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Resumen Introduccion Las infecciones neonatales por Candida spp. son eventos graves por su morbimortalidad, sin embargo, en paises en vias de desarrollo la informacion epidemiologica es insuficiente. El objetivo de este estudio fue describir la incidencia y los factores asociados a la infeccion invasiva por Candida spp. en una unidad de cuidados intensivos neonatales de Mexico. Metodos Estudio de casos y controles anidado en una cohorte y apareado por el peso al nacer. Se estimo la incidencia de infeccion neonatal invasiva por Candida spp., y para el analisis bivariado de los factores estudiados se uso la prueba de McNemar para contraste de hipotesis y analisis multivariado con regresion logistica. Resultados La incidencia de la infeccion fue de 2,27 eventos/1.000 RN vivos. Las especies identificadas fueron C. albicans 35,3% (n: 30), C. parapsilosis 30,6% (n: 26), C. glabrata 31,8% (n: 27) y 2 eventos con C. lipolytica. Los factores asociados a mayor riesgo fueron la ventilacion mecanica (OR: 3,04; IC 95%: 1,13-8,14), los antibioticos sistemicos (OR: 7,48; IC 95%: 1,30-42,9), el numero de esquemas antimicrobianos (OR: 2,02; IC 95%: 1,01-4,03) y los dias con nutricion parenteral total (OR: 1,14; IC 95%: 1,04-1,25) o con cateter venoso central (OR: 1,11; IC 95%: 1,02-1,20). La profilaxis con fluconazol disminuyo el riesgo (OR: 0,32; IC 95%: 0,12-0,84). Conclusiones Las intervenciones invasivas (cateter central, ventilacion mecanica y nutricion parenteral) y el uso de antimicrobianos incrementan el riesgo de infeccion neonatal por Candida spp., mientras que el fluconazol profilactico es protector.

Family history of thyroid disease (FHTD) constitutes a possible risk factor for congenital hypothyroidism (CH) in the general population; however, FHTD possible relationship with CH in subjects with Down syndrome (DS) has not yet been explored.To determine whether FHTD is associated with an increased incidence of CH in neonates with DS.Hospital-based case-control study in 220 neonates with DS. Thyroid function tests of 37 infants with DS and positive FHTD (cases) were compared with those of 183 newborns with DS without FHTD (control group). Data were analyzed using multivariate logistic regression analysis and adjusted odds ratios (aORs) with their respective 95 % confidence intervals (CI) were calculated.Nine newborns with DS in our sample had CH (4.1 %). In the multivariate analysis, FHTD showed an association with CH in neonates with DS (aOR = 8.3, 95 % CI: 2.0-34.3), particularly in males (aOR = 9.0, 95 % CI: 1.6-49.6). In contrast, newborns with DS without FHTD were less likely to suffer from CH (aOR = 0.4, 95 % CI: 0.1-0.8).Newborns with DS and FHTD have an eight-fold higher risk for CH, particularly when the index case is male. FHTD detailed evaluation can be an easy and accessible strategy to identify those newborns with DS at higher risk for CH.La historia familiar de enfermedad tiroidea (HFET) como factor de riesgo para hipotiroidismo congénito (HC), en síndrome de Down (SD) aún no ha sido explorada.Determinar si la HFET está asociada a mayor riesgo de HC en neonatos con SD.Estudio de casos y controles en 220 neonatos con SD. Se compararon las pruebas de función tiroidea (PFT) de 37 con SD e HFET (casos), frente a las PFT de 183 recién nacidos con SD sin HFET (grupo de referencia). Se realizó análisis de regresión logística multivariante y se calculó la razón de momios (RM) y sus respectivos intervalos de confianza del 95 % (IC 95 %).Nueve casos HC (4.1 %). El HC mostró asociación con la HFET (RMa = 8.3, IC 95 %: 2.0-34.3), particularmente en los varones (RMa = 9.0, IC 95 %: 1.6-49.6). La ausencia de HFET tuvo una RM de protección para HC (RMa = 0.4, IC 95 %: 0.1-0.8).La HFET puede es una estrategia fácil y accesible para identificar pacientes con SD con mayor riesgo de HC.

The intense competition of global markets stimulates a significant change in the way products are designed, manufactured, and delivered. Such a situation is forcing companies to consider the use of new tools to support this decision process. This paper describes an agent-based system implementing a novel consumer-based fuzzy multicriteria methodology to support the design of new products. It argues that a combination of marketing decision support systems, multicriteria and multiobjective methodologies, fuzzy models, and agent technologies could be a valuable tool to assist marketing managers in new product design applications. In the multi-agent system architecture, software agents were classified into types and organized in teams. The first includes interface, task, and information agents. The second reflects Simon’s decision-making process, including intelligence, design, and choice teams. The communication between agents is carried out using an ontology. An example of system operation attempting to get the design of new corn oil is presented using sequence diagrams.

Introduction: Prenatal corticosteroids reduce neonatal mortality and morbidity; however, there are few studies in developing countries, and with inconsistent results. The purpose of this study was to quantify the frequency of the use of prenatal corticosteroids and to estimate its effect on the morbidity and mortality of premature newborns. Methods: A retrospective cohort study was performed on premature newborns selected from a census conducted between January 2016 and August 2017. The use of corticosteroids was taken from the maternal records, and the dependent variables from the neonatal records. An analysis was made of the relationship using logistic regression, adjusted to gestational age and weight. Results: The study included 1083 premature infants of which 53.3% were male. The mean gestational age was 33.4 weeks. Corticosteroids were received by 42%, with latency ≥24 h in 23.6% and ≥48 h in 13.8%. Respiratory distress syndrome was observed in 35% (379/1083), early neonatal sepsis in 4.4% (48/1083), late neonatal sepsis in 10.7% (116/1083), intraventricular haemorrhage in 15.1% (137/908), chronic lung disease in 51.4% (165/321), and death in 22.3% (242/1083). Prenatal corticosteroids decreased the risk of death in children under 34 weeks (OR 0.63, 95% CI 0.40–0.98). The decrease was greater if they presented with latency ≥48 h (OR 0.40, 95% CI 0.20–0.80). The rest of the dependent variables were not modified by the intervention. Conclusions: In preterm infants, 42% received antenatal corticosteroids. In those with less than 34 weeks, there was a decrease in the risk of death without changes in morbidity. Resumen: Introducción: Los corticosteroides prenatales disminuyen la morbimortalidad neonatal, sin embargo, existen pocos estudios en países en vías de desarrollo, con resultados no consistentes. El objetivo fue cuantificar la frecuencia del uso de corticosteroides prenatales y estimar su efecto en la morbimortalidad de recién nacidos prematuros. Métodos: Estudio de cohorte retrospectivo; se seleccionaron los recién nacidos prematuros de un censo realizado entre enero de 2016 y agosto de 2017. De los expedientes maternos se registró el uso de corticosteroides; y de los expedientes de los neonatos se indagó las variables dependientes. La asociación se analizó con regresión logística, ajustada a la edad gestacional y el peso. Resultados: Se estudiaron 1.083 prematuros, el 53,3% de género masculino; la edad gestacional promedio fue 33,4 semanas. Recibieron corticosteroides el 42%, con latencia ≥24 horas el 23,6% y ≥48 horas el 13,8%. Presentaron síndrome de dificultad respiratoria el 35% (379/1083), sepsis neonatal temprana el 4,4% (48/1083), sepsis neonatal tardía el 10,7% (116/1083), hemorragia intraventricular el 15,1% (137/908), enfermedad pulmonar crónica el 51,4% (165/321) y muerte el 22,3% (242/1083). Los corticosteroides prenatales disminuyeron el riesgo de muerte en menores de 34 semanas (OR: 0,63, IC 95%: 0,40-0,98); el decremento fue mayor si presentaron latencia ≥48 horas (OR: 0,40; IC 95%: 0,20-0,80). El resto de variables dependientes no se modificó por la intervención. Conclusiones: El 42% de los prematuros recibe corticosteroides prenatales. En menores de 34 semanas se observó una disminución del riesgo de muerte sin modificación en la morbilidad.

