blood pressure (BP) is the leading cause of preventable death in the world. Yet, its global prevalence is increasing, and it remains poorly detected, treated, and controlled in both high- and low-resource settings. From the perspective of members of the International Society of Hypertension based in all regions, we reflect on the past, present, and future of hypertension care, highlighting key challenges and opportunities, which are often region-specific. We report that most countries failed to show sufficient improvements in BP control rates over the past three decades, with greater improvements mainly seen in some high-income countries, also reflected in substantial reductions in the burden of cardiovascular disease and deaths. Globally, there are significant inequities and disparities based on resources, sociodemographic environment, and race with subsequent disproportionate hypertension-related outcomes. Additional unique challenges in specific regions include conflict, wars, migration, unemployment, rapid urbanization, extremely limited funding, pollution, COVID-19-related restrictions and inequalities, obesity, and excessive salt and alcohol intake. Immediate action is needed to address suboptimal hypertension care and related disparities on a global scale. We propose a Global Hypertension Care Taskforce including multiple stakeholders and societies to identify and implement actions in reducing inequities, addressing social, commercial, and environmental determinants, and strengthening health systems implement a well-designed customized quality-of-care improvement framework.
|
|
| 22. |
- Abdulla, Maysaa, et al.
(författare)
-
Cell-of-origin determined by both gene expression profiling and immunohistochemistry is the strongest predictor of survival in patients with diffuse large B-cell lymphoma
- 2020
-
Ingår i: American Journal of Hematology. - : Wiley. - 0361-8609 .- 1096-8652. ; 95:1, s. 57-67
-
Tidskriftsartikel (refereegranskat)abstract
- The tumor cells in diffuse large B-cell lymphomas (DLBCL) are considered to originate from germinal center derived B-cells (GCB) or activated B-cells (ABC). Gene expression profiling (GEP) is preferably used to determine the cell of origin (COO). However, GEP is not widely applied in clinical practice and consequently, several algorithms based on immunohistochemistry (IHC) have been developed. Our aim was to evaluate the concordance of COO assignment between the Lymph2Cx GEP assay and the IHC-based Hans algorithm, to decide which model is the best survival predictor. Both GEP and IHC were performed in 359 homogenously treated Swedish and Danish DLBCL patients, in a retrospective multicenter cohort. The overall concordance between GEP and IHC algorithm was 72%; GEP classified 85% of cases assigned as GCB by IHC, as GCB, while 58% classified as non-GCB by IHC, were categorized as ABC by GEP. There were significant survival differences (overall survival and progression-free survival) if cases were classified by GEP, whereas if cases were categorized by IHC only progression-free survival differed significantly. Importantly, patients assigned as non-GCB/ABC both by IHC and GEP had the worst prognosis, which was also significant in multivariate analyses. Double expression of MYC and BCL2 was more common in ABC cases and was associated with a dismal outcome. In conclusion, to determine COO both by IHC and GEP is the strongest outcome predictor to identify DLBCL patients with the worst outcome.
|
|
| 23. |
|
|
| 24. |
- Carlsson, Anja M, et al.
(författare)
-
Plasmodium falciparum population dynamics during the early phase of anti-malarial drug treatment in Tanzanian children with acute uncomplicated malaria
- 2011
-
Ingår i: Malaria Journal. - : Springer Science and Business Media LLC. - 1475-2875 .- 1475-2875. ; 10, s. 380-
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:This study aimed to explore Plasmodium falciparum population dynamics during the early phase of anti-malarial drug treatment with artemisinin-based combination therapy in children with clinical malaria in a high transmission area in Africa.METHODS:A total of 50 children aged 1-10 years with acute uncomplicated P. falciparum malaria in Bagamoyo District, Tanzania, were enrolled. Participants were hospitalized and received supervised standard treatment with artemether-lumefantrine according to body weight in six doses over 3 days. Blood samples were collected 11 times, i.e. at time of diagnosis (-2 h) and 0, 2, 4, 8, 16, 24, 36, 48, 60 and 72 h after initiation of treatment. Parasite population dynamics were assessed using nested polymerase chain reaction (PCR)-genotyping of merozoite surface protein (msp) 1 and 2.RESULTS:PCR-analyses from nine sequential blood samples collected after initiation of treatment identified 20 and 21 additional genotypes in 15/50 (30%) and 14/50 (28%) children with msp1 and msp2, respectively, non-detectable in the pre-treatment samples (-2 and 0 h combined). Some 15/20 (75%) and 14/21 (67%) of these genotypes were identified within 24 h, whereas 17/20 (85%) and 19/21 (90%) within 48 h for msp1 and msp2, respectively. The genotype profile was diverse, and varied considerably over time both within and between patients, molecular markers and their respective families.CONCLUSION:PCR analyses from multiple blood samples collected during the early treatment phase revealed a complex picture of parasite sub-populations. This underlines the importance of interpreting PCR-outcomes with caution and suggests that the present use of PCR-adjustment from paired blood samples in anti-malarial drug trials may overestimate assessment of drug efficacy in high transmission areas in Africa.The study is registered at http://www.clinicaltrials.gov with identifier NCT00336375.
|
|
| 25. |
- Dahal, Prabin, et al.
