Clinical and biochemical evolution after partial dietary liberalization of two cases of galactosemia due to galactose mutarotase deficiency.

BACKGROUND: The recommended diet attitude in the recently described galactose mutarotase (GALM) deficiency is not yet established. We describe two 9-years twins who remain asymptomatic despite prolonged partial dietary liberalization from 18 months of age, after two periods of galactose-free diet. It represents the second report in Europe of GALM deficiency. CASE PRESENTATION: Two male monochorionic diamniotic twins were detected through newborn screening by galactosuria and increased total blood galactose. They started galactose dietary restriction with biochemical normalization. After exclusion of the three previously described types of galactosemia, a progressively galactose reintroduction was initiated. The clinical follow-up developed include neurological assessment and intelligence quotient, annual ophthalmological evaluation and biannual abdominal ultrasound; whereas the biochemical assessment comprises quarterly determinations of galactose 1-phosphate and galactosuria and annual determination of liver and renal function, 25-OH-vitamin D and calcium levels. Sanger sequencing of GALM gene was complemented by the study of gene dose using SNPs array and a protein modeling to study the conformational changes induced in GALM protein. In both siblings a novel and complete deletion of exon 4 in GALM gene was detected. Both remained asymptomatic, with normal growth and intellectual development, despite dietary liberalization. Evolutionarily, the biochemical profile in blood remained normal with intermittent galactosuria. CONCLUSIONS: The absence of clinical involvement after 7 years of dietary liberalization is interesting to expand the knowledge about the recommended dietary management in this pathology.

Muscle Network Connectivity Study in Diabetic Peripheral Neuropathy Patients.

Diabetic peripheral neuropathy (DPN) is a prevalent complication of chronic diabetes mellitus and has a significant impact on quality of life. DPN typically manifests itself as a symmetrical, length-dependent sensorimotor polyneuropathy with severe effects on gait. Surface electromyography (sEMG) is a valuable low-cost tool for assessing muscle activation patterns and precise identification of abnormalities. For the present study, we used information theory methods, such as cross-correlation (CC), normalized mutual information (NMI), conditional granger causality (CG-Causality), and transfer entropy (TE), to evaluate muscle network connectivity in three population groups: 33 controls (healthy volunteers, CT), 10 diabetic patients with a low risk of DPN (LW), and 17 moderate/high risk patients (MH). The results obtained indicated significant alterations in the intermuscular coupling mechanisms due to diabetes and DPN, with the TE group showing the best performance in detecting differences. The data revealed a significant increase in information transfer and muscle connectivity in the LW group over the CT group, while the MH group obtained significantly lower values for these metrics than the other two groups. These findings highlight the sEMG coupling metrics' potential to reveal neuromuscular mechanisms that could aid the development of targeted rehabilitation strategies and help monitor DPN patients.

Assessment of Muscle Coordination Changes Caused by the Use of an Occupational Passive Lumbar Exoskeleton in Laboratory Conditions.

The introduction of exoskeletons in industry has focused on improving worker safety. Exoskeletons have the objective of decreasing the risk of injury or fatigue when performing physically demanding tasks. Exoskeletons' effect on the muscles is one of the most common focuses of their assessment. The present study aimed to analyze the muscle interactions generated during load-handling tasks in laboratory conditions with and without a passive lumbar exoskeleton. The electromyographic data of the muscles involved in the task were recorded from twelve participants performing load-handling tasks. The correlation coefficient, coherence coefficient, mutual information, and multivariate sample entropy were calculated to determine if there were significant differences in muscle interactions between the two test conditions. The results showed that muscle coordination was affected by the use of the exoskeleton. In some cases, the exoskeleton prevented changes in muscle coordination throughout the execution of the task, suggesting a more stable strategy. Additionally, according to the directed Granger causality, a trend of increasing bottom-up activation was found throughout the task when the participant was not using the exoskeleton. Among the different variables analyzed for coordination, the most sensitive to changes was the multivariate sample entropy.

Determination of 3-monoiodotyrosine and 3,5-diiodotyrosine in newborn urine and dried urine spots by isotope dilution tandem mass spectrometry.

