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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.

As a consequence of industrial mining activity, high volumes of tailings are scattered around Mexico. Frequently, tailings contain heavy metals (HM) which entail threats against all organisms. The aim of this research was to identify plants and root fungal endophytes in polymetallic polluted tailings with the potential to be used in strategies of bioremediation. Four deposits of mine wastes, situated in a semi-arid region near urban and semi-urban populations, and agricultural areas, were studied. The physical and chemical characteristics of substrates, accumulation of HM in plant tissues, root colonization between arbuscular mycorrizal (AMF) and dark septate endophyte (DSE) fungi, and the identification of DSE fungi isolated from the roots of two plant species were studied. Substrates from all four sites exhibited extreme conditions: high levels in sand; low water retention; poor levels in available phosphorus and nitrogen content; and potentially toxic levels of lead (Pb), cadmium (Cd), and zinc (Zn). The native plants Lupinus campestris, Tagetes lunulata, and Cerdia congestiflora, as well as the exotic Cortaderia selloana and Asphodelus fistulosus, demonstrated a relevant potential role in the phytostabilization and/or phytoextraction of Pb, Cd, and Zn, according to the accumulation of metal in roots and translocation to shoots. Roots of eleven analyzed plant species were differentially co-colonized between AMF and DSE fungi; the presence of arbuscules and microsclerotia suggested an active physiological interaction. Fourteen DSE fungi were isolated from the inner area of roots of T. lunulata and Pennisetum villosum; molecular identification revealed the predominance of Alternaria and other Pleosporales. The use of native DSE fungi could reinforce the establishment of plants for biological reclamation of mine waste in semi-arid climate. Efforts are needed in order to accelerate a vegetation practice of mine wastes under study, which can reduce, in turn, their potential ecotoxicological impact on organisms, human populations, and agricultural areas.

Rituximab is a monoclonal antibody used in the treatment of lymphoma non-Hodgkin. This mAb is photosensitive as it is administrated to the patient by infusion/perfusion; therefore, photostability is a decisive factor in the efficacy of this biologic. To better understand the photodegradation mechanisms of Rituximab, this biologic was exposed to different irradiance conditions. We show in this study that this mAb photodegrade proportionally to irradiance intensities. The main modifications of Rituximab by irradiance correlate to the increase in aggregates, decrease in its Tm, acidic charge variants, oxidation of the Trp (36) in the heavy chain, and decrease in complement-dependent cytotoxicity (CDC) potency. To understand the relationship between real-life photo-exposition conditions and ICH standardized light tests, a full characterization was set up. Worst photo-stress cases were evaluated, 1 and 2 h under direct sunlight through a window, mimicking the ID65 electromagnetic radiation profile. Our results show that only exposition to direct sun irradiance during 2 h, (≈ 150 kluxes•h), increases critically soluble and insoluble aggregates, diminishing Tm, increasing acidic charge variants, and the photooxidation of the Trp (36) in the heavy chain measured by peptide mapping-RP-UPLC-MS. A decrease in CDC below 80% resulted under this condition, which correlates with physicochemical analyses. While inside light-room exposition (similar to ICH test) and ICH conditions do not have any contribution to the degradation of Rituximab measured by these physicochemical and biological analytical methods. These results indicate that exposition of Rituximab to below ≈ 75 kluxes•h of sun light cannot photodegrade critically this biologic inside of its primary container.

Introduction: Identifying effective drugs for Coronavirus disease 2019 (COVID-19) is urgently needed. An efficient approach is to evaluate whether existing approved drugs have anti-SARS-CoV-2 effects. The antiviral properties of lithium salts have been studied for many years. Their anti-inflammatory and immune-potentiating effects result from the inhibition of glycogen synthase kinase-3.& nbsp;Aims: To obtain pre-clinical evidence on the safety and therapeutic effects of lithium salts in the treatment of COVID-19.& nbsp;Results: Six different concentrations of lithium, ranging 2-12 mmol/L, were evaluated. Lithium inhibited the replication of SARS-CoV-2 virus in a dose-dependent manner with an IC50 value of 4 mmol/L. Lithium-treated wells showed a significantly higher percentage of monolayer conservation than viral control, particularly at concentrations higher than 6 mmol/L, verified through microscopic observation, the neutral red assay, and the determination of N protein in the supernatants of treated wells. Hamsters treated with lithium showed less intense disease with fewer signs. No lithium-related mortality or overt signs of toxicity were observed during the experiment. A trend of decreasing viral load in nasopharyngeal swabs and lungs was observed in treated hamsters compared to controls.& nbsp;Conclusions: These results provide pre-clinical evidence of the antiviral and immunotherapeutic effects of lithium against SARS-CoV-2, which supports an advance to clinical trials on COVID-19 & PRIME;s patients. The authors are indebted to CICDC staff for their collaborative support and dedication during the experiments. We are grateful to YJ Gonzalez ´ for her technical support, constructive discussions, and scientific input. We also thank J Delgado and SR Paez from Empresa Central de Laboratorios “Jos´e Isaac del Corral”, Havana, Cuba, for their invaluable contribution. We also thank JF Infante for the anatomopathological evaluation of hamsters. CE Rudd is supported by a grant from the Canadian Institutes of Health Research (CIHR).

