Susceptibility to tuberculosis is historically ascribed to an inadequate immune response that fails to control infecting mycobacteria. In zebrafish, we find that susceptibility to Mycobacterium ...marinum can result from either inadequate or excessive acute inflammation. Modulation of the leukotriene A4 hydrolase (LTA4H) locus, which controls the balance of pro- and anti-inflammatory eicosanoids, reveals two distinct molecular routes to mycobacterial susceptibility converging on dysregulated TNF levels: inadequate inflammation caused by excess lipoxins and hyperinflammation driven by excess leukotriene B4. We identify therapies that specifically target each of these extremes. In humans, we identify a single nucleotide polymorphism in the LTA4H promoter that regulates its transcriptional activity. In tuberculous meningitis, the polymorphism is associated with inflammatory cell recruitment, patient survival and response to adjunctive anti-inflammatory therapy. Together, our findings suggest that host-directed therapies tailored to patient LTA4H genotypes may counter detrimental effects of either extreme of inflammation.
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► Conserved eicosanoids are regulated by LTA4H activity and impact inflammatory state ► Genotype-directed modulation of TNF improves outcomes in a zebrafish tuberculosis model ► Drug therapies tailored to lta4h genotype improve infection outcome in zebrafish ► In humans, LTA4H genotype associates with responsiveness to therapy for TB meningitis
A polymorphism in a locus that controls the balance between pro- and anti-inflammatory mediators is predictive of response to anti-inflammatory therapy in tuberculous meningitis.
Abstract Introduction Individuals with hip fracture are at substantially increased risk of mortality. The aim of this study was to estimate the excess mortality attributable to hip fracture in ...elderly men and women. Methods The Dubbo Osteoporosis Epidemiology Study was designed as a prospective epidemiologic investigation, in which more than 2000 men and women aged 60+ as of 1989 had been followed for 21 years. During the follow-up period, the incidence of atraumatic hip fractures was ascertained by X-ray reports, and mortality was ascertained by the New South Wales Birth, Death and Marriage Registry. Relative survival ratios were estimated by taking into account the age-and-sex specific expected survival in the general Australian population from 1989 to 2010. Results During the follow-up period 151 women and 55 men sustained a hip fracture. Death occurred in 86 (57%) women and 36 (66%) men. In women, the cumulative relative survival post hip-fracture at 1, 5 and 10 years was 0.83 (95% confidence interval (CI) 0.76–0.89), 0.59 (95% CI 0.48–0.68), and 0.31 (95% CI 0.20–0.43), respectively; in men, the corresponding estimates of relative survival were: 0.63 (95% CI 0.48–0.75), 0.48 (95% CI 0.32–0.63), and 0.36 (95% CI 0.18–0.56). On average post hip-fracture women died 4 years earlier (median: 4.1, inter-quartile range (IQR) 1.7–7.8) and men died 5 years earlier (median = 4.8, IQR 2.4–7.0) than expected. For every six women and for every three men with hip fracture one extra death occurred above that expected in the background population. Conclusion Hip fracture is associated with reduced life expectancy, with men having a greater reduction than women, even after accounting for time-related changes in background mortality in the population. These data underscore that hip fracture is an independent clinical risk factor for mortality.
Abstract
We report on the highest spatial resolution measurement to date of magnetic fields (B-fields) in M17 using thermal dust polarization measurements taken by SOFIA/HAWC+ centered at a ...wavelength of 154
μ
m. Using the Davis–Chandrasekhar–Fermi method, in which the polarization angle dispersion calculated using the structure function technique is the quantity directly observed by SOFIA/HAWC+, we found the presence of strong B-fields of 980 ± 230 and 1665 ± 885
μ
G in the lower-density M17-N and higher-density M17-S regions, respectively. The B-field morphology in M17-N possibly mimics the fields in gravitationally collapsing molecular cores, while in M17-S the fields run perpendicular to the density structure. M17-S also displays a pillar feature and an asymmetric large-scale hourglass-shaped field. We use the mean B-field strengths to determine Alfvénic Mach numbers for both regions, finding that B-fields dominate over turbulence. We calculate the mass-to-flux ratio,
λ
, finding
λ
= 0.07 for M17-N and 0.28 for M17-S. These subcritical
λ
values are consistent with the lack of massive stars formed in M17. To study dust physics, we analyze the relationship between dust polarization fraction,
p
, emission intensity,
I
, gas column density,
N
(H
2
), polarization angle dispersion function,
S
, and dust temperature,
T
d
.
