Effect of D-002 on acetic acid-induced colitis in rats at single and repeated doses.

D-002 is a natural mixture of higher aliphatic primary alcohols purified from beeswax, with mild anti-inflammatory and effective antiulcer effects experimentally proved. Furthermore, it reduces leukotriene (LTB(4)) in the exudate of carrageenan-induced pleurisy and has a protective effect on the pre-ulcerative phase of carrageenan-induced colonic ulceration in the guinea pig. This study was conducted to determine the effect of D-002 on acetic acid-induced colitis in rats at single and repeated doses. In a first series, D-002 was orally administered at 25 and 50 mg kg(-1), 24 h before the induction of colitis, meanwhile, in a second series, it was administered 24 h after the induction of colitis. Two other series (III and IV) examined the protective and therapeutic effect of D-002 administered for 7 days at the same doses, before or after colitis induction. Significant reductions in wet weight, macroscopic injury, polymorphonuclear infiltration and wall thickness were observed in colonic mucosa of D-002-treated animals compared with controls in both protective and therapeutic alternatives. It is concluded that D-002 was effective to protect or prevent the damage associated to acetic acid-induced colitis.     

C-reactive protein to distinguish pneumonia from acute decompensated heart failure

Background:Patients with acute decompensated heart failure (ADHF) are frequently treated with unnecessary antibiotics since they are confused with pneumonia patients.Aim:To study the efficacy of measuring C-reactive protein (CRP) levels on admission and CRP velocity in differentiating ADHF from pneumonia.Methods:A retrospective observational study of ADHF and pneumonia patients admitted to a tertiary hospital during 2 years. Patients who were already treated with antibiotics on admission were excluded. Efficacy of CRP as a diagnostic marker was evaluated by using receiver operator curves (ROC).Results:Overall, 72 ADHF and 50 pneumonia patients were included in the study. The mean CRP levels on admission were 13.5 ± 13.5 mg/L for the ADHF patients and 127 ± 84 mg/L for the pneumonia patients (p < 0.001). CRP increases of ≥0.56 mg/L/h were diagnostic of pneumonia. CRP levels on admission together with CRP increases had a sensitivity of 0.96 and a specificity of 0.972 (p < 0.001) as markers to distinguish pneumonia from ADHF.Conclusions:This study emphasizes the dynamic nature of biomarkers. Demonstrating the efficiency of repeated CRP measurements in an acute setting will provide clinicians with a valuable tool for establishing the correct diagnosis and refraining from unnecessary use of antibiotics.     

Reproducibility of sagittal pelvic tilt measurements in normal subjects using digital inclinometry

Standing sagittal pelvic tilt posture is widely assessed qualitatively, yet no efficient non-invasive quantitatively method is available for measuring pelvic tilt position or its amplitude. The main objective of the current study was to assess the intra- and inter-tester reproducibility of digital inclinometry-based (DI) measurements of pelvic tilt in healthy subjects. Pelvic inclination was measured while standing in neutral position (NP), maximal anterior pelvic tilt (APT) and maximal posterior pelvic tilt (PPT) which served for calculating the total pelvic tilt (TPT) range of motion (TPT=PPT-APT). On two separate test occasions two convenience samples of healthy women and men (N=15 in each) were each measured by two different testers. In both groups the intra-tester reproducibility indices of NP, APT, PPT and TPT were acceptable as revealed by high and significant ICCs and low standard error of measurements (SEM). In women the inter-tester reproducibility indices, of the same variables, were high as distinguished by no significant differences between testers and high and significant ICCs. In men, significant differences were found in APT and PPT but the between-testers TPT scores were similar. Collectively these findings indicate that pelvic inclinometry yields acceptable reproducibility which in the light of the facility of the method may render it an efficient clinical tool.     

A harmonized segmentation protocol for hippocampal and parahippocampal subregions: Why do we need one and what are the key goals?

The advent of high‐resolution magnetic resonance imaging (MRI) has enabled in vivo research in a variety of populations and diseases on the structure and function of hippocampal subfields and subdivisions of the parahippocampal gyrus. Because of the many extant and highly discrepant segmentation protocols, comparing results across studies is difficult. To overcome this barrier, the Hippocampal Subfields Group was formed as an international collaboration with the aim of developing a harmonized protocol for manual segmentation of hippocampal and parahippocampal subregions on high‐resolution MRI. In this commentary we discuss the goals for this protocol and the associated key challenges involved in its development. These include differences among existing anatomical reference materials, striking the right balance between reliability of measurements and anatomical validity, and the development of a versatile protocol that can be adopted for the study of populations varying in age and health. The commentary outlines these key challenges, as well as the proposed solution of each, with concrete examples from our working plan. Finally, with two examples, we illustrate how the harmonized protocol, once completed, is expected to impact the field by producing measurements that are quantitatively comparable across labs and by facilitating the synthesis of findings across different studies. © 2016 Wiley Periodicals, Inc.     

