Publications by authors named "Magnus Karlsson"

466 Publications

Frequency-comb-calibrated swept-wavelength interferometry.

Opt Express 2021 Jul;29(15):24363-24372

Lasers are often used to characterize samples in a non-destructive manner and retrieve sensing information transduced in changes in amplitude and phase. In swept wavelength interferometry, a wavelength-tunable laser is used to measure the complex response (i.e. in amplitude and phase) of an optical sample. This technique leverages continuous advances in rapidly tunable lasers and is widely used for sensing, bioimaging and testing of photonic integrated components. However, the tunable laser requires an additional calibration step because, in practice, it does not tune at a constant rate. In this work, we use a self-referenced frequency comb as an optical ruler to calibrate the laser used in swept-wavelength interferometry and optical frequency domain reflectometry. This allows for realizing high-resolution complex spectroscopy over a bandwidth exceeding 10 THz. We apply the technique to the characterization of low-loss integrated photonic devices and demonstrate that the phase information can disentangle intrinsic from coupling losses in the characterization of high-Q microresonators. We also demonstrate the technique in reflection mode, where it can resolve attenuation and dispersion characteristics in integrated long spiral waveguides.
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http://dx.doi.org/10.1364/OE.430818DOI Listing
July 2021

Role of Dicer-Dependent RNA Interference in Regulating Mycoparasitic Interactions.

Microbiol Spectr 2021 Sep 22:e0109921. Epub 2021 Sep 22.

Department of Forest Mycology and Plant Pathology, Swedish University of Agricultural Sciencesgrid.6341.0, Uppsala, Sweden.

Dicer-like proteins (DCLs) play a vital role in RNA interference (RNAi), by cleaving RNA filament into small RNAs. Although DCL-mediated RNAi can regulate interspecific communication between pathogenic/mutualistic organisms and their hosts, its role in mycoparasitic interactions is yet to be investigated. In this study, we deleted genes in the mycoparasitic fungus and characterize the functions of DCL-dependent RNAi in mycoparasitism. Deletion of resulted in a mutant with reduced secondary metabolite production, antagonism toward the plant-pathogenic fungus , and reduced ability to control Fusarium foot rot disease on wheat, caused by Fusarium graminearum. Transcriptome sequencing of the interaction between the Δ strain and or F. graminearum identified the downregulation of genes coding for transcription factors, membrane transporters, hydrolytic enzymes, and secondary metabolites biosynthesis enzymes putatively involved in antagonistic interactions, in comparison with the wild-type interaction. A total of 61 putative novel microRNA-like RNAs (milRNAs) were identified in , and 11 were downregulated in the Δ mutant. In addition to putative endogenous gene targets, these milRNAs were predicted to target . and F. graminearum virulence factor genes, which showed an increased expression during interaction with the Δ mutant incapable of producing the targeting milRNAs. In summary, this study constitutes the first step in elucidating the role of RNAi in mycoparasitic interactions, with important implications for biological control of plant diseases, and poses the base for future studies focusing on the role of cross-species RNAi regulating mycoparasitic interactions. Small RNAs mediated RNA interference (RNAi) known to regulate several biological processes. Dicer-like endoribonucleases (DCLs) play a vital role in the RNAi pathway by generating sRNAs. In this study, we investigated a role of DCL-mediated RNAi in interference interactions between mycoparasitic fungus and the two fungal pathogens and Fusarium graminearum (here called mycohosts). We found that the mutants were not able to produce 11 sRNAs predicted to finetune the regulatory network of genes known to be involved in production of hydrolytic enzymes, antifungal compounds, and membrane transporters needed for antagonistic action of . We also found . sRNAs putatively targeting known virulence factors in the mycohosts, indicating RNAi-mediated cross-species communication. Our study expanded the understanding of underlying mechanisms of cross-species communication during interference interactions and poses a base for future works studying the role of DCL-based cross-species RNAi in fungal interactions.
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http://dx.doi.org/10.1128/Spectrum.01099-21DOI Listing
September 2021

Physical activity spectrum discriminant analysis-A method to compare detailed patterns between groups.

Scand J Med Sci Sports 2021 Sep 18. Epub 2021 Sep 18.

Department of Translational Medicine, Lund University, Malmö, Sweden.

Investigating physical activity (PA) patterns as a detailed intensity spectrum instead of crude intensity categories have improved the ability to analyze the relationship between measured PA and health variables. The aim of this methodological study was to introduce and investigate the utility of using detailed PA intensity spectrum compared to crude PA intensity categories for comparison of PA between groups and between repeated measures. The study sample consisted of two groups of children, where one group was scheduled for extended physical education (PE) by daily classes while the other group followed usual PE schedule. Accelerometer data was processed into traditional crude PA intensity categories and into detailed PA intensity spectrum. Multivariate partial least squares regression for discriminant analysis (PLS-DA) was applied for PA intensity spectrum group comparison and compared to traditional univariate statistical analysis. Repeated measures were investigated using independent PLS-DA as well as multilevel PLS-DA for paired analysis. While traditional analysis of crude PA intensity categories was unable to find any group differences, multivariate analysis of the PA intensity spectrum identified statistically significant differences. By the extension of multilevel PLS-DA for paired comparison, a clear difference in the PA intensity spectrum was demonstrated between repeated measures. In conclusion, analysis of detailed PA intensity spectrum demonstrates utility for comparing detailed PA data between groups and between repeated measures in interventional and observational research.
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http://dx.doi.org/10.1111/sms.14052DOI Listing
September 2021

Overcoming the quantum limit of optical amplification in monolithic waveguides.

Sci Adv 2021 Sep 15;7(38):eabi8150. Epub 2021 Sep 15.

Department of Microtechnology and Nanoscience, Chalmers University of Technology, 41296 Gothenburg, Sweden.

[Figure: see text].
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http://dx.doi.org/10.1126/sciadv.abi8150DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8443169PMC
September 2021

Methodology for Digital Transformation with Internet of Things and Cloud Computing: A Practical Guideline for Innovation in Small- and Medium-Sized Enterprises.

Sensors (Basel) 2021 Aug 9;21(16). Epub 2021 Aug 9.

Department of Science and Technology, Campus Norrköping, Linköping University, 60221 Norrköping, Sweden.

Researches on the Internet of Things (IoT) and cloud computing have been pervasive in both the academic and industrial world. IoT and cloud computing are seen as cornerstones to digital transformation in the industry. However, restricted by limited resources and the lack of expertise in information and communication technologies, small- and medium-sized enterprises (SMEs) have difficulty in achieving digitalization of their business. In this paper, we propose a reference framework for SMEs to follow as a guideline in the journey of digital transformation. The framework features a three-stage procedure that covers business, technology, and innovation, which can be iterated to drive product and business development. A case study about digital transformation taking place in the vertical plant wall industry is detailed. Furthermore, some solution design principles that are concluded from real industrial practice are presented. This paper reviews the digital transformation practice in the vertical plant wall industry and aims to accelerate the pace of SMEs in the journey of digital transformation.
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http://dx.doi.org/10.3390/s21165355DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8399212PMC
August 2021

A Sensing System Based on Public Cloud to Monitor Indoor Environment of Historic Buildings.

