Summary
Background
The sensitivity of current upper limit of normal (ULN) of serum alanine aminotransferase (ALT) levels for detecting chronic liver disease has been challenged recently.
Aim
To ...identify modulating factors for serum ALT levels and to refine its ULN threshold.
Methods
We enrolled 34 346 consecutive subjects who completed the health check‐up at Taipei Veterans General Hospital from 2002 to 2009. ULN was set for healthy ALT level to the 95th percentile of the reference healthy population.
Results
A group of 21 282 subjects were used as a training set to define an ULN with the highest sensitivity; afterwards, this ULN was validated in another set of 13 064 subjects. A reference healthy population was selected from the training set after excluding subjects with any abnormalities in independent risk factors associated with elevated serum ALT level (>40 IU/L) by multivariate analysis like body mass index, waist circumference, glucose, cholesterol, high‐density lipoprotein‐cholesterol, triglyceride, hepatitis B virus surface antigen, anti‐hepatitis C virus antibody and fatty liver. The new ULN of serum ALT level defined as the 95% percentile in the healthy population were 21 IU/L and 17 IU/L for men and women respectively. These cut‐off values had the highest Youden's index and areas under the corresponding receiver operating curves among four widely applied thresholds in both the training and validation sets.
Conclusions
The suggested threshold of upper limit of normal provides better discrimination between healthy and unhealthy status. Viral hepatitis, metabolic syndrome and fatty liver are the major risk factors of elevated serum alanine aminotransferase levels.
Resistance mutations A2058G and A2059G, within the 23S rRNA gene of Treponema pallidum, have been reported to cause treatment failures in patients receiving azithromycin for syphilis. Genotyping of ...T. pallidum strains sequentially isolated from patients with recurrent syphilis is rarely performed. From September 2009 to August 2013, we collected 658 clinical specimens from 375 patients who presented with syphilis for genotyping to examine the number of 60-bp repeats in the acidic repeat protein (arp) gene, T. pallidum repeat (tpr) polymorphism, and tp0548 gene, and to detect A2058G and A2059G point mutations by restriction fragment length polymorphism. Treponemal DNA was identified in 45.2% (n = 298) of the specimens that were collected from 216 (57.6%) patients; 268 (40.7%) specimens tested positive for the 23S rRNA gene, and were examined for macrolide resistance. Two isolates (0.7%) harboured the A2058G mutation, and no A2059G mutation was identified. A total of 14 strains of T. pallidum were identified, with 14f/f (57.5%) and 14b/c (10.0%) being the two predominant strains. Forty patients who presented with recurrent episodes of syphilis had T. pallidum DNA identified from the initial and subsequent episodes, with five cases showing strain discrepancies. One patient had two strains identified from different clinical specimens collected in the same episode. Our findings show that 14f/f is the most common T. pallidum strain in Taiwan, where the prevalence of T. pallidum strains that show A2058G or A2059G mutation remains low. Different genotypes of T. pallidum can be identified in patients with recurrent episodes of syphilis.
The field of mesoporous metal nanoarchitectonics offers several advantages which cannot be found elsewhere. These materials have been showcasing impressive enhancements of their electrochemical ...properties for further implementation, compared to their micro‐ and macroporous counterparts. Since the last few decades, various methods have been developed to achieve narrow pore size distribution with a tunable porosity and particle morphology. While hard templates offer a reliable and intuitive approach to synthesize mesoporous metals, the complexity of the technique and the use of harmful chemicals pushed several research groups to focus in other directions. For example, soft templates (e.g., lyotropic crystals, micelles assemblies) and solution phase methods (requiring to control reduction reactions) offer more and more possibilities in terms of available compositions and morphologies. Indeed, various metal (Pt, Pd, Au, Ru, etc.) can now be synthesized as dendritic, core@shell, hollow or polyhedral nanoparticles, with single‐ or multicomponents, alloyed or not, with unprecedented electrochemical activity.
Mesoporous metals are normally synthesized by templating methods (hard or soft), while dendritic nanostructures are instead fabricated by wet chemical methods. To date, a broad spectrum of nanoporous metals (including both microporous and mesoporous metals) with different sizes and shapes has been successfully prepared under various conditions. Recent progress relating to this emerging field is reviewed.
