Healthcare Avoidance in Aircraft Pilots Due to Concern for Aeromedical Certificate Loss: A Survey of 3765 Pilots.

OBJECTIVE: To study healthcare avoidance behavior in pilots related to fear of aeromedical certificate loss. METHODS: Voluntary participation in an anonymous survey distributed to U.S. pilots. RESULTS: A total of 3765 pilots were included in the analysis. There were 56.1% of pilots (n = 2111) who reported a history of healthcare avoidance behavior due fear for losing their aeromedical certificate. There were 45.7% who sought informal medical care (n = 1721) and 26.8% who misrepresented/withheld information on a written healthcare questionnaire for fear of aeromedical certificate loss (n = 994). CONCLUSIONS: Aircraft pilots may participate in healthcare avoidance behavior related to fear of losing their aeromedical certificate. Further work is necessary to address pilot healthcare avoidance.

Healthcare related aversion and care seeking patterns of female aviators in the United States.

Diagnosis of a new medical condition in pilots may precipitate the end of an aviation career or hobby. For this reason, a barrier exists for pilots to seek medical care due to fear of losing an aeromedical certificate. Females represent a growing proportion of pilots in the United States and data on healthcare seeking behavior in this cohort is sparse. We conducted an anonymous online survey of 154 female pilots and 131 female non-pilots in the United States. 83.7% of female pilots have experienced healthcare related aversion compared to 27.5% of non-pilots. 66.7% of female pilots had withheld information from a physician while 46.0% had delayed or forwent medical care due to concern for their medical status. Further studies should be conducted to inform policy change to address pilot healthcare barriers.

Pelvic floor rehabilitation for defecation disorders.

Pelvic floor rehabilitation is frequently recommended for defecation disorders, in both constipation and fecal incontinence. However, the lack of patient selection, together with the variety of rehabilitation methods and protocols, often jeopardize the results of this approach, causing difficulty in evaluating outcomes and addressing proper management, and above all, in obtaining scientific evidence for the efficacy of these methods for specific indications. The authors represent different gastroenterological and surgical scientific societies in Italy, and their aim was to identify the indications and agree on treatment protocols for pelvic floor rehabilitation of patients with defecation disorders. This was achieved by means of a modified Delphi method, utilizing a working team (10 members) which developed the statements and a consensus group (15 members, different from the previous ones) which voted twice also suggesting modifications of the statements.

Measurement of an Excess in the Yield of J/ψ at Very Low p_{T} in Pb-Pb Collisions at sqrt[s]_{NN}=2.76 TeV.

We report on the first measurement of an excess in the yield of J/ψ at very low transverse momentum (p_{T}<0.3 GeV/c) in peripheral hadronic Pb-Pb collisions at sqrt[s_{NN}]=2.76 TeV, performed by ALICE at the CERN LHC. Remarkably, the measured nuclear modification factor of J/ψ in the rapidity range 2.5

Multiplicity and transverse momentum evolution of charge-dependent correlations in pp, p-Pb, and Pb-Pb collisions at the LHC.

We report on two-particle charge-dependent correlations in pp, p-Pb, and Pb-Pb collisions as a function of the pseudorapidity and azimuthal angle difference, [Formula: see text] and [Formula: see text] respectively. These correlations are studied using the balance function that probes the charge creation time and the development of collectivity in the produced system. The dependence of the balance function on the event multiplicity as well as on the trigger and associated particle transverse momentum ([Formula: see text]) in pp, p-Pb, and Pb-Pb collisions at [Formula: see text] 7, 5.02, and 2.76 TeV, respectively, are presented. In the low transverse momentum region, for [Formula: see text] GeV/c, the balance function becomes narrower in both [Formula: see text] and [Formula: see text] directions in all three systems for events with higher multiplicity. The experimental findings favor models that either incorporate some collective behavior (e.g. AMPT) or different mechanisms that lead to effects that resemble collective behavior (e.g. PYTHIA8 with color reconnection). For higher values of transverse momenta the balance function becomes even narrower but exhibits no multiplicity dependence, indicating that the observed narrowing with increasing multiplicity at low [Formula: see text] is a feature of bulk particle production.

Inclusive quarkonium production at forward rapidity in pp collisions at [Formula: see text]TeV.

