Influence of the Stimulation Current on the Differences between Cell and Tissue Electrophysiological Simulations

This study compares stimulation waveforms for single-cell simulations. The alternatives include monophasic and biphasic current pulses, and a new waveform that resembles the transmembrane current responsible for conduction in tissue. Results indicate that the new stimulation produces the lowest mismatch between action potential markers simulated in cell and in tissue. In comparison with the monophasic stimulation, the new stimulation reduced cell-fiber differences by 99% for triangulation, by 95% for maximum transmembrane voltage, and by 76% for the maximum voltage slope. In conclusion, the new stimulation waveform could help to improve the trustworthiness of single-cell simulations in studies involving tissue-derived markers

Human synthetic lethal inference as potential anti-cancer target gene detection

Background: Two genes are called synthetic lethal (SL) if mutation of either alone is not lethal, but mutation of both leads to death or a significant decrease in organism's fitness. The detection of SL gene pairs constitutes a promising alternative for anti-cancer therapy. As cancer cells exhibit a large number of mutations, the identification of these mutated genes' SL partners may provide specific anti-cancer drug candidates, with minor perturbations to the healthy cells. Since existent SL data is mainly restricted to yeast screenings, the road towards human SL candidates is limited to inference methods. Results: In the present work, we use phylogenetic analysis and database manipulation (BioGRID for interactions, Ensembl and NCBI for homology, Gene Ontology for GO attributes) in order to reconstruct the phylogenetically-inferred SL gene network for human. In addition, available data on cancer mutated genes (COSMIC and Cancer Gene Census databases) as well as on existent approved drugs (DrugBank database) supports our selection of cancer-therapy candidates./nConclusions: Our work provides a complementary alternative to the current methods for drug discovering and gene target identification in anti-cancer research. Novel SL screening analysis and the use of highly curated databases would contribute to improve the results of this methodology

Bilateral Internuclear Ophthalmoplegia in a Patient with Devic's Neuromyelitis Optica

An unusual presentation of Devic's neuromyelitis optica (NMO) disease associated with bilateral internuclear ophthalmoplegia (INO) is described. A 32-year-old pregnant patient was diagnosed with NMO. First symptoms were headache and sudden visual loss in her right eye (RE). Eighteen months ago, she reported other neurologic symptoms such as paresthesia. Based on her visual field, fundoscopy and Ishihara test, she was diagnosed with retrobulbar neuritis of the RE. After delivery, new neurologic symptoms resembling transverse myelitis appeared. She was treated with methylprednisolone and plasmapheresis, which improved her visual acuity; however, a sudden bilateral INO appeared, with adduction defect and nystagmus with abduction in both eyes. No improvement was obtained after treatment with azathioprine and rituximab. Paresis of the legs and the right arm persisted, but double vision and OIN gradually disappeared. At the end, the patient had a residual exophoria in the RE and nystagmus with abduction in the left eye. Prevalence of NMO is lower than one case per one million inhabitants, and it is not likely to affect the encephalic trunk; furthermore, bilateral INO in NMO is rare. Two major criteria and at least two of the three minor ones are required to confirm a NMO diagnosis, and our patient fulfilled these diagnosis criteria

Do vegetation patch spatial patterns disrupt the spatial organization of plant species?

Thelong-range spatial autocorrelationwasevaluated based on the dispersal abilities of the species.Among the 106 species evaluated, 39%of thewoody species, 17% of the forbs, and 12% of the grasses exhibited disrupted long-range spatial autocorrelation where patches were small. The species that are more vulnerable to the effects of fragmentation tended to be those that have restricted dispersal, such as those that have short-range ispersal (atelechoric), e.g., Phlomis purpurea, Cistus albidus, Teucrium pseudochamaepytis, Brachypodium retusum, and the ballistic species, Genista spartioides. Helianthemumalmeriense is another vulnerable species that has actively restricted dispersal (antitelechory), which is common in arid regions. Wind dispersers such as Launaea lanifera were less vulnerable to the effects of fragmentation. Long-distance dispersers whose persistence depends on facilitative interactions with other individuals, e.g., allogamous species such as Thymus hyemalis, Ballota hirsuta, and Anthyllis cytisoides, exhibit disrupted long-range spatial autocorrelation when patch size is reduce

