| 1. |
- Ahlstrand, Erik, 1974-, et al.
(författare)
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Long-term molecular epidemiology of staphylococcus epidermidis blood culture isolates from patients with hematological malignancies
- 2014
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Ingår i: PLOS ONE. - San Francisco, USA : Public Library Science. - 1932-6203. ; 9:6
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Tidskriftsartikel (refereegranskat)abstract
- Staphylococcus epidermidis is an important cause of bloodstream infections in patients with hematological malignancies. Knowledge of the long-term epidemiology of these infections is limited. We surveyed all S. epidermidis blood culture isolates from patients treated for hematological malignancies at the University Hospital of Orebro, Sweden from 1980 to 2009. A total of 373 S. epidermidis isolates were identified and multilocus sequence typing, staphylococcal chromosome cassette mec (SCCmec) typing and standard antibiotic susceptibility testing were employed to characterize these isolates. The majority of the isolates 361/373 (97%) belonged to clonal complex 2, and the 373 isolates were divided into 45 sequence types (STs); Simpson's Diversity Index was 0.56. The most prevalent STs were ST2 (243/373, 65%) and ST215 (28/373, 8%). Ninety three percent (226/243) of the ST2 isolates displayed either SCCmec type III or IV. ST2 and 215 were isolated during the entire study period, and together these STs caused temporal peaks in the number of positive blood cultures of S. epidermidis. Methicillin resistance was detected in 213/273 (78%) of all isolates. In the two predominating STs, ST2 and ST215, methicillin resistance was detected in 256/271 isolates (95%), compared with 34/100 (34%) in other STs (p<0.001). In conclusion, in this long-term study of patients with hematological malignancies, we demonstrate a predominance of methicillin-resistant ST2 among S. epidermidis blood culture isolates.
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| 2. |
- Ahmadi, Zainab, et al.
(författare)
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Long-Term Oxygen Therapy 24 vs 15 h/day and Mortality in Chronic Obstructive Pulmonary Disease
- 2016
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Ingår i: PLOS ONE. - San Francisco : Public Library of Science. - 1932-6203. ; 11:9
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Tidskriftsartikel (refereegranskat)abstract
- Long-term oxygen therapy (LTOT) ≥ 15 h/day improves survival in hypoxemic chronic obstructive pulmonary disease (COPD). LTOT 24 h/day is often recommended but may pose an unnecessary burden with no clear survival benefit compared with LTOT 15 h/day. The aim was to test the hypothesis that LTOT 24 h/day decreases all-cause, respiratory, and cardiovascular mortality compared to LTOT 15 h/day in hypoxemic COPD. This was a prospective, observational, population-based study of COPD patients starting LTOT between October 1, 2005 and June 30, 2009 in Sweden. Overall and cause-specific mortality was analyzed using Cox and Fine-Gray regression, controlling for age, sex, prescribed oxygen dose, PaO2 (air), PaCO2 (air), Forced Expiratory Volume in one second (FEV1), WHO performance status, body mass index, comorbidity, and oral glucocorticoids. A total of 2,249 included patients were included with a median follow-up of 1.1 years (interquartile range, 0.6-2.1). 1,129 (50%) patients died and no patient was lost to follow-up. Higher LTOT duration analyzed as a continuous variable was not associated with any change in mortality rate (hazard ratio [HR] 1.00; (95% confidence interval [CI], 0.98 to 1.02) per 1 h/day increase above 15 h/day. LTOT exactly 24 h/day was prescribed in 539 (24%) patients and LTOT 15-16 h/day in 1,231 (55%) patients. Mortality was similar between the groups for all-cause, respiratory and cardiovascular mortality. In hypoxemic COPD, LTOT 24 h/day was not associated with a survival benefit compared with treatment 15-16 h/day. A design for a registry-based randomized trial (R-RCT) is proposed.
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| 3. |
- Ajab, Suad, et al.
(författare)
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The role of microbiota in immunotherapy outcomes in colorectal cancer patients : A protocol for a systematic review
- 2022
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 17:8
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Forskningsöversikt (refereegranskat)abstract
- In the human gut, there are many microbes, including bacteria, viruses and parasites. The imbalance in the numbers of each type of these microbes can translate into gastrointestinal disorders. Lately, different microbiota patterns have been associated with the levels of efficacy of immunotherapy in multiple cancer conditions. Studies have shown that patients with a more diverse gut microbiome respond better to immunotherapy than those with a homogeneous microbiome. This systematic review aims to identify and assess the available evidence on the efficacy of immunotherapy in treating colorectal cancer (CRC) patients and the effect of their microbiota on their treatment outcomes. The researchers will study the literature regarding CRC and immunotherapy outcomes to survey the different approaches employed to assess the treatment outcomes. A systematic search will be performed in five biomedical databases (PubMed, Scopus, Web of Science, Embase, and the Cochrane Library) in June-July, 2022. Also, open-access registers of clinical trials will be trawled. The search will be conducted without geographical or publication date restrictions; however, only papers published in the English language will be sought. Details regarding patients' diets, lifestyles, and characteristics will be assessed. We will define the primary outcome to compare CRC patients' immunotherapy responses with their gut microbiota composition. The systematic review methodology does not require ethics approval due to the nature of the study design. The systematic review results will be published in an open-access peer-reviewed journal.PROSPERO ID: CRD42021277691.
