Appendiceal sonography in children: A retrospective analysis as a platform for potential implementation of diagnostic categories

- Background Sonography is an important diagnostic tool in children with suspected appendicitis. Reported accuracy and appendiceal visualisation rates vary significantly, as does the management of equivocal ultrasound findings. The aim of this study was to audit appendiceal sonography at a tertiary children's hospital, and provide baseline data for a future prospective study. - Summary of work Records of children who underwent ultrasound studies for possible appendicitis between January 2008 and December 2010 were reviewed. Variables included patient demographics, sonographic appendix characteristics, and secondary signs. Descriptive statistics and analysis using ANOVA, Mann-Whitney U test, and ROC curves were performed. Mater Human Research Ethic Committee approval was granted. - Summary of results There were 457 eligible children. Using a dichotomous diagnostic model (including equivocal results), sensitivity was 89.6%, specificity 91.6%, and diagnostic yield of 40.7%. ROC curve analysis of a 6mm diameter cut-off was 0.88 AUC (95% CI 0.80 to 0.95). - Discussion and conclusions Sonography is an accurate test for acute appendicitis in children, with a high sensitivity and negative predictive value. A diameter of 6mm as an absolute cut-off in a binary model can lead to false findings. Results were compared with available literature. Recent publications propose categorising diameter1 and integrating secondary signs2 to improve accuracy and provide more meaningful results to clinicians. This study will be a benchmark for future studies with multiple diagnostic categorisation.

Methylenetetrahydrofolate reductase gene polymorphisms and risk of acute lymphoblastic leukemia in children

Methylenetetrahydrofolate reductase (MTHFR) is a critical enzyme in folate metabolism and is involved in DNA synthesis, DNA repair and DNA methylation. Genetic polymorphisms of this enzyme have been shown to impact several diseases, including cancer. Leukemias are malignancies arising from rapidly proliferating hematopoietic cells having great requirement of DNA synthesis. This case-control study was undertaken to analyze the association of the MTHFR gene polymorphisms 677 C"T and 1298 A"C and the risk of acute lymphoblastic leukemia in children. Materials and Methods: Eighty-six patients aged below 15 years with a confirmed diagnosis of acute lymphoblastic leukemia (ALL) and 99 matched controls were taken for this study. Analysis of the polymorphisms was done using the polymerase chain reaction -restriction fragment length polymorphism (PCR-RFLP) method. Results: Frequency of MTHFR 677 CC and CT were 85.9% and 14.1% in the controls, and 84.9% and 15.1% in the cases. The 'T' allele frequency was 7% and 7.5% in cases and controls respectively. The frequency of MTHFR 1298 AA, AC, and CC were 28.3%, 55.6% and 16.1% for controls and 23.3%, 59.3% and 17.4% for cases respectively. The 'C' allele frequency for 1298 A→C was 43.9% and 47% respectively for controls and cases. The odds ratio (OR) for C677T was 1.08 (95% CI 0.48- 2.45, p = 0.851) and OR for A1298C was 1.29(95% CI 0.65-2.29, p = 0.46) and OR for 1298 CC was 1.31 (95% CI 0.53-3.26, p =0.56). The OR for the combined heterozygous status (677 CT and 1298 AC) was 1.94 (95% CI 0.58 -6.52, p = 0.286). Conclusion: The prevalence of 'T' allele for 677 MTHFR polymorphism was low in the population studied. There was no association between MTHFR 677 C→T and 1298 A→C gene polymorphisms and risk of ALL, which may be due to the small sample size.

Cognitive Functioning in Alcohol and Other Substance Use Disorders in Young Adulthood : A Genetic Epidemiological Study