Resumen Introducción: Las infecciones causadas por enterobacterias productoras de β-talactamasas de espectro extendido (EP-BLEE) tienen implicaciones sobre la morbilidad y mortalidad neonatal. Objetivo: Describir la prevalencia de EP-BLEE en sepsis neonatal y los factores asociados. Métodos: Estudio de cohorte prospectivo, desde agosto del 2016 a agosto del 2017. Se incluyeron recién nacidos (RNs) ingresados en el Hospital Civil de Guadalajara “Dr. Juan I. Menchaca”. Mediante prueba de difusión de doble disco se indagó la presencia de EP-BLEE y su asociación con características clínicas y demográficas de los RNs. Resultados: Se estudiaron 1.501 RNs hospitalizados, con edad gestacional promedio de 36,3 semanas. Se diagnosticaron 196 eventos de sepsis neonatal, la etiología más frecuente fueron enterobacterias (45,5%); 88,8% demostraron resistencia a ampicilina y más de 42% a cefalosporinas de amplio espectro. El 22,9% presentó fenotipo BLEE positivo. Tener Apgar ≤ 7 a los cinco minutos de vida (OR 4,6; IC 95% 1,47-14,6) y edad gestacional < 37 semanas (OR 5,4; IC 95%1,04-27,7) incrementaron el riesgo. Conclusión: En las enterobacterias causantes de sepsis neonatal, 22,9% son EP-BLEE; la infección es más probable en pacientes con Apgar ≤ 7 a los cinco minutos de vida y en prematuros.

Introduction: Family history of thyroid disease (FHTD) as risk factor for congenital hypothyroidism (CH) in patients with Down syndrome (DS) has not yet been explored. Objective: To determine whether FHTD is associated with an increased risk for CH in DS. Method: Case-control study in 220 neonates with DS. Thyroid function tests of 37 infants with DS and FHTD (cases) were compared with those of 183 DS newborns without FHTD (reference group). Data were analyzed using multivariate logistic regression analysis and adjusted odds ratios (aORs) with their respective 95 % confidence intervals (CI) were calculated. Results: Nine newborns with DS in our sample had CH (4.1 %). FHTD showed an association with CH in neonates with DS (aOR = 8.3, 95 % CI: 2.0-34.3), particularly in males (aOR = 9.0, 95 % CI: 1.6-49.6). In contrast, newborns with DS without FHTD were less likely to suffer from CH (aOR = 0.4, 95 % CI: 0.1-0.8). Conclusions: FHTD detailed evaluation can be an easy and accessible strategy to identify those newborns with DS at higher risk for CH.

Two prominent, compatible accounts contend that Asian Americans and Latinos are not strongly connected to America's political parties and that their partisanship is responsive to identity threats. Donald Trump's political ascent presents a critical test, as Trump reoriented the Republican Party by foregrounding anti-immigrant hostility. Here, we test these perspectives using one of the first-ever population-based panels of Asian Americans and Latinos fielded 2016 to 2018. Across various empirical tests, we uncover surprising strength and stability in respondents’ partisan identities. In a period of pronounced anti-immigrant rhetoric, these groups remained steadfast in their party affiliation. We also show that pan-ethnic identities were stable over this period, that partisanship can shape subsequent pan-ethnic identities, and that few respondents describe the parties with reference to ethnic/racial groups in either year. By 2016, pan-ethnic identities were already stably integrated with partisanship, with little evidence of situational shifts in response to identity threats.

Lymexylidae is a small family of beetles with worldwide distribution. Only two species are recorded from Guatemala and Mexico: Atractocerus brasiliensis Lepeletier and Audinet-Serville and Melittomma brasiliensis (Laporte). New distributional records from Guatemala and Mexico are presented for these species. A distribution map and comments about a phoretic mite interaction are provided.

We report tunable RF-sputtered AZO nanofilms through of deposition conditions. Perfect adsorption of light was simulated in ENZ mode. The coupling condition of thickness and wavelength in perfect absorption was obtained by a Drude model. The fitted parameters range as follows: charge density, from 1.6 × 1020 to 4.4 × 1020 cm−3; mobilities, from 8.23 to 12.76 cm2 V−1 s−1; and resistivities, from 14.20 to 34.98 Ω cm. The so-called spectroscopy shape analysis is introduced for automatic detection of elusive XPS peaks and sample surface-etching classification.

This work describes a strategy to optimize a downstream processing of a recombinant human growth hormone (rhGH) by incorporating a quality by design approach toward meeting higher quality specifications. The optimized process minimized the presence of impurities and degradation by-products during manufacturing by the establishment of in-process controls. Capillary zone electrophoresis, reverse phase, and size-exclusion chromatographies were used as analytical techniques to establish new critical process parameters for the solubilization, capture, and intermediate purification steps aiming to maintain rhGH quality by complying with pharmacopeial specifications. The results indicated that the implemented improvements in the process allowed the optimization of the specific recovery and purification of rhGH without compromising its quality. In addition, this optimization facilitated the stringent removal of the remaining impurities in further polishing stages, as demonstrated by the analysis of the obtained active pharmaceutical ingredient.

Growing evidence shows that mass opinion varies by interview language, yet modest theory exists to explain this result. I propose a framework where language impacts survey response by making some political concepts more mentally accessible. I claim that concepts vary by how associated they are with certain languages, which means people are more likely to acquire a construct when it is tied to the tongue one speaks. Hence, recalling concepts from memory should be easier when the language a construct is linked to matches the tongue one interviews in, thereby intensifying people’s opinions. I test my theory by manipulating the interview language in two U.S. surveys of English/Spanish bilingual Latino adults. I generally find that language influences the accessibility of concepts. For example, subjects report higher opinion levels for concepts that are tied more to their interview language, such as American identity among English interviewees. Subjects who interview in English are also less likely to refuse completing items measuring knowledge about U.S. politics, and more likely to answer them quickly. Items reflecting constructs that are highly labile (e.g. anti-Obama affect) or very crystallized (e.g., partisanship) do not display these patterns. I then rule out that language effects are mostly mediated by a heightened sense of anxiety, anger, pride or efficacy that emerges when bilingual subjects interview in one of their languages.