p
decreases with intensity as
I
−
α
with
α
= 0.51.
p
tends to first increase with
T
d
, but then decreases at higher
T
d
. The latter feature, seen in M17-N at high
T
d
when
N
(H
2
) and
S
decrease, is evidence of the radiative torque disruption effect.
Context:
Higher body weight is associated with greater bone mineral density (BMD) and lower fracture risk. However, the relationship between abdominal fat mass (aFM) and fracture risk is unclear ...because of limited prospective data. The present study sought to examine the association between aFM, BMD, and fracture risk.
Methods:
The study was designed as a prospective investigation, in which a sample of 1126 participants (360 men and 766 women) aged 50 years or older had been continuously followed up for an average of 5 years. The mean age of participants was 71 years (range, 57–94 years). At baseline, BMD at the femoral neck and lumbar spine and aFM were measured by dual-energy X-ray absorptiometry. The incidence of low-trauma and nonpathological fractures was ascertained prospectively from X-ray reports.
Results:
During the follow-up period, 19 men and 107 women had sustained a fracture. In women, each 1-kg lower aFM was associated with a 50% higher risk of fracture (hazard ratio HR, 1.50; 95% confidence interval CI, 1.10–2.05) after adjustment for age, femoral neck BMD, falls, stature, physical activity, and prior fracture. Subgroup analysis by fracture type found that the association was mainly observed in clinical vertebral fracture (HR, 1.96; 95% CI, 1.22–3.13). In men, although there was no statistically significant association between aFM and fracture risk (HR, 1.15; 95% CI, 0.58–2.25), the strength of this finding is affected negatively by the low number of fractures.
Conclusions:
Lower abdominal fat was significantly associated with an higher fracture risk in women.
In recent decades, digital transformation has received growing attention worldwide, that has leveraged the explosion of digitized document data. In this paper, we address the problem of parsing ...publications, in particular, Vietnamese publications. The Vietnamese publications are well-known with high variant, diverse layouts, and some characters are equivocal in the visual form due to accent symbols and derivative characters that pose many challenges. To this end, we collect the UIT-DODV-Ext dataset: a challenging Vietnamese document image including scientific papers and textbooks with 5,000 fully annotated images. We introduce a general framework to parse Vietnamese publications containing two components: page object detection and caption recognition. We further conduct an extensive benchmark with various state-of-the-art object detection and text recognition methods. Finally, we present a hybrid parser which achieves the top place in the benchmark. Extensive experiments on the UIT-DODV-Ext dataset provide a comprehensive evaluation and insightful analysis.
Low baseline BMD, rate of BMD loss, weight loss, and weight fluctuation are significant predictors of all‐cause mortality in elderly men and women, independent of each other and of age, incident ...fracture, and concomitant diseases.
Introduction: Although low BMD has been shown to be associated with mortality in women, the effect of BMD is affected by weight and weight change and the contribution of these factors to mortality risk, particularly in men, is not known. This study examined the association between baseline BMD, rate of bone loss, weight loss, and weight fluctuation and all‐cause mortality risk in elderly men and women.
Materials and Methods: Data from 1059 women and 644 men, ≥60 years of age (as of 1989), of white background who participated in the Dubbo Osteoporosis Epidemiology Study were analyzed. All‐cause mortality was recorded annually between 1989 and 2004. BMD at the femoral neck was measured by DXA (GE‐LUNAR) at baseline and at approximately every 2 yr afterward. Data on incident osteoporotic fractures and concomitant diseases, including cardiovascular diseases, all types of cancer, and type I/II diabetes mellitus, was also recorded.
