Allopolyploid origin and diversification of the Hawaiian endemic mints.

Island systems provide important contexts for studying processes underlying lineage migration, species diversification, and organismal extinction. The Hawaiian endemic mints (Lamiaceae family) are the second largest plant radiation on the isolated Hawaiian Islands. We generated a chromosome-scale reference genome for one Hawaiian species, Stenogyne calaminthoides, and resequenced 45 relatives, representing 34 species, to uncover the continental origins of this group and their subsequent diversification. We further resequenced 109 individuals of two Stenogyne species, and their purported hybrids, found high on the Mauna Kea volcano on the island of Hawai'i. The three distinct Hawaiian genera, Haplostachys, Phyllostegia, and Stenogyne, are nested inside a fourth genus, Stachys. We uncovered four independent polyploidy events within Stachys, including one allopolyploidy event underlying the Hawaiian mints and their direct western North American ancestors. While the Hawaiian taxa may have principally diversified by parapatry and drift in small and fragmented populations, localized admixture may have played an important role early in lineage diversification. Our genomic analyses provide a view into how organisms may have radiated on isolated island chains, settings that provided one of the principal natural laboratories for Darwin's thinking about the evolutionary process.

Subgenome dominance shapes novel gene evolution in the decaploid pitcher plant Nepenthes gracilis.

Subgenome dominance after whole-genome duplication generates distinction in gene number and expression at the level of chromosome sets, but it remains unclear how this process may be involved in evolutionary novelty. Here we generated a chromosome-scale genome assembly of the Asian pitcher plant Nepenthes gracilis to analyse how its novel traits (dioecy and carnivorous pitcher leaves) are linked to genomic evolution. We found a decaploid karyotype and a clear indication of subgenome dominance. A male-linked and pericentromerically located region on the putative sex chromosome was identified in a recessive subgenome and was found to harbour three transcription factors involved in flower and pollen development, including a likely neofunctionalized LEAFY duplicate. Transcriptomic and syntenic analyses of carnivory-related genes suggested that the paleopolyploidization events seeded genes that subsequently formed tandem clusters in recessive subgenomes with specific expression in the digestive zone of the pitcher, where specialized cells digest prey and absorb derived nutrients. A genome-scale analysis suggested that subgenome dominance likely contributed to evolutionary innovation by permitting recessive subgenomes to diversify functions of novel tissue-specific duplicates. Our results provide insight into how polyploidy can give rise to novel traits in divergent and successful high-ploidy lineages.

KRAS-specific antibody binds to KRAS protein inside colorectal adenocarcinoma cells and inhibits its localization to the plasma membrane.

Colorectal cancer (CRC) is the third highest incidence cancer and a leading cause of cancer mortality worldwide. To date, chemotherapeutic treatment of advanced CRC that has metastasized has a dismayed success rate of less than 30%. Further, most (80%) sporadic CRCs are microsatellite-stable and are refractory to immune checkpoint blockade therapy. KRAS is a gatekeeper gene in colorectal tumorigenesis. Nevertheless, KRAS is 'undruggable' due to its structure. Thus, focus has been diverted to develop small molecule inhibitors for its downstream effector such as ERK/MAPK. Despite intense research efforts for the past few decades, no small molecule inhibitor has been in clinical use for CRC. Antibody targeting KRAS itself is an attractive alternative. We developed a transient ex vivo patient-derived matched mucosa-tumor primary culture to assess whether anti-KRAS antibody can be internalized to bind and inactivate KRAS. We showed that anti-KRAS antibody can enter live mucosa-tumor cells and specifically aggregate KRAS in the cytoplasm, thus hindering its translocation to the inner plasma membrane. The mis-localization of KRAS reduces KRAS dwelling time at the site where it tethers to activate downstream effectors. We previously showed that expression of SOX9 was KRAS-mutation-dependent and possibly a better effector than ERK in CRC. Herein, we showed that anti-KRAS antibody treated tumor cells have less intense SOX9 cytoplasmic and nuclear staining compared to untreated cells. Our results demonstrated that internalized anti-KRAS antibody inhibits KRAS function in tumor. With an efficient intracellular antibody delivery system, this can be further developed as combinatorial therapeutics for CRC and other KRAS-driven cancers.

Chromosomal instability and its effect on cell lines.

