Hyperpolarized Water for Coronary Artery Angiography and Whole-Heart Myocardial Perfusion Quantification.

Purpose: Water freely diffuses across cell membranes, making it suitable for measuring absolute tissue perfusion. In this study, we introduce an imaging method for conducting coronary artery angiography and quantifying myocardial perfusion across the entire heart using hyperpolarized water. Methods:1H was hyperpolarized using dissolution dynamic nuclear polarization (dDNP) with UV-generated radicals. Submillimeter resolution coronary artery images were acquired as 2D projections using a spoiled GRE (SPGRE) sequence gated on diastole. Dynamic perfusion images were obtained with a multi-slice SPGRE with diastole gating, covering the entire heart. Perfusion values were analyzed through histograms, and the most frequent estimated perfusion value (the mode of the distribution), was compared with the average values for 15O water PET from the literature. Results: A liquid state polarization of 10% at the time of the injection and a 30 s T1 in D2O TRIS buffer were measured. Both coronary artery and dynamic perfusion images exhibited good quality. The main and small coronary artery branches were well resolved. The most frequent estimated perfusion value is around 0.6 mL/g/min, which is lower than the average values obtained from the literature for 15O-water PET (around 1.1 and 1.5 mL/g/min). Conclusions: The study successfully demonstrated the feasibility of achieving high-resolution, motion-free coronary artery angiography and 3D whole-heart quantitative myocardial perfusion using hyperpolarized water.

iPREDICT: Characterization of Asthma Triggers and Selection of Digital Technology to Predict Changes in Disease Control.

Purpose: The iPREDICT program aimed to develop an integrated digital health solution capable of continuous data streaming, predicting changes in asthma control, and enabling early intervention. Patients and Methods: As part of the iPREDICT program, asthma triggers were characterized by surveying 221 patients (aged ≥18 years) with self-reported asthma for a risk-benefit analysis of parameters predictive of changes in disease control. Seventeen healthy volunteers (age 25-65 years) tested 13 devices to measure these parameters and assessed their usability attributes. Results: Patients identified irritants such as chemicals, allergens, weather changes, and physical activity as triggers that were the most relevant to deteriorating asthma control. Device testing in healthy volunteers revealed variable data formats/units and quality issues, such as missing data and low signal-to-noise ratio. Based on user preference and data capture validity, a spirometer, vital sign monitor, and sleep monitor formed the iPREDICT integrated system for continuous data streaming to develop a personalized/predictive algorithm for asthma control. Conclusion: These findings emphasize the need to systematically compare devices based on several parameters, including usability and data quality, to develop integrated digital technology programs for asthma care.

Risk and predictors of fractures in early rheumatoid arthritis - A long term follow up study of an inception cohort.

OBJECTIVES: To examine the risk of fractures in a cohort of patients with newly diagnosed rheumatoid arthritis (RA), compared to the background population, and predictors of fractures detectable early in RA. METHODS: An inception cohort of patients with RA (N = 233; 164 women/69 men, recruited 1995-2005) was evaluated according to a structured program, including repeated clinical assessments and measures of bone mineral density (BMD), from diagnosis to 10 years later. Matched population controls were identified using the national census register. Fractures through 2019 were identified based on ICD codes. Cox regression models were used to assess the risk of fractures in RA patients compared with controls, and for assessment of potential predictors for fractures in the RA population. RESULTS: RA patients had an increased risk of fractures (fully adjusted hazard ratio (HR) 1.52, 95 % CI 1.13; 2.06). In the RA cohort, high age, low body mass index, and low BMD were significant baseline predictors of future fractures in multivariate analyses, but baseline RA disease characteristics were not. Worse disability (i.e. higher Health Assessment Questionnaire (HAQ) scores) over time was significantly associated with increased risk of fractures (age-sex-adjusted HR 1.33 per SD, 95 % CI 1.09; 1.63) and there was an inverse association between BMD Z-scores over time and fractures. CONCLUSION: Patients with RA had higher risk of fractures than controls. Fracture risk was related to BMD at baseline and over time in patients with RA. In addition, worse disability (measured by HAQ) over time was associated with higher risk of fractures.

Time trends in proximal humeral fractures from 1944 to 2020 - A cohort study in Malmö, Sweden.

