Etiology, presentation and management of urinary tract infections in multiple sclerosis patients: A review of the current literature.

Urinary tract infections (UTIs) present a formidable challenge in the care of individuals affected by multiple sclerosis (MS). Lower urinary tract dysfunction is a prevalent issue among MS patients, predisposing them to an elevated risk of UTIs. When left untreated, UTIs can further exacerbate the already compromised quality of life in individuals with MS. The diagnosis and management of UTIs in MS patients necessitate a careful clinical evaluation. The objective of this review is to delineate preventive strategies and current and developing therapeutic approaches for preventing and treating UTIs associated with urinary dysfunction, catheterization, and upper urinary tract infections in patients with MS. Effectively addressing UTIs and urinary tract dysfunction in individuals with multiple sclerosis calls for a comprehensive, interdisciplinary approach.

Semen cryopreservation in men undergoing cancer treatment: a ten-year study.

BACKGROUND: The advancement of Assisted Reproductive Technologies and the improvement in sperm freezing made male fertility preservation widely available. This study aims to evaluate the impact of cancer diseases on semen parameters before cryopreservation and the reproductive outcomes of patients who have thawed their semen samples. METHODS: An observational, cohort study was conducted on cancer patients submitted to fertility preservation in AUSL-IRCCS of Reggio Emilia between 2007 and 2018. Semen samples were collected before cancer treatments, analyzed and frozen by rapid freezing. On request, these samples were thawed for Assisted Reproductive Technologies procedures. Semen parameters were compared between testicular versus other cancers. RESULTS: We included 329 patients with a successful cryopreservation in 94.5% of cases. Testicular cancer was associated with lower sperm volumes (P=0.041) and lower total sperm concentration (P=0.009) compared to other cancers. No difference was observed about sperm motility and morphology, while oligozoospermia was significantly more frequent in men with testicular cancer (P<0.001). In our cohort, the 8.4% of patients thawed their samples; the usage rate and the embryo transfer rate were significantly higher (P<0.05) among those with a testicular cancer, while pregnancy and livebirth rates did not differ. CONCLUSIONS: Male fertility preservation is feasible, easy to be performed, non-invasive and does not delay cancer treatments. Men affected by testicular cancer had worse semen parameters at cryopreservation but pregnancy and livebirth rates were similar to those achieved by men with other cancers and similar to those achieved with fresh sperm.

How adenomyosis changes throughout pregnancy: A retrospective cohort study.

OBJECTIVE: To study how adenomyosis changes during pregnancy and to possibly correlate these changes to maternal and fetal outcomes. METHODS: Retrospective exploratory cohort study including 254 women with a pre-conceptional/first-trimester scan to document adenomyosis and known obstetric outcome. If visible, adenomyosis signs were documented in each trimester and postpartum. Mann-Whitney U tests or χ2 tests were used for continuous and categorical variables, respectively. RESULTS: A globular uterus was reported in 79% (n = 52) of women with adenomyosis in the first trimester, in 38% (n = 20) and 2% (n = 1) of women in the second and third trimesters, respectively, and postpartum in 77% (n = 34) of women. Asymmetrical thickening (n = 20, 30%) and cysts (n = 15, 23%) were only visible in 1st trimester. Adenomyosis was associated with miscarriage (odds ratio [OR] 5.9, 95% confidence interval [CI] 2.4-14.9, P < 0.001) also in normal conception only (OR 5.1, 95% CI 1.8-14.2, P = 0.002) or adjusting for maternal age (adjusted OR 5.9, 95% CI 2.3-15.2, P < 0.001). Gestational age at delivery was lower in adenomyosis (P = 0.004); the cesarean section rate was higher than in controls (OR 2.5, 95% CI 1.3-4.8, P = 0.007) also adjusting for age (adjusted OR 2.07, 95% CI 1.06-4.08, P = 0.035). CONCLUSIONS: Signs of adenomyosis were visible but progressively disappeared in pregnancy; adenomyosis was associated with an increased risk of early miscarriage. Prospective studies are needed to confirm our results.

Prelabour rupture of the membranes at term: antibiotic overuse in Italy.