BACKGROUND: Cancer cell lines are invaluable model systems for biomedical research because they provide an almost unlimited supply of biological materials. However, there is considerable skepticism regarding the reproducibility of data derived from these in vitro models. RECENT FINDINGS: Chromosomal instability (CIN) is one of the primary issues associated with cell lines, which can cause genetic heterogeneity and unstable cell properties within a cell population. Many of these problems can be avoided with some precautions. Here we review the underlying causes of CIN, including merotelic attachment, telomere dysfunction, DNA damage response defects, mitotic checkpoint defects and cell cycle disturbances. CONCLUSION: In this review we summarize studies highlighting the consequences of CIN in various cell lines and provide suggestions on monitoring and controlling CIN during cell culture.

Genomic, transcriptomic, and metabolomic analysis of Oldenlandia corymbosa reveals the biosynthesis and mode of action of anti-cancer metabolites.

Plants accumulate a vast array of secondary metabolites, which constitute a natural resource for pharmaceuticals. Oldenlandia corymbosa belongs to the Rubiaceae family, and has been used in traditional medicine to treat different diseases, including cancer. However, the active metabolites of the plant, their biosynthetic pathway and mode of action in cancer are unknown. To fill these gaps, we exposed this plant to eight different stress conditions and combined different omics data capturing gene expression, metabolic profiles, and anti-cancer activity. Our results show that O. corymbosa extracts are active against breast cancer cell lines and that ursolic acid is responsible for this activity. Moreover, we assembled a high-quality genome and uncovered two genes involved in the biosynthesis of ursolic acid. Finally, we also revealed that ursolic acid causes mitotic catastrophe in cancer cells and identified three high-confidence protein binding targets by Cellular Thermal Shift Assay (CETSA) and reverse docking. Altogether, these results constitute a valuable resource to further characterize the biosynthesis of active metabolites in the Oldenlandia group, while the mode of action of ursolic acid will allow us to further develop this valuable compound.

Conservative antibiotic treatment of pediatric acute uncomplicated appendicitis during the COVID-19 pandemic: a prospective comparative cohort study.

BACKGROUND: Our study aimed to compare the clinical outcomes and cost-efficiency of antibiotic management versus laparoscopic appendectomy for acute uncomplicated appendicitis (AUA) in children during the COVID-19 pandemic when resources were limited and transmission risks uncertain. METHOD: In this prospective comparative cohort study, we analyzed the data of 139 children diagnosed with AUA meeting the following inclusion criteria: 5-18 years of age, symptoms duration of ≤ 48 h, appendix diameter ≤ 11 mm and no appendicolith. Treatment outcomes between non-operative management group (78/139) and upfront laparoscopic appendectomy group (61/139) were compared. Antibiotic regimes were intravenous ceftriaxone/metronidazole or amoxicillin/clavulanic acid for 48 h, followed by oral antibiotics to complete total 10-days course. RESULTS: 8/78 (10.3%) children had early failure (within 48 h) requiring appendectomy. 17/70 (24.3%) patients experienced late recurrence within mean follow-up time of 16.2 ± 4.7 months. There were no statistical differences in peri-operative complications, negative appendicectomy rate, and incidence of perforation and hospitalization duration between antibiotic and surgical treatment groups. Cost per patient in upfront surgical group was significantly higher ($6208.5 ± 5284.0) than antibiotic group ($3588.6 ± 3829.8; p = 0.001). CONCLUSION: Despite 24.3% risk of recurrence of appendicitis in 16.2 ± 4.7 months, antibiotic therapy for AUA appears to be a safe and cost-effective alternative to upfront appendectomy.

Genomic insights into rapid speciation within the world's largest tree genus Syzygium.

Species radiations, despite immense phenotypic variation, can be difficult to resolve phylogenetically when genetic change poorly matches the rapidity of diversification. Genomic potential furnished by palaeopolyploidy, and relative roles for adaptation, random drift and hybridisation in the apportionment of genetic variation, remain poorly understood factors. Here, we study these aspects in a model radiation, Syzygium, the most species-rich tree genus worldwide. Genomes of 182 distinct species and 58 unidentified taxa are compared against a chromosome-level reference genome of the sea apple, Syzygium grande. We show that while Syzygium shares an ancient genome doubling event with other Myrtales, little evidence exists for recent polyploidy events. Phylogenomics confirms that Syzygium originated in Australia-New Guinea and diversified in multiple migrations, eastward to the Pacific and westward to India and Africa, in bursts of speciation visible as poorly resolved branches on phylogenies. Furthermore, some sublineages demonstrate genomic clines that recapitulate cladogenetic events, suggesting that stepwise geographic speciation, a neutral process, has been important in Syzygium diversification.