The overproduction of recombinant proteins in Escherichia coli leads to insoluble aggregates of proteins called inclusion bodies (IBs). IBs are considered dynamic entities that harbor high percentages of the recombinant protein, which can be found in different conformational states. The production conditions influence the properties of IBs and recombinant protein recovery and solubilization. The E. coli growth in thermoinduced systems is generally carried out at 30 °C and then recombinant protein production at 42 °C. Since the heat shock response in E. coli is triggered above 34 °C, the synthesis of heat shock proteins can modify the yields of the recombinant protein and the structural quality of IBs. The objective of this work was to evaluate the effect of different pre-induction temperatures (30 and 34 °C) on the growth of E. coli W3110 producing the human granulocyte-macrophage colony-stimulating factor (rHuGM-CSF) and on the IBs structure in a λpL/pR-cI857 thermoinducible system. The recombinant E. coli cultures growing at 34 °C showed a ~ 69% increase in the specific growth rate compared to cultures grown at 30 °C. The amount of rHuGM-CSF in IBs was significantly higher in cultures grown at 34 °C. Main folding chaperones (DnaK and GroEL) were associated with IBs and their co-chaperones (DnaJ and GroES) with the soluble protein fraction. Finally, IBs from cultures that grew at 34 °C had a lower content of amyloid-like structure and were more sensitive to proteolytic degradation than IBs obtained from cultures at 30 °C. Our study presents evidence that increasing the pre-induction temperature in a thermoinduced system allows obtaining higher recombinant protein and reducing amyloid contents of the IBs. KEY POINTS: • Pre-induction temperature determines inclusion bodies architecture • In pre-induction (above 34 °C), the heat shock response increases recombinant protein production • Inclusion bodies at higher pre-induction temperature show a lower amyloid content.

The COVID-19 pandemic has extensively changed the state of psychological science from what research questions psychologists can ask to which methodologies psychologists can use to investigate them. In this article, we offer a perspective on how to optimize new research in the pandemic’s wake. Because this pandemic is inherently a social phenomenon—an event that hinges on human-to-human contact—we focus on socially relevant subfields of psychology. We highlight specific psychological phenomena that have likely shifted as a result of the pandemic and discuss theoretical, methodological, and practical considerations of conducting research on these phenomena. After this discussion, we evaluate metascientific issues that have been amplified by the pandemic. We aim to demonstrate how theoretically grounded views on the COVID-19 pandemic can help make psychological science stronger—not weaker—in its wake.

BackgroundCoinfections with fungi and bacteria in ocular pathologies are increasing at an alarming rate. Two of the main etiologic agents of infections on the corneal surface, such as Aspergillus fumigatus and Staphylococcus aureus, can form a biofilm. However, mixed fungal–bacterial biofilms are rarely reported in ocular infections. The implementation of cell cultures as a study model related to biofilm microbial keratitis will allow understanding the pathogenesis in the cornea. The cornea maintains a pathogen-free ocular surface in which human limbo-corneal fibroblast cells are part of its cell regeneration process. There are no reports of biofilm formation assays on limbo-corneal fibroblasts, as well as their behavior with a polymicrobial infection.ObjectiveTo determine the capacity of biofilm formation during this fungal–bacterial interaction on primary limbo-corneal fibroblast monolayers.ResultsThe biofilm on the limbo-corneal fibroblast culture was analyzed by assessing biomass production and determining metabolic activity. Furthermore, the mixed biofilm effect on this cell culture was observed with several microscopy techniques. The single and mixed biofilm was higher on the limbo-corneal fibroblast monolayer than on abiotic surfaces. The A. fumigatus biofilm on the human limbo-corneal fibroblast culture showed a considerable decrease compared to the S. aureus biofilm on the limbo-corneal fibroblast monolayer. Moreover, the mixed biofilm had a lower density than that of the single biofilm. Antibiosis between A. fumigatus and S. aureus persisted during the challenge to limbo-corneal fibroblasts, but it seems that the fungus was more effectively inhibited.ConclusionThis is the first report of mixed fungal–bacterial biofilm production and morphological characterization on the limbo-corneal fibroblast monolayer. Three antibiosis behaviors were observed between fungi, bacteria, and limbo-corneal fibroblasts. The mycophagy effect over A. fumigatus by S. aureus was exacerbated on the limbo-corneal fibroblast monolayer. During fungal–bacterial interactions, it appears that limbo-corneal fibroblasts showed some phagocytic activity, demonstrating tripartite relationships during coinfection.

