Miracle-dz/UniFAR-FTUs huggingface dataset:
Recognizing the tenascin‐X deficient type of Ehlers–Danlos syndrome: a cross‐sectional study in 17 patients

The tenascin‐X (TNX) deficient type Ehlers–Danlos syndrome (EDS) is similar to the classical type of EDS. Because of the limited awareness among geneticists and the challenge of the molecular analysis of the TNXB gene, the TNX‐deficient type EDS is probably to be under diagnosed. We therefore performed an observational, cross‐sectional study. History and physical examination were performed. Results of serum TNX measurements were collected and mutation analysis was performed by a combination of next‐generation sequencing (NGS), Sanger sequencing and multiplex ligation‐dependent probe amplification (MLPA). Included were 17 patients of 11 families with autosomal recessive inheritance and childhood onset. All patients had hyperextensible skin without atrophic scarring. Hypermobility of the joints was observed in 16 of 17 patients. Deformities of the hands and feet were observed frequently. TNX serum level was tested and absent in 11 patients (seven families). Genetic testing was performed in all families; 12 different mutations were detected, most of which are suspected to lead to non‐sense mRNA mediated decay. In short, patients with the TNX‐deficient type EDS typically have generalized joint hypermobility, skin hyperextensibility and easy bruising. In contrast to the classical type, the inheritance pattern is autosomal recessive and atrophic scarring is absent. Molecular analysis of TNXB in a diagnostic setting is challenging.
Baraitser–Winter cerebrofrontofacial syndrome

Baraitser–Winter cerebrofrontofacial syndrome (BWCFF) (BRWS; MIM #243310, 614583) is a rare developmental disorder affecting multiple organ systems. It is characterised by intellectual disability (mild to severe) and distinctive facial appearance (metopic ridging/trigonocephaly, bilateral ptosis, hypertelorism). The additional presence of cortical malformations (pachygyria/lissencephaly) and ocular colobomata are also suggestive of this syndrome. Other features include moderate short stature, contractures, congenital cardiac disease and genitourinary malformations. BWCFF is caused by missense mutations in the cytoplasmic beta‐ and gamma‐actin genes ACTB and ACTG1. We provide an overview of the clinical characteristics (including some novel findings in four recently diagnosed patients), diagnosis, management, mutation spectrum and genetic counselling.
Obesity in Childhood: definition and epidemiology

Obesity is defined as a condition where a pathological excess of body fat is present in an individual. Obesity develops when there is a discrepancy between energy intake and energy output. During its development the original steady-state is disturbed and after a period of positive energy balance, a new steady state at a higher level with an increase in body fat stores is achieved. Since the amount of body fat per se is difficult to determine exactly, for practical use, percentage overweight or the body mass index (BMI) is used to define and to track obesity in childhood. For a given BMI, adiposity varies with age, sex and ethnicity; however, BMI correlates reasonably well with body fat mass and the risk of obesity related diseases. Childhood obesity is one of the most complex and poorly understood clinical syndromes in pediatrics. Obesity is a common nutritional disorder among children and adolescents in the world. The percentage of overweight children and adolescents has increased by almost 50% in the past two decades. It has also been observed that about 40% of overweight children continue to have increased weight during adolescence and 75-80% of obese adolescents become obese adults. The majority of obesity in adulthood has its origin in childhood, which makes obesity a pediatric concern and the prevention and treatment of obesity a pediatric goal.
Effects of S906T polymorphism on the severity of a novel borderline mutation I692M in Nav1.4 cause periodic paralysis

