MGMT and MLH1 methylation in Helicobacter pylori-infected children and adults

AIM: To evaluate the association between Helicobacter pylori(H. pylori) infection and MLH1 and MGMT methylation and its relationship with microsatellite instability (MSI). METHODS: The methylation status of the MLH1 and MGMT promoter region was analysed by methylation specific methylation-polymerase chain reaction (MSPPCR) in gastric biopsy samples from uninfected or H. pylori -infected children (n = 50), from adults with chronic gastritis (n = 97) and from adults with gastric cancer (n = 92). MLH1 and MGMT mRNA expression were measured by real-time PCR and normalised to a constitutive gene (β actin). MSI analysis was performed by screening MSI markers at 4 loci (Bat-25, Bat-26, D17S250 and D2S123) with PCR; PCR products were analysed by single strand conformation polymorphism followed by silver staining. Statistical analyses were performed with either the χ 2 test with Yates continuity correction or Fisher's exact test, and statistical significance for expression analysis was assessed using an unpaired Student's t -test. RESULTS: Methylation was not detected in the promoter regions of MLH1 and MGMT in gastric biopsy samples from children, regardless of H. pylori infection status. The MGMT promoter was methylated in 51% of chronic gastritis adult patients and was associated with H. pylori infection (P < 0.05); this region was methylated in 66% of gastric cancer patients, and the difference in the percentage of methylated samples between these patients and those from H. pylori -infected chronic gastritis patients was statistically significant (P < 0.05). MLH1 methylation frequencies among H. pylori -infected and non-infected chronic gastritis adult patients were 13% and 7%, respectively. We observed methylation of the MLH1 promoter (39%) and increased MSI levels (68%) in samples from gastric cancer patients in comparison to samples from H. pylori -infected adult chronic gastritis patients (P < 0.001 and P < 0.01, respectively). The frequency of promoter methylation for both genes was higher in gastric cancer samples than in H. pylori -positive chronic gastritis samples (P < 0.05). The levels of MLH1 and MGMT mRNA were significantly reduced in chronic gastritis samples that were also hypermethylated (P < 0.01). MGMT promoter region was analysed by methylation specific methylation-polymerase chain reaction (MSPPCR) in gastric biopsy samples from uninfected or H. pylori -infected children (n = 50), from adults with chronic gastritis (n = 97) and from adults with gastric cancer (n = 92). MLH1 and MGMT mRNA expression were measured by real-time PCR and normalised to a constitutive gene (β actin). MSI analysis was performed by screening MSI markers at 4 loci (Bat-25, Bat-26, D17S250 and D2S123) with PCR; PCR products were analysed by single strand conformation polymorphism followed by silver staining. Statistical analyses were performed with either the χ 2 test with Yates continuity correction or Fisher's exact test, and statistical significance for expression analysis was assessed using an unpaired Student's t -test. RESULTS: Methylation was not detected in the promoter regions of MLH1 and MGMT in gastric biopsy samples from children, regardless of H. pylori infection status. The MGMT promoter was methylated in 51% of chronic gastritis adult patients and was associated with H. pylori infection (P < 0.05); this region was methylated in 66% of gastric cancer patients, and the difference in the percentage of methylated samples between these patients and those from H. pylori -infected chronic gastritis patients was statistically significant (P < 0.05). MLH1 methylation frequencies among H. pylori -infected and non-infected chronic gastritis adult patients were 13% and 7%, respectively. We observed methylation of the MLH1 promoter (39%) and increased MSI levels (68%) in samples from gastric cancer patients in comparison to samples from H. pylori -infected adult chronic gastritis patients (P < 0.001 and P < 0.01, respectively). The frequency of promoter methylation for both genes was higher in gastric cancer samples than in H. pylori -positive chronic gastritis samples (P < 0.05). The levels of MLH1 and MGMT mRNA were significantly reduced in chronic gastritis samples that were also hypermethylated (P < 0.01). CONCLUSION: In summary, MGMT and MLH1 methylation did not occur in earlier-stage H. pylori infections and thus might depend on the duration of infection. © 2013 Baishideng. All rights reserved.

