This randomized trial involving patients with osteoarthritis or rheumatoid arthritis who were at increased cardiovascular risk showed the noninferiority of celecoxib to naproxen or ibuprofen with ...respect to cardiovascular safety.
Nonsteroidal antiinflammatory drugs (NSAIDs) were introduced in the 1960s and became the most widely prescribed class of drugs in the world, with more than 100 million prescriptions issued annually in the United States alone.
1
NSAIDs inhibit cyclooxygenase (COX), which reduces pain and inflammation through the inhibition of prostaglandins. However, the COX enzyme is also present in gastric mucosa, where it stimulates gastroprotective prostaglandins. The identification of two isoforms, COX-1 and COX-2, and the recognition that antiinflammatory and analgesic effects are mediated through COX-2 inhibition — whereas the gastrointestinal toxic effects are linked to COX-1 inhibition — resulted in the development . . .
Programmed cell death (PCD), referring to apoptosis, autophagy and programmed necrosis, is proposed to be death of a cell in any pathological format, when mediated by an intracellular program. These ...three forms of PCD may jointly decide the fate of cells of malignant neoplasms; apoptosis and programmed necrosis invariably contribute to cell death, whereas autophagy can play either pro‐survival or pro‐death roles. Recent bulk of accumulating evidence has contributed to a wealth of knowledge facilitating better understanding of cancer initiation and progression with the three distinctive types of cell death. To be able to decipher PCD signalling pathways may aid development of new targeted anti‐cancer therapeutic strategies. Thus in this review, we present a brief outline of apoptosis, autophagy and programmed necrosis pathways and apoptosis‐related microRNA regulation, in cancer. Taken together, understanding PCD and the complex interplay between apoptosis, autophagy and programmed necrosis may ultimately allow scientists and clinicians to harness the three types of PCD for discovery of further novel drug targets, in the future cancer treatment.
Background
The aim of this study was to investigate the prevalence of epidemiologic and physician‐diagnosed pollen‐induced AR (PiAR) in the grasslands of northern China and to study the impact of the ...intensity and time of pollen exposure on PiAR prevalence.
Methods
A multistage, clustered and proportionately stratified random sampling with a field interviewer‐administered survey study was performed together with skin prick tests (SPT) and measurements of the daily pollen count.
Results
A total of 6043 subjects completed the study, with a proportion of 32.4% epidemiologic AR and 18.5% PiAR. The prevalence was higher in males than females (19.6% vs 17.4%, P = .024), but no difference between the two major residential and ethnic groups (Han and Mongolian) was observed. Subjects from urban areas showed higher prevalence of PiAR than rural areas (23.1% vs 14.0%, P < .001). Most PiAR patients were sensitized to two or more pollens (79.4%) with artemisia, chenopodium, and humulus scandens being the most common pollen types, which were similarly found as the top three sensitizing pollen allergens by SPT. There were significant regional differences in the prevalence of epidemiologic AR (from 18.6% to 52.9%) and PiAR (from 10.5% to 31.4%) among the six areas investigated. PiAR symptoms were positively associated with pollen counts, temperature, and precipitation (P < .05), but negatively with wind speed and pressure P < .05).
Conclusion
Pollen‐induced AR (PiAR) prevalence in the investigated region is extremely high due to high seasonal pollen exposure, which was influenced by local environmental and climate conditions.
This is the first meta-analysis of the pooled prevalence of insomnia in the general population of China. A systematic literature search was conducted via the following databases: PubMed, PsycINFO, ...EMBASE and Chinese databases (China National Knowledge Interne (CNKI), WanFang Data and SinoMed). Statistical analyses were performed using the Comprehensive Meta-Analysis program. A total of 17 studies with 115,988 participants met the inclusion criteria for the analysis. The pooled prevalence of insomnia in China was 15.0% (95% Confidence interval CI: 12.1%-18.5%). No significant difference was found in the prevalence between genders or across time period. The pooled prevalence of insomnia in population with a mean age of 43.7 years and older (11.6%; 95% CI: 7.5%-17.6%) was significantly lower than in those with a mean age younger than 43.7 years (20.4%; 95% CI: 14.2%-28.2%). The prevalence of insomnia was significantly affected by the type of assessment tools (Q = 14.1, P = 0.001). The general population prevalence of insomnia in China is lower than those reported in Western countries but similar to those in Asian countries. Younger Chinese adults appear to suffer from more insomnia than older adults.
CRD 42016043620.
