ESAT and M-CHAT as screening instruments for autism spectrum disorders at 18 months in the general population: issues of overlap and association with clinical referrals

The Modified Checklist for Autism in Toddlers (M-CHAT) and the Early Screening of Autistic Traits (ESAT) were designed to screen for autism spectrum disorders in very young children. The aim of this study was to explore proportions of children that screened positive on the ESAT or the M-CHAT and to investigate if screening positive on the ESAT and M-CHAT is associated with clinical referral by 18 months and other aspects of children’s development, health, and behavior. In this study, the mothers of 12,948 18-month-old children returned a questionnaire consisting of items from the ESAT and M-CHAT, plus questions about clinical and developmental characteristics. The M-CHAT identified more screen-positive children than the ESAT, but the ESAT was associated with more clinical referrals and tended to identify more children with medical, language, and behavioral problems. A post hoc analysis of combining the two instruments found this to be more effective than the individual instruments alone in identifying children referred to clinical services at 18 months. Further analysis at the level of single items is warranted to improve these screening instruments.     

Formulation and Evaluation of Sustained Release Extrudes Prepared via Novel Hot Melt Extrusion Technique

The purpose of the present investigation is to emphasize the application of hot-melt extrusion technique (HMET) for the preparation of sustained release matrix formulation of highly dosed, freely soluble drugs. In this study, sustained release multiple unit dosage of venlafaxine hydrochloride (VH) was prepared by HMET. Custom design was used to screen the effect of four factors-type of polymer (ethylcellulose and eudragit RSPO) (X ₁), amount of polymer (X ₂), type of plasticizer (DBS, ATBC, TEC, and PEG) (X ₃), and plasticizer concentration (X ₄), on the drug release at 8 h (Y1) and machine torque (Y2). The experiments were carried out according to a four-factor 16-run statistical model and subjected to 12-h dissolution study in purified water. The significance of the model was indicated by ANOVA. Results of in vitro release study indicate that formulations prepared with higher amount of ethylcellulose and DBC show significant retardation at 8 h. The result shows that increase in concentration of polymer with the combination of water insoluble plasticizer (DBS and ATBC) has better sustained release while increasing concentration of TEC and PEG results faster in vitro release. Besides that increase in plasticizer concentration helps in reducing the melt temperature and machine torque. The in vivo study was performed, and formulations were compared using area under the plasma concentration-time curve (AUC_0-∞), time to reach peak plasma concentration (T_max), and peak plasma concentration (C_max). The drug release profiles of extrudes were found to fit both diffusion and surface erosion models. Further to this, scanning electron microscopy, differential scanning calorimetry, and X-ray diffraction analysis of the hot-melt extrudates demonstrated that VH remained crystalline and was homogeneously dispersed throughout the polymer matrix.     

Hepatopulmonary syndrome associated with nodular regenerative hyperplasia after liver transplantation in a child

HPS is a significant complication of portal hypertension in children with chronic liver disease and is an established indication for LT. It is characterized clinically by the triad of pulmonary vascular dilatation causing hypoxemia in the setting of advanced liver disease. NRH, a cause of non‐cirrhotic portal hypertension, is characterized by diffuse benign transformation of the hepatic parenchyma into small regenerative nodules with minimal or no fibrosis. Development of NRH and HPS in pediatric LT recipients has not been reported, although occasional cases have been reported in adult LT recipients. In this report, we discuss a case of a three‐yr‐old male who developed HPS, two yr after LT. Pulmonary and cardiac causes for hypoxemia were ruled out by appropriate investigations including a chest X ray, echocardiogram, cardiac catheterization, and a CT angiographic study. The diagnosis of HPS was confirmed via bubble echocardiogram that demonstrated intrapulmonary shunting. Open liver biopsy revealed marked NRH. The patient underwent liver retransplantation that resulted in complete reversal of his pulmonary symptoms and normal oxygen saturations within three months after LT.     

Osteocyte death during orthodontic tooth movement in mice

Objective:To investigate the time course of osteocyte death in a mouse model of orthodontic tooth movement (OTM) and its association to the caspase-3 activation pathway and osteoclast formation.Materials and Methods:Twenty-five male wild type CD-1 mice (8–12 weeks old) were loaded with an orthodontic appliance. A spring delivering 10–12 g of force was placed between the right first molar and the incisor to displace the first molar mesially. The contralateral unloaded sides served as the control. The animals were equally divided into five different time points: 6, 12, 24, and 72 hours and 7 days of orthodontic loading. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, caspase-3 immunostaining, and tartrate-resistant acid phosphatase (TRAP) staining was performed on histologic sections of the first molars. The labeling was quantified in osteocytes on the compression side of the alveolar bone at each time point.Results:TUNEL labeling significantly increased at 12, 24, and 72 hours after orthodontic loading; the peak was observed at 24 hours. Elevated caspase-3 labeling was noted at 12, 24, and 72 hours and 7 days after loading, although the increase was not significant. Significant osteoclast formation was initially evident after 72 hours and progressively increased up to 7 days.Conclusions:Osteocyte death during OTM peaks at 24 hours, earlier than initial osteoclast activation. However, only a slight trend for increased caspase-3 activity suggests that other mechanisms might be involved in osteocyte death during OTM.     

Confirmatory in vivo Electrodiagnostic and Electromyographic Studies for Neuromuscular Junctional Blocking Action of Cleistanthus collinus Leaf Extract in Rat

Detailed electromyographic and electrodiagnostic studies were made on sciatic nerve–anterior tibialis muscle preparations in rat in vivo for the first time to confirm the neuromuscular junctional (NMJ) blocking action of Cleistanthus collinus leaf extract (CCLE) and the transient reversal of NMJ blockade by neostigmine. A sublethal dose of 175 mg dry leaf powder/kg body weight of rat caused NMJ blockade confirmed by a decremental response in nerve evoked compound muscle action potentials (NCMAPs). The study suggests the action of the toxic plant extract on acetylcholine (ACh) receptor sites. Muscle evoked compound muscle action potentials (MCMAPs) showed negligible decremental response suggesting the action at the NMJ level only and not on muscle excitation and contractility. The CCLE poisoning revealed a specific diagnostic EMG pattern which might be of help to clinicians in diagnosing Cleistanthus poisoning. The studies confirm that the leaf extract contains a proven and promising new NMJ blocker.