Objective
To quantify the risk of hip fracture, thromboembolism, stroke, myocardial infarction, pneumonia and sudden cardiac death associated with exposure to antipsychotics.
Methods
Systematic ...searches were conducted in Medline, Embase and PsycINFO from inception until 30/07/2018 for systematic reviews of observational studies. AMSTAR‐2 was used for the quality assessment of systematic reviews, while the strength of associations was measured using GRADE and quantitative umbrella review criteria (URC).
Results
Sixty‐eight observational studies from six systematic reviews were included. The association between antipsychotic exposure and pneumonia was the strongest URC = class I; GRADE = low quality; odds ratio (OR) = 1.84, 95% confidence interval (CI) = 1.62–2.09; participants = 28 726; age = 76.2 ± 12.3 years, followed by the association with hip fracture (URC = class II; GRADE = low quality; OR = 1.57, 95% CI = 1.42–1.74; participants = 5 288 118; age = 55.4 ± 12.5 years), and thromboembolism (URC = class II; GRADE = very low quality; OR = 1.55, 95% CI = 1.31–1.83; participants = 31 417 175; age = 55.5 ± 3.2 years). The association was weak for stroke (URC = class III; GRADE = very low quality; OR = 1.45, 95% CI = 1.24–1.70; participants = 65 700; age = 68.7 ± 13.8 years), sudden cardiac death (URC = class III; GRADE = very low quality; OR = 2.24, 95% CI = 1.45–3.46; participants = 77 488; age = 52.2 ± 6.2 years) and myocardial infarction (URC = class III; GRADE = very low quality; OR = 2.21, 95% CI = 1.41–3.46; participants = 399 868; age = 74.1 ± 9.3 years).
Conclusion
The most robust results were found for the risk of pneumonia, followed by the risk of hip fracture and thromboembolism. For stroke, sudden cardiac death and myocardial infarction, the strength of association was weak. The observational nature of the primary studies may represent a source of bias.
Background
To date, a systematic review of the evidence regarding the association between vitamin D and allergic diseases development has not yet been undertaken.
Objective
To review the efficacy and ...safety of vitamin D supplementation when compared to no supplementation in pregnant women, breastfeeding women, infants, and children for the prevention of allergies.
Methods
Three databases were searched through January 30, 2016, including randomized (RCT) and nonrandomized studies (NRS). Two reviewers independently extracted data and assessed the certainty in the body of evidence using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach.
Results
Among the 1932 articles identified, one RCT and four NRS were eligible. Very low certainty in the body of evidence across examined studies suggests that vitamin D supplementation for pregnant women, breastfeeding women, and infants may not decrease the risk of developing allergic diseases such as atopic dermatitis (in pregnant women), allergic rhinitis (in pregnant women and infants), asthma and/or wheezing (in pregnant women, breastfeeding women, and infants), or food allergies (in pregnant women). We found no studies of primary prevention of allergic diseases in children.
Conclusion
Limited information is available addressing primary prevention of allergic diseases after vitamin D supplementation, and its potential impact remains uncertain.
Summary
Background
Prevalence of allergic diseases in infants is approximately 10% reaching 20 to 30% in those with an allergic first‐degree relative. Prebiotics are selectively fermented food ...ingredients that allow specific changes in composition/activity of the gastrointestinal microflora. They modulate immune responses, and their supplementation has been proposed as an intervention to prevent allergies.
Objective
To assess in pregnant women, breastfeeding mothers, and infants (populations) the effect of supplementing prebiotics (intervention) versus no prebiotics (comparison) on the development of allergic diseases and to inform the World Allergy Organization guidelines.
Methods
We performed a systematic review of studies assessing the effects of prebiotic supplementation with an intention to prevent the development of allergies.
Results
Of 446 unique records published until November 2016 in Cochrane, MEDLINE, and EMBASE, 22 studies fulfilled a priori specified criteria. We did not find any studies of prebiotics given to pregnant women or breastfeeding mothers. Prebiotic supplementation in infants, compared to placebo, had the following effects: risk of developing eczema (RR: 0.68, 95% CI: 0.40 to 1.15), wheezing/asthma (RR, 0.37; 95% CI: 0.17 to 0.80), and food allergy (RR: 0.28, 95% CI: 0.08 to 1.00). There was no evidence of an increased risk of any adverse effects (RR: 1.01, 95% CI: 0.92 to 1.10). Prebiotic supplementation had little influence growth rate (MD: 0.92 g per day faster with prebiotics, 95% CI: 0 to 1.84) and the final infant weight (MD: 0.10 kg higher with prebiotics, 95% CI: −0.09 to 0.29). The certainty of these estimates is very low due to risk of bias and imprecision of the results.