Mesoporous silica nanoparticles (MSNs), one of the important porous materials, have garnered interest owing to their highly attractive physicochemical features and advantageous morphological ...attributes. They are of particular importance for use in diverse fields including, but not limited to, adsorption, catalysis, and medicine. Despite their intrinsic stable siliceous frameworks, excellent mechanical strength, and optimal morphological attributes, pristine MSNs suffer from poor drug loading efficiency, as well as compatibility and degradability issues for therapeutic, diagnostic, and tissue engineering purposes. Collectively, the desirable and beneficial properties of MSNs have been harnessed by modifying the surface of the siliceous frameworks through incorporating supramolecular assemblies and various metal species, and through incorporating supramolecular assemblies and various metal species and their conjugates. Substantial advancements of these innovative colloidal inorganic nanocontainers drive researchers in promoting them toward innovative applications like stimuli (light/ultrasound/magnetic)‐responsive delivery‐associated therapies with exceptional performance in vivo. Here, a brief overview of the fabrication of siliceous frameworks, along with discussions on the significant advances in engineering of MSNs, is provided. The scope of the advancement in terms of structural and physicochemical attributes and their effects on biomedical applications with a particular focus on recent studies is emphasized. Finally, interesting perspectives are recapitulated, along with the scope toward clinical translation.
Mesoporous silica nanoparticles (MSNs) have garnered enormous interest owing to their highly advantageous physicochemical and morphological attributes. Collectively, progression has been made by modifying the surface of the siliceous frameworks through incorporating diverse supramolecular assemblies. An overview of the fabrication of MSNs and discussions on significant advances in engineering of MSNs, along with their scope toward clinical translation, is provided.
Conspectus Well-constructed porous materials take an essential role in a wide range of applications, including energy conversion and storage systems, electrocatalysis, photocatalysis, and sensing. ...Although the tailored design of various nanoarchitectures has made substantial progress, simpler preparation methods are compelled to meet large-scale production requirements. Recently, advanced electrochemical deposition techniques have had a significant impact in terms of precise control upon the nanoporous architecture (i.e., pore size, surface area, pore structure, etc.), enabling access to a wide range of compositions. In this Account, we showcase the uniqueness of electrochemical deposition techniques, detail their implementation toward the synthesis of novel nanoporous metals, and finally outline the future research directions. Nanoporous metallic structures are attractive in that they can provide high surface area and large pore volume, easing mass transport of reactants and providing high accessibility to catalytically active metal surface. The great merit of the electrochemical deposition approach does not only lie in its versatility, being applicable to a wide range of compositions, but also in the nanoscale precision it affords when it comes to crystal growth control, which cannot be easily achieved by other bottom-up or top-down approaches. In this Account, we describe the significant progress made in the field of nanoporous metal designed through electrochemical deposition approaches using hard templates (i.e., porous silica, 3D templates of polymer and silica colloids) and soft templates (i.e., lyotropic liquid crystals, polymeric micelles). In addition, we will point out how it accounts for precise control over the crystal growth and describe the unique physical and chemical properties emerging from these novel materials. Up to date, our group has reported the synthesis of several nanoporous metals and alloys (e.g., Cu, Ru, Rh, Pd, Pt, Au, and their corresponding alloys) under various conditions through electrochemical deposition, while investigating their various potential applications. The orientation of the channel structure, the composition, and the nanoporosity can be easily controlled by selecting the appropriate surfactants or block copolymers. The inherent properties of the final product, such as framework crystallinity, catalytic activity, and resistance to oxidation, are depending on both the composition and pore structure, which in turn require suitable electrochemical conditions. This Account is divided into three main sections: (i) a history of electrochemical deposition using hard and soft templates, (ii) a description of the important mechanisms involved in the preparation of nanoporous materials, and (iii) a conclusion and future perspectives. We believe that this Account will promote a deeper understanding of the synthesis of nanoporous metals using electrochemical deposition methods, thus enabling new pathways to control nanoporous architectures and optimize their performance toward promising applications such as catalysis, energy storage, sensors, and so forth.
Summary
Background
Aspirin increases the risk of gastrointestinal bleeding.
Aim
To investigate the risk of lower gastrointestinal bleeding (LGIB) in aspirin users.
Methods
Low‐dose (75‐325 mg daily) ...aspirin users and controls matched by age, gender and enrollment time in a 1:5 ratio were selected from 1 million randomly sampled subjects in the National Health Insurance Research Database of Taiwan. Cox proportional hazard regression models were developed to evaluate the predictors of LGIB with adjustments for age, gender, comorbidities including coronary artery disease, ischaemic stroke, diabetes, hypertension, chronic kidney disease, liver cirrhosis, chronic obstructive pulmonary disease, dyslipidemia, uncomplicated peptic ulcer disease, history of peptic ulcer bleeding, and concomitant use of clopidogrel, ticlopidine, warfarin, nonsteroidal anti‐inflammatory drugs (NSAIDs), cyclooxygenase‐2 inhibitors, steroids, proton pump inhibitors (PPIs), histamine‐2 receptor antagonists (H2RAs), nitrates, alendronate, selective serotonin reuptake inhibitors (SSRIs) and calcium channel blockers.