BACKGROUND: The proper management of women with premature rupture of membrane (PROM) and not spontaneously entering in labour remains controversial. The aim of this study was to identify the current management for women with PROM at term according to the Group B Streptococcus (GBS) status across different Italian hospitals. METHODS: Anonymous online survey evaluating: the current practice of women with PROM in terms of management (expectant management vs. induction of labour) and antibiotic prophylaxis according to GBS status. RESULTS: In case of negative GBS status, the 82.4% of respondents wait until 24 hours before labour induction. Antibiotics are administered for prophylaxis in 35.3%, 27.5% and 2% at 18, 12 and 24 hours respectively. The remaining 35.3% of respondents are divided between those using antibiotics only with signs of infections or according to different risk factors (i.e. meconium-stained amniotic fluid or suspected infection). Neonates born from a mother with negative GBS status almost never (90.2%) receive prophylactic antibiotics. In case of positive GBS status, induction is started as soon as possible by 49.1% of respondents; the remnants choose to wait 6 (15.7%), 12 (17.6%), 18 (3.9%) and 24 (13.7%) hours. Antibiotics are administered as soon as possible by 78.4% of clinicians. In the neonates, 51% of neonatologist administer antibiotics upon clinical indications (suspected sepsis); 15.7% use antibiotics routinely or with a short interval between maternal antibiotics and delivery (17.6%). CONCLUSIONS: The management after PROM is highly heterogeneous with an inappropriate extension of antibiotic prophylaxis in cases with negative GBS status.

Complete hydatidiform mole in higher-order multiple pregnancies.

Molar degeneration of the trophoblast is a rare, yet possible, complication of pregnancies. Complete hydatidiform mole is the most common histological type among all trophoblastic tumors and it is the result of the fertilization of an empty oocyte from two sperms or by one sperm that then duplicates. Complete mole is characterized by hydropic degeneration of abnormal chorionic villi, diffused trophoblast hyperplasia and the absence of identifiable embryonic or fetal tissue; the hyperplastic trophoblast justifies the common finding of high serum beta HCG levels. Twin molar pregnancy is an uncommon obstetric event, and even less frequent are triplet/quadruplet molar pregnancies. We hereby report a case of a complete hydatidiform mole with two coexistent fetuses in a triplet pregnancy after in vitro fertilization procedure; the pregnancy ended with a therapeutic abortion. During the follow-up, the serum beta human chorionic gonadotropin concentration started to rise, and the diagnosis of post-molar gestational trophoblastic neoplasia was made and consequently methotrexate treatment was started. Due to the rarity of this condition, there are no specific guidelines for the management of multiple pregnancies complicated by complete hydatidiform mole. We therefore performed a review of the literature including all reported cases of triplets/quadruplets pregnancies complicated by complete mole of a fetus focusing on ultrasound diagnosis, treatment and outcomes of this rare and life-threatening condition.

Role of balloon tamponade during cesarean section in women with placenta previa: a systematic review and meta-analysis.

INTRODUCTION: To explore the role of balloon tamponade insertion in pregnancies complicated by placenta previa. EVIDENCE ACQUISITION: Medline, Embase and ClinicalTrials.gov databases were searched electronically on October 17. Inclusion criteria were women with placenta previa undergoing, compared to those not undergoing, balloon tamponade insertion at the time of the cesarean section (CS). The outcomes observed were total, intra- and post-operative estimated blood loss (EBL), need for blood transfusion, admission to intensive care unit (ICU), hysterectomy and additional surgical or medical procedures to achieve hemostasis. Results were reported as pooled odd ratios (OR) or mean difference (MD) according to the outcome investigated. EVIDENCE SYNTHESIS: Four studies (593 women) were included. Total EBL was significantly lower in women undergoing balloon tamponade insertion during CS compared to controls (MD: -556.3, 95% CI -496 to -617.0, P=0.001). Likewise, women undergoing balloon tamponade insertion had significantly lower intra- (MD: -699.8, 95% CI -766.1 to -633.5, P=0.001) and post-operative (MD: -1162 mL (95% CI -1211.1 to -1134.4, P<0.001) compared to women who did undergo such procedure. Furthermore, women undergoing balloon tamponade insertion had a significantly lower risk of requiring additional surgical (OR: 0.16, 95% CI 0.1-0.5, I2=0%; P=0.001) or medical (OR: 0.02, 95% CI 0.003-0.1, I2=0; P=0.001) procedures to achieve hemostasis. Conversely, there was no significant difference in either the need for blood transfusion (P=0.071), admission to ICU (P=0.459) or need for hysterectomy (P=0.312) between women undergoing, compared to those not undergoing, balloon tamponade insertion during CS for placenta previa. CONCLUSIONS: Elective balloon tamponade insertion at the time of CS for placenta previa seems to be associated with a lower EBL and a reduced risk of additional medical and surgical procedures to control hemostasis. Large and adequately powered randomized controlled trials are needed to validate these results and introduce elective balloon tamponade insertion at the time of CS for placenta previa in clinical practice.