The aim of our study was to determine the frequency and type of associated congenital anomalies in patients with isolated gastroschisis born at the Dr. Juan I. Menchaca Civil Hospital of Guadalajara (Guadalajara, México), and to explore its possible association with the included outcome variables. One hundred-eight cases with isolated gastroschisis were reviewed from 2009 to 2014. The occurrence of intestinal and extraintestinal associated anomalies (either secondary or primary) was prospectively assessed. The type of gastroschisis, length of hospital stay (LOS), and in-hospital mortality were outcome variables for statistical analysis. Of infants with gastroschisis, 52 (48.1%) had one or more associated anomalies (AA), with increased odds in males (OR = 2.3, 95%CI: 1.1-5.0). AA classified, as secondary and primary were present in 34.3 and 5.6% of patients, respectively. Of secondary AA, 25.9% were intestinal anomalies, and 17.6% were extraintestinal. Primary AA were congenital heart disease (n = 3), meningomyelocele, and hydrocephaly and amniotic band sequence in one instance, respectively. Multivariate logistic regression showed that secondary AA (both intestinal and extraintestinal) were associated with complex gastroschisis, prolonged LOS, and in-hospital death, whereas primary AA were not related to a worse outcome. Our results highlight the pathogenic importance of properly investigating and categorizing the presence of others secondary or primary AA when diagnosis of gastroschisis is made.

Neisseria meningitidis outer membrane vesicles or proteoliposomes (PLs) has been used as vaccines and adjuvant. Despite the presence of potentially toxic amounts of lipopolysaccharide (LPS), they have been shown to be safe, well tolerated, and immunogenic. This suggests that LPS-PL may have reduced LPS toxicity. We show here that the ability of PL to induce pro-inflammatory cytokine production in human U937 histiocytic cell line is significantly lesser than that of an equivalent concentration of purified LPS, thus confirming that certain components or physical properties of PL reduce the pro-inflammatory activity of their endogenous LPS. To investigate the mechanisms responsible for this protective effect, PLs were fractionated and assayed the ability of the resulting fractions to induce inflammatory cytokine expression. Several individual PLs fractions were more potent inducers of pro-inflammatory cytokine production than the unfractionated PLs. The majority of the pro-inflammatory activities appeared to be mediated by the presence of LPS in the fractions, as shown by the ability of an anti-CD14 antibody to block it. However, in two PL fractions, the production of IL-8 and to a lesser extent IL-6 was not inhibited by anti-CD14 treatment, indicating that pro-inflammatory components other than LPS could also be present in PL. Eight proteins present in the fractions were identified by n-terminal sequencing. Our results suggest that two of them PorB and particularly the RmpM protein may also contribute to the pro-inflammatory activity of N. meningitidis PL. Our results could support the development of PLs as vaccine adjuvant.

To estimate, on the basis of anthropometric and demographic variables, the depth (Dp) and diameter (Dm) of femoral and jugular vessels, which have been located and measured by ultrasound, in pediatric patients.750 measurements of Dp and Dm of the femoral vein (FV), femoral artery (FA) and internal jugular vein (IJV) were made in 125 pediatric patients. The values were correlated with patients' sex, weight, age, size and body surface area (BSA).Mean Dp values were 0.72 (0.34) cm for FA, 0.79 (0.35) cm for FV and 0.77 (0.24) cm for IJV. Mean antero-posterior Dm values were 0.37 (0.17) cm for FA, 0.42 (0.22) cm for FV and 0.59 (0.23) cm for IJV. In the studied pediatric patients, femoral and jugular vessels depth correlated with age, size, weight and BSA (FV, FA and IJV depth and diameter correlated with weight, size, age and body surface area in the studied pediatric patients. Correlation was better for femoral than for jugular vessels. Depth could be estimated from patients' weight and size, while diameter could be estimated from the size. Such estimations may facilitate the choice of vessels to be cannulated, length and diameter of cannulation needles and the diameter of catheters to be used in pediatric patients.Calcolare in base a variabili antropometriche e demografiche, la profondita’ (P) e il diametro (D) dei vasi femorali e giugulari dei pazienti pediatrici in seguito alla loro localizzazione e misurazione ecografica.Sono state effettuatte 750 misurazioni della P e del D della vena femorale (VF), arteria femorale (AF) e della vena giugulare interna (VGI) in 125 pazienti pediatrici. I valori ottenuti sono stati relazionati con il sesso, il peso, l’eta’, l’altezza e la superficie corporea.La P media dell’ AF (PAF) è risultata di 0.72 (0.34) cm, quella della VF (PVF) di 0.79 (0.35) cm e quella della VGI (PVGI) di 0.77 (0.24) cm. Il D anteroposteriore medio dell’ AF (DAF) fu di 0.37 (0.17) cm, quello della VF (DVF) èrisultato di 0.42 (0.22) cm e quello della VGI (DVGI) di 0.59 (0.23) cm. Nei pazienti pediatrici analizzati, è stata riscontrata una relazione tra i parametri di eta’, peso, altezza e superficie corporea e quelli della profondita’ dei vasi femorali e giugulari (R = 0.46–0.60), che pùo essere stimata secondo peso e altezza (PAF: R = 0.71; PVF: R = 0.72; PVGI R = 0.53). La relazione con il diametro vascolare è risultata maggiore per l’ AF e la VF (R = 0.81–0.89) e piu’ bassa per la VGI (R = 0.42–0.51), che può essere stimata in base all’altezza del paziente (DAF: R = 0.89; DVF: R = 0.86; DVGI: R = 0.52).La profondita’ e il diametro della VF, dell’AF e della VGI si possono relazionare al peso, altezza, eta’ e superficie corporea nei pazienti pediatrici del nostro studio. Questa relazione e’ maggiore per i vasi femorali rispetto ai vasi giugulari, rendendo possibile il calcolo della loro profondita’ in base al peso e all’altezza e il calcolo del loro diametro vascolare in base all’altezza. Questi calcoli possono essere utili per la scelta adeguata del vaso da canalizzare, per la scelta del tipo e del calibro dell’ago e del catetere da usare nei pazienti pediatrici.

To measure the depth (D p) and diameter (D m) of the internal jugular vein (IJV), femoral vein (FV), and femoral artery (FA) in pediatric patients to evaluate the clinical implications. This study included 125 pediatric patients. All of them underwent bilateral ultrasound study of vessels and were classified into three groups based on anthropometric and demographic parameters. Measured mean D p values were: 0.72 (0.34) cm for the FA, 0.79 (0.35) cm for the FV, and 0.77 (0.24) cm for the IJV. Mean antero-posterior D m values were: 0.37 (0.17) cm for the FA, 0.42 (0.22) cm for the FV, and 0.59 (0.23) cm for the IJV. D p and D m increased with age (A), weight (W), height (H), and body surface area (BSA). In the lower ranges of these variables, D p was similar for all three studied vessels (0.6–0.7 cm). In the higher ranges, femoral vessel D p values (1.1–1.2 cm) were larger than jugular ones (0.9 cm). Additionally, in these low ranges, IJV D m values were larger than femoral ones (0.45–0.50 vs. 0.25 cm). In the higher ranges, diameter values were similar (0.6–0.7 cm). In pediatric patients, major vessels can be located and their depth and diameter measured by vascular ultrasound. In younger patients, jugular and femoral vessels had similar depth values; in older ones, they had similar diameters. Ultrasound measurements in pediatric patients could facilitate the choice of the vessel to be cannulated, the catheter diameter, and the length of the needle to be used. Vascular canalization of IJV may be recommended as the first choice because of its low depth and large diameter.

