Association between faecal pH and fat absorption in children with cystic fibrosis on a controlled diet and enzyme supplements dose

[EN] Background Despite treatment with pancreatic enzyme replacement therapy (PERT), patients with cystic fibrosis (CF) can still suffer from fat malabsorption. A cause could be low intestinal pH disabling PERT. The aim of this study was to assess the association between faecal pH (as intestinal pH surrogate) and coefficient of fat absorption (CFA). Additionally, faecal free fatty acids (FFAs) were quantified to determine the amount of digested, but unabsorbed fat. Methods In a 24-h pilot study, CF patients followed a standardised diet with fixed PERT doses, corresponding to theoretical optimal doses determined by an in vitro digestion model. Study variables were faecal pH, fat and FFA excretion, CFA and transit time. Linear mixed regression models were applied to explore associations. Results In 43 patients, median (1st, 3rd quartile) faecal pH and CFA were 6.1% (5.8, 6.4) and 90% (84, 94), and they were positively associated (p < 0.001). An inverse relationship was found between faecal pH and total fat excretion (p < 0.01), as well as total FFA (p = 0.048). Higher faecal pH was associated with longer intestinal transit time (p = 0.049) and the use of proton pump inhibitors (p = 0.009). Conclusions Although the clinical significance of faecal pH is not fully defined, its usefulness as a surrogate biomarker for intestinal pH should be further explored. Impact Faecal pH is a physiological parameter that may be related to intestinal pH and may provide important physiopathological information on CF-related pancreatic insufficiency. Faecal pH is correlated with fat absorption, and this may explain why pancreatic enzyme replacement therapy is not effective in all patients with malabsorption related to CF. Use of proton pump inhibitors is associated to higher values of faecal pH. Faecal pH could be used as a surrogate biomarker to routinely monitor the efficacy of pancreatic enzyme replacement therapy in clinical practice. Strategies to increase intestinal pH in children with cystic fibrosis should be targeted.We acknowledge the support of the MyCyFAPP Project consortium. We especially thank the participation and the effort of the patients involved in the study and their families. This work was fully funded by the European Union and the Horizon 2020 Research and Innovation Framework Programme (PHC-26-2014 call Self management of health and disease: citizen engagement and mHealth) under grant number 643806.Calvo-Lerma, J.; Roca-Llorens, M.; Boon, M.; Colombo, C.; De Koning, B.; Fornés-Ferrer, V.; Masip, E.... (2021). Association between faecal pH and fat absorption in children with cystic fibrosis on a controlled diet and enzyme supplements dose. Pediatric Research. 89(1):205-210. https://doi.org/10.1038/s41390-020-0860-3S205210891Turck, D. et al. ESPEN-ESPGHAN-ECFS guidelines on nutrition care for infants, children, and adults with cystic fibrosis. Clin. Nutr. 35, 557–577 (2016).Borowitz, D., Baker, R. 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Physical–chemical behavior of dietary and biliary lipids during intestinal digestion and absorption. 2. Phase analysis and aggregation states of luminal lipids during duodenal fat digestionin healthy adult human beings. Biochemistry 29, 2041–2056 (1990).Calvo-Lerma, J. et al. A first approach for an evidence-based in vitro method to adjust pancreatic enzyme replacement therapy in cystic fibrosis. PLoS ONE 14, e0212459 (2019).Aburub, A. Comparison of pH and motility of the small intestine of healthy subjects and patients with symptomatic constipation using the wireless motility capsule. Int. J. Pharm. 544, 158–164 (2018).Calvo-Lerma, J. et al. Innovative approach for self-management and social welfare of children with cystic fibrosis in Europe: development, validation and implementation of an mHealth tool (MyCyFAPP). Br. Med. J. Open. 7, e014931 (2017).Calvo-Lerma, J. et al. 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Fat digestibility in meat products: influence of food structure and gastrointestinal conditions. Int. J. Food Sci. Nutr. 70, 530–539 (2019).Regan, P. T. et al. Reduced intraluminal bile acid concentrations and fat maldigestion in pancreatic insufficiency: correction by treatment. Gastroenterology 7, 285–289 (1979).Fallingborg, J. et al. pH‐profile and regional transit times of the normal gut measured by a radiotelemetry device. Aliment. Phamacol. Ther. 3, 605–614 (1989).Fallingborg, J. Intraluminal pH of the human gastrointestinal tract. Dan. Med Bull. 46, 183–196 (1999).Calvo-Lerma, J. et al. In vitro digestion models to assess lipolysis: the impact of the simulated conditions for gastrointestinal pH, bile salts and digestion fluids. Food Res. Int. 125, 108511 (2019).Kalantzi, L. Characterization of the human upper gastrointestinal contents under conditions simulating bioavailability/bioequivalence studies. Pharm. Res. 23, 165–176 (2006).Zelles, L. & Bai, Q. Y. 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Synergistic activation of AMPK prevents from polyglutamine-inducedtoxicity inCaenorhabditis elegans