Revisión de los principales test clínicos para evaluar la visión del color

Introducción Las deficiencias congénitas en la visión del color afectan a un 8% de la población masculina y a un 0, 5% de la femenina. El estudio de la visión del color es un proceso complejo debido a diversos factores: la propia psicofísica de la visión y la dificultad de establecer modelos matemáticos para su análisis, la vaga correlación de los resultados entre unos test y otros y la influencia de factores externos como la iluminación, la condición de los test o la experiencia del examinador y del paciente. En el presente documento se realiza una revisión simplificada de los principales test disponibles en la práctica clínica para evaluar la visión del color. Material y métodos Tras realizar una filtrada revisión preliminar de la bibliografía relacionada con el estudio de la visión del color en el motor de búsqueda PubMed, se determinaron los test mayormente utilizados en la práctica clínica. Se realizó una interpretación atendiendo a su frecuencia de uso y el propósito para el que eran utilizados. A continuación, se procedió con un estudio bibliográfico de cada test en particular, atendiendo al diseño de los estímulos presentados, su población diana y su sensibilidad y especificidad. Resultados De las 95 publicaciones que mostró el buscador PubMed, en 41 de ellas los investigadores utilizaron test de colores en su metodología. De los 64 test de color utilizados, 19 eran diferentes (contando como distintos los test adaptados por grupos de investigación, 4, y aquellos realizados online, 2). El orden de empleo de los test es el siguiente: test de Ishihara (10, 88%), Farnsworth-Munsell (7, 04%), Farnsworth-Munsell 100 Hue (6, 4%), Cambridge Colour Test (3, 84%), Hardy-Rand-Rittler (3, 2%), test propios desarrollados por los grupos (2, 56%), el anomaloscopio (1, 28%), los test online (1, 28%) y, finalmente, Colour Assessment and Diagnosis (0, 64%), Pflüger Trident Colour Plates (0, 64%), Toothguide Training Box (0, 64%), Lanthony Desaturated D-15 (0, 64%), City University Test (0, 64%), Universal Colour Discrimination Test (0, 64%) y Rabin Cone Contrast Test (0, 64%). Conclusiones El gold standard en cuanto a la evaluación de la visión del color es el anomaloscopio, instrumento incompatible con la práctica clínica diaria. Su manejo es relativamente complicado, exige disponibilidad de tiempo para su aplicación y es difícilmente comprensible por población infantil. Sin embargo, es posible alcanzar una fiel aproximación mediante la combinación de algunos de los test enumerados en este artículo. Los test expuestos son una buena alternativa para determinar la presencia de discromatopsias en ambientes cercanos a la práctica clínica diaria o en entornos menos controlados que un estudio clínico. El inconveniente principal del amplio elenco de test disponibles para el estudio de la visión del color es la dificultad para comparar los resultados entre test, ya que los datos publicados suelen tener unidades distintas, requiriendo experiencia para su correcta interpretación. En la actualidad, no existe unanimidad sobre qué test de color resulta ser el más completo; es recomendable utilizar al menos 2 para asegurar los diagnósticos y tener una información más completa sobre la percepción visual de los pacientes. Introduction: Congenital colour vision deficiencies affect 8% of the male and 0.5% of the female population. The study of colour vision is a complex process due to several factors: the psychophysics of vision itself, the difficulty to establish mathematical models for its analysis, the vague correlation of results between different tests, and the influence of external factors such as lighting, the tests condition, or the experience of the examiner and the patient. In the present document, a simplified review was carried out on the main colour vision tests available in clinical practice. Material and methods: Once a filtered preliminary review was made of the bibliography related to the study of colour vision using the PubMed search tool, the most used tests in clinical practice were selected according to their frequency of use and the purpose for which they were applied. A bibliographic study was then carried out on each particular test according to the design of the shown stimuli, its target population, and its sensitivity and specificity. Results: From the 95 publications found using the PubMed search tool, in 41 of them, colour tests were used by researchers in their methodology. From the 64 colour tests used, 19 of them were different (with 4 of them being different tests adapted by research groups, and 2 of them carried out online). The most used tests were the following: Ishihara test (10.88%), Farnsworth-Munsell (7.04%), Farnsworth-Munsell 100 Hue (6.4%), Cambridge Colour Test (3.84%), Hardy-Rand-Rittler (3.2%), tests developed by the groups (2.56%), the Anomaloscope (1.28%), the online tests (1.28%) and, finally, Colour Assessment and Diagnosis (0.64%), Pflüger Trident Colour Plates (0.64%), Toothguide Training Box (0.64%), Lanthony Desaturated D-15 (0.64%), City University Test (0.64%), Universal Colour Discrimination Test (0.64%), and Rabin Cone Contrast Test (0.64%). Conclusions: The Anomaloscope is the “gold standard” in terms of colour vision testing, despite its incompatibility with daily clinical practice. It is fairly complex to use, difficult to understand for children, and its practice requires having the time available. Nevertheless, it is possible to reach an accurate approximation through the combination of some of the tests listed in this article. The above mentioned tests are a good alternative to determine the presence of dyschromatopsia in settings closer to daily clinical practice or in less controlled settings than a clinical study. The major drawback among the wide range of tests available for the study of colour vision is the difficulty to compare results between tests, since units of the reported data are usually different, and experience is required for its correct interpretation. Currently, there is no consensus on which colour test is the most complete. It is, therefore, advisable to use at least 2 tests in order to ensure diagnoses, and have more extensive information about the visual perception of patients

