GNAO1 encephalopathy: broadening the phenotype and evaluating treatment and outcome

OBJECTIVE: To describe better the motor phenotype, molecular genetic features, and clinical course of GNAO1-related disease. METHODS: We reviewed clinical information, video recordings, and neuroimaging of a newly identified cohort of 7 patients with de novo missense and splice site GNAO1 mutations, detected by next-generation sequencing techniques. RESULTS: Patients first presented in early childhood (median age of presentation 10 months, range 0-48 months), with a wide range of clinical symptoms ranging from severe motor and cognitive impairment with marked choreoathetosis, self-injurious behavior, and epileptic encephalopathy to a milder phenotype, featuring moderate developmental delay associated with complex stereotypies, mainly facial dyskinesia and mild epilepsy. Hyperkinetic movements were often exacerbated by specific triggers, such as voluntary movement, intercurrent illnesses, emotion, and high ambient temperature, leading to hospital admissions. Most patients were resistant to drug intervention, although tetrabenazine was effective in partially controlling dyskinesia for 2/7 patients. Emergency deep brain stimulation (DBS) was life saving in 1 patient, resulting in immediate clinical benefit with complete cessation of violent hyperkinetic movements. Five patients had well-controlled epilepsy and 1 had drug-resistant seizures. Structural brain abnormalities, including mild cerebral atrophy and corpus callosum dysgenesis, were evident in 5 patients. One patient had a diffuse astrocytoma (WHO grade II), surgically removed at age 16. CONCLUSIONS: Our findings support the causative role of GNAO1 mutations in an expanded spectrum of early-onset epilepsy and movement disorders, frequently exacerbated by specific triggers and at times associated with self-injurious behavior. Tetrabenazine and DBS were the most useful treatments for dyskinesia

Comparison of the Amount of Temperature Rise in the Pulp Chamber of Teeth Treated with QTH, Second and Third Generation LED Light Curing Units: An In Vitro Study

Introduction: This in vitro study was designed to measure and compare the amount of temperature rise in the pulp chamber of the teeth exposed to different light curing units (LCU), which are being used for curing composite restorations.Methods: The study was performed in two settings; first, an in vitro and second was mimicking an in vivo situation. In the first setup of the study, three groups were formed according to the respective three light curing sources. i.e. Quartz-Tungsten-Halogen (QTH) unit and two light-emitting diode (LED) units (second and third generations). In the in vitro setting, direct thermal emission from three light sources at 3 mm and 6 mm distances, was measured with a k-type thermocouple, and connected to a digital thermometer. For a simulation of an in vivo situation, 30 premolar teeth were used. Class I Occlusal cavity of all the teeth [RM1] were prepared and they were restored with incremental curing of composite, after bonding agent application. While curing the bonding agent and composite in layers, the intrapulpal temperature rise was simultaneously measured with a k-type thermocouple.Results: The first setting of the study showed that the heat produced by irradiation with LCU was significantly less at 6 mm distance when compared to 3 mm distance. The second setting of the study showed that the rise of intrapulpal temperature was significantly less with third generation LED light cure units than with second generation LED and QTH light cure units.Conclusion: As the distance from the light source increases, less irradiation heat is produced. Third generation LED lights cause the least temperature change in the pulp chamber of single rooted teeth.

Design and development of Detector Simulator for Total Ionized Dose and ground checkout system of radiation monitoring instrument

This Paper describes the simulator development for the Total Ionizing Dose (TID) measurement of radiation monitoring instrument. The TID Detector (UDOS001-micro dosimeter) is a compact hybrid microcircuit which directly measures Total Ionizing Dose absorbed by an internal silicon test mass. The developed detector simulator, simulates the equivalent Total Ionized Dose absorbed from the space radiation and Ground checkout simulator receive the data from Radiation monitoring Instrument through UART and process it for the functional verification of the Radiation monitoring Instrument, which is discussed in the paper

Implementation of Child Healthcare System by Using Machine Learning Techniques

The focus of the article was paediatric healthcare for children under the age of five. This approach was designed with the goal of tracking children's development from infancy to age five. The goal of the child healthcare system is to provide treatment for growing children outside of hospitals. Nowadays, because we live in a purely digital age, we can provide parents the ability to monitor their child's development while they remain in their own country. Children's info can be uploaded by their parents.  The system can then assess the present development and growth status, spot unhealthy behaviours, anticipate potential chronic diseases, report health-related factors (such as vaccination coverage) that's in the immediate surroundings, and finally offer tailored solutions to avert health hazards as quickly as possible. The studies included in this study concentrate on utilising machine learning algorithms to forecast child healthcare. We put the system into practise using a decision tree for CHS, MySQL for reminders about immunizations, and the K-means Elbow technique for maternal registration and notification

