A Critical Analysis of Rectal Biopsy to Exclude Hirschsprung's Disease.

INTRODUCTION: Most Hirschsprung's disease (HD) are diagnosed in young children with increased risk ("red flag"). Older children (>6 months) require open rectal biopsy (ORB) with its own impact on risk and resources. We investigated if "red flag", age, and sex used in combination could exclude HD. MATERIALS AND METHODS: "Red flags" are risk factors associated with HD, including neonatal bowel obstruction, genetic association, failure of passage of meconium in <48 hours, infantile constipation, distension with vomiting, or family history. All rectal biopsies (2015-2018) were reviewed for indications, methods, and histopathological findings. Logistic regression analysis was adopted to assess predictive value of "red flag," age, and sex (p < 0.05* was significant). RESULTS: A total of 187 children underwent 84 suction rectal biopsies and 113 ORBs (n = 197 in total). Final histopathological diagnoses were non-HD (n = 154) and HD (n = 43). Total 78% of rectal biopsies were non-HD, of which 63% by ORB. Non-HD was associated with absence of "red flag" (49 vs. 16%*), increased age at biopsy (22 months vs. 28 days*), >6 months old (62 vs. 30%*), and female gender (54 vs. 16%*), compared with HD. In the absence of "red flag," 7/82 (9%) had HD (negative predictive value = 91%). Logistic regression analysis found absent "red flag" predicted non-HD biopsy with odds ratio 4.77 (1.38, 16.47), corrected for age and sex. CONCLUSION: Negative rectal biopsy rate for HD is very high. The majority required ORB. Although "red flag" and gender, but not age, have strong predictive values, it is inadequate for excluding HD. This study supports the need for alternative strategies in excluding HD.

Charismatic Nonverbal Displays by Leaders Signal Receptivity and Formidability, and Tap Approach and Avoidance Motivational Systems.

Status cues and signals act as guidance systems by regulating social approach and avoidance. Applied to leadership, we hypothesized that nonverbal displays conveying the dual-status messages of receptivity and formidability and the approach/avoidance motives they activate set conditions for charismatic, leader-follower relationships. We investigated perceptions of charisma, the nonverbal signals associated with them, the motives they energize, and the relationships they support across levels of analysis. At the social-perceptual level (studies 1a-d), eligible voters rated political leaders' traits after viewing silent, 30-s videos of speeches presented online. As predicted, perceptions of politicians' receptivity (warmth and attractiveness) and formidability (competence and power) were independently associated with perceptions of their charisma; perceptions of trustworthiness and authenticity showed weaker or negligible associations. Results were similar when the stimuli were female, Jamaican educational leaders. Leaders' nonverbal behavior was linked to perceptions of their receptivity, formidability, and charisma in study 2. At the brain systems level, studies 3a and 3b tested predictions that charismatic nonverbal performances stimulate equivalent degrees of approach and avoidance motivation in observers. Brain recordings via electroencephalography (EEG) were made while undergraduates viewed leaders rated high or low in charisma. Discrepancies in alpha activity in the left and the right frontal hemispheres (associated with approach and avoidance, respectively) were relatively diminished when participants viewed highly charismatic political leaders, indicating that approach and avoidance motives are energized in response to charismatic performances. The EEG patterns for Jamaican leaders were similar but not significant. At the group level of analysis, study 4 sought evidence that charismatic leaders create uniquely influential relationships with followers. Video recordings of student leaders interacting with pairs of unfamiliar students during a group decision-making task were assessed for leader receptivity, formidability, and charisma by independent sets of undergraduate judges. Perceptions of student leaders' receptivity and formidability predicted their charisma, and charismatic leaders were most influential in bringing followers to privately accept a controversial group decision. Across studies, evidence generally supported hypotheses generated from status cues theory: charismatic leadership builds upon the nonverbal projection of dual-status messages and the approach/avoidance motives they engender, setting conditions for a uniquely powerful brand of influence.

Epigenome-Wide Association Study Reveals Duration of Breastfeeding Is Associated with Epigenetic Differences in Children.