Hyperkalemic periodic paralysis (HyperPP) is a dominantly inherited muscle disease caused by mutations in SCN4A gene encoding skeletal muscle voltage gated Nav1.4 channels. We identified a novel Nav1.4 mutation I692M in 14 families out of the 104 genetically identified HyperPP families in the Neuromuscular Centre Ulm and is therefore as frequent as I693T (13 families out of 14 HyperPP families) in Germany. Surprisingly, in 13 families, a known polymorphism S906T was also present. It was on the affected allele in at least 10 families compatible with a possible founder effect in central Europe. All affected members suffered from episodic weakness; myotonia was also common. Compared with I692M patients, I692M‐S906T patients had longer weakness episodes, more affected muscles, CK elevation and presence of permanent weakness. Electrophysiological investigation showed that both mutants had incomplete slow inactivation and a hyperpolarizing shift of activation which contribute to membrane depolarization and weakness. Additionally, I692M‐S906T significantly enhanced close‐state fast inactivation compared with I692M alone, suggesting a higher proportion of inactivated I692M‐S906T channels upon membrane depolarization which may facilitate the initiation of weakness episodes and therefore clinical manifestation. Our results suggest that polymorphism S906T has effects on the clinical phenotypic and electrophysiological severity of a novel borderline Nav1.4 mutation I692M, making the borderline mutation fully penetrant.
Chondrodysplasia with multiple dislocations: comprehensive study of a series of 30 cases

The group of chondrodysplasia with multiple dislocations includes several entities, characterized by short stature, dislocation of large joints, hand and/or vertebral anomalies. Other features, such as epiphyseal or metaphyseal changes, cleft palate, intellectual disability are also often part of the phenotype. In addition, several conditions with overlapping features are related to this group and broaden the spectrum. The majority of these disorders have been linked to pathogenic variants in genes encoding proteins implicated in the synthesis or sulfation of proteoglycans (PG). In a series of 30 patients with multiple dislocations, we have performed exome sequencing and subsequent targeted analysis of 15 genes, implicated in chondrodysplasia with multiple dislocations, and related conditions. We have identified causative pathogenic variants in 60% of patients (18/30); when a clinical diagnosis was suspected, this was molecularly confirmed in 53% of cases. Forty percent of patients remain without molecular etiology. Pathogenic variants in genes implicated in PG synthesis are of major importance in chondrodysplasia with multiple dislocations and related conditions. The combination of hand features, growth failure severity, radiological aspects of long bones and of vertebrae allowed discrimination among the different conditions. We propose key diagnostic clues to the clinician.
Isolamento das bactérias causadoras de infecções urinárias e seu perfil de resistência aos antimicrobianos

Urinary tract infection (UTI) is among the most frequent causes bringing male and female patients to the municipal health units in search of treatment. This paper aims at identifying the microorganisms responsible for this infection and at establishing their resistance profile against the antibiotics most commonly used in the municipal network. One hundred and twenty samples from patients clinically suspect to have UTI were collected and differentiated in CLED, MacConkey e chromogenic EC culture media in the Microbiology Laboratory I of the “Centro Universitario Positivo-UNICEP”. Positive samples were identified and characterized by antibiogram. 63,64% of the infections were caused by Escherichia coli and 18,18% by Staphylococcus aureus. More than 60% of the infections occurred in the age range from 12 to 33 years. The high number of samples found contaminated is an indicator for a certain difficulty in following the instructions for sample collection. Another relevant data is that 35,8% of the analyzed samples came from pregnant women. The antibiotics to which the bacteria responsible for UTI are sensitive are in great part not available at the Unified Health System but most of the isolated E.coli bacteria and 100% of Saureus showed sensitivity to the drugs Nitrofurantoin and Sulfametoxazole-trimetropim, which are available in the health units. With a compatible clinical picture, an empirical treatment with the referred drugs can be considered adequate, however post-therapy control examinations would be ideal for avoiding the appearance of resistant strains in the community.
Ask Suicide-Screening Questions (ASQ): a brief instrument for the pediatric emergency department.