Ethylene insensitive 2 (EIN2) as a potential target gene to enhance Fusarium head blight disease resistance.

Fusarium head blight (FHB) caused by Fusarium graminearum (Fg) severely affects cereal crops, especially wheat and barley. FHB results in significant yield loss, reduces grain quality and contaminates grains with mycotoxin. The development of FHB-resistant cereal cultivars can be expedited through CRISPR gene editing. The Arabidopsis ethylene insensitive 2 (AtEIN2) plays a key role in ethylene signaling pathway and is critical for monitoring plant growth and defense responses. RNAi down-regulation of the wheat homolog TaEIN2 has been shown to enhance wheat FHB resistance. Here we generated site-specific mutations in AtEIN2 by CRISPR-editing. Detached inflorescence infection assays revealed that AtEIN2 knock-out (KO) mutants displayed enhanced Fg resistance and substantially reduced Fg spore production in planta. Gene expression profiling of defense genes revealed that impairment of AtEIN2 resulted in down-regulation of the ethylene signaling pathway while the salicylic acid signaling pathway was unaffected. Complementation of AtEIN2-KO plants with a barley orthologue, HvEIN2, restored Fg susceptibility, indicating that HvEIN2 is functionally equivalent to its Arabidopsis counterpart and, hence, may have a similar role in conditioning barley Fg susceptibility. These results provide insight into the defense role of EIN2 and a molecular and functional foundation for manipulating HvEIN2 to enhance FHB resistance in barley.

Surgical approach and functional outcome of redo pull-through for postoperative complications in Hirschsprung's disease.

AIM: To review our surgical experience and outcome of redo pull-through for various postoperative complications of Hirschsprung's disease. METHODS: A retrospective study was performed on children who underwent redo pull-through from 2016 to 2019. Operative methods and functional outcomes were compared between those with anastomotic complications (stricture and fistula, n = 12) and patients without anastomotic complications (n = 24) such as residual aganglionosis/transition zone, twisted pull-through and tight soave cuff. RESULT: 36 Patients (29 male and 7 female) were included with median age 6 (0.1-54) months at primary and 36 (9-144) months at redo pull-through. A transanal rectal mucosectomy and partial internal anal sphincterectomy (TRM-PIAS) pull-through with laparoscopic (n = 10, 27.8%) or laparotomy (n = 26, 72.2%) assisted techniques were performed for all patients during redo procedure. Patients with anastomotic complications had lower incidence of successful laparoscopic pull-through (0%), higher postoperative complications (25%) after redo surgery, but similar functional outcomes compared to those without anastomotic complications (41.6% underwent laparoscopic surgery, 4.2% complications). Patients with partial colectomy had significantly less soiling (36.4%) and enterocolitis (0%) compared to those with subtotal/total colectomy (79.2% soiling and 58.3% enterocolitis). CONCLUSION: TRM-PIAS with/without laparoscopic-assisted redo pull-through was effective in treating various complications after primary pull-through. The functional outcome is strongly associated with the length of residual colon after redo pull-though.

Isolated Scaphoid Dislocation From Low-Energy Wrist Trauma.

Isolated scaphoid dislocation is an extremely rare injury typically caused by high-energy trauma. We present the first observed case of isolated scaphoid dislocation resulting from a non-traumatic injury of the wrist in power-grip tension in a patient with a questionable history of Marfan Syndrome. A 20-year-old right-hand dominant man presented to the emergency department with right wrist pain and deformation after carrying a table. The patient reported a possible history of Marfan Syndrome, but it had never been definitively diagnosed. Imaging revealed radial dislocation of the scaphoid. Bedside closed reduction was performed followed by outpatient ligament reconstruction with return to normal activities at 6 months. Early diagnosis and management lead to an improved prognosis for isolated scaphoid dislocation. Regardless of patient history or mechanism of injury, treatment options include closed reduction, percutaneous fixation, and/or open reduction with internal fixation and ligamentous reconstruction.

Pyoderma Gangrenosum after Fat Grafting in Alloplastic Breast Reconstruction: An Unusual Outcome.