Cannabinoids prevent the differential long‐term effects of exposure to severe stress on hippocampal‐ and amygdala‐dependent memory and plasticity

Exposure to excessive or uncontrolled stress is a major factor associated with various diseases including posttraumatic stress disorder (PTSD). The consequences of exposure to trauma are affected not only by aspects of the event itself, but also by the frequency and severity of trauma reminders. It was suggested that in PTSD, hippocampal‐dependent memory is compromised while amygdala‐dependent memory is strengthened. Several lines of evidence support the role of the endocannabinoid (eCB) system as a modulator of the stress response. In this study we aimed to examine cannabinoids modulation of the long‐term effects (i.e., 1 month) of exposure to a traumatic event on memory and plasticity in the hippocampus and amygdala. Following exposure to the shock and reminders model of PTSD in an inhibitory avoidance light‐dark apparatus rats demonstrated: (i) enhanced fear retrieval and impaired inhibitory extinction (Ext), (ii) no long‐term potentiation (LTP) in the CA1, (iii) impaired hippocampal‐dependent short‐term memory in the object location task, (iv) enhanced LTP in the amygdala, and (v) enhanced amygdala‐dependent conditioned taste aversion memory. The cannabinoid CB1/2 receptor agonist WIN55‐212,2 (0.5mg/kg, i.p.) and the fatty acid amide hydrolase (FAAH) inhibitor URB597 (0.3mg/kg, i.p.), administered 2 hr after shock exposure prevented these opposing effects on hippocampal‐ and amygdala‐dependent processes. Moreover, the effects of WIN55‐212,2 and URB597 on Ext and acoustic startle were prevented by co‐administration of a low dose of the CB1 receptor antagonist AM251 (0.5mg/kg, i.p.), suggesting that the preventing effects of both drugs are mediated by CB1 receptors. Exposure to shock and reminders increased CB1 receptor levels in the CA1 and basolateral amygdala 1 month after shock exposure and this increase was also prevented by administering WIN55‐212,2 or URB597. Taken together, these findings suggest the involvement of the eCB system, and specifically CB1 receptors, in the opposite effects of severe stress on memory and plasticity in the hippocampus and amygdala.     

Maternal folic acid supplementation and infant birthweight in low‐ and middle‐income countries: A systematic review

The relationship between maternal folic acid supplementation in pregnancy and infant birthweight has not been well described in low‐ and middle‐income countries. We conducted a systematic review and meta‐analysis of the current evidence of the association between folic acid supplementation in pregnancy on three primary outcomes: the incidence of low birthweight, small for gestational age, and mean birthweight. Seventeen studies were identified, which satisfied the inclusion criteria, covering a total of 275,421 women from 13 cohort studies and four randomized controlled trials. For the primary outcome of mean birthweight (n = 9), the pooled mean difference between folic acid and control groups was 0.37 kg (95% confidence interval [CI]: 0.24 to 0.50), and this effect was larger in the randomized controlled trials (0.56, 95% CI: 0.15 to 0.97, n = 3). The pooled odds ratio was 0.59 for low birthweight (95% CI: 0.47 to 0.74, n = 10) among folic acid supplementation versus control. The pooled odds ratio for the association with small for gestational age was 0.63 (95% CI: 0.39 to 1.01, n = 5). Maternal folic acid supplementation in low‐ and middle‐income countries was associated with an increased mean birthweight of infants and decreases in the incidence of low birthweight and small for gestational age.     

Aggressive symptoms in children with tic disorders

Episodes of explosive anger and aggression are reported in patients with tic disorders and probably contribute to psychosocial stress and low quality of life. The source of these symptoms is controversial. The objective of the study was to study the relationship between tic disorders, their associated comorbidities, and aggressive behavior. The cohort included 47 children and adolescents (age 7–17 years) with Tourette syndrome or other chronic tic disorders attending a tertiary pediatric Tourette clinic. Associated psychopathology was assessed with the Yale Global Tic Severity Scale, Yale Brown Obsessive Compulsive Scale, Conners ADHD Rating Scale, Screen for Child Anxiety-Related Emotional Disorders, and Child Depression Inventory. Aggression was assessed with the Overt Aggression Scale and scores were compared with a group of 32 healthy age- and sex-matched children. There were no significant differences in aggression scores between the children with tic disorders and controls. Verbal aggression was the most prevalent type of aggression, found in 70% of the patients with tic disorders. The level of aggression was not correlated to tic severity. Comorbid attention-deficit hyperactivity disorder and obsessive–compulsive disorder increased the probability of aggressive behavior in patients with tic disorders. On regression analysis, the only significant predictor of aggression was the severity of attention-deficit hyperactivity disorder. This study suggests that there is no difference in aggressive behavior between children with tics without comorbidities and healthy children. It is possible that aggressive behavior in children with tic disorders is predominantly associated with comorbid attention-deficit hyperactivity disorder.

     

An open‐label extension long‐term study of the safety and efficacy of aripiprazole for irritability in children and adolescents with autistic disorder in Japan

Aim

The purpose of this study was to evaluate the long‐term safety and efficacy of aripiprazole in treating irritability in pediatric patients (6–17 years) with autistic disorder (AD) in Japan.

Methods

In this open‐label extension study, patients who had completed a previous randomized, double‐blind, placebo‐controlled 8‐week study were enrolled and were flexibly dosed with aripiprazole (1–15 mg/day) until the new indication of irritability in pediatric autism spectrum disorder was approved in Japan.

Results

Seventy (81%) out of 86 enrolled patients completed week‐48 assessments. The mean duration of treatment was 694.9 days. The mean daily dose of aripiprazole over the treatment period was 7.2 mg and the mean of the final dose was 8.5 mg. The most common treatment‐emergent adverse events (TEAE; ≥20%) included nasopharyngitis, somnolence, influenza, and increased weight. The majority of these TEAE were mild or moderate in severity, and there were no deaths, and no clinically relevant findings in laboratory values except prolactin decrease, vital signs, height, or ECG parameters. At week 48 (observed case), the mean change from baseline in the Irritability subscale score for the Aberrant Behavior Checklist Japanese Version was ?6.3 in prior placebo patients and ?2.6 in prior aripiprazole patients.

Conclusion

Aripiprazole was generally safe, well tolerated, and effective in the long‐term treatment of irritability associated with AD in Japanese pediatric patients.