Multi-Chemical Omics Analysis of the Symbiodiniaceae Durusdinium trenchii under Heat Stress.

The urgency of responding to climate change for corals necessitates the exploration of innovative methods to swiftly enhance our understanding of crucial processes. In this study, we employ an integrated chemical omics approach, combining elementomics, metabolomics, and volatilomics methodologies to unravel the biochemical pathways associated with the thermal response of the coral symbiont, Symbiodiniaceae Durusdinium trenchii. We outline the complimentary sampling approaches and discuss the standardised data corrections used to allow data integration and comparability. Our findings highlight the efficacy of individual methods in discerning differences in the biochemical response of D. trenchii under both control and stress-inducing temperatures. However, a deeper insight emerges when these methods are integrated, offering a more comprehensive understanding, particularly regarding oxidative stress pathways. Employing correlation network analysis enhanced the interpretation of volatile data, shedding light on the potential metabolic origins of volatiles with undescribed functions and presenting promising candidates for further exploration. Elementomics proves to be less straightforward to integrate, likely due to no net change in elements but rather elements being repurposed across compounds. The independent and integrated data from this study informs future omic profiling studies and recommends candidates for targeted research beyond Symbiodiniaceae biology. This study highlights the pivotal role of omic integration in advancing our knowledge, addressing critical gaps, and guiding future research directions in the context of climate change and coral reef preservation.

Distinct emissions of biogenic volatile organic compounds from temperate benthic taxa.

INTRODUCTION: Biogenic volatile organic compounds (BVOCs) are emitted by all organisms as intermediate or end-products of metabolic processes. Individual BVOCs perform important physiological, ecological and climatic functions, and collectively constitute the volatilome-which can be reflective of organism taxonomy and health. Although BVOC emissions of tropical benthic reef taxa have recently been the focus of multiple studies, emissions derived from their temperate counterparts have never been characterised. OBJECTIVES: Characterise the volatilomes of key competitors for benthic space among Australian temperate reefs. METHODS: Six fragments/fronds of a temperate coral (Plesiastrea versipora) and a macroalga (Ecklonia radiata) from a Sydney reef site were placed within modified incubation chambers filled with seawater. Organism-produced BVOCs were captured on thermal desorption tubes using a purge-and-trap methodology, and were then analysed using GC × GC - TOFMS and multivariate tests. RESULTS: Analysis detected 55 and 63 BVOCs from P. versipora and E. radiata respectively, with 30 of these common between species. Each taxon was characterised by a similar relative composition of chemical classes within their volatilomes. However, 14 and 10 volatiles were distinctly emitted by either E. radiata or P. versipora respectively, including the halogenated compounds iodomethane, tribromomethane, carbon tetrachloride and trichloromonofluoromethane. While macroalgal cover was 3.7 times greater than coral cover at the sampling site, P. versipora produced on average 17 times more BVOCs per cm2 of live tissue, resulting in an estimated contribution to local BVOC emission that was 4.7 times higher than E. radiata. CONCLUSION: Shifts in benthic community composition could disproportionately impact local marine chemistry and affect how ecosystems contribute to broader BVOC emissions.

Small Intestinal Polyp Burden in Pediatric Peutz-Jeghers Syndrome Assessed through Capsule Endoscopy: A Longitudinal Study.

The management of pediatric Peutz-Jeghers Syndrome (PJS) focuses on the prevention of intussusception complicating small intestinal (SI) polyposis. This hinges on the accurate appraisal of the polyp burden to tailor therapeutic interventions. Video Capsule Endoscopy (VCE) is an established tool to study SI polyps in children, but an in-depth characterization of polyp burden in this population is lacking. Methods: We performed a retrospective longitudinal cross-sectional analysis of VCE studies in pediatric PJS patients at our institution (CMKC) from 2010 to 2020. Demographic, clinical, and VCE findings reported by three reviewers in tandem were accrued. Polyp burden variables were modeled as functions of patient and study characteristics using linear mixed models adjusted for clustering. Results: The cohort included 15 patients. The total small bowel polyp count and largest polyp size clustered under 30 polyps and <20 mm in size. Luminal occlusion correlated closely with the estimated polyp size. Polyp distribution favored proximal (77%) over distal (66%) small bowel involvement. The adjusted largest polyp size was greater in males. Double Balloon Enteroscopy was associated with a decreased polyp burden. Conclusions: The polyp burden in pediatric PJS patients favors the proximal third of the small intestine, with relatively small numbers and a polyp size amenable to resection through enteroscopy. Male gender and older age were related to an increased polyp burden.

