Rapid Phenotype-Driven Gene Sequencing with the NeoSeq Panel: A Diagnostic Tool for Critically Ill Newborns with Suspected Genetic Disease

New genomic sequencing techniques have shown considerable promise in the field of neonatology, increasing the diagnostic rate and reducing time to diagnosis. However, several obstacles have hindered the incorporation of this technology into routine clinical practice. We prospectively evaluated the diagnostic rate and diagnostic turnaround time achieved in newborns with suspected genetic diseases using a rapid phenotype-driven gene panel (NeoSeq) containing 1870 genes implicated in congenital malformations and neurological and metabolic disorders of early onset (<2 months of age). Of the 33 newborns recruited, a genomic diagnosis was established for 13 (39.4%) patients (median diagnostic turnaround time, 7.5 days), resulting in clinical management changes in 10 (76.9%) patients. An analysis of 12 previous prospective massive sequencing studies (whole genome (WGS), whole exome (WES), and clinical exome (CES) sequencing) in newborns admitted to neonatal intensive care units (NICUs) with suspected genetic disorders revealed a comparable median diagnostic rate (37.2%), but a higher median diagnostic turnaround time (22.3 days) than that obtained with NeoSeq. Our phenotype-driven gene panel, which is specific for genetic diseases in critically ill newborns is an affordable alternative to WGS and WES that offers comparable diagnostic efficacy, supporting its implementation as a first-tier genetic test in NICUs

Presbyvestibulopathy, Comorbidities, and Perception of Disability: A Cross-Sectional Study

Objective: To assess the perception of disability in patients with presbyvestibulopathy and to determine the factors (demographic, balance test scores, and comorbidities) that determine higher levels of disability. Material and Methods: This was a cross-sectional study conducted in a tertiary university hospital. There were 103 patients who fulfilled the diagnostic criteria for presbyvestibulopathy and were included. Dizziness Handicap Inventory (DHI) score was the main variable used to quantify disability. Influence on DHI score, sex, age, time of evolution, equilibriometric parameters (posturographic scores and timed up and go test), history of falls, comorbidities (high blood pressure, diabetes, and dyslipidemia), psychotropic drug use, tobacco or alcohol use, living environment (urban or rural), and active lifestyle were analyzed. Results: Most of the DHI scores showed a moderate (46 patients, 44.7%) or severe (39 participants, 37.9%) handicap. DHI scores were higher in women (59.8 vs. 36.1, p < 0.001), patients with obesity (58.92 vs. 48.68; p = 0.019), benzodiazepine (59.9 vs. 49.1, p = 0.008) or other psychotropic drug (60.7 vs. 49.2, p = 0.017) users, and fallers (57.1 vs. 47.3, p = 0.048). There was also a significant positive correlation between DHI score, time (Rho coefficient: 0.371, p < 0.001), and steps (Rho coefficient: 0.284, p = 0.004) used in the TUG and with the short FES-I questionnaire (a shortened version of the Falls Efficacy Scale-International) score (Rho coefficient: 0.695, p < 0.001). DHI scores were lower in alcohol consumers than in non-drinkers (46.6 vs. 56, p = 0.048). No significant correlation was found between DHI scores and age, time of evolution, posturographic scores, comorbidities, environment (rural or urban), or active lifestyle. Conclusion: Most patients with presbyvestibulopathy show an important subjective perception of disability in relation to their symptoms. This perception is substantially higher in women than in men. The most influential factors are difficulties in walking, fear of falling, and obesity. Unique Identifier: NCT03034655, www.clinicaltrials.gov

Modified Timed Up and Go Test for Tendency to Fall and Balance Assessment in Elderly Patients With Gait Instability