OBJECTIVE To develop a brief screening instrument to assess the risk for suicide in pediatric emergency department patients. DESIGN A prospective, cross-sectional instrument-development study evaluated 17 candidate screening questions assessing suicide risk in young patients. The Suicidal Ideation Questionnaire served as the criterion standard. SETTING Three urban, pediatric emergency departments associated with tertiary care teaching hospitals. PARTICIPANTS A convenience sample of 524 patients aged 10 to 21 years who presented with either medical/surgical or psychiatric chief concerns to the emergency department between September 10, 2008, and January 5, 2011. MAIN EXPOSURES Participants answered 17 candidate questions followed by the Suicidal Ideation Questionnaire. MAIN OUTCOME MEASURES Sensitivity, specificity, predictive values, likelihood ratios, and area under the receiver operating characteristic curves of the best-fitting combinations of screening questions for detecting elevated risk for suicide. RESULTS A total of 524 patients were screened (344 medical/surgical and 180 psychiatric). Fourteen of the medical/surgical patients (4%) and 84 of the psychiatric patients (47%) were at elevated suicide risk on the Suicidal Ideation Questionnaire. Of the 17 candidate questions, the best-fitting model comprised 4 questions assessing current thoughts of being better off dead, current wish to die, current suicidal ideation, and past suicide attempt. This model had a sensitivity of 96.9% (95% CI, 91.3-99.4), specificity of 87.6% (95% CI, 84.0-90.5), and negative predictive values of 99.7% (95% CI, 98.2-99.9) for medical/surgical patients and 96.9% (95% CI, 89.3-99.6) for psychiatric patients. CONCLUSIONS A 4-question screening instrument, the Ask Suicide-Screening Questions (ASQ), with high sensitivity and negative predictive value, can identify the risk for suicide in patients presenting to pediatric emergency departments.
Mining for mitochondrial mechanisms: Linking known syndromes to mitochondrial function

Mitochondrial disorders (MDs) are caused by defects in 1 or multiple complexes of the oxidative phosphorylation (OXPHOS) machinery. MDs are associated with a broad range of clinical signs and symptoms, and have considerable clinical overlap with other neuromuscular syndromes. This overlap might be due to involvement of mitochondrial pathways in some of these non‐mitochondrial syndromes. Here, we give an overview of around 25 non‐mitochondrial syndromes, diagnosed in patients who were initially suspected to have a MD on the basis of clinical and biochemical parameters. In addition, we highlight the mitochondrial connections of 6 of these non‐mitochondrial syndromes (eg, Rett syndrome and Dravet syndrome) diagnosed in multiple patients. Further research to unravel the interplay between these genes and mitochondria may help to increase knowledge on these syndromes. Additionally, it may open new avenues for research on pathways interacting with mitochondrial function in order to find new targets for therapeutics to treat MDs. The data presented in this review underline the importance of careful assessment of clinical, genetic, and biochemical data in all patients suspected of a neuromuscular syndrome, and highlights the importance of the role of clinical geneticists, physicians, and clinical biochemists in recognizing the possible mitochondrial connection of non‐mitochondrial syndromes.
Cromolyn Therapy in Chronic Infantile Eczema

To the Editor. — The principal effect of cromolyn sodium (disodium cromoglycate) is believed to be inhibition of the release of chemical mediators on anaphylaxis from sensitized mast cells. 1 There are some indications 2,3 that cromolyn taken orally may inhibit the development of gastrointestinal manifestations of food allergy. Also, cromolyn may block the development of remote manifestations, such as urticaria, following ingestion of an offending food allergen. This report documents what is believed to be the first recorded use of cromolyn in the treatment of infantile eczema. Report of a Case. — The patient is a 6-year-old boy, whose eczema was first diagnosed at eight weeks of age. His disease was of sufficient intensity to require hospitalization on five occasions during the first 24 months of life. Intermittent therapy with oral steroids as well as nearly continuous application of topical steroids have been necessary to control his skin lesions. At five
Mechanical, Metabolic and Perceptual Response during Sprint Training

Abstract This study aimed to analyze perceptual, metabolic and mechanical responses to sprint training sessions. 9 male high-level sprinters performed 40 m running sprints up to a loss of 3% in speed, with 4 min rests between sets. Perceptual (rating of perceived exertion, RPE), mechanical (speed and countermovement jump height loss) and metabolic (blood lactate and ammonia) parameters were measured pre-exercise and after each sprint was performed. Relationships between the variables were calculated with a 90% confidence interval. Jump height loss showed almost perfect relationships with both blood lactate (r=0.96 (0.95 to 0.97)) and ammonia (r=0.95 (0.94 to 0.95)), whereas speed loss, number of sprints performed and RPE values showed large-very large relationships with blood lactate and ammonia. Furthermore, an almost perfect curvilinear relationship was observed between lactate and ammonia concentrations (R2=0.96 (0.95 to 0.97)). These results suggest that countermovement jump (CMJ) height can be used to quantify the fatigue induced during a typical sprint training session, and may prove a useful tool to facilitate individualized load monitoring. The results indicate that the CMJ is a better monitor of metabolic fatigue than traditional measures.
Rapid eye movement sleep in relation to overweight in children and adolescents.