Two-dimensional (2D) materials have been studied extensively as monolayers, vertical or lateral heterostructures. To achieve functionalization, monolayers are often patterned using soft lithography ...and selectively decorated with molecules. Here we demonstrate the growth of a family of 2D materials that are intrinsically patterned. We demonstrate that a monolayer of PtSe
can be grown on a Pt substrate in the form of a triangular pattern of alternating 1T and 1H phases. Moreover, we show that, in a monolayer of CuSe grown on a Cu substrate, strain relaxation leads to periodic patterns of triangular nanopores with uniform size. Adsorption of different species at preferred pattern sites is also achieved, demonstrating that these materials can serve as templates for selective self-assembly of molecules or nanoclusters, as well as for the functionalization of the same substrate with two different species.
Summary
Background
Little is known about the role of the microbiome in primary sclerosing cholangitis.
Aim
To explore the mucosa‐associated microbiota in primary sclerosing cholangitis (PSC) patients ...across different locations in the gut, and to compare it with inflammatory bowel disease (IBD)‐only patients and healthy controls.
Methods
Biopsies from the terminal ileum, right colon, and left colon were collected from patients and healthy controls undergoing colonoscopy. Microbiota profiling using bacterial 16S rRNA sequencing was performed on all biopsies.
Results
Forty‐four patients were recruited: 20 with PSC (19 with PSC‐IBD and one with PSC‐only), 15 with IBD‐only and nine healthy controls. The overall microbiome profile was similar throughout different locations in the gut. No differences in the global microbiome profile were found. However, we observed significant PSC‐associated enrichment in Barnesiellaceae at the family level, and in Blautia and an unidentified Barnesiellaceae at the genus level. At the operational taxa unit level, most shifts in PSC were observed in Clostridiales and Bacteroidales orders, with approximately 86% of shifts occurring within the former order.
Conclusions
The overall microbiota profile was similar across multiple locations in the gut from the same individual regardless of disease status. In this study, the mucosa associated‐microbiota of patients with primary sclerosing cholangitis was characterised by enrichment of Blautia and Barnesiellaceae and by major shifts in operational taxa units within Clostridiales order.
Melanoma treatment is being revolutionized by the development of effective immunotherapeutic approaches. These strategies include blockade of immune-inhibitory receptors on activated T cells; for ...example, using monoclonal antibodies against CTLA-4, PD-1, and PD-L1 (refs 3-5). However, only a subset of patients responds to these treatments, and data suggest that therapeutic benefit is preferentially achieved in patients with a pre-existing T-cell response against their tumour, as evidenced by a baseline CD8(+) T-cell infiltration within the tumour microenvironment. Understanding the molecular mechanisms that underlie the presence or absence of a spontaneous anti-tumour T-cell response in subsets of cases, therefore, should enable the development of therapeutic solutions for patients lacking a T-cell infiltrate. Here we identify a melanoma-cell-intrinsic oncogenic pathway that contributes to a lack of T-cell infiltration in melanoma. Molecular analysis of human metastatic melanoma samples revealed a correlation between activation of the WNT/β-catenin signalling pathway and absence of a T-cell gene expression signature. Using autochthonous mouse melanoma models we identified the mechanism by which tumour-intrinsic active β-catenin signalling results in T-cell exclusion and resistance to anti-PD-L1/anti-CTLA-4 monoclonal antibody therapy. Specific oncogenic signals, therefore, can mediate cancer immune evasion and resistance to immunotherapies, pointing to new candidate targets for immune potentiation.
The final results of the search for the lepton flavour violating decay
μ
+
→
e
+
γ
based on the full dataset collected by the MEG experiment at the Paul Scherrer Institut in the period 2009–2013 and ...totalling
7.5
×
10
14
stopped muons on target are presented. No significant excess of events is observed in the dataset with respect to the expected background and a new upper limit on the branching ratio of this decay of
B
(
μ
+
→
e
+
γ
)
<
4.2
×
10
-
13
(90 % confidence level) is established, which represents the most stringent limit on the existence of this decay to date.
A
bstract
We study the conjectured holographic duality between entanglement of purification and the entanglement wedge cross-section. We generalize both quantities and prove several information ...theoretic inequalities involving them. These include upper bounds on conditional mutual information and tripartite information, as well as a lower bound for tripartite information. These inequalities are proven both holographically and for general quantum states. In addition, we use the cyclic entropy inequalities to derive a new holographic inequality for the entanglement wedge cross-section, and provide numerical evidence that the corresponding inequality for the entanglement of purification may be true in general. Finally, we use intuition from bit threads to extend the conjecture to holographic duals of suboptimal purifications.
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