Calibrated prevalence of infertility in 30- to 49-year-old women according to different approaches: a cross-sectional population-based study.

STUDY QUESTION: How does the estimated prevalence of infertility among 30- to 49-year-old women vary when using different approaches to its measurement? SUMMARY ANSWER: The prevalence of women with difficulties in conceiving differed widely according to the measurement approach adopted. WHAT IS KNOWN ALREADY: Establishing the true magnitude of infertility as a public health problem is challenging, given that it is not categorized as a disability or chronic condition and may be largely unreported. The time required to conceive is an increasingly frequent concern among couples of reproductive age. Population-based studies do not consider multiple approaches to infertility measurement in the same sample. STUDY DESIGN, SIZE, DURATION: A face-to-face cross-sectional population-based survey of 443 women aged between 30 and 49 years residing in Huelva, southern Spain, was carried out. The sample size estimation was based on an assumed prevalence of infertility of 19%, a sampling error of ±4.84 percentage points, a design effect of 1.8 and a 95% confidence level. The information was collected in 2011. PARTICIPANTS/MATERIALS, SETTING, METHODS: Self-reported information was gathered on socio-demographic data, pregnancy history, time required to become pregnant and perception of difficulties in becoming pregnant. Eight approaches to the estimation of infertility prevalence were considered: diagnosed infertility, subjective infertility, 1-year infertility, primary infertility, secondary infertility and subfertility based on the time taken to conceive (6, 12 or 24 months). Calibration estimators (indirect estimation techniques) were used to extrapolate the infertility prevalences to the whole of Spain. MAIN RESULTS AND THE ROLE OF CHANCE: The response rate was 61.05%. Among 30- to 49-year-old Spanish women, 1.26% had a clinical diagnosis of infertility, 17.58% did not achieve pregnancy in 1 year (1-year infertility), 8.22% perceived difficulties in procreation (subjective infertility), 6.12% had not succeeded in having biological children (primary infertility) and 11.33% had not been able to have another biological child (secondary infertility). Finally, pregnancy was not achieved within 6, 12 and 24 months of starting to attempt conception in 19.98, 11.21 and 4.36% of women, respectively. These approaches to estimate the prevalence of infertility show similar socio-demographic patterns except for educational level. Calibration adjustments allowed extrapolation of these prevalences to Spain and a reduction of from 3.7 to 90.4% in their variances. LIMITATIONS, REASONS FOR CAUTION: The response rate was moderate but acceptable in comparison to similar studies. We only asked whether the women had practiced intercourse without contraceptive methods for >1 year. Hence, we could only calculate the time for which a couple were trying to become pregnant when the woman became pregnant, and we do not know whether it was longer than 1 year for the women failing to conceive. Future research should avoid this study weakness by gathering quantitative data on the months during which vaginal sexual intercourse was practiced, with no time limit. The only prevalence with a high coefficient of variation was that for diagnosed infertility, and our estimation for this prevalence should be interpreted with caution. WIDER IMPLICATIONS OF THE FINDINGS: Despite major differences according to the approach adopted, the prevalences of infertility estimated in our study are comparable with those obtained in other similar studies. A set of categories to measure infertility including subjective infertility, 1-year infertility and subfertility have been proposed here, which may be useful for cross-disciplinary comparisons of infertility in clinical and population-based studies. These measures may also assist health managers to tailor fertility resources and services to the real needs of the population and provide a more rapid and effective response to couples. Finally, the calibration adjustments (indirect estimation techniques) applied to the infertility prevalences help to maximize their generalization and improve accuracy. This technique may be considered as a model for application in other epidemiological studies.