Objective: To evaluate the quality of life in patients with endometriosis pelvic pain before and after the application of the levonorgestrel-releasing intrauterine system (LNG-IUS). Design: Open non-comparative study. Setting: Obstetrics and Gynecology Hospital at Monterrey, Mexico. Sample: 29 women aged 18 to 40 years with pelvic pain associated with endometriosis confirmed by laparoscopy. Methods: After laparoscopy but before LNG-IUS insertion (basal visit) and 6 months afterwards, modified Endometriosis Health Profile (EHP-30) was applied. Main outcomes measures: Size of change of questionnaire scores, need of additional analgesic therapy and adverse effects. Statistical Analysis: Differences in the questionnaire scores before and after intervention were analyzed by Student t-test. Results: Final analysis set included 29 women aged 31.7 ± 4.7 years years. The ASRM surgical staging of endometriosis was mild in 19.3 moderate in 13.7 and severe in 76% of the patients. The general perception of quality of life improved from 52 at baseline to 98% at six months (p < 0.001). Adverse events were mild in nature, 19 patients reported no adverse events during the study (65.5%). Two patients (6.9%) required the use of concomitant therapy with non-steroidal analgesics for relief of pain. Conclusion: The application of LNG-IUS in patients with pelvic pain associated with endometriosis improved significatively all aspects related with quality of life as measured with Endometriosis Health Profile (EHP-30). We concluded that LNGIUS may be an effective and convenient therapeutic alternative for the management of pain associated with endometriosis.

Implicit attitudes are automatic evaluations of objects: political candidates and parties, racial and ethnic groups, national symbols and consumer products, and so on. These responses are spontaneously triggered and hard to control, and can operate subconsciously. Implicit attitudes stand in contradistinction to their explicit variety: self-reported attitudes that people actively direct, control, and are conscious of. Public-opinion scholars have overwhelmingly centered on explicit attitudes, painting a portrait of mass opinion formation as slow, deliberative, and often dispassionate. But psychological research since the late 1970s has agglomerated into the view that much of people’s thinking is fast, automatic, and affectively charged—in a word, implicit. Heaped onto all this is the critical insight that implicit attitudes precede, and many times structure, their explicit counterparts. The implications for the study of public opinion are manifold. This article brings some order to all this by familiarizing readers with the conceptualization, measurement, and analysis of implicit attitudes in American public opinion.

Noninvasive ventilation (NIV) with conventional therapy improves the outcome of patients with acute respiratory failure due to hypercapnic decompensation of chronic obstructive pulmonary disease (COPD) or acute cardiogenic pulmonary edema (ACPE). This review summarizes the main effects of NIV in these pathologies. In COPD, NIV improves gas exchange and symptoms, reducing the need for endotracheal intubation, hospital mortality and hospital stay compared with conventional oxygen therapy. NIV may also avoid reintubation and may decrease the length of invasive mechanical ventilation. In ACPE, NIV accelerates the remission of symptoms and the normalization of blood gas parameters, reduces the need for endotracheal intubation, and is associated with a trend towards lesser mortality, without increasing the incidence of myocardial infarction. The ventilation modality used in ACPE does not affect the patient prognosis.

Infliximab is therapeutic monoclonal antibody (mAb) against TNF-α employed in the treatment of immunoinflammatory diseases. The development of biosimilar mAbs is a global strategy to increase drug accessibility and reduce therapy-associated costs. Herein we compared key physicochemical characteristics and biological activities produced by infliximab and infliximab-Probiomed in order to identify functionally relevant differences between the mAbs. Binding of infliximab-Probiomed to TNF-α was specific and had kinetics comparable to that of the reference product. Both mAbs had highly similar neutralizing efficacy in HUVEC cell cultures stimulated with TNF-α. In vitro induction of CDC and ADCC were also similar between the evaluated products. In vivo comparability was assessed using a transgenic mouse model of arthritis that expresses human TNF-α in a 13-week multiple-administration study. Infliximab and infliximab-Probiomed showed comparable efficacy, safety, and pharmacokinetic profiles. Our results indicate that infliximab-Probiomed has highly similar activities to infliximab in preclinical models, warranting a clinical evaluation of its biosimilarity.

Introduction To know the current characteristics and trends in the profile of family caregivers of elderly dependents is essential in order to promote multi-component interventions individualized to each situation and context that enhance the positive aspects of caregiving and minimize their negative aspects. The objective of this study was to determine the current characteristics of family caregivers of elderly dependents in northern Spain. Methods Cross-sectional study: 184 family caregivers of elderly dependents in the province of Cantabria were selected by simple random sample stratified according to Healthcare Centres. Different types of variables associated with the caregiver were collected by a structured interview. Comparisons between groups were performed by using the Chi2 or Student t-tests for categorical and quantitative variables respectively. Alpha error was set at 5%, and all test were two tailed. Results One hundred and fifty-three out of the 184 family caregivers (83.2%) were women and 31 (16.8%) men. The mean age of family caregivers was 60.98 years [SD = 10.69]. No differences were observed in terms of age according to sex. Regarding the sex and family relationship of caregivers, three predominant profiles were identified: daughters (n = 104, 56.5%); wives (n = 24, 13%); and sons (n = 22, 12%). Overall, daughters and sons accounted for 68.5% of the sample (n = 126), and partners (husbands and wives) accounted for 15.8% (n = 29). Statistically significant differences were found between female and male caregivers in terms of marital and employment status. Female caregivers were in a greater percentage “married” (70.6%) and male caregivers were in a greater percentage “single” or “divorced or separated” (54.8%), P = 0.005; 32.1% of family caregivers (n = 59) were retired. “Household tasks” were more prevalent among non-retired women than men. The men were unemployed to a greater extent. Restricting to daughters and sons, the statistically significant differences were maintained. Daughters were in a greater percentage “Married” (62.9%) and “housework” continued to be more prevalent in daughters than in sons (31.7% vs. 0%). Sons were “Single” or “Divorced or separated” and “unemployed” to a greater extent. The educational level was similar in men and women; 61.4% of the sample of family caregivers studied only primary studies. Regarding the sex of elderly dependents, statistical differences were also obtained (P Conclusions Three predominating profiles for family carers of elderly dependents have been identified in relation to sex and family relationship. In order of frequency, daughters, wives, and sons. It is observed in comparison with previous studies, a decrease in the gender gap, due to a progressive incorporation of unemployed men in the role of family caregiver. The progressive increase of employed women in the last decades and the impact of the economic crisis occurred in recent years increasing the number of unemployed sons, can explain our results. The progressive aging of the population that affects both caregivers and elderly dependents, support the maintained trend towards a gradual increase in the percentage of retired family caregivers.

