Control de calidad en nutrición parenteral neonatal, empleando como método validado el análisis bioquímico / Quality control in neonatal parenteral nutrition, using biochemical analysis as a validated method

Objetivos: El objetivo de este estudio es describir el método empleado como control de calidad en las nutriciones parenterales de neonatos en un hospital de tercer nivel, así como realizar un análisis estadístico de los resultados del mismo.Material y métodos: En nuestro centro se realiza un análisis bioquímico de los niveles de glucosa, potasio y calcio de todas las nutriciones parenterales neonatales como método de control de calidad. Dicho análisis se realiza mediante técnicas previamente validadas. Se evaluaron todas las nutriciones parenterales neonatales elaboradas durante el periodo comprendido entre julio de 2018 y noviembre de 2019. Todas las mezclas analizadas contenían lípidos. Para el análisis estadístico de los resultados se consideró un ±10% sobre la concentración teórica como margen de aceptación.Resultados: Se analizaron 950 mezclas y se obtuvieron las rectas de regresión lineal para establecer la correlación entre el valor teórico y real de los componentes analizados.Conclusiones: Destaca la importancia que tiene el establecimiento de un control de calidad de las nutriciones parenterales neonatales, para la detección y prevención de errores durante la preparación de las mismas y previamente a su dispensación. (AU)

Objectives: We aimed to describe the method used as neonatal parenteral nutrition quality control in a third level hospital, as well as to carry on a statistical analysis of its results.Methods: In our center, a biochemical analysis of glucose, potassium and calcium levels of all neonatal parenteral nutrition is performed as a quality control method. This analysis is carried out using previously validated techniques. All neonatal parenteral nutrition prepared during the period between July 2018 and November 2019 were evaluated. All the mixtures analyzed contained lipids. For the statistical analysis of the results, ±10% of the theoretical concentration was considered as the acceptance margin.Results: 950 mixtures were analyzed and linear regression lines were obtained to establish the correlation between the theoretical and real value of the analyzed components.Conclusions: In conclusion, the importance of establishing quality control of neonatal parenteral nutrition is highlighted, for the detection and prevention of errors during their preparation and prior to their dispensing. (AU)

Improved anaerobic digestion of swine manure by simultaneous ammonia recovery using gas-permeable membranes.

In feedstocks containing high ammonia (NH3) concentration, removal of the NH3 during the anaerobic digestion (AD) process can improve AD process performance. In the present study, the effect of NH3 removal using gas-permeable membrane (GPM) technology on AD process performance and biogas production was investigated using swine manure feedstock. Batch and semi-continuous AD experiments were carried out under mesophilic conditions. In the reactor with NH3 recovery, total ammonia nitrogen (TAN) concentration was reduced 28% in batch experiments and 23% on average in the semicontinuous experiment compared with the reactor without NH3 recovery. Free ammonia (FA) concentrations were also decreased by 23% and 4% on average in batch and semicontinuous experiments, respectively. These reductions in TAN and FA by GPM system positively impacted both the quality and quantity of the biogas produced by AD of swine manure. Specifically, the specific methane yield increased 9% in the batch experiment and 17% on average in the semicontinuous experiment. Furthermore, higher percentages of methane in biogas were obtained during AD retrofitted with GPM system, 24% increase in the batch experiment and 11% on average in the semicontinuous experiment (range 8.3-13.6%). Simultaneously, a uniform TAN recovery rate of 6.7 g N TAN per m2 of membrane and per day was obtained for the 205 days of semicontinuous operation; ammonia nitrogen was recovered in the form of ammonium sulphate solution. Therefore, the AD-GPM configuration produces beneficial results on biogas quantity and quality while recovering ammonia nitrogen in form of ammonium sulphate.

Defining level A IVIVC dissolution specifications based on individual in vitro dissolution profiles of a controlled release formulation.