We report on the inclusive production cross sections of [Formula: see text], [Formula: see text], [Formula: see text](1S), [Formula: see text](2S) and [Formula: see text](3S), measured at forward rapidity with the ALICE detector in [Formula: see text] collisions at a center-of-mass energy [Formula: see text] TeV. The analysis is based on data collected at the LHC and corresponds to an integrated luminosity of 1.23 pb[Formula: see text]. Quarkonia are reconstructed in the dimuon-decay channel. The differential production cross sections are measured as a function of the transverse momentum [Formula: see text] and rapidity y, over the [Formula: see text] ranges [Formula: see text] GeV/c for [Formula: see text], [Formula: see text] GeV/c for all other resonances, and for [Formula: see text]. The cross sections, integrated over [Formula: see text] and y, and assuming unpolarized quarkonia, are [Formula: see text] [Formula: see text]b, [Formula: see text] [Formula: see text]b, [Formula: see text] nb, [Formula: see text] nb and [Formula: see text] nb, where the first uncertainty is statistical and the second one is systematic. These values agree, within at most [Formula: see text], with measurements performed by the LHCb collaboration in the same rapidity range.

7keto-stigmasterol and 7keto-cholesterol induce differential proteome changes to intestinal epitelial (Caco-2) cells.

Recent studies have expanded the appreciation of the roles of oxysterols triggering inflammatory, immune cytotoxic and apoptotic processes, but have not been considered for proteome analysis. A comparative proteomic study in intestinal epithelial cell cultures incubated (60 µM/24 h) with 7keto-cholesterol or 7keto-stigmasterol was performed. The influence of both compounds was studied following the nLC-TripleTOF analysis. Findings were compared to results for control cultures. In the principal component analysis (PCA) of proteome patterns, two components were extracted accounting for 99.8% of the variance in the protein expression. PCA analysis clearly discriminated between the perturbations in the proteome of cell cultures incubated with 7keto-cholesterol and 7keto-stigmasterol. These proteins participate in mitochondrial function, lipid homeostasis, inflammation and immunity and cell proliferation. Remarkable differences between proteome patterns in cell cultures exposed to 7keto-cholesterol and 7keto-stigmasterol affect macrophage migration inhibitory factor, apolipoprotein E, Bcl-2-associated transcription factor and cellular retinoic acid-binding protein. Besides, exposure to 7keto-stigmasterol increased the concentration of ubiquitin-conjugating enzyme E2 and the mitochondrial superoxide dismutase protein. Such findings raise new questions about safety studies and the regulatory potential of oxysterols in the differentiation and function of intestinal and associated immune cells, their response to environmental stimuli and impairment of absorption processes.

Effect of ß-cryptoxanthin plus phytosterols on cardiovascular risk and bone turnover markers in post-menopausal women: a randomized crossover trial.

BACKGROUND AND AIM: Post-menopausal women are at higher risk of cardiovascular disease and bone demineralization. Phytosterols (PS) may be used for hypercholesterolemia in some groups and ß-cryptoxanthin (ß-Cx) displays a unique anabolic effect on bone. Our aim was to assess the changes in cardiovascular and bone turnover markers from the oral intake of ß-Cx and PS in post-menopausal women. METHODS AND RESULTS: A randomized, double-blind, crossover study with ß-Cx (0.75 mg/day) and PS (1.5 g/day), single and combined, was performed in 38 postmenopausal women. Diet was supplemented with 1 × 250 mL milk-based fruit drink/day for 4 weeks with a wash-out period of 4-weeks in between. Serum ß-Cx and PS were determined by UPLC and CG-FID respectively. Outcome variables included markers of bone turnover and cardiovascular risk. Biological effect was assessed by paired t test and generalized estimating equations analysis that included the previous treatment, the order of intervention and the interactions. The intake of beverages containing ß-Cx and PS brought about a significant increase in serum levels of ß-Cx, ß-sitosterol and campesterol. Intervention caused changes in almost all the markers while the order, previous treatment and the interaction did not reach statistical significance. Only the intake of the beverage containing ß-Cx plus PS brought about significant decreases in total cholesterol, c-HDL, c-LDL and bone turnover markers. CONCLUSIONS: ß-Cx improves the cholesterol-lowering effect of PS when supplied simultaneously and this combination may also be beneficial in reducing risk of osteoporosis. CLINICAL TRIAL REGISTRY: ClinicalTrials.gov number NCT01074723.