Training Habits of Eumenorrheic Active Women during the Different Phases of Their Menstrual Cycle: A Descriptive Study

This research was supported by the Pre-competitive Projects for Early Stage Researchers Program from the University of Granada (ref: PPJIA2020.03). The authors would like to thank all the participants.This study meets the ethical standards of theWorld Medical Association’s Declaration of Helsinki (2013), and it was approved by the Institutional Review Board (Universidad de La Frontera, Temucho, Chile, 005_19).Informed consent was obtained from all subjects involved in the study.The purpose of this study was to examine the training habits of eumenorrheic active women during their menstrual cycle (MC), and its perceived influence on physical performance regarding their athletic level. A group of 1250 sportswomen filled in a questionnaire referring to demographic information, athletic performance and MC-related training habits. Of the participants, 81% reported having a stable duration of MC, with most of them (57%) lasting 26-30 days. Concerning MC-related training habits, 79% indicated that their MC affects athletic performance, although 71% did not consider their MC in their training program, with no differences or modifications in training volume or in training intensity for low-level athletes (LLA) and high-level athletes (HLA) with hormonal contraceptive (HC) use. However, LLA with a normal MC adapted their training habits more, compared with HLA, also stopping their training (47.1% vs. 16.1%, respectively). Thus, different training strategies should be designed for HLA and LLA with a normal MC, but this is not so necessary for HLA and LLA who use HC. To sum up, training adaptations should be individually designed according to the training level and use or non-use of HC, always taking into account the pain suffered during the menstrual phase in most of the athletes.Pre-competitive Projects for Early Stage Researchers Program from the University of Granada PPJIA2020.0

Age norms for grating acuity and contrast sensitivity in children using eye tracking technology

Key messages: Visual acuity is the most used method to assess visual function in children. Contrast sensitivity complements the information provided for visual acuity, but it is not commonly used in clinical practice. Digital devices are increasingly used as a method to evaluate visual function, due to multiple advantages. Testing with these devices can improve the evaluation of visual development in children from a few months of age. Visual acuity and contrast sensitivity tests, using eye tracking technology, are able to measure visual function in children across a wide range of ages, objectively, quickly and without need of an experienced examiner. Purpose: To report age-normative values for grating visual acuity and contrast sensitivity in healthy children using a digital device with eye tracking technology and to validate the grating acuity test. Methods: In the first project of the study, we examined healthy children aged between 6 months and 7 years with normal ophthalmological assessment. Grating visual acuity (VA) and contrast sensitivity (CS) were assessed using a preferential gaze paradigm with a DIVE (Device for an Integral Visual Examination) assisted with eye tracking technology to provide age norms. For the validation project, we compared LEA grating test (LGT) with DIVE VA in a group of children aged between 6 months and 4 years with normal and abnormal visual development. Results: Fifty-seven children (2.86 ± 1.55 years) were examined with DIVE VA test and 44 successfully completed DIVE CS test (3.06 ± 1.41 years). Both, VA and CS values increased with age, mainly along the first two years of life. Sixty-nine patients (1.34 ± 0.61 years) were included in the DIVE VA test validation. The mean difference between LGT and DIVE VA was − 1.05 ± 4.54 cpd with 95% limits of agreement (LoA) of − 9.95–7.84 cpd. Agreement between the two tests was higher in children younger than 1 year with a mean difference of − 0.19 ± 4.02 cpd. Conclusions: DIVE is an automatic, objective and reliable tool to assess several visual function parameters in children, and it has good agreement with classical VA tests, especially for the first stage of life

T-Wave Morphology Restitution Predicts Sudden Cardiac Death in Patients With Chronic Heart Failure

BACKGROUND: Patients with chronic heart failure are at high risk of sudden cardiac death (SCD). Increased dispersion of repolarization restitution has been associated with SCD, and we hypothesize that this should be reflected in the morphology of the T-wave and its variations with heart rate. The aim of this study is to propose an electrocardiogram (ECG)-based index characterizing T-wave morphology restitution (TMR), and to assess its association with SCD risk in a population of chronic heart failure patients. METHODS AND RESULTS: Holter ECGs from 651 ambulatory patients with chronic heart failure from the MUSIC (MUerte Súbita en Insuficiencia Cardiaca) study were available for the analysis. TMR was quantified by measuring the morphological variation of the T-wave per RR increment using time-warping metrics, and its predictive power was compared to that of clinical variables such as the left ventricular ejection fraction and other ECG-derived indices, such as T-wave alternans and heart rate variability. TMR was significantly higher in SCD victims than in the rest of patients (median 0.046 versus 0.039, P<0.001). When TMR was dichotomized at TMR=0.040, the SCD rate was significantly higher in the TMR≥0.040 group (P<0.001). Cox analysis revealed that TMR≥0.040 was strongly associated with SCD, with a hazard ratio of 3.27 (P<0.001), independently of clinical and ECG-derived variables. No association was found between TMR and pump failure death. CONCLUSIONS: This study shows that TMR is specifically associated with SCD in a population of chronic heart failure patients, and it is a better predictor than clinical and ECG-derived variables