Alcohol and other substance use disorders (SUDs) result in great costs and suffering for individuals and families and constitute a notable public health burden. A multitude of factors, ranging from biological to societal, are associated with elevated risk of SUDs, but at the level of individuals, one of the best predictors is a family history of SUDs. Genetically informative twin and family studies have consistently indicated this familial risk to be mainly genetic. In addition, behavioral and temperamental factors such as early initiation of substance use and aggressiveness are associated with the development of SUDs. These familial, behavioral and temperamental risk factors often co-occur, but their relative importance is not well known. People with SUDs have also been found to differ from healthy controls in various domains of cognitive functioning, with poorer verbal ability being among the most consistent findings. However, representative population-based samples have rarely been used in neuropsychological studies of SUDs. In addition, both SUDs and cognitive abilities are influenced by genetic factors, but whether the co-variation of these traits might be partly explained by overlapping genetic influences has not been studied. Problematic substance use also often co-occurs with low educational level, but it is not known whether these outcomes share part of their underlying genetic influences. In addition, educational level may moderate the genetic etiology of alcohol problems, but gene-environment interactions between these phenomena have also not been widely studied. The incidence of SUDs peaks in young adulthood rendering epidemiological studies in this age group informative. This thesis investigated cognitive functioning and other correlates of SUDs in young adulthood in two representative population-based samples of young Finnish adults, one of which consisted of monozygotic and dizygotic twin pairs enabling genetically informative analyses. Using data from the population-based Mental Health in Early Adulthood in Finland (MEAF) study (n=605), the lifetime prevalence of DSM-IV any substance dependence or abuse among persons aged 21—35 years was found to be approximately 14%, with a majority of the diagnoses being alcohol use disorders. Several correlates representing the domains of behavioral and affective factors, parental factors, early initiation of substance use, and educational factors were individually associated with SUDs. The associations between behavioral and affective factors (attention or behavior problems at school, aggression, anxiousness) and SUDs were found to be largely independent of factors from other domains, whereas daily smoking and low education were still associated with SUDs after adjustment for behavioral and affective factors. Using a wide array of neuropsychological tests in the MEAF sample and in a subsample (n=602) of the population-based FinnTwin16 (FT16) study, consistent evidence of poorer verbal cognitive ability related to SUDs was found. In addition, participants with SUDs performed worse than those without disorders in a task assessing psychomotor processing speed in the MEAF sample, whereas no evidence of more specific cognitive deficits was found in either sample. Biometrical structural equation models of the twin data suggested that both alcohol problems and verbal ability had moderate heritabilities (0.54—0.72), and that their covariation could be explained by correlated genetic influences (genetic correlations -0.20 to -0.31). The relationship between educational level and alcohol problems, studied in the full epidemiological FT16 sample (n=4,858), was found to reflect both genetic correlation and gene-environment interaction. The co-occurrence of low education and alcohol problems was influenced by overlapping genetic factors. In addition, higher educational level was associated with increased relative importance of genetic influences on alcohol problems, whereas environmental influences played a more important role in young adults with lower education. In conclusion, SUDs, especially alcohol abuse and dependence, are common among young Finnish adults. Behavioral and affective factors are robustly related to SUDs independently of many other factors, and compared to healthy peers, young adults who have had SUDs during their life exhibit significantly poorer verbal cognitive ability, and possibly less efficient psychomotor processing. Genetic differences between individuals explain a notable proportion of individual differences in risk of alcohol dependence, verbal ability, and educational level, and the co-occurrence of alcohol problems with poorer verbal cognition and low education is influenced by shared genetic backgrounds. Finally, various environmental factors related to educational level in young adulthood moderate the relative importance of genetic factors influencing the risk of alcohol problems, possibly reflecting differences in social control mechanisms related to educational level.

Phonological Mean Length of Utterance as an indicator of typical and impaired phonological development in children acquiring Finnish