Symbiont Identity Impacts the Microbiome and Volatilome of a Model Cnidarian-Dinoflagellate Symbiosis.

The symbiosis between cnidarians and dinoflagellates underpins the success of reef-building corals in otherwise nutrient-poor habitats. Alterations to symbiotic state can perturb metabolic homeostasis and thus alter the release of biogenic volatile organic compounds (BVOCs). While BVOCs can play important roles in metabolic regulation and signalling, how the symbiotic state affects BVOC output remains unexplored. We therefore characterised the suite of BVOCs that comprise the volatilome of the sea anemone Exaiptasia diaphana ('Aiptasia') when aposymbiotic and in symbiosis with either its native dinoflagellate symbiont Breviolum minutum or the non-native symbiont Durusdinium trenchii. In parallel, the bacterial community structure in these different symbiotic states was fully characterised to resolve the holobiont microbiome. Based on rRNA analyses, 147 unique amplicon sequence variants (ASVs) were observed across symbiotic states. Furthermore, the microbiomes were distinct across the different symbiotic states: bacteria in the family Vibrionaceae were the most abundant in aposymbiotic anemones; those in the family Crocinitomicaceae were the most abundant in anemones symbiotic with D. trenchii; and anemones symbiotic with B. minutum had the highest proportion of low-abundance ASVs. Across these different holobionts, 142 BVOCs were detected and classified into 17 groups based on their chemical structure, with BVOCs containing multiple functional groups being the most abundant. Isoprene was detected in higher abundance when anemones hosted their native symbiont, and dimethyl sulphide was detected in higher abundance in the volatilome of both Aiptasia-Symbiodiniaceae combinations relative to aposymbiotic anemones. The volatilomes of aposymbiotic anemones and anemones symbiotic with B. minutum were distinct, while the volatilome of anemones symbiotic with D. trenchii overlapped both of the others. Collectively, our results are consistent with previous reports that D. trenchii produces a metabolically sub-optimal symbiosis with Aiptasia, and add to our understanding of how symbiotic cnidarians, including corals, may respond to climate change should they acquire novel dinoflagellate partners.

Novel blended SNRPE-related spliceosomopathy phenotype characterized by microcephaly and congenital atrichia.

Variants in genes encoding core components of the spliceosomes are associated with craniofacial syndromes, collectively called craniofacial spliceosomopathies. SNRPE encodes a core component of pre-mRNA processing U-rich small nuclear ribonuclear proteins (UsnRNPs). Heterozygous variants in SNRPE have been reported in six families with isolated hypotrichosis simplex in addition to one case of isolated non syndromic congenital microcephaly. Here, we report a patient with a novel blended phenotype of microcephaly and congenital atrichia with multiple congenital anomalies due to a de novo intronic SNRPE deletion, c.82-28_82-16del, which results in exon skipping. As discussed within, this phenotype, which we propose be named SNRPE-related syndromic microcephaly and hypotrichosis, overlaps other craniofacial splicesosomopathies.

Insurance denials and diagnostic rates in a pediatric genomic research cohort.

PURPOSE: This study aimed to assess the amount and types of clinical genetic testing denied by insurance and the rate of diagnostic and candidate genetic findings identified through research in patients who faced insurance denials. METHODS: Analysis consisted of review of insurance denials in 801 patients enrolled in a pediatric genomic research repository with either no previous genetic testing or previous negative genetic testing result identified through cross-referencing with insurance prior-authorizations in patient medical records. Patients and denials were also categorized by type of insurance coverage. Diagnostic findings and candidate genetic findings in these groups were determined through review of our internal variant database and patient charts. RESULTS: Of the 801 patients analyzed, 147 had insurance prior-authorization denials on record (18.3%). Exome sequencing and microarray were the most frequently denied genetic tests. Private insurance was significantly more likely to deny testing than public insurance (odds ratio = 2.03 [95% CI = 1.38-2.99] P = .0003). Of the 147 patients with insurance denials, 53.7% had at least 1 diagnostic or candidate finding and 10.9% specifically had a clinically diagnostic finding. Fifty percent of patients with clinically diagnostic results had immediate medical management changes (5.4% of all patients experiencing denials). CONCLUSION: Many patients face a major barrier to genetic testing in the form of lack of insurance coverage. A number of these patients have clinically diagnostic findings with medical management implications that would not have been identified without access to research testing. These findings support re-evaluation of insurance carriers' coverage policies.

Recurrent FOXP4 nonsense variant in two unrelated patients: Association with neurodevelopmental disease and congenital diaphragmatic hernia.