Sensors (Basel) 2021 Aug 4;21(16). Epub 2021 Aug 4.

Department of Science and Technology, Campus Norrköping, Linköping University, SE-601 74 Norrköping, Sweden.

Monitoring the indoor environment of historic buildings helps to identify potential risks, provide guidelines for improving regular maintenance, and preserve cultural artifacts. However, most of the existing monitoring systems proposed for historic buildings are not for general digitization purposes that provide data for smart services employing, e.g., artificial intelligence with machine learning. In addition, considering that preserving historic buildings is a long-term process that demands preventive maintenance, a monitoring system requires stable and scalable storage and computing resources. In this paper, a digitalization framework is proposed for smart preservation of historic buildings. A sensing system following the architecture of this framework is implemented by integrating various advanced digitalization techniques, such as Internet of Things, Edge computing, and Cloud computing. The sensing system realizes remote data collection, enables viewing real-time and historical data, and provides the capability for performing real-time analysis to achieve preventive maintenance of historic buildings in future research. Field testing results show that the implemented sensing system has a 2% end-to-end loss rate for collecting data samples and the loss rate can be decreased to 0.3%. The low loss rate indicates that the proposed sensing system has high stability and meets the requirements for long-term monitoring of historic buildings.
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http://dx.doi.org/10.3390/s21165266DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8398254PMC
August 2021

Postural orientation, what to expect in youth athletes? A cohort study on data from the Malmö Youth Sport Study.

BMC Sports Sci Med Rehabil 2021 Jul 24;13(1):76. Epub 2021 Jul 24.

Department of Health Sciences, Lund University, Lund, Sweden.

Background: Studies investigating postural orientation in uninjured youth athletes are scarce. Understanding how postural orientation during functional performance tests change with age in uninjured athletes has the potential to enhance awareness of changes in performance after injury and to set realistic goals for injured athletes. Thus, the aim of this study was to explore postural orientation during functional tasks at early adolescence, and changes in postural orientation from early to middle adolescence and relate this to sex, type of sport and right leg lean body mass (RLLBM).

Methods: In this cohort study 144 (38% female) youth athletes (mean age 13.5 years, SD 0.3) were included at baseline and 86 of these at follow up 2 years later. Four functional performance tests were visually evaluated for Postural Orientation Errors (POEs) with an ordinal scale, ranging from 0 (good) to 2 (poor), yielding a maximum total POE score of 51, and RLLBM by dual energy X-ray absorptiometry.

Results: Improvements were observed in the total POE score from baseline to follow-up, median difference - 10 and - 7 (p < 0.001) for female and male athletes, respectively. At follow-up, female athletes had lower total POE score (median 18) than males (median 24) (p = 0.01). There were no differences in POE scores between sports type (team, individual, aesthetic) (p = 0.20-0.98) and no relationship between total POE score and RLLBM (r = 0.09, p = 0.42).

Conclusions: POEs appear to be quite common in young athletic population, but improvements are achieved over time. At mid-adolescence, female athletes seem to have less POEs than males. Neither sport type nor RLLBM seem to influence postural orientation.
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http://dx.doi.org/10.1186/s13102-021-00307-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8306364PMC
July 2021

Serum glycine levels are associated with cortical bone properties and fractures risk in men.

J Clin Endocrinol Metab 2021 Jul 23. Epub 2021 Jul 23.

Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.

Context: In a recent study a pattern of 27 metabolites, including serum glycine, associated with bone mineral density (BMD).

Objective: To investigate associations for serum and urinary glycine levels with BMD, bone microstructure and fracture risk in men.

Methods: In the population based MrOS Sweden study (men, 69-81 years) serum glycine and BMD were measured at baseline (n=965) and 5-year follow up (n=546). Cortical and trabecular bone parameters of the distal tibia were measured at follow-up using high resolution peripheral quantitative computed tomography. Urinary (n=2,682) glycine was analyzed at baseline. X-ray validated fractures (n=594) were ascertained during a median follow-up of 9.6 years. Associations were evaluated using linear regression (bone parameters) or Cox regression (fractures).

Results: Circulating glycine levels were inversely associated with femoral neck (FN)-BMD. A meta-analysis (n=7,543) combining MrOS Sweden data with data from three other cohorts confirmed a robust inverse association between serum glycine levels and FN-BMD (p=7.7 x 10 -9). Serum glycine was inversely associated with the bone strength parameter failure load in the distal tibia (p=0.002), mainly as a consequence of an inverse association with cortical cross-sectional area and a direct association with cortical porosity. Both serum and urinary glycine levels predicted major osteoporotic fractures (serum, HR per SD increase = 1.20, 95% CI 1.03-1.40; urine HR=1.13, 95% CI 1.02-1.24). These fracture associations were only marginally reduced in models adjusted for FRAX with BMD.

Conclusions: Serum and urinary glycine are indirectly associated with FN-BMD and cortical bone strength, and directly associated with fracture risk in men.
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http://dx.doi.org/10.1210/clinem/dgab544DOI Listing
July 2021

Comparative analyses of the Hymenoscyphus fraxineus and Hymenoscyphus albidus genomes reveals potentially adaptive differences in secondary metabolite and transposable element repertoires.

BMC Genomics 2021 Jul 4;22(1):503. Epub 2021 Jul 4.

Department of Forest Mycology and Plant Pathology, Swedish University of Agricultural Sciences, Almas Allé 5, Box 7026, SE-750 07, Uppsala, Sweden.

Background: The dieback epidemic decimating common ash (Fraxinus excelsior) in Europe is caused by the invasive fungus Hymenoscyphus fraxineus. In this study we analyzed the genomes of H. fraxineus and H. albidus, its native but, now essentially displaced, non-pathogenic sister species, and compared them with several other members of Helotiales. The focus of the analyses was to identify signals in the genome that may explain the rapid establishment of H. fraxineus and displacement of H. albidus.

Results: The genomes of H. fraxineus and H. albidus showed a high level of synteny and identity. The assembly of H. fraxineus is 13 Mb longer than that of H. albidus', most of this difference can be attributed to higher dispersed repeat content (i.e. transposable elements [TEs]) in H. fraxineus. In general, TE families in H. fraxineus showed more signals of repeat-induced point mutations (RIP) than in H. albidus, especially in Long-terminal repeat (LTR)/Copia and LTR/Gypsy elements. Comparing gene family expansions and 1:1 orthologs, relatively few genes show signs of positive selection between species. However, several of those did appeared to be associated with secondary metabolite genes families, including gene families containing two of the genes in the H. fraxineus-specific, hymenosetin biosynthetic gene cluster (BGC).

Conclusion: The genomes of H. fraxineus and H. albidus show a high degree of synteny, and are rich in both TEs and BGCs, but the genomic signatures also indicated that H. albidus may be less well equipped to adapt and maintain its ecological niche in a rapidly changing environment.
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http://dx.doi.org/10.1186/s12864-021-07837-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8254937PMC
July 2021

Reduction of the Adverse Impacts of Fungal Mycotoxin on Proximate Composition of Feed and Growth Performance in Broilers by Combined Adsorbents.