The aim of this study was to examine the applicability of the Phonological Mean Length of Utterance (pMLU) method to the data of children acquiring Finnish, for both typically developing children and children with a Specific Language Impairment (SLI). Study I examined typically developing children at the end of the one-word stage (N=17, mean age 1;8), and Study II analysed children s (N=5) productions in a follow-up study with four assessment points (ages 2;0, 2;6, 3;0, 3;6). Study III was carried out in the form of a review article that examined recent research on the phonological development of children acquiring Finnish and compared the results with general trends and cross-linguistic findings in phonological development. Study IV included children with SLI (N=4, mean age 4;10) and age-matched peers. The analyses in Studies I, II and IV were made using the quantitative pMLU method. In the pMLU method, pMLU values are counted for both the words that the children targeted (so-called target words) and the words produced by the children. When the child s average pMLU value was divided with the average target word pMLU value, it is possible to examine that child s accuracy in producing the words with the Whole-Word Proximity (PWP) value. In addition, the number of entirely correctly produced words is counted to obtain the Whole-Word Correctness (PWC) value. Qualitative analyses were carried out in order to examine how the children s phoneme inventories and deficiencies in phonotactics would explain the observed pMLU, PWP and PWC values. The results showed that the pMLU values for children acquiring Finnish were relatively high already at the end of the one-word stage (Study I). The values were found to reflect the characteristics of the ambient language. Typological features that lead to cross-linguistic differences in pMLU values were also observed in the review article (Study III), which noted that in the course of phonological acquisition there are a large number of language-specific phenomena and processes. Study II indicated that overall the children s phonological development during the follow-up period was reflected in the pMLU, PWP and PWC values, although the method showed limitations in detecting qualitative differences between the children. Correct vowels were not scored in the pMLU counts, which led to some misleadingly high pMLU and PWP results: vowel errors were only reflected in the PWC values. Typically developing children in Study II reached the highest possible pMLU results already around age 3;6. At the same time, the differences between the children with SLI and age-matched peers in the pMLU values were very prominent (Study IV). The values for the children with SLI were similar to the ones reported for two-year-old children. Qualitative analyses revealed that the phonologies of the children with SLI largely resembled the ones of younger, typically developing children. However, unusual errors were also witnessed (e.g., vowel errors, omissions of word-initial stops, consonants added to the initial position in words beginning with a vowel). This dissertation provides an application of a new tool for quantitative phonological assessment and analysis in children acquiring Finnish. The preliminary results suggest that, with some modifications, the pMLU method can be used to assess children s phonological development and that it has some advantages compared to the earlier, segment-oriented approaches. Qualitative analyses complemented the pMLU s observations on the children s phonologies. More research is needed in order to verify the levels of the pMLU, PWP and PWC values in children acquiring Finnish.

Vitamin D deficiency in children with chronic illnesses: Predisposing and protecting factors

This thesis assesses clinical differences in patients with low and high vitamin D levels. The factors analyzed included the underlying disease, body size, age, ethnic background, use of vitamin D supplements and the season when the blood sample was taken. Fifty patients with the lowest and 50 patients with the highest vitamin D concentrations were selected from a cohort of 1351 chronically ill children and adolescents who had had their vitamin D status assessed at Children's Hospital. Protective factors appeared to be the usage of vitamin D supplements and young age, especially age <2 years. Predisposing factors included non-Finnish ethnic background and older age, especially age 12-18 years. High vitamin D values were more prevalent in the summer and autumn and low values in the winter and spring. Patients with non-Finnish background were overrepresented in the low value group. No differences regarding the underlying diseases could be detected. Conclusions: In the Northern latitudes UVB-radiation is insufficient for vitamin D synthesis. Vitamin D recommendations appear to be inadequate to fulfill the needs of chronically ill patients whose requirements for vitamin D are elevated compared to the general population. New guidelines for vitamin D supplementation are needed particularly for those at risk of developing vitamin D deficiency.

Non-polio enteroviruses and their association with acute diarrhea in children in India

A causative agent in approximately 40% of diarrhea] cases. still remains unidentified. Though many enteroviruses (EVs) are transmitted through fecal-oral route and replicate in the intestinal cells, their association with acute diarrhea has not so far been recognized due to lack of detailed epidemiological investigations. This long-term, detailed molecular epidemiological study aims to conclusively determine the association of non-polio enteroviruses (NPEVs) with acute diarrhea in comaparison with rotavirus (RV) in children. Diarrheal stool specimens from 2161 children aged 0-2 years and 169 children between 2 and 9 years, and 1800 normal stool samples from age-matched healthy children between 0 and 9 years were examined during 2008-2012 for enterovirus (oral polio vaccine strains (OPVs) and NPEVs). Enterovirus serotypes were identified by complete VP1 gene sequence analysis. Enterovirus and rotavirus were detected in 19.01% (380/2330) and 13.82% (322/2330) diarrheal stools. During the study period, annual prevalence of EV- and RV-associated diarrhea ranged between 8% and 22%, but with contrasting seasonal prevalence with RV predominating during winter months and NPEV prevailing in other seasons. NPEVs are associated with epidemics-like outbreaks during which they are detected in up to 50% of diarrheic children, and in non-epidemic seasons in 0-10% of the patients. After subtraction of OPV-positive diarrheal cases (1.81%), while NPEVs are associated with about 17% of acute diarrhea, about 6% of healthy children showed asymptomatic NPEV excretion. Of 37 NPEV serotypes detected in diarrheal children, seven echovirus types 1, 7, 11, 13, 14, 30 and 33 are frequently observed, with Ell being more prevalent followed by E30. In conclusion, NPEVs are significantly associated with acute diarrhea, and NPEVs and rotavirus exhibit contrasting seasonal predominance. This study signifies the need for a new direction of research on enteroviruses involving systematic analysis of their contribution to diarrheal burden. (C) 2013 Elsevier B.V. All rights reserved.