11 páginas, 4 figuras. Supplementary material related to this article can be found, in the online version, at doi: https://doi.org/10.1016/j.phrs.2020.105105.Expression of abnormally long polyglutamine (polyQ) tracks is the source of a range of dominant neurodegenerative diseases, such as Huntington disease. Currently, there is no treatment for this devastating disease, although some chemicals, e.g., metformin, have been proposed as therapeutic solutions. In this work, we show that metformin, together with salicylate, can synergistically reduce the number of aggregates produced after polyQ expression in Caenorhabditis elegans. Moreover, we demonstrate that incubation polyQ-stressed worms with low doses of both chemicals restores neuronal functionality. Both substances are pleitotropic and may activate a range of different targets. However, we demonstrate in this report that the beneficial effect induced by the combination of these drugs depends entirely on the catalytic action of AMPK, since loss of function mutants of aak-2/AMPKα2 do not respond to the treatment. To further investigate the mechanism of the synergetic activity of metformin/salicylate, we used CRISPR to generate mutant alleles of the scaffolding subunit of AMPK, aakb-1/AMPKβ1. In addition, we used an RNAi strategy to silence the expression of the second AMPKβ subunit in worms, namely aakb-2/AMPKβ2. In this work, we demonstrated that both regulatory subunits of AMPK are modulators of protein homeostasis. Interestingly, only aakb-2/AMPKβ2 is required for the synergistic action of metformin/salicylate to reduce polyQ aggregation. Finally, we showed that autophagy acts downstream of metformin/salicylate-related AMPK activation to promote healthy protein homeostasis in worms.We thank the CGC, funded by the NIH Office of ResearchInfrastructure Programs (P40 OD010440), for worm strains. [...] RPVMis aMiguel Servet type IIresearcher (CPII16/00004) funded by Institutode Salud Carlos III (ISCIII, Madrid, Spain). Grants from the ISCIII wereused to perform this work (PI14/00949 and PI17/00011). All grantsfrom ISCIII are co-financed by the European Development RegionalFund”A way to achieve Europe”(ERDF). JBY holds a grant from theGeneralitat Valenciana and the European Social Fund (ACIF/2019/249). Some equipment used in this work has been funded in partnershipbetween the Generalitat Valenciana (Conselleria de Sanitat I SalutPública, Valencian Community, Spain) and European Funds (ERDF/FSE), through the call "Improvement of research infrastructures for rarediseases”CV FEDER 2014-2020. This work has been partially supportedby a grant from the Fundació Telemarató de la TV3 (Reference 559),which covered the work of MDS. The funds from the ISCIII are partiallysupported by the European Regional Development Fund. RPVM is also aMarie Curie fellow (CIG322034, EU). This work has been partiallysupported by a grant from the CIBERER (ACCI2016), a grant from theFundación Ramón Areces (CIVP19S8119) and anAyuda Miguel Gilgrantto RPVM (VII Convocatoria Ayudas a la Investigación MHER, 2019Peer reviewe

Zulassigkeit der schriftlichen Zeugenvernehmung(III)