Toxins (Basel) 2021 06 21;13(6). Epub 2021 Jun 21.

Department of Veterinary Pathology and Microbiology, Faculty of Veterinary Medicine, University of Nigeria, Nsukka 410001, Nigeria.

Synergistic interaction of adsorbents in reducing the adverse impacts of mycotoxin on performance and proximate composition of broiler feeds was investigated. Fungal growth was induced by sprinkling water on the feed. + bentonite, kaolin + bentonite or + kaolin adsorbent combinations (1.5 g/kg feed) were added and the feeds were stored in black polythene bags. An untreated group was kept as a positive control while fresh uncontaminated feed was used as a negative control. Mycotoxins were extracted from the feeds and quantified using reverse phase HPLC. Proximate composition, nutrient digestibility of the feeds, feed intake and weight gain of the broilers were measured. Deoxynivalenol (DON) concentration in the contaminated/untreated feed was 347 µg/kg while aflatoxin B1 (AFB1) was 34 µg/kg. Addition of bentonite and kaolin in the contaminated feed reduced AFB1 and DON to significantly lower levels. Feed intake and weight gain were low in the broilers fed the contaminated feed. The carbohydrate level was significantly ( < 0.05) reduced from 62.31 to 40.10%, crude protein digestibility dropped from 80.67 to 49.03% in the fresh feed and contaminated feed respectively. Addition of the adsorbents ( and bentonite) significantly ( < 0.05) improved these parameters.
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http://dx.doi.org/10.3390/toxins13060430DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8235260PMC
June 2021

What Cut-Point in Gait Speed Best Discriminates Community-Dwelling Older Adults With Mobility Complaints From Those Without? A Pooled Analysis From the Sarcopenia Definitions and Outcomes Consortium.

J Gerontol A Biol Sci Med Sci 2021 Sep;76(10):e321-e327

University of Florida, Gainesville, USA.

Background: Cut-points to define slow walking speed have largely been derived from expert opinion.

Methods: Study participants (13 589 men and 5043 women aged ≥65years) had walking speed (m/s) measured over 4-6 m (mean ± SD: 1.20 ± 0.27 m/s in men and 0.94 ± 0.24 m/s in women.) Mobility limitation was defined as any self-reported difficulty with walking approximately 1/4 mile (prevalence: 12.6% men, 26.4% women). Sex-stratified classification and regression tree (CART) models with 10-fold cross-validation identified walking speed cut-points that optimally discriminated those who reported mobility limitation from those who did not.

Results: Among 5043 women, CART analysis identified 2 cut-points, classifying 4144 (82.2%) with walking speed ≥0.75 m/s, which we labeled as "fast"; 478 (9.5%) as "intermediate" (walking speed ≥0.62 m/s but <0.75 m/s); and 421 (8.3%) as "slow" (walking speed <0.62 m/s). Among 13 589 men, CART analysis identified 3 cut-points, classifying 10 001 (73.6%) with walking speed ≥1.00 m/s ("very fast"); 2901 (21.3%) as "fast" (walking speed ≥0.74 m/s but <1.00 m/s); 497 (3.7%) as "intermediate" (walking speed ≥0.57 m/s but <0.74 m/s); and 190 (1.4%) as "slow" (walking speed <0.57 m/s). Prevalence of self-reported mobility limitation was lowest in the "fast" or "very fast" (11% for men and 19% for women) and highest in the "slow" (60.5% in men and 71.0% in women). Rounding the 2 slower cut-points to 0.60 m/s and 0.75 m/s reclassified very few participants.

Conclusions: Cut-points in walking speed of approximately 0.60 m/s and 0.75 m/s discriminate those with self-reported mobility limitation from those without.
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http://dx.doi.org/10.1093/gerona/glab183DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8436986PMC
September 2021

Physical exercise is associated with beneficial bone mineral density and body composition in young adults with childhood-onset inflammatory bowel disease.

Scand J Gastroenterol 2021 Jun 4;56(6):699-707. Epub 2021 May 4.

Department of Pediatrics, Institute of Clinical Sciences, The Sahlgrenska Academy at University of Gothenburg and Queen Silvia's Children's Hospital, Gothenburg, Sweden.

Background: Patients with inflammatory bowel disease (IBD) have an increased risk of compromised bone mineral density (BMD) and body composition. There are limited data on the physical exercise (PE) habits of patients with childhood-onset IBD and on the associations between PE and BMD and body composition.

Patients And Methods: In total, 72 young adults with childhood-onset IBD and 1341 normative young adult controls answered questionnaires regarding PE [hours/week (h/w)] in the last 12 months. BMD and body composition were measured with dual x-ray absorptiometry (DXA) and presented as age- and gender-adjusted Z-scores for BMD, skeletal muscle index (SMI, the weight of lean mass in arms and legs/m), and percentage body fat (Fat %).

Results: A total of 41 (57%) patients with IBD engaged in PE during the previous 12 months, as compared to 913 (68%) of the controls ( = .053). Sedentary patients had significantly lower median BMD, SMI, and Fat % Z-scores than the controls with corresponding PE habits (all  < .05). In contrast, highly active (>4 h/week) patients had total body BMD, SMI, and Fat % in the same range as the controls with corresponding PE levels ( = .151,  = .992, and  = .189, respectively), albeit with lower BMDs in the spine ( = .007) and femoral neck ( = .015). Using multiple regression analyses, a diagnosis of childhood-onset IBD was independently associated with inferior BMD and body composition, regardless of the amount of PE.

Conclusion: Physical exercise is associated with beneficial bone mineral density and body composition in patients with IBD despite the negative effects of the disease.
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http://dx.doi.org/10.1080/00365521.2021.1913759DOI Listing
June 2021

Musculoskeletal Benefits from a Physical Activity Program in Primary School are Retained 4 Years after the Program is Terminated.

Calcif Tissue Int 2021 Oct 29;109(4):405-414. Epub 2021 Apr 29.

Clinical and Molecular Osteoporosis Research Unit, Department of Orthopedics, Skane University Hospital (SUS), 20502, Malmo, Sweden.

Daily school physical activity (PA) improves musculoskeletal traits. This study evaluates whether the benefits remain 4 years after the intervention. We followed 45 boys and 36 girls who had had 40 min PA/school day during the nine compulsory school years and 21 boys and 22 girls who had had 60 min PA/school week (reference), with measurements at baseline and 4 years after the program terminated. Bone mineral content (BMC; g) and bone mineral density (BMD; g/cm) were measured by dual-energy X-ray absorptiometry and knee flexion peak torque relative to total body weight (PTTBW) at a speed of 180 degrees/second with a computerized dynamometer. Group differences are presented as mean differences (adjusted for sex and duration of follow-up period) with 95% confidence intervals. The total gain bone mass [mean difference in spine BMC +32.0 g (14.6, 49.4) and in arms BMD of +0.06 g/cm (0.02, 0.09)] and gain in muscle strength [mean difference in PTTBW +12.1 (2.0, 22.2)] were greater in the intervention than in the control group. There are still 4 years after the intervention indications of benefits in both bone mass and muscle strength gain. Daily school PA may counteract low bone mass and inferior muscle strength in adult life. ClinicalTrials.gov.NCT000633828 retrospectively registered 2008-11-03.
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http://dx.doi.org/10.1007/s00223-021-00853-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8429376PMC
October 2021

Time trends in pediatric hand fracture incidence in Malmö, Sweden, 1950-2016.

