Epoxide of diosgenin acetate synthesis: DoE for diastereoselective yield optimization, antimicroibial, antioxidant and antiproliferative effects.

Diosgenin and its derivatives have proved a huge importance in diverse biological activities. The optimized production of the diastereoisomers of the epoxide of diosgenin acetate by means of mCPBA is reported herein. This transformation had a previous design of experiments using the application of a statistical factorial DoE of 4 parameters (nk), where one variable is varied at a time, while others stay constant. The temperature showed the greatest effect on the reaction yield; so, at 298 K the diastereomeric ratio 3:1 of α and ß-epoxides, normally found, was raised to 1:1. Time was the second significant variable, but due to its high correlation with temperature, 30 min were required for a global 90% conversion at least. These diastereoisomers were characterized both isolated and in the mixtures obtained, to determine their antioxidant, antimicrobial and antiproliferative activity, finding a low antioxidant capacity by DPPH, but antimicrobial activity at the level of penicillin in gram negative bacteria by 1ß better to 1α. The antiproliferative capacity was higher for diastereoisomer ß, agreeing with the proportion of the mixture obtained by different conditions, increasing this in relation to the amount of this diastereoisomer present in hormone-dependent cancer cell lines such as Hela, PC-3 and MCF-7, with 10.0 µM obtained values of viability at 21.8 %, 35.8 % and 12.3 % respectively. DoE optimization allows to manipulate the ratio between diastereoisomers with the minimum number of experiments, extending the analysis of the effect of the ratio between diastereoisomers and the in silico potential as well as the biological activity.

Deep Seated Density Anomalies Across the Iberia-Africa Plate Boundary and Its Topographic Response.

The modes in which the lithosphere deforms during continental collision and the mechanisms involved are not well understood. While continental subduction and mantle delamination are often invoked in tectonophysical studies, these processes are difficult to be confirmed in more complex tectonic regions such as the Gibraltar Arc. We study the present-day density and compositional structure of the lithosphere along a transect running from South Iberia to North Africa crossing the western Gibraltar Arc. This region is located in the westernmost continental segment of the African-Eurasian plates, characterized by a diffuse transpressive plate boundary. An integrated and self-consistent geophysical-petrological methodology is used to model the lithosphere structure variations and the thermophysical properties of the upper mantle. The crustal structure is mainly constrained by seismic experiments and geological data, whereas the composition of the lithospheric mantle is constrained by xenolith data. The results show large lateral variations in the topography of the lithosphere-asthenosphere boundary. We distinguish different chemical lithospheric mantle domains that reproduce the main trends of the geophysical observables and the modeled P and S wave seismic velocities. A sublithospheric body colder than the surrounding mantle is needed beneath the Betics-Rif to adjust the measured potential fields. We link this body to the Iberian slab localized just to the east of the profile and having some effect on the geoid and Bouguer anomalies. Local isostasy allows explaining most of the topography, but an elastic thickness higher than 10 km is needed to explain local misfits between the Atlas and the Rif Mountains.

Probiotics to prevent necrotising enterocolitis and nosocomial infection in very low birth weight preterm infants.

The aim of the study was to determine whether routine probiotic supplementation (RPS) with Lactobacillus rhamnosus GG (LGG) or Lactobacillus acidophilus +Lactobacillus bifidum is associated with reduced risk of necrotising enterocolitis (NEC)≥Stage II in preterm neonates born at ≤32 weeks' gestation. We conducted a retrospective cohort study on the effect of probiotic supplementation in very low birth weight infants in our neonatal unit by comparing two periods: before and after supplementation. The incidence of NEC≥Stage II, late-onset sepsis and all-cause mortality was compared for an equal period 'before' (Period I) and 'after' (Period II) RPS with LGG or L. acidophillus+L. bifidum. Multivariate logistic regression analysis was conducted to adjust for relevant confounders. The study population was composed of 261 neonates (Period I v. II: 134 v. 127) with comparable gestation duration and birth weights. In <32 weeks, we observed a significant reduction in NEC≥Stage II (11·3 v. 4·8 %), late-onset sepsis (16 v. 10·5 %) and mortality (19·4 v. 2·3 %). The benefits in neonates aged ≤27 weeks did not reach statistical significance. RPS with LGG or L. acidophillus+L. bifidum is associated with a reduced risk of NEC≥Stage II, late-onset sepsis and mortality in preterm neonates born at ≤32 weeks' gestation.