High levels of 3-mono- and 3,5-diiodotyrosine (MIT and DIT, respectively) in urine have been related to iodotyrosine dehalogenase 1 deficiency, a type of congenital hypothyroidism. However, the determination of MIT and DIT in urine is not included in newborn screening programs performed in clinical laboratories to detect inborn errors of metabolism. We report here on the development of an analytical method for the determination of MIT and DIT in newborn urine and dried urine spots (DUS) by Liquid Chromatography Isotope Dilution tandem Mass Spectrometry (LC-IDMSMS). The development included the synthesis of 15N-monoiodotyrosine and 13C2-diiodotyrosine through the iodination of 15N-tyrosine and 13C2-tyrosine, respectively, using bis(pyridine)iodonium(I) tetrafluoroborate (IPy2BF4). Both labelled analogues were added at the beginning of the sample preparation procedure and used to develop both single- and double-spike LC-IDMS methods for the determination of MIT and DIT. The developed double spike methodology was able to quantify and correct possible MIT ↔ DIT interconversions throughout the sample preparation, which was observed for concentrated urine samples but not for DUS. Suppression matrix effects on the absolute signals of MIT and DIT were observed in urine samples but did not affect the IDMS results as recoveries on urine samples at different dilution factors could be considered quantitative. Method detection limits were 0.018 and 0.046 ng g-1 (limits of quantification 0.06 and 0.15 ng g-1) by single-spike IDMS, for MIT and DIT, respectively, in the analysis of urine samples and 0.07 and 0.05 ng g-1 (limits of quantification 0.23 and 0.17 ng g-1) for MIT and DIT, respectively, in the analysis of DUS. No significant differences were obtained for MIT concentrations in the analysis of the same newborn samples stored as liquid urine or DUS when the results were corrected for the creatinine content. Finally, 36 DUS samples from healthy newborns were analyzed and MIT was detected in all samples at low ng mg-1creatinine levels.

Assessment of a Passive Lumbar Exoskeleton in Material Manual Handling Tasks under Laboratory Conditions.

Manual material handling tasks in industry cause work-related musculoskeletal disorders. Exoskeletons are being introduced to reduce the risk of musculoskeletal injuries. This study investigated the effect of using a passive lumbar exoskeleton in terms of moderate ergonomic risk. Eight participants were monitored by electromyogram (EMG) and motion capture (MoCap) while performing tasks with and without the lumbar exoskeleton. The results showed a significant reduction in the root mean square (VRMS) for all muscles tracked: erector spinae (8%), semitendinosus (14%), gluteus (5%), and quadriceps (10.2%). The classic fatigue parameters showed a significant reduction in the case of the semitendinosus: 1.7% zero-crossing rate, 0.9% mean frequency, and 1.12% median frequency. In addition, the logarithm of the normalized Dimitrov's index showed reductions of 11.5, 8, and 14% in erector spinae, semitendinosus, and gluteus, respectively. The calculation of range of motion in the relevant joints demonstrated significant differences, but in almost all cases, the differences were smaller than 10%. The findings of the study indicate that the passive exoskeleton reduces muscle activity and introduces some changes of strategies for motion. Thus, EMG and MoCap appear to be appropriate measurements for designing an exoskeleton assessment procedure.

Optimized Feature Subset Selection Using Genetic Algorithm for Preterm Labor Prediction Based on Electrohysterography.

Electrohysterography (EHG) has emerged as an alternative technique to predict preterm labor, which still remains a challenge for the scientific-technical community. Based on EHG parameters, complex classification algorithms involving non-linear transformation of the input features, which clinicians found difficult to interpret, were generally used to predict preterm labor. We proposed to use genetic algorithm to identify the optimum feature subset to predict preterm labor using simple classification algorithms. A total of 203 parameters from 326 multichannel EHG recordings and obstetric data were used as input features. We designed and validated 3 base classifiers based on k-nearest neighbors, linear discriminant analysis and logistic regression, achieving F1-score of 84.63 ± 2.76%, 89.34 ± 3.5% and 86.87 ± 4.53%, respectively, for incoming new data. The results reveal that temporal, spectral and non-linear EHG parameters computed in different bandwidths from multichannel recordings provide complementary information on preterm labor prediction. We also developed an ensemble classifier that not only outperformed base classifiers but also reduced their variability, achieving an F1-score of 92.04 ± 2.97%, which is comparable with those obtained using complex classifiers. Our results suggest the feasibility of developing a preterm labor prediction system with high generalization capacity using simple easy-to-interpret classification algorithms to assist in transferring the EHG technique to clinical practice.

