Upper gastrointestinal bleeding (UGIB), especially peptic ulcer bleeding, remains one of the most important cause of hospitalisation and mortality world wide. In Asia, with a high prevalence of ...Helicobacter pylori infection, a potential difference in drug metabolism, and a difference in clinical management of UGIB due to variable socioeconomic environments, it is considered necessary to re-examine the International Consensus of Non-variceal Upper Gastrointestinal Bleeding with emphasis on data generated from the region. The working group, which comprised experts from 12 countries from Asia, recommended the use of the Blatchford score for selection of patients who require endoscopic intervention and which would allow early discharge of patients at low risk. Patients' comorbid conditions should be included in risk assessment. A pre-endoscopy proton pump inhibitor (PPI) is recommended as a stop-gap treatment when endoscopy within 24 h is not available. An adherent clot on a peptic ulcer should be treated with endoscopy combined with a PPI if the clot cannot be removed. Routine repeated endoscopy is not recommended. High-dose intravenous and oral PPIs are recommended but low-dose intravenous PPIs should be avoided. COX-2 selective non-steroidal anti-inflammatory drugs combined with a PPI are recommended for patients with very high risk of UGIB. Aspirin should be resumed soon after stabilisation and clopidogrel alone is no safer than aspirin plus a PPI. When dual antiplatelet agents are used, prophylactic use of a PPI reduces the risk of adverse gastrointestinal events.
We compile and analyze approximately 200 trigonometric parallaxes and proper motions of molecular masers associated with very young high-mass stars. Most of the measurements come from the BeSSeL ...Survey using the VLBA and the Japanese VERA project. These measurements strongly suggest that the Milky Way is a four-arm spiral, with some extra arm segments and spurs. Fitting log-periodic spirals to the locations of the masers, allowing for "kinks" in the spirals and using well-established arm tangencies in the fourth Galactic quadrant, allows us to significantly expand our view of the structure of the Milky Way. We present an updated model for its spiral structure and incorporate it into our previously published parallax-based distance-estimation program for sources associated with spiral arms. Modeling the three-dimensional space motions yields estimates of the distance to the Galactic center, , the circular rotation speed at the Sun's position, km s−1, and the nature of the rotation curve. Our data strongly constrain the full circular velocity of the Sun, km s−1, and its angular velocity, km s−1 kpc-1. Transforming the measured space motions to a Galactocentric frame which rotates with the Galaxy, we find non-circular velocity components typically 10 km s−1. However, near the Galactic bar and in a portion of the Perseus arm we find significantly larger non-circular motions. Young high-mass stars within 7 kpc of the Galactic center have a scale height of only 19 pc, and thus are well suited to define the Galactic plane. We find that the orientation of the plane is consistent with the IAU-defined plane to within 0 1, and that the Sun is offset toward the north Galactic pole by pc. Accounting for this offset places the central supermassive black hole, Sgr A*, in the midplane of the Galaxy. The measured motions perpendicular to the plane of the Galaxy limit precession of the plane to 4 km s−1 at the radius of the Sun. Using our improved Galactic parameters, we predict the Hulse-Taylor binary pulsar to be at a distance of 6.54 0.24 kpc, assuming its orbital decay from gravitational radiation follows general relativity.
Host immune peptides, including cathelicidins, have been reported to possess anticancer properties. We previously reported that LL-37, the only cathelicidin in humans, suppresses the development of ...colon cancer. In this study, the potential anticancer effect of FK-16, a fragment of LL-37 corresponding to residues 17 to 32, on cultured colon cancer cells was evaluated. FK-16 induced a unique pattern of cell death, marked by concurrent activation of caspase-independent apoptosis and autophagy. The former was mediated by the nuclear translocation of AIF and EndoG whereas the latter was characterized by enhanced expression of LC3-I/II, Atg5 and Atg7 and increased formation of LC3-positive autophagosomes. Knockdown of Atg5 or Atg7 attenuated the cytotoxicity of FK-16, indicating FK-16-induced autophagy was pro-death in nature. Mechanistically, FK-16 activated nuclear p53 to upregulate Bax and downregulate Bcl-2. Knockdown of p53, genetic ablation of Bax, or overexpression of Bcl-2 reversed FK-16-induced apoptosis and autophagy. Importantly, abolition of AIF/EndoG-dependent apoptosis enhanced FK-16-induced autophagy while abolition of autophagy augmented FK-16-induced AIF-/EndoG-dependent apoptosis. Collectively, FK-16 induces caspase-independent apoptosis and autophagy through the common p53-Bcl-2/Bax cascade in colon cancer cells. Our study also uncovered previously unknown reciprocal regulation between these two cell death pathways.