(författare)
-
Competing risk events in antimalarial drug trials in uncomplicated Plasmodium falciparum malaria : a WorldWide Antimalarial Resistance Network individual participant data meta-analysis
- 2019
-
Ingår i: Malaria Journal. - : BMC. - 1475-2875 .- 1475-2875. ; 18
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Therapeutic efficacy studies in uncomplicated Plasmodium falciparum malaria are confounded by new infections, which constitute competing risk events since they can potentially preclude/pre-empt the detection of subsequent recrudescence of persistent, sub-microscopic primary infections.Methods: Antimalarial studies typically report the risk of recrudescence derived using the Kaplan-Meier (K-M) method, which considers new infections acquired during the follow-up period as censored. Cumulative Incidence Function (CIF) provides an alternative approach for handling new infections, which accounts for them as a competing risk event. The complement of the estimate derived using the K-M method (1 minus K-M), and the CIF were used to derive the risk of recrudescence at the end of the follow-up period using data from studies collated in the WorldWide Antimalarial Resistance Network data repository. Absolute differences in the failure estimates derived using these two methods were quantified. In comparative studies, the equality of two K-M curves was assessed using the log-rank test, and the equality of CIFs using Gray's k-sample test (both at 5% level of significance). Two different regression modelling strategies for recrudescence were considered: cause-specific Cox model and Fine and Gray's sub-distributional hazard model.Results: Data were available from 92 studies (233 treatment arms, 31,379 patients) conducted between 1996 and 2014. At the end of follow-up, the median absolute overestimation in the estimated risk of cumulative recrudescence by using 1 minus K-M approach was 0.04% (interquartile range (IQR): 0.00-0.27%, Range: 0.00-3.60%). The overestimation was correlated positively with the proportion of patients with recrudescence [Pearson's correlation coefficient (rho): 0.38, 95% Confidence Interval (CI) 0.30-0.46] or new infection [rho: 0.43; 95% CI 0.35-0.54]. In three study arms, the point estimates of failure were greater than 10% (the WHO threshold for withdrawing antimalarials) when the K-M method was used, but remained below 10% when using the CIF approach, but the 95% confidence interval included this threshold.Conclusions: The 1 minus K-M method resulted in a marginal overestimation of recrudescence that became increasingly pronounced as antimalarial efficacy declined, particularly when the observed proportion of new infection was high. The CIF approach provides an alternative approach for derivation of failure estimates in antimalarial trials, particularly in high transmission settings.
|
|
| 26. |
- Dahal, Prabin, et al.
(författare)
-
Temporal distribution of Plasmodium falciparum recrudescence following artemisinin-based combination therapy : an individual participant data meta-analysis
- 2022
-
Ingår i: Malaria Journal. - : Springer Nature. - 1475-2875 .- 1475-2875. ; 21
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The duration of trial follow-up affects the ability to detect recrudescent infections following anti-malarial treatment. The aim of this study was to explore the proportions of recrudescent parasitaemia as ascribed by genotyping captured at various follow-up time-points in treatment efficacy trials for uncomplicated Plasmodium falciparum malaria.Methods: Individual patient data from 83 anti-malarial efficacy studies collated in the WorldWide Antimalarial Resistance Network (WWARN) repository with at least 28 days follow-up were available. The temporal and cumulative distributions of recrudescence were characterized using a Cox regression model with shared frailty on study-sites. Fractional polynomials were used to capture non-linear instantaneous hazard. The area under the density curve (AUC) of the constructed distribution was used to estimate the optimal follow-up period for capturing a P. falciparum malaria recrudescence. Simulation studies were conducted based on the constructed distributions to quantify the absolute overestimation in efficacy due to sub-optimal follow-up.Results: Overall, 3703 recurrent infections were detected in 60 studies conducted in Africa (15,512 children aged < 5 years) and 23 studies conducted in Asia and South America (5272 patients of all ages). Using molecular genotyping, 519 (14.0%) recurrences were ascribed as recrudescent infections. A 28 day artemether-lumefantrine (AL) efficacy trial would not have detected 58% [95% confidence interval (CI) 47-74%] of recrudescences in African children and 32% [95% CI 15-45%] in patients of all ages in Asia/South America. The corresponding estimate following a 42 day dihydroartemisinin-piperaquine (DP) efficacy trial in Africa was 47% [95% CI 19-90%] in children under 5 years old treated with > 48 mg/kg total piperaquine (PIP) dose and 9% [95% CI 0-22%] in those treated with <= 48 mg/kg PIP dose. In absolute terms, the simulation study found that trials limited to 28 days follow-up following AL underestimated the risk of recrudescence by a median of 2.8 percentage points compared to day 63 estimates and those limited to 42 days following DP underestimated the risk of recrudescence by a median of 2.0 percentage points compared to day 42 estimates. The analysis was limited by few clinical trials following patients for longer than 42 days (9 out of 83 trials) and the imprecision of PCR genotyping which overcalls recrudescence in areas of higher transmission biasing the later distribution.Conclusions: Restricting follow-up of clinical efficacy trials to day 28 for AL and day 42 for DP will miss a proportion of late recrudescent treatment failures but will have a modest impact in derived efficacy. The results highlight that as genotyping methods improve consideration should be given for trials with longer duration of follow-up to detect early indications of emerging drug resistance.
|
|
| 27. |
- Taddeo, EP, et al.