Morphological integration between the cranial base and the face in children and adults

The primary aim of the present study was to assess morphological covariation between the face and the basicranium (midline and lateral), and to evaluate patterns of integration at two specific developmental stages. A group of 71 children (6-10 years) was compared with a group of 71 adults (20-35 years). Lateral cephalometric radiographs were digitized and a total of 28 landmarks were placed on three areas; the midline cranial base, the lateral cranial base and the face. Geometric morphometric methods were applied and partial least squares analysis was used to evaluate correlation between the three shape blocks. Morphological integration was tested both with and without removing the effect of allometry. In children, mainly the midline and, to a lesser extent, the lateral cranial base were moderately correlated to the face. In adults, the correlation between the face and the midline cranial base, which ceases development earlier than the lateral base, was reduced. However, the lateral cranial base retained and even strengthened its correlation to the face. This suggests that the duration of common developmental timing is an important factor that influences integration between craniofacial structures. However, despite the apparent switch of primary roles between the cranial bases during development, the patterns of integration remained stable, thereby supporting the role of genetics over function in the establishment and development of craniofacial shape.

Systemic therapy of atopic dermatitis in children and adults

Systemic therapy is required in patients with severe atopic dermatitis (AD) refractory to adequate topical therapy. The aim of a systemic therapy is the rapid and efficient improvement of skin symptoms and pruritus in acute exacerbation and/or the long-term control of severe chronic disease. A number of immunosuppressive and immunomodulating substances are available that may efficiently reduce skin inflammation and thus lead to a relief of symptoms including pruritus. The excellent effects of cyclosporine as short-term as well as maintenance therapy have been documented in several studies in children and adults. Furthermore, other immunosuppressive substances such as azathioprine, mycophenolate mofetil and methotrexate are effective in patients with moderate to severe AD. Intravenous immunoglobulins and γ-interferon exert immunomodulatory effects and thus may improve severe AD. Biological agents are a new approach in AD therapy since they may specifically target cells, cytokines or mediators involved in the pathogenesis of AD.

Reproducibility of acute mountain sickness in children and adults: a prospective study

Although a history of previous acute mountain sickness (AMS) is commonly used for providing advice and recommending its prophylaxis during subsequent exposure, the intraindividual reproducibility of AMS during repeated high-altitude exposure has never been examined in a prospective controlled study.

Serum concentrations of lectin-pathway components in healthy neonates, children and adults: mannan-binding lectin (MBL), M-, L-, and H-ficolin, and MBL-associated serine protease-2 (MASP-2)

This study aimed to measure serum concentrations of five lectin-pathway components, mannan-binding lectin (MBL), M-ficolin, L-ficolin, H-ficolin, and MBL-associated serine protease-2 (MASP-2), in healthy neonates and children, to determine if they change with age and to compare them with serum concentrations in healthy adults. Concentrations were measured in 141 preterm and 30 term neonates, in 120 children including infants and adolescents, and in 350 adults (97 for L-ficolin) by inhouse time-resolved immunofluorometric assays or commercially available enzyme-linked immunosorbent assays. The adjacent categories method applying Wilcoxon-Mann-Whitney tests was used to determine age categories where concentrations differed significantly. Displaying serum concentration vs. age, an inverted-U shape (higher concentrations in children than in neonates and adults) was found for MBL and the ficolins, and an S-shape for MASP-2. Serum concentrations of all five lectin-pathway components were significantly lower in preterm neonates <32-wk gestational age compared to older neonates, infants, and children. Only M-ficolin in children >1 yr and H-ficolin in term neonates and in children were found to be comparable with adult values. MBL, M-, L-, and H-ficolin, and MASP-2 serum concentrations show important changes with age. The respective normal ranges for adults should not be used in the pediatric population. The age-specific pediatric ranges established here may be used instead.

Cochlear implantation in children and adults in Switzerland

The cochlear implant (CI) is one of the most successful neural prostheses developed to date. It offers artificial hearing to individuals with profound sensorineural hearing loss and with insufficient benefit from conventional hearing aids. The first implants available some 30 years ago provided a limited sensation of sound. The benefit for users of these early systems was mostly a facilitation of lip-reading based communication rather than an understanding of speech. Considerable progress has been made since then. Modern, multichannel implant systems feature complex speech processing strategies, high stimulation rates and multiple sites of stimulation in the cochlea. Equipped with such a state-of-the-art system, the majority of recipients today can communicate orally without visual cues and can even use the telephone. The impact of CIs on deaf individuals and on the deaf community has thus been exceptional. To date, more than 300,000 patients worldwide have received CIs. In Switzerland, the first implantation was performed in 1977 and, as of 2012, over 2,000 systems have been implanted with a current rate of around 150 CIs per year. The primary purpose of this article is to provide a contemporary overview of cochlear implantation, emphasising the situation in Switzerland.