Sexual health in Spanish postmenopausal women presenting at outpatient clinics.

OBJECTIVE: One of the most common complaints among postmenopausal women is a change in sexual drive. The aim of this study was to assess the current state of sexual health in Spanish postmenopausal women who present at outpatient gynecology clinics. METHOD: In this multicenter, observational, cross-sectional, questionnaire-based study, a survey was conducted that included 3026 Spanish postmenopausal women in a routine clinical setting in outpatient gynecology clinics at public and private institutions throughout Spain. We used the Women's Sexual Function questionnaire, which has been validated in Spain. RESULTS: In the multivariate analysis, we found that the best indicators of sexual health in postmenopausal women were a higher education (p < 0.001), working or previously worked (p < 0.001), a stable partner (p < 0.001), living in an urban area (p < 0.01), healthy habits and received information about menopause (p < 0.001). CONCLUSION: These results indicate that it is important to provide health education and information about menopause and the complaints associated with this period in a woman's life.

Estudio de prevalencia del trastorno por déficit de atención e hiperactividad en niños en régimen de acogimiento residencial / Prevalence study of attention deficit hyperactivity disorder in children in residential care

INTRODUCCIÓN: Los niños que se encuentran en régimen de acogimiento residencial constituyen un colectivo de riesgo en el que los problemas médicos pueden alcanzar altas tasas, especialmente aquellos relacionados con la esfera psicológica, donde el trastorno por déficit de atención e hiperactividad (TDAH) es una de las alteraciones del neurodesarrollo más frecuentes. OBJETIVO: El propósito de este estudio fue determinar la prevalencia de TDAH en los niños de un centro de acogida en Albuñol (Granada) en 2016. Material y Métodos. En este estudio transversal se incluyeron los 106 niños de edades comprendidas entre los 5 y los 17 años del Centro Hogar "Cristo Rey". La evaluación psicométrica se basó en la Escala de Vanderbilt de TDAH. Las funciones ejecutivas se evaluaron mediante el Behavior Rating Inventory of Executive Function (BRIEF) en aquellos participantes que cumplieron los criterios de Vanderbilt, y también se aplicaron los criterios del DSM-5 en la entrevista clínica para reforzar el diagnóstico de TDAH. RESULTADOS: La prevalencia de TDAH fue del 17.9% en nuestro grupo, siendo el subtipo inatento el más frecuente. CONCLUSIONES: La prevalencia de TDAH en el centro de acogida "Cristo Rey" fue notablemente elevada en comparación con la prevalencia en niños de la población general. Es necesario seguir investigando acerca de las comorbilidades relacionadas con el TDAH en niños en régimen de acogimiento residencial. Deberían instaurarse programas de detección e intervención en centros de acogida por las repercusiones que puede llegar a tener el TDAH

INTRODUCTION: Children in residential care constitute a risk group in which medical problems can reach high rates, especially those concerned to the psychological sphere, including attention deficit hyperactivity disorder (ADHD), one of the most common neurodevelopmental disorders. OBJECTIVE: The purpose of this study was to determine the prevalence of ADHD in children in a foster care institution in Albuñol (Granada) in 2016. MATERIALS AND METHODS: This cross-sectional descriptive study included 106 children aged 5 to 17 years from "Cristo Rey" foster care institution. Psychometric evaluation was based on Vanderbilt ADHD Diagnostic Rating Scale. Executive functions were tested using the Behavior Rating Inventory of Executive Function (BRIEF) in participants who met Vandebilt criteria, as well Diagnostic and DSM- 5 criteria were applied in a clinical interview to strengthen ADHD diagnosis. RESULTS: The prevalence of ADHD was determined to be 17.9 % in our group, with innatentional subtype being the most important. CONCLUSION: Prevalence of ADHD in "Cristo Rey" foster care institution was visibly high in comparison with estimated prevalence in children general population. Research is needed to identify comorbidities in children in residential care suffering from ADHD. ADHD detection and intervention programmes in residential care must be developed because of its repercussion

Factors determining the use of hormonal therapy and phytotherapy in Spanish postmenopausal women.