(författare)
-
Mitochondrial Proton Leak Regulated by Cyclophilin D Elevates Insulin Secretion in Islets at Nonstimulatory Glucose Levels
- 2020
-
Ingår i: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 69:2, s. 131-145
-
Tidskriftsartikel (refereegranskat)abstract
- Fasting hyperinsulinemia precedes the development of type 2 diabetes. However, it is unclear whether fasting insulin hypersecretion is a primary driver of insulin resistance or a consequence of the progressive increase in fasting glycemia induced by insulin resistance in the prediabetic state. Herein, we have discovered a mechanism that specifically regulates non–glucose-stimulated insulin secretion (NGSIS) in pancreatic islets that is activated by nonesterified free fatty acids, the major fuel used by β-cells during fasting. We show that the mitochondrial permeability transition pore regulator cyclophilin D (CypD) promotes NGSIS, but not glucose-stimulated insulin secretion, by increasing mitochondrial proton leak. Islets from prediabetic obese mice show significantly higher CypD-dependent proton leak and NGSIS compared with lean mice. Proton leak–mediated NGSIS is conserved in human islets and is stimulated by exposure to nonesterified free fatty acids at concentrations observed in obese subjects. Mechanistically, proton leak activates islet NGSIS independently of mitochondrial ATP synthesis but ultimately requires closure of the KATP channel. In summary, we have described a novel nonesterified free fatty acid–stimulated pathway that selectively drives pancreatic islet NGSIS, which may be therapeutically exploited as an alternative way to halt fasting hyperinsulinemia and the progression of type 2 diabetes.
|
|
| 28. |
|
|
| 29. |
- van Rhee, Koen P., et al.
(författare)
-
Pooled Population Pharmacokinetic Analysis and Dose Recommendations for Ciprofloxacin in Intensive Care Unit Patients with Obesity
- 2024
-
Ingår i: Journal of Clinical Pharmacology. - 0091-2700.
-
Tidskriftsartikel (refereegranskat)abstract
- Recent studies have explored the influence of obesity and critical illness on ciprofloxacin pharmacokinetics. However, variation across the subpopulation of individuals with obesity admitted to the intensive care unit (ICU) with varying renal function remains unexamined. This study aims to characterize ciprofloxacin pharmacokinetics in ICU patients with obesity and provide dose recommendations for this special population. Individual patient data of 34 ICU patients with obesity (BMI >30 kg/m2) from four studies evaluating ciprofloxacin pharmacokinetics in ICU patients were pooled and combined with data from a study involving 10 individuals with obesity undergoing bariatric surgery. All samples were collected after intravenous administration. Non-linear mixed effects modeling and simulation were used to develop a population pharmacokinetic model and describe ciprofloxacin exposure in plasma. Model-based dose evaluations were performed using a pharmacokinetic/pharmacodynamic target of AUC/MIC >125. The data from patients with BMI ranging from 30.2 to 58.1 were best described by a two-compartment model with first-order elimination and a proportional error model. The inclusion of Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) as a covariate on clearance reduced inter-individual variability from 57.3% to 38.5% (P <.001). Neither body weight nor ICU admission significantly influenced clearance or volume of distribution. Renal function is a viable predictor for ciprofloxacin clearance in ICU patients with obesity, while critical illness and body weight do not significantly alter clearance. As such, body weight and critical illness do not need to be accounted for when dosing ciprofloxacin in ICU patients with obesity. Individuals with CKD-EPI >60 mL/min/1.73 m2 may require higher dosages for the treatment of pathogens with minimal inhibitory concentration ≥0.25 mg/L.
|
|
| 30. |
- Ababneh, Nidaa A., et al.
(författare)
-
Identification of APTX disease-causing mutation in two unrelated Jordanian families with cerebellar ataxia and sensitivity to DNA damaging agents
- 2020
-
Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 15:8
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Ataxia with oculomotor apraxia type 1 (AOA1) is a rare autosomal recessive cerebellar ataxia, caused by mutations in the APTX gene. The disease is characterized by early-onset cerebellar ataxia, oculomotor apraxia and severe axonal polyneuropathy. The aim of this study was to detect the disease-causing variants in two unrelated consanguineous Jordanian families with cerebellar ataxia using whole exome sequencing (WES), and to correlate the identified mutation(s) with the clinical and cellular phenotypes. METHODS: WES was performed in three affected individuals and segregation analysis of p.W279* APTX candidate variant was performed. Expression levels of APTX were measured in patients' skin fibroblasts and peripheral blood mononuclear cells, followed by western blot analysis in skin fibroblasts. Genotoxicity assay was performed to detect the sensitivity of APTX mutated cells to H2O2, MMC, MMS and etoposide. RESULTS: A recurrent homozygous nonsense variant in APTX gene (c.837G>A, p.W279*) was revealed in all affected individuals. qRT-PCR showed normal APTX levels in peripheral blood and lower levels in fibroblast cells. However, western blot showed the absence of APTX protein in patients' skin fibroblasts. Significant hypersensitivity to H2O2, MMC and etoposide and lack of sensitivity to MMS were noted. CONCLUSIONS: This is the first study to report the identification of a nonsense variant in the APTX gene (c.837G>A; p.W279*) in AOA1 patients within the Jordanian population. This study confirmed the need of WES to assist in the diagnosis of cerebellar ataxia and it emphasizes the importance of studying the pathophysiology of the APTX gene.
|
|
| 31. |
- Abbas, Nahla, et al.