[High prevalence of vitamin D deficiency among spanish obese children and adolescents]. / Elevada prevalencia de déficit de vitamina D entre los niños y adolescentes obesos españoles'

INTRODUCTION: Vitamin D deficiency has been associated with extra-skeletal outcomes such as, insulin resistance, type 2 diabetes, and cardiovascular disease. The aim of this study is to determine the prevalence of vitamin D deficiency among obese children and adolescents in Spain and to analyze the relationship between 25-OH-vitamin D (25-OH-D) levels and markers of abnormal glucose metabolism. PATIENTS AND METHODS: A cross-sectional study was conducted in which the clinical and biochemical data were recorded for 120 obese and 50 non-overweight children in Pediatric Clinics from January 2011 to January 2013. RESULTS: The mean 25-OH-D levels among obese children was 19.5 ng/ml and among non-overweight children was 31.6 ng/ml. 58,3% of obese subjects, and 10% of non-overweight subjects had vitamin D deficiency. Serum 25-OH-D levels were lower in winter. Higher HOMA-SDS (3.8 versus 2.4), and triglycerides (97 versus 81 mg/dl) were found in vitamin D deficient obese children compared to obese children without vitamin D deficiency. A negative correlation was found between 25-OH-D levels and HOMA in absolute values (r=-0.2; P=.04) that was not maintained when HOMA-SDS was analyzed. CONCLUSIONS: There is a high prevalence of vitamin D deficiency among obese children with a multifactorial etiology. A lower 25-OH-D level could be a risk factor for developing insulin resistance and type 2 diabetes in obese population.

Masa ventricular izquierda, espirometría basal forzada y perfil de adipocitocinas en niños obesos con y sin síndrome metabólico / Left ventricular mass, forced baseline spirometry and adipocytokine profiles in obese children with and without metabolic syndrome

Introducción: En los últimos años, se ha constatado un aumento de las alteraciones de la función cardiaca y pulmonar entre los pacientes obesos. Asimismo, también se ha demostrado que la obesidad es un estado de inflamación crónica. Por ello, hipotetizamos que los niños obesos con síndrome metabólico presentan un porcentaje superior de hipertrofia de ventrículo izquierdo y una espirometría alterada, secundaria a un mayor grado de inflamación. Pacientes y métodos: Estudio de la masa ventricular izquierda mediante ecografía, análisis de espirometría basal forzada mediante espirómetro (FlowScreen) y determinación de perfil de adipocitocinas (adiponectina, IL-6, leptina, MCP-1, PCR-hs, RBP-4, TNF-alfa y visfatina) a niños peripuberales obesos con y sin síndrome metabólico. Resultados: Se incluyó en el estudio a 41 pacientes (20 niñas y 21 niños), 20 de los cuales (10 niños y 10 niñas) presentaban síndrome metabólico. De las adipocitocinas estudiadas, leptina, PCR-hs y MCP-1, y el cociente leptina/adiponectina mostraron valores sustancialmente superiores en el grupo de síndrome metabólico (p<0,01). El análisis de la masa ventricular izquierda y la espirometría no evidenciaron diferencias entre los 2 grupos estudiados. Sin embargo, considerando la muestra completa, el 9,5% de los sujetos tenían ya una hipertrofia ventricular izquierda. Por otro lado, no se encontraron correlaciones significativas entre los datos antropométricos y el perfil de adipocitocinas, ni tampoco con masa ventricular izquierda ni con la espirometría. Conclusión: En el momento del estudio, la masa ventricular izquierda y la espirometría parecen no relacionarse con parámetros inflamatorios en el niño obeso(AU)

Introduction: Recent reports have shown an increase in changes in cardiac and pulmonary function among obese patients. Furthermore, it has also been demonstrated that obesity is a state of chronic inflammation. We hypothesized that obese children with metabolic syndrome exhibit a higher percentage of left ventricular hypertrophy and altered spirometry values due to higher levels of inflammation. Patients and methods: Left ventricular mass was studied using echocardiography, baseline forced spirometry by spirometer (FlowScreen) and adipocytokine profiles (adiponectin, IL-6, leptin, MCP-1, PCR-Hs, RBP-4, TNF-alpha and visfatin) were evaluated in peripubertal obese children with and without metabolic syndrome. Results: Forty-one patients (20 girls and 21 boys) were included in the study, 20 of whom (10 boys and 10 girls) were subjects with metabolic syndrome. Of the adipocytokines studied, only leptin, hs-CRP, MCP-1, and the leptin/adiponectin ratio yielded values that were substantially greater in the group with metabolic syndrome (P<0.01). An analysis of left ventricular mass index and baseline spirometry showed no differences between the groups studied. However, of the entire cohort, 9.5% had left ventricular hypertrophy. No significant relationship was found between anthropometric data and adipocytokines and the parameters used to study left ventricular mass and spirometry values on the other. Conclusion: At the time the study was performed, left ventricular mass and baseline forced spirometry did not appear to be influenced by inflammatory mechanisms(AU)

