Preliminary identification of key miRNAs,signaling pathways,and genes associated with Hirschsprung’s disease by analysis of tissue microRNA expression profiles

Background

Hirschsprung’s disease (HSCR) is a congenital gut motility disorder of infants, and if left untreated, it is fatal to the affected infants. This study aimed to identify key microRNAs (miRNAs), signaling pathways and genes involved in the pathogenesis of HSCR.

Methods

The miRNA microarray dataset GSE77296 was downloaded. Nine colon tissue samples were available: six from HSCR patients and three matched control samples. Differentially expressed miRNAs (DEMs) were identified after data preprocessing. Target genes of the selected upregulated and downregulated DEMs were predicted. In addition, functional enrichment analyses for the selected DEMs and target genes were conducted. Finally, interaction networks between the DEMs and target genes were constructed.

Results

A total of 162 DEMs (73 upregulated and 89 downregulated) were obtained. A total of 2511 DEM-target gene pairs for the 40 selected DEMs were identified, including 1645 pairs for the upregulated DEMs and 866 pairs for the downregulated DEMs. The upregulated DEM miR-141-3p and down-regulated DEM miR-30a-3p were identified as key miRNAs by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment and network analyses. Besides, KEGG pathway enrichment analysis revealed that pathways in cancer and the mitogen-activated protein kinase (MAPK) signaling pathway were key pathways. The key genes frizzled class receptor 3 (FZD3) and docking protein 6 (DOK6) were obtained through the DEM-target gene interaction networks.

Conclusion

Two key miRNAs (miR-141-3p and miR-30a-3p), the MAPK signaling pathway and two key genes (FZD3 and DOK6) were implicated in the pathogenesis of HSCR.

     

The effects of infant media usage: what do we know and what should we learn?

The rise of infant TV viewing began in the late 1990s and has become an increasingly common occurrence. Today, over 90% of children begin watching TV regularly before the age of 2 years in spite of recommendations to the contrary. This article reviews what is known about the effects of infant TV viewing on multiple domains of child development including language, cognition and attentional capacity as well as directions for future research.
Conclusion: No studies to date have demonstrated benefits associated with early infant TV viewing. The preponderance of existing evidence suggests the potential for harm. Parents should exercise due caution in exposing infants to excessive media.     

Is television viewing associated with social isolation? Roles of exposure time, viewing context, and violent content

OBJECTIVE: To estimate associations between children's peer integration and amount of time they spend (1) watching television, (2) watching violent television, and (3) co-viewing television with friends. DESIGN: Survey using nationally representative data from the Panel Study of Income Dynamics-Child Development Supplement Wave 1. SETTING: Nationwide survey of families with young children performed in 1997. PARTICIPANTS: Of 3562 children, 1356 had sufficient data for inclusion in analyses (563 children aged 6 to 8 years and 793 children aged 9 to 12 years). MAIN EXPOSURE: Total time viewing television, with and without friends present, and time viewing violent and nonviolent television content. MAIN OUTCOME MEASURE: Amount of time children spent with friends as reported in two 24-hour activity diaries. RESULTS: Viewing violent programs (but not nonviolent programs) was negatively related to time children spent with friends (aged 6-8 years, unstandardized regression coefficient [beta] = - 0.34, 95% confidence interval [CI], - 0.59 to - 0.08; aged 9-12 years, beta = - 0.41, 95% CI, - 0.65 to - 0.18). More time viewing television with friends was associated with more time engaging in other activities with friends (aged 6-8 years, beta = 0.98, 95% CI, 0.61 to 1.36; aged 9-12 years, beta = 1.03, 95% CI, 0.72 to 1.34). CONCLUSIONS: The more time that children spent viewing violent programs, the less time they spent with their friends. While this study cannot determine the direction of effects for this relationship, a cyclical process between violent media and peer integration best explains the findings. To optimize social development and mental health, children's access to violent media should be limited.     

In the critically ill, nothing-by-mouth infant, would enteral administration of simulated amniotic fluid improve feeding tolerance compared with the current practice of no therapy? An evidence-based review

Necrotizing enterocolitis (NEC ) can be a devastating disease in the NIC U population. The current standard of practice of not providing enteral nutrition to the critically ill and the premature infant is thought to result in pathophysiologic changes of the gastrointestinal (GI) tract that may result in the development of NEC. Various methods of preventing or reducing the incidence of NEC in the NIC U have been explored. One such method is the enteral administration of simulated amniotic fluid (SAF). This article compares, contrasts, and reviews the available evidence regarding the use of SAF feedings as a means of reducing GI tract changes associated with nothing-by-mouth (NPO) status.     

Are parental vaccine safety concerns associated with receipt of measles-mumps-rubella, diphtheria and tetanus toxoids with acellular pertussis, or hepatitis B vaccines by children?