(författare)
-
Flow Variation of the Major Tributaries of Tigris River Due to Climate Change
- 2019
-
Ingår i: Engineering. - : Scientific Research Publishing. - 1947-3931 .- 1947-394X. ; 11:8, s. 437-442
-
Tidskriftsartikel (refereegranskat)abstract
- Iraq relies greatly on the flow of the Euphrates and Tigris Rivers and their tributaries. Five tributaries namely Khabour, Greater Zab, Lesser Zab, AlAd- hiam and Daylia, which are the major tributaries of Tigris River, sustain Northern Iraq Region, a semi-arid, mainly a pastureland. These tributaries contribute about 24 km3 of water annually. The discharge in the tributaries, in recent times, has been suffering increasing variability contributing to more severe droughts and floods apparently due to climate change. This is because there were no dams constructed outside Iraq previously. For an appropriate appreciation, Soil Water Assessment Tool (SWAT) model was used to evaluate the impact of climate change on their discharge for a half-centennial lead time to 2046-2064 and a centennial lead time to 2080-2100. The suitability of the model was first evaluated, and then, outputs from six GCMs were incorporated to evaluate the impacts of climate change on water resources under three emission scenarios: A1B, A2 and B1. The results showed that wa-ter resources are expected to decrease with time.
|
|
| 32. |
|
|
| 33. |
- Abdulla, Mouhamed, 1979, et al.
(författare)
-
Vehicle-to-Vehicle Communications with Urban Intersection Path Loss Models
- 2016
-
Ingår i: 2016 IEEE Globecom Workshops, GC Wkshps 2016 - Proceedings. ; , s. 1-6
-
Konferensbidrag (refereegranskat)abstract
- Vehicle-to-vehicle (V2V) communication can improve road safety and traffic efficiency, particularly around critical areas such as intersections. We analytically derive V2V success probability near an urban intersection, based on empirically supported line-of-sight (LOS), weak-line-of-sight (WLOS), and nonline-of-sight (NLOS) channel models. The analysis can serve as a preliminary design tool for performance assessment over different system parameters and target performance requirements.
|
|
| 34. |
|
|
| 35. |
- Ahmed, Engy, et al.
(författare)
-
Remediation and recycling of chromium from tannery wastewater using combined chemical-biological treatment system
- 2016
-
Ingår i: Process Safety and Environmental Protection. - : Elsevier BV. - 0957-5820 .- 1744-3598. ; 104, s. 1-10
-
Tidskriftsartikel (refereegranskat)abstract
- Tannery wastewater containing chromium (Cr) is one of the most serious problems in leather industry. In order to develop an effective and eco-friendly treatment technology, a combined chemical-biological treatment system was performed for Cr remediation and recycling. The aim of the present study is to design a laboratory scale system using chemical precipitation of Cr(III) combined with biological removal of Cr(VI) from tannery wastewater, and to investigate the possibility of recycling the recovered Cr(III) in the tanning industry. Chemical precipitation of Cr(III) was carried out using lime and cement dust. The actinomycete strain Kitasatosporia sp. was used in microcosm studies for Cr(VI) bioremoval. Moreover, parameters such as type of porous medium, inoculum size, flow rate and culture conditions were investigated. The precipitated Cr(III) that was recovered from the chemical precipitation stage was recycled in the leather tanning industry. Our findings indicate that the maximum Cr(III) precipitation (98%) was achieved using 2 g/100 mL of lime and 2 h of settling rate. On the other hand, microcosm columns using sand that was inoculated with induced culture (OD600 = 2.43) and flow rate (2 mL/min) gave the maximum recovery (99%) of Cr(VI). The experimental Cr(III) was successfully recycled in the tanning process and the experimental leathers showed comparable properties as same as the leathers tanned with commercial Cr(III). Thus, we concluded that using combined chemical-biological treatment system for Cr remediation from tanning wastewater together with recycling process for the recovered Cr(III) is a promising strategy for economic and environmental friendly tanning industry.
|
|
| 36. |
- Al-Henhena, Nawal, et al.
(författare)
-
Chemopreventive effects of Strobilanthes crispus leaf extract on azoxymethane-induced aberrant crypt foci in rat colon
- 2015
-
Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 5
-
Tidskriftsartikel (refereegranskat)abstract
- In this work, microscopic and histological studies suggest that Strobilanthes crispus ethanol extract reduce azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) in rats. S. crispus is considered a traditional medicine and used as an antioxidant. Its leaf contains a large amount of phenolic compounds to which its radical scavenging role is attributed and enhance its ability to eradicate oxidative stress reactions. The study was designed to determine the chemopreventive effect of S. crispus ethanol extract in vivo and in vitro by elucidating the effect of the extract on intermediate biomarkers which can be used as effective predictors of colon cancer. S. crispus was analyzed for DPPH free radical scavenging, nitric oxide (NO) and ferric acid reduction. The results indicated that S. crispus oral administration significantly inhibited colorectal carcinogenesis induced by AOM as revealed by the reduction in the number of ACF. S. crispus down-regulated the expression of PCNA, Bcl2 and beta-catenin. Additionally, it exerted a pronounced inhibitory effect on MDA and NO levels and stimulatory effect on CAT and GPx activities. These results demonstrate that S. crispus is a chemopreventive agent for colorectal cancer through the suppression of early and intermediate carcinogenic phases that may be related to its flavonoid content.
|
|
| 37. |
- Al-Henhena, Nawal, et al.