Fusarium solani has drawn phytopathogenic, biotechnological, and medical interest. In humans, it is associated with localized infections, such as onychomycosis and keratomycosis, as well as invasive infections in immunocompromised patients. One pathogenicity factor of filamentous fungi is biofilm formation. There is still only scarce information about the in vitro mechanism of the formation and composition of F. solani biofilm. In this work, we describe the biofilm formed by a clinical keratomycosis isolate in terms of its development, composition and susceptibility to different antifungals and ultraviolet light (UV) at different biofilm formation stages. We found five biofilm formation stages using scanning electron microscopy: adherence, germination, hyphal development, maturation, and cell detachment. Using epifluorescence microscopy with specific fluorochromes, it was elucidated that the extracellular matrix consists of carbohydrates, proteins, and extracellular DNA. Specific inhibitors for these molecules showed significant biofilm reductions. The antifungal susceptibility against natamycin, voriconazole, caspofungin, and amphotericin B was evaluated by metabolic activity and crystal violet assay, with the F. solani biofilm preformation to 24 h increased in resistance to natamycin, voriconazole, and caspofungin, while the biofilm preformation to 48 h increased in resistance to amphotericin B. The preformed biofilm at 24 h protected and reduced UV light mortality. F. solani isolate could produce a highly structured extra biofilm; its cellular matrix consists of carbohydrate polymers, proteins, and eDNA. Biofilm confers antifungal resistance and decreases its susceptibility to UV light. The fungal biofilm functions as a survival strategy against antifungals and environmental factors.

High-density lipoprotein (HDL) is considered a complex plasma-circulating particle with subfractions that vary in function, size, and chemical composition. We sought to test the effects of HDL, and HDL subfractions on insulin secretion and cholesterol efflux in the β-cell line MIN-6.We used total HDL and HDL subfractions 2a, 2b, 3a, 3b, and 3c, isolated from human plasma, to test insulin secretion under different glucose concentrations as well as insulin content and cholesterol efflux in the insulinoma MIN-6 cell line.Incubation of MIN-6 cells with low glucose and total HDL increased insulin release two-fold. Meanwhile, when high glucose and HDL were used, insulin release increased more than five times. HDL subfractions 2a, 2b, 3a, 3b, and 3c elicited higher insulin secretion and cholesterol efflux than their respective controls, at both low and high glucose concentrations. The insulin content of the MIN-6 cells incubated with low glucose and any of the five HDL subclasses had a modest reduction compared with their controls. However, there were no statistically significant differences between each HDL subfraction on their capacity of eliciting insulin secretion, insulin content, or cholesterol efflux.HDL can trigger insulin secretion under low, normal, and high glucose conditions. We found that all HDL subfractions exhibit very similar capacity to increase insulin secretion and cholesterol efflux. This is the first report demonstrating that HDL subfractions act both as insulin secretagogues (under low glucose) and insulin secretion enhancers (under high glucose) in the MIN-6 cell line.

The skin glands of amphibian species hold a major component of their innate immunity, namely a unique set of antimicrobial peptides (AMPs). Although most of them have common characteristics, differences in AMP sequences allow a huge repertoire of biological activity with varying degrees of efficacy. We present the first study of the AMPs from

Silver nanoparticles (AgNPs) are known to interact with proteins, leading to modifications of the plasmonic absorption that can be used to monitor this interaction, entailing a promising application for sensing adsorption of therapeutic proteins in primary containers. First, transmission electron microscopy in combination with plasmonic absorption and light scattering responses were used to characterize AgNPs and protein-AgNP complexes, including its concentration dependence, using two therapeutic molecules as models: a monoclonal antibody (mAb) and a synthetic copolymer (SC). Upon interaction, a protein corona was formed around AgNPs with the consequent shifting and broadening of their characteristic surface plasmon resonance (SPR) band (400 nm) to 410 nm and longer wavelenghts. Additional studies revealed secondary and three-dimensional structure modifications of model proteins upon interaction with AgNPs by circular dichroism and fluorescence techniques, respectively. Based on the modification of the SPR condition of AgNPs upon interaction with proteins, we developed a novel protein-sensing application of AgNPs in primary containers. This strategy was used to conduct a compatibility assessment of model proteins towards five commercially available prefillable glass syringe (PFS) models. mAb- and SC-exposed PFSs showed that 74 and 94% of cases were positive for protein adsorption, respectively. Interestingly, protein adsorption on 15% of total tested PFSs was negligible (below the nanogram level). Our results highlight the need of a case-by-case compatibility assessment of therapeutic proteins and their primary containers. This strategy has the potential to be easily applied on other containers and implemented during early-stage product development by pharmaceutical companies and for routine use during batch release by packaging manufacturers.

To determine whether a short 6-session protocol of tonic/ phasic exercises can enhance quality of life and muscular strength in patients with urinary incontinence (UI).A prospective before-after study was performed in 67 patients with UI referred to the Rehabilitation Department of the Santa Cristina University Hospital in Madrid, Spain. In the initial assessment, the patient's personal details, predisposing factors and type of UI were registered. Patients received lifestyle recommendations. The ICIQ-SF/I-QOL questionnaires/scales were completed at the beginning and end of treatment. The manometric evaluation was registered in the first and last assessment by the MYOMEDThe mean age was 52.1±12.7 years and 94% of the patients (n=63) were women. The maximum and mean strength of the pelvic floor contraction was 26.4±15.6 and 5.3±3.9mmHg, respectively, which significantly increased after treatment to 35.5±19.6 and 7.6±4.4mmHg (P.0001). The ICIQ-SF score was 10.1±5 and significantly decreased to 6.6±4.6 (P0.0001). The I-QOL score significantly increased from 66.1±21.9 to 77.9±18.1 points (P.0001). The I-QOL ALB subscale (avoidance and limiting behaviour) increased from 63.7±22.6 to 77.3±17.8 (P.0001); the I-QoL PSI subscale (psychosocial impact) increased from 73.8±23.9 to 82.5±18.7 (P=.0004); and the I-QOL SE subscale (social embarrassment) increased from 56.5±23.7 to 70.5±22.1 (P.0001).Manometric feedback reduces UI and improves both quality of life and manometric values. This short 6-session protocol could be applied in other public and private centres and could provide economic benefits to the health system and to patients.