The reverse osmosis (RO) brackish water desalination plant described in this article has been operating without acid in the pretreatment and only using two types of antiscalants (this was the first experience of 40,000 operating hours in Canaries). This work describes the graphical evolution of all the daily operating information of the first five years. A study of the normalization and standardization of the information about the five years of the evolution of the plant for fixed feedwater conditions, operating pressure, and system recovery is shown too, so that the performance evaluation of the plant can be indicated correctly. Likewise, this article describes the graphic evolution of thse brine Langelier saturation index (real and theoric values). The conclusions of this study and the operating experience are intended to get a practical and optimum design method of RO brackish water desalination plants.

Since the advent of public opinion polling, scholars have extensively documented the relationship between survey response and interviewer characteristics, including race, ethnicity, and gender. This paper extends this literature to the domain of language-of-interview, with a focus on Latino political opinion. We ascertain whether, and to what degree, Latinos’ reported political attitudes vary by the language they interview in. Using several political surveys, including the 1989–1990 Latino National Political Survey and the 2006 Latino National Survey, we unearth two key patterns. First, language-of-interview produces substantively important differences of opinion between English and Spanish interviewees. This pattern is not isolated to attitudes that directly or indirectly involve Latinos (e.g., immigration policy, language policy). Indeed, it emerges even in the reporting of political facts. Second, the association between Latino opinion and language-of-interview persists even after statistically controlling for, among other things, individual differences in education, national origin, citizenship status, and generational status. Together, these results suggest that a fuller understanding of the contours of Latino public opinion can benefit by acknowledging the influence of language-of-interview.

The coexistence of different water homeostasis abnormalities following neurosurgery represents a diagnostic and therapeutic challenge for intensive care units. This paper reports the case of a 13 year-old boy who underwent surgery for a suprasellar tumour and, immediately after surgery, developed a cerebral abscess, persistent diabetes insipidus (DI) as well as cerebral salt wasting syndrome (CSWS). The early onset of CSWS following DI has been associated with a poor prognosis and increased mortality. In cases in which these abnormalities coexist, the increased polyuria secondary to the rise in natriuresis associated with CSWS might be erroneously interpreted as a sign of poor control of the DI, thereby leading to therapeutic mistakes. Treatment basically consists of restoring electrolytes and the joint administration of desmopressin and fludrocortisone.

In the current competitive environment, great emphasis is placed on the knowledge and skills of the workforce as important elements in achieving organizational goals. As this focus on employee skills has increased, so have organizational programs and initiatives to ensure that the training in place to develop those skills is not sporadic, but rather part of a continuous effort toward keeping employee skills up to date. It becomes fundamental, in this context, to understand such programs and evaluate their impact, both within companies and externally, in terms of their decision making and business results. This paper aims to do that, through a study of the work-related training practices of industrial firms in the Northern-Spanish region of Asturias. In addition, it develops a new variable – training intensity – and examines its impact on the planning, execution and evaluation of training programs in these firms. Among other findings, our study confirms that training-intensive firms have a more defined strategic approach to the market and are generally more conscious of business competition than their non-training-intensive competitors. Implications for management are also presented. info:eu-repo/semantics/publishedVersion

Etanercept is a recombinant fusion protein approved for the treatment of TNF-αmediated diseases such as rheumatoid arthritis (RA), psoriasis, psoriatic arthritis, and ankylosing spondylitis. Herein, we present an evaluation of the physicochemical and biological properties of a biosimilar etanercept and its reference product followed by a clinical study in patients diagnosed with RA intended to demonstrate comparability of their immunomodulatory activity. Identity analyses showed a total correspondence of the primary and higher-order structure between the two products. In regard to intrinsic heterogeneity, both products showed to be highly heterogenous; however the biosimilar etanercept exhibited similar charge and glycan heterogeneity intervals compared to the reference product. Apoptosis inhibition assay also showed that, despite the high degree of heterogeneity exhibited by both products, no significant differences exist in theirin vitroactivity. Finally, the clinical assessment conducted in RA-diagnosed patients did not show significant differences in the evaluated pharmacodynamic markers of both products. Collectively, the results from the comparability exercise provide convincing evidence that the evaluated biosimilar etanercept can be considered an effective alternative for the treatment of RA.

We have arrived at the end of my investigative journey, as it were. But what is one to conclude from the various layers of results paraded across the previous chapters? The lessons are many. The objective behind this concluding chapter, therefore, is to bring order to this potentially unwieldy prospect by discussing the larger meaning of implicit attitudes for the study of immigration politics, specifically, and non-immigration politics, more generally. To effectively accomplish this task, I revisit – ever so briefly – the primary theoretical current running through this book, and the main tributaries of evidence on which it now draws. Against this backdrop, I discuss the implications of these findings for political scientists, especially those who study mass public opinion. This discussion forms the core of this chapter, and I organize it around five main points. First, I consider what my results suggest about the nature of public opposition to illegal and legal immigration, given the indelible role played by implicit attitudes toward Latinos in contemporary times. Second, I clarify how and why the evidence in this book establishes the viability of implicit attitudes and their corresponding measures for political science research. Third, I discuss the connection between implicit attitudes and ongoing debates over the nature of public opinion. Fourth, I explain the relationship between implicit attitudes and the idealized democratic citizen. And fifth, I spell out the implications of implicit attitudes for the political prospects of immigration reforms. Let's begin this effort by first reviewing my claims and evidence. Bottom Lines I defined implicit attitudes as basic affective evaluations of political objects. As such, they reflect citizens’ learned but unspoken judgments of political objects as good or bad , favorable or unfavorable , or pleasant or unpleasant . I explained that implicit attitudes are steeped in automaticity. They are spontaneously activated, hard to control, and can operate outside of immediate awareness. Implicit attitudes, I pointed out, arise from people's mental capacity for associative reasoning. Even as part of our mind deliberates and reflects on political information, another part of our brain is engaged in identifying broad, but stable representations of what is typical in our environments. This part of our mind is geared toward uncovering, learning, and storing recurring patterns in information we encounter. And it is based on these patterns that we develop implicit attitudes toward political objects.