(författare)
-
Chemopreventive Efficacy of Andrographis paniculata on Azoxymethane-Induced Aberrant Colon Crypt Foci In Vivo
- 2014
-
Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:11
-
Tidskriftsartikel (refereegranskat)abstract
- Andrographis paniculata is a grass-shaped medicinal herb, traditionally used in Southeast Asia. The aim of this study was to evaluate the chemoprotective effects of A. paniculata on colorectal cancer. A. paniculata ethanol extract was tested on azoxymethane (AOM)-induced aberrant crypt foci (ACF) in vivo and in vitro. A. paniculata treated groups showed a significant reduction in the number of ACF of the treated rats. Microscopically, ACF showed remarkably elongated and stratified cells, and depletion of the submucosal glands of AOM group compared to the treated groups. Histologically, staining showed slightly elevated masses above the surrounding mucosa with oval or slit-like orifices. Immunohistochemically, expression of proliferating cell nuclear antigen (PCNA) and beta-catenin protein were down-regulated in the A. paniculata treated groups compared to the AOM group. When colon tissue was homogenized, malondialdehyde (MDA) and nitric oxide (NO) levels were significantly decreased, whereas superoxide dismutase (SOD) activity was increased in the treated groups compared to the AOM group. A. paniculata ethanol extract showed antioxidant and free radical scavenging activity, as elucidated by the measure of oxidative stress markers. Further, the active fractions were assessed against cell lines of CCD841 and HT29 colon cancer cells.
|
|
| 38. |
- Al-Henhena, Nawal, et al.
(författare)
-
Evaluation of chemopreventive potential of Strobilanthes crispus against colon cancer formation in vitro and in vivo
- 2015
-
Ingår i: BMC Complementary and Alternative Medicine. - : Springer Science and Business Media LLC. - 1472-6882. ; 15
-
Tidskriftsartikel (refereegranskat)abstract
- Background: With cancer being one of the major causes of death around the world, studies are ongoing to find new chemotherapeutic leads. There are common mechanisms for colorectal cancer (CRC) formation. Several are connected with oxidative stress-induced cell apoptosis and others are related to imbalanced homeostasis or intake of drugs/toxins. Plants that have been used for decades in folk and traditional medicine have been accepted as one of the commonest sources of discovered natural agents of cancer chemotherapy and chemoprevention. The aim was to study the antioxidant and chemopreventive effects of Strobilanthes crispus on colorectal cancer formation. Methods: Five groups of rats were injected subcutaneously with AOM, 15 mg/kg body weight, each once weekly for 2 weeks. The cancer group was continued on 10 % Tween-20 feeding for 8 weeks. The standard drug group was continued on 35 mg/kg 5-fluorouracil intraperitoneal injection twice a week for 8 weeks, and the experimental groups were continued on 250 and 500 mg/kg S. crispus extract oral feeding for 8 weeks, respectively. The normal group was injected subcutaneously with normal saline once a week for 2 weeks, followed by oral administration of 10 % Tween-20 for 8 weeks. All the rats were sacrificed after 10 weeks. The colons were evaluated grossly and histopathologically for aberrant crypt foci (ACF). Gene expression was performed for Bax, Bcl2, Defa24, Slc24a3, and APC genes by real-time PCR. S. crispus and its fractions were evaluated for their chemopreventive effects against human colorectal adenocarcinoma cell line HT29 and cytotoxicity for normal human colon epithelial cell line CCD 841, and the active fraction was assessed for its components. Results: We observed significant decrease in total colonic ACF formation, malonaldehyde (MDA) and lactate dehydrogenase (LDH), increase in superoxide dismutase (SOD), up-regulation of APC, Bax and Slc24a3, and down-regulation of Defa24 and Bcl-2 in rats treated with Strobilanthes crispus. Conclusion: Our results support the in vivo protection of S. crispus against CRC formation (azoxymethane-induced aberrant crypt foci) and suggest that the mechanism is highly specific to protect from oxidative insults and the following apoptotic cascade.
|
|
| 39. |
|
|
| 40. |
- Al-Rawabdeh, Abdulla M., et al.
(författare)
-
A GIS-based drastic model for assessing aquifer vulnerability in Amman-Zerqa groundwater basin, Jordan
- 2013
-
Ingår i: Engineering. - : Scientific Research Publishing, Inc.. - 1947-3931 .- 1947-394X. ; :5, s. 490-504
-
Tidskriftsartikel (refereegranskat)abstract
- Amman-Zerqa Basin (AZB) is a major basin in Jordan. The concentration of economic, agricultural and social activities within the basin makes it of prime importance to Jordan. Intensive agricultural practices are widespread and located close to groundwater wells, which pose imminent threats to these resources. Groundwater contamination is of particular concern as groundwater resources are the principal source of water for irrigation, drinking and industrial activities. A DRASTIC model integrated with, and GIS tool has been used to evaluate the groundwater vulnerability of AZB. The Drastic index map showed that only 1.2% of the basin’s total area of 3792 km2 lies in the no vulnerable zone and about 69% is classified as having low pollution potential. The results also revealed that about 30% of the catchment area is moderately susceptible to pollution potential and slightly 1% is potentially under high pollution risk. These results suggest that almost one third of the AZB is at moderate risk of pollution potential. These areas are mainly in the north-east and central parts of the basin where the physical factors like gentle slope and high water table well support the chances of getting shallow aquifer water polluted. Areas with high vulnerable pollution are mainly the central of Amman old city.
|
|
| 41. |
- Alzeyadi, Ali, et al.