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| 4. |
- Akhras, Michael S., et al.
(författare)
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The Sequencing Bead Array (SBA), a Next-Generation Digital Suspension Array
- 2013
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:10
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Tidskriftsartikel (refereegranskat)abstract
- Here we describe the novel Sequencing Bead Array (SBA), a complete assay for molecular diagnostics and typing applications. SBA is a digital suspension array using Next-Generation Sequencing (NGS), to replace conventional optical readout platforms. The technology allows for reducing the number of instruments required in a laboratory setting, where the same NGS instrument could be employed from whole-genome and targeted sequencing to SBA broad-range biomarker detection and genotyping. As proof-of-concept, a model assay was designed that could distinguish ten Human Papillomavirus (HPV) genotypes associated with cervical cancer progression. SBA was used to genotype 20 cervical tumor samples and, when compared with amplicon pyrosequencing, was able to detect two additional co-infections due to increased sensitivity. We also introduce in-house software Sphix, enabling easy accessibility and interpretation of results. The technology offers a multi-parallel, rapid, robust, and scalable system that is readily adaptable for a multitude of microarray diagnostic and typing applications, e. g. genetic signatures, single nucleotide polymorphisms (SNPs), structural variations, and immunoassays. SBA has the potential to dramatically change the way we perform probe-based applications, and allow for a smooth transition towards the technology offered by genomic sequencing.
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| 5. |
- Al-Maslamani, Muna, et al.
(författare)
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First characterisation of antimicrobial susceptibility and resistance of Neisseria gonorrhoeae isolates in Qatar, 2017-2020
- 2022
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Ingår i: PLOS ONE. - : PLOS. - 1932-6203. ; 17:3
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Tidskriftsartikel (refereegranskat)abstract
- Limited data are available regarding antimicrobial resistance in Neisseria gonorrhoeae strains circulating in WHO Eastern Mediterranean Region (EMR). We investigated the antimicrobial susceptibility/resistance of N. gonorrhoeae isolates to five antimicrobials (ceftriaxone, azithromycin, ciprofloxacin, tetracycline, and benzylpenicillin) currently or previously used for gonorrhoea treatment in Qatar, 2017-2020. Minimum inhibitory concentrations (MICs; mg/L) of antimicrobials were determined using Etest on gonococcal isolates collected during January 1, 2017-August 30, 2020 at Hamad Medical Corporation, a national public healthcare provider. During 2017-2020, resistance in isolates from urogenital sites of 433 patients was 64.7% (95% CI: 59.5-69.6%; range: 43.9-78.7%) for ciprofloxacin, 50.7% (95% CI: 45.3-56.1%; range: 41.3-70.4%) for tetracycline, and 30.8% (95% CI: 26.3-35.6%; range: 26.7-35.8%) for benzylpenicillin. Percentage of isolates non-susceptible to azithromycin was 4.1% (95% CI: 2.0-7.4%; range: 2.7-4.8%) and all (100%) isolates were susceptible to ceftriaxone. Two (1.6%) isolates from 2019 and one (2.2%) isolate from 2020 had high-level resistance to azithromycin (MIC≥256 mg/L). Overall, 1.0% (4/418) of isolates had a ceftriaxone MIC of 0.25 mg/L, which is at the ceftriaxone susceptibility breakpoint (MIC≤0.25 mg/L). Treatment with ceftriaxone 250 mg plus azithromycin 1 g can continuously be recommended for gonorrhoea therapy in Qatar. Continued quality-assured gonococcal AMR surveillance is warranted in EMR.
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| 6. |
- Almon, Ricardo, 1965-, et al.