Non-polio enterovirus association with persistent diarrhea in children as revealed by a follow-up study of an Indian cohort during the first two years of life

Background: We recently reported significant association of non-polio enteroviruses (NPEVs) with acute diarrhea in children. Persistent diarrhea (PD) remains a major cause of morbidity and mortality in infants below two years of age in developing countries. Understanding age-dependent frequency and duration of NPEV infections is important to determine their association with persistent diarrhea and disease burden. Objectives: A cohort of 140 infants was followed for 6 months to 2 years of age to determine the frequency, duration, and association with PD of NPEV infections in comparison with rotavirus and other agents. Study design: Stool samples were collected every 14 days, and diarrheal episodes and their duration were recorded. Enteroviruses were characterized by RT-PCR and VP1 gene sequence analysis, rotavirus by electropherotyping, and other agents by PCR. Results: Of 4545 samples, negative for oral polio vaccine strains, 3907 (85.96%) and 638 (14.04%) were NPEV-negative and NPEV-positive, respectively, representing 403 (8.87%) infection episodes. About 68% of NPEV infections occurred during the first year with every child having at least one episode lasting between four days and four months. Approximately 38% and 22% of total diarrheal episodes were positive for NPEV and RV, respectively. While about 18% of NPEV infection episodes were associated with diarrhea, 6% being persistent, 13% of total diarrheal episodes were persistent involving infections by monotype NPEV strains or sequential infections by multiple strains and other agents. Conclusions: This is the first report revealing NPEVs as the single most frequently and persistently detected viral pathogen in every PD episode. (C) 2014 Elsevier B.V. All rights reserved.

Maintaining local displacive disorders in Na0.5Bi0.5TiO3 piezoceramics by K0.5Bi0.5TiO3 substitution

A comprehensive global and local structural characterization using X-ray and neutron diffraction, and EXAFS have been performed to investigate the effect of electrical poling on the structure of (1-x)Na0.5Bi0.5TiO3-(x)K0.5Bi0.5TiO3 compositions. While the annealed samples showed definite indication of presence of local displacive disorders in all the compositions studied (0 ing the samples. The tendency of electric field to reduce the local displacive disorder decreased with increasing K0.5Bi0.5TiO3 content in the samples. (C) 2016 Elsevier Ltd. All rights reserved.

Insulin analog preparations and their use in children and adolescents with type 1 diabetes mellitus.

Standard or 'traditional' human insulin preparations such as regular soluble insulin and neutral protamine Hagedorn (NPH) insulin have shortcomings in terms of their pharmacokinetic and pharmacodynamic properties that limit their clinical efficacy. Structurally modified insulin molecules or insulin 'analogs' have been developed with the aim of delivering insulin replacement therapy in a more physiological manner. In the last 10 years, five insulin analog preparations have become commercially available for clinical use in patients with type 1 diabetes mellitus: three 'rapid' or fast-acting analogs (insulin lispro, aspart, and glulisine) and two long-acting analogs (insulin glargine and detemir). This review highlights the specific pharmacokinetic properties of these new insulin analog preparations and focuses on their potential clinical advantages and disadvantages when used in children and adolescents with type 1 diabetes mellitus. The fast-acting analogs specifically facilitate more flexible insulin injection timing with regard to meals and activities, whereas the long-acting analogs have a more predictable profile of action and lack a peak effect. To date, clinical trials in children and adolescents have been few in number, but the evidence available from these and from other studies carried out in adults with type 1 diabetes suggest that they offer significant benefits in terms of reduced frequency of nocturnal hypoglycemia, better postprandial blood glucose control, and improved quality of life when compared with traditional insulins. In addition, insulin detemir therapy is unique in that patients may benefit from reduced risk of excessive weight, particularly during adolescence. Evidence for sustained long-term improvements in glycosylated hemoglobin, on the other hand, is modest. Furthermore, alterations to insulin/insulin-like growth factor I receptor binding characteristics have also raised theoretical concerns that insulin analogs may have an increased mitogenic potential and risk of tumor development, although evidence from both in vitro and in vivo animal studies do not support this assertion. Long-term surveillance has been recommended and further carefully designed prospective studies are needed to evaluate the overall benefits and clinical efficacy of insulin analog therapy in children and adolescents with type 1 diabetes.