CONTEXT Short sleep duration is associated with obesity, but few studies have examined the relationship between obesity and specific physiological stages of sleep. OBJECTIVE To examine specific sleep stages, including rapid eye movement (REM) sleep and stages 1 through 4 of non-REM sleep, in relation to overweight in children and adolescents. DESIGN, SETTING, AND PARTICIPANTS A total of 335 children and adolescents (55.2% male; aged 7-17 years) underwent 3 consecutive nights of standard polysomnography and weight and height assessments as part of a study on the development of internalizing disorders (depression and anxiety). MAIN OUTCOME MEASURES Body mass index (calculated as weight in kilograms divided by height in meters squared) z score and weight status (normal, at risk for overweight, overweight) according to the body mass index percentile for age and sex. RESULTS The body mass index z score was significantly related to total sleep time (beta = -0.174), sleep efficiency (beta = -0.027), and REM density (beta = -0.256). Compared with normal-weight children, overweight children slept about 22 minutes less and had lower sleep efficiency, shorter REM sleep, lower REM activity and density, and longer latency to the first REM period. After adjustment for demographics, pubertal status, and psychiatric diagnosis, 1 hour less of total sleep was associated with approximately 2-fold increased odds of overweight (odds ratio = 1.85), 1 hour less of REM sleep was associated with about 3-fold increased odds (odds ratio = 2.91), and REM density and activity below the median increased the odds of overweight by 2-fold (odds ratio = 2.18) and 3-fold (odds ratio = 3.32), respectively. CONCLUSIONS Our results confirm previous epidemiological observations that short sleep time is associated with overweight in children and adolescents. A core aspect of the association between short sleep duration and overweight may be attributed to reduced REM sleep. Further studies are needed to investigate possible mechanisms underpinning the association between diminished REM sleep and endocrine and metabolic changes that may contribute to obesity.
Propriocepção de joelho em jovens e idosas praticantes de exercícios físicos

A propriocepcao e um mecanismo neuromuscular que descreve informacoes neurais originadas nas articulacoes, musculos e tendoes. Este estudo verificou a propriocepcao de joelho em jovens e idosas praticantes de exercicios fisicos. Participaram do estudo 44 mulheres - 22 idosas (media de idade 69,4 anos) e 22 jovens, idade media 22,5). A propriocepcao foi avaliada pelo senso de posicao articular, sendo a participante solicitada a reposicionar o membro inferior dominante previamente estendido ou flexionado pelo avaliador. Os ângulos de flexao e extensao do joelho foram sorteado, utilizando-se nos testes um goniometro fixo a perna da participante. Considerou-se como variavel o valor absoluto do erro, isto e, a diferenca em graus entre o ângulo proposto e o ângulo reproduzido pela avaliada. Os dados foram tratados estatisticamente, com nivel de significância de p<0,05. A media de erro das idosas foi 6,75±3,01o e, das jovens, 5,73±4,24o, nao havendo diferenca estatisticamente significativa (p=0,249) entre os grupos. Concluiu-se que, apesar da propriocepcao sofrer um declinio com a idade, possivelmente devido a pratica de exercicios fisicos o grupo de idosas apresentou resultados similares ao das jovens, sugerindo que a pratica de exercicios fisicos constitui uma estrategia benefica para atenuar o declinio provocado pelo envelhecimento.
Genomewide association analysis followed by a replication study implicates a novel candidate gene for neuroticism.