Entropy of city street networks linked to future spatial navigation ability.

The cultural and geographical properties of the environment have been shown to deeply influence cognition and mental health1-6. Living near green spaces has been found to be strongly beneficial7-11, and urban residence has been associated with a higher risk of some psychiatric disorders12-14-although some studies suggest that dense socioeconomic networks found in larger cities provide a buffer against depression15. However, how the environment in which one grew up affects later cognitive abilities remains poorly understood. Here we used a cognitive task embedded in a video game16 to measure non-verbal spatial navigation ability in 397,162 people from 38 countries across the world. Overall, we found that people who grew up outside cities were better at navigation. More specifically, people were better at navigating in environments that were topologically similar to where they grew up. Growing up in cities with a low street network entropy (for example, Chicago) led to better results at video game levels with a regular layout, whereas growing up outside cities or in cities with a higher street network entropy (for example, Prague) led to better results at more entropic video game levels. This provides evidence of the effect of the environment on human cognition on a global scale, and highlights the importance of urban design in human cognition and brain function.

Ultrasound screening for fetal anomalies in a single center: diagnostic performances twenty years after the Eurofetus Study.

PURPOSE: To establish the accuracy of ultrasound in detecting fetal anomalies looking at the concordance between prenatal and postnatal diagnosis. MATERIALS AND METHODS: Retrospective analysis of concordance between prenatal and postnatal/autoptic diagnosis of fetuses with congenital abnormalities. Data are from a single center (Policlinico di Modena); all fetuses included were born between 2017 and 2018 and with a follow-up of at least 6 months. We included all deliveries (including perinatal deaths) and termination of pregnancy (TOP) for fetal indication. We calculated sensibility, sensitivity, Positive and Negative Likelihood Ratio, positive and negative predictive value of ultrasound. RESULTS: During the study period 5920 deliveries, including perinatal deaths, and 28 TOP for fetal indication were registered at our center. The prevalence of congenital malformations was 2.6% (153/5920). At least one ultrasound was performed in our center in 1250 women delivering in our unit. All 28 TOP had the anomaly scan performed in our center. Among the total 1278 women scanned in our unit, there were 128 (10%) suspicious scans. In 5/128 (3.9%) cases we diagnosed a false alarm; in 8/128 (6.2%) cases an evolutive malformation with in-utero regression. The prenatal diagnosis was confirmed in 77 (60.2%) cases at birth and in 28/128 (21.9%) at postmortem analysis while there were 10/128 false positive (7.8%). Among the 153 congenital malformations diagnosed at birth, the anomaly scan was performed in our Prenatal Medicine Unit in 92 (60.1%) fetuses. Among these, there were 15 false negatives (9.8%) while in 77/92 (83.7%) the malformation at birth agreed with the sonographic diagnosis. Sensitivity and specificity of ultrasound were 87.5% (IC95 80.2-92.8%) and 99.1% (IC95 98.4-99.6%) respectively with a Positive Likelihood Ratio and Negative Likelihood Ratio of 101.3 (IC95 54.5-188.5) and 0.13 (IC95 0.08-0.2); Positive Predictive Value and Negative Predictive Value were 91.3% (IC95 85-95.1%) and 98.7(IC95 98-99.2%). CONCLUSION: Anomaly scan in pregnancy allows the diagnosis of congenital malformations with a sensibility of 87.5% and specificity of 99.1%. The main limitations of this study are its retrospective design and that it was conducted in a single referral center.

