We conducted a genome-wide association study of pancreatic cancer in 3,851 affected individuals (cases) and 3,934 unaffected controls drawn from 12 prospective cohort studies and 8 case-control ...studies. Based on a logistic regression model for genotype trend effect that was adjusted for study, age, sex, self-described ancestry and five principal components, we identified eight SNPs that map to three loci on chromosomes 13q22.1, 1q32.1 and 5p15.33. Two correlated SNPs, rs9543325 (P = 3.27 × 10−11, per-allele odds ratio (OR) 1.26, 95% CI 1.18-1.35) and rs9564966 (P = 5.86 × 10−8, per-allele OR 1.21, 95% CI 1.13-1.30), map to a nongenic region on chromosome 13q22.1. Five SNPs on 1q32.1 map to NR5A2, and the strongest signal was at rs3790844 (P = 2.45 × 10−10, per-allele OR 0.77, 95% CI 0.71-0.84). A single SNP, rs401681 (P = 3.66 × 10−7, per-allele OR 1.19, 95% CI 1.11-1.27), maps to the CLPTM1L-TERT locus on 5p15.33, which is associated with multiple cancers. Our study has identified common susceptibility loci for pancreatic cancer that warrant follow-up studies.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Coffee and tea contain numerous antimutagenic and antioxidant components and high levels of caffeine that may protect against colorectal cancer (CRC). We investigated the association between coffee ...and tea consumption and CRC risk and studied potential effect modification by CYP1A2 and NAT2 genotypes, enzymes involved in the metabolization of caffeine. Data from 477,071 participants (70.2% female) of the European Investigation into Cancer and Nutrition (EPIC) cohort study were analyzed. At baseline (1992–2000) habitual (total, caffeinated and decaffeinated) coffee and tea consumption was assessed with dietary questionnaires. Cox proportional hazards models were used to estimate adjusted hazard ratio's (HR) and 95% confidence intervals (95% CI). Potential effect modification by genotype‐based CYP1A2 and NAT2 activity was studied in a nested case–control set of 1,252 cases and 2,175 controls. After a median follow‐up of 11.6 years, 4,234 participants developed CRC (mean age 64.7 ± 8.3 years). Total coffee consumption (high vs. non/low) was not associated with CRC risk (HR 1.06, 95% CI 0.95–1.18) or subsite cancers, and no significant associations were found for caffeinated (HR 1.10, 95% CI 0.97–1.26) and decaffeinated coffee (HR 0.96, 95% CI 0.84–1.11) and tea (HR 0.97, 95% CI 0.86–1.09). High coffee and tea consuming subjects with slow CYP1A2 or NAT2 activity had a similar CRC risk compared to non/low coffee and tea consuming subjects with a fast CYP1A2 or NAT2 activity, which suggests that caffeine metabolism does not affect the link between coffee and tea consumption and CRC risk. This study shows that coffee and tea consumption is not likely to be associated with overall CRC.
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Coffee and tea contain numerous compounds that may protect against colorectal cancer (CRC). In this study of more than 475,000 participants over more than a decade, the authors investigated whether coffee or tea consumption is associated with an altered risk of developing CRC. They also asked whether genetic variations in two enzymes involved in caffeine metabolism (CYP1A2 and NAT2) might affect this risk. They conclude that neither consumption patterns, nor genetic differences in caffeine metabolism, appear to have a significant impact on CRC risk.
The intervertebral disc (IVD) allows flexibility to the vertebral column, and transfers the predominant axial loads during daily activities. Its axial biomechanical behaviour is poroelastic, due to ...the water-binding and releasing capacity of the nucleus pulposus. Degeneration of the intervertebral disc presumably affects both the instantaneous elastic response to the load on the IVD and the subsequent interstitial flow of fluid. This study aims to quantify the poroelastic behaviour of the IVD and its change with degeneration, as defined by the magnetic resonance imaging-based Pfirrmann Score (PS). For a period of ten days, 36 human lumbar IVDs were loaded with a simulated physiological axial loading regime, while deformation was monitored. The IVDs responded to the loads with instantaneous elastic and slow poroelastic axial deformation. Several mechanical parameters changed throughout the first five days of the experiment, until the IVDs settled into a dynamic equilibrium. In this equilibrium, degeneration was significantly related to a decrease in disc height loss during the daytime high load phase (ρ = -0.49), and to a decrease in the rate of this deformation during the final half hour of each day (ρ = -0.53). These properties were related to the nucleus glycosaminoglycan/hydroxyproline (GAG/HYP) ratio, rather than GAG content alone, indicating that remodelling of the extracellular matrix reduces poroelastic properties of the IVD. This implies that the degenerated discs have a reduced capacity to bind water and/or a reduced resistance against fluid flow. The resulting loss in hydrostatic pressure may further change cell behaviour in the nucleus pulposus.