BACKGROUND: Most studies infer increasing incidence of proximal humeral fractures (PHF) from the 1950´s until the 1990´s. Recent time trends are less clear. OBJECTIVES: Our primary objective was to identify time trends in the age- and sex-adjusted adult incidence of PHF in Malmö, Sweden, from year 1944 until 2020. Our secondary objectives were to describe the variation in incidence according to age, the monthly distribution, and to compare data from the two most recent decades with earlier. STUDY DESIGN AND METHODS: Malmö has one emergency hospital where acute fractures are treated. We identified PHF in adult patients (≥ 18 years) by reviewing relevant radiology examinations during 17 sample years from year 1944 to 2020. We used jointpoint analyses to estimate time trends. RESULTS: We identified 3 031 PHF during the study period (3 231 161 person years), 73% were sustained by women with mean age of 69 years (mean age in men 59). Joinpoint analyses indicated an increase in the age- and sex-adjusted incidence of PHF from year 1944 (52 per 100 000 person years) until 1977 (120 per 100 000) and thereafter a decrease until 2020 (85 per 100 000). A seasonal variation with more fractures during winter months, was apparent in earlier but not recent decades. CONCLUSIONS: The age- and sex-adjusted incidence of PHF increased in Malmö, Sweden, from the 1940´s until year 1977 and thereafter decreased until 2020. More fractures were seen during winter months in earlier but not recent decades.

Predictive value of sarcopenia components for all-cause mortality: findings from population-based cohorts.

BACKGROUND: Low grip strength and gait speed are associated with mortality. However, investigation of the additional mortality risk explained by these measures, over and above other factors, is limited. AIM: We examined whether grip strength and gait speed improve discriminative capacity for mortality over and above more readily obtainable clinical risk factors. METHODS: Participants from the Health, Aging and Body Composition Study, Osteoporotic Fractures in Men Study, and the Hertfordshire Cohort Study were analysed. Appendicular lean mass (ALM) was ascertained using DXA; muscle strength by grip dynamometry; and usual gait speed over 2.4-6 m. Verified deaths were recorded. Associations between sarcopenia components and mortality were examined using Cox regression with cohort as a random effect; discriminative capacity was assessed using Harrell's Concordance Index (C-index). RESULTS: Mean (SD) age of participants (n = 8362) was 73.8(5.1) years; 5231(62.6%) died during a median follow-up time of 13.3 years. Grip strength (hazard ratio (95% CI) per SD decrease: 1.14 (1.10,1.19)) and gait speed (1.21 (1.17,1.26)), but not ALM index (1.01 (0.95,1.06)), were associated with mortality in mutually-adjusted models after accounting for age, sex, BMI, smoking status, alcohol consumption, physical activity, ethnicity, education, history of fractures and falls, femoral neck bone mineral density (BMD), self-rated health, cognitive function and number of comorbidities. However, a model containing only age and sex as exposures gave a C-index (95% CI) of 0.65(0.64,0.66), which only increased to 0.67(0.67,0.68) after inclusion of grip strength and gait speed. CONCLUSIONS: Grip strength and gait speed may generate only modest adjunctive risk information for mortality compared with other more readily obtainable risk factors.

Higher serum free thyroxine levels are associated with increased risk of hip fractures in older men.

Overt and subclinical hyperthyroidism are associated with an increased fracture risk, but whether thyroid hormones are associated with fracture risk in individuals with normal thyroid-stimulating hormone (TSH) has mostly been investigated in women. Therefore, we investigated if serum levels of free thyroxine (FT4) or TSH are associated with fracture risk in Swedish men. We followed (median 12.2 yr) elderly men (n = 1825; mean age 75, range 69-81 yr) participating in the Gothenburg and Malmö subcohorts of the prospective, population-based MrOS-Sweden study. The statistical analyses included Cox proportional hazards regression. Men receiving levothyroxine treatment were excluded. In our total cohort, serum FT4 (per SD increase) was associated with increased risk of major osteoporotic fractures (MOFs; n = 479; fully adjusted hazard ratio [HR] 1.14, 95% CI, 1.05-1.24) and hip fractures (n = 207; HR 1.18, 95% CI, 1.04-1.33). Also, in men with normal TSH (n = 1658), FT4 (per SD increase) was significantly associated with increased risk of MOF and hip fractures. Furthermore, men in the highest FT4 quartile had a 1.5-fold increase in hip fracture risk compared with men in the three lower FT4 quartiles, both in the total population and in men with normal TSH (fully adjusted: HR 1.45, 95% CI, 1.04-2.02 and HR 1.51, 95% CI, 1.07-2.12, respectively). In contrast, the risk of MOF was not statistically different in the highest FT4 quartile compared with the three lower FT4 quartiles. Finally, serum TSH was not associated with fracture risk after full adjustment for covariates. In conclusion, serum FT4, but not serum TSH, is a predictor of hip fracture risk in elderly Swedish men. Additionally, there was an association between FT4 (per SD increase) and the risk of MOF.