La telerehabilitación durante la pandemia COVID-19: experiencia de las familias de niños con condiciones crónicas complejas / Telerehabilitation during the COVID-19 pandemic: experience of families of children with complex chronic conditions

La telerehabilitación ha sido una solución rápida y efectiva para la atención de pacientes durante la pandemia COVID-19. Nuestro objetivo ha sido describir la experiencia de las familias de niños con condiciones crónicas complejas (CCC) asistidos con la modalidad de telerehabilitación durante la pandemia. Materiales y métodos: Se ha realizado un estudio observacional, descriptivo y transversal de tipo encuesta online. Se encuestaron familias de niños (1 mes a 5 años de edad) con al menos una CCC que recibieron seguimiento interdisciplinario a distancia durante la pandemia de 2 o más áreas de rehabilitación (kinesiología, fonoaudiología y terapia ocupacional) pertenecientes al Servicio de Kinesiología del Hospital de Pediatría Juan P Garrahan, durante marzo a octubre de 2020. Resultados: El 88,3% de los participantes (n=43) se expresó satisfecho con la modalidad de telerehabilitación. Entre los facilitadores seleccionados por los participantes se mencionan la reducción de tiempos, mayor frecuencia de consultas, disminución de gastos por traslados y mayor comodidad, mientras que entre las barreras se destacaron: el no vínculo con profesionales, alargue en tiempos de tratamiento, problemas de conectividad. El análisis estadístico no indicó diferencias significativas entre quienes se reportaron como más satisfechos según su estrato social (alto o bajo), la disponibilidad de wifi propio, o respecto a la edad del niño. Se reportaron diferencias significativas en cuanto a la distancia al hospital (p=0.034). Conclusión: Esta forma de intervención ofreció nuevas posibilidades de atención que podrían considerarse a futuro en el seguimiento de nuestros pacientes. (AU)

Telerehabilitation has been a fast and effective solution in patient care during the COVID-19 pandemic. Our aim was to describe the experience of families of children with complex chronic conditions (CCC) treated through telerehabilitation during the pandemic. Materials and methods: An observational, descriptive, cross-sectional, online survey study was conducted. Families of children (1 month to 5 years of age) with at least one CCC who received interdisciplinary remote follow-up during the pandemic from two or more rehabilitation areas (physical therapy, speech therapy, and occupational therapy) belonging to the Department of Physical Therapy of Hospital de Pediatría Juan P Garrahan, from March to October 2020, were surveyed. Results: 88.3% of the participants (n=43) expressed satisfaction with the telerehabilitation modality. Among the facilitators selected by the participants, the following were mentioned: time saving, greater frequency of consultations, reduction of travel expenses and greater comfort, while among the barriers, the following stood out: no connection with the professionals, longer treatment times, connectivity problems. Statistical analysis did not show significant differences between those who reported being more satisfied according to socioeconomic level (high or low), availability of their own wifi connection, or age of the child. A significant difference was found for distance to the hospital (p=0.034). Conclusion: This type of intervention provided new possibilities of care that could be considered in the future follow-up of our patients (AU)

Maternal and neonatal outcomes of pregnancies complicated by late fetal growth restriction undergoing induction of labor with dinoprostone compared with cervical balloon: A retrospective, international study.

INTRODUCTION: The aim of this study was to compare vaginal dinoprostone and mechanical methods for induction of labor (IOL) in pregnancies complicated by late fetal growth restriction. MATERIAL AND METHODS: Multicenter, retrospective, cohort study involving six referral centers in Italy and Spain. Inclusion criteria were pregnancies complicated by late fetal growth restriction as defined by Delphi consensus criteria. The primary outcome was the occurrence of uterine tachysystole; secondary outcomes were either cesarean delivery or operative vaginal delivery for non-reassuring fetal status, a composite score of adverse neonatal outcome and admission to neonatal intensive care unit (NICU). Univariate and multivariate logistic regression analysis was used to analyze the data. RESULTS: A total of 571 pregnancies complicated by late fetal growth restriction undergoing IOL (391 with dinoprostone and 180 with mechanical methods) were included in the analysis. The incidence of uterine tachysystole (19.2% vs. 5.6%; p = 0.001) was higher in women undergoing IOL with dinoprostone than in those undergoing IOL with mechanical methods. Similarly, the incidence of cesarean delivery or operative delivery for non-reassuring fetal status (25.6% vs. 17.2%; p = 0.027), composite adverse neonatal outcome (26.1% vs. 16.7%; p = 0.013) and NICU admission (16.9% vs. 5.6%; p < 0.001) was higher in women undergoing IOL with dinoprostone than in those undergoing IOL with mechanical methods. At logistic regression analysis, IOL with mechanical methods was associated with a significantly lower risk of uterine tachysystole (odds ratio 0.26, 95% confidence interval 0.13-0.54; p < 0.001). CONCLUSIONS: In pregnancies complicated by late fetal growth restriction, IOL with mechanical methods is associated with a lower risk of uterine tachysystole, cesarean delivery or operative delivery for non-reassuring fetal status, and adverse neonatal outcome compared with pharmacological methods.