Plants defend themselves against infection by biotic attackers by producing distinct phytohormones. Especially jasmonic acid (JA) and salicylic acid (SA) are well known defense-inducing hormones. ...Here, the effects of MeJA and SA on the Arabidopsis thaliana kinome were monitored using PepChip arrays containing kinase substrate peptides to analyze posttranslational interactions in MeJA and SA signaling pathways and to test if kinome profiling can provide leads to predict posttranslational events in plant signaling. MeJA and SA mediate differential phosphorylation of substrates for many kinase families. Also some plant specific substrates were differentially phosphorylated, including peptides derived from Phytochrome A, and Photosystem II D protein. This indicates that MeJA and SA mediate cross-talk between defense signaling and light responses. We tested the predicted effects of MeJA and SA using light-mediated upward leaf movement (differential petiole growth also called hyponastic growth). We found that MeJA, infestation by the JA-inducing insect herbivore Pieris rapae, and SA suppressed low light-induced hyponastic growth. MeJA and SA acted in a synergistic fashion via two (partially) divergent signaling routes. This work demonstrates that kinome profiling using PepChip arrays can be a valuable complementary ∼omics tool to give directions towards predicting behavior of organisms after a given stimulus and can be used to obtain leads for physiological relevant phenomena in planta.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
A large proportion of people who sustain a whiplash injury will have persistent pain, disability, and participation problems. Several prognostic factors for functional recovery have been reported in ...the literature but these factors are often evaluated based on differing implementations in clinical practice. Additionally, physiotherapists also rely on their clinical intuition to estimate the functional prognosis of their patients, but this is seldom measured in experimental research. Furthermore, no study to date has explored the associations between clinical intuition, clinically estimated factors, and objectively measured factors for functional recovery of patients with Whiplash-Associated Disorders (WAD).
The aim of this exploratory study is to evaluate associations between prognostic factors for functional recovery, based on routinely collected data in a specialized primary care physiotherapy practice in a consecutive sample of patients (n = 523) with WAD.
Three sources of prognostic factors were selected: (1) physiotherapists' synthesis of clinical intuition in terms of high-risk, inconclusive risk, or low-risk for functional recovery, (2) patient-registered factors from history taking, and (3) patient-reported prognostic factors derived from questionnaires. Prognostic factors were selected based on the literature, recommendations in Dutch clinical practice guidelines, and consensus between experts. Spearman's rank correlation coefficients were calculated to explore the associations between sources of prognostic factors, using a cutoff ≥0.25 for acceptable association.
Associations between physiotherapists' intuitive synthesis and patient-registered variables were substantial (
= 0.86), between patient-registered variables and patient-reported variables fair (ranging from 0.30 to 0.41) to substantial (ranging from 0.69 to 0.73), and between physiotherapists intuitive synthesis and patient-reported variables fair (ranging from 0.30 to 0.37).
When estimating prognosis for functional recovery using clinical reasoning, physiotherapists should integrate patients' registered experience of their course of recovery, as well as the timeline after an accident, with their own synthesis of clinical intuition regarding prognostic factors in patients with WAD.
This study was performed in order to assess morbidity and mortality associated with major lower extremity amputation according to an extensive complication registration system used in our hospital.
...All consecutive patients who underwent lower limb major extremity amputation were included from January 1996 until December 2002. Complications were prospectively registered according to our standard complication registration system.
In 97 patients 122 amputations were performed including 45 above (AKA) and 77 below (BKA) knee amputations. The conversion rate from below to above knee amputation was 14%. In 65 patients 107 complications occurred (67%). The incidence of wound infection was 10% in the BKA group and 2% in the AKA group. The most frequently reported complications were pressure sores (8%) or originating from the urinary tract (13%). The hospital mortality for BKA was 9% and for AKA 18%. Long-term survival was 62% at 1 year, 50% at 2 years and 29% at 5 years.