Optimisation in the multidisciplinary approach to patients with hepatitis C in the era of direct-acting antivirals. / Optimización en el abordaje multidisciplinar del paciente con hepatitis C en la era de los antivirales de acción directa.

The advents of current direct-acting antiviral treatments has revolutionised the therapeutic approach to hepatitis C, increasing cure rates to above 90% and substantially simplifying treatment, which translates into benefits for patients, clinicians and the health system. These new drugs allow cure to be achieved, irrespective of the patient's characteristics, with tolerability similar to that of placebo and few drug reactions with concomitant medication. This in turn improves patients' quality of life and wellbeing. Moreover, these drugs allow multidisciplinary optimisation of the approach to patients with hepatitis C, thus reducing both short- and long-term costs. All these factors facilitate treatment universality, with treatments that are less influenced by specific factors and that allow better results to be obtained in a larger number of patients. Elimination of hepatitis C is now a real possibility. Supplement information: This article is part of a supplement entitled "The value of simplicity in hepatitis C treatment", which is sponsored by Gilead. © 2019 Elsevier España, S.L.U. All rights reserved.

Personality disorders do not affect treatment outcomes for chronic HCV infection in Spanish prisoners: the Perseo study.

BACKGROUND: The link between infection with hepatitis C virus (HCV) and personality disorders (PD) has not been investigated in detail. The aim of this study was to compare the effectiveness of HCV treatment in prisoners with and without PD. METHODS: We performed a prospective multicentre study in inmates from 25 Spanish prisons who had been treated with pegylated interferon alfa-2a plus ribavirin in 2011. PD diagnosis was based on the Personality Diagnostic Questionnaire-4+. We calculated adjusted Odds Ratios (AOR) and 95 % confidence intervals (95 % CI) using logistic regression. RESULTS: The sample included 236 patients (mean age: 40.3 years, 92.8 % male, 79.2 % intravenous drug users, and 26.3 % HIV-coinfected). The prevalence of PD was 72.5 %. 32.2 % of patients discontinued treatment; this percentage was higher in patients with HCV genotypes 1/4 (AOR = 3.55; CI:1.76-7.18) and those without PD (AOR = 2.51; 1.23-5.11). Treatment discontinuation was mainly for penitentiary reasons (40.3 %): release or transfer between prisons. The rate of sustained viral response (SVR) was 52.1 % by ITT and 76.9 % by observed treatment (OT). SVR was higher among patients with genotype 2 or 3, and those with low baseline HCV-RNA. We did not observe any differences between individuals with and without PD in term of SVR, HCV genotype or HIV infection. CONCLUSIONS: Our results support the safety and clinical effectiveness of the treatment of chronic HCV infection in correctional facilities, both in prisoners with PD and those without. Our data support non-discrimination between patients with and without PD when offering treatment for HCV infection to prison inmates. TRIAL REGISTRATION: Trial registration number (TRN) NCT01900886 . Date of registration: July 8, 2013.

Directly observed therapy for chronic hepatitis C: a randomized clinical trial in the prison setting.

BACKGROUND: The diagnosis and treatment of chronic hepatitis C are major concerns in prisons. OBJECTIVES: The aim of this randomized clinical trial was to determine the extent to which directly observed therapy (DOT) improved the efficacy of the standard treatment for chronic hepatitis C in the prison setting. PATIENTS AND METHODS: A randomized clinical trial was carried out to evaluate the efficacy of a DOT compared with a self-administered therapy in prison inmates who underwent standard treatment for chronic hepatitis C (based on pegylated interferon alpha-2a and ribavirin). RESULTS: A total of 252 inmates were randomized, of which 244 were analyzed: 109 in the DOT group and 135 in the non-DOT group. The mean age was 35.88 years (SD 6.54), 94.3% were men, 72.1% reported intravenous drug use, 21.3% were HIV co-infected, and 55.3% had genotype 1 or 4. The patients received the study treatment for a median time of 33.9 weeks in the overall sample. Sustained virological response was achieved in 60.6% (95% CI, 51.17-69.22) of the DOT group and in 65.9% (95% CI, 57.59-73.38) of the standard therapy group (risk ratio=0.92; 95% CI, 0.76-1.12). The mean proportion of patients continuing the treatment was 83% (SD=31). Adverse events were reported in 93.4% of the patients, and serious adverse events were reported in 8.2%, with no significant differences between groups. CONCLUSIONS: Sustained virological response was remarkably high, although there were no differences between groups, probably due to high treatment adherence.