Regulatory guidelines recommend that, when a level A IVIVC is established, dissolution specification should be established using averaged data and the maximum difference between AUC and Cmax between the reference and test formulations cannot be greater than 20%. However, averaging data assumes a loss of information and may reflect a bias in the results. The objective of the current work is to present a new approach to establish dissolution specifications using a new methodology (individual approach) instead of average data (classical approach). Different scenarios were established based on the relationship between in vitro-in vivo dissolution rate coefficient using a level A IVIVC of a controlled release formulation. Then, in order to compare this new approach with the classical one, six additional batches were simulated. For each batch, 1000 simulations of a dissolution assay were run. Cmax ratios between the reference formulation and each batch were calculated showing that the individual approach was more sensitive and able to detect differences between the reference and the batch formulation compared to the classical approach. Additionally, the new methodology displays wider dissolution specification limits than the classical approach, ensuring that any tablet from the new batch would generate in vivo profiles which its AUC or Cmax ratio will be out of the 0.8-1.25 range, taking into account the in vitro and in vivo variability of the new batches developed.

IVIVC approach based on carbamazepine bioequivalence studies combination.

The aim of the present study was to explore the feasibility of obtaining an IVIVC by combination of data from two bioequivalence (BE) studies of carbamazepine (CBZ) in order to assess if the previously published dissolution media and conditions could be applicable to any other oral immediate release (IR) CBZ products with conventional excipients. Twenty-four healthy male subjects from two BE study received one IR dose of the test (test 1 or 2) or the reference formulation (Tegretol, 400 mg). Dissolution studies of the IR CBZ tablets were performed in two different laboratories. In order to develop IVIVC, individual or average data analysis were considered. A level C, level B and level A correlation have been successfully developed by combining data from different BE studies of CBZ immediate release drug products. A level A IVIVC was developed with all four datasets with a good R2 for all the combinations of in vivo and in vitro data. A dissolution medium containing 1% SLS has demonstrated its suitability as the universal biopredictive dissolution medium, even if different batches and in vivo/in vitro studies were combined.

Circulating microRNAs in Huntington's disease: Emerging mediators in metabolic impairment.

Huntington's disease (HD) is a hereditary neurodegenerative disease, with peripheral consequences that negatively contribute to quality of life. Circulating microRNAs (cmiRNAs) are being explored for their roles in intercellular communication and gene expression regulation, which allows gaining insight into the regulation of crosstalk between neuronal and peripheral tissues. Here, we explore the cmiRNA profile of plasma samples from fifteen symptomatic patients, with 40-45 CAG repeats in the HTT gene, and seven healthy matched controls. Isolated miRNAs from plasma samples were run against human miRNome panels, which have sequences for 752 human mature miRNAs. We found that 168 cmiRNAs are altered in symptomatic patients. Considering Bonferroni's correction, miR-877-5p, miR-223-3p, miR-223-5p, miR-30d-5p, miR-128, miR-22-5p, miR-222-3p, miR-338-3p, miR-130b-3p, miR-425-5p, miR-628-3p, miR-361-5p, miR-942 are significantly increased in HD patients as compared with controls. Moreover, after patient's organization according to approved HD scales, miR-122-5p is significantly decreased in HD patients with Unified Huntington's Disease Rating Scale >24, whereas an increase in miR-100-5p levels and a decrease in miR-641 and miR-330-3p levels were recorded when patients were rearranged by Total Functional Capacity. These results suggest that cmiRNA profile could be further modified by disease progression, making cmiRNAs useful as monitoring biomarkers. Analysis of target genes indicated a general overexpression of cmiRNAs implicated in metabolism regulation. Profiling cmiRNA of HD subjects opens the possibility of personalized therapies for different groups of HD patients, based on disease modifiers: regulation of altered pathways might contribute to not only alleviate disease symptoms, but also influence HD progression.

Olanzapine depot exposure in male rats: Dose-dependent lipogenic effects without concomitant weight gain.

Treatment with second-generation antipsychotic agents such as olanzapine frequently results in metabolic adverse effects, e.g. hyperphagia, weight gain and dyslipidaemia in patients of both genders. The molecular mechanisms underlying metabolic adverse effects are still largely unknown, and studies in rodents represent an important approach in their exploration. However, the validity of the rodent model is hampered by the fact that antipsychotics induce weight gain in female, but not male, rats. When administered orally, the short half-life of olanzapine in rats prevents stable plasma concentrations of the drug. We recently showed that a single intramuscular injection of long-acting olanzapine formulation yields clinically relevant plasma concentrations accompanied by several dysmetabolic features in the female rat. In the current study, we show that depot injections of 100-250 mg/kg olanzapine yielded clinically relevant plasma olanzapine concentrations also in male rats. In spite of transient hyperphagia, however, olanzapine resulted in weight loss rather than weight gain. The resultant negative feed efficiency was accompanied by a slight elevation of thermogenesis markers in brown adipose tissue for the highest olanzapine dose, but the olanzapine-related reduction in weight gain remains to be explained. In spite of the absence of weight gain, an olanzapine dose of 200mg/kg or above induced significantly elevated plasma cholesterol levels and pronounced activation of lipogenic gene expression in the liver. These results confirm that olanzapine stimulates lipogenic effects, independent of weight gain, and raise the possibility that endocrine factors may influence gender specificity of metabolic effects of antipsychotics in the rat.