An extensive registration system provides us with a detailed insight into the incidence, consequence and cause of complications. Major lower extremity amputations are still associated with considerable morbidity and mortality.
Recently, some US cohorts have shown a moderate association between red and processed meat consumption and mortality supporting the results of previous studies among vegetarians. The aim of this ...study was to examine the association of red meat, processed meat, and poultry consumption with the risk of early death in the European Prospective Investigation into Cancer and Nutrition (EPIC).
Included in the analysis were 448,568 men and women without prevalent cancer, stroke, or myocardial infarction, and with complete information on diet, smoking, physical activity and body mass index, who were between 35 and 69 years old at baseline. Cox proportional hazards regression was used to examine the association of meat consumption with all-cause and cause-specific mortality.
As of June 2009, 26,344 deaths were observed. After multivariate adjustment, a high consumption of red meat was related to higher all-cause mortality (hazard ratio (HR) = 1.14, 95% confidence interval (CI) 1.01 to 1.28, 160+ versus 10 to 19.9 g/day), and the association was stronger for processed meat (HR = 1.44, 95% CI 1.24 to 1.66, 160+ versus 10 to 19.9 g/day). After correction for measurement error, higher all-cause mortality remained significant only for processed meat (HR = 1.18, 95% CI 1.11 to 1.25, per 50 g/d). We estimated that 3.3% (95% CI 1.5% to 5.0%) of deaths could be prevented if all participants had a processed meat consumption of less than 20 g/day. Significant associations with processed meat intake were observed for cardiovascular diseases, cancer, and 'other causes of death'. The consumption of poultry was not related to all-cause mortality.
The results of our analysis support a moderate positive association between processed meat consumption and mortality, in particular due to cardiovascular diseases, but also to cancer.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
We investigated whether a varied consumption of vegetables and fruits is associated with lower lung cancer risk in the European Prospective Investigation into Cancer and Nutrition study.
After a mean ...follow-up of 8.7 years, 1,613 of 452,187 participants with complete information were diagnosed with lung cancer. Diet diversity scores (DDS) were used to quantify the variety in fruit and vegetable consumption. Multivariable proportional hazards models were used to assess the associations between DDS and lung cancer risk. All models were adjusted for smoking behavior and the total consumption of fruit and vegetables.
With increasing variety in vegetable subgroups, risk of lung cancer decreases hazard ratios (HR), 0.77; 95% confidence interval (CI), 0.64-0.94 highest versus lowest quartile; P trend = 0.02. This inverse association is restricted to current smokers (HR, 0.73; 95% CI, 0.57-0.93 highest versus lowest quartile; P trend = 0.03). In continuous analyses, in current smokers, lower risks were observed for squamous cell carcinomas with more variety in fruit and vegetable products combined (HR/two products, 0.88; 95% CI, 0.82-0.95), vegetable subgroups (HR/subgroup, 0.88; 95% CI, 0.79-0.97), vegetable products (HR/two products, 0.87; 95% CI, 0.79-0.96), and fruit products (HR/two products, 0.84; 95% CI, 0.72-0.97).
Variety in vegetable consumption was inversely associated with lung cancer risk among current smokers. Risk of squamous cell carcinomas was reduced with increasing variety in fruit and/or vegetable consumption, which was mainly driven by the effect in current smokers.
Independent from quantity of consumption, variety in fruit and vegetable consumption may decrease lung cancer risk.
Based on the metastable electron-pair energy band in a two-dimensional (2D) periodic potential obtained previously by Hai and Castelano J. Phys.: Condens. Matter
26
, 115502 (2014), we present in ...this work a Hamiltonian of many electrons consisting of single electrons and electron pairs in the 2D system. The electron-pair states are metastable of energies higher than those of the single-electron states at low electron density. We assume two different scenarios for the single-electron band. When it is considered as the lowest conduction band of a crystal, we compare the obtained Hamiltonian with the phenomenological model Hamiltonian of a boson-fermion mixture proposed by Friedberg and Lee Phys. Rev. B
40
, 6745 (1989). Single-electron-electron-pair and electron-pair-electron-pair interaction terms appear in our Hamiltonian and the interaction potentials can be determined from the electron-electron Coulomb interactions. When we consider the single-electron band as the highest valence band of a crystal, we show that holes in this valence band are important for stabilization of the electron-pair states in the system.
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