Vectorgastrogram: dynamic trajectory and recurrence quantification analysis to assess slow wave vector movement in healthy subjects.

Functional gastric disorders entail chronic or recurrent symptoms, high prevalence and a significant financial burden. These disorders do not always involve structural abnormalities and since they cannot be diagnosed by routine procedures, electrogastrography (EGG) has been proposed as a diagnostic alternative. However, the method still has not been transferred to clinical practice due to the difficulty of identifying gastric activity because of the low-frequency interference caused by skin-electrode contact potential in obtaining spatiotemporal information by simple procedures. This work attempted to robustly identify the gastric slow wave (SW) main components by applying multivariate variational mode decomposition (MVMD) to the multichannel EGG. Another aim was to obtain the 2D SW vectorgastrogram VGGSW from 4 electrodes perpendicularly arranged in a T-shape and analyse its dynamic trajectory and recurrence quantification (RQA) to assess slow wave vector movement in healthy subjects. The results revealed that MVMD can reliably identify the gastric SW, with detection rates over 91% in fasting postprandial subjects and a frequency instability of less than 5.3%, statistically increasing its amplitude and frequency after ingestion. The VGGSW dynamic trajectory showed a statistically higher predominance of vertical displacement after ingestion. RQA metrics (recurrence ratio, average length, entropy, and trapping time) showed a postprandial statistical increase, suggesting that gastric SW became more intense and coordinated with a less complex VGGSW and higher periodicity. The results support the VGGSW as a simple technique that can provide relevant information on the "global" spatial pattern of gastric slow wave propagation that could help diagnose gastric pathologies.

Automatic semantic segmentation of EHG recordings by deep learning: An approach to a screening tool for use in clinical practice.

BACKGROUND AND OBJECTIVE: Preterm delivery is an important factor in the disease burden of the newborn and infants worldwide. Electrohysterography (EHG) has become a promising technique for predicting this condition, thanks to its high degree of sensitivity. Despite the technological progress made in predicting preterm labor, its use in clinical practice is still limited, one of the main barriers being the lack of tools for automatic signal processing without expert supervision, i.e. automatic screening of motion and respiratory artifacts in EHG records. Our main objective was thus to design and validate an automatic system of segmenting and screening the physiological segments of uterine origin in EHG records for robust characterization of uterine myoelectric activity, predicting preterm labor and help to promote the transferability of the EHG technique to clinical practice. METHODS: For this, we combined 300 EHG recordings from the TPEHG DS database and 69 EHG recordings from our own database (Ci2B-La Fe) of women with singleton gestations. This dataset was used to train and evaluate U-Net, U-Net++, and U-Net 3+ for semantic segmentation of the physiological and artifacted segments of EHG signals. The model's predictions were then fine-tuned by post-processing. RESULTS: U-Net 3+ outperformed the other models, achieving an area under the ROC curve of 91.4 % and an average precision of 96.4 % in detecting physiological activity. Thresholds from 0.6 to 0.8 achieved precision from 93.7 % to 97.4 % and specificity from 81.7 % to 94.5 %, detecting high-quality physiological segments while maintaining a trade-off between recall and specificity. Post-processing improved the model's adaptability by fine-tuning both the physiological and corrupted segments, ensuring accurate artifact detection while maintaining physiological segment integrity in EHG signals. CONCLUSIONS: As automatic segmentation proved to be as effective as double-blind manual segmentation in predicting preterm labor, this automatic segmentation tool fills a crucial gap in the existing preterm delivery prediction system workflow by eliminating the need for double-blind segmentation by experts and facilitates the practical clinical use of EHG. This work potentially contributes to the early detection of authentic preterm labor women and will allow clinicians to design individual patient strategies for maternal health surveillance systems and predict adverse pregnancy outcomes.