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.

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.

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.

Traditional strategies for production of thermo-induced recombinant protein in Escherichia coli consist of a two-phase culture, with an initial growth stage at low temperature (commonly 30 °C) followed by a production stage where temperature is increased stepwise (commonly up to 42 °C). A disadvantage of such strategies is that growth is inhibited upon temperature increase, limiting the duration of the production stage and consequently limiting recombinant protein production. In this work, a novel oscillatory thermo-induction strategy, consisting on temperature fluctuations between 37 and 42 °C or 30 and 42 °C, was tested for improving recombinant protein production. In addition, the induction schemes were combined with one of three different nutrient feeding strategies: two exponential and one linear. Recombinant human preproinsulin (HPPI), produced under control of the λPL-cI857 system in the E. coli BL21 strain, was used as the model protein. Compared to the conventional induction scheme at constant temperature (42 °C), longer productive times were attained under oscillatory induction, which resulted in a 1.3- to 1.7-fold increase in maximum HPPI concentration. Temperature oscillations led to a 2.3- to 4.0-fold increase in biomass accumulation and a decrease of 48–62% in the concentration of organic acids, compared to conventional induction. Under constant induction, growth ceased upon temperature increase and the maximum concentration of HPPI was 3.9 g/L, regardless of the post-induction feeding strategy used. In comparison, the combination of temperature oscillations and a high nutrient-feeding rate allowed sustained growth after induction and reaching up to 5.8 g/L of HPPI.

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.

At the laboratory scale, sudden step increases from 30 to 42 degrees C can be readily accomplished when expressing heterologous proteins in heat-inducible systems. However, for large scale-cultures only slow ramp-type increases in temperature are possible due to heat transfer limitations, where the heating rate decreases as the scale increases. In this work, the transcriptional and metabolic responses of a recombinant Escherichia coli strain to temperature-induced synthesis of pre-proinsulin in high cell density cultures were examined at different heating rates. Heating rates of 6, 1.7, 0.8, and 0.4 degrees C/min were tested in a scale-down approach to mimic fermentors of 0.1, 5, 20, and 100 m(3), respectively. The highest yield and concentration of recombinant protein was obtained for the slowest heating rate. As the heating rate increased, the yield and maximum recombinant protein concentration decreased, whereas a larger fraction of carbon skeletons was lost as acetate, lactate, and formate. Compared to 30 degrees C, the mRNA levels of selected heat-shock genes at 38 and 42 degrees C, as quantified by qRT-PCR, increased between 2- to over 42-fold when cultures were induced at 6, 1.7, and 0.8 degrees C/min, but no increase was observed at 0.4 degrees C/min. Only small increases (between 1.5- and 4-fold) in the expression of the stress genes spoT and relA were observed at 42 degrees C for cultures induced at 1.7 and 6 degrees C/min, suggesting that cells subjected to slow temperature increases can adapt to stress. mRNA levels of genes from the transcription-translation machinery (tufB, rpoA, and tig) decreased between 40% and 80% at 6, 1.7 and 0.8 degrees C/min, whereas a transient increase occurred for 0.4 degrees C/min at 42 degrees C. mRNA levels of the gene coding for pre-proinsulin showed a similar profile to transcripts of heat-shock genes, reflecting a probable analogous induction mechanism. Altogether, the results obtained indicate that slow heating rates, such as those likely to occur in conventional large-scale fermentors, favored heterologous protein synthesis by the thermo-inducible expression system used in this report. Knowledge of the effect of heating rate on bacterial physiology and product formation is useful for the rational design of scale-down and scale-up strategies and optimum recombinant protein induction schemes.

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.

UV spectrophotometric measurement is a widely accepted and standardized routine analysis for quantitation of highly purified proteins; however, the reliability of the results strictly depends on the accuracy of the employed extinction coefficients. In this work, an experimental estimation of the differential refractive index (dn/dc), based on dry weight measurements, was performed in order to determine accurate extinction coefficients for four biotherapeutic proteins and one synthetic copolymer after separation in a size-exclusion ultra-performance liquid chromatograph coupled to an ultraviolet, multiangle light scattering and refractive index (SE-UPLC-UV-MALS-RI) multidetection system. The results showed small deviations with respect to theoretical values, calculated from the specific amino acid sequences, for all the studied immunoglobulins. Nevertheless, for proteins like etanercept and glatiramer acetate, several considerations, such as glycan content, partial specific volume, polarizability, and higher order structure, should be considered to properly calculate theoretical extinction coefficient values. Herein, these values were assessed with simple approximations. The precision of the experimentally obtained extinction coefficients, and its convergence towards the theoretical values, makes them useful for characterization and comparability exercises. Also, these values provide insight into the absorbance and scattering properties of the evaluated proteins. Overall, this methodology is capable of providing accurate extinction coefficients useful for development studies.

