Aminoacylase 1 deficiency: case report on three affected siblings.

Background: Aminoacylase 1 (ACY1, EC 3.5.1.14) deficiency (ACY1D) is a very rare inherited metabolic disease (IMD) with autosomal recessive inheritance (OMIM #609924). Up to date, only 15 cases have been reported in the literature. It is diagnosed by detecting acetylated amino acids among the patient's urine organic acids by gas chromatography-mass spectrometry. Its clinical manifestations are highly variable, ranging from severe neurological symptoms to being asymptomatic. Case Description: We present a 14-year-old boy with mild intellectual disability, speech sound disorder and non-alcoholic fatty liver disease who exhibited increased urinary excretion of N-acetylalanine, N-acetylmethionine and N-acetylglutamine during testing for inherited metabolic disorders. A suspected ACY1D was subsequently confirmed by targeted next generation sequencing, which revealed the presence of a homozygous pathogenic missense mutation in the ACY1 gene, c.1057C>T (p.Arg353Cys). The proband underwent speech education with good outcome. The same homozygous mutation in ACY1 gene was found in the boy's two brothers, who exhibited slightly varied intellectual abilities. Follow-up examinations of the siblings revealed no deterioration in their mental skills. Conclusions: These results suggest that uneven mental abilities in pediatric patients with various disorders including autism spectrum disorder may be sufficient grounds to warrant metabolic testing for ACY1D. The acylglycines urine excretion could be a promising novel metabolic marker for ACY1D testing.

Di-4-ANEPPS Modulates Electrical Activity and Progress of Myocardial Ischemia in Rabbit Isolated Heart.

AIMS: Although voltage-sensitive dye di-4-ANEPPS is a common tool for mapping cardiac electrical activity, reported effects on electrophysiological parameters are rather. The main goals of the study were to reveal effects of the dye on rabbit isolated heart and to verify, whether rabbit isolated heart stained with di-4-ANEPPS is a suitable tool for myocardial ischemia investigation. METHODS AND RESULTS: Study involved experiments on stained (n = 9) and non-stained (n = 11) Langendorff perfused rabbit isolated hearts. Electrophysiological effects of the dye were evaluated by analysis of various electrogram (EG) parameters using common paired and unpaired statistical tests. It was shown that staining the hearts with di-4-ANEPPS leads to only short-term sporadic prolongation of impulse conduction through atria and atrioventricular node. On the other hand, significant irreversible slowing of heart rate and ventricular conduction were found in stained hearts as compared to controls. In patch clamp experiments, significant inhibition of sodium current density was observed in differentiated NG108-15 cells stained by the dye. Although no significant differences in mean number of ventricular premature beats were found between the stained and the non-stained hearts in ischemia as well as in reperfusion, all abovementioned results indicate increased arrhythmogenicity. In isolated hearts during ischemia, prominent ischemic patterns appeared in the stained hearts with 3-4 min delay as compared to the non-stained ones. Moreover, the ischemic changes did not achieve the same magnitude as in controls even after 10 min of ischemia. It resulted in poor performance of ischemia detection by proposed EG parameters, as was quantified by receiver operating characteristics analysis. CONCLUSION: Our results demonstrate significant direct irreversible effect of di-4-ANEPPS on spontaneous heart rate and ventricular impulse conduction in rabbit isolated heart model. Particularly, this should be considered when di-4-ANEPPS is used in ischemia studies in rabbit. Delayed attenuated response of such hearts to ischemia might lead to misinterpretation of obtained results.

Haloperidol affects coupling between QT and RR intervals in guinea pig isolated heart.

Prolonged QT interval is an independent risk factor for development of ventricular arrhythmias. Haloperidol is one of the drugs inducing QT prolongation. Previous studies showed that haloperidol affects not only QT duration but also heart rate (RR interval). The present work focused on relationship between QT and RR and its changes under acute and chronic haloperidol administration. The study included 14 male guinea pigs divided into control and haloperidol-treated group. After 21-days administration of haloperidol or vehiculum, electrograms in isolated hearts were recorded. QT/RR and dQT/dRR coupling were calculated. Chronic haloperidol administration significantly decreases the coupling between QT and RR. Acute haloperidol exposure significantly decreases the dQT/dRR coupling in both treated and untreated guinea pig hearts. Flatter QT/RR relationship reveals a lack of QT adaptation to increased heart rate. It should be emphasized that in such situation ECG recording will not show significant QT prolongation evaluated according to clinical rules. However, if QT interval does not adapt to increased heart rate sufficiently, the risk of ventricular arrhythmias may be increased despite practically normal QT interval length. The results are supported by findings in biochemical analyses, which proved eligibility of the used model.