Two Glass Transitions Associated to Different Dynamic Disorders in the Nematic Glassy State of a Non-Symmetric Liquid Crystal Dimer Dopped with gamma-Alumina Nanoparticles

In the present work, the nematic glassy state of the non-symmetric LC dimer -(4-cyanobiphenyl-4-yloxy)--(1-pyrenimine-benzylidene-4-oxy) undecane is studied by means of calorimetric and dielectric measurements. The most striking result of the work is the presence of two different glass transition temperatures: one due to the freezing of the flip-flop motions of the bulkier unit of the dimer and the other, at a lower temperature, related to the freezing of the flip-flop and precessional motions of the cyanobiphenyl unit. This result shows the fact that glass transition is the consequence of the freezing of one or more coupled dynamic disorders and not of the disordered phase itself. In order to avoid crystallization when the bulk sample is cooled down, the LC dimer has been confined via the dispersion of -alumina nanoparticles, in several concentrations.

Prenatal stress modifies hippocampal synaptic plasticity and spatial learning in young rat offspring

Clinical studies demonstrate that prenatal stress causes cognitive deficits and increases vulnerability to affective disorders in children and adolescents. The underlying mechanisms are not yet fully understood. Here, we reported that prenatal stress (10

Measurement of respiratory acoustic impedance in children by a modified forced oscillation method

An introduction to a modified forced oscillation method, square-wave excitation technique, including fundamentals and methods, as used in respiratory function examination. On the basis of experimental results and theoretical predictions, we suggest that Respiratory Acoustic Impedance (RAI) measurement by spectral analysis can significantly improve estimation of contribution to RAI from different part of respiratory tract. The outcome is of considerable interest in the study of lung disease, such as COPD and asthma in young children.

Effects of Naotan Pill on repair of neural cells and cognitive disorders in juvenile rats following hypoxia and ischemia

BACKGROUND: Hypoxia and ischemia induce neuronal damage, decreased neuronal numbers and synaptophysin levels, and deficits in learning and memory functions. Previous studies have shown that lycium barbarum polysaccharide, the most effective component of barbary wolfberry fruit, has protective effects on neural cells in hypoxia-ischemia. OBJECTIVE: To investigate the effects of Naotan Pill on glutamate-treated neural cells and on cognitive function in juvenile rats following hypoxia-ischemia. DESIGN, TIME AND SETTING: The randomized, controlled, in vivo study was performed at the Cell Laboratory of Lanzhou University, Lanzhou Institute of Modern Physics of Chinese Academy of Sciences, and Department of Traditional Chinese Medicine of Gansu Provincial Rehabilitation Center Hospital, China from December 2005 to August 2006. The cellular neurobiology, in vitro experiment was conducted at the Institute of Human Anatomy, Histology, Embryology and Neuroscience, School of Basic Medical Sciences, Lanzhou University, and Department of Traditional Chinese Medicine of Gansu Provincial Rehabilitation Center Hospital, China from March 2007 to January 2008. MATERIALS: Naotan Pill, composed of barbary wolfberry fruit, danshen root, grassleaf sweetflag rhizome, and glossy privet fruit, was prepared by Gansu Provincial Rehabilitation Center, China. Rabbit anti-synaptophysin, choline acetyl transferase polyclonal antibody, streptavidin-biotin complex kit and diaminobenzidine kit (Boster, Wuhan, China), as well as glutamate (Hualian, Shanghai, China) were used in this study. METHODS: Cortical neural cells were isolated from neonatal Wistar rats. Neural cell damage models were induced using glutamate, and administered Naotan Pill prior to and following damage. A total of 54 juvenile Wistar rats were equally and randomly assigned into model, Naotan Pill, and sham operation groups. The left common carotid artery was ligated, and then rat models of hypoxic-ischemic injury were assigned to the model and Naotan Pill groups. At 2 days following model induction, rats in the Naotan Pill group were administered Naotan Pill suspension for 21 days. In the model and sham operation groups, rats received an equal volume of saline. MAIN OUTCOME MEASURES: Neural cell morphology was observed using an inverted phase contrast microscope. Survival rate of neural cells was measured by MTT assay. Synaptophysin and choline acetyl transferase expression was observed in the hippocampal CA1 region of juvenile rats using immunohistochemistry. Cognitive function was tested by the Morris water maze. RESULTS: Pathological changes were detected in glutamate-treated neural cells. Neural cell morphology remained normal after Naotan Pill intervention. Absorbance and survival rate of neural cells were significantly greater following Naotan Pill intervention, compared to glutamate-treated neural cells (P < 0.05). Synaptophysin and choline acetyl transferase expression was lowest in the hippocampal CA1 region in the model group and highest in the sham operation group. Significant differences among groups were observed (P < 0.05). Escape latency and swimming distance were significantly longer in the model group compared to the Naotan Pill group (P < 0.05). CONCLUSION: Naotan Pill exhibited protective and repair effects on glutamate-treated neural cells. Naotan Pill upregulated synaptophysin and choline acetyl transferase expression in the hippocampus and improved cognitive function in rats following hypoxia-ischemia.