(författare)
-
A Novel Coating Method for Create Filter Media Capable to Remove Phosphate from Wastewater Effectively
- 2019
-
Ingår i: Engineering. - : Scientific Research Publishing. - 1947-3931 .- 1947-394X. ; 11:8, s. 443-463
-
Tidskriftsartikel (refereegranskat)abstract
- Filtration materials coating with metallic oxides represented a good method for phosphate sorption. However, most of the researchers utilize chemicals as a source of metallic oxides and heating process to set the chemicals over the filtration materials. This study is aimed to introduce the furnace bottom ash FBA as a source of metallic oxides; it is available free because it is dumped as a waste material from power generation plants. The method of creating new filter media involves coating the limestone and sand by FBA, and the ordinary Portland cement OPC utilized as binder to binding the mixture materials. The water is the factor which is responsible for activating the OPC. All factors such as mixed materials ratio, water content and age of reaction have subjected to optimization process. The results revealed that the optimal mixture for phosphate removal consists of 40% FBA, 5% OPC from dry weight of supporting material, 35% water ratio from the total weight of FBA and OPC, and 14 days are enough to complete the materials reaction. Limestone-furnace bottom ash LFBA indicated high capacity for phosphate sorption and possibility of efficiency regenerate. This study demonstrates a new method for coating the filtration materials more convenient with sustainability approach.
|
|
| 42. |
- Arnbjornsson, E., et al.
(författare)
-
The level of copper, zinc and certain free amino acids in the plasma of patients with acute appendicitis
- 1985
-
Ingår i: Nutrition Research. - 0271-5317. ; 5:SUPPL. 1
-
Tidskriftsartikel (refereegranskat)abstract
- Many forms of inflammatory conditions are associated with alterations in physiology, metabolism and concentrations of trace elements such as copper, magnesium, zinc and calcium and of amino acid patterns and C-Reactive protein levels in plasma (1). Decreased levels of zinc and a reciprocal increase of copper in plasma has been seen in many human diseases (2). Nothing concrete is documented concerning these changes in acute appendicitis. The present study was performed to investigate the possible changes in the levels of trace elements such as copper, zinc, magnesium and calcium and electrophoretic patterns, C-Reactive protein and amino acid patterns in plasma in patients admitted for suspected acute appendicitis. The effect of surgical trauma on copper and zinc levels was also investigated.
|
|
| 43. |
- Bhattarai, Achuyt, et al.
(författare)
-
Impact of artemisinin-based combination therapy and insecticide-treated nets on malaria burden in Zanzibar
- 2007
-
Ingår i: PLoS Medicine. - : Public Library of Science (PLoS). - 1549-1277 .- 1549-1676. ; 4:11, s. e309-
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe Roll Back Malaria strategy recommends a combination of interventions for malaria control. Zanzibar implemented artemisinin-based combination therapy (ACT) for uncomplicated malaria in late 2003 and long-lasting insecticidal nets (LLINs) from early 2006. ACT is provided free of charge to all malaria patients, while LLINs are distributed free to children under age 5 y (“under five”) and pregnant women. We investigated temporal trends in Plasmodium falciparum prevalence and malaria-related health parameters following the implementation of these two malaria control interventions in Zanzibar.Methods and FindingsCross-sectional clinical and parasitological surveys in children under the age of 14 y were conducted in North A District in May 2003, 2005, and 2006. Survey data were analyzed in a logistic regression model and adjusted for complex sampling design and potential confounders. Records from all 13 public health facilities in North A District were analyzed for malaria-related outpatient visits and admissions. Mortality and demographic data were obtained from District Commissioner's Office. P. falciparum prevalence decreased in children under five between 2003 and 2006; using 2003 as the reference year, odds ratios (ORs) and 95% confidence intervals (CIs) were, for 2005, 0.55 (0.28–1.08), and for 2006, 0.03 (0.00–0.27); p for trend < 0.001. Between 2002 and 2005 crude under-five, infant (under age 1 y), and child (aged 1–4 y) mortality decreased by 52%, 33%, and 71%, respectively. Similarly, malaria-related admissions, blood transfusions, and malaria-attributed mortality decreased significantly by 77%, 67% and 75%, respectively, between 2002 and 2005 in children under five. Climatic conditions favorable for malaria transmission persisted throughout the observational period.ConclusionsFollowing deployment of ACT in Zanzibar 2003, malaria-associated morbidity and mortality decreased dramatically within two years. Additional distribution of LLINs in early 2006 resulted in a 10-fold reduction of malaria parasite prevalence. The results indicate that the Millennium Development Goals of reducing mortality in children under five and alleviating the burden of malaria are achievable in tropical Africa with high coverage of combined malaria control interventions.
|
|
| 44. |
- Bissinger, Rosi, et al.