Multi-stage SVM approach for cardiac arrhythmias detection in short single-lead ECG recorded by a wearable device.

OBJECTIVE: Use of wearable ECG devices for arrhythmia screening is limited due to poor signal quality, small number of leads and short records, leading to incorrect recognition of pathological events. This paper introduces a novel approach to classification (normal/'N', atrial fibrillation/'A', other/'O', and noisy/'P') of short single-lead ECGs recorded by wearable devices. APPROACH: Various rhythm and morphology features are derived from the separate beats ('local' features) as well as the entire ECGs ('global' features) to represent short-term events and general trends respectively. Various types of atrial and ventricular activity, heart beats and, finally, ECG records are then recognised by a multi-level approach combining a support vector machine (SVM), decision tree and threshold-based rules. MAIN RESULTS: The proposed features are suitable for the recognition of 'A'. The method is robust due to the noise estimation involved. A combination of radial and linear SVMs ensures both high predictive performance and effective generalisation. Cost-sensitive learning, genetic algorithm feature selection and thresholding improve overall performance. The generalisation ability and reliability of this approach are high, as verified by cross-validation on a training set and by blind testing, with only a slight decrease of overall F1-measure, from 0.84 on training to 0.81 on the tested dataset. 'O' recognition seems to be the most difficult (test F1-measures: 0.90/'N', 0.81/'A' and 0.72/'O') due to high inter-patient variability and similarity with 'N'. SIGNIFICANCE: These study results contribute to multidisciplinary areas, focusing on creation of robust and reliable cardiac monitoring systems in order to improve diagnosis, reduce unnecessary time-consuming expert ECG scoring and, consequently, ensure timely and effective treatment.

Effect of increased left ventricle mass on ischemia assessment in electrocardiographic signals: rabbit isolated heart study.

BACKGROUND: Detailed quantitative analysis of the effect of left ventricle (LV) hypertrophy on myocardial ischemia manifestation in ECG is still missing. The associations between both phenomena can be studied in animal models. In this study, rabbit isolated hearts with spontaneously increased LV mass were used to evaluate the effect of such LV alteration on ischemia detection criteria and performance. METHODS: Electrophysiological effects of increased LV mass were evaluated on sixteen New Zealand rabbit isolated hearts under non-ischemic and ischemic conditions by analysis of various electrogram (EG) parameters. To reveal hearts with increased LV mass, LV weight/heart weight ratio was proposed. Standard paired and unpaired statistical tests and receiver operating characteristics analysis were used to compare data derived from different groups of animals, monitor EG parameters during global ischemia and evaluate their ability to discriminate between unchanged and increased LV as well as non-ischemic and ischemic state. RESULTS: Successful evaluation of both increased LV mass and ischemia is lead-dependent. Particularly, maximal deviation of QRS and area under QRS associated with anterolateral heart wall respond significantly to even early phase (the 1st-3rd min) of ischemia. Besides ischemia, these parameters reflect increased LV mass as well (with sensitivity reaching approx. 80%). However, the sensitivity of the parameters to both phenomena may lead to misinterpretations, when inappropriate criteria for ischemia detection are selected. Particularly, use of cut-off-based criteria defined from control group for ischemia detection in hearts with increased LV mass may result in dramatic reduction (approx. 15%) of detection specificity due to increased number of false positives. Nevertheless, criteria adjusted to particular experimental group allow achieving ischemia detection sensitivity of 89-100% and specificity of 94-100%, respectively. CONCLUSIONS: It was shown that response of the heart to myocardial ischemia can be successfully evaluated only when taking into account heart-related factors (such as LV mass) and other methodological aspects (such as recording electrodes position, selected EG parameters, cut-off criteria, etc.). Results of this study might be helpful for developing new clinical diagnostic strategies in order to improve myocardial ischemia detection in patients with LV hypertrophy.

Breath Analysis Using a Time-of-Flight Camera and Pressure Belts.

The proper way of breathing is important for everyone. Healthy people often do not follow respiration until breathing problems start-during stress or during sport activity in physiological cases. More serious cases are stroke, injury, or surgery of the chest and others. So, learning to breathe correctly and/or breathing diagnosis is considerable for many reasons. Two novel methods of breath analysis suitable for diagnostics and rehabilitation are presented. The first technique utilizes pressure belts fastened to the patient's belly and chest, and the second method relies on a SwissRanger SR-4000 time-of-flight camera. The measurement principles are described together with the advantages and disadvantages of the applied techniques. The SwissRanger camera depth calibration is proposed to facilitate better results during the breath analysis. The methods are tested on a group of students to provide a comparison of their individual performances. As it was demonstrated, presented methods proved to work reliably. The method based on time-of-flight camera seems to be more suitable for diagnosis, while the method based on pressure belts is more suitable for rehabilitation and biofeedback applications.