Comparability between a biosimilar and its reference product requires the evaluation of critical quality attributes that may impact on its pharmacological response. Herein we present a physicochemical characterization of a biosimilar trastuzumab focused on the attributes related to the pharmacokinetic response. Capillary isoelectrofocusing (cIEF) and cation exchange chromatography (CEX) were used to evaluate charge heterogeneity; glycosylation profiles were assessed through hydrophilic interaction liquid chromatography (HILIC); aggregates content was evaluated through size exclusion chromatography (SEC) while binding affinity to FcRn was evaluated using isothermal titration calorimetry (ITC). The biosimilar trastuzumab and its reference product exhibited a high degree of similarity for the evaluated attributes. In regard to the pharmacokinetic parameters, randomized, double blind, and two-arm parallel and prospective study was employed after the administration of a single intravenous dose in healthy volunteers. No significant differences were found between the pharmacokinetic profiles of both products. Our results confirm that similarity of the critical quality attributes between a biosimilar product, obtained from a different manufacturing process, and the reference product resulted in comparable pharmacokinetic profiles, diminishing the uncertainty related to the biosimilar’s safety and efficacy.

Rituximab is a chimeric monoclonal antibody employed for the treatment of CD20-positive B-cell non-Hodgkin’s lymphoma, chronic lymphocytic leukemia, rheumatoid arthritis, granulomatosis with polyangiitis and microscopic polyangiitis. It binds specifically to the CD20 antigen expressed on pre-B and consequently on mature B-lymphocytes of both normal and malignant cells, inhibiting their proliferation through apoptosis, CDC, and ADCC mechanisms. The immunomodulatory activity of rituximab is closely related to critical quality attributes that characterize its chemical composition and spatial configuration, which determine the recognition of CD20 and the binding to receptors or factors involved in its effector functions, while regulating the potential immunogenic response. Herein, we present a physicochemical and biological characterization followed by a pharmacodynamics and immunogenicity study to demonstrate comparability between two products containing rituximab. The physicochemical and biological characterization revealed that both products fit within the same response intervals exhibiting the same degree of variability. With regard to clinical response, both products depleted CD20+ B-cells until posttreatment recovery and no meaningful differences were found in their pharmacodynamic profiles. The evaluation of anti-chimeric antibodies did not show differential immunogenicity among products. Overall, these data confirm that similarity of critical quality attributes results in a comparable immunomodulatory activity.

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.

It remains unknown whether human papillomaviruses (HPVs) in semen affect sperm DNA integrity. We investigated whether the presence of these viruses in semen was associated with an elevated sperm DNA fragmentation index. Semen samples of 22 normozoospermic patients undergoing infertility treatment, nine fertile donors and seven fertile men with a risk of HPV infection (genital warts or condylomas) were included in the study. The samples were examined by an INNO-LiPA test PCR-based reverse hybridisation array that identifies 28 types of HPVs as simple or multiple infections. Sperm DNA integrity was determined by sperm chromatin dispersion assay (SCD). Our preliminary findings demonstrate an increase in HPV infection in infertile men with respect to fertile men. However, the sperm DNA fragmentation index was not increased in semen containing these viruses.

Turner syndrome is diagnosed by the combination of certain phenotypic characteristics with the absence of one of the X chromosome. This absence may be total or partial, as occurs in isochromosomes Xq. The phenotypic consequences of these depend on two factors: the characteristics of the lost genes and the percentage of cells 45, X in mosaicisms. The clinical features also change with the cytogenetic pattern. Short stature is the most common phenotypic manifestation, as it is due to the haploinsufficiency of the SHOX gene on the short arm of X chromosomes. Thus, when there is isochromosomes on the long arms, short stature is always present. However, the typical features of this syndrome could be absent, and the diagnosis can be delayed. This occurred in our patients, who will not be able to obtain optimum benefits with growth hormone treatment.

The Health Administration Agencies of many municipalities in Greater Buenos Aires (GBA) receive frequent reports on triatomines in houses. The aim of this work was to identify and describe the dispersal foci of Triatoma infestans in an urban neighborhood of GBA, and contribute to the knowledge of the epidemiological situation in the region. In June 1998, potentially infested places were entomologically evaluated. T. infestans was only detected in a hen building for egg production, which housed approximately 6,000 birds. A total of 2,930 insects were collected. Density was about 9 triatomines/m(2). The proportions of fifth instar nymphs and adults were significantly higher than those of the other stages (p0.001). The number of triatomines collected largely exceeded the highest domestic infestation found in one house from rural endemic areas of Argentina. Though triatomines were negative for Trypanosoma cruzi, they could acquire the parasite by coming in contact with infected people living in GBA. Besides, the numerous and widely distributed places housing hens and chickens, would favor the settlement of the vector. Together, both facts may constitute a risk of parasitic vectorial transmission. It is recommended to intensify systematic activities of vector search and case detection in GBA.

