In patients with celiac disease, gluten triggers an immune reaction that damages small intestinal villi and may increase long-term risk of gastrointestinal cancer. However, the health impacts of ...gluten in the general population are understudied. We aimed to examine the association between gluten intake and risk of digestive system cancers among individuals without celiac disease.
We leveraged longitudinal data from 3 prospective cohorts, the Nurses' Health Study (1984-2018, 73,166 women aged 65.1 ± 10.8 years), Nurses' Health Study II (1991-2017, 90,423 women aged 49.1 ± 8.2 years), and Health Professionals Follow-Up Study (1986-2016, 42,617 men aged 64.8 ± 10.8 years). Using Cox proportional hazards regression, we estimated hazard ratios and 95% confidence intervals of digestive system cancers according to quintiles of gluten intake assessed from food frequency questionnaires.
During 4,801,513 person-years of follow-up, we documented 6231 incident digestive system cancer cases among 3 cohorts. After adjusting for a wide-range of risk factors, including body mass index, physical activity, diet quality, gluten intake was not associated with an increased risk of digestive system cancer, with a hazard ratio of 0.94 (95% confidence interval, 0.87-1.02) comparing the highest with the lowest quintile of gluten intake (P trend = .05). Similar null associations were found for individual digestive system cancers: oral cavity and oropharyngeal cancer, esophageal cancer, stomach cancer, small intestine cancer, colorectal cancer, pancreatic cancer, gallbladder cancer, and liver cancer.
Gluten intake was not associated with risk of digestive system cancers in adults without celiac disease. Restricting dietary gluten is unlikely to be beneficial to the prevention of digestive system cancers in the general population.
The extension of the cosmic-ray spectrum beyond 1 petaelectronvolt (PeV; 10
electronvolts) indicates the existence of the so-called PeVatrons-cosmic-ray factories that accelerate particles to PeV ...energies. We need to locate and identify such objects to find the origin of Galactic cosmic rays
. The principal signature of both electron and proton PeVatrons is ultrahigh-energy (exceeding 100 TeV) γ radiation. Evidence of the presence of a proton PeVatron has been found in the Galactic Centre, according to the detection of a hard-spectrum radiation extending to 0.04 PeV (ref.
). Although γ-rays with energies slightly higher than 0.1 PeV have been reported from a few objects in the Galactic plane
, unbiased identification and in-depth exploration of PeVatrons requires detection of γ-rays with energies well above 0.1 PeV. Here we report the detection of more than 530 photons at energies above 100 teraelectronvolts and up to 1.4 PeV from 12 ultrahigh-energy γ-ray sources with a statistical significance greater than seven standard deviations. Despite having several potential counterparts in their proximity, including pulsar wind nebulae, supernova remnants and star-forming regions, the PeVatrons responsible for the ultrahigh-energy γ-rays have not yet been firmly localized and identified (except for the Crab Nebula), leaving open the origin of these extreme accelerators.
Background
Besides physical activity as a target for dementia prevention, sedentary behaviour is hypothesized to be a potential target in its own right. The rising number of persons with dementia and ...lack of any effective treatment highlight the urgency to better understand these modifiable risk factors. Therefore, we aimed to investigate whether higher levels of sedentary behaviour are associated with reduced global cognitive functioning and slower cognitive decline in older persons without dementia.
Methods
We used five population cohorts from Greece, Australia, USA, Japan, and Singapore (HELIAD, PATH, SALSA, SGS, and SLAS2) from the Cohort Studies of Memory in an International Consortium. In a coordinated analysis, we assessed the relationship between sedentary behaviour and global cognitive function with the use of linear mixed growth model analysis (mean follow-up range of 2.0–8.1 years).
Results
Baseline datasets combined 10,450 older adults without dementia with a mean age range between cohorts of 66.7–75.1 years. After adjusting for multiple covariates, no cross-sectional association between sedentary behaviour and cognition was found in four studies. One association was detected where more sedentary behaviour was cross-sectionally linked to higher cognition levels (SLAS2,
B
= 0.118 (0.075; 0.160),
P
< 0.001). Longitudinally, there were no associations between baseline sedentary behaviour and cognitive decline (
P
> 0.05).
Conclusions
Overall, these results do not suggest an association between total sedentary time and lower global cognition in older persons without dementia at baseline or over time. We hypothesize that specific types of sedentary behaviour may differentially influence cognition which should be investigated further. For now, it is, however, too early to establish undifferentiated sedentary time as a potential effective target for minimizing cognitive decline in older adults without dementia.
