Colorectal cancer is one of the most common cancers in Western countries. The World Health Organisation identifies diet as a critical risk factor in the development and progression of this disease ...and the protective role of high levels of fruit and vegetable consumption. Several studies have shown that apples contain several phenolic compounds that are potent anti-oxidants in humans. However, little is known about other beneficial properties of apple phenolics in cancer. We have used the HT29, HT115 and CaCo-2 cell lines as
in vitro models to examine the effect of apple phenolics (0.01–0.1% apple extract) on key stages of colorectal carcinogenesis, namely; DNA damage (Comet assay), colonic barrier function (TER assay), cell cycle progression (DNA content assay) and invasion (Matrigel assay). Our results indicate that a crude extract of apple phenolics can protect against DNA damage, improve barrier function and inhibit invasion (
p
<
0.05). The anti-invasive effects of the extract were enhanced with twenty-four hour pretreatment of cells (
p
<
0.05). We have shown that a crude apple extract from waste, rich in phenolic compounds, beneficially influences key stages of carcinogenesis in colon cells
in vitro.
Periconceptional nutrition (PCN) can influence foetal hypothalamo-pituitary adrenal (HPA) axis function and alter cortisol secretion with possible consequences for maturation and growth of major ...organs, gestation length and behaviour. We examined effects of PCN on phenotype and survival of the neonatal lamb in 466 Merino ewes allocated to treatments providing 70%, 100% and 150% respectively, of maintenance requirements for 17 days prior and 6 days after insemination. Gestation length and birth weight for lambs in PCN treatment groups was similar (P>0.05) but low PCN decreased the size of the neonate (crown-rump-length and metacarpal length P<0.05). A subset of lambs euthanased at 5 days of age further showed that low PCN decreased the amount of peri-renal fat (P<0.05) and increased liver mass (P<0.05) while high PCN increased neck thymus and ovary mass (P<0.05). Neonatal lambs from low PCN ewes returned faster to their mothers after release (P<0.05) and contacted the udder in the shortest time (P<0.05). Significant interactions between PCN treatment and sex (P<0.05) and between PCN treatment and ewe age (P<0.05) were also observed for time lambs took to follow the ewe. Survival of lambs was similar but potential differences may have been masked by favourable weather conditions. In conclusion, this study provides evidence of significant changes in lamb growth and development dependent on PCN and, for the first time, links these changes with significant changes in behaviour of the neonate. The impact of these effects on lamb survival and potential reproductive capacity of female offspring remains to be determined.
Prosthetic arteriovenous grafts (AVGs) conventionally used for hemodialysis are associated with inferior primary patency rates and increased risk of infection compared with autogenous vein grafts. We ...tissue-engineered an AVG grown from neonatal human dermal fibroblasts entrapped in bovine fibrin gel that is then decellularized. This graft is both "off-the-shelf" (nonliving) and completely biological. Grafts that are 6 mm in diameter and about 15 cm in length were evaluated in a baboon model of hemodialysis access in an axillary-cephalic or axillary-brachial upper arm AVG construction procedure. Daily antiplatelet therapy was given. Grafts underwent both ultrasound assessment and cannulation at 1, 2, 3, and 6 months and were then explanted for analysis. Excluding grafts with cephalic vein outflow that rapidly clotted during development of the model, 3- and 6-month primary patency rates were 83% (5 of 6) and 60% (3 of 5), respectively. At explant, patent grafts were found to be extensively recellularized (including smoothelin-positive smooth muscle cells with a developing endothelium on the luminal surface). We observed no calcifications, loss of burst strength, or outflow stenosis, which are common failure modes of other graft materials. There was no overt immune response. We thus demonstrate the efficacy of an off-the-shelf AVG that is both acellular and completely biological.