Pyoderma gangrenosum (PG) is a rare and painful inflammatory skin disorder that has been recently associated with breast surgery. It is commonly mistaken for postoperative ischemia or wound infection and does not show response to antibiotics or debridement. We describe the first case of post-surgical PG (PSPG) after alloplastic breast reconstruction involving fat grafting. A 47-year-old woman underwent bilateral mastectomy and 2-stage alloplastic breast reconstruction, with fat grafting from the abdomen. Two days post-surgery, she developed bilateral erythema with tender grouped pustules that progressed rapidly into necrotic ulcerations. She did not respond to antibiotics and serial debridement. Subsequent biopsy confirmed a diagnosis of PG. She was started on steroid therapy and responded well. She was discharged on a steroid regimen, local wound care, and eventually a T-cell inhibitor. Over the next 12 months, her wounds healed without surgical intervention. PSPG has been observed in a variety of reconstructive breast surgeries, but never reported in the setting of fat grafting. As PG involves subcutaneous fat, fat grafting may accelerate and exacerbate the course of disease. Treatment for PSPG includes systemic steroid therapy or other immunomodulatory agents (or both). Surgical management remains controversial, as serial debridement and reconstruction have shown to exacerbate and stimulate disease progression. A long-term follow-up is recommended to monitor for wound healing. Delayed diagnosis of PG in breast reconstruction patients can lead to severe morbidity and disfigurement. This is first case of PSPG following fat grafting in the literature.

Time course response of inflammatory markers in pediatric appendicitis.

PURPOSE: We aim to evaluate the diagnostic value and time course response of the triple inflammatory markers: white blood cell count (WBC), neutrophil percentage (Neu), and C-reactive protein (CRP) in pediatric acute appendicitis. METHODS: A retrospective review of clinical data pertaining to 1391 patients admitted with suspicion for pediatric appendicitis from 2012 to 2017 was conducted. Triple inflammatory markers were acquired upon admission. Appendicitis was confirmed histologically post-appendectomy. The diagnostic value and time course response of these markers was trended in relation to the duration of abdominal pain on admission. RESULTS: 718 patients had histologically confirmed appendicitis. WBC and Neu demonstrate high sensitivity for early appendicitis at 94.6% and 80.0% at Day 1, while CRP demonstrates highest sensitivity of 97.9% at Day 4. The triple markers had poor overall diagnostic value when interpreted individually, however, had a high combined sensitivity of 99.7% and negative predictive value of 98.7% regardless of duration of disease. Overall negative appendectomy rate was 6.7% (n = 52). Among 19 patients with triple markers negative who underwent appendectomy, 17 (89.5%) were histologically normal. CONCLUSIONS: The triple inflammatory markers have limited diagnostic value when interpreted individually, but are strong discriminators of pediatric appendicitis when combined. Their high sensitivity and negative predictive value could potentially help patients avoid unnecessary admissions or costly imaging studies, and reduce negative appendectomy rates. In addition, their objective nature confers an advantage over existing clinical scoring systems which comprise subjective elements.

Congenital or acquired? Obstructive jaundice in reoperated duodenal atresia.

A 55-day-old boy was transferred to our unit with intestinal obstruction and obstructive jaundice after two neonatal operations for duodenal atresia and intestinal malrotation. Abdominal ultrasound showed dilated intrahepatic and extrahepatic ducts with cut-off at the distal common bile duct (CBD). He underwent emergency laparotomy for adhesive intestinal obstruction with a contained abscess from mid-jejunal perforation. Biliary dissection was not attempted due to poor preoperative nutritional status. Tube cholecystostomy was created for biliary decompression. Postoperative magnetic resonance cholangiopancreatography showed dilated CBD with cut-off at the ampulla but did not demonstrate pancreaticobiliary maljunction (PBMJ). The diagnostic dilemma was whether our patient had congenital PBMJ or had developed biliary stricture from perioperative ischaemic scarring. He underwent definitive surgery at 7 months: excision of dilated CBD with Roux-en-Y hepaticojejeunal reconstruction, excisional tapering duodenoplasty and jejunostomy creation. Intraoperative finding was type I choledochal cyst and subsequently confirmed on histology. Postoperative recovery was uneventful and bilirubin levels normalised.

Randomised controlled trial of dexmedetomidine sedation vs general anaesthesia for inguinal hernia surgery on perioperative outcomes in infants.