Sublethal ischemic preconditioning (IPC) is a powerful inducer of ischemic brain tolerance. However, its underlying mechanisms are still not well understood. In this study, we chose four different ...IPC paradigms, namely 5 min (5 min duration), 5×5 min (5 min duration, 2 episodes, 15-min interval), 5×5×5 min (5 min duration, 3 episodes, 15-min intervals), and 15 min (15 min duration), and demonstrated that three episodes of 5 min IPC activated autophagy to the greatest extent 24 h after IPC, as evidenced by Beclin expression and LC3-I/II conversion. Autophagic activation was mediated by the tuberous sclerosis type 1 (TSC1)-mTor signal pathway as IPC increased TSC1 but decreased mTor phosphorylation. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and hematoxylin and eosin staining confirmed that IPC protected against cerebral ischemic/reperfusion (I/R) injury. Critically, 3-methyladenine, an inhibitor of autophagy, abolished the neuroprotection of IPC and, by contrast, rapamycin, an autophagy inducer, potentiated it. Cleaved caspase-3 expression, neurological scores, and infarct volume in different groups further confirmed the protection of IPC against I/R injury. Taken together, our data indicate that autophagy activation might underlie the protection of IPC against ischemic injury by inhibiting apoptosis.
Summary
Background
Coeliac disease has been linked to anxiety and depression. However, their association with mucosal healing is unknown.
Aim
To examine the relationship between anxiety, depression ...and mucosal healing in coeliac disease.
Methods
Between 1969 and 2008, we collected data on all small intestinal biopsies with villous atrophy from Sweden's 28 pathology departments. We restricted our cohort to individuals with data on follow‐up biopsy (either persistent villous atrophy n = 3317 or mucosal healing n = 4331). Through Cox regression, we estimated hazard ratios (HRs) for anxiety or depression.
Results
During follow‐up, 123 (2.8/1000 person‐years) individuals with mucosal healing had developed anxiety, compared to 94 (2.1/1000 person‐years) with persistent villous atrophy. Mucosal healing was hence associated with a higher risk of future anxiety (HR = 1.49; 95% CI = 1.12‐1.96). Similarly, 167 (3.8/1000 person‐years) individuals with mucosal healing developed depression, compared to 148 (3.3/1000 person‐years) with persistent villous atrophy, corresponding to a HR of 1.25 (95% CI = 0.99‐1.59). Mucosal healing was more common in individuals with prior diagnoses of anxiety or depression before follow‐up biopsy. Anxiety diagnosed between diagnostic and follow‐up biopsy for coeliac disease was associated with an almost nine‐fold increased chance of mucosal healing (odds ratio = 8.94; 95%CI = 2.03‐39.27).
Conclusion
Anxiety and depression are more common in coeliac disease patients with mucosal healing, both before and after follow‐up biopsy, an association potentially mediated through more vigilant compliance with a gluten‐free diet. This finding raises concern that achieving the goal of mucosal healing may come at a cost of an increased risk of mood disorders.
We present a new determination of the smallest neutrino mixing angle θ_{13} and the mass-squared difference Δm_{32}^{2} using a final sample of 5.55×10^{6} inverse beta-decay (IBD) candidates with ...the final-state neutron captured on gadolinium. This sample is selected from the complete dataset obtained by the Daya Bay reactor neutrino experiment in 3158 days of operation. Compared to the previous Daya Bay results, selection of IBD candidates has been optimized, energy calibration refined, and treatment of backgrounds further improved. The resulting oscillation parameters are sin^{2}2θ_{13}=0.0851±0.0024, Δm_{32}^{2}=(2.466±0.060)×10^{-3} eV^{2} for the normal mass ordering or Δm_{32}^{2}=-(2.571±0.060)×10^{-3} eV^{2} for the inverted mass ordering.
Full text
Available for:
CMK, CTK, FMFMET, NUK, UL
Aging is associated with cognitive decline and memory loss in humans. In rats, aging-associated neuronal excitability changes and impairments in learning have been extensively studied in the ...hippocampus. Here, we investigated the roles of L-type calcium channels (LTCCs) in the rat piriform cortex (PC), in comparison with those of the hippocampus. We employed spatial and olfactory tasks that involve the hippocampus and PC. LTCC blocker nimodipine administration impaired spontaneous location recognition in adult rats (6-9 months). However, the same blocker rescued the spatial learning deficiency in aged rats (19-23 months). In an odor-associative learning task, infusions of nimodipine into either the PC or dorsal CA1 impaired the ability of adult rats to learn a positive odor association. Again, in contrast, nimodipine rescued odor associative learning in aged rats. Aged CA1 neurons had higher somatic expression of LTCC Cav1.2 subunits, exhibited larger afterhyperpolarization (AHP) and lower excitability compared with adult neurons. In contrast, PC neurons from aged rats showed higher excitability and no difference in AHP. Cav1.2 expression was similar in adult and aged PC somata, but relatively higher in PSD95- puncta in aged dendrites. Our data suggest unique features of aging-associated changes in LTCCs in the PC and hippocampus.