Orthodontic and orthopaedic treatment for anterior open bite in children

BackgroundAnterior open bite occurs when there is a lack of vertical overlap of the upper and lower incisors. the aetiology is multifactorial including: oral habits, unfavourable growth patterns, enlarged lymphatic tissue with mouth breathing. Several treatments have been proposed to correct this malocclusion, but interventions are not supported by strong scientific evidence.ObjectivesThe aim of this systematic review was to evaluate orthodontic and orthopaedic treatments to correct anterior open bite in children.Search methodsThe following databases were searched: the Cochrane Oral Health Group's Trials Register (to 14 February 2014); the Cochrane Central Register of Controlled Trials (CENTRAL)(The Cochrane Library 2014, Issue 1); MEDLINE via OVID (1946 to 14 February 2014); EMBASE via OVID (1980 to 14 February 2014); LILACS via BIREME Virtual Health Library (1982 to 14 February 2014); BBO via BIREME Virtual Health Library (1980 to 14 February 2014); and SciELO (1997 to 14 February 2014). We searched for ongoing trials via ClinicalTrials.gov (to 14 February 2014). Chinese journals were handsearched and the bibliographies of papers were retrieved.Selection criteriaAll randomised or quasi-randomised controlled trials of orthodontic or orthopaedic treatments or both to correct anterior open bite in children.Data collection and analysisTwo review authors independently assessed the eligibility of all reports identified.Risk ratios (RRs) and corresponding 95% confidence intervals (CIs) were calculated for dichotomous data. the continuous data were expressed as described by the author.Main resultsThree randomised controlled trials were included comparing: effects of Frankel's function regulator-4 (FR-4) with lip-seal training versus no treatment; repelling-magnet splints versus bite-blocks; and palatal crib associated with high-pull chincup versus no treatment.The study comparing repelling-magnet splints versus bite-blocks could not be analysed because the authors interrupted the treatment earlier than planned due to side effects in four of ten patients.FR-4 associated with lip-seal training (RR = 0.02 (95% CI 0.00 to 0.38)) and removable palatal crib associated with high-pull chincup (RR = 0.23 (95% CI 0.11 to 0.48)) were able to correct anterior open bite.No study described: randomisation process, sample size calculation, there was not blinding in the cephalometric analysis and the two studies evaluated two interventions at the same time. These results should be therefore viewed with caution.Authors' conclusionsThere is weak evidence that the interventions FR-4 with lip-seal training and palatal crib associated with high-pull chincup are able to correct anterior open bite. Given that the trials included have potential bias, these results must be viewed with caution. Recommendations for clinical practice cannot be made based only on the results of these trials. More randomised controlled trials are needed to elucidate the interventions for treating anterior open bite.