Plant sterols from foods in inflammation and risk of cardiovascular disease: a real threat?

High dietary intakes of cholesterol together with sedentary habits have been identified as major contributors to atherosclerosis. The latter has long been considered a cholesterol storage disease; however, today atherosclerosis is considered a more complex disease in which both innate and adaptive immune-inflammatory mechanisms as well as bacteria play a major role, in addition to interactions between the arterial wall and blood components. This scenario has promoted nutritional recommendations to enrich different type of foods with plant sterols (PS) because of their cholesterol-lowering effects. In addition to cholesterol, PS can also be oxidized during food processing or storage, and the oxidized derivatives, known as phytosterol oxidation products (POPs), can make an important contribution to the negative effects of both cholesterol and cholesterol oxidation oxides (COPs) in relation to inflammatory disease onset and the development of atherosclerosis. Most current research efforts have focused on COPs, and evaluations of the particular role and physiopathological implications of specific POPs have been only inferential. Appreciation of the inflammatory role described for both COPs and POPs derived from foods also provides additional reasons for safety studies after long-term consumption of PS. The balance and relevance for health of all these effects deserves further studies in humans. This review summarizes current knowledge about the presence of sterol oxidation products (SOPs) in foods and their potential role in inflammatory process and cardiovascular disease.

Relative expression of cholesterol transport-related proteins and inflammation markers through the induction of 7-ketosterol-mediated stress in Caco-2 cells.

Human diets contain sterol oxidation products that can induce cytotoxic effects, mainly caused by cholesterol oxides. However, phytosterol oxides effects have been less extensively investigated. This study evaluates the production of inflammatory biomarkers (IL-1ß, IL-8, IL-10, TNFα) and the influence of gene expression transporters and enzymes related to cholesterol absorption and metabolism (NPC1L1, ABCG5/8, HMGCoA, ACAT) produced by 7-ketosterols (stigmasterol/cholesterol) in Caco-2 cells. These effects were linked to intracellular signaling pathways by using several inhibitors. Results showed 7-ketostigmasterol to have a greater proinflammatory potential than 7-ketocholesterol. In non-pre-treated cells, only efflux transporters were down-regulated by 7-ketosterols, showing a greater influence upon ABCG5 expression. Cell-pre-incubation with bradykinin induced changes in ABCG expression levels after 7-ketostigmasterol-incubation; however, the energetic metabolism inhibition reduced NPC1L1 expression only in 7-ketocholesterol-incubated cells. In non-pre-treated cells, HMG-CoA was up-regulated by both 7-ketosterols. However, exposure to inhibitors down-regulated the expression levels, mainly in 7-ketocholesterol-incubated cells. While ACAT expression values in non-pre-treated cells were unchanged, exposure to inhibitors caused down-regulation of mRNA levels. These results suggest that internalization and excretion of 7-ketostigmasterol is probably influenced by [Ca]i, which also could mediate HMGCoA activity in POPs metabolism. However, energetic metabolism and reducing equivalents exert different influences upon the 7-ketosterol internalization.

Gangliosides and sialic acid effects upon newborn pathogenic bacteria adhesion: an in vitro study.

The effect of the main gangliosides (GM(1), GM(3), GD(3)) and free sialic acid (Neu5Ac) upon the adhesion of pathogenic bacteria implicated in infant diarrhoea is assessed in vitro using the Caco-2 cell line. Concentrations of the bioactive compounds found in the bioaccessible (soluble) fraction of infant formula and human milk are employed. Bacterial adhesion behaviour included enterotoxigenic Escherichia coli (ETEC), enteropathogenic E.coli (EPEC), Listeria monocytogenes, Salmonella entericaserovartyphi, Shigella sonnei, Campylobacter jejuni and Helicobacter pylori. Three different approaches were assayed: pre-incubation of bacteria and compounds before addition to cells (competition); pre-incubation of the cells with compounds (exclusion); and pre-incubation of cells with bacteria (displacement). Furthermore, the spatial localization of the most abundant gangliosides, GM(3) and GD(3), in Caco-2 cells has been determined using confocal microscopy. Results show that GM(3), GD(3), GM(1) and Neu5Ac at the assayed concentrations are able to interfere with the adhesion of several pathogenic bacteria involved in neonatal diseases-the greatest effect corresponding to Neu5Ac, followed by GD(3), GM(1) and GM(3). Gangliosides GM(3) and GD(3) are located in the apical and basolateral membranes of the Caco-2 cells.