Recovery pattern after decompression of central lumbar spinal stenosis: a prospective observational cohort study.

BACKGROUND: Detailed preoperative information is associated with superior outcomes. We aimed to describe the recovery pattern after decompression of central lumbar spinal stenosis (CLSS). METHODS: 50 patients aged 51-85 years who underwent decompression without fusion due to CLSS were followed from before to after surgery (post-op day 1, 7, and 14). Back and leg pain were evaluated using the Numeric Rating Scale (NRS; 0 = no pain 0, 10 = worst pain) and quality of life using the EuroQol-5D index (0 = death, 1 = best), and EQ-5D-visual analogue scale (VAS; 0 = worst, 100 = best). RESULTS: NRS leg pain was reduced from preoperative to first postoperative day by 5.2 (6.1, 4.3) (mean (95%CI)], and NRS back pain from postoperative day 1-7 by 0.6 (1.2, 0.03) and from day 7 to 14 by 0.7 (1.3, 0.2)]. In contrast, EQ-5D index increased from preoperative to first postoperative day by 0.09 (0.06, 0.13) and from day 1 to 7 by 0.05 (0.02,0.08), and EQ-5D VAS from preoperative to first postoperative day by 13.7 (9.1, 18.3) and from day 1 to 7 by 6.0 (2.0, 10.0). After two weeks, 51% of the patients had improved above the minimal clinically important difference (MCID) in back pain and 71% in leg pain. CONCLUSIONS: Patients scheduled for decompression due to CLSS should be informed that improvement in leg pain and quality of life in general can be expected within one day of surgery, that quality of life improves a little further in the first postoperative week, and that back pain improves in the first 2 postoperative weeks. In most patients, decompression without fusion due to CLSS seems to achieve clinically relevant improvement within 2 weeks.

Phase-locked, pre-amplified optical injection locking at low input powers.

Optical injection locking generally occurs when light from a master laser is unidirectionally injected into a slave laser, such that the injected light overcomes spontaneous emission inside the cavity, and forces the slave laser to behave as a frequency copy of the master. Here, we study the limits of stability for optically pre-amplified optical injection locking in the case of large added noise on the input field and in the presence of a phase locked loop which minimizes the frequency offset between master and slave lasers. We present a set of modified rate equations which we use to describe the physics of the system near the limit of stable injection locking, and report on phase slips which occur due to injected noise momentarily destabilizing the system. We then provide experimental evidence to support the behavior seen in simulation, and are able to successfully recover a CW wave at -80 dBm black box input power (-70 dBm for phase slip free operation), providing 20 dBm of output power from the injection locked slave laser.

Transcriptomic analysis identifies candidate genes for Aphanomyces root rot disease resistance in pea.

