Accuracy of the fetal cerebroplacental ratio for the detection of intrapartum compromise in nonsmall fetuses.

OBJECTIVE: To study the accuracy of the cerebroplacental ratio (CPR) for the detection of intrapartum fetal compromise (IFC) in fetuses growing over the 10th centile. METHODS: This was a prospective study of 569 nonsmall fetuses attending the day hospital unit of a tertiary hospital that underwent an ultrasound examination at 36-40 weeks, and were delivered within 4 weeks of examination. IFC was defined as a composite of: abnormal intrapartum fetal heart rate or intrapartum fetal scalp pH < 7.20 requiring cesarean section, neonatal umbilical cord pH < 7.20, 5' Apgar score < 7 and postpartum admission to neonatal or pediatric intensive care units. The accuracy of CPR for the prediction of IFC was calculated alone and in combination with other perinatal parameters using univariate and multivariate logistic regression models, which alternatively included the onset of labor to evaluate the influence of induction of labor (IOL) on IFC and a brief composite adverse outcome of two parameters to prove the strength of the approach. RESULTS: The incidence of IFC was 17.9%. CPR sensitivity was 30.4% for a false positive rate (FFR) of 10 and 14.7% for a FPP of 5% (AUC = 0.62, p < 0.001). The multivariate analysis showed that only fetal gender and parity increased the predictive accuracy of CPR alone, although the improvement was poor (AUC = 0.67, p < 0.001). No differences were observed using any of the alternative models. Finally, IOL had no influence of IFC. CONCLUSION: Despite their apparent normality, a proportion of fetuses growing over the 10th centile suffer IFC. Some of them are suitable for detection by means of CPR

Progression of Doppler changes in early-onset small for gestational age fetuses. How frequent are the different progression sequences?

OBJECTIVE: To evaluate the progression of Doppler abnormalities in early-onset fetal smallness (SGA). METHODS: A total of 948 Doppler examinations of the umbilical artery (UA), middle cerebral artery (MCA) and ductus venosus (DV), belonging to 405 early-onset SGA fetuses, were studied, evaluating the sequences of Doppler progression, the interval examination-labor at which Doppler became abnormal and the cumulative sum of Doppler anomalies in relation with labor proximity. RESULTS: The most frequent sequences were that in which only the UA pulsatility index (PI) became abnormal (42.1%) and that in which an abnormal UA PI appeared first, followed by an abnormal MCA PI (24.2%). In general, 71.3% of the fetuses followed the classical progression sequence UA→MCA→DV, mostly in the early stages of growth restriction (84.1%). In addition, the UA PI was the first parameter to be affected (9 weeks before delivery), followed by the MCA PI and the DV PIV (1 and 0 weeks). Finally, the UA PI began to sum anomalies 5 weeks before delivery, while the MCA and DV did it at 3 and 1 weeks before the pregnancy ended. CONCLUSIONS: In early-onset SGA fetuses, Doppler progression tends to follow a predictable order, with sequential changes in the umbilical, cerebral and DV impedances