Combinatorial gene therapy induces regression of hepatic encephalopathy.

Capillarization of the sinusoid impedes the clearance of neurotoxic substances in liver fibrosis. These events may result in hepatic encephalopathy. Neurological and hepatic features of rats after bile duct ligation (BDL) supplemented with Manganese (BDL+Mn(2+)) were examined. The 4-week-old BDL rats had elevated levels of ammonia and were concomitantly fed with 1 mg ml(-1) of MnCl(2) in drinking water (BDL/Mn(+2)). Five out of fifteen rats were killed and the serum, liver and brain tissue (striatum and substantia nigra) were recovered. Of the remaining BDL/Mn(+2)-cirrhotic animals (n=10), five were injected with a combination of Adenovirus-human plasminogen activator (Ad-huPA) and Adenovirus-matrix metalloproteinase-8 (Ad-MMP-8) (3 × 10(11)+1.5 × 10(11) vector particles per kg), and five with 4.5 × 10(11) vector particles per kg of Adenovirus-ß-galactosidase (Ad-ß-Gal). This treatment was carried on for 10 days. The BDL/Mn(+2) rats displayed tremor, rigidity and gait abnormalities, which improved notably with combinatorial gene therapy, as well as motor coordination. Liver fibrosis was evidently less after treatment with Ad-huPA+Ad-MMP-8 (25%). In the brain (striatum), Ad-huPA+Ad-MMP-8 treatment rendered higher concentrations of dopamine compared with Ad-ß-Gal-treated encephalopathic rats (210 and 162 ng g(-1) of tissue, respectively). The BDL/Mn(+2) animals and controls treated with Ad-ß-Gal showed abnormal morphology in astrocytes (gliosis) in striatum and substantia nigra, in which expressions of green fibrillar acidic protein and tyrosine hydroxylase were altered. These abnormalities decreased with Ad-huPA+Ad-MMP-8 treatment. Importantly, the latter animals showed an increment in sprouting of nervous fibers in substantia nigra. Combinatorial gene therapy improves neuroanatomical and neurochemical characteristics similar to human hepatic encephalopathy.

Phosphocalcic metabolism after biliopancreatic diversion.

BACKGROUND: Malabsorptive techniques to treat morbid obesity have been followed by alterations in phosphocalcic metabolism. Knowledge of the preoperative situation is important to assess the influence of these techniques on phosphocalcic metabolism and to consider treatments for these alterations. METHODS: 61 consecutive morbidly obese patients (50 women, 11 men, age 19 to 63 years) having had biliopancreatic diversion (BPD) were studied in a prospective manner. Preoperative and postoperative levels of calcium, phosphorus, 25-hydroxyvitamin D, tartrate resistant acid phosphate, plasma parathormone (PTH), tubular absorption of phosphate, and urinary calcium and pyridinolines were analyzed, as well as the potential risk factors for their alterations. Follow-up of all patients was a minimum of 4 years. RESULTS: Before BPD, 42.3% of patients presented an increase in PTH and 54% a decrease in the 25-OH vitamin D, but the values of calcium and plasma phosphorus maintained at normal level. 81.8% of the patients with an increase in the PTH maintained high levels after BPD, while 60% of those with a normal preoperative PTH also presented hyperparathyroidism 4 years after the intervention. A correlation between the levels of plasma PTH and body mass index was not found. CONCLUSION: Morbid obesity is accompanied by a high percentage of hyperparathyroidism. BPD produces malabsorption of vitamin D during the first years, favoring the persistence or appearance of hyperparathyroidism. It is important to recognize and treat the secondary hyperparathyroidism. The postoperative period could necessitate more energetic interventions to get more efficient control of the phosphocalcic metabolism.