BACKGROUND: Neonates and infants undergoing general anaesthesia for hernia surgery are at risk of perioperative cardiorespiratory adverse events. The use of regional anaesthesia with dexmedetomidine preserves airway tone and may potentially avoid these complications. This study compares the perioperative conditions and adverse events between dexmedetomidine sedation with caudal block and general anaesthesia with caudal block for inguinal hernia surgery in infants. METHODS: A randomised controlled trial was conducted in a tertiary hospital in Singapore involving 104 infants younger than 3 months, who were randomised to receive either dexmedetomidine sedation (DEX) with caudal block or general sevoflurane anaesthesia with tracheal intubation and caudal block (GA) for inguinal hernia surgery. Perioperative conditions, haemodynamics and adverse events were compared between groups. RESULTS: Fifty-one infants received DEX and 48 infants received GA. In the DEX group, 46 infants (90.2%) had their operations completed solely under this technique, two (3.9%) were converted to general anaesthesia with intubation, and three (5.9%) required brief administration of nitrous oxide or low-dose sevoflurane. Overall, 96.1% of infants in the DEX group did not require intubation. Perioperative conditions were similar in both groups. The DEX group had significantly lower heart rates and higher mean arterial pressures intraoperatively. Two infants in the DEX group (3.9%) required postoperative intensive care admission compared with six infants (12.5%) in the GA group. CONCLUSIONS: Dexmedetomidine sedation with caudal block provides a feasible alternative to general anaesthesia in infants undergoing hernia surgery. This technique avoids the need for tracheal intubation, which may be beneficial in neonates. CLINICAL TRIAL REGISTRATION: NCT02559102.

A novel noninvasive appendicitis score with a urine biomarker.

PURPOSE: The aim of our study was to develop an appendicitis score incorporating a urine biomarker, Leucine rich alpha-2-glycoprotein (LRG), for evaluation of children with abdominal pain. METHODS: From January to August 2017 we prospectively enrolled children aged 4-16 years old admitted for suspected appendicitis. Urine samples for LRG analysis were obtained preoperatively and quantified by enzyme-linked immunosorbent assay (ELISA) after correction for patient hydration status. The diagnosis of appendicitis was based on operative findings and histology. Logistic regression was used to identify prospective predictors. RESULTS: A total of 148 patients were recruited, of which 42(28.4%) were confirmed appendicitis. Our Appendicitis Urinary Biomarker (AuB) model incorporated urine LRG with 3 clinical predictors: 'constant pain', 'right iliac fossa tenderness', 'pain on percussion'. Area under the ROC curve for AuB was 0.82 versus 0.78 for the Pediatric Appendicitis Score (PAS) on the same cohort of patients. A model-calculated risk score of <0.15 is interpreted as low risk of appendicitis. Sensitivity for the AuB at this cutoff was 97.6%, specificity 37.7%, negative predictive value 97.6%, positive predictive value 38.3%, and negative likelihood ratio 0.06. CONCLUSION: The noninvasive AuB score appears promising as a diagnostic tool for excluding appendicitis in children without the need for blood sampling. TYPE OF STUDY: Study of diagnostic test. LEVEL OF EVIDENCE: Level III.

Ex Vivo Major Histocompatibility Complex I Knockdown Prolongs Rejection-free Allograft Survival.

BACKGROUND: Widespread application of vascularized composite allotransplantation (VCA) is currently limited by the required lifelong systemic immunosuppression and its associated morbidity and mortality. This study evaluated the efficacy of ex vivo (after procurement but before transplantation) engineering of allografts using small interfering RNA to knockdown major histocompatibility complex I (MHC-I) and prolong rejection-free survival. METHODS: Endothelial cells (ECs) were transfected with small interfering RNA targeted against MHC-I (siMHC-I) for all in vitro experiments. MHC-I surface expression and knockdown duration were evaluated using quantitative polymerase chain reaction (qPCR) and flow cytometry. After stimulating Lewis recipient cytotoxic lymphocytes (CTL) with allogeneic controls or siMHC-I-silenced ECs, lymphocyte proliferation, CTL-mediated and natural killer-mediated EC lysis were measured. Using an established VCA rat model, allografts were perfused ex vivo with siMHC-I before transplantation. Allografts were analyzed for MHC-I expression and clinical/histologic evidence of rejection. RESULTS: Treatment with siMHC-I resulted in 80% knockdown of mRNA and 87% reduction in cell surface expression for up to 7 days in vitro (P < 0.05). Treatment of ECs with siMHC-I reduced lymphocyte proliferation and CTL-mediated cytotoxicity (77% and 50%, respectively, P < 0.01), without increasing natural killer-mediated cytotoxicity (P = 0.66). In a rat VCA model, ex vivo perfusion with siMHC-I reduced expression in all tissue compartments by at least 50% (P < 0.05). Knockdown prolonged rejection-free survival by 60% compared with nonsense-treated controls (P < 0.05). CONCLUSIONS: Ex vivo siMHC-I engineering can effectively modify allografts and significantly prolong rejection-free allograft survival. This novel approach may help reduce future systemic immunosuppression requirements in VCA recipients.