OBJECTIVES: To identify parental perceptions regarding vaccine safety and assess their relationship with the immunization status of children.Design, Setting, and PARTICIPANTS: Case-control study based on a survey of a sample of households participating in the 2000-2001 National Immunization Survey, a quarterly random-digit-dialing sample of US children aged 19 to 35 months. Three groups of case children not up-to-date for 3 vaccines were compared with control children who were up-to-date for each respective vaccine.Main Outcome Measure Measles-containing or measles-mumps-rubella, diphtheria and tetanus toxoids and pertussis or diphtheria and tetanus toxoids with acellular pertussis, and hepatitis B vaccination coverage. RESULTS: Among those sampled from the 2000-2001 National Immunization Survey, the household response rate was 2315 (52.1%) of 4440. Most respondents (>90%) in all groups believed vaccinations are important. In each case-control group, there was no significant difference between the percentage of case and control parents expressing general vaccine safety (range, 53.5%-64.1%). However, case parents were more likely to have asked that their child not be vaccinated for reasons other than illness (range, 10.2%-13.7% vs range, 2.9%-5.3%, respectively) and to believe their children received too many vaccinations (range, 3.4%-7.6% vs range, 0.8%-1.0%, respectively). Among the case-control group receiving a measles-containing or measles-mumps-rubella vaccination, only a small percentage of parents knew about the alleged association between autism and measles-mumps-rubella vaccinations (8.2%), and case parents were more likely to believe it than control parents (4.4% vs 1.5%, respectively; chi(2) P =.04). CONCLUSIONS: Despite belief in the importance of immunization by a vast majority of parents, the majority of parents had concerns regarding vaccine safety. Strategies to address important misperceptions about vaccine safety as well as additional research assessing vaccine safety are needed to ensure public confidence.     

How well are infant and young child World Health Organization (WHO) feeding indicators associated with growth outcomes? An example from Cambodia

We assessed eight World Health Organization (WHO) core child feeding indicators for their association with stunting and underweight in Cambodia in 2000 and 2005. We compared the feeding data from the Cambodian Demographic and Health Surveys for 2000 with 2005 for 0-24 months children using the WHO feeding indicators, with stunting and underweight as outcomes. Prevalence of stunting and underweight was significantly less in 2005 than in 2000 among children aged 0-5 and 6-11 months, but stunting among children 18-23 months remained >50%. Prevalence of compliance with seven of the eight core healthy feeding indicators was higher in 2005. Exclusive breastfeeding among 0-5 months infants increased more than fivefold; among 6-11 and 12-17 months children, prevalence of feeding diversity and meeting a minimally acceptable diet, while improved, remained ≈25%. Modelling showed compliance with breastfeeding indicators was associated with reduced risk of underweight in 0-5 months infants, no association between compliance with feeding indicators and growth outcomes in other ages, and a significant association of higher relative wealth with growth outcomes overall. Between 2000 and 2005, Cambodia stabilized and focused resources on infant feeding. Prevalence of meeting the WHO feeding indicators improved, but modelling indicated that, in general, relative wealth, not feeding practices, was associated with improved growth outcomes. Yet, over 50% of children 18-23 months were stunted in 2005. Similar to the success with breastfeeding, focus on complementary feeding of 6-23 months children may reduce the risk of stunting in Cambodia.     

Is baby too warm? The use of infant clothing,bedding and home heating in Victoria,Australia.

Overheating of infants has been associated with a raised risk for sudden infant death syndrome (SIDS). Data on the use of heating, bedding and clothing and other measures affecting the thermal environment of 4 week old infants were collected at a home interview for infants of women born in Australia (Anglo-Celtic background), in Southern Europe, in Asia and of women who had a planned out-of-hospital birth. These groups have different risks of SIDS not explained by the classic social and perinatal risk factors nor associated with the currently promoted 'new' risk factors. Thermal insulation of the infant's bedding and clothing and excess thermal insulation (for any observed room temperature) were calculated. Bed sharing differed significantly between the groups as did the use of a sheepskin, tucking in firmly, the closing of doors and windows and the use of heating in the infant's room. After stratifying by bed sharing practice and season of interview, it was found that bed sharing infants had more thermal insulation than those sleeping alone irrespective of season of interview. Infants sleeping alone in the Asian-born and Southern European-born groups were kept warmer than infants in the other two groups. Cultural factors appear to affect the thermal environment in which infants are raised. Some bed sharing infants in all four groups were inappropriately warm, particularly in colder weather, but this was more likely in the Asian-born (low risk) group than in the home birth (high risk) group. These results do not explain the differences in SIDS incidence between the groups.     