[Health surveillance of workers exposed to asbestos: an example of cooperation between the occupational prevention system and the national health system]. / La Vigilancia de la Salud de los trabajadores expuestos al amianto: ejemplo de colaboracion entre el sistema de prevencion de riesgos laborales y el sistema nacional de salud.

The Ministry of Health and Consumer Affairs and the Autonomous Governments of Spain have designed and agreed by consensus with the sanitary professionals and major employer's organizations and Unions a Integral Health Surveillance Programme of asbestos-exposed workers, in order to assure appropriate, uniform and harmonized action throughout the national territory with relation to these workers. PROGRAM DESCRIPTION: This initiative started from the Occupational Health Working group of the Interterritorial Council, with inputs from the Asbestos Working Group of the National Occupational Safety and Health Commission. It was agreed with occupational medicine and infirmary professionals and was approved by the Health and Labour authorities. The program is organised in seven main activities. CURRENT PROGRAM STATUS: two years after the Programme approval a total of 5778 workers are included in the Registry of asbestos-exposed workers. 208 workers have COPD, 198 benign pleural disease, 8 lung cancer, 10 mesothelioma and 7 workers have other cancers possibly related to asbestos (gastric, larynx and colon cancer). REMARKS: the agreement and participation reached in this Programme allow achieving much higher coverage of occupational prevention policies than those obtained with a mere law approval, as we could see during the second year of implementation of the Programme in which the number of attended workers has doubled.

La vigilancia de la salud de los trabajadores expuestos al amianto: ejemplo de colaboración entre el sistema de prevención de riesgos laborales y el sistema nacional de salud / Health surveillance of workers exposed to asbestos: an example of co-operation between the occupational prevention system and the national health system

El Ministerio de Sanidad y Consumo y las Comunidades Autónomashan diseñado y consensuado con los profesionales sanitariosy las organizaciones empresariales y sindicales representativas unPlan Integral de Vigilancia de la Salud de los Trabajadores que hanestado expuestos a Amianto, con el objetivo de garantizar una intervenciónadecuada, uniforme y armonizada de estos trabajadores entodo el territorio nacional. La elaboración del Programa partió delGrupo de Trabajo de Salud Laboral del Consejo Interterritorial, seenriqueció con las aportaciones del Grupo de Trabajo Amianto de laComisión Nacional de Seguridad y Salud en el Trabajo, fue consensuadocon los profesionales de la medicina y enfermería del trabajo,y fue aprobado por las autoridades sanitarias y laborales. El Programaconsta de siete grandes bloques de actividades. Dos años despuésde aprobado el Programa, el estado de implantación en las ComunidadesAutónomas es desigual. Las principales dificultades para supuesta en marcha se encuentran en la elaboración del Registro deexpuestos. Un total de 5.778 trabajadores están incluidos en el Registro.208 trabajadores tienen EPOC, 198 alteraciones pleurales benignas,8 cáncer de pulmón, 10 mesotelioma y 7 presentan otros cáncerescon posible relación con el amianto (gástrico, de laringe y colon). El consenso y la participación alcanzados alrededor de este Programaestán permitiendo lograr coberturas de las políticas de prevenciónde riesgos laborales muy superiores a las que se consiguen conla mera actuación institucional y elaboración de normativa, ya que ensólo los dos primeros años de implantación del Programa se ha duplicadoel número de trabajadores atendidos

The Ministry of Health and Consumer Affairs and the AutonomousGovernments of Spain have designed and agreed by consensuswith the sanitary professionals and major employer's organizationsand Unions a Integral Health Surveillance Programme ofasbestos-exposed workers, in order to assure appropriate, uniformand harmonized action throughout the national territory with relationto these workers. Program description: this initiative startedfrom the Occupational Health Working group of the InterterritorialCouncil, with inputs from the Asbestos Working Group of theNational Occupational Safety and Health Commission. It was agreedwith occupational medicine and infirmary professionals and wasapproved by the Health and Labour authorities. The program isorganised in seven main activities. Current Program status: twoyears after the Programme approval a total of 5,778 workers areincluded in the Registry of asbestos-exposed workers. 208 workershave COPD, 198 benign pleural disease, 8 lung cancer, 10 mesotheliomaand 7 workers have other cancers possibly related toasbestos (gastric, larynx and colon cancer). Remarks: the agreementand participation reached in this Programme allow achievingmuch higher coverage of occupational prevention policies than those obtained with a mere law approval, as we could see duringthe second year of implementation of the Programme in which thenumber of attended workers has doubled

Standardized approach for microsatellite instability detection in colorectal carcinomas.