Results: In the multivariable Cox's proportional hazards model with adjustment for age, incident fractures, and concomitant diseases, the following variables were independent risk factors of all‐cause mortality in men: rate of BMD loss of at least 1%/yr, rate of weight loss of at least 1%/yr, and weight fluctuation (defined by the CV) of at least 3%. In women, in addition to the significant factors observed in men, lower baseline BMD was also an independent risk factor of mortality. In both sexes, baseline weight was not an independent and significant predictor of mortality risk. Approximately 36% and 22% of deaths in women and men, respectively, were attributable to the four risk factors.
Conclusions: These data suggest that, although low BMD was a risk factor of mortality in women, it was not a risk factor of mortality in men. However, high rates of BMD loss, weight loss, and weight fluctuation were also independent predictors of all‐cause mortality in elderly men and women, independent of age, incident fracture, and concomitant diseases.
In recent years, pharmaceutical active compounds (PhACs) have attained global prevalence. The behavior of PhACs in agricultural soils is complex and depends on several factors, such as the nature of ...the compounds and their physicochemical characteristics, which affect their fate and potential threats to human health, ecosystems, and the environment. The detection of residual pharmaceutical content is possible in both agricultural soils and environmental matrices. PhACs are commonly found in agricultural soil, with concentrations varying significantly, ranging from as low as 0.048 ng g−1 to as high as 1420.76 mg kg−1. The distribution and persistence of PhACs in agriculture can lead to the leaching of these toxic pollutants into surface water, groundwater, and vegetables/plants, resulting in human health risks and environmental pollution. Biological degradation or bioremediation plays a critical role in environmental protection and efficiently eliminates contamination by hydrolytic and/or photochemical reactions. Membrane bioreactors (MBRs) have been investigated as the most recent approach for the treatment of emerging persistent micropollutants, including PhACs, from wastewater sources. MBR- based technologies have proven to be effective in eliminating pharmaceutical compounds, achieving removal rates of up to 100%. This remarkable outcome is primarily facilitated by the processes of biodegradation and metabolization. In addition, phytoremediation (i.e., constructed wetlands), microalgae-based technologies, and composting can be highly efficient in remediating PhACs in the environment. The exploration of key mechanisms involved in pharmaceutical degradation has revealed a range of approaches, such as phytoextraction, phytostabilization, phytoaccumulation, enhanced rhizosphere biodegradation, and phytovolatilization. The well-known advanced/tertiary removal of sustainable sorption by biochar, activated carbon, chitosan, etc. has high potential and yields excellent quality effluents. Adsorbents developed from agricultural by-products have been recognized to eliminate pharmaceutical compounds and are cost-effective and eco-friendly. However, to reduce the potentially harmful impacts of PhACs, it is necessary to focus on advanced technologies combined with tertiary processes that have low cost, high efficiency, and are energy-saving to remove these emerging pollutants for sustainable development.
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•PhACs behavior in agricultural soils is a complex process and has become a global issue.•PhACs are commonly found in agricultural soil, ranging from 0.048 ng g−1 to 1420.76 mg kg−1.•The presence of PhACs in agriculture poses risks to food safety and security.•Antibiotic residues have adverse effects on flora, fauna, and human health through food chains.•MBR-based technologies effectively remove PhACs, achieving up to 100% removal.
Abstract Introduction Approximately 10% of hip fracture patients die during hospitalization; however, it is not clear what risk factors contribute to the excess mortality. This study sought to ...examine risk factors of, and to develop prognostic model for, predicting in-hospital mortality among hip fracture patients. Methods We studied outcomes among 410 men and 1094 women with a hip fracture who were admitted to a major-teaching-hospital in Sydney (Australia) between 1997 and 2007. Clinical data, including concomitant illnesses, were obtained from inpatient data. The primary outcome of the study was in-hospital mortality regardless of length of stay. A Log-binomial regression model was used to identify risk factors for in-hospital mortality. Using the identified risk factors, prognostic nomograms were developed for predicting short term risk of mortality for an individual. Results The median duration of hospitalization was 9 days. During hospitalization, the risk of mortality was higher in men (9%) than in women (4%). After adjusting for multiple risk factors, increased risk of in-hospital mortality was associated with advancing age (rate ratio RR for each 10-year increase in age: 1.91 95% confidence interval CI: 1.47 to 2.49), in men (RR 2.13; 95% CI 1.41 to 3.22), and the presence of comorbid conditions on admission (RR for one or more comorbid conditions vs. none: 2.30; 95% CI 1.52 to 3.48). Specifically, the risk of mortality was increased in patients with a pre-existing congestive heart failure (RR 3.02; 95% CI: 1.65 to 5.54), and liver disease (RR 4.75; 95% CI: 1.87 to 12.1). These factors collectively accounted for 69% of the risk for in-hospital mortality. A nomogram was developed from these risk factors to individualize the risk of in-hospital death following a hip fracture. The area under the receiver operating characteristic curve of the final model containing age, sex and comorbid conditions was 0.76. Conclusion These data suggest that among hip fracture patients, advancing age, gender (men), and pre-existing concomitant diseases such as congestive heart failure and liver disease were the main risk factors for in-hospital mortality. The nomogram developed from this study can be used to convey useful prognostic information to help guide treatment decisions.