J Orthop Surg Res 2021 Apr 9;16(1):245. Epub 2021 Apr 9.

Clinical and Molecular Osteoporosis Research Unit, Department of Clinical Sciences and Orthopedics, Lund University, Skåne University Hospital, SE-205 02, Malmö, Sweden.

Background: The hand is the second most fractured region in children. It is therefore important to update fracture epidemiology to be able to identify time trends for adequate health care planning. This study reports pediatric hand fracture incidence 2014-2016 and, using published data, also long-term time trends in 1950-2016.

Patients And Methods: The Swedish city of Malmö, with 328,494 inhabitants in 2016, has only one hospital. We used the hospital radiological archive, medical charts, and diagnosis registry to identify hand fractures in city residents < 16 years in 2014-2016. These data were compared to those from three published studies that evaluated periods in 1950-2006. Differences between two periods were calculated as both unadjusted and age- and sex-adjusted incident rate ratios (IRR) with 95% confidence intervals (95% CI). We used joinpoint regression to estimate time trends during the entire period and present annual percent changes (APC) with 95% CI.

Results: In 2014-2016 phalangeal fractures accounted for 71% of all hand fractures, metacarpal fractures for 24%, and carpal fractures for 5%. We identified 615 hand fractures (419 in boys and 196 in girls) during 181,617 person-years in 2014-2016, resulting in an unadjusted pediatric hand fracture incidence of 339/100,000 person-years (boys 452/100,000 person-years and girls 220/100,000 person-years). The age-adjusted incidence 2014-2016 was similar to 2005-2006, the most recently evaluated period (IRR in boys 0.9; 95% CI 0.8 to 1.01, and in girls 1.0; 95% CI 0.8 to 1.2). Looking at the entire period 1950-2016, we found that age-adjusted incidence increased in 1950-1979, in boys by APC + 3.8%; 95% CI 3.0 to 4.5 and in girls by + 3.9%; 95% CI 2.8 to 5.0, but decreased in 1979-2016, in boys by - 0.7%; 95% CI - 1.4 to - 0.003, and girls by - 1.3%; 95% CI - 2.4 to - 0.1.

Conclusions: Phalangeal fractures accounted for about three quarters of all hand fractures. The age-adjusted hand fracture incidence increased in both sexes in 1950-1979 and decreased in 1979-2016.

Level Of Evidence: III.
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http://dx.doi.org/10.1186/s13018-021-02380-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8034127PMC
April 2021

Sarcopenia Definitions as Predictors of Fracture Risk Independent of FRAX , Falls, and BMD in the Osteoporotic Fractures in Men (MrOS) Study: A Meta-Analysis.

J Bone Miner Res 2021 07 8;36(7):1235-1244. Epub 2021 Apr 8.

Centre for Metabolic Bone Diseases, University of Sheffield, Sheffield, UK.

Dual-energy X-ray absorptiometry (DXA)-derived appendicular lean mass/height (ALM/ht ) is the most commonly used estimate of muscle mass in the assessment of sarcopenia, but its predictive value for fracture is substantially attenuated by femoral neck (fn) bone mineral density (BMD). We investigated predictive value of 11 sarcopenia definitions for incident fracture, independent of fnBMD, fracture risk assessment tool (FRAX ) probability, and prior falls, using an extension of Poisson regression in US, Sweden, and Hong Kong Osteoporois Fractures in Men Study (MrOS) cohorts. Definitions tested were those of Baumgartner and Delmonico (ALM/ht only), Morley, the International Working Group on Sarcopenia, European Working Group on Sarcopenia in Older People (EWGSOP1 and 2), Asian Working Group on Sarcopenia, Foundation for the National Institutes of Health (FNIH) 1 and 2 (using ALM/body mass index [BMI], incorporating muscle strength and/or physical performance measures plus ALM/ht ), and Sarcopenia Definitions and Outcomes Consortium (gait speed and grip strength). Associations were adjusted for age and time since baseline and reported as hazard ratio (HR) for first incident fracture, here major osteoporotic fracture (MOF; clinical vertebral, hip, distal forearm, proximal humerus). Further analyses adjusted additionally for FRAX-MOF probability (n = 7531; calculated ± fnBMD), prior falls (y/n), or fnBMD T-score. Results were synthesized by meta-analysis. In 5660 men in USA, 2764 Sweden and 1987 Hong Kong (mean ages 73.5, 75.4, and 72.4 years, respectively), sarcopenia prevalence ranged from 0.5% to 35%. Sarcopenia status, by all definitions except those of FNIH, was associated with incident MOF (HR = 1.39 to 2.07). Associations were robust to adjustment for prior falls or FRAX probability (without fnBMD); adjustment for fnBMD T-score attenuated associations. EWGSOP2 severe sarcopenia (incorporating chair stand time, gait speed, and grip strength plus ALM) was most predictive, albeit at low prevalence, and appeared only modestly influenced by inclusion of fnBMD. In conclusion, the predictive value for fracture of sarcopenia definitions based on ALM is reduced by adjustment for fnBMD but strengthened by additional inclusion of physical performance measures. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
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http://dx.doi.org/10.1002/jbmr.4293DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7611727PMC
July 2021

Childhood Distal Forearm Fracture Incidence in Malmö, Sweden 1950 to 2016.

J Wrist Surg 2021 Apr 4;10(2):129-135. Epub 2020 Dec 4.

Clinical and Molecular Osteoporosis Research Unit, Department of Clinical Sciences and Orthopedics, Lund University, Skåne University Hospital, Malmö, Sweden.

 Distal forearm fracture is the most common pediatric fracture. As studies have indicated time trends in fracture incidence, we wanted to update the epidemiology and estimate time trends between 1950 and 2016 in Malmö, Sweden.  The city of Malmö, Sweden, had 318,107 inhabitants (58,585 of the population was aged <16 years) in 2014 and one hospital. We, therefore, used the hospital diagnosis registry and hospital medical records to identify and classify distal forearm fractures 2014 to 2016 in children aged 0 to 15 years. For long-term trend calculations, we also included published data from 1950 to 2006 (resulting in 17 evaluated years) and used joinpoint regression to estimate annual percent changes (APC). To describe differences in incidence between two periods, we calculated incident rate ratios (IRR) with 95% confidence intervals (95% CI) to describe uncertainty.  Childhood distal forearm fracture incidence in 2014 to 2016 was 546/100,000 person-years (660 in boys and 427 in girls). The age-adjusted incidence in 2014 to 2016 and in 2005 to 2006 was similar (boys IRR 1.0, 95% CI: 0.9-1.2 and girls IRR 1.1, 95% CI: 0.9-1.3). Time-trend analyses from 1950 to 2016 revealed increasing age-adjusted incidence in both boys (APC +0.9%, 95% CI: 0.7-1.2) and girls (APC +0.6%, 95% CI: 0.3-0.9).  Distal forearm fracture incidence was similar in 2014 to 2016 and in 2005 to 2006. Age-adjusted incidence had increased in both sexes from 1950 to 2016.  This is a Level III b study.
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http://dx.doi.org/10.1055/s-0040-1720965DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8012093PMC
April 2021

Fungal -Intrinsic Protein Aquaporin from : Structural and Functional Considerations.