Pregnant woman infected by Coronavirus disease (COVID-19) and calcifications of the fetal bowel and gallbladder.

COVID-19 was declared to be a pandemic due to the rapid increase of cases around the world, including the number of pregnant women. Data about vertical transmission of COVID-19 are still limited and controversial: in most cases, although a positive mother, the virus could not be isolated in amniotic fluid, cord blood, breast milk or neonatal throat swab in these patients. No data have been published about possible intrauterine sonographic signs of infection. A pregnant woman was diagnosed with SARS-CoV-2 at 35+5 weeks of gestation and managed conservatively at home. At transabdominal ultrasound at 38+3 weeks, fetal bowel and gallbladder calcifications were noted. CMV and other infectious agents were ruled out; an iterative caesarean section was performed at 38+5 weeks without complications. Placenta resulted negative for SARS-CoV-2; the umbilical cord blood sample was IgG positive and IgM negative as per maternal infection. The baby developed respiratory distress syndrome requiring endotracheal surfactant administration and nasal-CPAP for one day but nasopharyngeal swabs at birth and after 48 hours were SARS-CoV-2 negative. Neonatal abdominal ultrasound showed normal liver, acalculous gallbladder with mild parietal thickening. The baby was discharged in good conditions. Although gallbladder calcifications and echogenic bowel are highly suspicious of viral infection and were thought to be due to the vertical transmission of SARS-CoV-2, these findings were not corroborated by the results of our diagnostic tests; these sonographic findings might represent a false positive of fetal infection in mother affected by COVID-19 since vertical transmission appears to be rare.

Perinatal outcomes of twin pregnancies affected by early twin-twin transfusion syndrome: A systematic review and meta-analysis.

INTRODUCTION: Twin-to-twin transfusion syndrome (TTTS) is associated with a high risk of perinatal mortality and morbidity if not treated. However, the optimal timing and management in case of early (occurring < 18 weeks) TTTS has not been established yet. MATERIAL AND METHODS: This is a systematic review and meta-analysis aiming at evaluating the outcomes of monochorionic diamniotic twin pregnancies complicated by early (ie before 18 weeks) TTTS according to different management options (expectant, laser therapy, amnioreduction or cord occlusion). The primary outcome was mortality, including single and double intrauterine, neonatal and perinatal death. Secondary outcomes were: composite morbidity, neuromorbidity, respiratory distress syndrome, admission to neonatal intensive care unit, intact survival (defined as survival free from neurological complications) and preterm birth < 32 weeks of gestation. All outcomes were reviewed according to the different management options (expectant, laser therapy, amnioreduction or cord occlusion) and reported FOR the overall population of twins, and for the donor and recipient separately. Subgroup analysis for TTTS occurring before 16 weeks of gestation was performed. Random-effect meta-analyses of proportions were used to analyse the data. RESULTS: Thirteen studies were included. Early TTTS occurred in 14.3% (95% confidence interval [CI] 11.9-17.0) of cases. The incidence of intrauterine death was 19.0% (95% CI 2.6-45.5) in twins managed expectantly, 32.4% (95% CI 16.5-50.7) in those who received laser treatment and 12.5% (95% CI 4.8-23.0) in those treated with amnioreduction. The incidence of neonatal death was 22.6% (95% CI 4.2-49.8) in twins managed expectantly, 24.7% (95% CI 0.5-80.3) in those who received laser and 20.2 (95% CI 5.8-43.4) in those who had amnioreduction; it was not possible to compute the incidence of these outcomes in twins undergoing cord occlusion because of insufficient sample and lack of reporting of most of the observed outcomes. Overall, the incidence of perinatal death was 43.9% (95% CI 5.9-87.7) in twins managed expectantly, 47.3% (95% CI 21.4-70.0) in those treated with laser and 28.5% in those who had amnioreduction. CONCLUSIONS: Twin pregnancies affected by early TTTS are at substantial risk of perinatal mortality and morbidity; however, the data come from very small studies with a high risk of selection bias.