Background. In 2000, results of a multinational trial demonstrated that a 2-month course of rifampin and pyrazinamide (RZ) was as effective as isoniazid (INH) in reducing tuberculosis in human ...immunodeficiency virus (HIV)—infected individuals with latent tuberculosis infection (LTBI). After the release of new guidelines, the Centers for Disease Control and Prevention received reports of severe hepatotoxicity associated with the use of the RZ regimen for the treatment of LTBI in the general population. To better understand the occurrence of hepatotoxicity in an HIV-infected population, we conducted a more detailed analysis of the liver function test results obtained in the multinational trial of RZ. Methods. At study entry, patients were required to have a bilirubin level of ⩽2.5 mg/dL and both an aspartate aminotransferase (AST) level and an alkaline phosphatase level of ⩽5 times the upper limit of normal. Patients with acute hepatitis were excluded. At months 1 and 2 of the study, all patients had bilirubin and AST levels measured. Results. There was no difference between the RZ and INH groups with regard to AST level or bilirubin level at baseline. An increase in the AST level of ⩾40 U/L was associated with the use of INH and older age; and an increase in the bilirubin level of ⩾0.5 mg/dL was associated with the use of RZ, male sex, and nonwhite race (P < .05). An absolute AST level of >250 U/L occurred in 12 of 745 INH recipients and in 15 of 721 RZ recipients (P = .56), and an absolute bilirubin level of >2.5 mg/dL occurred in 5 of 743 INH recipients and 13 of 718 RZ recipients (P = .06). Conclusions. These data demonstrate very little liver injury associated with either INH or RZ in the HIV-infected subjects, leaving unclear the reasons for serious RZ-related liver damage in the general population.
Abstract
Funding Acknowledgements
Type of funding sources: Public grant(s) – EU funding. Main funding source(s): EU Horizon 2020 SME Instrument.
Background
Epicardial ganglionated plexi (GP) play a ...significant role in the initiation and maintenance of atrial fibrillation. However, modulation of this effect, through GP ablation, has had limited success; outcomes being confounded by unnecessary atrial tissue ablation and inability to access and ablate all of the atrial GPs. Selective pulsed field ablation (PFA) of GPs, using epicardial access, provides the opportunity to better identify the role of GP ablation in the treatment of atrial fibrillation.
Purpose
This study aimed to assess the safety and feasibility of selective GP ablation in patients undergoing elective coronary artery bypass grafting (CABG). It was hypothesized that GP ablation would provide an acute extension of atrial tissue refractoriness, which constitutes its antiarrhythmic effect.
Methods
Using a monopolar, monophasic PFA system, atrial GPs were ablated in nineteen patients with or without atrial fibrillation, undergoing CABG. The Oblique Sinus GP, Right Superior GP, Transverse Sinus GP, Left Superior GP and Ligament of Marshall GP were each ablated with up to sixty PFA pulses of 1000 V amplitude and 100 µs pulse width. Atrial Effective Refractory Period (AERP) was measured before and after all GP ablations, at the left atrial appendage (LAA) and on the right atrium (RA). Patients were monitored through to discharge for post-operative atrial fibrillation (POAF).
Results
Complete ablation of the GPs was performed in nineteen patients (aged 63.4 ± 6.6 years, 63.1% male) immediately after sternotomy. Electric field pulses were ECG-gated, with energy delivery during the ventricular refractory period. All GP sites were successfully accessed and ablated; all patients progressed immediately to their planned elective surgery and were discharged on schedule. Procedure time, for all GP ablations and AERP measurements was in the range 35-45 minutes. Thirteen valid pre- and post-ablation datasets were obtained. AERP (LAA and RA combined) increased upon GP ablation on average by 23% (220 ± 46 ms pre-ablation versus 269 ± 59 ms post-ablation, p = 0.002). Four patients experienced POAF; there was no evident correlation between POAF and AERP data. Only three of the enrolled patients had a prior history of AF; none of these exhibited AF on 24-hour Holter monitoring at 3-month follow-up.
Conclusions
Selective epicardial PFA of GPs is feasible and safe. An acute increase in atrial tissue refractoriness is promising but further studies are required to see how this translates to longer term outcomes in symptomatic AF patients and in a percutaneous epicardial access setting.
Abstract The gut microbiota interacts with the host via neuroimmune, neuroendocrine and neural pathways. These pathways are components of the brain-gut-microbiota axis and preclinical evidence ...suggests that the microbiota can recruit this bidirectional communication system to modulate brain development, function and behaviour. The pathophysiology of depression involves neuroimmune-neuroendocrine dysregulation. However, the extent to which changes in gut microbiota composition and function mediate the dysregulation of these pathways is unknown. Thirty four patients with major depression and 33 matched healthy controls were recruited. Cytokines, CRP, Salivary Cortisol and plasma Lipopolysaccharide binding protein were determined by ELISA. Plasma tryptophan and kynurenine were determined by HPLC. Fecal samples were collected for 16s rRNA sequencing. A Fecal Microbiota transplantation was prepared from a sub group of depressed patients and controls and transferred by oral gavage to a microbiota-deficient rat model. We demonstrate that depression is associated with decreased gut microbiota richness and diversity. Fecal microbiota transplantation from depressed patients to microbiota-depleted rats can induce behavioural and physiological features characteristic of depression in the recipient animals, including anhedonia and anxiety-like behaviours, as well as alterations in tryptophan metabolism. This suggests that the gut microbiota may play a causal role in the development of features of depression and may provide a tractable target in the treatment and prevention of this disorder.