[Left ventricular mass, forced baseline spirometry and adipocytokine profiles in obese children with and without metabolic syndrome]. / Masa ventricular izquierda, espirometría basal forzada y perfil de adipocitocinas en niños obesos con y sin síndrome metabólico.

INTRODUCTION: Recent reports have shown an increase in changes in cardiac and pulmonary function among obese patients. Furthermore, it has also been demonstrated that obesity is a state of chronic inflammation. We hypothesized that obese children with metabolic syndrome exhibit a higher percentage of left ventricular hypertrophy and altered spirometry values due to higher levels of inflammation. PATIENTS AND METHODS: Left ventricular mass was studied using echocardiography, baseline forced spirometry by spirometer (FlowScreen) and adipocytokine profiles (adiponectin, IL-6, leptin, MCP-1, PCR-Hs, RBP-4, TNF-( and visfatin) were evaluated in peripubertal obese children with and without metabolic syndrome. RESULTS: Forty-one patients (20 girls and 21 boys) were included in the study, 20 of whom (10 boys and 10 girls) were subjects with metabolic syndrome. Of the adipocytokines studied, only leptin, hs-CRP, MCP-1, and the leptin/adiponectin ratio yielded values that were substantially greater in the group with metabolic syndrome (P<.01). An analysis of left ventricular mass index and baseline spirometry showed no differences between the groups studied. However, of the entire cohort, 9.5% had left ventricular hypertrophy. No significant relationship was found between anthropometric data and adipocytokines and the parameters used to study left ventricular mass and spirometry values on the other. CONCLUSION: At the time the study was performed, left ventricular mass and baseline forced spirometry did not appear to be influenced by inflammatory mechanisms.

Opinión de los usuarios del servicio de consultas terapéuticas del Centro Andaluz de Información y Documentación de Medicamentos sobre sus publicaciones / Users opinion of the therapeutic consultation service of the Andalusian Center of Information and Documentation of publications about drugs

Objetivo: El objetivo de este estudio era conocer la opinión que los usuarios del Servicio de Consultas Terapéuticas del Centro Andaluz de Documentación e Información de Medicamentos tenían sobre las publicaciones editadas por el centro. Metodología: Se realizó un estudio descriptivo transversal entre los profesionales sanitarios que realizaron consultas al centro durante el periodo comprendido entre el 1 de junio de 2003 y el 31 de mayo de 2004. La recogida de información se realizó mediante un cuestionario telefónico expresamente diseñado para el estudio. Resultados: Se cumplimentaron un total de 127 cuestionarios, obteniéndose una tasa de contacto del 94,8% y una tasa de respuesta del 100%. La mayoría de los participantes del estudio eran farmacéuticos de hospital y médicos de Atención Primaria, con una media de edad de 43 años. Del total de encuestados, el 81,1% eran receptores de las publicaciones, de los que el 60,2y el 37,0% consideró que éstas eran de utilidad alta y muy alta, respectivamente, para su desempeño professional (AU)

Objective: This aim of the study was to know the users' opinion of the published editions carried out by the Andalusian Documentation and Drug Information Center. Methodology: A cross descriptive study among public health workers, who once asked the center for consultation from June1st, 2003 to May 31st 2004, has been carried out. The compilation of the information has been made by a designed telephone questionnaire specially designed for the study. Results: 127 questionnaires have been ful filled, with a contact rate was of 94.8% and a response rate of 100%. Most of the participants of the study were hospital pharmacists and family doctors with an average age of 43 years. An 81.1% of those polled received the published editions, of which 60.2% and 37.0% considered them to be of high and very high utility for their professional activity, respectively (AU) - and hospitalizations, suggesting the need to take preventive measures as regards to the malnutrition of these patients (AU)

Changes in Trypanosoma cruzi phospholipid turnover induced by parasite contact with cell membranes.