Clinical validation of cutoff target ranges in newborn screening of metabolic disorders by tandem mass spectrometry: a worldwide collaborative project.

PURPOSE: To achieve clinical validation of cutoff values for newborn screening by tandem mass spectrometry through a worldwide collaborative effort. METHODS: Cumulative percentiles of amino acids and acylcarnitines in dried blood spots of approximately 25­30 million normal newborns and 10,742 deidentified true positive cases are compared to assign clinical significance, which is achieved when the median of a disorder range is, and usually markedly outside, either the 99th or the 1st percentile of the normal population. The cutoff target ranges of analytes and ratios are then defined as the interval between selected percentiles of the two populations. When overlaps occur, adjustments are made to maximize sensitivity and specificity taking all available factors into consideration. RESULTS: As of December 1, 2010, 130 sites in 45 countries have uploaded a total of 25,114 percentile data points, 565,232 analyte results of true positive cases with 64 conditions, and 5,341 cutoff values. The average rate of submission of true positive cases between December 1, 2008, and December 1, 2010, was 5.1 cases/day. This cumulative evidence generated 91 high and 23 low cutoff target ranges. The overall proportion of cutoff values within the respective target range was 42% (2,269/5,341). CONCLUSION: An unprecedented level of cooperation and collaboration has allowed the objective definition of cutoff target ranges for 114 markers to be applied to newborn screening of rare metabolic disorders.

[Beginnings, evolution and current situation of the Newborn Screening Programs in Spain.] / Inicio, evolución y situación actual de los Programas de Cribado Neonatal en España.

Newborn Screening Programs (NSP) in Spain were born in the city of Granada in 1968. Till the 1980s, they were developed around the so-called "National Plan for Preventing Subnormality", covering up to 30% of the Spanish newborns. From 1982, when the health system management was transferred to the different autonomous regions, the NSP began to expand, and the bases to transform them into an organized and multidisciplinary activity, integrated and coordinated from the National Health System were settled. Despite this expansion, it is not until the 1990s when their coverage reaches almost 100% newborns in Spain. NSP grew up asymmetrically across the different autonomous regions. In 2005 and 2006 the scientific societies SEQC (Spanish Society of Clinical Chemistry) and AECNE (Spanish Society of Newborn Screening), coordinated by the Health Promotion Area of the General Directorate of Public Health, gathered together the necessary information to elaborate a report on the NSP in Spain addressed to the Interterritorial Council of the National Health System. In July 2013, that Council approved the seven diseases that should be part of each region newborn screening panel, being the first step towards the NSP harmonization in Spain. Currently, the NSP include between 8 and 29 diseases in their panels, thus more still more efforts are needed in order to achieve a higher uniformity.

Los Programas de Cribado Neonatal (PCN) nacen en España en Granada en el año 1968. Posteriormente, y hasta los años 80, se fueron desarrollando en torno al llamado "Plan Nacional de Prevención de la Subnormalidad" con una cobertura cercana al 30% de los recién nacidos españoles. A partir de 1982, con el inicio de la gestión de la sanidad a las comunidades autónomas (CCAA), los PCN se expandieron y se comenzaron a sentar las bases para que éstos se convirtieran en una actividad organizada y multidisciplinar, integrados y coordinados desde el Sistema de Salud. A pesar de dicha expansión no es hasta el inicio de la década de los 90 cuando se consigue una cobertura próxima al 100% de los RN en España. Los PCN fueron creciendo de forma muy asimétrica en las diferentes CCAA y en los años 2005 y 2006 las Sociedades Científicas SEQC (Sociedad Española de Química Clínica) y AECNE (Asociación Española de Cribado Neonatal), con la coordinación del Área de Promoción de la Salud de la Dirección General de Salud Pública, recopilaron la información y elaboraron un informe, sobre los PCN en España para el Consejo Interterritorial del sistema Nacional de Salud (CISNS). En julio de 2013 este Consejo aprobó las siete enfermedades que debían formar parte del panel de detección de los PCN territoriales, primer paso hacia la armonización de estos programas. Actualmente, los PCN incluyen entre 8 y 29 enfermedades por lo que es necesario seguir trabajando para conseguir una mayor uniformidad.