BACKGROUND: Aphanomyces euteiches is a soil-borne oomycete that causes root rot in pea and other legume species. Symptoms of Aphanomyces root rot (ARR) include root discoloration and wilting, leading to significant yield losses in pea production. Resistance to ARR is known to be polygenic but the roles of single genes in the pea immune response are still poorly understood. This study uses transcriptomics to elucidate the immune response of two pea genotypes varying in their levels of resistance to A. euteiches. RESULTS: In this study, we inoculated roots of the pea (P. sativum L.) genotypes 'Linnea' (susceptible) and 'PI180693' (resistant) with two different A. euteiches strains varying in levels of virulence. The roots were harvested at 6 h post-inoculation (hpi), 20 hpi and 48 hpi, followed by differential gene expression analysis. Our results showed a time- and genotype-dependent immune response towards A. euteiches infection, involving several WRKY and MYB-like transcription factors, along with genes associated with jasmonic acid (JA) and abscisic acid (ABA) signaling. By cross-referencing with genes segregating with partial resistance to ARR, we identified 39 candidate disease resistance genes at the later stage of infection. Among the genes solely upregulated in the resistant genotype 'PI180693', Psat7g091800.1 was polymorphic between the pea genotypes and encoded a Leucine-rich repeat receptor-like kinase reminiscent of the Arabidopsis thaliana FLAGELLIN-SENSITIVE 2 receptor. CONCLUSIONS: This study provides new insights into the gene expression dynamics controlling the immune response of resistant and susceptible pea genotypes to A. euteiches infection. We present a set of 39 candidate disease resistance genes for ARR in pea, including the putative immune receptor Psat7g091800.1, for future functional validation.

A meta-analysis of previous falls and subsequent fracture risk in cohort studies.

The relationship between self-reported falls and fracture risk was estimated in an international meta-analysis of individual-level data from 46 prospective cohorts. Previous falls were associated with an increased fracture risk in women and men and should be considered as an additional risk factor in the FRAX® algorithm. INTRODUCTION: Previous falls are a well-documented risk factor for subsequent fracture but have not yet been incorporated into the FRAX algorithm. The aim of this study was to evaluate, in an international meta-analysis, the association between previous falls and subsequent fracture risk and its relation to sex, age, duration of follow-up, and bone mineral density (BMD). METHODS: The resource comprised 906,359 women and men (66.9% female) from 46 prospective cohorts. Previous falls were uniformly defined as any fall occurring during the previous year in 43 cohorts; the remaining three cohorts had a different question construct. The association between previous falls and fracture risk (any clinical fracture, osteoporotic fracture, major osteoporotic fracture, and hip fracture) was examined using an extension of the Poisson regression model in each cohort and each sex, followed by random-effects meta-analyses of the weighted beta coefficients. RESULTS: Falls in the past year were reported in 21.4% of individuals. During a follow-up of 9,102,207 person-years, 87,352 fractures occurred of which 19,509 were hip fractures. A previous fall was associated with a significantly increased risk of any clinical fracture both in women (hazard ratio (HR) 1.42, 95% confidence interval (CI) 1.33-1.51) and men (HR 1.53, 95% CI 1.41-1.67). The HRs were of similar magnitude for osteoporotic, major osteoporotic fracture, and hip fracture. Sex significantly modified the association between previous fall and fracture risk, with predictive values being higher in men than in women (e.g., for major osteoporotic fracture, HR 1.53 (95% CI 1.27-1.84) in men vs. HR 1.32 (95% CI 1.20-1.45) in women, P for interaction = 0.013). The HRs associated with previous falls decreased with age in women and with duration of follow-up in men and women for most fracture outcomes. There was no evidence of an interaction between falls and BMD for fracture risk. Subsequent risk for a major osteoporotic fracture increased with each additional previous fall in women and men. CONCLUSIONS: A previous self-reported fall confers an increased risk of fracture that is largely independent of BMD. Previous falls should be considered as an additional risk factor in future iterations of FRAX to improve fracture risk prediction.

Comparative Effectiveness of eConsent: Systematic Review.