Nursing Home-Acquired Pneumonia: a 10 year single-centre experience

Background: Pneumonia among nursing home (NH) residents has increased considerably in recent years, but it remains unclear whether it should be considered as community-acquired pneumonia (CAP) or a new category of infection. Methods 150 consecutive cases of NH-acquired pneumonia (NHAP) (from 1 February 1997 to 1 July 2007) were analysed. Results: Patients (median age, 82 years; range, 77-87 years) showed numerous co-morbidities, (neurological, 55%; pulmonary, 38%; cardiac, 35%) and severe disability for daily activities (partial, 32%; total, 31%). Cases of NHAP were mainly classified as mild to moderate according to the CRB-65 score (CRB-65 classes 0-1 and 2, 41% each). In-hospital and 30-day mortality were 8.7% and 20%, respectively. Aetiology was defined in 57 cases (38%). The most common isolates were Streptococcus pneumoniae (58%), Enterobacteriaceae (Gram-negative bacteria (GNB)) (9%), atypical bacteria (7%), respiratory viruses (5%), methicillin-resistant Staphylococcus aureus (MRSA) (5%) and Legionella pneumophila (5%). The most frequent causes of treatment inadequacy were use of β-lactams alone (25%) and lack of aspiration assessment (15%). Prognostic factors of 1-month mortality were neurological comorbidities (OR 4.5; 95% CI 1.3 to 15.7; p=0.020), septic shock (OR 6.6; 95% CI 1.3 to 34.0; p=0.025), pleural effusion (OR 3.6; 95% CI 1.1 to 11.7; p=0.036) and isolation of GNB or MRSA (OR 16.4; 95% CI 2.1 to 128.9; p=0.008). Conclusions: The patients show clinical characteristics (eg, age and co-morbidities) comparable with those with hospital-acquired pneumonia. However, microbiological and mortality data of patients with NHAP are more similar to the data of those with CAP. Isolation of GNB or MRSA was associated with increased mortality risk. CAP empirical antibiotic coverage is still indicated in NHAP, although specific risk factors for multidrug-resistant infections should be assessed on an individual basis

HGF -rs12536657 and Ocular Biometric Parameters in Hyperopic Children, Emmetropic Adolescents, and Young Adults: A Multicenter Quantitative Trait Study

Introduction. Even though ocular refractive state is highly heritable and under strong genetic control, the identification of susceptibility genes remains a challenge. Several HGF (hepatocyte growth factor) gene variants have been associated with ocular refractive errors and corneal pathology. Purpose. Here, we assess the association of an HGF gene variant, previously reported as associated with hyperopia, and ocular biometric parameters in a multicenter Spanish cohort. Methods. An observational prospective multicenter cross-sectional study was designed, including a total of 403 unrelated subjects comprising 188 hyperopic children (5 to 17 years) and 2 control groups: 52 emmetropic adolescents (13 to 17 years) and 163 emmetropic young adults (18 to 28 years). Each individual underwent a comprehensive eye examination including cycloplegic refraction, and topographic and ocular biometric analysis. Genomic DNA was extracted from oral swabs. HGF single nucleotide polymorphism (SNP) rs12536657 was genotyped. Genotypic, allelic, and logistic regression analyses were performed comparing the different groups. A quantitative trait association test analyzing several biometric parameters was also performed using generalized estimating equations (GEEs) adjusting for age and gender. Results. No association between rs12536657 and hyperopia was found through gender-adjusted logistic regression comparing the hyperopic children with either of the two control groups. Significant associations between mean topographic corneal curvature and rs12536657 for G/A (slope = +0.32; CI 95%: 0.04-0.60; p=0.023) and A/A (slope = +0.76; CI 95%: 0.12-1.40; p=0.020) genotypes were observed with the age- and gender-adjusted univariate GEE model. Both flat and steep corneal topographic meridians were also significantly associated with rs12536657 for the G/A and A/A genotypes. No association was found between rs12536657 and any other topographic or biometric measurements. Conclusions. Our results support a possible role for HGF gene variant rs12536657 in corneal curvature in our population. To our knowledge, this is the first multicenter quantitative trait association study of HGF genotypes and ocular biometric parameters comprising a pediatric cohort