Evaluation of the cytotoxic effect of 7keto-stigmasterol and 7keto-cholesterol in human intestinal (Caco-2) cells.

The biological implications of cholesterol oxidation products have been investigated, though research on plant sterol oxidation products is scarce and in some cases contradictory. The cytotoxicity of 7keto(k)-stigmasterol versus 7keto(k)-cholesterol at different concentrations (0-120 µM) and incubation times (4-24h), in intestinal epithelial cells (Caco-2 cells) was evaluated. The 3-[4,5-dimethylthiazol-2-yl]-2,3-diphenyl tetrazolium bromide and neutral red uptake tests, mitochondrial membrane potential (ΔΨm), and relative DNA and RNA contents in the cell cycle phases were determined. Possible interaction effects between 7k-derivatives or non-oxidized stigmasterol were monitored. Endo/lysosomal activity was not impaired by either oxide. 7k-cholesterol showed a deleterious effect upon the mitochondrial compartment after 24h of exposure (120 µM), as well as upon ΔΨm when incubated at all concentrations (12/24h). Only cells incubated with 7k-cholesterol (120 µM) exhibited a decrease in RNA proportion in the G1 population. The presence of 7k-stigmasterol or stigmasterol with 7k-cholesterol reduced the deleterious metabolic effects upon mitochondrial functionality and integrity and the distribution of RNA contents in G1 and G2 phases. A decrease in the G1 phase proportion was detected in cells exposed to mixtures, without alterations in RNA content. The results obtained indicate the absence of 7k-stigmasterol cytotoxicity in Caco-2 cells and its capacity to reduce 7k-cholesterol toxicity.

Mineral and/or milk supplementation of fruit beverages helps in the prevention of H2O2-induced oxidative stress in Caco-2 cells.

INTRODUCTION: Fruit beverages are commonly supplemented with milk, vitamins and/or minerals in order to improve their healthy effects by providing some bioactive components that can act additively or synergistically against oxidative stress. AIMS: To test whether iron, zinc, and milk added to fruit beverages do not affect the cytoprotective effect against oxidative damage to Caco-2 cells through GSH-related enzymes induction and cell cycle progression preservation, in comparison with non-supplemented fruit beverage. METHODS: Caco-2 cells were incubated 24 h with the bioaccessible fraction (BF) of eight fruit beverages with/without iron and/or zinc, and/or milk, and then challenged with H2O2 (5 mmol L-1 -2 h). Mitochondrial enzyme activities (MTT test), GSH-Rd and GSH-Px enzyme activities, cell cycle progression and caspase-3 activity were measured. RESULTS AND DISCUSSION: Fruit beverages prevented the deleterious effect of H2O2 on cell viability, with almost all samples reaching control basal levels. Only independent iron or zinc supplementation with/without milk exerted positive effects upon GSH-Rd activity. Both minerals with milk, afforded improved preservation of GSH-Px activity. All samples prevented the decrease in the G1 phase of cell cycle induced by H2O2, except iron supplemented samples with/without milk, but none of them avoided the increase in sub-G1 phase. However, this fact was not associated to caspase-3 activity, with a probable positive effect of zinc upon this parameter. CONCLUSION: Mineral and/or milk supplementation of fruit beverages helps in the prevention of oxidative stress in Caco-2 cells based on cell viability maintenance, GSH-related enzymes activation, cell cycle distribution preservation and inhibition of caspase-3 activation.

Polyphenolic profile and antiproliferative activity of bioaccessible fractions of zinc-fortified fruit beverages in human colon cancer cell lines.