Disfagia pediátrica: rol del fonoaudiólogo como parte de un equipo interdisciplinario en el Hospital Juan P. Garrahan / Dysphagia in children: The role of the speech therapist in the interdisciplinary team of Hospital Juan P. Garrahan

Introducción: El 80% de los niños con condiciones médicas crónicas complejas presentan alteración de la conducta alimentaria. Dada la heterogeneidad de los diagnósticos y la complejidad en el manejo de la disfagia pediátrica, es muy importante la intervención de equipos especializados. Objetivo: Evaluación de la evolución de los niños con trastornos de la deglución y/o conducta alimentaria atendidos durante el año 2017 por el equipo interdisciplinario de deglución y conducta alimentaria, del Hospital de Pediatría Juan P. Garrahan. Material y métodos: Estudio analítico, prospectivo y longitudinal con la intervención de un equipo interdisciplinario. Se incluyeron todos los pacientes evaluados durante el año 2017. Se realizó evaluación clínica de la deglución que permitió detectar dificultades durante el momento de la alimentación. Se dieron pautas de estimulación y modificación de consistencias y se derivó a tratamiento oportuno. Se midió porcentaje de destete de soporte nutricional (SN) y/o aumento del aporte por vía oral. Resultados: evaluamos 153 pacientes, 39% mujeres, 90% menores de 3 años de edad y el 75% en apoyo nutricional. El 72% presentó trastorno de la deglución exclusivamente o asociado a trastorno de la conducta alimentaria. El 68% fue seguido en más de una oportunidad. El 36% de los pacientes que ingresaron con requerimiento de SN lograron el destete (sin diferencia significativa entre los que tenían o no trastorno deglutorio p=0.85 y los que tenían o no traqueostomía p=0,88) y 40% aumentó el aporte por vía oral dentro del grupo que no logró el destete. Se observó una diferencia estadísticamente significativa en el destete de los pacientes que concurrieron al espacio de la clínica con respecto a los que no(p=0,016) y mayor tiempo de intervención entre quienes lograron el destete y quienes no, 5,2 ± 3,1 vs 3,45 ± 3,1 meses (p=0,0099). Conclusión: Es esencial el trabajo interdisciplinario y especializado en niños con trastornos de la deglución. La intervención del fonoaudiólogo como parte del equipo es fundamental para una detección precoz y correcto abordaje de la disfagia (AU)

Of all children with chronic complex medical conditions, 80% have eating behavior disorders. Given the heterogeneity of the diagnoses and the complexity of the management of dysphagia in children, intervention of a specialized medical team is essential. Objective: Evaluation of the outcome in children with swallowing and/or eating behavior disorders seen during 2017 by the interdisciplinary group of swallowing and eating behavior disorders at Hospital de Pediatría Juan P. Garrahan. Material and methods: An analytical, prospective and longitudinal study with intervention by an interdisciplinary team. All patients evaluated during 2017 were included. Swallowing was clinically assessed to identify eating disorders. Indications were given for stimulation and food consistency and patients were referred for adequate treatment. The rates of weaning from nutritional support (NS) and/or increase of oral food intake were measured. Results: 153 patients were evaluated, 39% were female, 90% younger than 3 years of age, and 75% AN. Overall, 72% had swallowing difficulties only or associated with an eating behavior disorder; 68% was followed on more than one occasion. Thirty-six percent of the patients who were admitted with NS requirement could be weaned (without a significant difference between those who had a swallowing disorder and those who did not p=0.85 and those that did and did not have a tracheostomy p=0.88) and oral food intake increased in 40% of the patients in the group that could not be weaned. A statistically significant difference was found in the weaning of patients who attended the clinic and those who did not (p=0.016) and longer intervention time between those who could be weaned and those who could not, 5.2 ± 3.1 vs 3.45 ± 3.1 months (p=0.0099). Conclusion: Interdisciplinary and specialized care is necessary for children with swallowing disorders. Intervention of a speech therapist as part of the team is fundamental for the early detection and adequate management of dysphagia (AU)

Designing valid and optimised standard addition calibrations: Application to the determination of anions in seawater.