To investigate the possibility that cell contact could initiate a series of signals in both the host cell and the flagellate protozoan Trypanosoma cruzi, we studied [32P]-phospholipid turnover during parasite interaction with cellular membranes in vitro. Lipid alterations were produced in the parasite during the initial period of contact with the plasma membranes of human erythrocytes. In the presence of calcium an increment in phosphatidylethanolamine was observed with a concomitant decrease in phosphatidic acid fractions, whereas these modifications were not observed in the absence of calcium. There was an evident decrease in phosphatidylcholine and a shift in the phosphatidylinositol/lysophosphatidylethanolamine fraction among the phospholipids of major turnover in the absence or presence of calcium. Among the minor labeled species, lysophosphatidylcholine reached levels that duplicated control values, whereas the amounts of lysophosphatidylinositol, phosphatidylinositol 4-phosphate, and phosphatidylinositol 4,5-bisphosphate diminished by over 50%. All of these variations indicate that the parasite's contact with plasma membranes induces changes involving T. cruzi phospholipids and suggest the participation of these compounds in the activation of intracellular mechanisms that might be important during the life cycle of this parasite.

Biphasic and dose-dependent accumulation of INSP3 in Trypanosoma cruzi stimulated by a synthetic peptide carrying a chicken alpha D-globin fragment.

A synthetic peptide corresponding to residues 1 to 40 of chicken alpha D-globin stimulated the accumulation of inositol phosphates (InsPs) in Trypanosoma cruzi epimastigotes. This accumulation was shown to be biphasic and dose-dependent. The enhanced inositol trisphosphate (InsP3) accumulation occurred at the third minute with a subsequent increase which is not transient, but sustained over a much longer period. Another peptide carrying residues 35 to 73 was less active. These results evidenced the activation of the phosphoinositide phospholipase C activity in response to peptides that bind specifically to T. cruzi epimastigote cells.

Carbachol stimulates inositol phosphate formation transiently in Trypanosoma cruzi.

The effect of carbachol on Trypanosoma cruzi epimastigote forms was studied. Suspension of epimastigote cells prelabelled with myo[3H]-inositol were incubated at 28 degrees C in the presence of carbachol. The levels of inositol phosphate after the challenge of carbachol were determined to see if the accumulation of inositol phosphate was time-dependent. In the presence of Li+ the levels of IP3 and IP4 were significantly increased during the 3 min. with a peak at 1 min. after the carbachol challenge. This effect was suppressed by atropine. The results show that carbachol influences rapid changes in phosphoinositide metabolism and they are time-dependent involving second-messenger systems associated with the generation of IP3. In addition they would suggest that this IP3 generation is through a receptor-mediated process linked to phospholipase C by a G-protein.

Phospholipids of Trypanosoma cruzi: increase of polyphosphoinositides and phosphatidic acid after cholinergic stimulation.

We have studied the effect of carbamoylcholine in Trypanosoma cruzi epimastigote forms prelabelled with [32P]-Pi. Suspensions of cells were incubated at 28 degrees C to measure changes in the levels of [32P]-labelled phospholipids after stimulation. The presence of this cholinergic agonist induced changes in the phosphoinositide metabolism; a shift in the levels of phosphatidylinositol 4,5-bisphosphate (PIP2), phosphatidylinositol 4-phosphate (PIP) and phosphatidic acid (PA) was observed, whereas the levels of the other glycerophospholipids were not changed. This study shows that carbamoylcholine either directly or indirectly influences changes in phosphoinositide metabolism.