Brain mechanisms of quantity are similar in 5-year-old children and adults

Both 5-year-old children and adults determine the quantity of a number by the use of a similar parietal lobe mechanism. Event related potentials indicate that input from Arabic digits and from dot patterns reach areas involved in determining quantity about 200 ms after input. However, voluntary key presses indicating the relation of the input to the quantity five take almost three times as long in children. The ability to trace the networks of brain areas involved in the learning of school subjects should aid in the design and testing of educational methods.

There lived a wicked dragon : an environmental coloring book for children and adults /

Presents children in grade 1 through 3 with information about environmental dangers and ecology.

Attentional bias toward fear-related stimuli: An investigation with nonselected children and adults and children with anxiety disorders

Research investigating anxiety-related attentional bias for emotional information in anxious and nonanxious children has been equivocal with regard to whether a bias for fear-related stimuli is unique to anxious children or is common to children in general. Moreover, recent cognitive theories have proposed that an attentional bias for objectively threatening stimuli may be common to all individuals, with this effect enhanced in anxious individuals. The current study investigated whether an attentional bias toward fear-related pictures could be found in nonselected children (n = 105) and adults (n = 47) and whether a sample of clinically anxious children (n = 23) displayed an attentional bias for fear-related pictures over and above that expected for nonselected children. Participants completed a dot-probe task that employed fear-related, neutral, and pleasant pictures. As expected, both adults and children showed a stronger attentional bias toward fear-related pictures than toward pleasant pictures. Consistent with some findings in the childhood domain, the extent of the attentional bias toward fear-related pictures did not differ significantly between anxious children and nonselected children. However, compared with nonselected children, anxious children showed a stronger attentional bias overall toward affective picture stimuli. (C) 2004 Elsevier Inc. All rights reserved.

Why children and adults sometimes (but not always) compute implicatures

Noveck (2001) argued that children even as old as 11 do not reliably endorse a scalar interpretation of weak scalar terms (some, might, or) (cf. Braine & Rumain, 1981; Smith, 1980). More recent studies suggest, however, that children's apparent failures may depend on the experimental demands (Papafragou & Musolino, 2003). Although previous studies involved children of different ages as well as different tasks, and are thus not directly comparable, nevertheless a common finding is that children do not seem to derive scalar implicatures to the same extent as adults do. The present article describes a series of experiments that were conducted with Italian speaking subjects (children and adults), focusing mainly on the scalar term some. Our goal was to carefully examine the specific conditions that allow the computation of implicatures by children. In so doing, we demonstrate that children as young as 7 (the youngest age of the children who participated in the Noveck study) are able to compute implicatures in experimental conditions that properly satisfy certain contextual prerequisites for deriving such implicatures. We also present further results that have general consequences for the research methodology employed in this area of study. Our research indicates that certain tasks mask children's understanding of scalar terms, not only including the task used by Noveck, but also tasks that employ certain explicit instructions, such as the training task used by Papafragou & Musolino (2003). Our findings indicate further that, although explicit training apparently improves children's ability to draw implicatures, children nevertheless fail to achieve adult levels of performance for most scalar terms even in such tasks, and that the effects of instruction do not last beyond the training session itself for most children. Another relevant finding of the present study is that some of the manipulations of the experimental context have an effect on all subjects, whereas others produce effects on just a subset of children. Individual differences of this kind may have been concealed in previous research because performance by individual subjects was not reported. Our general conclusions are that even young children (7-year olds) have the prerequisites for deriving scalar implicatures, although these abilities are revealed only when the conversational background is natural.

Testing the protracted lexical restructuring hypothesis: The effects of position and acoustic-phonetic clarity on sensitivity to mispronunciations in children and adults

Although developmental increases in the size of the position effect within a mispronunciation detection task have been interpreted as consistent with a view of the lexical restructuring process as protracted, the position effect itself might not be reliable. The current research examined the effects of position and clarity of acoustic-phonetic information on sensitivity to mispronounced onsets in 5- and 6-year-olds and adults. Both children and adults showed a position effect only when mispronunciations also differed in the amount of relevant acoustic-phonetic information. Adults' sensitivity to mispronounced second-syllable onsets also reflected the availability of acoustic-phonetic information. The implications of these findings are discussed in relation to the lexical restructuring hypothesis. (c) 2006 Elsevier Inc. All rights reserved.