(författare)
-
Thrombospondin-1/CD47 signaling modulates transmembrane cation conductance, survival, and deformability of human red blood cells
- 2020
-
Ingår i: Cell Communication and Signaling. - : Springer Nature. - 1478-811X. ; 18:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Thrombospondin-1 (TSP-1), a Ca2+-binding trimeric glycoprotein secreted by multiple cell types, has been implicated in the pathophysiology of several clinical conditions. Signaling involving TSP-1, through its cognate receptor CD47, orchestrates a wide array of cellular functions including cytoskeletal organization, migration, cell-cell interaction, cell proliferation, autophagy, and apoptosis. In the present study, we investigated the impact of TSP-1/CD47 signaling on Ca2+ dynamics, survival, and deformability of human red blood cells (RBCs).Methods: Whole-cell patch-clamp was employed to examine transmembrane cation conductance. RBC intracellular Ca2+ levels and multiple indices of RBC cell death were determined using cytofluorometry analysis. RBC morphology and microvesiculation were examined using imaging flow cytometry. RBC deformability was measured using laser-assisted optical rotational cell analyzer.Results: Exposure of RBCs to recombinant human TSP-1 significantly increased RBC intracellular Ca2+ levels. As judged by electrophysiology experiments, TSP-1 treatment elicited an amiloride-sensitive inward current alluding to a possible Ca2+ influx via non-selective cation channels. Exogenous TSP-1 promoted microparticle shedding as well as enhancing Ca2+- and nitric oxide-mediated RBC cell death. Monoclonal (mouse IgG1) antibody-mediated CD47 ligation using 1F7 recapitulated the cell death-inducing effects of TSP-1. Furthermore, TSP-1 treatment altered RBC cell shape and stiffness (maximum elongation index).Conclusions: Taken together, our data unravel a new role for TSP-1/CD47 signaling in mediating Ca2+ influx into RBCs, a mechanism potentially contributing to their dysfunction in a variety of systemic diseases.
|
|
| 45. |
- Chiang, Chern-En, et al.
(författare)
-
Suboptimal Control of Lipid Levels : Results from 29 Countries Participating in the Centralized Pan-Regional Surveys on the Undertreatment of Hypercholesterolaemia (CEPHEUS)
- 2016
-
Ingår i: Journal of Atherosclerosis and Thrombosis. - : Japan Atherosclerosis Society. - 1880-3873 .- 1340-3478. ; 23:5, s. 567-587
-
Tidskriftsartikel (refereegranskat)abstract
- Aim: Five multicentre, cross-sectional Centralized Pan-Regional Surveys on the Undertreatment of Hypercholesterolaemia (CEPHEUS) were conducted in 29 countries across Asia, Western Europe, Eastern Europe, the Middle East, and Africa. The surveys assessed the current use and efficacy of lipid-lowering drugs (LLDs) worldwide and identified possible patient and physician characteristics associated with failure to attain low-density lipoprotein cholesterol (LDL-C) goals. The aim of this analysis was to consolidate the global results from these surveys. Methods: The surveys involved patients aged >= 18 years who had been prescribed LLDs for at least 3 months without dose changes for at least 6 weeks. A single visit was scheduled for data collection, including fasting plasma lipid and glucose levels. Cardiovascular risk profile and LDL-C goal attainment were assessed according to the 2004 updated US National Cholesterol Education Program Adult Treatment Panel III guidelines. Results: In total, 35 121 patients (mean age: 60.4 years) were included, and 90.3% had been prescribed statin monotherapy. Overall, only 49.4% of patients reached their recommended LDL-C level. LDL-C goals were attained in 54.8% (5084/9273) and 22.8% (3287/14 429) of patients were at high and very high cardiovascular risk, respectively. Factors associated with an increased likelihood of LDL-C goal attainment were lower baseline cardiovascular risk; presence of diabetes mellitus, hypertension, or history of cardiovascular disease; and treatment with simvastatin, atorvastatin, or rosuvastatin (vs. all other LLDs). Conclusion: LDL-C goal attainment in patients taking LLDs is suboptimal worldwide, particularly in patients at high and very high cardiovascular risk.
|
|
| 46. |
- Deane, Colleen S., et al.
(författare)
-
The acute transcriptional response to resistance exercise : impact of age and contraction mode
- 2019
-
Ingår i: Aging. - : Impact Journals LLC. - 1945-4589 .- 1945-4589. ; 11:7, s. 2111-2126
-
Tidskriftsartikel (refereegranskat)abstract
- Optimization of resistance exercise (RE) remains a hotbed of research for muscle building and maintenance. However, the interactions between the contractile components of RE (i.e. concentric (CON) and eccentric (ECC)) and age, are poorly defined. We used transcriptomics to compare age-related molecular responses to acute CON and ECC exercise. Eight young (21 +/- 1 y) and eight older (70 +/- 1 y) exercise-naive male volunteers had vastus lateralis biopsies collected at baseline and 5 h post unilateral CON and contralateral ECC exercise. RNA was subjected to next-generation sequencing and differentially expressed (DE) genes tested for pathway enrichment using Gene Ontology (GO). The young transcriptional response to CON and ECC was highly similar and older adults displayed moderate contraction-specific profiles, with no GO enrichment. Age-specific responses to ECC revealed 104 DE genes unique to young, and 170 DE genes in older muscle, with no GO enrichment. Following CON, 15 DE genes were young muscle-specific, whereas older muscle uniquely expressed 147 up-regulated genes enriched for cell adhesion and blood vessel development, and 28 down-regulated genes involved in mitochondria! respiration, amino acid and lipid metabolism. Thus, older age is associated with contraction-specific regulation often without clear functional relevance, perhaps reflecting a degree of stochastic age-related dysregulation.
|
|
| 47. |
- Hajrezaie, Maryam, et al.