Neuronal defects an etiological factor in congenital pelviureteric junction obstruction?

INTRODUCTION: Congenital pelviureteric junction obstruction (PUJO) is one of the most frequent causes of neonatal hydronephrosis. Obstruction at the PUJ has potential severe adverse outcomes, such as renal damage. While pyeloplasty has been established as the definitive treatment, the exact pathophysiology of congenital PUJO remains unknown. Recent research has proposed neuronal innervation defects as an etiological factor in congenital PUJO. We aim to study the expression of various neuronal markers in PUJO specimens compared with controls, and evaluate whether severity of renal disease or dysfunction pre-operatively is related to expression of neuronal markers in resected PUJO specimens. MATERIALS AND METHODS: All consecutive patients who underwent dismembered pyeloplasty at KK Women's and Children's Hospital, Singapore, for intrinsic PUJO from 2008 to 2012 were included. Patients with other co-occurring renal pathologies were excluded. Controls were obtained from nephrectomy patients with Wilm's tumor or other benign renal conditions during the same period. Specimens were stained immunohistochemically with neuronal markers protein gene product 9.5 (PGP9.5), synaptophysin, and S-100, and with CD-117, a marker for interstitial cells of Cajal (Table). Levels of expression of the markers were assessed semiquantitatively (decreased, increased or no change) in comparison with controls by two independent observers. Pre-operative data of patients' renal anatomical (ultrasonography measurements of renal pelvis size) and functional parameters (differential renal function measured using MAG-3 renal scans) were obtained. DISCUSSION: Thirty-eight PUJO specimens (38 renal units) and 20 controls were studied. Mean patient age at pyeloplasty was 25.3 months (2.9-167.6 months). Median pre-operative pelvic size was 25.0 mm (17.0-50.0 mm). Both PUJO specimens and controls showed great heterogeneity in distribution of innervation. All four immunohistochemical markers were not predictive of significant pre-operative renal pelvis dilation or pre-operative diminished renal function of the operated kidney. CONCLUSIONS: There exists marked variability in expression of neuronal markers synaptophysin, PGP9.5, and S-100, and CD-117 in PUJO specimens compared with controls. Our results show no clinical significance of the expression of neuronal markers in predicting degree of pre-operative renal pelvis dilation or differential renal function. The heterogeneity of expression of neuronal markers in PUJO specimens and controls in our population is at variance with prior studies. The etiology of PUJO is likely to be complex and multifactorial.

Anorectal malformation & Hirschsprung's disease: A cross-sectional comparison of quality of life and bowel function to healthy controls.

BACKGROUND: Patients with anorectal malformation (ARM) and Hirschsprung's disease (HD) face long-term disturbance in bowel function even after definitive surgery. This study evaluates the quality of life (QOL) of patients with ARM and HD, and compares them to healthy controls using self-report questionnaires. METHODOLOGY: A prospective study was performed recruiting patients with ARM or HD from September 2013 to December 2014 who had primary surgery done in our institution at least 2 years prior to participation. Age-matched and gender-matched controls were enrolled from our patients with minor outpatient complaints. All participants completed the following PedsQL™ scales (maximum score 100): 4.0 Generic Core Scales, 3.0 General Well-Being (GWB) Scale and 2.0 Family Impact (FI) Module. All were also scored on bowel function (BFS), with a maximum score 20. Appropriate statistical analysis was performed, with significance level <0.05. RESULTS: There were 193 participants: 87 controls, 62 ARM, 44 HD. When comparing Core, GWB and FI scores, there were no significant differences between groups although controls had best scores indicating best QOL and general wellbeing, with least impact of the child's health on the family. BFS was significantly different with controls having best and ARM worst scores. There were no significant differences in scores between parent and child indicating intradyad consistency. There was significant positive correlation between BFS and Core (p<0.0001), and between BFS and GWB scores (p<0.005); and significant negative correlation between BFS and FI scores (p<0.0001). CONCLUSIONS: Bowel function impacts quality of life. Those with ARM and HD can achieve good quality of life comparable to controls, based on patient and caregiver self-reported outcomes. TYPE OF STUDY: Prospective comparative study LEVEL OF EVIDENCE: Level II.