INTRODUCTION: Colorectal cancer risks could be reduced by polyphenol-rich diets that inhibit tumour cell growth. AIMS: To determine the polyphenolic profile of four fruit beverages (FbZn, FbZnFe, FbZnM and FbZnFeM) as affected by the presence of Zn with/without Fe and with/without skimmed milk, and the digestion conditions. To evaluate the antiproliferative activity of bioaccessible fractions against Caco-2 and HT-29 cells. To clarify whether cell cycle arrest and/or apoptosis is involved in their possible antiproliferative activity. METHODS: The polyphenolic profiles were analyzed by RP-HPLC-DAD before and after in vitro gastrointestinal digestion. Cell proliferation and viability were measured using Trypan blue test, mitochondrial enzyme activity by means MTT test, cell cycle distribution using flow cytometry and apoptosis by means Hoechst dye. RESULTS AND DISCUSSION: The presence of zinc, iron and/or milk decreased the soluble extractable phenolic content before digestion probably by chelate formation, FbZn and FbZnFe being the samples with the highest soluble extractable phenolics. After digestion, a decrease in phenolics was observed in all zinc-fortified samples (up to 32% with respect to the original fruit beverages) - the FbZnFeM sample showing the lowest soluble extractable phenolic content, though with the lowest percentage decrease in phenolics (14%). FbZnM digest (approximately 50 microM total soluble extractable phenolics) was the sample that most inhibited Caco-2 and HT-29 cell proliferation after 24 h of incubation, without cytotoxicity. The specific combination of phytochemicals in FbZnM digest proved cytostatic and significantly suppressed proliferation through cell cycle arrest in the S-phase in both cell lines, without apoptosis.

[Laryngotracheal separation as treatment for severe bronchopulmonary aspiration]. / Separación laringotraqueal como tratamiento de la aspiración broncopulmonar grave.

We present the case of a patient with brain stem tumour and severe chronic aspiration. The bilateral dysfunction of lower cranial nerves and the severe gastroesophageal reflux contributed to the aspirations. Despite medical treatment and cuffed tracheotomy tube, she required almost constant hospitalization for a year and a half due to respiratory infections. Laryngotracheal separation dramatically reduced the infections and improved her quality of life.

Persistent dysphagia after laparoscopic fundoplication for gastro-esophageal reflux disease.

Persistent postoperative dysphagia is a potentially severe complication of fundoplication for gastroesophageal reflux disease (GERD). The aim of this retrospective study was to analyze our experience of laparoscopic fundoplication for GERD in 276 consecutive patients, to determine the frequency of postoperative dysphagia and assess treatments and outcomes. There was no relation between preoperative dysphagia, present in 24 patients (8.7%), and postoperative DeMeester grade 2 or 3 dysphagia, present in 25 patients (9.1%). Ten (3.6%) patients had clinically significant postoperative dysphagia, eight (2.9%) underwent esophageal dilation, with symptom improvement in five. Four (1.4%) of our patients (two with failed dilation) and 11 patients receiving antireflux surgery elsewhere, underwent re-operation for persistent dysphagia 12 months (median) after the first operation. DeMeester grade 0 or 1 dysphagia was obtained in 10/13 evaluable patients. Our experience is fully consistent with that of the recent literature. Redo surgery is necessary in only a small fraction of operated patients with GERD with good probability of resolving the dysphagia. Best outcomes are obtained when an anatomical cause of the dysphagia is documented preoperatively.

As2O3-induced oxidative stress and cycle progression in a human intestinal epithelial cell line (Caco-2).

Foods and drinking water are the main routes for human exposure to inorganic arsenic, the intestinal epithelium being the first barrier against such exogenous toxicants. The present study evaluates the effect of As(III) (0.5-25 microM) upon Caco-2 cells as an intestinal epithelia model. Cell viability, intracellular formation of reactive oxygen species (ROS), mitochondrial membrane potential (Deltapsim) changes, and cell cycle distribution in exposed cultures were evaluated. The intracellular production of ROS was seen to increase in a non-dose dependent manner at all concentrations tested, with impairment of cell mitochondrial enzyme function secondary to a loss of Deltapsim. Concentrations between 0.5 and 5 microM induce cell cycle transition from phase G1 to phase S, with no significant alteration in the proportion of cells in phase G2. These data suggest that As(III) could induce intestinal oxidative stress-cytotoxicity at mitochondrial functional level, and affect cell cycle progression. The data presented in this work may also suggest the impairment of essential survival processes in Caco-2 cells, induced after exposure to As(III) (1-25 microM). Oxidative stress and alteration of mitochondrial functionality could be early indicators of arsenic-induced cytotoxicity, with the resulting abnormal progression of the cell cycle.