BACKGROUND: Providing informed consent means agreeing to participate in a clinical trial and having understood what is involved. Flawed informed consent processes, including missing dates and signatures, are common regulatory audit findings. Electronic consent (eConsent) uses digital technologies to enable the consenting process. It aims to improve participant comprehension and engagement with study information and to address data quality concerns. OBJECTIVE: This systematic literature review aimed to assess the effectiveness of eConsent in terms of patient comprehension, acceptability, usability, and study enrollment and retention rates, as well as the effects of eConsent on the time patients took to perform the consenting process ("cycle time") and on-site workload in comparison with traditional paper-based consenting. METHODS: The systematic review was conducted and reported in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Ovid Embase and Ovid MEDLINE were systematically searched for publications reporting original, comparative data on the effectiveness of eConsent in terms of patient comprehension, acceptability, usability, enrollment and retention rates, cycle time, and site workload. The methodological validity of the studies that compared outcomes for comprehension, acceptability, and usability across paper consent and eConsent was assessed. Study methodologies were categorized as having "high" validity if comprehensive assessments were performed using established instruments. RESULTS: Overall, 37 publications describing 35 studies (13,281 participants) were included. All studies comparing eConsenting and paper-based consenting for comprehension (20/35, 57% of the studies; 10 with "high" validity), acceptability (8/35, 23% of the studies; 1 with "high" validity), and usability (5/35, 14% of the studies; 1 with "high" validity) reported significantly better results with eConsent, better results but without significance testing, or no significant differences in overall results. None of the studies reported better results with paper than with eConsent. Among the "high" validity studies, 6 studies on comprehension reported significantly better understanding of at least some concepts, the study on acceptability reported statistically significant higher satisfaction scores, and the study on usability reported statistically significant higher usability scores with eConsent than with paper (P<.05 for all). Cycle times were increased with eConsent, potentially reflecting greater patient engagement with the content. Data on enrollment and retention were limited. Comparative data from site staff and other study researchers indicated the potential for reduced workload and lower administrative burden with eConsent. CONCLUSIONS: This systematic review showed that compared with patients using paper-based consenting, patients using eConsent had a better understanding of the clinical trial information, showed greater engagement with content, and rated the consenting process as more acceptable and usable. eConsent solutions thus have the potential to enhance understanding, acceptability, and usability of the consenting process while inherently being able to address data quality concerns, including those related to flawed consenting processes.

Multilayer integration in silicon nitride: decoupling linear and nonlinear functionalities for ultralow loss photonic integrated systems.

Silicon nitride is an excellent material platform for its extremely low loss in a large wavelength range, which makes it ideal for the linear processing of optical signals on a chip. Moreover, the Kerr nonlinearity and the lack of two-photon absorption in the near infrared enable efficient nonlinear optics, e.g., frequency comb generation. However, linear and nonlinear operations require distinct engineering of the waveguide core geometry, resulting in a tradeoff between optical loss and single-mode behavior, which hinders the development of high-performance, ultralow-loss linear processing blocks on a single layer. Here, we demonstrate a dual-layer photonic integration approach with two silicon-nitride platforms exhibiting ultralow optical losses, i.e., a few dB/m, and individually optimized to perform either nonlinear or linear processing tasks. We demonstrate the functionality of this approach by integrating a power-efficient microcomb with an arrayed waveguide grating demultiplexer to filter a few frequency comb lines in the same monolithically integrated chip. This approach can significantly improve the integration of linear and nonlinear optical elements on a chip and opens the way to the development of fully integrated processing of Kerr nonlinear sources.

Factors Associated With Circulating Sex Hormones in Men : Individual Participant Data Meta-analyses.