Building the information and knowledge society has involved the development of numerous projects and initiatives all over the world. Portugal is no exception. This work is based on the analysis of the ALO Digital Project, which involves a series of strategies developed at the local e-government level in four Portuguese counties near Lisbon (i.e. Amadora, Loures, Odivelas and Vila Franca de Xira). Having the residents of the four counties involved as the target, this paper aims to identify the level of electronic service use resulting from the implementation of the ALO Digital Project. A questionnaire was administered and the results of a regression analysis demonstrate that the project is still at low level of online service sophistication. Additionally, despite users' overall satisfaction, implementation difficulties were noticed. In practical terms, this reveals a type of service more related to information consultation, downloading and printing documentation, and supports the premise that a change of focus and direction of local e-government is needed to substantially improve the life of the individual citizen. info:eu-repo/semantics/publishedVersion

Central vascular cannulation is not a risk-free procedure, especially in pediatric patients. Newborn and infants are small and low-weighted, their vascular structures have high mobility because of tissue laxity and their vessels are superficial and with small diameter. These characteristics, together with the natural anatomical variability and poor collaboration of small children, make this technique more difficult to apply. Therefore, ultrasound imaging is increasingly being used to locate vessels and guide vascular access in this population. Objective (a) To present a model that simulates the vascular system for training ultrasound-guided vascular access in pediatrics patients; (b) to ultrasound-guided vascular cannulation in the model. Results The model consisted of two components: (a) muscular component: avian muscle, (b) vascular component: elastic tube-like structure filled with fluid. 864 ecoguided punctures was realized in the model at different vessel depth and gauge measures were simulated, for two medical operators with different degree of experience. The average depth and diameter of vessel cannulated were 1.16 (0.42) cm and 0.43 (0.1) cm, respectively. The average number of attempts was of 1.22 (0.62). The percentage of visualization of the needle was 74%. The most frequent maneuver used for the correct location, was the modification of the angle of the needle and the relocation of the guidewire in 24% of the cases. The average time for the correct cannulations was 41 (35.8) s. The more frequent complications were the vascular perforation (11.9%) and the correct vascular puncture without possibility of introducing the guidewire (1.2%). The rate of success was 96%. Conclusions The model simulates the anatomy (vascular and muscular structures) of a pediatric patient. It is cheap models, easily reproducible and a useful tool for training in ultrasound-guided puncture and cannulation.

Aliment Pharmacol Ther 2012; 35: 275–283 Summary Background Ciclosporin has proven to be effective in patients with corticosteroid-refractory ulcerative colitis (UC). When therapy with this drug fails, infliximab can be considered to avoid colectomy. The efficacy and safety of this sequential approach remain unknown. Aim To assess the efficacy and safety profile of treatment with infliximab after failure of ciclosporin in patients with a corticosteroid-refractory flare of UC. Methods Retrospective review of medical records of patients with a corticosteroid-refractory flare of UC who did not respond to ciclosporin and received salvage therapy with infliximab within a month of discontinuing ciclosporin. The severity of the flare and response to the treatment were graded using the Lichtiger index. Cumulative rates of colectomy were calculated using Kaplan–Meier analysis. Cox regression analysis was performed to identify predictors of colectomy. To evaluate the safety profile of this treatment strategy, any adverse event occurring after the first infusion of infliximab was considered. Results The study population comprised 47 patients with corticosteroid-refractory UC treated with infliximab after failure of ciclosporin. The median baseline Lichtiger index was 13. The mean time from the last ciclosporin dose to the first infliximab infusion was 6 days. After the first infliximab infusion, 13% of patients achieved remission, and 74% partial response. Of the 35 patients who received the third infliximab infusion, 60% achieved remission, and 37% partial response. Fourteen patients (30%) underwent colectomy. The rate of adverse events was 23%. One death occurred in a 40-year-old man who failed ciclosporin and infliximab and underwent surgery 10 days after the first infliximab infusion; he died of nosocomial pneumonia. Conclusions Treatment with infliximab makes it possible to avoid colectomy in two-thirds of corticosteroid-refractory UC patients in whom ciclosporin fails. However, the rates of adverse events and mortality mean that the decision to administer sequential therapy (ciclosporin–infliximab) should be taken on an individual basis.

Objetivo: Describir las características epidemiológicas, clínicas y evolutivas de los pacientes pediátricos con traumatismo craneoencefálico grave (TCEG). Material y método: Revisión de los pacientes ingresados en una unidad de medicina intensiva pediátrica (UMIP) con TCEG en el periodo comprendido entre julio de 1983 y diciembre de 2009. Resultados: De los 389 pacientes con traumatismo craneoencefálico (TCE) ingresados en nuestra unidad durante el periodo de estudio, presentaron TCEG 174 (45%). La media de edad de este grupo fue 67±9 meses, con una puntuación media en la escala de Glasgow (GCS) de 5,5±1,8 y una puntuación PRISM media de 10,7±6,7. La etiología más frecuente de los TCEG fueron los accidentes de tráfico (56%), aunque en la última década existe una disminución significativa de su incidencia (el 58,5 frente al 45,3%; p

OBJECTIVE: To describe the factors associated to morbidity-mortality in pediatric patients with severe head injury (SHI). MATERIAL AND METHOD: A review was made of the patients admitted to the Pediatric Intensive Care Unit (PICU) with SHI between July 1983 and December 2009. RESULTS: Of the 389 patients with head injuries, 174 (45%) presented SHI. The mean age of these subjects was 67 (9) months, with a Glasgow Coma Score (GCS) of 5.5 (1.8) and a PRISM score of 10.6 (6.7). Thirty-nine percent of the patients showed diffuse encephalic injury (DEI) in the computed tomography (CT) study. Seventy-nine percent of the patients subjected to intracranial pressure monitoring (ICP) presented intracranial hypertension. These patients had a greater incidence of serious sequelae (66.7 vs. 23.1%; p=0.01). Sequelae of clinical relevance were recorded in 59 patients (34%), and proved serious in 64% of the cases. The mortality rate among the patients with SHI was 24.7%, and mortality was significantly associated with a lower GCS score, hyperglycemia, intracranial hypertension and the presence of mydriasis or shock. The mortality rate associated to severe DEI was significantly higher than in the case of mild-moderate DEI (87.5 vs. 7.2%; p Language: es

Objetivo: Describir los factores asociados a la morbilidad y mortalidad de los pacientes pediátricos con traumatismo craneoencefálico grave (TCEG). Material y método: Revisión de los pacientes ingresados en una unidad de medicina intensiva pediátrica (UMIP) con TCEG en el periodo comprendido entre julio de 1983 y diciembre de 2009. Resultados: De los 389 pacientes con TCE ingresados en nuestra unidad durante el periodo de estudio, presentaron TCEG 174 (45%). La edad media de este grupo fue de 67±9 meses, con una puntuación media en la escala de Glasgow (GCS) de 5,5±1,8 y una puntuación PRISM media de 10,6±6,7. El 39% de los pacientes presentaron lesión encefálica difusa (LED) grave en la TAC. Un 79% de los pacientes en los que se monitorizó la presión intracraneal (PIC) presentaron hipertensión intracraneal (HIC). Estos pacientes tuvieron una mayor incidencia de secuelas graves que aquellos que no desarrollaron HIC (66,7 vs 23,1%; p=0,01). Las secuelas de relevancia clínica se encontraron en 59 pacientes (34%), y fueron graves en el 64% de los mismos. La mortalidad de los pacientes con TCEG fue de un 25% y se asoció de forma significativa a una menor puntuación del GCS, a la existencia de hiperglucemia o HIC, a la presencia de midriasis o shock y a la necesidad de ventilación mecánica. La mortalidad de la LED grave fue significativamente más elevada que la LED leve-moderada (87,5 vs 7,2%; p

Aedes aegypti (L.) (Diptera: Culicidae) control programmes in Cuba rely on the application of the organophosphate temephos for larval control. Hence, the monitoring of resistance to this insecticide is an essential component of such programmes. Here, 15 field populations from different municipalities of Havana City were assayed for resistance to temephos. High levels of resistance were detected in all strains and resistance ratios were highly correlated with esterase activity (P = 0.00001). Populations from three municipalities were tested in both 2006 and 2008; resistance and esterase activities both significantly increased during this 2-year period. Synergist studies demonstrated that neither glutathione transferases nor monooxygenases were associated with the increase in resistance to temephos in this period. The duration of the efficacy of commercial formulations of temephos in controlling Ae. aegypti populations in Havana City was reduced by the high level of temephos resistance observed; hence these data are of clear operational significance for the dengue control programme in Cuba. New integrated strategies to avoid further increases in temephos resistance in Cuba are necessary.