Conclusions
Currently available evidence on prebiotic supplementation to reduce the risk of developing allergies is very uncertain.
The instrument suite of the European Spallation Source Jackson, A.J.; Toft-Petersen, R.; Beran, P. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
03/2020, Letnik:
957, Številka:
-
Journal Article
Recenzirano
Odprti dostop
An overview is provided of the 15 neutron beam instruments making up the initial instrument suite of the European Spallation Source (ESS), and being made available to the neutron user community. The ...ESS neutron source consists of a high-power accelerator and target station, providing a unique long-pulse time structure of slow neutrons. The design considerations behind the time structure, moderator geometry and instrument layout are presented.
The 15-instrument suite consists of two small-angle instruments, two reflectometers, an imaging beamline, two single-crystal diffractometers; one for macromolecular crystallography and one for magnetism, two powder diffractometers, and an engineering diffractometer, as well as an array of five inelastic instruments comprising two chopper spectrometers, an inverse-geometry single-crystal excitations spectrometer, an instrument for vibrational spectroscopy and a high-resolution backscattering spectrometer. The conceptual design, performance and scientific drivers of each of these instruments are described.
All of the instruments are designed to provide breakthrough new scientific capability, not currently available at existing facilities, building on the inherent strengths of the ESS long-pulse neutron source of high flux, flexible resolution and large bandwidth. Each of them is predicted to provide world-leading performance at an accelerator power of 2 MW. This technical capability translates into a very broad range of scientific capabilities. The composition of the instrument suite has been chosen to maximise the breadth and depth of the scientific impact of the early years of the ESS, and provide a solid base for completion and further expansion of the facility.
Farnesoid X receptor (FXR) is the master regulator of bile acid (BA) homeostasis because it controls BA synthesis, influx, efflux, and detoxification in the gut/liver axis. Deregulation of BA ...homeostasis has been linked to hepatocellular carcinoma (HCC), and spontaneous hepatocarcinogenesis has been observed in FXR‐null mice. This dreaded liver neoplasm has been associated with both FXR gene deletion and BA‐mediated metabolic abnormalities after inactivation of FXR transcriptional activity. In the present study, we addressed the hypothesis that intestinal selective FXR reactivation would be sufficient to restore the fibroblast growth factor 15 (FGF15)/cholesterol‐7alpha‐hydroxylase (Cyp7a1) enterohepatic axis and eventually provide protection against HCC. To this end, we generated FXR‐null mice with re‐expression of constitutively active FXR in enterocytes (FXR−/−iVP16FXR) and corresponding control mice (FXR−/−iVP16). In FXR‐null mice, intestinal selective FXR reactivation normalized BA enterohepatic circulation along with up‐regulation of intestinal FXR transcriptome and reduction of hepatic BA synthesis. At 16 months of age, intestinal FXR reactivation protected FXR‐null mice from spontaneous HCC development that occurred in otherwise FXR‐null mice. Activation of intestinal FXR conferred hepatoprotection by restoring hepatic homeostasis, limiting cellular proliferation through reduced cyclinD1 expression, decreasing hepatic inflammation and fibrosis (decreased signal transducer and activator of transcription 3 activation and curtailed collagen deposition). Conclusion: Intestinal FXR is sufficient to restore BA homeostasis through the FGF15 axis and prevent progression of liver damage to HCC even in the absence of hepatic FXR. Intestinal‐selective FXR modulators could stand as potential therapeutic intervention to prevent this devastating hepatic malignancy, even if carrying a somatic FXR mutation. (Hepatology 2015;61:161–170)
The objective of this study was to evaluate the effects of the partial replacement of NaCl by blends of KCl and CaCl2 on the physicochemical, microbiological, and sensory properties of jerked beef. ...For that, in the dry and wet salting stages, 50% NaCl of the control treatment (FC1) was replaced by 50% KCl (F1), 50% CaCl2 (F2), and a blend containing 25% KCl and 25% CaCl2 (F3) at equivalent concentrations based on the ionic strength. All reformulated treatments presented a significant sodium reduction when compared to the control (27.57% F1, 41.59% F2, and 36.74% F3). The CaCl2 blends resulted in final products with bitter taste and rancid aroma accompanied by a higher TBARS and shear force and lower a* values (P < .05). The substitute salts did not affect the microbiological stability (P > .05). The present results demonstrate that adding 50% KCl may be a good strategy to reduce sodium in jerked beef.
•50% NaCl was replaced by blends of KCl and CaCl2 to reduce sodium in jerked beef.•Blends with CaCl2 increased bitter taste and rancid aroma in reformulated jerked beef.•Reduced sodium product stability was maintained with blends of CaCl2 and KCl.•KCl was the best salt substitute to preserve sensory properties of reduced sodium jerked beef.