Biomolecules 2021 02 23;11(2). Epub 2021 Feb 23.

Université Clermont Auvergne, INRAE, PIAF, 63000 Clermont-Ferrand, France.

The major intrinsic protein (MIP) superfamily is a key part of the fungal transmembrane transport network. It facilitates the transport of water and low molecular weight solutes across biomembranes. The fungal uncharacterized X-Intrinsic Protein (XIP) subfamily includes the full protein diversity of MIP. Their biological functions still remain fully hypothetical. The aim of this study is still to deepen the diversity and the structure of the XIP subfamily in light of the MIP counterparts-the aquaporins (AQPs) and aquaglyceroporins (AQGPs)-and to describe for the first time their function in the development, biomass accumulation, and mycoparasitic aptitudes of the fungal bioagent . The fungus-XIP clade, with one member (XIP), is one of the three clades of MIPs that make up the diversity of MIPs, along with the AQPs (three members) and the AQGPs (three members). XIP resembles those of strict aquaporins, predicting water diffusion and possibly other small polar solutes due to particularly wider ar/R constriction with a Lysine substitution at the LE2 position. The XIP loss of function in ∆XIP mutants slightly delays biomass accumulation but does not impact mycoparasitic activities. ∆MIP forms colonies similar to wild type; however, the hyphae are slightly thinner and colonies produce rare chlamydospores in PDA and specific media, most of which are relatively small and exhibit abnormal morphologies. To better understand the molecular causes of these deviant phenotypes, a wide-metabolic survey of the ∆XIPs demonstrates that the delayed growth kinetic, correlated to a decrease in respiration rate, is caused by perturbations in the pentose phosphate pathway. Furthermore, the null expression of the gene strongly impacts the expression of four expressed -encoding genes of , a plausible compensating effect which safeguards the physiological integrity and life cycle of the fungus. This paper offers an overview of the fungal XIP family in the biocontrol agent which will be useful for further functional analysis of this particular MIP subfamily in vegetative growth and the environmental stress response in fungi. Ultimately, these findings have implications for the ecophysiology of spp. in natural, agronomic, and industrial systems.
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http://dx.doi.org/10.3390/biom11020338DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7927018PMC
February 2021

Comparative genomics highlights the importance of drug efflux transporters during evolution of mycoparasitism in subgenus (Fungi, Ascomycota, Hypocreales).

Evol Appl 2021 Feb 28;14(2):476-497. Epub 2020 Sep 28.

Department of Forest Mycology and Plant Pathology Swedish University of Agricultural Sciences Uppsala Sweden.

Various strains of the mycoparasitic fungal species are used commercially as biological control agents for the control of fungal plant diseases in agricultural crop production. Further improvements of the use and efficacy of in biocontrol require a mechanistic understanding of the factors that determines the outcome of the interaction between and plant pathogenic fungi. Here, we determined the genome sequences of 11 strains, representing five species in subgenus , and performed a comparative genomic analysis with the aim to identify gene families evolving under selection for gene gains or losses. Several gene families predicted to encode proteins involved in biosynthesis of secondary metabolites, including polyketide synthases, nonribosomal peptide syntethases and cytochrome P450s, evolved under selection for gene gains ( ≤ .05) in the subgenus lineage. This was accompanied with gene copy number increases ( ≤ .05) in ATP-binding cassette (ABC) transporters and major facilitator superfamily (MFS) transporters predicted to contribute to drug efflux. Most species were also characterized by high numbers of auxiliary activity (AA) family 9 lytic polysaccharide monooxygenases, AA3 glucose-methanol-choline oxidoreductases and additional carbohydrate-active enzyme gene families with putative activity (or binding) towards xylan and rhamnose/pectin substrates. Particular features of the genome included expansions ( ≤ .05) of the ABC-B4 multidrug resistance transporters, the ABC-C5 multidrug resistance-related transporters and the 2.A.1.3 drug:H + antiporter-2 MFS drug resistance transporters. The ABC-G1 pleiotropic drug resistance transporter gene in was induced ( ≤ .009) by exposure to the antifungal mycotoxin zearalenone (1121-fold) and various fungicides. Deletion of resulted in mutants with reduced ( < .001) growth rates on media containing the fungicides boscalid, fenhexamid and iprodione. Our results emphasize the role of biosynthesis of, and protection against, secondary metabolites in subgenus .
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http://dx.doi.org/10.1111/eva.13134DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7896725PMC
February 2021

Liposuction of Breast Cancer-Related Arm Lymphedema Reduces Fat and Muscle Hypertrophy.

Lymphat Res Biol 2021 Mar 2. Epub 2021 Mar 2.

Department of Clinical Sciences, Lund University, Malmö, Sweden.

Adipose tissue deposition is a known consequence of lymphedema. A previous study showed that the affected arm in patients with nonpitting breast cancer-related lymphedema (BCRL) had a mean excess volume of 73% fat and 47% muscle. This condition impairs combined physiotherapy as well as more advanced microsurgical methods. Liposuction is, therefore, a way of improving the effects of treatment. This study aims to evaluate the tissue changes in lymphedematous arms after liposuction and controlled compression therapy (CCT) in patients with nonpitting BCRL. Eighteen women with an age of 61 years and a duration of arm lymphedema (BCRL) of 9 years were treated with liposuction and CCT. Tissue composition of fat, lean (muscle), and bone mineral was analyzed through dual energy X-ray absorptiometry (DXA) before, and at 3 and 12 months after surgery. Excess volumes were also measured with plethysmography. The median DXA preoperative excess volume was 1425 mL (704 mL fat volume, 651 mL lean volume). The DXA excess volume at 3 months after surgery was 193 mL (-196 mL fat volume, 362 mL lean volume). At 12 months after surgery, the median excess DXA volume was 2 mL (-269 mL fat volume, 338 mL lean volume). From before surgery to 3 months after surgery, the median DXA excess volume reduced by 85% ( < 0.001) (fat volume reduction 128% ( < 0.001), lean volume reduction 37% ( = 0.016)). From before surgery to 12 months after surgery, it reduced by 100% ( < 0.001) (fat volume reduction 139% [ < 0.001], lean volume reduction 54% [ = 0.0013]). Liposuction and CCT effectively remove the excess fat in patients with nonpitting BCRL, and a total reduction of excess arm volume is achievable. A postoperative decrease in excess muscle volume is also seen, probably due to the reduced weight of the arm postoperatively.
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http://dx.doi.org/10.1089/lrb.2020.0120DOI Listing
March 2021

, bentonite, and kaolin as adsorbents for reducing the adverse impacts of mycotoxin contaminated feed on broiler histopathology and hemato-biochemical changes.