OBJECTIVE: To identify women's sociodemographic and variables related to health care with the prescription of hormonal therapy (HT) and phytotherapy (PT) in Spanish postmenopausal women. METHOD: The survey consisted of a multicenter, observational, cross-sectional, questionnaire-based investigation and was conducted among 3022 postmenopausal women. RESULTS: Of all the women, 31.8% reported the use of systemic HT or PT sometime in their lives. Hot flushes and information received about menopause were the most important variables that influence HT and PT use, although far more intense symptoms were observed in those who were inclined to use HT. The use of HT or PT was more frequently reported among women with high levels of education, who came from private clinics and lived in urban areas. Women who had primary ovarian insufficiency or surgical menopause were inclined to use HT. CONCLUSION: Hot flushes and information received about menopause are the most important variables that influence HT and PT use.

Effects of water deficit on radicle apex elongation and solute accumulation in Zea mays L.

In this study, we examined the effects of water deficit on the elongation of radicles of maize seedlings and on the accumulation of solutes in the radicle apices of two maize varieties: VS-22 (tolerant) and AMCCG-2 (susceptible). Sections of radicle corresponding to the first 2 mm of the primary roots were marked with black ink, and the seedlings were allowed to grow for 24, 48, and 72 h in polyvinyl chloride (PVC) tubes filled with vermiculite at three different water potentials (Ψ(w), -0.03, -1.0, and -1.5 MPa). The radicle elongation, sugar accumulation, and proline accumulation were determined after each of the growth periods specified above. The Ψ(w) of the substrate affected the dynamics of primary root elongation in both varieties. In particular, the lowest Ψ(w) (-1.5 MPa) inhibited root development by 72% and 90% for the VS-22 and AMCCG-2 varieties, respectively. The osmotic potential (Ψ(o)) was reduced substantially in both varieties to maintain root turgor; however, VS-22 had a higher root turgor (0.67 MPa) than AMCCG-2 (0.2 MPa). These results suggest that both varieties possess a capacity for osmotic adjustment. Sugar began to accumulate within the first 24 h of radicle apex growth. The sugar concentration was higher in VS-22 root apices compared to AMCCG-2, and the amount of sugar accumulation increased with a decrease in Ψ(w). Significant amounts of trehalose accumulated in VS-22 and AMCCG-2 (29.8 µmol/g fresh weight [FW] and 5.24 µmol/g FW, respectively). Starch accumulation in the root apices of these two maize varieties also differed significantly, with a lower level in VS-22. In both varieties, the proline concentration also increased as a consequence of the water deficit. At 72 h, the proline concentration in VS-22 (16.2 µmol/g FW) was almost 3 times greater than that in AMCCG-2 (5.19 µmol/g FW). Trehalose also showed a 3-fold increase in the tolerant variety. Accumulation of these solutes in the root growth zone may indicate an osmotic adjustment (OA) to maintain turgor pressure.

Saco y pseudosaco. Su importancia en el diagnóstico diferencial ecográfico de la gestación ectópica / Gestational sac and pseudosac. Their importance in ultrasound diagnosis of ectopic pregnancies

En el presente trabajo los autores tratarán de revisar los aspectos prácticos más relevantes y novedosos en relación con el diagnóstico y tratamiento de la gestación ectópica. Presentamos el caso de una paciente que acudió a la consulta de urgencias por metrorragia escasa en el primer trimestre de la gestación y en el que la presencia de un pseudosaco intrauterino dificultó el diagnóstico diferencial entre una gestación eutópica anembrionada, un embarazo heterotópico y un ectópico tubárico. El cuadro cursó con rotura espontánea de este último durante el proceso diagnóstico y precisó tratamiento con legrado evacuador y salpingectomía perlaparotómica, siendo la evolución posterior de la paciente favorable (AU)

We report the case of a pregnant woman who presented to the emergency department with slight vaginal bleeding in the first trimester of pregnancy. The the differential diagnosis between eutopic, heterotopic and tubal ectopic pregnancy was hampered by the presence of an intrauterine pseudosac. The clinical course was complicated by spontaneous rupture of a tubal ectopic pregnancy, which required curettage and laparotomic salpingectomy. The postoperative outcome was favorable. The present article reviews the most important and novel practical features related to the diagnosis and treatment of ectopic pregnancies (AU)

Urinary excretion of phenolic acids by infants and children: a randomised double-blind clinical assay.