Degradation of Contaminants of Emerging Concern by Electrochemical Oxidation: Coupling of Ultraviolet and Ultrasound Radiations.

In this work, we study the electrochemical oxidation of methyl red, a dye present in textile industrial effluents, which is selected as the model for the degradation of Contaminants of Emerging Concern. The influence of the initial pollutant concentration (1-5 mg dm-3), applied current density (2-15 mA cm-2), and the coupling of ultraviolet or ultrasound radiation have been studied using a titanium plate as anode. The results show that electrochemical oxidation is able to efficiently remove methyl red, and the process efficiency decreases with the initial pollutant concentration. At high applied current densities, efficiency drastically decreases due to a less effective mass transfer of the pollutant on the anodic surface. On one hand, the coupling of ultrasound entails an antagonistic effect on the process efficiency, which is probably due to a massive formation of oxidant radicals followed by a fast recombination process. On the other hand, the coupling of ultraviolet radiation increases the process efficiency. Concomitantly to the oxidation processes, titanium electrode produces rising TiO2-anatase nanoparticles, boosting the mineralization process. This new finding sets up a significant improvement over conventional photocatalysis treatments using TiO2-anatase as a catalyst due to synergistic effects coming from the coupling of the electrochemical oxidation and photocatalysis process with Ti anode.

Inter-laboratory analytical improvement of succinylacetone and nitisinone quantification from dried blood spot samples.

BACKGROUND: Nitisinone is used to treat hereditary tyrosinemia type 1 (HT-1) by preventing accumulation of toxic metabolites, including succinylacetone (SA). Accurate quantification of SA during newborn screening is essential, as is quantification of both SA and nitisinone for disease monitoring and optimization of treatment. Analysis of dried blood spots (DBS) rather than plasma samples is a convenient method, but interlaboratory differences and comparability of DBS to serum/plasma may be issues to consider. METHODS: Eight laboratories with experience in newborn screening and/or monitoring of patients with HT-1 across Europe participated in this study to assess variability and improve SA and nitisinone concentration measurements from DBS by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Quantification of nitisinone from both DBS and plasma was performed to assess sample comparability. In addition, efforts to harmonize laboratory procedures of SA and nitisinone quantifications during 5 rounds of analysis are described. RESULTS: Nitisinone levels measured from DBS and plasma strongly correlated (R 2 = 0.93). Due to partitioning of nitisinone to the plasma, levels were higher in plasma by a factor of 2.34. In the initial assessment of laboratory performance, all had linear calibrations of SA and nitisinone although there was large inter-laboratory variability in actual concentration measurements. Subsequent analytical rounds demonstrated markedly improved spread and precision over previous rounds, an outcome confirmed in a final re-test round. CONCLUSION: The study provides guidance for the determination of nitisinone and SA from DBS and the interpretation of results in the clinic. Inter-laboratory analytical harmonization was demonstrated through calibration improvements.

[Evaluation and perspective of 20 years of neonatal screening in Galicia. Program results.] / Evaluación y perspectiva de 20 años de cribado neonatal en Galicia. Resultados del programa.

Galician newborn screening program for early detection of endocrine and metabolic diseases began in 1978 and was a pioneer in expanded newborn screening in Spain with the incorporation of mass spectrometry in July 2000. As a primary objective, 28 diseases are screened, including those recommended SNS except sickle cell anemia which is in the inclusion phase. In its 20-year history, 404,616 newborns (nb) have been analyzed, identifying 547 cases affected by the diseases included, with a global incidence of 1: 739 newborns and 1: 1.237 of the screened inborn errors of metabolism (IEM) (1:1.580 nb if excluding benign hyperphenylalaninemia-HPA), with an average participation of 99.35%, progressively higher during the analyzed period. Among the pathologies screened, congenital hypothyroidism (1:2.211 nb), cystinuria (1:4.129 nb) and HPA (1:5.699 nb), followed by phenylketonuria and cystic fibrosis (1:10,936 nb) stand out for their incidence. Sixty-six cases of false positives were identified (seventeen of them in relation to maternal pathology) and five false negatives, being the overall PPV and NPV of the program respectively of 89.2% and 99.99%, with a sensitivity of 99.09% and a specificity of 99.98%. The mortality rate of diagnosed CME patients is 1.52%, with eleven cases presenting symptoms prior to the screening result (2%). The intelligence quotient of IEM patients at risk of neurological involvement is normal in more than 95% of cases.