Vet World 2021 Jan 5;14(1):23-32. Epub 2021 Jan 5.

Department of Forest Mycology and Plant Pathology, Swedish University of Agricultural Sciences, SLU, Box 7026, SE-75007 Uppsala, Sweden.

Background And Aim: , bentonite and kaolin were used to reduce the adverse effects of mold-contaminated diet on broilers. The aim of the study was to evaluate the impact of , bentonite, and kaolin in reducing the adverse effects of mold (fungal) contaminated diet on broilers. Specifically, we investigated the histopathological, hematological, and serum biochemical changes associated with broilers fed mold-contaminated diets supplemented with these three adsorbents. We also isolated and identified the common fungal contaminants in the poultry feeds as well as the mycotoxins they produced.

Materials And Methods: Hundred broilers (3-weeks-old) were randomly grouped into five dietary treatments, basal feed (negative control), feed contaminated with mold, mold-contaminated feed+, mold-contaminated feed+bentonite, and mold-contaminated feed+kaolin. The fungal contaminants in the feeds were isolated and molecularly identified while the mycotoxins in the feed where analyzed using high-performance liquid chromatography. Blood samples of birds from each group were analyzed for hematology and serum biochemistry. The liver, spleen, kidney, and bursa of Fabricius of the birds were excised and analyzed for histopathological changes.

Results: The most common fungal contaminants in the feeds were (33.3%) species, followed by species (22.2%). The mold-contaminated feed had the highest number of fungal contaminants, 55.6%, while the negative control (basal feed group) had none. Total aflatoxin and deoxynivalenol were high in the mold-contaminated feed (53.272 μg/kg and 634.5 μg kg, respectively), but these were reduced by the addition of adsorbents to the feed. The birds fed mold-contaminated feed had significantly (p<0.05) reduced red blood cell count counts, packed cell volume, and hemoglobin but increased white blood cell count compared to the negative control. Liver enzyme activity (alanine transaminase, aspartate aminotransferase, and alkaline phosphatase) and cholesterol concentration increased significantly (p<0.05) in the group fed mold-contaminated feed while the serum albumin and total protein decreased significantly (p0.05) in comparison with the negative control. Adverse histopathological changes were observed in the liver, kidney, spleen, and bursa of Fabricius in the group fed mold-contaminated feed. Addition of , bentonite or kaolin in the mold-contaminated feed ameliorated these toxic effects.

Conclusion: The observed histopathological lesions were consistent with mycotoxicosis in birds and were mild in the adsorbent treated groups. Kaolin had a higher protective effect against mycotoxicosis than the two other adsorbents.
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http://dx.doi.org/10.14202/vetworld.2021.23-32DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7896915PMC
January 2021

Improved prediction of fracture risk leveraging a genome-wide polygenic risk score.

Genome Med 2021 02 3;13(1):16. Epub 2021 Feb 3.

Centre for Clinical Epidemiology, Lady Davis Institute for Medical Research, Jewish General Hospital, Room H-413, 3755 Chemin de la Côte-Sainte-Catherine, Montreal, Quebec, H3T 1E2, Canada.

Background: Accurately quantifying the risk of osteoporotic fracture is important for directing appropriate clinical interventions. While skeletal measures such as heel quantitative speed of sound (SOS) and dual-energy X-ray absorptiometry bone mineral density are able to predict the risk of osteoporotic fracture, the utility of such measurements is subject to the availability of equipment and human resources. Using data from 341,449 individuals of white British ancestry, we previously developed a genome-wide polygenic risk score (PRS), called gSOS, that captured 25.0% of the total variance in SOS. Here, we test whether gSOS can improve fracture risk prediction.

Methods: We examined the predictive power of gSOS in five genome-wide genotyped cohorts, including 90,172 individuals of European ancestry and 25,034 individuals of Asian ancestry. We calculated gSOS for each individual and tested for the association between gSOS and incident major osteoporotic fracture and hip fracture. We tested whether adding gSOS to the risk prediction models had added value over models using other commonly used clinical risk factors.

Results: A standard deviation decrease in gSOS was associated with an increased odds of incident major osteoporotic fracture in populations of European ancestry, with odds ratios ranging from 1.35 to 1.46 in four cohorts. It was also associated with a 1.26-fold (95% confidence interval (CI) 1.13-1.41) increased odds of incident major osteoporotic fracture in the Asian population. We demonstrated that gSOS was more predictive of incident major osteoporotic fracture (area under the receiver operating characteristic curve (AUROC) = 0.734; 95% CI 0.727-0.740) and incident hip fracture (AUROC = 0.798; 95% CI 0.791-0.805) than most traditional clinical risk factors, including prior fracture, use of corticosteroids, rheumatoid arthritis, and smoking. We also showed that adding gSOS to the Fracture Risk Assessment Tool (FRAX) could refine the risk prediction with a positive net reclassification index ranging from 0.024 to 0.072.

Conclusions: We generated and validated a PRS for SOS which was associated with the risk of fracture. This score was more strongly associated with the risk of fracture than many clinical risk factors and provided an improvement in risk prediction. gSOS should be explored as a tool to improve risk stratification to identify individuals at high risk of fracture.
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http://dx.doi.org/10.1186/s13073-021-00838-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7860212PMC
February 2021

Genome-wide meta-analysis of muscle weakness identifies 15 susceptibility loci in older men and women.

Nat Commun 2021 01 28;12(1):654. Epub 2021 Jan 28.

Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.

Low muscle strength is an important heritable indicator of poor health linked to morbidity and mortality in older people. In a genome-wide association study meta-analysis of 256,523 Europeans aged 60 years and over from 22 cohorts we identify 15 loci associated with muscle weakness (European Working Group on Sarcopenia in Older People definition: n = 48,596 cases, 18.9% of total), including 12 loci not implicated in previous analyses of continuous measures of grip strength. Loci include genes reportedly involved in autoimmune disease (HLA-DQA1 p = 4 × 10), arthritis (GDF5 p = 4 × 10), cell cycle control and cancer protection, regulation of transcription, and others involved in the development and maintenance of the musculoskeletal system. Using Mendelian randomization we report possible overlapping causal pathways, including diabetes susceptibility, haematological parameters, and the immune system. We conclude that muscle weakness in older adults has distinct mechanisms from continuous strength, including several pathways considered to be hallmarks of ageing.
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http://dx.doi.org/10.1038/s41467-021-20918-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7844411PMC
January 2021

Fungal cross-talk: an integrated approach to study distance communication.

Fungal Genet Biol 2021 03 23;148:103518. Epub 2021 Jan 23.