CONTEXT Neuroticism is a trait that reflects a tendency toward negative mood states. It has long been linked to internalizing psychiatric conditions, such as anxiety and depression, and it accounts for much of the substantial comorbidity seen between these disorders. OBJECTIVE To identify common genetic variants that affect neuroticism to better understand (the comorbidity between) a broad range of psychiatric disorders and to develop effective treatments. DESIGN, SETTING, AND PARTICIPANTS More than 420,000 genetic markers were tested for their association with neuroticism in a genomewide association study (GWAS). The GWAS sample consisted of 1227 healthy individuals ascertained from a US national sampling frame and available from the National Institute of Mental Health genetics repository. The most promising markers were subsequently tested in a German replication sample comprising 1880 healthy individuals. MAIN OUTCOME MEASURES A strict definition of replication (same marker, same direction of effects, and same measure) combined with a threshold we proposed previously for declaring significance in genetic studies that ensures a mean probability of producing false-positive findings of less than 10%. RESULTS The most promising results in the GWAS and replication samples were single-nucleotide polymorphisms (SNPs) in the gene MAMDC1. These SNPs all tagged the same 2 haplotypes and had P values of 10(-5) to 10(-6) in the GWAS sample and of . 006 to . 02 in the replication sample. Furthermore, the replication involved the same SNPs and the same direction of effects. In a combined analysis of all data, several SNPs were significant according to the threshold that allows for 10% false-positive findings. CONCLUSIONS The small effect sizes may limit the prognostic, diagnostic, and therapeutic use of SNP markers such as those in MAMDC1. However, the present study demonstrates the potential of a GWAS to discover potentially important pathogenic pathways for which clinically more powerful (bio)markers may eventually be developed.
Pattern of seizure disorders in children in Eastern Nepal

Abstract The present study was undertaken to find out the prevalence, pattern and etiology of seizure disorders iThe present study was undertaken to find out the prevalence, pattern and etiology of seizure disorders in children attending at a tertiary care center of a teaching hospital. The prevalence of seizure disorder was 3.9/1,000. Generalized seizures were reported in 69.5%, partial seizures in 19% and unclassified seizures in 11.4% of cases. Cranial computerized tomography (CT) scan could be performed in 87 (82.8%) patients and was abnormal in 66 (75.8%) cases. Neurocysticercosis was the most common (31%) etiology detected, followed by brain atrophy 10 (11.4%) and cerebral dysgenesis in seven (8%) children. The electroencephalogram (EEG) was abnormal in 48/87 (55.1%) cases and showed generalized discharges in 30 (62.5%) and focal slowing/discharges in 18 (37.5%) patients. In conclusion, CT scan and EEG should be undertaken in children with seizures to find out the etiological diagnosis so that specific treatment and antiepileptic drugs can be chosen for effective control.
Neuroprotective Core Measures 1–7: A Developmental Care Journey: Transformations in NICU Design and Caregiving Attitudes

Abstract The neonatal intensive care unit (NICU) at Mercy Kids Hospital-Springfield (Missouri) recently embarked on a transformational developmental care journey. The catalyst for transformation was the impending construction of a new 48-bed NICU with single-family rooms. The shift to a new design represented the departure from an older, traditional open-bay NICU, which provided an opportunity for honest reflection on both the current neonatal physical environment (NICU), as well as current caregiving-practices. NICU staff verbalized a desire to change not only the physical environment, but wanted to change their culture of caregiving by embarking on a journey toward improved neuroprotective family-centered developmentally supportive care. Utilizing the Neonatal Integrative Developmental Care Model as a framework, Mercy identified specific goals and aim statements within each of the model's seven core measures (Newborn and Infant Nursing Reviews. 2013;13:9–22). This manuscript outlines the steps Mercy took to achieve success on each core measure goal and illustrates how physical and cultural transformation can occur within the NICU setting.
Simulation of Morphology Changes in Drying Leaves

We introduce a biologically motivated simulation technique for the realistic shape deformation of drying leaves. In contrast to skeleton‐based leaf deformation, our approach simulates the whole leaf surface to capture the fine details of desiccated leaves. We represent a leaf as a triangulated double‐layer structure that consists of a Delaunay triangulation discretized along the vein structure and its corresponding Voronoi diagram. This structure can generate not only sharp creases along leaf veins, but also the complicated curling and crumpling on the leaf surface. The loss of water is the major factor that controls the inhomogeneous shrinkage of drying leaves. The proposed osmotic water flow successfully models the gradual changes of dehydrated regions advancing towards the veins. We demonstrate the robustness of our method by comparing a sequence of simulated morphology changes with photographs of real leaves.