Background. Tuberculous meningitis (TBM) is the most devastating form of tuberculosis, yet very little is known about the pathophysiology. We hypothesized that the genotype of leukotriene A₄ ...hydrolase (encode by LTA4H), which determines inflammatory eicosanoid expression, influences intracerebral inflammation, and predicts survival from TBM. Methods. We characterized the pretreatment clinical and intracerebral inflammatory phenotype and 9-month survival of 764 adults with TBM. All were genotyped for single-nucleotide polymorphism rs17525495, and inflammatory phenotype was defined by cerebrospinal fluid (CSF) leukocyte and cytokine concentrations. Results. LTA4H genotype predicted survival of human immunodeficiency virus (HIV)=uninfected patients, with TT-genotype patients significantly more likely to survive TBM than CC-genotype patients, according to Cox regression analysis (univariate P = .040 and multivariable P = .037). HIV-uninfected, TT-genotype patients had high CSF proinflammatory cytokine concentrations, with intermediate and lower concentrations in those with CT and CC genotypes. Increased CSF cytokine concentrations correlated with more-severe disease, but patients with low CSF leukocytes and cytokine concentrations were more likely to die from TBM, HIV infection independently predicted death due to TBM (hazard ratio, 3.94; 95% confidence interval, 2.79-5.56) and was associated with globally increased CSF cytokine concentrations, independent of LTA4H genotype. Conclusions. LTA4H genotype and HIV infection influence pretreatment inflammatory phenotype and survival from TBM. LTA4H genotype may predict adjunctive corticosteroid responsiveness in HIV-uninfected individuals.
In elderly men and women, asymptomatic vertebral deformity was found to be associated with subsequent risk of symptomatic fractures, particularly vertebral fracture, and increased risk of mortality ...after a fracture.
Introduction: Vertebral deformity is associated with an increased risk of fracture and mortality. However, it is unclear whether the three events of vertebral deformity, fracture, and mortality are linked with each other and what role BMD plays in these linkages.
Materials and Methods: Vertebral deformity was determined from quantitative analysis of thoracolumbar spine X‐rays in 300 randomly individuals (114 men and 186 women) ⩾60 years of age (as of mid‐1989), who were randomly selected from the prospective Dubbo Osteoporosis Epidemiology Study. Incidence of atraumatic fractures and subsequent mortality were ascertained from 1989 to 2003. Cox's proportional hazards model was used to determine the association between asymptomatic vertebral deformities, osteoporotic fractures, and risk of mortality.
Results: The prevalence of asymptomatic vertebral deformity was 31% in men and 17% in women. During the follow‐up period, subjects with vertebral deformity had a significantly higher risk of any fracture than those without vertebral deformity (44% versus 29%; hazards ratio HR, 2.2; 95% CI, 1.4‐3.7), particularly symptomatic vertebral fracture (relative risk RR, 7.4; 95% CI, 3.2‐17.0). Mortality rate was highest after a symptomatic fracture among those with vertebral deformity (HR, 9.0; 95% CI, 3.1‐26.0). These associations were independent of age, sex, and BMD.
Conclusion: Vertebral deformity was a strong predictor of subsequent risk of fractures, particularly symptomatic vertebral fracture, and may modify fracture‐associated mortality in both elderly men and women.
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