Several small studies have shown associations between breastfeeding and genome-wide DNA methylation (DNAm). We performed a comprehensive Epigenome-Wide Association Study (EWAS) to identify associations between breastfeeding and DNAm patterns in childhood. We analysed DNAm data from the Isle of Wight Birth Cohort at birth, 10, 18 and 26 years. The feeding method was categorized as breastfeeding duration >3 months and >6 months, and exclusive breastfeeding duration >3 months. EWASs using robust linear regression were performed to identify differentially methylated positions (DMPs) in breastfed and non-breastfed children at age 10 (false discovery rate of 5%). Differentially methylated regions (DMRs) were identified using comb-p. The persistence of significant associations was evaluated in neonates and individuals at 18 and 26 years. Two DMPs, in genes SNX25 and LINC00840, were significantly associated with breastfeeding duration >6 months at 10 years and was replicated for >3 months of exclusive breastfeeding. Additionally, a significant DMR spanning the gene FDFT1 was identified in 10-year-old children who were exposed to a breastfeeding duration >3 months. None of these signals persisted to 18 or 26 years. This study lends further support for a suggestive role of DNAm in the known benefits of breastfeeding on a child's future health.

Duration of breastfeeding is associated with leptin (LEP) DNA methylation profiles and BMI in 10-year-old children.

BACKGROUND: Breastfeeding is protective against many long-term diseases, yet the mechanisms involved are unknown. Leptin gene (LEP) is reported to be associated with body mass index (BMI). On the other hand, breastfeeding duration has been found to be associated with DNA methylation (DNAm) of the LEP gene. Therefore, epigenetic regulation of LEP may represent the mechanism underlying the protective effect of breastfeeding duration against obesity. METHODS: In the Isle of Wight Birth Cohort, peripheral blood DNAm at 23 cytosine-phosphate-guanine sites (CpGs) in the LEP locus in 10-year-old (n = 297) samples and 16 CpGs in 18-year-old (n = 305) samples, were generated using the Illumina Infinium MethylationEPIC and HumanMethylation450 Beadchips respectively and tested for association with breastfeeding duration (total and exclusive) using linear regression. To explore the association between breastfeeding durations and genome-wide DNAm, epigenome-wide association studies (EWASs) and differential methylation region (DMR) analyses were performed. BMI trajectories spanning the first 18 years of life were used as the outcome to test the association with breastfeeding duration (exposure) using multi-nominal logistic regression. Mediation analysis was performed for significant CpG sites. RESULTS: Both total and exclusive breastfeeding duration were associated with DNAm at four LEP CpG sites at 10 years (P value < 0.05), and not at 18 years. Though no association was observed between breastfeeding duration and genome-wide DNAm, DMR analyses identified five significant differentially methylated regions (Sidak adjusted P value < 0.05). Breastfeeding duration was also associated with the early transient overweight trajectory. Furthermore, DNAm of LEP was associated with this trajectory at one CpG site and early persistent obesity at another, though mediation analysis was not significant. CONCLUSIONS: Breastfeeding duration is associated with LEP methylation at age 10 years and BMI trajectory. LEP DNAm is also significantly associated with BMI trajectories throughout childhood, though sample sizes were small. However, mediation analysis did not demonstrate that DNAm of LEP explained the protective effect of breastfeeding against childhood obesity.

Neonatal Appendicitis and Incarcerated Inguinal Hernia: Case Report and Review of the Literature.

Neonatal appendicitis carries a high mortality rate. We describe a peculiar case presented after an incarcerated hernia manually reduced in a 4-week-old male neonate with ipsilateral undescended testis. Laparoscopy allowed a prompt recognition of an unexpected intra-abdominal life-threatening condition. Pathogenesis, treatment, and outcome are discussed on the light of a comprehensive literature review.

Role of intraglomerular circuits in shaping temporally structured responses to naturalistic inhalation-driven sensory input to the olfactory bulb.