A strategy for designing valid standard addition calibrations and for optimising their uncertainty is presented. The design of calibrations involves the development of models of the sensitivity and precision of the instrumental signal, in a wide range of analyte concentration (or any other studied quantity), and the definition of sample dilution and standard addition procedures that allow fulfilling the assumptions of the linear unweighted regression model in, typically, a smaller range of standard addition calibrations. Calibrators are prepared by diluting the sample and adding analyte with negligible uncertainty to fit in a concentration range where signals are homoscedastic. The minimisation of the uncertainty is supported on detailed measurement uncertainty models function of the calibrators preparation procedure and of analytical instrumentation performance. The number of collected signals replicates is defined by balancing their impact on the estimated expanded uncertainty, the resources needed and the target (maximum) uncertainty for the intended use of measurements. The calibration design strategy was successfully applied to the determination of the mass concentration (mg L(-1)) of Cl(-), Br(-), NO3(-) and SO4(-2) in seawater by ion chromatography. A target expanded uncertainty of 20% was defined for the determination of Cl(-), NO3(-) and SO4(-2), or 40% for the determination of the smaller mass concentration of Br(-). The developed measurement model produced reliable predictions of the measurement uncertainty from approximate concentration of the analyte in the sample, before its accurate quantification, thus proving optimisation is effective. Predictions are more prone to the variability of the measurement uncertainty estimation if based on low number of calibrators signals. The reported relative expanded uncertainty ranged from 7.1% to 49%.

Carotenoid stability in fruits, vegetables and working standards - effect of storage temperature and time.

The effects of freezing and storage temperature on the mass fraction of α- and ß-carotene, ß-cryptoxanthin, lutein, lycopene and zeaxanthin in minimally processed fresh food products, were evaluated after sample preparation, extraction and saponification (only when strictly necessary). Effects of freezing and long-term stability were studied at two temperatures, -20 and -70°C, using high performance liquid chromatography (reversed phase columns, UV-Vis diode array detector) at time points during storage; measurement uncertainty was included in the evaluation. Stability of working standard solutions was also examined. Freezing did not affect the carotenoid mass fraction under the conditions studied. Carotenoids in orange, cherry, peach, apple, and kale were stable (except α-carotene and zeaxanthin in peach) for 13, 9.7, 5.7, 2.5 and 7.5months, respectively. For these food sample matrices, no significant difference between the freezing/storage at -20 and -70°C was observed. Standard solutions (0.05-5µg/mL) were stable for at least 6months at -70°C, except lycopene which at 0.05µg/mL was apparently stable only for six weeks.

Weighted calibration with reduced number of signals by weighing factor modelling: application to the identification of explosives by ion chromatography.

The linear weighted regression model (LW) can be used to calibrate analytical instrumentation in a range of quantities (e.g. concentration or mass) wider than possible by the linear unweighted regression model, LuW (i.e. the least squares regression model), since this model can be applied when signals are not equally precise through the calibration range. If precision of signals varies within the calibration range, the regression line should be defined taking into account that more precise signals are more reliable and should count more to define regression parameters. Nevertheless, the LW requires the determination of the variation of signals precision through the calibration range. Typically, this information is collected experimentally for each calibration, requiring a large number of replicate collection of signals of calibrators. This work proposes reducing the number of signals needed to perform LW calibrations by developing models of weighing factors robust to daily variations of instrument sensibility. These models were applied to the determination of the ionic composition of the water soluble fraction of explosives. The adequacy of the developed models was tested through the analysis of control standards, certified reference materials and the ion balance of anions and cations in aqueous extracts of explosives, considering the measurement uncertainty estimated by detailed metrological models. The high success rate of the comparisons between estimated and known quantity values of reference solutions, considering results uncertainty, proves the validity of developed metrological models. The relative expanded measurement uncertainty of single determinations ranged from 1.93% to 35.7% for calibrations performed along 4 months.

Evaluation of the performance of the determination of anions in the water soluble fraction of atmospheric aerosols.

The knowledge of the mass of particulate matter in air, its chemical composition and emission sources is of relevance for taking decisions concerning air quality management in urban areas. The interpretation of these data is a function of the quality of the measurement results expressed by their uncertainties. This study aimed at developing models of the performance of the determination of anions in the water-soluble fraction of atmospheric aerosols, capable of determining, separately, the contribution of aerosols sampling, extraction of water-soluble fraction of atmospheric aerosols and quantification, by ion chromatography, of anions in the extract. The sampling procedure was assessed from the dispersion of results of duplicate parallel sampling after subtracting the analytical component of this dispersion. These models are used to evaluate the adequacy of the measurement procedure for the determination of urban aerosol composition and to support strategies for reducing measurement uncertainty or cost of analysis. The method performance was studied for the following ranges considering extract dilution up to five times: 0.23-8 µg m(-3) for chloride and nitrate, and 0.093-3.25 µg m(-3) for sulphate. Measurements are fit for the analysis of urban aerosols since the relative expanded measurement uncertainty is smaller than a maximum value of 40%. The percentage contribution of the uncertainty components varies with the analyte and its mass concentration, the major components being 24-93% for the extraction, 43-59% for sampling, 0.2-28% for the interpolation of the sample signal in the calibration curve and 4-8% for air volume measurement. The typical composition of analysed air is: (1.12±0.26) µg m(-3), (1.02±0.30) µg m(-3) and (0.76±0.22) µg m(-3) of chloride, nitrate and sulphate in the water soluble fraction of aerosol, respectively, for a confidence level of approximately 95% considering a coverage factor of 2.