In the present work, different foods including banana, potato, cassava, onion, garlic, polenta, rice balls and beef patties were investigated in relation to the possible endogenous formation of ...3-monochloropropane-1,2-diol fatty acid esters (bound 3-MCPD) and carry-over of these contaminants from the oil due to fat uptake during frying. For that, the samples were fried in two different types of oil and bound 3-MCPD was determined by using an indirect method based on acid transesterification and gas chromatography coupled to mass spectrometry analysis. The compounds were not detected in the fried foods when corn oil containing non-significant levels of bound 3-MCPD (<0.05 mg kg
−1
) was used, indicating no endogenous formation during frying. On the other hand, when the same foods were fried in palm oil containing 1.64 mg kg
−1
of bound 3-MCPD, the mean concentrations ranged from 0.12 to 0.25 mg kg
−1
, indicating a clear carry-over of the contaminants. In this case, a good correlation was observed between the levels of the compounds in fried samples and water loss/fat uptake.
Cholesterol homeostasis is critical for cellular proliferation. Liver X receptor (LXR) α and β are the nuclear receptors responsible for regulation of cholesterol metabolism. In physiological ...conditions, high intracellular cholesterol levels cause increased synthesis of oxysterols, which activate LXR, thus triggering a transcriptional response for cholesterol secretion and catabolism. Here we employed a mouse model of partial hepatectomy (PH) to dissect the molecular pathways connecting cholesterol homeostasis, cellular proliferation, and LXR. First, we show that hepatic cholesterol content increases after PH, whereas the entire LXR transcriptome is down‐regulated. Although LXR messenger RNA (mRNA) levels are unmodified, LXR target genes are significantly down‐regulated on day 1 after PH and restored to control levels on day 7, when the liver reaches normal size. The inactivation of LXR following PH is related to the reduced oxysterol availability by way of decreased synthesis, and increased sulfation and secretion. On the contrary, cholesterol synthesis is up‐regulated, and extracellular matrix remodeling is enhanced. Second, we show that reactivation of LXR by way of a synthetic ligand determines a negative modulation of hepatocyte proliferation. This effect is sustained by the reactivation of hepatic cholesterol catabolic and secretory pathways, coupled with a significant reduction of cholesterol biosynthesis. Our data unveil a previously unrecognized and apparently paradoxical scenario of LXR modulation. During liver regeneration LXR activity is abated in spite of increasing intracellular cholesterol levels. Turning off LXR‐transcriptional pathways is crucial to guaranteeing the requisite intracellular cholesterol levels of regenerating hepatocytes. In line with this hypothesis, pharmacological LXR reactivation during PH significantly reduces liver regeneration capacity. (HEPATOLOGY 2010.)
Tumours can be viewed as aberrant tissues or organs sustained by tumorigenic stem-like cells that engage into dysregulated histo/organogenetic processes. Paragangliomas, prototypical organoid tumours ...constituted by dysmorphic variants of the vascular and neural tissues found in normal paraganglia, provide a model to test this hypothesis. To understand the origin of paragangliomas, we built a biobank comprising 77 cases, 18 primary cultures, 4 derived cell lines, 80 patient-derived xenografts and 11 cell-derived xenografts. We comparatively investigated these unique complementary materials using morphofunctional, ultrastructural and flow cytometric assays accompanied by microRNA studies. We found that paragangliomas contain stem-like cells with hybrid mesenchymal/vasculoneural phenotype, stabilized and expanded in the derived cultures. The viability and growth of such cultures depended on the downregulation of the miR-200 and miR-34 families, which allowed high PDGFRA and ZEB1 protein expression levels. Both tumour tissue- and cell culture-derived xenografts recapitulated the vasculoneural paraganglioma structure and arose from mesenchymal-like cells through a fixed developmental sequence. First, vasculoangiogenesis organized the microenvironment, building a perivascular niche which in turn supported neurogenesis. Neuroepithelial differentiation was associated with severe mitochondrial dysfunction, not present in cultured paraganglioma cells, but acquired in vivo during xenograft formation. Vasculogenesis was the Achilles’ heel of xenograft development. In fact, imatinib, that targets endothelial-mural signalling, blocked paraganglioma xenograft formation (11 xenografts from 12 cell transplants in the control group versus 2 out of 10 in the treated group,
P
= 0.0015). Overall our key results were unaffected by the
SDHx
gene carrier status of the patient, characterized for 70 out of 77 cases. In conclusion, we explain the biphasic vasculoneural structure of paragangliomas and identify an early and pharmacologically actionable phase of paraganglioma organization.
The given and family names of two co-authors were incorrect in the published article. The correct spelling should read as: Sampath Chandra Prasad and Vinagolu K Rajasekhar.
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