OBJECTIVES: The present study, which is part of the ISRCTN16968287 clinical assay, is aimed at determining the effects of cranberry syrup or trimethoprim treatment for UTI. METHODS: This Phase III randomised clinical trial was conducted at the San Cecilio Clinical Hospital (Granada, Spain) with a study population of 192 patients, aged between 1 month and 13 years. Criteria for inclusion were a background of recurrent UTI, associated or otherwise with vesico-ureteral reflux of any degree, or renal pelvic dilatation associated with urinary infection. Each child was randomly given 0.2 mL/Kg/day of either cranberry syrup or trimethoprim (8 mg/mL). The primary and secondary objectives, respectively, were to determine the risk of UTI and the levels of phenolic acids in urine associated with each intervention. RESULTS: With respect to UTI, the cranberry treatment was non-inferior to trimethoprim. Increased urinary excretion of ferulic acid was associated with a greater risk of UTI developing in infants aged under 1 year (RR 1.06; CI 95% 1.024-1.1; P = 0.001). CONCLUSIONS: The results obtained show the excretion of ferulic acid is higher in infants aged under 1 year, giving rise to an increased risk of UTI, for both treatment options.

Efecto de la pérdida prematura de molares primarios sobre la relación horizontal incisiva

La perdida prematura de molares primarios predispone a maloclusiones incluyendo apinamiento, impactacion de dientes permanentes y alteracion de la relacion molar y canina. El objetivo del presente estudio es determinar el efecto de las perdidas prematuras de molares primarios sobre la relacion incisiva horizontal. El estudio es documental, retrospectivo y observacional. Se evaluaron los registros ortodoncicos (historias clinicas, fotografias y radiografias) de 209 pacientes con edades entre 4 a 15 anos. La relacion incisiva horizontal se considero normal (grupo 1) cuando hubo contacto entre en borde incisal del incisivo inferior con la cara palatina del superior, aumentada (grupo 2) cuando habia distancia positiva entre ellos y negativa (grupo3) cuando los bordes incisales se encontraban a tope o en mordida cruzada. Los datos se analizaron utilizando coeficiente Pearson (p.0,001). El 22 por ciento (45 pacientes) presento perdidas prematuras. La prevalencia de perdidas prematuras no tuvo diferencia significativa entre generos y fue mayor en el grupo de 7 a 9 anos. De los pacientes con perdidas prematuras, 6 (13,3 por ciento) se clasifico en el grupo 1; 12 (26,7 por ciento) en el grupo 2 y 27 (60 por ciento) en el grupo 3. Hubo asociacion positiva entre el numero de molares perdidos y la presencia de mordida cruzada anterior, siendo la media de molares perdidos mayor (4, 7) en el grupo 3. Se demostro que las perdidas prematuras de molares primarios tienen una relacion estadisticamentesignificativa con la mordida cruzada anterior, siendo posible que la falta de soporteoclusal posterior favorezca el desplazamiento protrusivo de la mandibula. (AU) FONTE

Normalization of the sleep-wake pattern and melatonin and 6-sulphatoxy-melatonin levels after a therapeutic trial with melatonin in children with severe epilepsy.

This study evaluated the sleep-wake pattern, plasma melatonin levels and the urinary excretion of its metabolite, 6-sulphatoxy-melatonin among children with severe epileptic disorders, before and after a therapeutic trial with melatonin. Ten paediatric patients, suffering from severe epileptic disorders, were selected and given a nightly dose of 3 mg of a placebo, for 1 wk; for the next 3 months, the placebo was replaced with a nightly dose of 3 mg of melatonin. At the end of each treatment period, the urinary excretion of 6-sulphatoxy-melatonin (for the intervals 09.00 - 21:00 hr or 21:00-09:00 hr) and plasma levels of melatonin (recorded at 01:00, 05:00, 09:00, 13:00, 17:00 and 21:00 hr) were recorded, over a period of 24 hr; an actigraph record was also kept. Sleep efficiency among patients who received melatonin was significantly higher than among those given the placebo, with fewer night-time awakenings. Periodic plasma melatonin levels were regained and a better control gained of convulsive episodes, in that the number of seizures decreased. We conclude that melatonin is a good regulator of the sleep-wake cycle for paediatric patients suffering from severe epilepsy, moreover, it to a better control of convulsive episodes.