A Wavelet-Based ECG Delineation Method: Adaptation to an Experimental Electrograms with Manifested Global Ischemia.

We present a novel wavelet-based ECG delineation method with robust classification of P wave and T wave. The work is aimed on an adaptation of the method to long-term experimental electrograms (EGs) measured on isolated rabbit heart and to evaluate the effect of global ischemia in experimental EGs on delineation performance. The algorithm was tested on a set of 263 rabbit EGs with established reference points and on human signals using standard Common Standards for Quantitative Electrocardiography Standard Database (CSEDB). On CSEDB, standard deviation (SD) of measured errors satisfies given criterions in each point and the results are comparable to other published works. In rabbit signals, our QRS detector reached sensitivity of 99.87% and positive predictivity of 99.89% despite an overlay of spectral components of QRS complex, P wave and power line noise. The algorithm shows great performance in suppressing J-point elevation and reached low overall error in both, QRS onset (SD = 2.8 ms) and QRS offset (SD = 4.3 ms) delineation. T wave offset is detected with acceptable error (SD = 12.9 ms) and sensitivity nearly 99%. Variance of the errors during global ischemia remains relatively stable, however more failures in detection of T wave and P wave occur. Due to differences in spectral and timing characteristics parameters of rabbit based algorithm have to be highly adaptable and set more precisely than in human ECG signals to reach acceptable performance.

Heart rate variability in children with inflammatory bowel diseases.

OBJECTIVE: Heart rate variability (HRV) oscillations are used in the detection of autonomic instabilities in various clinical disorders. METHODS: We compared the HRV as a possible marker of chronic distress in children with inflammatory bowel disease (IBD) with HRV frequencies in the healthy controls. Participants were 29 children with IBD (19 Crohn's disease and 10 ulcerative colitis), 25 children were in remission and 4 presented mild disease activity. They were compared with the control group of 35 healthy children of the same age (13-16 years-old). RESULTS: In HRV assessment, adolescents with IBD had significantly lower levels of the spectral activity in an LF band in all three positions; lower levels of VLF in both supine positions; and the ratio of the spectral activity at LF/HF was significantly lower in the second post (standing). CONCLUSION: These results indicate children with IBD have less adaptability to stress.

Quality of life in adolescents with inflammatory bowel disease and their parents--comparison with healthy controls.

OBJECTIVE: Inflammatory bowel diseases (IBD) are chronic diseases with a significant impact on quality of life (QoL). The aim of the study was to examine the QoL in children with IBD and their families, depression and anxiety for both the children and their parents. METHODS: Participants were 29 adolescents with IBD (19 individuals suffered from the Crohn disease, another ten had ulcerative colitis) and 40 healthy controls of the same age (13-16 years). The probands and their parents completed questionnaires measuring the quality of life (KidScreen-10, PedsQL), depression (CDI, BDI-II), and anxiety (SAD, BAI). RESULTS: The QoL measured by questionnaires did not differ between the adolescent participants, but it was significantly lower in the parents of the children with IBD than in the parents of the healthy controls. The parents of the IBD children scored lower in the Family Impact Module Total Scale Score and the parental Health-Related QoL Summary Score. The fathers of the IBD children also had a lower level of the Family Functioning Summary Score. There wasn't any difference in the levels of anxiety and depressive symptoms among the IBD adolescents and the controls. CONCLUSIONS: The parents of the children with IBD experience lower QoL than the parents with the healthy children. The children with IBD show similar symptoms of depression, anxiety, and QoL as the healthy controls.

Sleep scoring using artificial neural networks.

Rapid development of computer technologies leads to the intensive automation of many different processes traditionally performed by human experts. One of the spheres characterized by the introduction of new high intelligence technologies substituting analysis performed by humans is sleep scoring. This refers to the classification task and can be solved - next to other classification methods - by use of artificial neural networks (ANN). ANNs are parallel adaptive systems suitable for solving of non-linear problems. Using ANN for automatic sleep scoring is especially promising because of new ANN learning algorithms allowing faster classification without decreasing the performance. Both appropriate preparation of training data as well as selection of the ANN model make it possible to perform effective and correct recognizing of relevant sleep stages. Such an approach is highly topical, taking into consideration the fact that there is no automatic scorer utilizing ANN technology available at present.