Mucosal immune responses are an early and important line of defense against pathogens. The current understanding of the mucosal immune system allows us to consider the use of nasal immunization for induction of antigen-specific immune responses at the mucosal surface and the systemic compartment. Mucosal adjuvants are key for developing novel mucosal vaccines and represent 1 approach to improving mucosal and systemic immunity. However, few mucosal vaccine adjuvants are currently approved for human use. Neisseria meningitidis B proteoliposome-derived cochleate (AFCo1 — Adjuvant Finlay Cochleate 1) has been demonstrated to be a potent mucosal adjuvant. The present work demonstrates that intranasal immunization of 3 doses of tetanus toxoid (TT) coadministered with AFCo1 in mice promotes high systemic and mucosal responses. The anti-TT IgG serum titers and the mucosal anti-TT IgA in saliva and vaginal wash were significantly higher than TT alone. The analysis of antibody subclasses showed that intranasal administration of AFCo1 + TT induced not only IgG1 but also IgG2a anti-TT antibodies at levels comparable to those obtained with TT vaccine (vax-TET). These data support the fact that AFCo1 is a potent mucosal adjuvant in nasal immunization to a coadministered protein antigen.

The study of Latino public opinion has renewed interest in the relationship between language and survey response. However, extant research generally relies on statistical methods that cannot distinguish between two related yet distinct types of language effects in Latino surveys: (1) differences inattitudeand (2) differences inmeasuresof attitude. The former reflects varied levels of a latent attitude between English and Spanish interviewees. The latter—formally known as Differential Item Functioning (DIF)—refers to linguistic differences in the interpretation of survey items, which lead Latino respondents to misreport their level of attitude. This paper proposes Multiple Indicators Multiple Causes models to decouple these two types of language effects. Using this modeling framework, I examine language differences in measures of subjective and factual political attitudes from theLatino National Survey(2006). I find that the language of interview systematically colors Latinos' interpretation of survey items, even after controlling for measurement error and individual differences in the latent variable being assessed. I then show through an applied analysis how ignoring language DIF can yield misleading inferences about hypothesized relationships between variables. Together, these findings highlight a need for greater theoretical work on the psychological origins of language effects in multilingual political surveys.

The Safe, Accountable, Flexible, Efficient Transportation Equity Act: A Legacy for Users (SAFETEA-LU) legislation calls for the establishment of a Safe Routes to School program in each state that is funded for the five fiscal years from 2005 through 2009. States are required to spend between 70% and 90% for infrastructure and between 10% and 30% on noninfrastructure programs. For each of these components of the program to be successful, the built environment of the community surrounding the school needs to support all modes of travel. Much of the emphasis in Safe Routes to School programs has focused on increasing walking in neighborhoods with the characteristics that support walking, such as high-density residential areas close to schools and connected grid and pedestrian amenities. Using Hillsborough County, Florida, as a case study, this paper focuses on barriers to walking and bicycling to school by examining how decisions about school siting, school attendance boundaries, street network characteristics, and other factors controlled by local governments and school boards affect the potential for children to walk to school.

Objetivo. Valorar la seguridad y efectividad de un protocolo de sedoanalgesia para procedimientos invasivos en pacientes pediátricos. Diseño. Estudio prospectivo observacional. Ámbito. Una unidad de medicina intensiva pediátrica (UMIP) de un hospital de tercer nivel. Pacientes. 110 niños sometidos a procedimientos invasivos bajo sedoanalgesia durante un período de 3 años. Intervenciones. Se aplicó un protocolo de sedoanalgesia para los procedimientos invasivos con: fentanilo (1-2 mcg/kg con dosis máxima de 100 mcg para la primera dosis y 50 mcg para siguientes) y propofol (1-2 mg/kg con dosis máxima de 100 mg para la primera dosis y 50 mg para las siguientes). El objetivo fue alcanzar un grado III-IV en la escala de Ramsay modificada y amnesia del procedimiento. Variables principales. a) Los tiempos hasta: sedoanalgesia, recuperación, duración del procedimiento y estancia en la unidad de Medicina Intensiva Pediátrica; b) dosis medias de los fármacos administrados; c) grado de sedoanalgesia y amnesia y d) efectos adversos. Resultados. Se realizaron 500 sedoanalgesias para 634 procedimientos a 110 niños. La patología más frecuente fue la onco-hematológica (91%), siendo la punción lumbar con tratamiento intratecal el procedimiento más realizado: (48,5%). No recordaron el mismo el 96,8% de los pacientes, consiguiéndose sedoanalgesia óptima en el 93,4%. Estos pacientes, respecto a aquellos con un menor grado de sedoanalgesia, presentaron un descenso de la presión arterial sistólica (88 ± 19 frente a 98 ± 14 mmHg; p < 0,001), de la frecuencia cardíaca (88 ± 17 frente a 91 ± 25 lpm; p < 0,05) y de la frecuencia respiratoria (19 ± 6 frente a 23 ± 11 respiraciones por minuto; p < 0,05). El tiempo medio hasta la sedoanalgesia fue de 4,62 ± 3,69 minutos y el tiempo de estancia en la UMIP fue de 41,8 ± 19 minutos. La incidencia de complicaciones fue del 6,6% (apnea, hipotensión, bradicardia), resolviéndose éstas con ventilación manual y/o expansión de volumen. Conclusiones. El protocolo de sedoanalgesia para procedimientos invasivos consiguió una sedoanalgesia óptima con amnesia del procedimiento en la casi totalidad de los casos. La monitorización y las medidas de estabilización permitieron el control de las complicaciones presentadas. Objective. Apply a sedoanalgesic (SA) protocol for invasive procedures (PI) in pediatric patients and evaluate its effectiveness and safety. Design. Prospective observational study. Scope. Pediatric Intensive Care Unit (PICU) of third level hospital. Patients. A total of 110 children subjected to invasive procedures under sedoanalgesia with propofol and fentanyl. Intervention. Sedoanalgesic protocol for invasive procedure was applied with: fentanyl (1-2 mcg/kg with maximum dose of 100 mcg for first dose and 50 mcg for the next) and propofol (1-2 mg/kg with maximum of 100 mg for first dose and 50 mg for the next). The objective was to reach III-IV sedoanalgesic grade for modified Ramsay scale and amnesia related to invasive procedure. Main endpoints. a) time to sedoanalgesia and recovery, length for invasive procedure and stay in the Pediatric Intensive Care Unit; b) mean dose of drug; c) sedoanalgesic grade and amnesia related to invasive procedure and d) adverse events. Results. Five hundreds SA were made for 634 IP in 110 children. The most common conditions were oncohematologics (91%), the spinal tap for intrathecal treatment was the most frequent IP (48.5%). Most of the patients (96.8%) did not recall the procedure and an optimum SA was obtained in 93.4%. Patients profoundly sedated presented a significant fall of systolic arterial pressure (88 ± 19 vs 98 ± 14 mmHg, p < 0.001) compared to those with minor SA level, as well as heart rate (88 ± 17 vs 91 ± 25 bpm, p < 0.05) and respiratory rate (19 ± 6 vs 23 ± 11 bpm, p < 0.05). Mean time to reach adequate sedation was 4.62 ± 3.69 minutes and stay time in PICU 41.8 ± 19. Complication incidence was 6.6% (apnea, hypotension, bradycardia), these were resolved with manual ventilation and/or volume expansion. Conclusions. SA protocol reached its goal of: a) effectiveness: SA achieved was optimal, with amnesia of the procedure in almost all patients and b) safety: complications were controlled due to monitorization and stabilization measurements.