El Programa Gallego para la Detección Precoz de Enfermedades Endocrinas y Metabólicas se inició en 1978 y fue pionero en España en el cribado neonatal ampliado con la incorporación de la espectrometría de masas en julio de 2000. Como objetivo primario se criban veintiocho enfermedades, incluyendo las de la cartera básica del Servicio Nacional de Salud excepto la anemia de células falciformes, que está en fase de inclusión. En sus veinte años de trayectoria se analizaron 404.616 recién nacidos (RN), identificando 547 casos afectos de las enfermedades incluidas, con una incidencia global de 1:739 RN vivos y de 1:1.237 RN de las enfermedades metabólicas congénitas (EMC) cribadas (1:1.580 RN excluyendo la hiperfenilalaninemia benigna-HPA), con una participación media del 99,35%, progresivamente creciente durante el período analizado. Entre las patologías cribadas destacan por su incidencia el hipotirodismo congénito (1:2.211 RN), la cistinuria (1:4.129 RN) y la HPA (1:5.699 RN), seguida de fenilcetonuria y fibrosis quística (1:10.936 RN). Se identificaron sesenta y seis casos de falsos positivos (diecisiete de los mismos en relación con patología materna) y cinco falsos negativos, siendo el VPP (valor predictivo positivo) y el VPN (valor predictivo negativo) global del programa del 89,2% y 99,99%, respectivamente, con una sensibilidad de 99,09% y una especificidad del 99,98%. La tasa de mortalidad de los pacientes con EMC diagnosticados fue del 1,52%, presentando once casos sintomatología previa al resultado del cribado (2%). El cociente intelectual de los pacientes con EMC y riesgo de afectación neurológica es normal en más del 95% de los casos.

A Surface Electromyogram Evaluation of the Postural Freedom Effects in Laparoscopic Surgery.

It has been demonstrated that laparoscopic procedures benefit patients in terms of recovery time, exposure to infections and trauma. Nevertheless, it increases the number of problems for the surgeons, including the frequency and duration of awkward postures for surgeons. The repetition of these movements is considered the main cause for musculoskeletal disorders in surgeons' upper limbs. The goal of this study is to evaluate the muscular activity and muscular fatigue effect produced by both, a conventional instrument and an instrument provided with the Postural Freedom (PF) feature; which consists in a ball socket articulation that allows a variable handle-to-shaft angle, on a conventional laparoscopic pistol-grip handle. Seventeen participants were evaluated during a static simulation using both instruments. Surface electromyography was used to compare the instruments in terms of muscular activity in each target position and muscular fatigue produced in the muscles trapezius, deltoids, biceps, and flexor carpi radialis. Trapezius and deltoids were the muscles most affected. Entrance and exit targets and targets facing the participants showed the higher muscular activity values. The PF prototype reduced muscular activity in all the muscles and in the majority of the target positions showing a reduction greater than 70% of the activity required by the trapezius and deltoid muscles in comparison to the conventional tool. Muscular fatigue was produced by both instruments but it presented lower frequency values with PF prototype. The results indicated that the use of conventional instruments impacts negatively on muscular activity during laparoscopic procedures, in terms of positions adopted. The PF feature in laparoscopic instrumentation reduced the muscular activity and also decreased the signals of muscular fatigue in the muscles evaluated in comparison with the conventional tool.

Identification of the slow wave component of the electroenterogram from Laplacian abdominal surface recordings in humans.