In this letter, we investigate the optical properties of packed monodisperse silica submicron spheres by means of optical transmission measurements. The results are compatible with a three dimensional face centered cubic order in these solid structures. The lattice parameter of these structures, and therefore their optical properties, can be easily tuned through the sphere size (between 200 and 700 nm) thus covering the whole visible and near infrared spectrum.Comisión Interministerial de Ciencia y Tecnología MAT94-072

Assessing gastro-intestinal related quality of life in cystic fibrosis: Validation of PedsQL GI in children and their parents

Background: Most patients with cystic fibrosis (CF) suffer from pancreatic insufficiency, leading to fat malabsorption, malnutrition and abdominal discomfort. Until recently, no specific tool was available for assessing gastro-intestinal related quality of life (GI QOL) in patients with CF. As the Horizon2020 project MyCyFAPP aims to improve GI QOL by using a newly designed mobile application, a sensitive and reliable outcome measure was needed. We aimed to study the applicability of the existing child-specific Pediatric Quality of Life Inventory, Gastrointestinal Symptoms Scales and Module (PedsQL GI) in children with CF. Methods: A multicenter, prospective observational study was performed in 6 European centers to validate the PedsQL GI in children with CF during 3 months. Results: In total, 248 children and their parents were included. Within-patient variability of PedsQL GI was low (24.11), and there was reasonable agreement between children and parents (ICC 0.681). Nine of 14 subscales were informative (no ceiling effect). The PedsQL GI and the median scores for 4 subscales were significantly lower in patients compared to healthy controls. Positive associations were found between PedsQL GI and age (OR = 1.044, p = 0.004) and between PedsQL GI and BMI z-score (OR = 1.127, p = 0.036). PedsQL GI correlated with most CFQ-R subscales (r 0.268 to 0.623) and with a Visual Analogue Scale (r = 0.20). Conclusions: PedsQL GI is a valid and applicable instrument to assess GI QOL in children with CF. Future research efforts should examine the responsiveness of the CF PedsQL GI to change in the context of clinical interventions and trials

Magnetic Properties of Monomer and Dimer Tetrahedral VOx Entities Dispersed on Amorphous Silica-based Materials: Prediction of EPR Parameters from Relativistic DFT Calculations and Broken Symmetry Approach to Exchange Couplings

Molecular structures of the isolated tetrahedral oxovanadium(IV) and bridged μ-oxo-divanadium(IV) complexes hosted by the clusters mimicking surfaces of amorphous silica-based materials were investigated using density functional theory (DFT) calculations. Principal values of the g and A tensors for the monomer vanadyl species were obtained using the coupled-perturbed DFT level of theory and the spin–orbit mean-field approximation (SOMF). Magnetic exchange interaction for the μ-oxo bridged vanadium(IV) dimer was investigated within the broken symmetry approach. An antiferromagnetic coupling of the individual magnetic moments of the vanadium(IV) centers in the [VO–O–VO]2+ bridges was revealed and discussed in detail. The coupling explains pronounced decrease of the electron paramagnetic resonance signal (EPR) intensity, observed for the reduced VOx/SiO2 samples with the increasing coverage of vanadia, in terms of transformation of the paramagnetic monomer species into the dimers with S = 0 ground state

Allocating Family Responsibilities for Dependent Older People in Mexico and Peru

This paper applies different analytical frameworks to explore processes of family bargaining about providing care for dependent older people in Mexico and Peru. These frameworks include cultural norms, life course effects and material exchange. The paper is based on 19 in-depth qualitative family case studies, which are linked to a wider set of quantitative survey data. Care arrangements and bargaining processes are revealed to be highly gendered, and largely conform to prevailing cultural norms. Rather than neutral and objective, the self-identified role as main carer is found to be subjective and potentially ambiguous. The few men who self-identify as main carers are more likely to play an indirect, organisational role than engage directly in daily care. As such, bargaining mainly relates to which woman performs the main care role, and large family networks mean that there is usually more than one candidate carer. Bargaining can occur inter-generationally and conjugally, but bargaining between siblings is of particular importance. Bargaining is framed by the uncertain trajectory of older people’s care needs, and arrangements are sometimes reconfigured in response to changing care needs or family circumstances. Taking the narratives at face value, the influence of life course effects on bargaining and care arrangements is more obvious than material exchange. There are, however, indications that economic considerations, particularly inheritance, still play an important behind the scenes role