Agitation is common in patients with Alzheimer's disease and is distressing to both patients and their caregivers. In this randomized trial of 272 patients with Alzheimer's disease who had agitated ...behavior that did not respond to a psychosocial treatment program, donepezil (5 mg for 4 weeks and 10 mg for 8 weeks) was not more effective than placebo in reducing agitation.
In patients with Alzheimer's disease who had agitated behavior that did not respond to a psychosocial treatment program, donepezil was not more effective than placebo in reducing agitation.
Alzheimer's disease causes a progressive decline in cognitive and functional ability and distress on the part of both patients and their caregivers. Agitation, a cluster of related symptoms that includes anxiety, irritability, and motor restlessness, leading to behaviors such as pacing, wandering, shouting, and aggression,
1
is seen in 24% of people with Alzheimer's disease who live in the community
2
and in 48% of those living in residential care facilities.
3
Behavioral and psychological symptoms in Alzheimer's disease are distressing to caregivers
4
,
5
and often precipitate the transition to residential care.
6
Atypical neuroleptic agents remain the mainstay of drug treatment despite only . . .
The PHENIX Forward Silicon Vertex Detector Aidala, C.; Anaya, L.; Anderssen, E. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
08/2014, Letnik:
755
Journal Article
Recenzirano
Odprti dostop
A new silicon detector has been developed to provide the PHENIX experiment with precise charged particle tracking at forward and backward rapidity. The Forward Silicon Vertex Tracker (FVTX) was ...installed in PHENIX prior to the 2012 run period of the Relativistic Heavy Ion Collider (RHIC). The FVTX is composed of two annular endcaps, each with four stations of silicon mini-strip sensors, covering a rapidity range of 1.2<|η|<2.2 that closely matches the two existing PHENIX muon arms. Each station consists of 48 individual silicon sensors, each of which contains two columns of mini-strips with 75μm pitch in the radial direction and lengths in the ϕ direction varying from 3.4mm at the inner radius to 11.5mm at the outer radius. The FVTX has approximately 0.54million strips in each endcap. These are read out with FPHX chips, developed in collaboration with Fermilab, which are wire bonded directly to the mini-strips. The maximum strip occupancy reached in central Au–Au collisions is approximately 2.8%. The precision tracking provided by this device makes the identification of muons from secondary vertices away from the primary event vertex possible. The expected distance of closest approach (DCA) resolution of 200μm or better for particles with a transverse momentum of 5 GeV/c will allow identification of muons from relatively long-lived particles, such as D and B mesons, through their broader DCA distributions.
Gas accretion onto some massive black holes (MBHs) at the centers of galaxies actively powers luminous emission, but most MBHs are considered dormant. Occasionally, a star passing too near an MBH is ...torn apart by gravitational forces, leading to a bright tidal disruption flare (TDF). Although the high-energy transient Sw 1644+57 initially displayed none of the theoretically anticipated (nor previously observed) TDF characteristics, we show that observations suggest a sudden accretion event onto a central MBH of mass about 10 6 to 10 7 solar masses. There is evidence for a mildly relativistic outflow, jet collimation, and a spectrum characterized by synchrotron and inverse Compton processes; this leads to a natural analogy of Sw 1644+57 to a temporary smaller-scale blazar.
Angiotensin-converting enzyme (ACE) is a dipeptidyl carboxy-peptidase that generates the vasoconstricting peptide angiotensin II and inactivates the vasodilating peptide bradykinin. The gene encoding ...ACE is composed of two homologous regions and codes for both a somatic and testis isoenzyme. Experiments with hypertensive rats and some, but not other, studies of humans suggest that sequences at or linked to the gene influence blood pressure. The testis-specific form of ACE has its own promoter within intron 12 (ref. 14), is encoded by the 3' region of the gene, and is found only in postmeiotic spermatogenic cells and sperm. Its function is unknown. Here we investigate the role of the Ace gene in blood pressure control and reproduction using mice generated to carry an insertional mutation that is designed to inactivate both forms of ACE. All homozygous female mutants were found to be fertile, but the fertility of homozygous male mutants was greatly reduced. Heterozygous males but not females had blood pressures that were 15-20 mm Hg less than normal, although both male and female heterozygotes had reduced serum ACE activity.
PDF