Antioxidant capacity of infant fruit beverages: influence of storage and in vitro gastrointestinal digestion.

AIM: The total antioxidant capacity of three beverages based on fruit juice, milk and cereals, intended for infants and young children up to 3 years of age was evaluated by two methods Trolox Equivalent Antioxidant Capacity and Oxygen Radical Absorption Capacity. RESULTS: According to the total antioxidant values obtained by both methods, the beverages can be ranked as follows: grape-orange-banana > peach-apple > pineapple-banana. Ascorbic acid was the main contributor (60%) to the total antioxidant capacity, while the contribution of skimmed milk was less than 1.2%. After one month of storage at -20 degrees C, significant losses (p < 0.05) in total antioxidant capacity were found, though these were lower than 3% and therefore lacked nutritional significance. The bioaccessible fractions (maximum soluble fraction in simulated gastrointestinal media) of the beverages, obtained by in vitro gastrointestinal digestion, had antioxidant activities significantly lower (p < 0.05) than the original beverages, though the loss of antioxidant activity was always lower than 19%--thus indicating the stability of the total antioxidant capacity under the applied conditions. CONCLUSIONS: The total antioxidant capacity values of the bioaccessible fraction show that most antioxidants are available for absorption after digestion, and might contribute to the beneficial effects attributed to antioxidants.

New vaccines require potent adjuvants like AFPL1 and AFCo1.

Neisseria meningitidis B proteoliposome (AFPL1 when used as adjuvant) and its derivative-Cochleate (AFCo1) contain immunopotentiating and immunomodulating properties and delivery system capacities required for a good adjuvant. Additionally, they contain meningococcal protective antigens and permit packaging of other antigens and pathogen-associated molecular patterns (PAMP). Consequently, we hypothesized that they would function as good vaccine adjuvants for their own antigens and also for non-related antigens. AFPL1 is a detergent-extracted outer membrane vesicle of N. meningitidis B transformed into AFCo1 in calcium environment. Both are produced at Finlay Institute under good manufacture practices (GMP) conditions. We show their exceptional characteristics: combining in the same structure, the potentiator activity, polarizing agents and delivery system capacities; presenting multimeric protein copies; containing multiprotein composition and multi and synergistic PAMP components; acting with incorporated or co-administrated antigens; inducing type I IFN-gamma and IL-12 cytokines suggesting the stimulation of human plasmocytoid precursor and conventional dendritic cells, respectively, inducing a preferential Th1 immune response with TCD4(+), TCD8(+), cross-presentation and cytotoxic T-lymphocyte (CTL) in vivo responses; and functioning by parenteral and mucosal routes. AFPL1-AFCo1 protective protein constitutions permit per se their function as a vaccine. In addition to Phase IV Men BC vaccine, AFPL1 has ended the preclinical stage in an allergy vaccine and is concluding the preclinical stage of a nasal meningococcal vaccine. In conclusion, AFPL1 and AFCo1 induced signal 1, 2 and 3 polarizing to a Th1 (including CTL) response when they acted directly as vaccines or were used as adjuvants with incorporated or co-administered antigens by parenteral or mucosal routes. Both are very promising adjuvants.

Bioaccessibility and transport by Caco-2 cells of organoarsenical species present in seafood.

Organoarsenical standards and raw and cooked seafood (DORM-2, sole, and Greenland halibut) were subjected to in vitro gastrointestinal digestion to estimate arsenic bioaccessibility (maximum soluble concentration in gastrointestinal medium). The in vitro digestion did not modify the chemical form of the organoarsenic species standards. In seafood, bioaccessibility was 67.5-100% for arsenobetaine (AB), 30% for dimethylarsinic acid (DMA), 45% for tetramethylarsonium ion (TETRA), and >50% for trimethylarsine oxide (TMAO). Cooking induced no changes in bioaccessible contents. In addition, transport by Caco-2 cells, an intestinal epithelia model, was evaluated from organoarsenical standards and DORM-2. For standards, transport ranged from 1.7% for AB to 15.5% for TETRA. In DORM-2, transport was observed for only AB (12%), with far higher efficiency than in the case of the standard solution, thus illustrating the interest of using whole foods for studying bioavailability.