Department of Agriculture, Food and Environment, University of Pisa, Pisa, Italy.

Despite the interest on fungi as eukaryotic model systems, the molecular mechanisms regulating the fungal non-self-recognition at a distance have not been studied so far. This paper investigates the molecular mechanisms regulating the cross-talk at a distance between two filamentous fungi, Trichoderma gamsii and Fusarium graminearum which establish a mycoparasitic interaction where T. gamsii and F. graminearum play the roles of mycoparasite and prey, respectively. In the present work, we use an integrated approach involving dual culture tests, comparative genomics and transcriptomics to investigate the fungal interaction before contact ('sensing phase'). Dual culture tests demonstrate that growth rate of F. graminearum accelerates in presence of T. gamsii at the sensing phase. T. gamsii up-regulates the expression of a ferric reductase involved in iron acquisition, while F. graminearum up-regulates the expression of genes coding for transmembrane transporters and killer toxins. At the same time, T. gamsii decreases the level of extracellular interaction by down-regulating genes coding for hydrolytic enzymes acting on fungal cell wall (chitinases). Given the importance of fungi as eukaryotic model systems and the ever-increasing genomic resources available, the integrated approach hereby presented can be applied to other interactions to deepen the knowledge on fungal communication at a distance.
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http://dx.doi.org/10.1016/j.fgb.2021.103518DOI Listing
March 2021

Association between circulating furin levels, obesity and pro-inflammatory markers in children.

Acta Paediatr 2021 06 5;110(6):1863-1868. Epub 2021 Feb 5.

Clinical and Molecular Osteoporosis Research Unit, Departments of Orthopaedics and Clinical Sciences, Skåne University Hospital, Lund University, Malmö, Sweden.

Aim: To, in children, investigate the associations between serum furin, obesity, overweight, body fat and circulating markers reflecting adipose tissue or systemic inflammation.

Methods: We analysed furin, leptin, adipocyte fatty acid-binding protein, triglycerides, interleukin (IL)-6, IL-8 and C-reactive protein in serum from 166 children in the Pediatric Osteoporosis Prevention (POP) study collected at mean age (SD) 9.9 (0.6) years. Children were classified as low-to-normal weight, overweight or obese. Total body fat mass (kg), trunk fat mass (kg) and total body lean mass (kg) were measured by dual-energy X-ray absorptiometry. Body fat percentage (%) was calculated.

Results: We found that circulating furin levels were higher in children with obesity and overweight compared with children with low-to-normal weight (p < 0.001 and p = 0.006, respectively). Also, there were positive correlations between circulating furin, total body fat mass, trunk fat mass, body fat percentage, triglycerides, adipokines and pro-inflammatory markers.

Conclusion: This study indicates associations between furin, adiposity and a pro-inflammatory milieu in children. We suggest that future studies investigate the role of furin in fat tissue inflammation and associated increased risk of cardiometabolic diseases in children. Studies should also investigate whether higher furin levels could be a link between obesity and severe coronavirus disease 2019 in children.
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http://dx.doi.org/10.1111/apa.15774DOI Listing
June 2021

Predictors of radiographic erosion and joint space narrowing progression in patients with early rheumatoid arthritis: a cohort study.

Arthritis Res Ther 2021 01 14;23(1):27. Epub 2021 Jan 14.

Rheumatology, Department of Clinical Sciences Malmö, Lund University, Jan Waldenströms gata 1B, SE-205 02, Malmö, Sweden.

Background: Radiographic damage in rheumatoid arthritis (RA) includes erosions and joint space narrowing (JSN). Different mechanisms may underlie their development. The objective of this study was to evaluate predictors of these entities separately.

Methods: Consecutive early RA patients (symptom duration ≤12 months) from a defined area (Malmö, Sweden) recruited during 1995-2005 were investigated. Radiographs of hands and feet were scored by a trained reader according to the modified Sharp-van der Heijde score. Fat mass and lean mass distribution were measured at baseline using dual energy x-ray absorptiometry. Potential predictors of erosion and JSN progression from inclusion to the 5-year follow-up were evaluated.

Results: Two hundred and thirty-three patients were included. Radiographs at baseline and 5 years were available for 162 patients. The median (interquartile) progression of erosion and JSN scores were 4 (0-8) and 8 (1-16), respectively. Rheumatoid factor (RF) was a robust significant predictor of both erosion and JSN score progression. In adjusted analyses, anti-CCP antibodies predicted erosions while the erythrocyte sedimentation rate was predictive of both outcomes. Smoking and high baseline disease activity (DAS28 > 5.1) predicted progression of erosions. Baseline erosion score was associated with progression of both erosion and JSN progression, while baseline JSN score was predictive only of the progression of JSN. Overweight/obesity (BMI ≥ 25 kg/m) was a significant negative predictor of JSN score progression (β = - 0.14, p = 0.018, adjusted for RF, age, baseline JSN score) also when additionally adjusting for ever smoking (p = 0.041). Among female patients, this effect was observed in those of estimated post-menopausal age (> 51 years), but not in younger women. The truncal to peripheral fat ratio was associated with less JSN score progression in women, but not in men.

Conclusions: Overweight RA patients had less JSN progression, independent of smoking status. This effect was seen in particular among older women (mainly post-menopausal), but not younger. Truncal fat was associated with less JSN progression in female patients. Smoking predicted erosion progression, and erosions may precede JSN. BMI and fat distribution may influence cartilage damage in early RA and might be related to hormonal factors.
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http://dx.doi.org/10.1186/s13075-020-02413-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7809738PMC
January 2021

Association Between Bone Mineral Density and Autoantibodies in Patients With Rheumatoid Arthritis.

Arthritis Rheumatol 2021 06 10;73(6):921-930. Epub 2021 May 10.

Leiden University Medical Center, Leiden, The Netherlands.

Objective: Autoantibodies, such as anti-citrullinated protein antibodies (ACPAs), have been described as inducing bone loss in rheumatoid arthritis (RA), which can also be reflected by bone mineral density (BMD). We therefore examined the association between osteoporosis and autoantibodies in two independent RA cohorts.

Methods: Dual x-ray absorptiometry (DXA) of the lumbar spine and left hip was performed in 408 Dutch patients with early RA during 5 years of follow-up and in 198 Swedish patients with early RA during 10 years of follow-up. The longitudinal effect of ACPAs and other autoantibodies on several BMD measures was assessed using generalized estimating equations.

Results: In the Dutch cohort, significantly lower BMD at baseline was observed in ACPA-positive patients compared to ACPA-negative patients, with an estimated marginal mean BMD in the left hip of 0.92 g/cm (95% confidence interval [95% CI] 0.91-0.93) versus 0.95 g/cm (95% CI 0.93-0.97) (P = 0.01). In line with this, significantly lower Z scores at baseline were noted in the ACPA-positive group compared to the ACPA-negative group (estimated marginal mean Z score in the left hip of 0.18 [95% CI 0.08-0.29] versus 0.48 [95% CI 0.33-0.63]) (P < 0.01). However, despite clear differences at baseline, ACPA positivity was not associated with greater decrease in absolute BMD or Z scores over time. Furthermore, there was no association between BMD and higher levels of ACPAs or other autoantibodies (rheumatoid factor and anti-carbamylated protein antibodies). In the Swedish cohort, ACPA-positive patients tended to have a higher prevalence of osteopenia at baseline (P = 0.04), but again, ACPA positivity was not associated with an increased prevalence of osteopenia or osteoporosis over time.