Abstract
The establishment of a possible connection between neutrino emission and gravitational-wave (GW) bursts is important to our understanding of the physical processes that occur when black ...holes or neutron stars merge. In the Daya Bay experiment, using the data collected from December 2011 to August 2017, a search was performed for electron-antineutrino signals that coincided with detected GW events, including GW150914, GW151012, GW151226, GW170104, GW170608, GW170814, and GW170817. We used three time windows of ±10, ±500, and ±1000 s relative to the occurrence of the GW events and a neutrino energy range of 1.8 to 100 MeV to search for correlated neutrino candidates. The detected electron-antineutrino candidates were consistent with the expected background rates for all the three time windows. Assuming monochromatic spectra, we found upper limits (90% confidence level) of the electron-antineutrino fluence of (1.13 − 2.44)×10
11
cm
−2
at 5 MeV to 8.0×10
7
cm
−2
at 100 MeV for the three time windows. Under the assumption of a Fermi-Dirac spectrum, the upper limits were found to be (5.4 − 7.0)×10
9
cm
−2
for the three time windows.
The purpose of this study was to explore the effect of micro ribonucleic acid (miR)-145 on the apoptosis of chondrocytes in osteoarthritis (OA), and to research the association between its targeting ...on B-cell lymphoma-2 (Bcl-2)/adenovirus E1B 19 kDa interacting protein 3 (BNIP3) and Notch signaling pathway and chondrocyte apoptosis.
The mouse model of OA was established via surgery, and chondrocytes were isolated and cultured in vitro. Then, the chondrocytes were transfected with miR-145 inhibitor, miR-145 mimics, miR-negative control (NC), BNIP3-siRNA and BNIP3-vector, respectively, with those normally cultured as the control. After that, the expression levels of miR-145 and BNIP3 in cells were detected via quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR), the apoptosis rate was detected via flow cytometry, and the apoptosis level was detected using terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. Moreover, the target gene sequences were predicted and compared using the software, and the BNIP3 Luciferase reporter vectors containing predicted target sites for miR-145 were constructed. Finally, the protein expressions of BNIP3, Notch1, and P21 were determined through Western blotting.
The results of qRT-PCR showed that in OA chondrocytes, the expression of miR-145 was lower than that in normal chondrocytes (p<0.05), while the mRNA and protein expressions of BNIP3 were higher than those in normal chondrocytes (p<0.05). According to flow cytometry, the apoptosis rate was (4.4±0.6)% in normal cartilage tissues and (29.2±2.1)% in OA cartilage tissues. Overexpression of miR-145 significantly reduced chondrocyte apoptosis (p<0.05), while overexpression of BNIP3 markedly increased chondrocyte apoptosis (p<0.05). In addition, the Luciferase reporter system showed that miR-145 mimics evidently inhibited BNIP3 (p<0.05) and suppressed the Notch signaling pathway (p<0.05), while BNIP3 enhanced the expression of Notch signaling pathway (p<0.05).
MiR-145 can reduce OA-induced chondrocyte apoptosis through targeted inhibition on BNIP3 and regulation on Notch signaling pathway.
A new measurement of the reactor antineutrino flux and energy spectrum by the Daya Bay reactor neutrino experiment is reported. The antineutrinos were generated by six 2.9 GWth nuclear reactors and ...detected by eight antineutrino detectors deployed in two near（560 m and 600 m flux-weighted baselines） and one far（1640 m flux-weighted baseline） underground experimental halls. With 621 days of data, more than 1.2 million inverse beta decay（IBD） candidates were detected. The IBD yield in the eight detectors was measured, and the ratio of measured to predicted flux was found to be 0.946±0.020（0.992±0.021） for the Huber＋Mueller（ILL＋Vogel） model. A 2.9σ deviation was found in the measured IBD positron energy spectrum compared to the predictions. In particular, an excess of events in the region of 4–6 MeV was found in the measured spectrum, with a local significance of 4.4σ. A reactor antineutrino spectrum weighted by the IBD cross section is extracted for model-independent predictions.
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