The electroenterogram (EEnG) is a surface recording of the myoelectrical activity of the smooth muscle layer of the small intestine. It is made up of two signals: a low-frequency component, known as the slow wave (SW), and high-frequency signals, known as spike bursts (SB). Most methods of studying bowel motility are invasive due to the difficult anatomic access of the intestinal tract. Abdominal surface EEnG recordings could be a noninvasive solution for monitoring human intestinal motility. However, surface EEnG recordings in humans present certain problems, such as the low amplitude of the signals and the influence of physiological interference such as the electrocardiogram (ECG) and respiration. In this study, a discrete estimation of the abdominal surface Laplacian potential was obtained using Hjorth's method. The objective was to analyze the enhancement given by Laplacian EEnG estimation compared to bipolar recordings. Eight recording sessions were carried out on eight healthy human volunteers in a state of fasting. First, the ECG interference content present in the bipolar signals and in the Laplacian estimation were quantified and compared. Secondly, to identify the SW component of the EEnG, respiration interference was removed by using an adaptive filter, and spectral estimation techniques were applied. The following parameters were obtained: the dominant frequency (DF) of the signals, stability of the rhythm (RS) of the DF detected and the percentage of DFs within the typical frequency range for the SW (TFSW). Results show the better ability of the Laplacian estimation to attenuate ECG interference, as compared to bipolar recordings. As regards the identification of the SW component of the EEnG, after removing respiration interference, the mean value of the DF in all abdominal surface recording channels and in their Laplacian estimation ranged from 0.12 to 0.14 Hz (7.3 to 8.4 cycles min(-1) (cpm)). Furthermore in 80% of the cases, the detected DFs were inside the typical human SW frequency range, and the ratio of frequency change in the surface bipolar and Laplacian estimation signals, in 90% of the cases, was within the frequency change accepted for human SW. Significant statistical differences were also found between the DF of all surface signals (bipolar and Laplacian estimation) and the DF of respiration. In conclusion, it was demonstrated that the discrete Laplacian potential estimation attenuated the physiological interference present in bipolar surface recordings, especially ECG. Furthermore, a slow frequency component, whose frequency, rhythm stability and amplitude fitted with the SW patterns in humans, was identified in bipolar and Laplacian estimation signals. This could be a useful non-invasive tool for monitoring intestinal activity by abdominal surface recordings.

Adaptive filtering of ECG interference on surface EEnGs based on signal averaging.

An external electroenterogram (EEnG) is the recording of the small bowel myoelectrical signal using contact electrodes placed on the abdominal surface. It is a weak signal affected by possible movements and by the interferences of respiration and, principally, of the cardiac signal. In this paper an adaptive filtering technique was proposed to identify and subsequently cancel ECG interference on canine surface EEnGs by means of a signal averaging process time-locked with the R-wave. Twelve recording sessions were carried out on six conscious dogs in the fasting state. The adaptive filtering technique used increases the signal-to-interference ratio of the raw surface EEnG from 16.7 +/- 6.5 dB up to 31.9 +/- 4.0 dB. In addition to removing ECG interference, this technique has been proven to respect intestinal SB activity, i.e. the EEnG component associated with bowel contractions, despite the fact that they overlap in the frequency domain. In this way, more robust non-invasive intestinal motility indicators can be obtained with correlation coefficients of 0.68 +/- 0.09 with internal intestinal activity. The method proposed here may also be applied to other biological recordings affected by cardiac interference and could be a very helpful tool for future applications of non-invasive recordings of gastrointestinal signals.

Noninvasive measurement and analysis of intestinal myoelectrical activity using surface electrodes.

Intestinal myoelectrical activity (IMA), which determines bowel mechanical activity, is the result of two components: a low-frequency component [slow wave (SW)] that is always present, and a high-frequency component [spike bursts (SB)] which is associated with bowel contractions. Despite of the diagnostic significance of internal recordings of IMA, clinical application of this technique is limited due to its invasiveness. Thus, surface recording of IMA which is also called electroenterogram (EEnG) could be a solution for noninvasive monitoring of intestinal motility. The aim of our work was to identify slow wave and spike burst activity on surface EEnG in order to quantify bowel motor activity. For this purpose, we conducted simultaneous recordings of IMA in bowel serosa and on abdominal surface of five Beagle dogs in fast state. Surface EEnG was studied in spectral domain and frequency bands for slow wave and spike burst energy were determined. Maximum signal-to-interference ratio (7.5 dB +/- 36%) on SB frequency band was obtained when reducing upper frequency limit of signal analysis. Energy of external EEnG in reduced SB frequency band (2-7.9 Hz) presented a high correlation (0.71 +/- 7%) with internal intensity of contractions. Our results suggest that energy of SB can be quantified on external EEnG which could provide a noninvasive method for monitoring intestinal mechanical activity.