Efficacy of epoetin-beta 30.000 IU/week in correcting anaemia in patients with gastrointestinal tumours subjected to concomitant chemoradiotherapy

OBJECTIVE: The aim of the project was to assess the effectiveness and safety of weekly epoetin-beta (EB) in patients with gastrointestinal cancer (GIC) subjected to concomitant chemoradiotherapy (CCTRT). METHODS: In this clinical prospective and multicentre cohort study EB was administered at a dose of 30,000 IU/ week, during CCTRT and in the four weeks thereafter, and suspended if haemoglobin (Hb) increased >2 g/dl or Hb >12-13 g/dl. Effectiveness was defi ned as Hb increase ≥1 g/dl vs. baseline. Time to response, treatment toxicity and transfusion requirements were also assessed. RESULTS: EB was effective in 75.8% of the evaluable population within a median of four weeks from EB initiation, without blood transfusions. Over 80% of all patients remained below the threshold (Hb ≤13 g/dl) and no study drug-related adverse reactions were recorded. CONCLUSION: Weekly EB proved to be effective and well tolerated by patients with GIC subjected to CCTRT (AU)

Melatonin and elimination of kynurenines in children with Down's syndrome.

BACKGROUND: Heightened activity of superoxide dimutase is an effect derived from the gene dose in the trisomy of Down's syndrome (DS), and has been related to the increased production of hydrogen peroxide and with greater lipid peroxidation. Many of the degenerative changes observed in patients with DS have been associated with the pathological effects of free radicals, and for this reason it is of interest to determine the levels present in these patients of powerful antioxidant molecules such as melatonin, and of metabolites with important neuroprotector and neurotoxic consequences such as those derived from the kynurenine pathway. PATIENTS AND METHODS: A study was made of 15 children with DS, together with a control group of 15 non-DS children, matched for age and sex, examined at the Hospital Costa del Sol, Marbella, Spain. Serum melatonin and serotonin were analyzed by RIA; urinary tryptophan metabolites (kynurenine pathway) were determined during periods of light and darkness (09.00-21.00 h and 21.00-9.00 h) by thin-layer chromatography. RESULTS: The mean values of serotonin and melatonin were found to be lower in the patients with DS, although the level of nocturnal secretion of melatonin was higher. Urinary excretion of kynurenine was lower in the patients with DS, although greater quantities of kynurenic acid and anthranilic acid were excreted. CONCLUSIONS: Patients with DS present levels of plasma melatonin and urinary kynurenine that are lower than the corresponding levels in the control population, together with higher values of kynurenic acid and anthranilic acid. These circumstances constitute an added risk to these patients of damage by free radicals.

Overweight and obesity as risk factors for the asymptomatic carrier state of Neisseria meningitidis among a paediatric population.

We analysed the asymptomatic carrier state of Neisseria meningitidis in a sample of 339 children. We obtained data for the children's weight and height, in order to calculate the body mass index (BMI). The cutoff points defined by Cole were employed in determining the BMI, and the population was divided into three groups: normal, overweight and obese. Twenty carriers of N. meningitidis were identified. There was found to be a statistically significant trend to increased risk of being a carrier with increased BMI (z=2.03; P=0.04); after adjusting for age using the Mantel-Haenszel weighting method, this relationship was strengthened (z=2.38; P=0.01). Paediatric patients with increased BMI in the range of obesity present a three times greater risk of being carriers of N. meningitidis than non-obese patients, with a trend for this risk to increase with higher BMI.

Effects on the glutathione pool of the insulin-induced hypoglycaemia test.