According to the World Health Organization, the incidence of malignant neoplasms and endocrine, blood, and immune disorders will increase in the upcoming decades along with the demand of affordable treatments. In response to this need, the development of biosimilar drugs is increasing worldwide. The approval of biosimilars relies on the compliance with international guidelines, starting with the demonstration of similarity in their physicochemical and functional properties against the reference product. Subsequent clinical studies are performed to demonstrate similar pharmacological behavior and to diminish the uncertainty related to their safety and efficacy. Herein we present a comparability exercise between a biosimilar trastuzumab and its reference product, by using a hierarchical strategy with an orthogonal approach, to assess the physicochemical and biological attributes with potential impact on its pharmacokinetics, pharmacodynamics, and immunogenicity. Our results showed that the high degree of similarity in the physicochemical attributes of the biosimilar trastuzumab with respect to the reference product resulted in comparable biological activity, demonstrating that a controlled process is able to provide consistently the expected product. These results also constitute the basis for the design of subsequent delimited pharmacological studies, as they diminish the uncertainty of exhibiting different profiles.

Varios genes intervienen en la morfogénesis de la corteza suprarrenal, entre ellos el gen DAX-1. Presentamos una nueva mutación del gen DAX-1 en un varón de 18 años que padeció fracaso suprarrenal completo en el período neonatal, hipogonadismo hipogonadotropo y talla baja patológica.Ingresó a los 16 días por presentar un síndrome pierde-sal con hiperpotasemia. Se mantuvo sin tratamiento hasta los 2 años, cuando comenzó progresivamente con anorexia, avidez por la sal, desmedro, hiperpigmentación cutánea y finalmente choque, hipoglucemia, hiponatremia, acidosis metabólica e hiperpotasemia.Inició espontáneamente el desarrollo puberal, pero fue incompleto. Recibió tratamiento con testosterona-depot. El volumen testicular definitivo alcanzado fue de 6¦ml con una pubarquia V. Su talla final ha sido 150¦cm (talla diana 164¦cm).El estudio genético del gen DAX-1 mostró la mutación g 2080-2081 ins a en la primera posición del codón 168, que produce una parada prematura de la proteína DAX en la posición 184. : Various genes play a role in the morphogenesis of the adrenal cortex, among them the DAX-1 gene. We report an 18-year-old man who showed complete adrenal failure in the neonatal period, hypogonadotropic hypogonadism and pathological short stature associated with a mutation of the DAX-1 gene that has not previously been described. The patient was admitted to hospital at the age of 16 days due to salt-losing syndrome with hyperpotassemia. After this episode, he received no treatment for 2 years, when he began to show progressive anorexia, salt avidity, asthenia, cutaneous hyperpigmentation and finally shock, with hypoglycemia, hyponatremia, metabolic acidosis and hyperpotassemia.Puberal development was spontaneous but incomplete. The patient received treatment with testosterone-depot. He reached a definitive testicular volume of 6 ml and pubarche V. His final height is 150 cm (target height 164¦cm).Amplification of the DAX-1 gene showed mutation g 2080-2081 insertion in the first position of codon 168, which produces a premature shutdown of protein DAX-1 at position 184.

Objetivos: Estudiar aspectos del desarrollo puberal en adolescentes obesas, y la influencia de la pérdida de peso en las mismas Métodos: Estudio retrospectivo y longitudinal de 26 adolescentes con peso normal y 46 obesas al inicio de la pubertad. Estas últimas se dividieron en dos grupos (normales y obesas) según su índice de masa corporal (IMC) al final de la pubertad. Se comparan: talla, edad cronológica, ósea y velocidad de crecimiento en los tres grupos Resultados: De las adolescentes obesas al iniciar la pubertad, el 63% permanecieron obesas al finalizarlaLas adolescentes obesas estudiadas tenían una talla significativamente mayor que las no obesas al inicio de la pubertad (143,2 ± 6,96 y 138,9 ± 5,95 cm, respectivamente; p < 0,01). Sin embargo, no existieron diferencias significativas en las tallas finales de ambos grupos; tampoco entre las obesas que perdieron peso y las que noNo hubo diferencias en las edades cronológicas ni óseas a lo largo del desarrollo puberal en ninguno de los gruposLa velocidad de crecimiento global durante la pubertad en el grupo de obesas fue significativamente menor que en el grupo control (6,18 ± 1,94 y 6,90 ± 1,27 cm/año, respectivamente; p < 0,02). Sin embargo, no hubo diferencias entre las obesas que perdieron peso y las que no Conclusiones: Las obesas tienen una ganancia de talla superior en la infancia pero inferior durante la adolescencia. La talla final es parecida en ambos grupos. El inicio y final de la pubertad son parejos y la maduración ósea similar. La pérdida de peso de las obesas durante la pubertad no altera el patrón global de crecimiento : Objectives: To study several aspects of puberal development in obese adolescent girls, and the influence of weight loss on these aspects Methods: A longitudinal retrospective study was performed of a sample of 26 adolescent girls with normal weight and46 obese adolescent girls at the onset of puberty. The obese teenagers were further divided into two groups (normal and obese) according to their body mass index (BMI) at the end of puberty. Height, chronological and bone age, and growth velocity were evaluated in both groups Results: Of the teenagers who were obese at the onset of puberty, 63 % remained obese at the end of pubertyThe obese teenagers were significantly taller than non-obese teenagers at the onset of puberty (143.2 ± 6.96 vs 138.9 ± 5.95 cm, respectively; p < 0.01). However, there were no differences between the two groups in final height. No differences were found between obese teenagers who lost weight and those who did notThere were no differences in chronological or bone age throughout puberal development in any of the groupsThe mean growth velocity during puberty was significantly lower in obese teenagers than in non-obese teenagers (6.18 ± 1.94 and 6.90 ± 127 cm/year, respectively; p < 0.02). However, there were no differences between obese teenagers who lost weight and those who did not Conclusions: Height gain in obese girls is greater in childhood but lower in adolescence. Final height is similar in both groups. Chronological age at the onset and end of puberty and bone maturation are similar in both groups. Weight loss during puberty does not modify growth pattern during this period of development