Olfaction in mammals is a dynamic process driven by the inhalation of air through the nasal cavity. Inhalation determines the temporal structure of sensory neuron responses and shapes the neural dynamics underlying central olfactory processing. Inhalation-linked bursts of activity among olfactory bulb (OB) output neurons [mitral/tufted cells (MCs)] are temporally transformed relative to those of sensory neurons. We investigated how OB circuits shape inhalation-driven dynamics in MCs using a modeling approach that was highly constrained by experimental results. First, we constructed models of canonical OB circuits that included mono- and disynaptic feedforward excitation, recurrent inhibition and feedforward inhibition of the MC. We then used experimental data to drive inputs to the models and to tune parameters; inputs were derived from sensory neuron responses during natural odorant sampling (sniffing) in awake rats, and model output was compared with recordings of MC responses to odorants sampled with the same sniff waveforms. This approach allowed us to identify OB circuit features underlying the temporal transformation of sensory inputs into inhalation-linked patterns of MC spike output. We found that realistic input-output transformations can be achieved independently by multiple circuits, including feedforward inhibition with slow onset and decay kinetics and parallel feedforward MC excitation mediated by external tufted cells. We also found that recurrent and feedforward inhibition had differential impacts on MC firing rates and on inhalation-linked response dynamics. These results highlight the importance of investigating neural circuits in a naturalistic context and provide a framework for further explorations of signal processing by OB networks.

The incidence of intraabdominal abscess formation following laparoscopic appendicectomy in children: a systematic review and meta-analysis.

AIMS: Recent systematic reviews have suggested an increased incidence of intraabdominal abscess (IAA) formation following laparoscopic appendicectomy (LA) compared with the open approach (OA). As the majority of these analyses have focused on appendicectomy in adults, our aim was to review the evidence base for pediatric patients. SUBJECTS AND METHODS: We performed a comprehensive review of relevant studies published between 1990 and 2012. Specific inclusion and exclusion criteria were used to identify studies that investigated the incidence of IAA following LA and OA in pediatric patients. The primary outcome measure in the present meta-analysis was IAA formation, and secondary outcomes included wound infection (WI) and incidence of postoperative small bowel obstruction (SBO). RESULTS: Sixty-six studies with a total of 22,060 pediatric patients were included: 56.5% OA and 43.5% LA. There was no overall difference in the incidence of IAA formation: 2.7% for OA (333/12,460) versus 2.9% for LA (282/9600) (P=.25). However, OA patients had a higher incidence of wound infection: 3.7% for OA (337/9228) versus 2.2% for LA (183/8154) (P<.001). Moreover, the incidence of SBO was lower in patients undergoing LA: 0.4% LA (86/5767) versus 1.5% (29/6840) (P<.001). CONCLUSIONS: The IAA incidence is comparable in LA versus OA in pediatric patients. LA confers a significantly lower risk of other postoperative complications, including WI and SBO.

Synaptic patterning of left-right alternation in a computational model of the rodent hindlimb central pattern generator.

Establishing, maintaining, and modifying the phase relationships between extensor and flexor muscle groups is essential for central pattern generators in the spinal cord to coordinate the hindlimbs well enough to produce the basic walking rhythm. This paper investigates a simplified computational model for the spinal hindlimb central pattern generator (CPG) that is abstracted from experimental data from the rodent spinal cord. This model produces locomotor-like activity with appropriate phase relationships in which right and left muscle groups alternate while extensor and flexor muscle groups alternate. Convergence to this locomotor pattern is slow, however, and the range of parameter values for which the model produces appropriate output is relatively narrow. We examine these aspects of the model's coordination of left-right activity through investigation of successively more complicated subnetworks, focusing on the role of the synaptic architecture in shaping motoneuron phasing. We find unexpected sensitivity in the phase response properties of individual neurons in response to stimulation and a need for high levels of both inhibition and excitation to achieve the walking rhythm. In the absence of cross-cord excitation, equal levels of ipsilateral and contralateral inhibition result in a strong preference for hopping over walking. Inhibition alone can produce the walking rhythm, but contralateral inhibition must be much stronger than ipsilateral inhibition. Cross-cord excitatory connections significantly enhance convergence to the walking rhythm, which is achieved most rapidly with strong crossed excitation and greater contralateral than ipsilateral inhibition. We discuss the implications of these results for CPG architectures based on unit burst generators.

A comparative study examining open inguinal herniotomy with and without hernioscopy to laparoscopic inguinal hernia repair in a pediatric population.