BACKGROUND: Ubiquitous mutations in microsatellite DNA sequences define a specific type of genetic instability, termed microsatellite instability (MSI). Various approaches have been used to identify the presence and degree of MSI. To define standard diagnostic criteria for MSI, we developed and tested a mathematical model. METHODS: We designed an algorithm for the efficient characterization of MSI and used it to analyze data on six microsatellite markers in colorectal carcinoma and normal tissues from 415 patients. Theoretical models considering one, two, or three populations were tested against the data collected. RESULTS: The observed frequencies of MSI in our series of samples best fit a two-population model, stable and unstable, defined by instability in two or more of four to six markers analyzed. MSI was observed in 7.5% of the tumors. The misclassification rate was less than 5% when any four loci were analyzed and less than 1% when the six markers were used. A stepwise strategy, consisting first of a bulk screening of two loci and then a second screening of two to four additional markers, provided excellent sensitivity (>/=97%) and specificity (100%). Tumors with MSI had distinctive genetic and clinicopathologic features, including better patient survival. CONCLUSION: To assess the presence of MSI in colorectal cancer, we have developed a simple, sensitive, and specific approach based on the apparent good fit of the data to a two-population model. Its application to a prospective series of patients with colorectal carcinomas demonstrates that the presence of MSI characterizes a subset of less aggressive tumors.

Red queen dynamics, competition and critical points in a model of RNA virus quasispecies.

RNA viruses offer a unique opportunity for the study of evolution at the molecular level. Recent experiments involving clonal populations of RNA viruses have shown that competition among virus strains of approximately equal relative fitness can result in the eventual competitive exclusion of one of the species. As competition proceeds in time, both the winners and the losers exhibited absolute gains in fitness, consistent with the "Red Queen" hypothesis of evolution. Further experiments involving closely related evolving quasispecies revealed a highly predictable nonlinear behavior suggesting a deterministic component in the underlying quasispecies dynamics. This is apparently in contradiction with the standard view of RNA virus evolution as a highly unpredictable process. In this paper we present a simple model which allows previous hypothesis to be tested and provides an interpretation for the observed experimental results.

Tracking recurrent quantitative genomic alterations in colorectal cancer: allelic losses in chromosome 4 correlate with tumor aggressiveness.

Allelic imbalances are common events in cancer cells. Quantitative alterations in specific chromosomal loci have been linked to activation (gain) or inactivation (loss) of genes with a proven impact on tumor cell biology. The aim of this study was to detect new chromosomal regions recurrently altered in colorectal tumorigenesis and with a potential effect on patient's outcome. We have analyzed a series of human colorectal tumor biopsy specimens by using the DNA fingerprinting technique arbitrarily primed PCR. This approach provided information on 95 different loci randomly selected and distributed through out the cell's genome. Eight sequences displayed recurrent alterations associated with diminished patient survival. Four of them (showing allelic losses) were located in chromosome 4, one sequence in chromosome 2, and one sequence in chromosome 17. The chromosomal origin of the two remaining sequences could not be determined. Fine mapping of chromosome 4 bands suggested that there are at least two regions in chromosome 4 (4p14-16 and 4q21-28) susceptible to containing tumor suppressor genes the loss of which may affect tumor aggressiveness.

Menstrual cycle and profiles of suicidal behaviour.

The first (or menstrual) and fourth (or premenstrual) week of the menstrual cycle may be associated with many suicide attempts in women. The study sample included 113 Spanish women who attempted suicide and contacted an emergency service. Inclusion criteria were as follows: fertility; regular menstrual cycles; lack of oral contraceptives; and willingness to see a psychiatrist. The incidence of suicide attempts in the first week (36%) was significantly higher than that in the remaining weeks (second week, 19%; third week 16%; fourth week, 29%). A correspondence analysis suggested that suicide attempts were associated with differences in demographics and clinical profiles. In particular, suicide attempts in the third week were correlated with a severe history of psychiatric problems and a lower level of education. The limitations of this study are its exclusiveness to hospitalized cases and its use of patient reports to date menstruation.