In this work, a high-resolution CGE method for quantification and purity determination of recombinant proteins was developed, involving a single-component inclusion bodies (IBs) solubilization solution. Different recombinant proteins expressed as IBs were used to show method capabilities, using recombinant interferon-β 1b as the model protein for method validation. Method linearity was verified in the range from 0.05 to 0.40 mg/mL and a determination coefficient (r(2) ) of 0.99 was obtained. The LOQs and LODs were 0.018 and 0.006 mg/mL, respectively. RSD for protein content repeatability test was 2.29%. In addition, RSD for protein purity repeatability test was 4.24%. Method accuracy was higher than 90%. Specificity was confirmed, as the method was able to separate recombinant interferon-β 1b monomer from other aggregates and impurities. Sample content and purity was demonstrated to be stable for up to 48 h. Overall, this method is suitable for the analysis of recombinant proteins in IBs according to the attributes established on the International Conference for Harmonization guidelines.

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.

The prevalence of diseases related to asbestos exposure requires the development of monitoring programs and specific health care protocols. The aim of this study is to determine the opinions and expectations of former workers of an asbestos factory, in order to adapt the care process to the needs of the affected population, and to learn about the activity of the association that represents them.Qualitative study. Focus groups with former employees of a corrugated asbestos factory, members of the association AVIDA (Seville). Recording and transcription of interviews. Discourse analysis with Nudist Vivo 1.0.All respondents have health problems, including asbestosis, lung cancer and mesothelioma. Through the association, they are involved in an ongoing process of negotiation with the public administration, to improve healthcare, achieve recognition as having an occupational disease and the payment of compensation. The lack of monitoring and continuity in care is designated as the major problem in the current care process. They welcome the creation of special care units, the good treatment received and the quality of technical instruments in the public health system. On the contrary, they criticize the difficulties in finding an accurate diagnosis, the lack of continuity of care, and the bureaucratic difficulties and lack of specific care directed to affected relatives. The participants' expectations highlight their intention to participate in the development of future programs and protocols.This study confirms the multifactor nature of diseases related to asbestos exposure and the importance of determining the needs and demands of the affected population in order to improve health care.

To describe the factors associated to morbidity-mortality in pediatric patients with severe head injury (SHI).A review was made of the patients admitted to the Pediatric Intensive Care Unit (PICU) with SHI between July 1983 and December 2009.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%; p0.001). The independent mortality risk factors in the pediatric patients with SHI were found to be the presence of mydriasis (OR: 31.27), intracranial hypertension (OR: 13.23) and hyperglycemia (OR: 3.10).a) SHI in pediatric patients was associated with high morbidity-mortality; b) intracranial hypertension was associated to the development of serious sequelae; c) independent mortality risk factors were the existence of mydriasis, intracranial hypertension and hyperglycemia.

To describe the epidemiology, clinical manifestations and evolutive characteristics of pediatric patients with severe head injury (SHI).A review was made of the patients admitted to the pediatric intensive care unit (PICU) with SHI between July 1983 and December 2009.Of the 389 patients with head injuries admitted to the PICU during the study period, 174 (45%) presented SHI. The mean age in this group was of 67±9 months, with a Glasgow Coma Score (GCS) of 5.5±1.8 and a PRISM score of 10.7±6.7. The most frequent etiology of SHI was traffic accidents (56%), though these have decreased significantly in the last decade (58.5% vs 45.3%; P.001). Twenty-one percent of the patients required evacuation of the lesions detected by computed tomography (CT), and 39% presented severe diffuse encephalic injury (DEI). Seventy-nine percent of the patients in whom intracranial pressure (ICP) was monitored presented intracranial hypertension. Sequelae of clinical relevance were recorded in 59 patients (39%), and proved serious in 64% of the cases. The mortality rate in this patient series was 24.7%. Intracranial hypertension decreased significantly in the last decade (88% vs 54%; P.05), and clinical recovery has improved (23.3% vs 63.1%; P.001).a) The incidence of traffic accidents has decreased in the last decade in the studied population; b) patients with SHI in which ICP was monitored showed a high incidence of intracranial hypertension; c) morbidity-mortality among pediatric patients with SHI has decreased over the course of the study period.

To evaluate a telephone-information service on health issues for children before its implementation. To determine the overall assessment of the service and quality of the information available from the perspective of a potential user population.Simulation of a telephone call to the telephone service and further evaluation using qualitative techniques.Primary and special care in the city of Granada.Parents, who were not health professionals, of children between 0 and 14 years old, resident in Andalusia and recruited from both primary care and hospitals throughout the city of Granada. A comprehensive assessment of service and quality of information offered through interviews and focus groups. The number of participants was established on two criteria: evaluation of the whole range of information provided by the telephone service; response saturation.The overall service assessment was positive, emphasising the quick and easy access to information, time saving and confidence building. The information received was described as clear, easily understood and expressed in a respectful tone. To improve the service it has been suggested that the calls be free and that the range of information topics available should be extended.The methodology used is novel, as most telephone services are evaluated after they have been put in place and without the participation of the future users.