Juvenile papillomatosis of the breast in a male infant with Noonan syndrome, café au lait spots, and family history of breast carcinoma

Juvenile papillomatosis (JP) of the breast is a rare condition, usually affecting women under 30 years of age. Although this is considered a benign lesion, follow-up is recommended for the patient and family since there is an association with a family history of breast carcinoma and increased risk of development of breast carcinoma. We report an infant with JP, Noonan syndrome (NS), café au lait spots, and family history of breast carcinoma. Seven previously reported cases of JP in males exist, two occurring in infants. The association between JP and NS has not been previously reported.     

Hirschsprung’s disease associated with Down syndrome: a meta-analysis of incidence, functional outcomes and mortality

Purpose

Down syndrome (DS) is the most frequent chromosomal abnormality associated with Hirschsprung’s disease (HD). It has often been suggested that this association results in poorer outcomes with regard to postoperative complications, continence and mortality. On the other hand, the results after surgical treatment of HD in patients with DS are reportedly similar to those in cases with HD alone. The objective of this study was to determine the incidence of DS in cohorts with HD, and to compare pre-/postoperative complications, functional outcome and mortality between cohorts with and without coexisting DS.

Methods

A systematic literature-based search for relevant cohorts was conducted using multiple online databases. The number of DS cases in HD cohorts was recorded and data on pre-/postoperative complications, functional outcome and mortality were extracted. Pooled odds ratios with 95 % confidence intervals were calculated using meta-analysis methodology.

Results

Sixty-one articles met defined inclusion criteria, comprising data from 16,497 patients with HD. The overall incidence of DS among them was 7.32 %. Vice versa, the incidence of HD in 29,418 patients with DS was 2.62 %. There were no significant differences regarding the male-to-female ratio between cohorts with and without coexisting DS (4:1 vs. 3:1 respectively; P = 0.5376). The rate of additional comorbidities was significantly higher in HD associated with DS (P < 0.0001). Recto-sigmoid HD was in both cohorts the most common type of HD (P = 0.8231). Long-segment HD was significantly more frequent in HD with coexisting DS (P = 0.0267), while total colonic aganglionosis occurred significantly more often in HD without DS (P = 0.0003). There were no significant differences in preoperative constipation/obstruction (P = 0.5967), but the rate of preoperative enterocolitis was significantly higher in HD associated with DS (P = 0.0486). Postoperative complications such as recurrent enterocolitis (P = 0.0112) and soiling (P = 0.0002) were significantly more frequent in HD with coexisting DS. Although not statistically significant, fecal incontinence (P = 0.1014) and persistent constipation (P = 0.1670) occurred more often after surgical treatment of HD with DS. The mortality rate was significantly higher in HD associated with DS (P < 0.0001).

Conclusions

The association of HD with DS is well-recognized with an incidence of 7.32 %. A large number of patients with DS continue to have persistent bowel dysfunction after surgical treatment of HD. Our data provide strong evidence that the coexistence of HD and DS is associated with higher rates of pre-/postoperative enterocolitis, poorer functional outcomes and increased mortality.     

Necrosis of the epididymis in a premature infant with patent ductus arteriosus and diastolic aortic steal: ischemia or torsion?

We describe a case of isolated ischemic necrosis of the epididymis in a premature newborn with aortic steal syndrome, secondary to a large patent ductus arteriosus (PDA). Neither this finding nor the possible underlying pathogenesis has been previously described. CONCLUSION: In this report our knowledge of the potential complications of PDA in the premature neonate is extended.     

Is being overweight associated with behavioural problems in childhood and adolescence? Findings from the Mater-University study of pregnancy and its outcomes

Aims: To examine the associations between being overweight and behavioural problems at ages 5 and 14. Methods: Birth cohort study of 2875 individuals who were born in Brisbane between 1981 and 1984 and who were followed up at ages 5 and 14 years. Behavioural problems were defined as scoring above the 90th centile on Achenbach''s child behavioural checklist. Results: In cross-sectional analyses there was no association between being overweight and behavioural problems in either females at age 5. At age 14 females who were overweight were more likely than those who were normal weight to experience behavioural problems. However, there was no association between being overweight and behavioural problems at age 14 among males. The prevalence of behavioural problems increased linearly across the distribution of body mass index in females at age 14. In prospective analyses, among participants who had no behavioural problems at age 5, there was no association between being overweight at age 5 and behavioural problems at age 14 in either sex. Females who were overweight at age 5 and normal weight at age 14 had reduced odds of behavioural problems at age 14. Conclusions: Among adolescent females there is a positive linear association between body size and behavioural problems. However, no such association was found in adolescent males, or in either sex at age 5 years, and in prospective analyses being overweight at age 5 was not associated with behavioural problems in either sex at age 14.