Pseudomonas aeruginosa acid phosphatase. Activation by divalent cations and inhibition by aluminium ion.

In Pseudomonas aeruginosa, the effect of different cations on the acid phosphatase activity was studied in order to acquire more information related to a previously proposed mechanism, involving the coordinated action of this enzyme with phospholipase C. Although the natural substrate of this enzyme is phosphorylcholine, in order to avoid the possible interaction of its positive charge and those of the different cations with the enzyme molecule, the artificial substrate p-nitrophenylphosphate was utilized. Kinetic studies of the activation of acid phosphatase (phosphorylcholine phosphatase) mediated by divalent cations Mg2+, Zn2+ and Cu2+ revealed that all these ions bind to the enzyme in a compulsory order (ordered bireactant system). The Km values obtained for p-NPP in the presence of Mg2+, Zn2+ and Cu2+ were 1.4 mM, 1.0 mM and 3.5 mM, respectively. The KA values for the same ions were 1.25 mM, 0.05 mM and 0.03 mM, respectively. The Vmax obtained in the presence of Cu2+ was about twofold higher than that obtained in the presence of Mg2+ or Zn2+. The inhibition observed with Al3+ seems to be a multi-site inhibition. The K'app and n values, from the Hill plot, were about 0.25 mM and 4.0 mM, respectively, which were independent of the metal ion utilized as activator. It is proposed that the acid phosphatase may exert its action under physiological conditions, depending on the availability of either one of these metal ions.

Pseudomonas aeruginosa cholinesterase and phosphorylcholine phosphatase: two enzymes contributing to corneal infection.

Choline, acetylcholine and betaine used as the sole carbon, nitrogen or carbon and nitrogen source increase cholinesterase activity in addition to phosphorylcholine phosphatase and phospholipase C activities in Pseudomonas aeruginosa. The cholinesterase activity catalyses the hydrolysis of acetylthiocholine (Km approx. 0.13 mM) and propionylthiocholine (Km approx. 0.26 mM), but not butyrylthiocholine, which is a pure competitive inhibitor (Ki 0.05 mM). Increasing choline concentrations in the assay mixture decreased the affinity of cholinesterase for acetylthiocholine, but in all cases prevented inhibition raised by high substrate concentrations. Considering the properties of these enzymes, and the fact that in the corneal epithelium there exists a high acetylcholine concentration and that Pseudomonas aeruginosa produces corneal infection, it is proposed that these enzymes acting coordinately might contribute to the breakdown of the corneal epithelial membrane.

Identification of the Pseudomonas aeruginosa acid phosphatase as a phosphorylcholine phosphatase activity.

Choline, betaine and N,N-dimethylglycine as the sole carbon and nitrogen source induced a periplasmic acid phosphatase activity in Pseudomonas aeruginosa. This enzyme produced the highest rates of hydrolysis in phosphorylcholine and phosphorylethanolamine among the various phosphoric esters tested. At saturating concentrations of Mg2+, the Km values were 0.2 and 0.7 mM for phosphorylcholine and phosphorylethanolamine respectively. At high concentrations both compounds were inhibitors of the enzyme activity. The Ksi values for phosphorylcholine and phosphorylethanolamine were 1.0 and 3.0 mM respectively. The higher catalytic efficiency was that of phosphorylcholine. Considering these results it is possible to suggest that the Pseudomonas aeruginosa acid phosphatase is a phosphorylcholine phosphatase. The existence of this activity which is induced jointly with phospholipase C by different choline metabolites, in a high phosphate medium, suggests that the attack of Pseudomonas aeruginosa on the cell host may also be produced under conditions of high phosphate concentrations, when the alkaline phosphatase is absent.

Pseudomonas aeruginosa acid phosphatase contains an anionic site with a trimethyl subsite. Kinetic evidences obtained with alkylammonium ions.