The characteristics of social settings are increasingly being recognized as important factors influencing the health of individuals. This study examines the association of neighborhood physical and social disorganization with alcohol consumption in a sample of adolescents 12- to 15-years-old residing in communities of the San Juan metropolitan area with high availability of illicit drugs.The sampling frame was developed encompassing all census sectors in three municipalities of the San Juan metropolitan area with outdoor illegal drug-selling areas operating within them. Consent from parents and their adolescent offspring was obtained from 691 of these households for a response rate of 96%. Alcohol use was measured by asking adolescents if they had consumed alcohol during the last 12 months. Neighborhood social disorganization included hearing gunfire in the neighborhood, seeing neighbors selling stolen merchandise and drugs, vandalism, neighbors using alcohol and drugs, and seeing persons carrying weapons. Neighborhood physical disorganization included the presence of abandoned vehicles and buildings in the neighborhood, graffiti, and places where people go to inject drugs.Multiple logistic regression analysis revealed that older participants were more likely to use alcohol. Neighborhood social disorder was significantly associated with alcohol use. The strong positive gradient between neighborhood social disorder and alcohol use remained highly significant after controlling by sociodemographic characteristics. In contrast, neighborhood physical disorder was not significantly associated with alcohol use.These findings suggest that social signs of neighborhood disorganization have a more direct influence over adolescents' behaviors than the physical signs. Health professionals need to be cognizant of the strong effects that social environments have on adolescents and develop strategies to address these when intervening with adolescents.

Lupus nephritis is associated with an unfavorable outcome. Its incidence is higher in children. It has been the impression of pediatric nephrologists and rheumatologists in Puerto Rico that the clinical manifestations in Puerto Rican children differ from what has been described in other geographic regions. The potential deleterious effects of sun exposure could suggest that Puerto Rican children living in the Island are at high risk for severe nephritis.To describe the manifestations and identify predictors of patient and renal survival, we reviewed the medical charts of children diagnosed with lupus nephritis in Puerto Rico between 1987-2001.Mesangial glomerulonephritis (Type II) was the most common histopathological lesion observed. We observed a high incidence of nephritis among males, with a male: female ratio of 1:1.9.The presence of type IV nephritis and need for acute dialysis at presentation were identified as predictors of poor clinical outcome (development of end stage renal disease or death).

Hemolytic Uremic Syndrome (HUS) consists ofa triad of acquired hemolytic anemia, thrombocytopenia, and renal failure that occurs acutely in otherwise healthy individuals. HUS may be divided into two broad categories, typical, preceded by a diarrheal prodrome, and atypical. The clinical symptoms of HUS as well as its course, prognosis, and response to treatment appear to be significantly influenced by a number of factors, including age at onset, type and severity of underlying infections, and/or systemic diseases. A retrospective case series review of five patients diagnosed with Hemolytic Uremic Syndrome at the Pediatric University Hospital in Puerto Rico between 1997-2007 was performed. The study showed that the incidence of HUS in children in Puerto Rico is lower than other countries. However, the majority of cases have an atypical presentation, which places our patients at higher risk for life-threatening complications.

25 years ago was first reported in Cuba and in the western hemisphere an emergent disease: eosinophilic meningoencephalitis due to Angiostrongylus cantonensis larvae.To collect in a summary form the accumulated experience and the findings of the study of this parasitosis during the period in the Western hemisphere.There have been collected the first evidences, the parasitological and malacological findings, the experimental and molecular studies on immunology and neuroimmunology, the clinic-pathological findings in children and adults with the particularities of this diseases in our environment with special emphasis in the never-before scientific findings reported. It has been documented the testimony, the main findings among the malacological studies, the role of the immunoglobulin E and the mechanism involved in the central nervous system, the intrathecal synthesis patterns of immunoglobulins and the clinical elements in children and adults.

Apply a sedoanalgesic (SA) protocol for invasive procedures (PI) in pediatric patients and evaluate its effectiveness and safety.Prospective observational study.Pediatric Intensive Care Unit (PICU) of third level hospital.A total of 110 children subjected to invasive procedures under sedoanalgesia with propofol and fentanyl.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.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, p0.001) compared to those with minor SA level, as well as heart rate (88 +/- 17 vs 91 +/- 25 bpm, p0.05) and respiratory rate (19 +/- 6 vs 23 +/- 11 bpm, p0.05). 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.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.

To show that the ceramic produced at the Institute for Materials Research, National Autonomous University of Mexico, is an appropriate replacement of bone graft in patients with bone tumors, benign tumors, pseudoarthrosis and arthrodesis treated at "General Ignacio Zaragoza" Regional Hospital.An experimental, longitudinal study using bovine ceramic xenoimplants in patients covered by the Security and Social Services Institute for Civil Servants (ISSSTE), regardless of age and gender, all of whom consented to receiving the ceramic xenoimplant. Patients who did not consent or who discontinued treatment were excluded. A total of 24 patients were enrolled from March 1st to August 31st, 2006; two patients were withdrawn due to treatment discontinuation. They underwent X-ray evaluation of bone healing using the Montoya classification.The sample is composed of 14 male and 8 female patients, with a mean age of 46.6 years, and a standard deviation (s=) of 13.8. The most frequent indication was arthrodesis in 10 patients (45.45%), pseudoarthrosis in 6 (27.27%), benign tumors in 3 (13.63%), and bone defects in 3 (13.63%). Type II to type IV bone healing was observed in the sample.The use of ceramic xenoimplants is appropriate as a replacement of bone graft in patients with arthrodesis and bone defects, thus avoiding the need for autologous bone graft. This results in a decreased patient morbidity.