BACKGROUND: Various factors modulate circulating testosterone in men, affecting interpretation of testosterone measurements. PURPOSE: To clarify factors associated with variations in sex hormone concentrations. DATA SOURCES: Systematic literature searches (to July 2019). STUDY SELECTION: Prospective cohort studies of community-dwelling men with total testosterone measured using mass spectrometry. DATA EXTRACTION: Individual participant data (IPD) (9 studies; n = 21 074) and aggregate data (2 studies; n = 4075). Sociodemographic, lifestyle, and health factors and concentrations of total testosterone, sex hormone-binding globulin (SHBG), luteinizing hormone (LH), dihydrotestosterone, and estradiol were extracted. DATA SYNTHESIS: Two-stage random-effects IPD meta-analyses found a nonlinear association of testosterone with age, with negligible change among men aged 17 to 70 years (change per SD increase about the midpoint, -0.27 nmol/L [-7.8 ng/dL] [CI, -0.71 to 0.18 nmol/L {-20.5 to 5.2 ng/dL}]) and decreasing testosterone levels with age for men older than 70 years (-1.55 nmol/L [-44.7 ng/dL] [CI, -2.05 to -1.06 nmol/L {-59.1 to -30.6 ng/dL}]). Testosterone was inversely associated with body mass index (BMI) (change per SD increase, -2.42 nmol/L [-69.7 ng/dL] [CI, -2.70 to -2.13 nmol/L {-77.8 to -61.4 ng/dL}]). Testosterone concentrations were lower for men who were married (mean difference, -0.57 nmol/L [-16.4 ng/dL] [CI, -0.89 to -0.26 nmol/L {-25.6 to -7.5 ng/dL}]); undertook at most 75 minutes of vigorous physical activity per week (-0.51 nmol/L [-14.7 ng/dL] [CI, -0.90 to -0.13 nmol/L {-25.9 to -3.7 ng/dL}]); were former smokers (-0.34 nmol/L [-9.8 ng/dL] [CI, -0.55 to -0.12 nmol/L {-15.9 to -3.5 ng/dL}]); or had hypertension (-0.53 nmol/L [-15.3 ng/dL] [CI, -0.82 to -0.24 nmol/L {-23.6 to -6.9 ng/dL}]), cardiovascular disease (-0.35 nmol/L [-10.1 ng/dL] [CI, -0.55 to -0.15 nmol/L {-15.9 to -4.3 ng/dL}]), cancer (-1.39 nmol/L [-40.1 ng/dL] [CI, -1.79 to -0.99 nmol/L {-51.6 to -28.5 ng/dL}]), or diabetes (-1.43 nmol/L [-41.2 ng/dL] [CI, -1.65 to -1.22 nmol/L {-47.6 to -35.2 ng/dL}]). Sex hormone-binding globulin was directly associated with age and inversely associated with BMI. Luteinizing hormone was directly associated with age in men older than 70 years. LIMITATION: Cross-sectional analysis, heterogeneity between studies and in timing of blood sampling, and imputation for missing data. CONCLUSION: Multiple factors are associated with variation in male testosterone, SHBG, and LH concentrations. Reduced testosterone and increased LH concentrations may indicate impaired testicular function after age 70 years. Interpretation of individual testosterone measurements should account particularly for age older than 70 years, obesity, diabetes, and cancer. PRIMARY FUNDING SOURCE: Medical Research Future Fund, Government of Western Australia, and Lawley Pharmaceuticals. (PROSPERO: CRD42019139668).

Active tunable WDM demultiplexer with intrinsic gain based on vectorial parametric amplification.

We report on the realization of an active tunable wavelength division multiplexing (WDM) demultiplexer based on vectorial parametric amplification in a highly nonlinear bismuth-oxide fiber. The demultiplexing of a 10 Gbits/s WDM channel is demonstrated with little power penalty. The compact device integrates wavelength conversion and filtering functions while providing parametric gain. Furthermore, the proposed scheme could be extended to perform time division multiplexing (TDM) and WDM simultaneously.

3D Finite Element Models Reconstructed From 2D Dual-Energy X-Ray Absorptiometry (DXA) Images Improve Hip Fracture Prediction Compared to Areal BMD in Osteoporotic Fractures in Men (MrOS) Sweden Cohort.

Bone strength is an important contributor to fracture risk. Areal bone mineral density (aBMD) derived from dual-energy X-ray absorptiometry (DXA) is used as a surrogate for bone strength in fracture risk prediction tools. 3D finite element (FE) models predict bone strength better than aBMD, but their clinical use is limited by the need for 3D computed tomography and lack of automation. We have earlier developed a method to reconstruct the 3D hip anatomy from a 2D DXA image, followed by subject-specific FE-based prediction of proximal femoral strength. In the current study, we aim to evaluate the method's ability to predict incident hip fractures in a population-based cohort (Osteoporotic Fractures in Men [MrOS] Sweden). We defined two subcohorts: (i) hip fracture cases and controls cohort: 120 men with a hip fracture (<10 years from baseline) and two controls to each hip fracture case, matched by age, height, and body mass index; and (ii) fallers cohort: 86 men who had fallen the year before their hip DXA scan was acquired, 15 of which sustained a hip fracture during the following 10 years. For each participant, we reconstructed the 3D hip anatomy and predicted proximal femoral strength in 10 sideways fall configurations using FE analysis. The FE-predicted proximal femoral strength was a better predictor of incident hip fractures than aBMD for both hip fracture cases and controls (difference in area under the receiver operating characteristics curve, ΔAUROC = 0.06) and fallers (ΔAUROC = 0.22) cohorts. This is the first time that FE models outperformed aBMD in predicting incident hip fractures in a population-based prospectively followed cohort based on 3D FE models obtained from a 2D DXA scan. Our approach has potential to notably improve the accuracy of fracture risk predictions in a clinically feasible manner (only one single DXA image is needed) and without additional costs compared to the current clinical approach. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Multiple rearrangements and low inter- and intra-species mitogenome sequence variation in the Heterobasidion annosum s.l. species complex.