Alterations of gut microbiota are associated with colorectal cancer (CRC) in different populations and several bacterial species were found to contribute to the tumorigenesis. The potential use of ...gut microbes as markers for early diagnosis has also been reported. However, cohort specific noises may distort the structure of microbial dysbiosis in CRC and lead to inconsistent results among studies. In this regard, our study targeted at exploring changes in gut microbiota that are universal across populations at species level.
Based on the combined analysis of 526 metagenomic samples from Chinese, Austrian, American, and German and French cohorts, seven CRC-enriched bacteria (Bacteroides fragilis, Fusobacterium nucleatum, Porphyromonas asaccharolytica, Parvimonas micra, Prevotella intermedia, Alistipes finegoldii, and Thermanaerovibrio acidaminovorans) have been identified across populations. The seven enriched bacterial markers classified cases from controls with an area under the receiver-operating characteristics curve (AUC) of 0.80 across the different populations. Abundance correlation analysis demonstrated that CRC-enriched and CRC-depleted bacteria respectively formed their own mutualistic networks, in which the latter was disjointed in CRC. The CRC-enriched bacteria have been found to be correlated with lipopolysaccharide and energy biosynthetic pathways.
Our study identified potential diagnostic bacterial markers that are robust across populations, indicating their potential universal use for non-invasive CRC diagnosis. We also elucidated the ecological networks and functional capacities of CRC-associated microbiota.
Since the seminal work of Zhang in 2016, donor–acceptor cyanoarene-based fluorophores, such as 1,2,3,5-tetrakis(carbazol-9-yl)-4,6-dicyanobenzene (4CzIPN), have been widely applied in photoredox ...catalysis and used as excellent metal-free alternatives to noble metal Ir- and Ru-based photocatalysts. However, all the reported photoredox reactions involving this chromophore family are based on harnessing the energy from a single visible light photon, with a limited range of redox potentials from −1.92 to +1.79 V vs SCE. Here, we document the unprecedented discovery that this family of fluorophores can undergo consecutive photoinduced electron transfer (ConPET) to achieve very high reduction potentials. One of the newly synthesized catalysts, 2,4,5-tri(9H-carbazol-9-yl)-6-(ethyl(phenyl)amino)isophthalonitrile (3CzEPAIPN), possesses a long-lived (12.95 ns) excited radical anion form, 3CzEPAIPN•–*, which can be used to activate reductively recalcitrant aryl chlorides (E red ≈ −1.9 to −2.9 V vs SCE) under mild conditions. The resultant aryl radicals can be engaged in synthetically valuable aromatic C–B, C–P, and C–C bond formation to furnish arylboronates, arylphosphonium salts, arylphosphonates, and spirocyclic cyclohexadienes.
Associative learning, a critical learning principle to improve an individual's adaptability, has been emulated by few organic electrochemical devices. However, complicated bias schemes, high write ...voltages, as well as process irreversibility hinder the further development of associative learning circuits. Here, by adopting a poly(3,4-ethylenedioxythiophene):tosylate/Polytetrahydrofuran composite as the active channel, we present a non-volatile organic electrochemical transistor that shows a write bias less than 0.8 V and retention time longer than 200 min without decoupling the write and read operations. By incorporating a pressure sensor and a photoresistor, a neuromorphic circuit is demonstrated with the ability to associate two physical inputs (light and pressure) instead of normally demonstrated electrical inputs in other associative learning circuits. To unravel the non-volatility of this material, ultraviolet-visible-near-infrared spectroscopy, X-ray photoelectron spectroscopy and grazing-incidence wide-angle X-ray scattering are used to characterize the oxidation level variation, compositional change, and the structural modulation of the poly(3,4-ethylenedioxythiophene):tosylate/Polytetrahydrofuran films in various conductance states. The implementation of the associative learning circuit as well as the understanding of the non-volatile material represent critical advances for organic electrochemical devices in neuromorphic applications.
Colorectal cancer (CRC) development has been associated with increased proportions of Bacteroides fragilis and certain Streptococcus, Fusobacterium, and Peptostreptococcus species in the intestinal ...microbiota. We investigated associations between bacteremia from specific intestinal microbes and occurrence of CRC.