(författare)
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Association of the European lactase persistence variant (LCT-13910 C > T Polymorphism) with obesity in the Canary Islands
- 2012
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Ingår i: PLOS ONE. - San Francisco : Public Library Science. - 1932-6203. ; 7:8
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Tidskriftsartikel (refereegranskat)abstract
- Background: European lactose tolerance genotype (LCT -13910 C>T, rs4988234) has been positively associated to body mass indexes (BMI) in a meta-analysis of 31,720 individuals of northern and central European descent. A strong association of lactase persistence (LP) with BMI and obesity has also been traced in a Spanish Mediterranean population. The aim of this study was to analyze a potential association of LP compared to lactase non-persistence (LNP) with BMI in inhabitants of the Canary Islands of Spain using Mendelian randomization.Methods: A representative, randomly sampled population of adults belonging to the Canary Islands Nutrition Survey (ENCA) in Spain, aged 18-75 years (n = 551), was genotyped for the LCT - 13910 C>T polymorphism. Milk consumption was assessed by a validated questionnaire. Anthropometric variables were directly measured. WHO classification of BMI was used.Results: LP individuals were significantly more obese than LNP subjects (chi(2) = 10.59; p < 0.005). LP showed in a multivariate linear regression analysis showed a positive association of LP with BMI compared to LNP, (beta = 0.96; 95% CI: 0.08-1.85, p = 0.033). In a multinomial logistic regression analysis normal range weight LP subjects showed an odds ratio for obesity of 2.41; 95% CI 1.39-418, (p = 0.002) compared to LNP.Conclusions: The T-13910 of the allele LCT-13910 C>T polymorphism is positively associated with BMI. LP increases significantly the risk to develop obesity in the studied population. The LCT-13910 C>T polymorphism stands proxy for the lifetime exposure pattern, milk intake, that may increase susceptibility to obesity and to obesity related pathologies.
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| 7. |
- Alpkvist, Helena, et al.
(författare)
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Clinical and Microbiological Factors Associated with High Nasopharyngeal Pneumococcal Density in Patients with Pneumococcal Pneumonia
- 2015
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Ingår i: PLOS ONE. - : Public Library Science. - 1932-6203. ; 10:10
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Tidskriftsartikel (refereegranskat)abstract
- Background: We aimed to study if certain clinical and/or microbiological factors are associated with a high nasopharyngeal (NP) density of Streptococcus pneumoniae in pneumococcal pneumonia. In addition, we aimed to study if a high NP pneumococcal density could be useful to detect severe pneumococcal pneumonia.Methods: Adult patients hospitalized for radiologically confirmed community-acquired pneumonia were included in a prospective study. NP aspirates were collected at admission and were subjected to quantitative PCR for pneumococcal DNA (Spn9802 DNA). Patients were considered to have pneumococcal etiology if S. pneumoniae was detected in blood culture and/ or culture of respiratory secretions and/or urinary antigen test.Results: Of 166 included patients, 68 patients had pneumococcal DNA detected in NP aspirate. Pneumococcal etiology was noted in 57 patients (84%) with positive and 8 patients (8.2%) with negative test for pneumococcal DNA (p<0.0001). The median NP pneumococcal density of DNA positive patients with pneumococcal etiology was 6.83 log(10) DNA copies/mL (range 1.79-9.50). In a multivariate analysis of patients with pneumococcal etiology, a high pneumococcal density was independently associated with severe pneumonia (Pneumonia Severity Index risk class IV-V), symptom duration >= 2 days prior to admission, and a medium/high serum immunoglobulin titer against the patient's own pneumococcal serotype. NP pneumococcal density was not associated with sex, age, smoking, co-morbidity, viral co-infection, pneumococcal serotype, or bacteremia. Severe pneumococcal pneumonia was noted in 28 study patients. When we studied the performance of PCR with different DNA cut-off levels for detection of severe pneumococcal pneumonia, we found sensitivities of 54-82% and positive predictive values of 37-56%, indicating suboptimal performance.Conclusions: Pneumonia severity, symptom duration similar to 2 days, and a medium/high serum immunoglobulin titer against the patient's own serotype were independently associated with a high NP pneumococcal density. NP pneumococcal density has limited value for detection of severe pneumococcal pneumonia.
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| 8. |
- Andersson, Anneli, 1992-, et al.