Introduction: Mitochondria are essential organelles in the eukaryotic cells and responsible for the energy production but are also involved in many other functions including virulence of some fungal species. Although the evolution of fungal mitogenomes have been studied at some taxonomic levels there are still many things to be learned from studies of closely related species. Methods: In this study, we have analyzed 60 mitogenomes in the five species of the Heterobasidion annosum sensu lato complex that all are necrotrophic pathogens on conifers. Results and Discussion: Compared to other fungal genera the genomic and genetic variation between and within species in the complex was low except for multiple rearrangements. Several translocations of large blocks with core genes have occurred between the five species and rearrangements were frequent in intergenic areas. Mitogenome lengths ranged between 108 878 to 116 176 bp, mostly as a result of intron variation. There was a high degree of homology of introns, homing endonuclease genes, and intergenic ORFs among the five Heterobasidion species. Three intergenic ORFs with unknown function (uORF6, uORF8 and uORF9) were found in all five species and was located in conserved synteny blocks. A 13 bp long GC-containing self-complementary palindrome was discovered in many places in the five species that were optional in presence/absence. The within species variation is very low, among 48 H. parviporum mitogenomes, there was only one single intron exchange, and SNP frequency was 0.28% and indel frequency 0.043%. The overall low variation in the Heterobasidion annosum sensu lato complex suggests a slow evolution of the mitogenome.

Distribution and Environmental Drivers of Fungal Denitrifiers in Global Soils.

The microbial process of denitrification is the primary source of the greenhouse gas nitrous oxide (N2O) from terrestrial ecosystems. Fungal denitrifiers, unlike many bacteria, lack the N2O reductase, and thereby are sources of N2O. Still, their diversity, global distribution, and environmental determinants, as well as their relative importance, compared to bacterial and archaeal denitrifiers, remain unresolved. Employing a phylogenetically informed approach to analyze 1,980 global soil and rhizosphere metagenomes for the denitrification marker gene nirK, which codes for the copper dependent nitrite reductase in denitrification, we show that fungal denitrifiers are sparse, yet cosmopolitan and that they are dominated by saprotrophs and pathogens. Few showed biome-specific distribution patterns, although members of the Fusarium oxysporum species complex, which are known to produce substantial amounts of N2O, were proportionally more abundant and diverse in the rhizosphere than in other biomes. Fungal denitrifiers were most frequently detected in croplands, but they were most abundant in forest soils when normalized to metagenome size. Nevertheless, the overwhelming dominance of bacterial and archaeal denitrifiers suggests a much lower fungal contribution to N2O emissions than was previously estimated. In relative terms, they could play a role in soils that are characterized by a high carbon to nitrogen ratio and a low pH, especially in the tundra as well as in boreal and temperate coniferous forests. Because global warming predicts the proliferation of fungal pathogens, the prevalence of potential plant pathogens among fungal denitrifiers and the cosmopolitan distribution of these organisms suggest that fungal denitrifier abundance may increase in terrestrial ecosystems. IMPORTANCE Fungal denitrifiers, in contrast to their bacterial counterparts, are a poorly studied functional group within the nitrogen cycle, even though they produce the greenhouse gas N2O. To curb soil N2O emissions, a better understanding of their ecology and distribution in soils from different ecosystems is needed. Here, we probed a massive amount of DNA sequences and corresponding soil data from a large number of samples that represented the major soil environments for a broad understanding of fungal denitrifier diversity at the global scale. We show that fungal denitrifiers are predominantly cosmopolitan saprotrophs and opportunistic pathogens. Fungal denitrifiers constituted, on average, 1% of the total denitrifier community. This suggests that earlier estimations of fungal denitrifier abundance, and, thereby, it is also likely that the contributions of fungal denitrifiers to N2O emissions have been overestimated. Nevertheless, with many fungal denitrifiers being plant pathogens, they could become increasingly relevant, as soilborne pathogenic fungi are predicted to increase with ongoing climate change.