Objective: To compare the results from the modified Timed Up and Go Test (TUG) with posturographic variables, the subjective perception of disability due to gait instability, and the number of falls in a sample of the elderly population with imbalance, to confirm that the TUG Test is a useful clinical instrument to assess the tendency to fall in individuals of this age group. Materials and Methods: Cross-sectional study conducted in a tertiary university hospital, in 174 people aged 65 years or older with gait instability. Modified TUG Test was performed; time, step count and the need for support during the test were the analyzed variables. They were compared with the number of falls, Computerized Dynamic Posturography scores, and questionnaires scores (Dizziness Handicap Inventory and a shortened version of the Falls Efficacy Scale-International). Results: The average time to complete the TUG Test was 21.24 +/- 8.18 s, and the average step count was 27.36 +/- 7.93. One hundred two patients (58.6%) required no support to complete the test, whereas the other 72 (41.4%) used supports. The time taken to complete the Test was significantly related with having or not having fallen in the previous year, with the scores of the questionnaires, and with various parameters of dynamic posturography. A higher percentage of patients who took more than 15 s had fallen in the previous year than those who took up to 15 s to complete the test [P = 0.012; OR = 2.378; 95% CI (1.183, 4.780)]. No significant correlation was found between the step count and the number of falls in the previous year, with falling during the test or not, or with being a single or a frequent faller. No relation was found between the need for supports and the number of falls, with having or not having fallen in the previous year, or with being a single or frequent faller. Conclusion: The modified TUG Test is in relation with the presence or absence of falls. Time is the essential parameter for analyzing the risk of falling and the 15-s threshold is a good value to differentiate elderly patients at high risk of falling. Unique Identifier: NCT03034655, www.clinicaltrials.gov

LipoDDx: a mobile application for identification of rare lipodystrophy syndromes

BACKGROUND: Lipodystrophy syndromes are a group of disorders characterized by a loss of adipose tissue once other situations of nutritional deprivation or exacerbated catabolism have been ruled out. With the exception of the HIV-associated lipodystrophy, they have a very low prevalence, which together with their large phenotypic heterogeneity makes their identification difficult, even for endocrinologists and pediatricians. This leads to significant delays in diagnosis or even to misdiagnosis. Our group has developed an algorithm that identifies the more than 40 rare lipodystrophy subtypes described to date. This algorithm has been implemented in a free mobile application, LipoDDx(R). Our aim was to establish the effectiveness of LipoDDx(R). Forty clinical records of patients with a diagnosis of certainty of most lipodystrophy subtypes were analyzed, including subjects without lipodystrophy. The medical records, blinded for diagnosis, were evaluated by 13 physicians, 1 biochemist and 1 dentist. Each evaluator first gave his/her results based on his/her own criteria. Then, a second diagnosis was given using LipoDDx(R). The results were analysed based on a score table according to the complexity of each case and the prevalence of the disease. RESULTS: LipoDDx(R) provides a user-friendly environment, based on usually dichotomous questions or choice of clinical signs from drop-down menus. The final result provided by this app for a particular case can be a low/high probability of suffering a particular lipodystrophy subtype. Without using LipoDDx(R) the success rate was 17 +/- 20%, while with LipoDDx(R) the success rate was 79 +/- 20% (p < 0.01). CONCLUSIONS: LipoDDx(R) is a free app that enables the identification of subtypes of rare lipodystrophies, which in this small cohort has around 80% effectiveness, which will be of help to doctors who are not experts in this field. However, it will be necessary to analyze more cases in order to obtain a more accurate efficiency value

El aprendizaje cooperativo como estrategia metodol?gica para la ense?anza del ?rea de lenguaje en los estudiantes de grado 3? de b?sica primaria