We performed a retrospective study after collecting data on 13,096 adult patients (exposed group) in Hong Kong hospitalized with bacteremia (identified by blood culture test) without a previous diagnosis of cancer from January 1, 2006 through December 31, 2015. We collected data on intestinal microbes previously associated with CRC (genera Bacteroides, Clostridium, Filifactor, Fusobacterium, Gemella, Granulicatella, Parvimonas, Peptostreptococcus, Prevotella, Solobacterium, and Streptococcus). Clinical information, including patient demographics, comorbid medical conditions, date of bacteremia, and bacterial species identified, were collected. The incidence of biopsy-proved CRC was compared between the exposed and unexposed (patients without bacteremia matched for age, sex, and comorbidities) groups.
The risk of CRC was increased in patients with bacteremia from B fragilis (hazard ratio HR = 3.85, 95% CI = 2.62–5.64, P = 5.5 × 10−12) or Streptococcus gallolyticus (HR = 5.73, 95% CI = 2.18–15.1, P = 4.1 × 10−4) compared with the unexposed group. In addition, the risk of CRC was increased in patients with bacteremia from Fusobacterium nucleatum (HR = 6.89, 95% CI = 1.70–27.9, P = .007), Peptostreptococcus species (HR = 3.06, 95% CI = 1.47–6.35, P = .003), Clostridium septicum (HR = 17.1, 95% CI = 1.82–160, P = .013), Clostridium perfringens (HR = 2.29, 95% CI = 1.16–4.52, P = .017), or Gemella morbillorum (HR = 15.2, 95% CI = 1.54–150, P = .020). We observed no increased risk in patients with bacteremia caused by microbes not previously associated with colorectal neoplasms.
In a retrospective analysis of patients hospitalized for bacteremia, we associated later diagnosis of CRC with B fragilis and S gallolyticus and other intestinal microbes. These bacteria might have entered the bloodstream from intestinal dysbiosis and perturbed barrier function. These findings support a model in which specific members of the intestinal microbiota promote colorectal carcinogenesis. Clinicians should evaluate patients with bacteremia from these species for neoplastic lesions in the colorectum.
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Inflammatory bowel disease is a global disease in the 21st century. We aimed to assess the changing incidence and prevalence of inflammatory bowel disease around the world.
We searched MEDLINE and ...Embase up to and including Dec 31, 2016, to identify observational, population-based studies reporting the incidence or prevalence of Crohn's disease or ulcerative colitis from 1990 or later. A study was regarded as population-based if it involved all residents within a specific area and the patients were representative of that area. To be included in the systematic review, ulcerative colitis and Crohn's disease needed to be reported separately. Studies that did not report original data and studies that reported only the incidence or prevalence of paediatric-onset inflammatory bowel disease (diagnosis at age <16 years) were excluded. We created choropleth maps for the incidence (119 studies) and prevalence (69 studies) of Crohn's disease and ulcerative colitis. We used temporal trend analyses to report changes as an annual percentage change (APC) with 95% CI.
We identified 147 studies that were eligible for final inclusion in the systematic review, including 119 studies of incidence and 69 studies of prevalence. The highest reported prevalence values were in Europe (ulcerative colitis 505 per 100 000 in Norway; Crohn's disease 322 per 100 000 in Germany) and North America (ulcerative colitis 286 per 100 000 in the USA; Crohn's disease 319 per 100 000 in Canada). The prevalence of inflammatory bowel disease exceeded 0·3% in North America, Oceania, and many countries in Europe. Overall, 16 (72·7%) of 22 studies on Crohn's disease and 15 (83·3%) of 18 studies on ulcerative colitis reported stable or decreasing incidence of inflammatory bowel disease in North America and Europe. Since 1990, incidence has been rising in newly industrialised countries in Africa, Asia, and South America, including Brazil (APC for Crohn's disease +11·1% 95% CI 4·8–17·8 and APC for ulcerative colitis +14·9% 10·4–19·6) and Taiwan (APC for Crohn's disease +4·0% 1·0–7·1 and APC for ulcerative colitis +4·8% 1·8–8·0).
At the turn of the 21st century, inflammatory bowel disease has become a global disease with accelerating incidence in newly industrialised countries whose societies have become more westernised. Although incidence is stabilising in western countries, burden remains high as prevalence surpasses 0·3%. These data highlight the need for research into prevention of inflammatory bowel disease and innovations in health-care systems to manage this complex and costly disease.
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