In old men Scheuermann's disease is not associated with neck or back pain: a Swedish cohort study.

BACKGROUND AND PURPOSE: Scheuermann's disease is characterized by kyphosis and frequently mild back pain. As the level of kyphosis may progress over time, also the level of pain may increase. We evaluated the prevalence of Scheuermann's disease, and their pain, in Swedish elderly men. PATIENTS AND METHODS: The Osteoporotic Fractures in Men (MrOS) Study Sweden (n = 3,014) is a population-based prospective observational study of community-living men aged 69-81 years. At baseline, participants answered a questionnaire including history of neck/back pain during the preceding year and characteristics of any pain (severity, sciatica, and neurological deficits). Lateral thoracic/lumbar spine radiographs were taken of 1,453 men. We included the 1,417 men with readable radiographs. Scheuermann's disease was defined as 3 or more consecutive vertebrae with > 5° wedging with no other explanation for the deformity. RESULTS: 92 of the 1,417 men (6.5%, 95% confidence interval 5.3-7.9) had Scheuermann's disease. 31% of men with and 31% without Scheuermann's disease reported neck pain (P = 0.90) and 51% with and 55% without the disease reported back pain (P = 0.4). Among men with Scheuermann's disease and back pain, none reported severe pain, 57% moderate, and 43% mild, compared with 7%, 50%, and 44% in those without Scheuermann's disease (P = 0.2). In those with Scheuermann's disease 63% reported no sciatica, 15% sciatica without neurological deficits, and 22% sciatica with neurological deficits, compared with 56%, 16%, and 28% in those without the disease (P = 0.6). CONCLUSION: The prevalence of Scheuermann's disease in elderly Swedish men is between 5.3% and 7.9%. The condition seems at this age not to be associated with neck or back pain.

Insights into the ecological generalist lifestyle of Clonostachys fungi through analysis of their predicted secretomes.

Introduction: The fungal secretome comprise diverse proteins that are involved in various aspects of fungal lifestyles, including adaptation to ecological niches and environmental interactions. The aim of this study was to investigate the composition and activity of fungal secretomes in mycoparasitic and beneficial fungal-plant interactions. Methods: We used six Clonostachys spp. that exhibit saprotrophic, mycotrophic and plant endophytic lifestyles. Genome-wide analyses was performed to investigate the composition, diversity, evolution and gene expression of Clonostachys secretomes in relation to their potential role in mycoparasitic and endophytic lifestyles. Results and discussion: Our analyses showed that the predicted secretomes of the analyzed species comprised between 7 and 8% of the respective proteomes. Mining of transcriptome data collected during previous studies showed that 18% of the genes encoding predicted secreted proteins were upregulated during the interactions with the mycohosts Fusarium graminearum and Helminthosporium solani. Functional annotation of the predicted secretomes revealed that the most represented protease family was subclass S8A (11-14% of the total), which include members that are shown to be involved in the response to nematodes and mycohosts. Conversely, the most numerous lipases and carbohydrate-active enzyme (CAZyme) groups appeared to be potentially involved in eliciting defense responses in the plants. For example, analysis of gene family evolution identified nine CAZyme orthogroups evolving for gene gains (p ≤ 0.05), predicted to be involved in hemicellulose degradation, potentially producing plant defense-inducing oligomers. Moreover, 8-10% of the secretomes was composed of cysteine-enriched proteins, including hydrophobins, important for root colonization. Effectors were more numerous, comprising 35-37% of the secretomes, where certain members belonged to seven orthogroups evolving for gene gains and were induced during the C. rosea response to F. graminearum or H. solani. Furthermore, the considered Clonostachys spp. possessed high numbers of proteins containing Common in Fungal Extracellular Membranes (CFEM) modules, known for their role in fungal virulence. Overall, this study improves our understanding of Clonostachys spp. adaptation to diverse ecological niches and establishes a basis for future investigation aiming at sustainable biocontrol of plant diseases.

Political deafness may impede transition to biological control.

Biological control has developed into a realistic alternative to replace chemical pesticides. A long-awaited paradigm shift is now adopted by the European Commission through a proposed new Regulation on sustainable use of plant protection products. Unfortunately, the scientific framework underpinning biocontrol is seriously neglected, impeding transition to sustainable plant production.