Hypercholesterolemia Impaired Sperm Functionality in Rabbits

Hypercholesterolemia represents a high risk factor for frequent diseases and it has also been associated with poor semen quality that may lead to male infertility. The aim of this study was to analyze semen and sperm function in diet-induced hypercholesterolemic rabbits. Twelve adult White New Zealand male rabbits were fed ad libitum a control diet or a diet supplemented with 0.05% cholesterol. Rabbits under cholesterol-enriched diet significantly increased total cholesterol level in the serum. Semen examination revealed a significant reduction in semen volume and sperm motility in hypercholesterolemic rabbits (HCR). Sperm cell morphology was seriously affected, displaying primarily a “folded head”-head fold along the major axe-, and the presence of cytoplasmic droplet on sperm flagellum. Cholesterol was particularly increased in acrosomal region when detected by filipin probe. The rise in cholesterol concentration in sperm cells was determined quantitatively by Gas chromatographic-mass spectrometric analyses. We also found a reduction of protein tyrosine phosphorylation in sperm incubated under capacitating conditions from HCR. Interestingly, the addition of Protein Kinase A pathway activators -dibutyryl-cyclic AMP and iso-butylmethylxanthine- to the medium restored sperm capacitation. Finally, it was also reported a significant decrease in the percentage of reacted sperm in the presence of progesterone. In conclusion, our data showed that diet-induced hypercholesterolemia adversely affects semen quality and sperm motility, capacitation and acrosomal reaction in rabbits; probably due to an increase in cellular cholesterol content that alters membrane related events

Non-pharmacological treatment of hypertension in primary health care: A comparative clinical trial of two education strategies in health and nutrition

<p>Abstract</p> <p>Background</p> <p>Poor adherence to non-pharmacological treatment of hypertension represents a serious challenge for public health policies in several countries. This study was conducted to compare two intervention strategies regarding the adherence of adult women to dietary changes recommended for the treatment of hypertension in a community covered by Primary Health Care Unit.</p> <p>Methods</p> <p>This study is a randomized controlled trial of a sample composed of 28 women with hypertension enrolled in the Primary Health Care Unit located in the urban area of southeastern Brazil. The participants were already undergoing treatment for hypertension but devoid of nutritional care; and were divided into two groups, each composed of 14 individuals, who received interventions that consisted of two different strategies of nutritional guidance: monthly health education workshops alone (Group 1) and combined with family orientation through home visits (Group 2). Adherence to nutritional guidelines was evaluated by dietary, anthropometric, clinical and serum biochemical parameters, measured before and after the interventions. Knowledge on control and risk of hypertension was also investigated. The study lasted five months.</p> <p>Results</p> <p>Mean age was 55.6 (± 2.8) and 50.7 (± 6.5) in the groups 1 and 2, respectively. The home orientation strategy promoted greater adherence to dietary changes, leading to a statistically significant improvement in the clinical, anthropometric, biochemical and dietary parameters. The group 2 reduced the consumption of risk foods (p = 0.01), oil (p = 0.002) and sugar (p = 0.02), and decreased body mass index (-0.7 kg/m²; p = 0.01); waist circumference (-4.2 cm; p = 0.001), systolic blood pressure (-13 mm HG; p = 0.004) and glycemia (-18.9 mg/dl; p = 0. 01). In group 1 only waist circumference (-2 cm; p = 0.01) changed significantly.</p> <p>Conclusion</p> <p>Nutritional orientations at the household level were more effective with regard to the adherence of individuals to non-pharmacological treatment of hypertension, regarding the reduction of clinical and behavioral risk parameters.</p