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.

To study several aspects of puberal development in obese adolescent girls, and the influence of weight loss on these aspects.A longitudinal retrospective study was performed of a sample of 26 adolescent girls with normal weight and 46 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.Of the teenagers who were obese at the onset of puberty, 63 % remained obese at the end of puberty. The 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; p0.01). 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 not. There were no differences in chronological or bone age throughout puberal development in any of the groups. The 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; p0.02). However, there were no differences between obese teenagers who lost weight and those who did not.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.

Heart transplantation currently provides the most effective treatment for advanced heart failure. However, medical therapy for this condition has also improved, heart donors are scarce and the cost of the procedure is high. Therefore the indications and management of these patients need reevaluation.To analyze the results of 24 patients submitted to heart transplantation for end-stage heart failure needing repeated hospitalizations and i.v. inotropes for compensation.The group was comprised by 21 men and 3 women with a mean age of 36.8 years, mean left ventricular ejection fraction 19 +/- 4.5%, mean systolic pulmonary artery pressure 48 +/- 13 mmHg (24-70) and mean pulmonary vascular resistance 2.6 Wood Units (1-5). Fourteen patients (58%) had a previous median sternotomy. Immunosuppression did not include induction therapy and steroids were discontinued early.Operative mortality was 4% at 30 days. Actuarial survival at one year was 90% and at 5 years 72%. Freedom from rejection at one year was 76% and at 5 years 50%. Freedom from infection was 70% at one year and 56.5% at five years. All patients with more than 3 months of follow-up were in functional class I.These results justify the proposed modifications for transplantation protocols.

Accumulation of polymorphonuclear neutrophils (PMN) into the subarachnoidal space is one of the hallmarks of Neisseria meningitidis infection. In this study, we evaluated the ability of outer membrane vesicles (OMV) from N. meningitidis B to stimulate cytokine production by neutrophils. We found that PMN stimulated in vitro by OMV produce proinflammatory cytokines and chemokines including tumor necrosis factor alpha (TNF-alpha), interleukin-1beta (IL-1beta), IL-8, macrophage inflammatory protein 1alpha (MIP-1alpha), and MIP-1beta. A considerable induction of gamma interferon (IFN-gamma)-inducible protein 10 (IP-10) mRNA transcripts, as well as extracellular IP-10 release, was also observed when neutrophils were stimulated by OMV in combination with IFN-gamma. Furthermore, PMN stimulated by OMV in the presence of IFN-gamma demonstrated an enhanced capacity to release TNF-alpha, IL-1beta, IL-8, and MIP-1beta compared to stimulation with OMV alone. In line with its downregulatory effects on neutrophil-derived proinflammatory cytokines, IL-10 potently inhibited TNF-alpha, IL-1beta, IL-8, and MIP-1beta production triggered by OMV. Finally, a neutralizing anti-TNF-alpha monoclonal antibody (MAb) did not influence the release of IL-8 and MIP-1beta induced by OMV, therefore excluding a role for endogenous TNF-alpha in mediating the induction of chemokine release by OMV. In contrast, the ability of lipopolysaccharide from N. meningitidis B to induce the production of IL-8 and MIP-1beta was significantly inhibited by anti-TNF-alpha MAb. Our results establish that, in response to OMV, neutrophils produce a proinflammatory profile of cytokines and chemokines which may not only play a role in the pathogenesis of meningitis but may also contribute to the development of protective immunity to serogroup B meningococci.

It has been proved that there is an inspiratory muscle dysfunction in mitral stenosis; Although its causes still remain unknown.To evaluate the effect of percutaneous balloon mitral valvuloplasty (PMV) on inspiratory muscle performance (IMP) in patients with mitral stenosis (mitral area1.5 cm2).We studied IMP in 8 patients (35 +/- 10 years) before and 3 months after successful PMV. Inspiratory muscle strength was studied by measuring maximal statistical inspiratory mouth pressure (MIP). Endurance was evaluated using a two minute incremental threshold loading test in order to obtain the maximal sustainable inspiratory pressure (SIP), with the maximal sustainable load (MSL) the patients could sustain for 2 minutes.Mitral valvuloplasty increased mean cardiac index from 3.1 +/- 0.3 to 4.15 +/- 0.3 l/min/m2 (p0.01), and significantly decreased mean pulmonary and capillary pressures. The MIP value(118 +/- 6 cmH2O), similar to that of normal group, increased to 137 +/- 7 cmH2O (p0.01). SIP and maximal sustainable load were 52 +/- 3 cmH2O and 294 +/- 29 g respectively, lower than normal subjects (p0.05). They increased after PMV to 80 +/- 3 cmH2O and 463 +/- 26 g respectively (p0.001).PMV improved inspiratory muscle function in patients with severe mitral stenosis, probably secondary to a decrease work of breath and improvement of ventricular function.