Results
A total of 53 805 aspirin users and 269 025 controls were included. Aspirin group had a higher incidence of LGIB within 1 year than control group (0.20% vs 0.06%, P<.0001). Aspirin (hazard ratio HR: 2.75, 95% confidence interval CI: 2.06‐3.65), NSAIDs (HR: 8.61, 95% CI: 3.28‐22.58), steroids (HR: 10.50, 95% CI: 1.98‐55.57), SSRIs (HR: 11.71, 95% CI: 1.40‐97.94), PPIs (HR: 8.47, 95% CI: 2.26‐31.71), and H2RAs (HR: 10.83, 95% CI: 2.98‐39.33) were significantly associated with LGIB.
Conclusions
The risk of LGIB was higher in low‐dose aspirin users than in aspirin nonusers in this nationwide cohort. Low‐dose aspirin, NSAIDs, steroids, SSRIs, PPIs and H2RAs were independent risk factors for LGIB.
Linked ContentThis article is linked to Taha and Chen et al papers. To view these articles visit https://doi.org/10.1111/apt.14114 and https://doi.org/10.1111/apt.14138.
A number of patient-specific and leukemia-associated factors are related to the poor outcome in older patients with acute myeloid leukemia (AML). However, comprehensive studies regarding the impact ...of genetic alterations in this group of patients are limited. In this study, we compared relevant mutations in 21 genes between AML patients aged 60 years or older and those younger and exposed their prognostic implications. Compared with the younger patients, the elderly had significantly higher incidences of PTPN11, NPM1, RUNX1, ASXL1, TET2, DNMT3A and TP53 mutations but a lower frequency of WT1 mutations. The older patients more frequently harbored one or more adverse genetic alterations. Multivariate analysis showed that DNMT3A and TP53 mutations were independent poor prognostic factors among the elderly, while NPM1 mutation in the absence of FLT3/ITD was an independent favorable prognostic factor. Furthermore, the status of mutations could well stratify older patients with intermediate-risk cytogenetics into three risk groups. In conclusion, older AML patients showed distinct genetic alterations from the younger group. Integration of cytogenetics and molecular mutations can better risk-stratify older AML patients. Development of novel therapies is needed to improve the outcome of older patients with poor prognosis under current treatment modalities.
Hierarchically porous carbons (HPCs) with 1D to 3D network are attracting vast interest due to their potential technological application profile ranging from electrochemical capacitors, lithium ion ...batteries, solar cells, hydrogen storage systems, photonic material, fuel cells, sorbent for toxic gas separation and so on. Natural raw-materials such as biomass-biopolymer derived hierarchical nanostructured carbons are especially attractive for their uniform pore dimensions which can be adjustable over a wide range of length scales. Good electrical conductivity, high surface area, and excellent chemical stability are unique physicochemical properties which are responsible for micro/nanostructured porous carbon to be highly trusted candidate for emerging nanotechnologies. This review focuses on the 'out-of-the-box' synthetic techniques capable of deriving HPC with superior application profiles. The article presents the promising scope of accessing HPCs from (1) hard-templating, soft-templating, and non-templating routes, (2) biopolymers with a major focus on non-templating strategies. Subsequently, emerging strategies of hetero-atom doping in porous carbon nanostructures are discussed. The review will highlight the contribution of synergistic effect of macro-meso-micropores on a range of emerging applications such as CO
2
capture, carbon photonic crystal sensors, Li-S batteries, and supercapacitor. Mechanism of ion transport and buffering, electrical double layer enhancement have been discussed in the context of pore structure and shapes. We will also show the differences of HPC and ordered mesoporous carbon (OMC) in terms of their synthesis strategies and choices of template for self-assembly. How the remarkable mechanical strength of the HPCs can be achieved by selecting self-assembling template, whereas collapse of mesostructure
via
decomposition of framework occurs due to poor thermal stability or high N-content of the carbon source will be discussed.
Access to hierarchically porous carbons from polymers and biopolymers
via
a non-templating route has emerged as a promising strategy for a range of energy applications.
Although two‐dimensional (2D) carbon materials are widely investigated, a well‐defined 2D carbon nanosheet with an ordered mesostructure has rarely been realized. Monolayer‐ordered mesoporous carbon ...nanosheets (OMCNS) were prepared through confinement assembly of resol and F127 in the interlayer of montmorillonite (MONT). The nanoscale distance of the interlayer space of MONT only allow the assembly of resol and F127 in the same plane, leading to ordered mesopores perpendicular to carbon nanosheets, and favor the formation of sp2 carbon, resulting in a high degree of graphitization. The mesopores on the carbon nanosheets provide efficient ion diffusion, and the high degree of graphitization provides a fast electron‐transport route, enabling OMCNS as excellent electrode materials for electric double layer capacitors.
Ordered mesoporous carbon nanosheets (OMCNS) were prepared through confinement assembly of resol (see picture: blue) and F127 (yellow) in the interlayer of montmorillonite (MONT). The nanoscale interlayer space of MONT only allows the assembly of resol and F127 in the same plane, leading to ordered mesopores perpendicular to carbon nanosheets after carbonization.
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