AIMS: Open herniotomy with or without hernioscopy has been performed in our unit for a decade. Since 2005 the laparoscopic repair was also introduced. The aims of this study were: (1) to compare detection rates for direct visualization of the contralateral deep inguinal ring via the known sac using a 70 degrees scope and via umbilical 30 degrees laparoscopy and (2) to compare operative timings, metachronous and recurrence rates for the three different management pathways for inguinal hernia. METHODS: A retrospective case note review was carried out over a 29 month period since the introduction of the laparoscopic hernia repair. All patients with inguinal hernia were identified from the work load of six surgeons encompassing the three methods of hernia management. Case notes were retrieved and the data analyzed using SPSS v.17. RESULTS: A total of 308 patients had 326 hernias performed. Follow-up ranged from 3 months to 1 year (median 8 months). The male-female ratio was 4:1. Of the patients, 12% were neonates; 299 children presented with unilateral hernia. Of those, 164 (55%) children had open herniotomy without contralateral inspection, and 5 (3%) had metachronous hernia; 77 (26%) children had an open herniotomy with 70 degrees hernioscopy; 2 (3%) children, who were considered to have closed contralateral deep inguinal ring during hernioscopy, had metachronous hernia, and 58 (19%) children had a laparoscopic hernia repair and none of them had metachronous hernia. Detection of contralateral patent deep inguinal ring for 70 degrees hernioscopy and 30 degrees laparoscopy was 10 (13%) and 16 (28%), respectively (P = 0.0465). Operative timing was significantly longer for laparoscopic repair (P < or = 0.0001). During the study period there were 11 recurrences; 9 (5%) in the open only group and 2 (3%) in the laparoscopic group. CONCLUSIONS: The results of the laparoscopic inguinal hernia repair are important for discussion as operative methods differ from that of herniotomy. The detection rate of contralateral patent deep inguinal ring appears to be higher for direct visualization via umbilical 30 degrees laparoscopy versus 70 degrees scope via the hernia sac. Whilst laparoscopy offers potential advantage of improved visualization, longer term prospective data collection is needed to compare these methods of operative hernia management.

Challenges in the prenatal and post-natal diagnosis of mediastinal cystic hygroma: a case report.

INTRODUCTION: Cystic hygroma is a benign congenital neoplasm that mostly presents as a soft-tissue mass in the posterior triangle of the neck. Pure mediastinal lesions are uncommon; the vast majority are asymptomatic and are an incidental finding in adulthood. The diagnosis is often made intra- or postoperatively. Prenatal identification is exceptional and post-natal diagnosis also proves challenging. CASE PRESENTATION: We report one such case that was mistaken for other entities in both the prenatal and immediate post-natal period. Initial and follow-up antenatal ultrasound scans demonstrated a multicystic lesion in the left chest, and the mother was counselled about the possibility of her baby having a congenital diaphragmatic hernia. Initial post-natal chest radiographs were reported as normal. An echocardiogram and thoracic computed tomography scan confirmed a complex multiloculated cystic mediastinal mass. The working diagnoses were of a mediastinal teratoma or congenital cystic adenomatous malformation. At operation, the lesion was compressed by the left lung and was found to be close to the left phrenic nerve, which was carefully identified and preserved. After excision, histopathological examination of the mass confirmed the diagnosis of cystic hygroma. Postoperative dyspnoea was observed secondary to paradoxical movement of the left hemidiaphragm and probable left phrenic neuropraxia. This settled conservatively with excellent recovery. CONCLUSION: Despite the fact that isolated intrathoracic cystic hygroma is a rare entity, it needs to be considered in the differential diagnosis of foetal and neonatal mediastinal masses, particularly for juxtadiaphragmatic lesions. The phrenic nerve is not identifiable on prenatal ultrasound imaging, and it is therefore understandable that a mass close to the diaphragm may be mistaken for a congenital diaphragmatic hernia because of the location, morphology and potential phrenic nerve compression. Post-natal diagnosis may also be misleading as many mediastinal cystic masses have similar appearances on imaging. Therefore, as well as cystic architecture, special consideration needs to be given to the anatomical location and effect on local structures.