Pathological role of serum- and glucocorticoid-regulated kinase 1 in adverse ventricular remodeling.

BACKGROUND: Heart failure is a growing cause of morbidity and mortality. Cardiac phosphatidylinositol 3-kinase signaling promotes cardiomyocyte survival and function, but it is paradoxically activated in heart failure, suggesting that chronic activation of this pathway may become maladaptive. Here, we investigated the downstream phosphatidylinositol 3-kinase effector, serum- and glucocorticoid-regulated kinase-1 (SGK1), in heart failure and its complications. METHODS AND RESULTS: We found that cardiac SGK1 is activated in human and murine heart failure. We investigated the role of SGK1 in the heart by using cardiac-specific expression of constitutively active or dominant-negative SGK1. Cardiac-specific activation of SGK1 in mice increased mortality, cardiac dysfunction, and ventricular arrhythmias. The proarrhythmic effects of SGK1 were linked to biochemical and functional changes in the cardiac sodium channel and could be reversed by treatment with ranolazine, a blocker of the late sodium current. Conversely, cardiac-specific inhibition of SGK1 protected mice after hemodynamic stress from fibrosis, heart failure, and sodium channel alterations. CONCLUSIONS: SGK1 appears both necessary and sufficient for key features of adverse ventricular remodeling and may provide a novel therapeutic target in cardiac disease.

Development and validation of a grouping method for pesticides analysed in foodstuffs.

The cost effective monitoring of hundreds of pesticide residues in foodstuffs of vegetable origin involves the definition of groups of analytes associated with homogeneous performance parameters of the used analytical method. The performance of the analytical method only needs to be tested on a daily base for some of these group's compounds. This work proposes a strategy for defining groups of compounds with homogeneous physical-chemical properties based on the evaluation of the similarity of the multivariate pattern of five of these properties namely: molar mass, melting point, vapour pressure at 20 °C, n-octanol-water partition coefficient and solubility in water at 20 or 25 °C. Three independent and competing multivariate analysis tools, namely Principal Component Analysis, Hierarchical Clustering and K-Mean Clustering were used. This strategy was successfully used to group 100 pesticides into nine clusters, with 1-40 pesticides, represented by a compound with within group average properties. The developed grouping method was validated using physical-chemical data from other references or compounds and produced groups consistent with the performance of the studied determination of pesticide residues in dried red bean. The mean analyte recoveries of groups with larger dimension are statistically different for a confidence level of 95%. The within group coefficients of variance of mean analyte recoveries of larger groups ranged from 6.7% to 8.5%. This grouping method can reduce the number of recovery tests performed for the validation of the analytical method or test quality control.

Optimization of the determination of chemical oxygen demand in wastewaters.

Chemical oxygen demand (COD) is one of the most relevant chemical parameters for the management of wastewater treatment facilities including the control of the quality of an effluent. The adequacy of decisions based on COD values relies on the quality of the measurements. Cost effective management of the minor sources of uncertainty can be applied to the analytical procedure without affecting measurement quality. This work presents a detailed assessment of the determination of COD values in wastewaters, according to ISO6060:1989 standard, which can support reduction of both measurement uncertainty and cost of analysis. This assessment includes the definition of the measurement traceability chain and the validation of the measurement procedure supported on sound and objective criteria. Detailed models of the measurement performance, including uncertainty, developed from the Differential Approach, were successfully validated by proficiency tests. The assumption of the measurement function linearity of the uncertainty propagation law was tested through the comparison with the numerical Kragten method. The gathered information supported the definition of strategies for measurement uncertainty or cost reduction. The developed models are available as electronic supplementary material, in an MS-Excel file, to be updated with the user's data.