(författare)
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Attention-deficit/hyperactivity disorder and smoking habits in pregnant women
- 2020
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Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 15:6
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Tidskriftsartikel (refereegranskat)abstract
- Background: Attention-deficit/hyperactivity disorder (ADHD) has been associated with an increased risk of tobacco smoking, and more difficulties with smoking cessation compared to non-ADHD individuals. Women with ADHD may therefore show elevated rates of smoking during pregnancy.Aims: To examine the association between ADHD and smoking habits among pregnant women in Sweden and Norway.Methods: Women pregnant for the first time were identified in Sweden (n = 622,037), and Norway (n = 293,383), of which 1.2% (n = 7,444), and 1.7% (n = 4,951) were defined as having ADHD, respectively. Data on smoking habits were collected early and late in pregnancy.Results: In Sweden, ADHD was associated with an increased risk of smoking early in pregnancy, adjusted risk ratio (adjRR) 2.69 (95% confidence interval, 2.58-2.81), and late in pregnancy, adjRR 2.95 (2.80-3.10). Similar findings were observed in the Norwegian data, early in pregnancy, adjRR 2.31 (2.21-2.40), and late in pregnancy, adjRR 2.56 (2.42-2.70). Women with ADHD were more likely to continue smoking during pregnancy, compared to women without ADHD, both in Sweden adjRR 1.13 (1.10-1.17), and in Norway, adjRR 1.16 (1.12-1.20). Having a sibling diagnosed with ADHD was associated with an increased risk of smoking early and late in pregnancy, in both Sweden and Norway.Conclusions: Women with ADHD are considerably more likely to smoke early and late in (their first) pregnancy and are less likely to stop smoking between the two time points. Smoking, early and late in pregnancy, co-aggregates in families with ADHD. Smoking prevention and intervention programs should be targeted towards women with ADHD, specifically during their childbearing years, to ensure better mother and child outcomes.
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| 9. |
- Andersson, Erik, 1988-, et al.
(författare)
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Subphenotypes of inflammatory bowel disease are characterized by specific serum protein profiles
- 2017
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Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 12:10
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Genetic and immunological data indicate that inflammatory bowel disease (IBD) are characterized by specific inflammatory protein profiles. However, the serum proteome of IBD is still to be defined. We aimed to characterize the inflammatory serum protein profiles of Crohn's disease (CD) and ulcerative colitis (UC), using the novel proximity extension assay.Methods: A panel of 91 inflammatory proteins were quantified in a discovery cohort of CD (n = 54), UC patients (n = 54), and healthy controls (HCs; n = 54). We performed univariate analyses by t-test, with false discovery rate correction. A sparse partial least-squares (sPLS) approach was used to identify additional discriminative proteins. The results were validated in a replication cohort.Results: By univariate analysis, 17 proteins were identified with significantly different abundances in CD and HCs, and 12 when comparing UC and HCs. Additionally, 64 and 45 discriminant candidate proteins, respectively, were identified with the multivariate approach. Correspondingly, significant cross-validation error rates of 0.12 and 0.19 were observed in the discovery cohort. Only FGF-19 was identified from univariate comparisons of CD and UC, but 37 additional discriminant candidates were identified using the multivariate approach. The observed cross-validation error rate for CD vs. UC remained significant when restricting the analyses to patients in clinical remission. Using univariate comparisons, 16 of 17 CD-associated proteins and 8 of 12 UC-associated proteins were validated in the replication cohort. The area under the curve for CD and UC was 0.96 and 0.92, respectively, when the sPLS model from the discovery cohort was applied to the replication cohort.Conclusions: By using the novel PEA method and a panel of inflammatory proteins, we identified proteins with significantly different quantities in CD patients and UC patients compared to HCs. Our data highlight the potential of the serum IBD proteome as a source for identification of future diagnostic biomarkers.
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| 10. |
- Andersson, Henrik, et al.
(författare)
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Apoptotic neutrophils augment the inflammatory response to Mycobacterium tuberculosis infection in human macrophages
- 2014
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Ingår i: PLOS ONE. - : PLOS. - 1932-6203. ; 9:7
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Tidskriftsartikel (refereegranskat)abstract
- Macrophages in the lung are the primary cells being infected by Mycobacterium tuberculosis (Mtb) during the initial manifestation of tuberculosis. Since the adaptive immune response to Mtb is delayed, innate immune cells such as macrophages and neutrophils mount the early immune protection against this intracellular pathogen. Neutrophils are short-lived cells and removal of apoptotic cells by resident macrophages is a key event in the resolution of inflammation and tissue repair. Since anti-inflammatory activity is not compatible with effective immunity to intracellular pathogens, we therefore investigated how uptake of apoptotic neutrophils modulates the function of Mtb-activated human macrophages. We show that Mtb infection exerts a potent proinflammatory activation of human macrophages with enhanced gene activation and release of proinflammatory cytokines and that this response was augmented by apoptotic neutrophils. The enhanced macrophage response is linked to apoptotic neutrophil-driven activation of the NLRP3 inflammasome and subsequent IL-1β signalling. We also demonstrate that apoptotic neutrophils not only modulate the inflammatory response, but also enhance the capacity of infected macrophages to control intracellular growth of virulent Mtb. Taken together, these results suggest a novel role for apoptotic neutrophils in the modulation of the macrophage-dependent inflammatory response contributing to the early control of Mtb infection.
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