Clinical Outcomes in 3343 Children and Adults with Rheumatic Heart Disease from 14 Low and Middle Income Countries: 2-Year Follow-up of the Global Rheumatic Heart Disease Registry (the REMEDY study)

BACKGROUND: -There are few contemporary data on the mortality and morbidity associated with rheumatic heart disease (RHD) or information on their predictors. We report the two year follow-up of individuals with RHD from 14 low and middle income countries in Africa and Asia.

METHODS: -Between January 2010 and November 2012, we enrolled 3343 patients from 25 centers in 14 countries and followed them for two years to assess mortality, congestive heart failure (CHF), stroke or transient ischemic attack (TIA), recurrent acute rheumatic fever (ARF), and infective endocarditis (IE).

RESULTS: -Vital status at 24 months was known for 2960 (88.5%) patients. Two thirds were female. Although patients were young (median age 28 years, interquartile range 18 to 40), the two year case fatality rate was high (500 deaths, 16.9%). Mortality rate was 116.3/1000 patient-years in the first year and 65.4/1000 patient-years in the second year. Median age at death was 28.7 years. Independent predictors of death were severe valve disease (hazard ratio (HR) 2.36, 95% confidence interval (CI) 1.80-3.11), CHF (HR 2.16, 95% CI 1.70-2.72), New York Heart Association functional class III/IV (HR 1.67, 95% CI 1.32-2.10), atrial fibrillation (AF) (HR 1.40, 95% CI 1.10-1.78) and older age (HR 1.02, 95% CI 1.01-1.02 per year increase) at enrolment. Post-primary education (HR 0.67, 95% CI 0.54-0.85) and female sex (HR 0.65, 95%CI 0.52-0.80) were associated with lower risk of death. 204 (6.9%) had new CHF (incidence, 38.42/1000 patient-years), 46 (1.6%) had a stroke or TIA (8.45/1000 patient-years), 19 (0.6%) had ARF (3.49/1000 patient-years), and 20 (0.7%) had IE (3.65/1000 patient-years). Previous stroke and older age were independent predictors of stroke/TIA or systemic embolism. Patients from low and lower-middle income countries had significantly higher age- and sex-adjusted mortality compared to patients from upper-middle income countries. Valve surgery was significantly more common in upper-middle income than in lower-middle- or low-income countries.

CONCLUSIONS: -Patients with clinical RHD have high mortality and morbidity despite being young; those from low and lower-middle income countries had a poorer prognosis associated with advanced disease and low education. Programs focused on early detection and treatment of clinical RHD are required to improve outcomes.

English syllable confusion and imitation in Korean bilingual and monolingual children and adults