Conclusion: The presence of ACPAs is associated with significantly lower BMD at baseline, but not with greater BMD loss over time in treated RA patients. These results suggest that ACPAs alone do not appear to contribute to bone loss after disease onset when disease activity is well-managed.
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http://dx.doi.org/10.1002/art.41623DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8251600PMC
June 2021

Lung function is associated with tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) levels in school-aged children.

Respir Med 2021 01 24;176:106235. Epub 2020 Nov 24.

Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden; Department of Translational Medicine, Clinical Physiology and Nuclear Medicine, Skåne University Hospital (SUS), Malmö, Sweden. Electronic address:

Background: Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) is a cytokine with inflammatory and apoptotic properties. A complex relationship exists between TRAIL and the lung where both elevated TRAIL and TRAIL deficiency are associated with lung impairment. In neonatal mice, TRAIL is thought to translate respiratory infections into chronic lung disease but the association between TRAIL and lung function in childhood has not been assessed.

Aim: To assess the cross-sectional relationship between TRAIL levels and lung function in school-aged children.

Methods: The study cohort consisted of 170 school-aged children attending four schools in Malmö, Sweden. Lung volumes, impulse oscillometry (IOS) and serum TRAIL were measured for all children. Linear regression was used to assess changes in lung function per 1-SD increase in TRAIL. General linear models were used to assess mean lung function by tertiles (T) of TRAIL.

Results: Mean age was 9.9 years (±0.6). A 1-SD increase in TRAIL was associated with lower values of FEV and FEV/VC (change in FEV (L) and FEV/VC ratio: -0.047, p-value 0.002, and -0.011, p-value 0.020, respectively) and higher values of lung resistance (change in R and R (kPa/(L/s)): 0.035, p-value <0.001 and 0.027, p-value 0.004, respectively). These associations remained significant after excluding children with pre-existing lung disease. Higher TRAIL levels were associated with more negative values for X in general linear models (Mean X (kPa/(L/s)) in T1 (low TRAIL): -0.193 vs T3 (high TRAIL): -0.216, p-value 0.026).

Conclusions: High TRAIL levels are significantly associated with markers of pulmonary airflow obstruction in school-aged children.
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http://dx.doi.org/10.1016/j.rmed.2020.106235DOI Listing
January 2021

Endoplasmic reticulum stress in human chronic wound healing: Rescue by 4-phenylbutyrate.

Int Wound J 2021 Feb 22;18(1):49-61. Epub 2020 Nov 22.

Dermatology and Venereology Division, Department of Medicine (Solna), Karolinska Institutet, Stockholm, Sweden.

During wound healing, cells have a high rate of protein synthesis and many proteins need to be folded post-translationally to function, which occurs in the endoplasmic reticulum (ER). In addition to proliferation, several cellular stress conditions, such as hypoxia, in the wound micro-environment lead to the accumulation of unfolded or misfolded proteins in the ER, causing ER stress. Eukaryotic cells have a signalling system to manage ER stress called the unfolded protein response (UPR). Mild UPR activation has a beneficial homeostatic effect; however, excessive UPR induces cell death. Herein, we examined venous leg ulcer biopsies versus normal acute incisional wounds in age-matched elderly subjects and found a large increase in ER stress markers. To study the underlying mechanism, we established several cell cultures from amputated legs from the elderly that showed inherent ER stress. While both keratinocytes and fibroblasts migration was impaired by ER stress, migration of elderly leg skin keratinocytes was markedly improved after treatment with the chemical chaperone and clinically established drug 4-phenylbutyrate (4-PBA) and demonstrated a reduction in ER stress markers. In a full-thickness human skin wound healing model, 4-PBA improved the reepithelialisation rate, which suggests it as a promising drug repurposing candidate for wound healing.
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http://dx.doi.org/10.1111/iwj.13525DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7949014PMC
February 2021

Modulation format dependence on transmission reach in phase-sensitively amplified fiber links.

Opt Express 2020 Nov;28(23):34623-34638

We quantify the maximum transmission reach for phase-insensitive amplifier (PIA) and phase-sensitive amplifier (PSA) links with different modulation formats and show that the maximum transmission reach increase (MTRI) when using PSAs compared to PIAs is enhanced for higher-order modulation formats. The higher-order modulation formats are more susceptible to smaller phase rotations from nonlinearities, and PSAs are efficient in mitigating these smaller phase distortions. Numerical simulations were performed for single- and multi-span PIA and PSA links with single and multiple wavelength channels. We obtain a significant enhancement in the MTRI with PSAs compared to PIAs when using higher-order modulation formats for both the single- and multi-channel systems in single- and multi-span links. We verify the enhancement with a single-span, single-channel system experiment. We also demonstrate, for the first time, a 64-QAM modulation format fiber transmission in phase-sensitively amplified link, with a 13.3-dB maximum allowable span loss increase compared to a phase-insensitively amplified link.
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http://dx.doi.org/10.1364/OE.403475DOI Listing
November 2020

Functional characterization of the AGL1 aegerolysin in the mycoparasitic fungus Trichoderma atroviride reveals a role in conidiation and antagonism.

Mol Genet Genomics 2021 Jan 14;296(1):131-140. Epub 2020 Oct 14.

Department of Forest Mycology and Plant Pathology, Uppsala Biocenter, Swedish University of Agricultural Sciences, P.O. Box 7026, 75007, Uppsala, Sweden.

Aegerolysins are small secreted pore-forming proteins that are found in both prokaryotes and eukaryotes. The role of aegerolysins in sporulation, fruit body formation, and in lysis of cellular membrane is suggested in fungi. The aim of the present study was to characterize the biological function of the aegerolysin gene agl1 in the mycoparasitic fungus Trichoderma atroviride, used for biological control of plant diseases. Gene expression analysis showed higher expression of agl1 during conidiation and during growth in medium supplemented with cell wall material from the plant pathogenic fungus Rhizoctonia solani as the sole carbon source. Expression of agl1 was supressed under iron-limiting condition, while agl1 transcript was not detected during T. atroviride interactions with the prey fungi Botrytis cinerea or R. solani. Phenotypic analysis of agl1 deletion strains (Δagl1) showed reduced conidiation compared to T. atroviride wild type, thus suggesting the involvement of AGL1 in conidiation. Furthermore, the Δagl1 strains display reduced antagonism towards B. cinerea and R. solani based on a secretion assay, although no difference was detected during direct interactions. These data demonstrate the role of AGL1 in conidiation and antagonism in the mycoparasitic fungus T. atroviride.
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http://dx.doi.org/10.1007/s00438-020-01732-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7840653PMC
January 2021
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