95 p.El aprendizaje cooperativo se centra en que los estudiantes trabajen en grupo para alcanzar una meta en com?n, meta que es construida vali?ndose de la responsabilidad de cada uno de los miembros del grupo. Teniendo en cuenta la importancia del aprendizaje cooperativo en el proceso de ense?anza-aprendizaje, la presente investigaci?n tiene como objetivo dise?ar una propuesta metodol?gica del aprendizaje cooperativo como estrategia para la ense?anza del ?rea de Lenguaje en los estudiantes de grado tercero de b?sica primaria de la Instituci?n Educativa San Bernardo de Montel?bano-C?rdoba, como grupo piloto. Teniendo en cuenta este objetivo, se estableci? como eje de referencia un enfoque de car?cter cualitativo descriptivo, en donde se utilizaron como t?cnicas de recolecci?n de la informaci?n la observaci?n directa, la entrevista semiestructurada, la encuesta y el an?lisis documental. La informaci?n recolectada permiti? determinar que la pr?ctica pedag?gica implementada por la docente de este grado, no considera los fundamentos, los principios y los modelos del aprendizaje cooperativo. Aunque, en las clases de lenguaje se desarrollan actividades grupales, la docente no tiene el control del tiempo de dichas actividades, las cuales no posibilitan la interacci?n entre los estudiantes, la expresi?n de las opiniones individuales y la construcci?n del conocimiento de manera conjunta, todas estas caracter?sticas propias del aprendizaje cooperativo. Por tal motivo, se dise?? una propuesta de intervenci?n fundamentada en los postulados del aprendizaje cooperativo que permitir? la construcci?n de escenarios de interrelaci?n y construcci?n de conocimientos de manera conjunta entre los estudiantes.Cooperative learning focuses on students working in the group to achieve a common goal, a goal that is built using the responsibility of each member of the group. Taking into account the importance of cooperative learning in the teaching-learning process, the present research aims to design a methodological idea of cooperative learning as a strategy for the teaching of the area of language in the students of third grade of elementary school of the educational institution San Bernardo of Montel?bano-C?rdoba. Taking into account this objective, a qualitative descriptive approach was established as a reference axis, where it is used as collection techniques of direct observation information, semi-structured interview, survey and documentary analysis. The information collected allowed the pedagogical practice implemented by the teacher of this grade, no consideration the fundamentals, principles and models of cooperative learning. Although in the language classes the group activities are developed, the teacher does not have the control of the time of the activities, which there is no possibility of the interaction between the students, the expression of the individual opinions and the construction of the knowledge of the Together, all these characteristics of cooperative learning. For this reason, a proposal of intervention was designed based on the postulates of cooperative learning that allows the construction of interrelation scenarios and the construction of knowledge jointly among the students

Vestibular Rehabilitation Using Posturographic System in Elderly Patients with Postural Instability: Can the Number of Sessions Be Reduced?

Purpose: Vestibular rehabilitation (VR) using posturography systems has proved useful in improving balance among elderly patients with postural instability. However, its high cost hinders its use. The objective of this study is to assess whether two different protocols of VR with posturography, one of them longer (ten sessions) and the other shorter (five sessions), show significant differences in the improvement of balance among old patients with instability. Patients and Methods: This is a prospective, experimental, single-center (Department of Otorhinolaryngology of a tertiary referral hospital), randomized (into balanced patient blocks) study with two parallel arms, in 40 people over 65 years of age, with instability and at a high risk of falling. The percentage of the average balance (composite) in the sensory organization test (SOT) of the CDP (main outcome measure), other CDP scores, time and steps in the "timed up and go" test, scores of Dizziness Handicap Inventory (DHI), short Falls Efficacy Scale - International (short FES-I), and Vertiguard were compared before and 3 weeks after VR between both intervention groups. Results: The two treatment groups (20 patients per group) were comparable in age, sex, and pre-VR balance evaluation. In both groups, we observed a significant improvement in global balance (composite) after VR (49+/-11.34 vs 57+/-13.48, p=0.007, in the group undergoing 10 sessions; 51+/-12.55 vs 60+/-12.99, p=0.002, 5 sessions). In both groups, we also observed improvements in other posturographic parameters (in the SOT and limits of stability) but not in the timed up and go scores or in the questionnaires. Comparison of the improvement level achieved in both groups revealed no significant differences between them. Conclusion: The protocols of vestibular rehabilitation by posturography of 5 sessions in elderly patients with postural instability are as effective as those of 10 sessions for improving balance among elderly patients with postural instability. Trial Registration: ClinicalTrials.gov identifier: NCT03034655. Registered on 25 January 2017