In this work the action of the following compounds upon Ps. aeruginosa acid phosphatase has been studied: 1) alkylammonium compounds; 2) aminoalcohols and aminoacids with different substituents (-H, -CH2OH and -CH3) attached to the nitrogen atom; 3) alcohols analogous to some compounds of the above series, but without the amino group. It was found that the enzyme inhibition was more effective with N-trimethylated compounds than with the triethylated ones. The degree of inhibition depended on the number of methyl groups bound to the nitrogen atom. Taking into account the choline and betaine series the hydroxyl derivatives showed more affinity for the enzyme than the carboxylated ones. In each series the Ki values increased with the decrease of methyl groups bound to the nitrogen atom. The presence of a positively charged nitrogen atom in the molecule of the effector was essential. These results enable us to confirm that in the molecule of Ps. aeruginosa acid phosphatase there exists an anionic site with one subsite with affinity for methyl groups.

Pseudomonas aeruginosa acid phosphatase and cholinesterase induced by choline and its metabolic derivatives may contain a similar anionic peripheral site.

Different compounds derived from choline, and obtained by demethylation or by oxidation of the primary alcohol group with subsequent N-demethylation, were tested as inducer agents of acid phosphatase and cholinesterase in Ps. aeruginosa. It was found that betaine and dimethylglycine were the most effective inducers of both enzyme activities. These metabolites including choline itself, were not inducers of acid phosphatase and cholinesterase in other Gram-negative bacteria such as: Escherichia coli, Salmonella typhimurium, Shigella flexneri, Enterobacter liquefacciens and Proteus mirabilis. The acid phosphatase activities found in these bacteria were not inhibited in vitro by choline, betaine and phosphorylcholine. From these results it may be concluded that the acid phosphatase activity from Ps. aeruginosa is different from the same activity observed in the other bacteria. In addition, it is also shown that Ps. aeruginosa acid phosphatase and cholinesterase were inhibited by a number of compounds containing a positively charged amino group, with methyl or ethyl groups bound to it. These results seem to confirm that Ps. aeruginosa acid phosphatase and cholinesterase may contain a similar anionic site.

Induction of acid phosphatase and cholinesterase activities in Ps. aeruginosa and their in-vitro control by choline, acetylcholine and betaine.

Choline, acetylcholine and betaine used as a sole carbon source, effectuate in Ps. aeruginosa an acid phosphatase activity in addition to a cholinesterase activity. Induction of both enzyme activities was repressed by succinate or glucose. Cyclic AMP failed to relieve the repression produced by these compounds. Substrates not related to choline and used as a sole source of carbon, were inefficient to produce induction of both enzymes. The in-vitro action of choline, acetylcholine and betaine on Ps. aeruginosa acid phosphatase and cholinesterase has also been studied. To perform these studies periplasmic extracts obtained by EDTA-lysozyme treatment of the cells grown on choline or betaine as sole source of carbon, were used. Acid phosphatase activity was competitively inhibited by betaine, whereas the inhibition produced by choline and acetylcholine showed competitive and noncompetitive components. Cholinesterase activity was noncompetitively inhibited by betaine. At low acetylthiocholine concentration choline was an inhibitor of cholinesterase, whereas at high substrate concentration choline raised the hydrolysis rate of acetylthiocholine. These findings allow the conclusion that acid phosphatase and cholinesterase are specifically induced by choline and its metabolites derivatives. Kinetic results led us to postulate that acid phosphatase and cholinesterase contain a similar allosteric site. This site would either be of an anionic nature or show affinity to a methyl group or display both characteristics.

Acetylcholinesterase from rat red cells and cholinesterase of Pseudomonas aeruginosa: different types of inhibition by atropine.

The inhibition by atropine of cholinesterase from Pseudomonas aeruginosa has been studied in parallel with the membrane bound acetylcholinesterase from rat red cells. Acetylcholinesterase of rat red cells, like other animal cholinesterases, was competitively inhibited while the cholinesterase from Pseudomonas aeruginosa was partially non competitively inhibited by atropine. These results clearly indicated a different behavior of cholinesterase from Pseudomonas aeruginosa in comparison with the enzyme of Pseudomonas fluorescens and other animal cholinesterases.