(författare)
-
Biochanin A Gastroprotective Effects in Ethanol-Induced Gastric Mucosal Ulceration in Rats
- 2015
-
Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:3
-
Tidskriftsartikel (refereegranskat)abstract
- Background Biochanin A notable bioactive compound which is found in so many traditional medicinal plant. In vivo study was conducted to assess the protective effect of biochanin A on the gastric wall of Spraguedawley rats' stomachs. Methodology The experimental set included different animal groups. Specifically, four groups with gastric mucosal lesions were receiving either a) Ulcer control group treated with absolute ethanol (5 ml/kg), b) 20 mg/kg of omeprazole as reference group, c) 25 of biochanin A, d) 50 mg/kg of biochanin A. Histopathological sectioning followed by immunohistochemistry staining were undertaken to evaluate the influence of the different treatments on gastric wall mucosal layer. The gastric secretions were collected in the form of homogenate and exposed to superoxide dismutase (SOD) and nitric oxide enzyme (NO) and the level of malondialdehyde (MDA) and protein content were measured. Ulceration and patchy haemorrhage were clearly observed by light microscopy. The morphology of the gastric wall as confirmed by immunohistochemistry and fluorescent microscopic observations, exhibited sever deformity with notable thickness, oedematous and complete loss of the mucosal coverage however the biochanin-pretreated animals, similar to the omeprazole-pretreated animals, showed less damage compared to the ulcer control group. Moreover, up-regulation of Hsp70 protein and down-regulation of Bax protein were detected in the biochanin A pre-treated groups and the gastric glandular mucosa was positively stained with Periodic Acid Schiff (PAS) staining and the Leucocytes infiltration was commonly seen. Biochanin A displayed a great increase in SOD and NO levels and decreased the release of MDA. Conclusions This gastroprotective effect of biochanin A could be attributed to the enhancement of cellular metabolic cycles perceived as an increase in the SOD, NO activity, and decrease in the level of MDA, and also decrease in level of Bax expression and increase the Hsp70 expression level.
|
|
| 48. |
- Hendriksen, Rene S., et al.
(författare)
-
Global monitoring of antimicrobial resistance based on metagenomics analyses of urban sewage
- 2019
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1
-
Tidskriftsartikel (refereegranskat)abstract
- © 2019, The Author(s). Antimicrobial resistance (AMR) is a serious threat to global public health, but obtaining representative data on AMR for healthy human populations is difficult. Here, we use metagenomic analysis of untreated sewage to characterize the bacterial resistome from 79 sites in 60 countries. We find systematic differences in abundance and diversity of AMR genes between Europe/North-America/Oceania and Africa/Asia/South-America. Antimicrobial use data and bacterial taxonomy only explains a minor part of the AMR variation that we observe. We find no evidence for cross-selection between antimicrobial classes, or for effect of air travel between sites. However, AMR gene abundance strongly correlates with socio-economic, health and environmental factors, which we use to predict AMR gene abundances in all countries in the world. Our findings suggest that global AMR gene diversity and abundance vary by region, and that improving sanitation and health could potentially limit the global burden of AMR. We propose metagenomic analysis of sewage as an ethically acceptable and economically feasible approach for continuous global surveillance and prediction of AMR.
|
|
| 49. |
- Karimian, Hamed, et al.
(författare)
-
The Chemopreventive Effect of Tanacetum Polycephalum Against LA7-Induced Breast Cancer in Rats and the Apoptotic Effect of a Cytotoxic Sesquiterpene Lactone in MCF7 Cells : A Bioassay-Guided Approach
- 2015
-
Ingår i: Cellular Physiology and Biochemistry. - : S. Karger AG. - 1015-8987 .- 1421-9778. ; 36:3, s. 988-1003
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Tanacetum polycephalum L. Schultz-Bip is a member of the Asteraceae family. This study evaluated the chemopreventive effect of a T. polycephalum hexane extract (TPHE) using in in vivo and in vitro models. Methods and Results: Five groups of rats: normal control, cancer control, TPHE low dose, TPHE high dose and positive control (tamoxifen) were used for the in vivo study. Histopathological examination showed that TPHE significantly suppressed the carcinogenic effect of LA7 tumour cells. The tumour sections from TPHE-treated rats demonstrated significantly reduced expression of Ki67 and PCNA compared to the cancer control group. Using a bioassay-guided approach, the cytotoxic compound of TPHE was identified as a tricyclic sesquiterpene lactone, namely, 8 beta-hydroxyl-4 beta, 15-dihydrozaluzanin C (HDZC). Signs of early and late apoptosis were observed in MCF7 cells treated with HDZC and were attributed to the mitochondrial intrinsic pathway based on the up-regulation of Bax and the down-regulation of Bcl-2. HDZC induced cell cycle arrest in MCF7 cells and increased the expression of p21 and p27 at the mRNA and protein levels. Conclusion: This results of this study substantiate the anticancer effect of TPHE and highlight the involvement of HDZC as one of the contributing compounds that act by initiating mitochondrial-mediated apoptosis.
|
|
| 50. |
|
|