The growth hormone (GH) stimulation test shows that hypoglycaemia can cause the generation of free radicals, or reactive oxygen species (ROS), together with the migration of amino acids, glutathione and various ions to the interior of fat or muscle cells. The aim of the present study is to evaluate the splitting of plasma glutathione into its two fractions, oxidized (GSSG) and reduced (GSH), after the induction of hypoglycaemia with insulin in the course of the GH stimulation test. We studied 41 short children (47% boys and 53% girls) at the Paediatric Department of the San Cecilio Hospital (Granada, Spain) to evaluate their size and growth. A GH stimulation test using insulin-induced hypoglycaemia was carried out, and GSSG and GSH values in plasma were determined. The glutathione level is associated with the level of glucose reached at 30 min after initiating the test. This provoked an initial reduction in the GSH/GSSG ratio, which fell to a minimum at 30 min after starting the test, although the values rose again at 60 min. The results obtained show that the insulin-induced GH stimulation test produces a decrease in plasma levels of the glutathione pool, that persists at least for 2 hours following the beginning of the test.

Serum melatonin concentration in the child with non-organic failure to thrive: comparison with other types of stress.

Human beings must adapt both to novel, unfavourable conditions and to circumstances of physical or psychological isolation. The initial response to stress depends fundamentally on the activation of the HPA axis. In regaining homeostatic equilibrium, melatonin plays a role due to its synchronising and anti-stress properties. To study the role of melatonin and the pineal gland in the organic and/or behavioural response to acute or chronic stress, 311 children were divided into two large groups: 1) Control Group - 121 healthy children classified, in turn, into 4 control subgroups, one for each pathology being studied; 2) Problem Groups, classified as traumatic stress (n=58), surgical stress (n=38), psychic stress (n=64) and febrile stress (n=30), according to pre-established clinical criteria. These groups were sub-classified according to the degree (low or high) and duration (acute or chronic) of the stress. This study used a case controlled, cross sectional design. Serum melatonin was measured by radioimmunoassay (RIA). In all the situations of acute stress, melatonin increased at a rate directly proportional to the severity and/or duration of the stress-causing stimulus. In contrast, in chronic stress, i.e. the Affective Deprivation Syndrome (or Psychological Dwarfism) with or without non-organic failure to thrive, resulted in the opposite response with a significant reduction of melatonin. In conclusion, in acute stress an increase in the bioavailability of melatonin could contribute to maintaining homeostatic balance. The lack of an appropriate response to acute stress could make some groups of patients (Affective deprivation syndrome with or without growth failure) predisposed to suffer depressive symptoms associated with a wide range of neurological, endocrinological or immunological consequences.

Influence of the antioxidant content of saliva on dental caries in an at-risk community.

OBJECTIVE: This study aims to evaluate the relationship between the total antioxidant capacity of saliva and the presence of dental caries in deciduous and permanent teeth, in a group of Saharan children. METHODS: The dental examination was carried out in accordance with the recommendations of the World Health Organization (WHO). The total antioxidant capacity of the saliva was determined by colorimetry. RESULTS: The total antioxidant capacity (TAC) of the saliva of patients with caries in deciduous teeth was 2.89 1/IC50 greater than among those without. We observed a statistically significant linear regression between the number of deciduous teeth affected by caries and the total antioxidant capacity of the saliva: y = 0.24 + 0.53 x TAC saliva (t = 2.93; p = 0.004) (95% CI of b: 0.018-0.088). CONCLUSIONS: Our results show that the amount of caries in deciduous teeth is in direct proportion to the observed TAC of saliva, and that the presence of caries in deciduous teeth is associated with caries in permanent teeth.

The presence of precursors of benign pre-B lymphoblasts (hematogones) in the bone marrow of a paediatric patient with cytomegalovirus infection.

Hematogones are normal B-lymphoid precursors that multiply in the bone marrow of small children and of adults with ferropenic anaemia, neuroblastoma or idiopathic thrombocytopenic purpura. They are not normally found in peripheral blood, and the immunophenotype is virtually indistinguishable from that of B lymphoblasts. We discuss the case of a 3-month infant with an active cytomegalovirus infection, with hepatitis and pancytopenia associated with 13% hematogones in the bone marrow.