Growth and nutrition in children with Ataxia telangiectasia

Background: Ataxia telangiectasia (A-T) is a rare multisystem disease with high early mortality from lung disease and cancer. Nutritional failure adversely impacts outcomes in many respiratory diseases. Several factors influence nutrition in children with A-T. We hypothesised that children with A-T have progressive growth failure and that early gastrostomy tube feeding (percutaneous endoscopic gastrostomy, or PEG) is a favourable management option with good nutritional outcomes. Methods: Data were collected prospectively on weight, height and body mass index (BMI) at the national paediatric A-T clinic. Adequacy and safety of oral intake was assessed. Nutritional advice was given at each multidisciplinary review. Results: 101 children (51 girls) had 222 measurements (32 once, 32 twice, 24 thrice) between 2009 and 2016. Median (range) age was 9.3 (1.5 to 18.4) years. Mean (sd) weight, height and BMI Z-scores were respectively -1.03(1.57), -1.17 (1.18) and -0.36 (1.43). 35/101 children had weight Z-scores below -2 on at least one occasion. Weight, height and BMI Z-scores declined over time. Decline was most obvious after 8 years of age. 14/101 (13.9%) children had a PEG, with longitudinal data available for 12. In a nested case control study, there was a trend for improvement in weight in those with a PEG (p = 0.06). Conclusions: A-T patients decline in growth over time. There is an urgent need for new strategies, including an understanding of why growth falters. We suggest early proactive consideration of PEG from age 8 years onwards in order to prevent progressive growth failure

MOST OF THE HELICOBACTER PYLORI ISOLATES ARE RESISTANT TO LEVOFLOXACIN IN NORTH INDIA

Objective: Helicobacter pylori related gastro-duodenal diseases can be cured by proper treatment therapy. In India, the commercially available classic treatment therapy (proton pump inhibitor, amoxicillin, and clarithromycin) for bacterial eradication is available. However, antibiotic resistance to the commonly used triple regimen is increasing very rapidly. Considering that treatment including levofloxacin may be an alternative to the classic regimen. Therefore, we aimed to verify H. pylori isolates susceptibility to levofloxacin in India.Methods: H. pylori were cultured from 56 patients suffering from different gastro-duodenal diseases. Minimum Inhibitory concentration to levofloxacin was determined by agar dilution method.Results: The clinical diagnosis of 56 patients who were H. pylori culture positive were Gastro Esophageal Reflux Disease (GERD) (n=23), Non-erosive reflux Disease (NERD) (n=22), Non Ulcer Dyspepsia (NUD) (n=3), Antral Gastritis (n=2), Duodenal ulcer (n=1) and others (n=5). Of the 56 H. pylori isolates, the prevalence of levofloxacin resistance was found in 41 H. pylori isolates (73.2%). Conclusion: We found that three-fourth of the isolated H. pylori strains of North India showed resistance to levofloxacin which is used for H. pylori treatment in other countries. Therefore, the conventional triple therapy comprising amoxicillin and clarithromycin is more appropriate for anti H. pylori management in India.Â

Further investigation of confirmed urinary tract infection (UTI) in children under five years: a systematic review.

Background: Further investigation of confirmed UTI in children aims to prevent renal scarring and future complications. Methods: We conducted a systematic review to determine the most effective approach to the further investigation of confirmed urinary tract infection (UTI) in children under five years of age. Results: 73 studies were included. Many studies had methodological limitations or were poorly reported. Effectiveness of further investigations: One study found that routine imaging did not lead to a reduction in recurrent UTIs or renal scarring. Diagnostic accuracy: The studies do not support the use of less invasive tests such as ultrasound as an alternative to renal scintigraphy, either to rule out infection of the upper urinary tract (LR- = 0.57, 95%CI: 0.47, 0.68) and thus to exclude patients from further investigation or to detect renal scarring (LR+ = 3.5, 95% CI: 2.5, 4.8). None of the tests investigated can accurately predict the development of renal scarring. The available evidence supports the consideration of contrast-enhanced ultrasound techniques for detecting vesico-ureteric reflux (VUR), as an alternative to micturating cystourethrography (MCUG) (LR+ = 14.1, 95% CI: 9.5, 20.8; LR- = 0.20, 95%CI: 0.13, 0.29); these techniques have the advantage of not requiring exposure to ionising radiation. Conclusion: There is no evidence to support the clinical effectiveness of routine investigation of children with confirmed UTI. Primary research on the effectiveness, in terms of improved patient outcome, of testing at all stages in the investigation of confirmed urinary tract infection is urgently required

A survey of falls in people with dystonia.

ObjectiveDystonia is a chronic and sometimes progressive neurological disorder causing abnormalities in movement and function. We conducted a preliminary survey to investigate whether people with dystonia experience falls and to identify contributing factors to falls in this population.MethodsAn online survey of people with dystonia was conducted in November 2015. Respondents were asked to complete demographic information, three questionnaires (the Falls Self-Efficacy Scale International [FES-I], the Activities-based Balance Confidence Scale [ABC] and the Functional Disability Questionnaire [FDQ]), and to report any falls sustained during the previous 6 months.ResultsThirty-nine percent of the 122 respondents reported falling in the previous 6 months and 65% of fallers were diagnosed with dystonia not affecting the lower limbs. Fallers reported lower falls self-efficacy and balance confidence with higher functional disability. Both falling scales correlated with self-reported functional disability. Linear regression analysis for falls prediction revealed the variables FES-I and FDQ accounted for almost 30% of the falls in this dystonia population.ConclusionThis survey indicates that fear of falling and balance confidence are impaired in people with dystonia, possibly impacting on function and falls. Further investigation into balance, function and falls in this population is required