In the present study, Korean-English bilingual (KEB) and Korean monolingual (KM) children, between the ages of 8 and 13 years, and KEB adults, ages 18 and older, were examined with one speech perception task, called the Nonsense Syllable Confusion Matrix (NSCM) task (Allen, 2005), and two production tasks, called the Nonsense Syllable Imitation Task (NSIT) and the Nonword Repetition Task (NRT; Dollaghan & Campbell, 1998). The present study examined (a) which English sounds on the NSCM task were identified less well, presumably due to interference from Korean phonology, in bilinguals learning English as a second language (L2) and in monolinguals learning English as a foreign language (FL); (b) which English phonemes on the NSIT were more challenging for bilinguals and monolinguals to produce; (c) whether perception on the NSCM task is related to production on the NSIT, or phonological awareness, as measured by the NRT; and (d) whether perception and production differ in three age-language status groups (i.e., KEB children, KEB adults, and KM children) and in three proficiency subgroups of KEB children (i.e., English-dominant, ED; balanced, BAL; and Korean-dominant, KD). In order to determine English proficiency in each group, language samples were extensively and rigorously analyzed, using software, called Systematic Analysis of Language Transcripts (SALT). Length of samples in complete and intelligible utterances, number of different and total words (NDW and NTW, respectively), speech rate in words per minute (WPM), and number of grammatical errors, mazes, and abandoned utterances were measured and compared among the three initial groups and the three proficiency subgroups. Results of the language sample analysis (LSA) showed significant group differences only between the KEBs and the KM children, but not between the KEB children and adults. Nonetheless, compared to normative means (from a sample length- and age-matched database provided by SALT), the KEB adult group and the KD subgroup produced English at significantly slower speech rates than expected for monolingual, English-speaking counterparts. Two existing models of bilingual speech perception and production—the Speech Learning Model or SLM (Flege, 1987, 1992) and the Perceptual Assimilation Model or PAM (Best, McRoberts, & Sithole, 1988; Best, McRoberts, & Goodell, 2001)—were considered to see if they could account for the perceptual and production patterns evident in the present study. The selected English sounds for stimuli in the NSCM task and the NSIT were 10 consonants, /p, b, k, g, f, θ, s, z, ʧ, ʤ/, and 3 vowels /I, ɛ, æ/, which were used to create 30 nonsense syllables in a consonant-vowel structure. Based on phonetic or phonemic differences between the two languages, English sounds were categorized either as familiar sounds—namely, English sounds that are similar, but not identical, to L1 Korean, including /p, k, s, ʧ, ɛ/—or unfamiliar sounds—namely, English sounds that are new to L1, including /b, g, f, θ, z, ʤ, I, æ/. The results of the NSCM task showed that (a) consonants were perceived correctly more often than vowels, (b) familiar sounds were perceived correctly more often than unfamiliar ones, and (c) familiar consonants were perceived correctly more often than unfamiliar ones across the three age-language status groups and across the three proficiency subgroups; and (d) the KEB children perceived correctly more often than the KEB adults, the KEB children and adults perceived correctly more often than the KM children, and the ED and BAL subgroups perceived correctly more often than the KD subgroup. The results of the NSIT showed (a) consonants were produced more accurately than vowels, and (b) familiar sounds were produced more accurately than unfamiliar ones, across the three age-language status groups. Also, (c) familiar consonants were produced more accurately than unfamiliar ones in the KEB and KM child groups, and (d) unfamiliar vowels were produced more accurately than a familiar one in the KEB child group, but the reverse was true in the KEB adult and KM child groups. The KEB children produced sounds correctly significantly more often than the KM children and the KEB adults, though the percent correct differences were smaller than for perception. Production differences were not found among the three proficiency subgroups. Perception on the NSCM task was compared to production on the NSIT and NRT. Weak positive correlations were found between perception and production (NSIT) for unfamiliar consonants and sounds, whereas a weak negative correlation was found for unfamiliar vowels. Several correlations were significant for perceptual performance on the NSCM task and overall production performance on the NRT: for unfamiliar consonants, unfamiliar vowels, unfamiliar sounds, consonants, vowels, and overall performance on the NSCM task. Nonetheless, no significant correlation was found between production on the NSIT and NRT. Evidently these are two very different production tasks, where immediate imitation of single syllables on the NSIT results in high performance for all groups. Findings of the present study suggest that (a) perception and production of L2 consonants differ from those of vowels; (b) perception and production of L2 sounds involve an interaction of sound type and familiarity; (c) a weak relation exists between perception and production performance for unfamiliar sounds; and (d) L2 experience generally predicts perceptual and production performance. The present study yields several conclusions. The first is that familiarity of sounds is an important influence on L2 learning, as claimed by both SLM and PAM. In the present study, familiar sounds were perceived and produced correctly more often than unfamiliar ones in most cases, in keeping with PAM, though experienced L2 learners (i.e., the KEB children) produced unfamiliar vowels better than familiar ones, in keeping with SLM. Nonetheless, the second conclusion is that neither SLM nor PAM consistently and thoroughly explains the results of the present study. This is because both theories assume that the influence of L1 on the perception of L2 consonants and vowels works in the same way as for production of them. The third and fourth conclusions are two proposed arguments: that perception and production of consonants are different than for vowels, and that sound type interacts with familiarity and L2 experience. These two arguments can best explain the current findings. These findings may help us to develop educational curricula for bilingual individuals listening to and articulating English. Further, the extensive analysis of spontaneous speech in the present study should contribute to the specification of parameters for normal language development and function in Korean-English bilingual children and adults.