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. D. & Stallings, V. Consensus report on nutrition for pediatric patients with cystic fibrosis. J. Pediatr. Gastroenterol. Nutr. 35, 246–259 (2002).Fieker., A., Philpott, J. & Armand, M. Enzyme replacement therapy for pancreatic insufficiency: present and future. Clin. Exp. Gastroenterol. 4, 55 (2011).Sitrin, M. D. Digestion and Absorption of Carbohydrates and Proteins in the Gastrointestinal System 137–158 (Springer, Dordrecht, 2014).Gelfond, D. et al. Intestinal pH and gastrointestinal transit profiles in cystic fibrosis patients measured by wireless motility capsule. Dig. Dis. Sci. 58, 2275–2281 (2013).Robinson, P. J. et al. Duodenal pH in cystic fibrosis and its relationship to fat malabsorption. Dig. Dis. Sci. 35, 1299–1304 (1990).Hunter, J. E. Studies on effects of dietary fatty acids as related to their position on triglycerides. Lipids 36, 655–668 (2001).Hernell, O., Staggers, J. E. & Carey, M. C. 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. Clinical validation of an evidence-based method to adjust pancreatic enzyme replacement therapy through a prospective interventional study in paediatric patients with cystitic fibrosis. PLoS ONE 14, e0213216 (2019).Koumantakls, G. & Radciltf, F. J. Estimating fat in feces by near-infrared reflectance spectroscopy. Clin. Chem. 33, 502–506 (1987).Rivero-Marcotegui, A. et al. Water, fat, nitrogen, and sugar content in feces: reference intervals in children. Clin. Chem. 44, 1540–1544 (1998).Korpi-Steiner, N. L. et al. Comparative analysis of fecal fat quantitation via nuclear magnetic resonance spectroscopy (1H NMR) and gravimetry. Clin. Chim. Acta 400, 33–36 (2009).Dorsey, J. et al. Fat malabsorption in cystic fibrosis: comparison of quantitative fat assay and a novel assay using fecal lauric/behenic acid. J. Pediatr. Gastroenterol. Nutr. 50, 441–446 (2010).Proesmans, M. & De Boeck, K. Omeprazole, a proton pump inhibitor, improves residual steatorrhoea in cystic fibrosis patients treated with high dose pancreatic enzymes. Eur. J. Pediatr. 162, 760–763 (2003).Paz-Yépez, C. et al. Influence of particle size and intestinal conditions on in vitro lipid and protein digestibility of walnuts and peanuts. Food Res. Int. 119, 951–959 (2019).Moore, C. G. et al. Recommendations for planning pilot studies in clinical and translational sciences. Clin. Transl. Sci. 4, 332–337 (2011).Fitzpatrick, J. J. & Kazer, M. W. Encyclopedia of Nursing Research 3rd edn, Vol. 440 (Springer, New York, 2011).Isaac, S. & Michael, W. B. Handbook in Research and Evaluation (Educational and Industrial Testing Services, San Diego, 1995).Asensio-Grau, A. et al. Effect of cooking methods and intestinal conditions on lipolysis, proteolysis and xanthophylls bioaccessibility of eggs. J. Funct. Foods 46, 579–586 (2018).Asensio-Grau, A. et al. 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. Fractionation of fatty acids derived from soil lipids by solid phase extraction and their quantitative analysis by GC-MS. Soil Biol. Biochem. 25, 495–507 (1993).Fiorentini, G. et al. Effect of lipid sources with different fatty acid profiles on intake, nutrient digestion and ruminal fermentation of feedlot nellore steers. Asian-Australas. J. Anim. Sci. 28, 1583 (2015).Perman, J. A., Modler, S. & Olson, A. C. Role of pH in production of hydrogen from carbohydrates by colonic bacterial flora. Studies in vivo and in vitro. J. Clin. Invest. 67, 643–650 (1981).Sellin, J. H. & Hart, R. Glucose malabsorption associated with rapid intestinal transit. Am. J. Gastroenterol. 87, 5 (1992).Tran, T. M. D. et al. Effects of a proton-pump inhibitor in cystic fibrosis. Acta Pediatr. 87, 553–558 (1998).Ayoub, F., Lascano, J. & Morelli, G. Proton pump inhibitor use is associated with an increased frequency of hospitalization in patients with cystic fibrosis. Gastroenterol. Res. 10, 288 (2017)

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

Efecto de la hipercolesterolemia en la via Ras/MAPK durante la capacitación espermática y la reacción acrosomal en conejo new zeland

La hipercolesterolemia es un factor de riesgo para la salud humana. Sin embargo, elcolesterol es un componente de las membranas celulares y caveolina 1 es una proteínaimplicada en su metabolismo. Las caveolinas son una familia de proteínas asociadas avarias funciones de la célula, como transducción de señales, el transporte intracelular, yel control del crecimiento celular y tumoral supresor. Su función depende de suasociación con microdominios de membrana ricos en colesterol proporcionando unvínculo entre la membrana celular y la fisiología espermática. Por lo tanto, el nivelplasmático y celular de este esterol es esencial para la expresión de caveolina 1. En estainvestigación, hemos propuesto que la caveolina 1 posee efecto regulador sobre laseñalización a través de la Ras/MAPK debido a la hipercolesterolemi

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

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