De novo variants in FOXP4 were recently associated with a neurodevelopmental disorder characterized by speech and language delay, growth abnormalities, hypotonia, and variable congenital abnormalities, including congenital diaphragmatic hernia, cervical spine abnormalities, strabismus, cryptorchidism, and ptosis. The variant spectrum in this small cohort was limited to de novo missense except for one frameshift, the inheritance of which was unknown. Variants tested in vitro exhibited reduced repressor transcriptional activity, indicating loss of function is the likely mechanism of disease, but only one frameshift variant was reported. Here, we report four affected individuals from two unrelated families heterozygous for a nonsense variant, c.1893C > G, p.Tyr631*, in FOXP4. The phenotype of the affected children includes developmental delay, feeding difficulties in infancy, and similar facial features. In both cases, the variant was inherited from a parent with mild or even subclinical features. Interestingly, one patient presented with congenital diaphragmatic hernia, as reported in two other FOXP4 patients. This report implicates FOXP4 truncating variants in human disease and highlights the wide phenotypic spectrum and variable expressivity.

Microbiome insights into pediatric familial adenomatous polyposis.

BACKGROUND: Individuals with familial adenomatous polyposis (FAP) harbor numerous polyps with inevitable early progression to colon cancer. Complex microbiotic-tumor microenvironment perturbations suggest a dysbiotic relationship between polyp and microbiome. In this study, we performed comprehensive analyses of stool and tissue microbiome of pediatric FAP subjects and compared with unaffected cohabiting relatives through 16S V4 region amplicon sequencing and machine learning platforms. RESULTS: Within our FAP and control patient population, Firmicutes and Bacteroidetes were the predominant phyla in the tissue and stool samples, while Proteobacteria dominated the polyp/non-polyp mucosa. A decline in Faecalibacterium in polyps contrasted with a decline in Bacteroides in the FAP stool. The alpha- and beta-diversity indices differed significantly within the polyp/non-polyp groups, with a concurrent shift towards lower diversity in polyps. In a limited 3-year longitudinal study, the relative abundance of Proteobacteria and Fusobacteria was higher in polyps compared to non-polyp and stool specimens over time. Through machine learning, we discovered that Archaeon_enrichment_culture_clone_A13, Micrococcus_luteus, and Eubacterium_hallii in stool and PL-11B10, S1-80, and Blastocatellaceae in tissues were significantly different between patients with and without polyps. CONCLUSIONS: Detection of certain bacterial concentrations within stool or biopsied polyps could serve as adjuncts to current screening modalities to help identify higher-risk patients.

Symbiosis induces unique volatile profiles in the model cnidarian Aiptasia.

The establishment and maintenance of the symbiosis between a cnidarian host and its dinoflagellate symbionts is central to the success of coral reefs. To explore the metabolite production underlying this symbiosis, we focused on a group of low molecular weight secondary metabolites, biogenic volatile organic compounds (BVOCs). BVOCs are released from an organism or environment, and can be collected in the gas phase, allowing non-invasive analysis of an organism's metabolism (i.e. 'volatilomics'). We characterised volatile profiles of the sea anemone Aiptasia (Exaiptasia diaphana), a model system for cnidarian-dinoflagellate symbiosis, using comprehensive two-dimensional gas chromatography coupled with time-of-flight mass spectrometry. We compared volatile profiles between: (1) symbiotic anemones containing their native symbiont, Breviolum minutum; (2) aposymbiotic anemones; and (3) cultured isolates of B. minutum. Overall, 152 BVOCs were detected, and classified into 14 groups based on their chemical structure, the most numerous groups being alkanes and aromatic compounds. A total of 53 BVOCs were differentially abundant between aposymbiotic anemones and B. minutum cultures; 13 between aposymbiotic and symbiotic anemones; and 60 between symbiotic anemones and cultures of B. minutum. More BVOCs were differentially abundant between cultured and symbiotic dinoflagellates than between aposymbiotic and symbiotic anemones, suggesting that symbiosis may modify symbiont physiology more than host physiology. This is the first volatilome analysis of the Aiptasia model system and provides a foundation from which to explore how BVOC production is perturbed under environmental stress, and ultimately the role they play in this important symbiosis.

Genomic answers for children: Dynamic analyses of >1000 pediatric rare disease genomes.

PURPOSE: This study aimed to provide comprehensive diagnostic and candidate analyses in a pediatric rare disease cohort through the Genomic Answers for Kids program. METHODS: Extensive analyses of 960 families with suspected genetic disorders included short-read exome sequencing and short-read genome sequencing (srGS); PacBio HiFi long-read genome sequencing (HiFi-GS); variant calling for single nucleotide variants (SNV), structural variant (SV), and repeat variants; and machine-learning variant prioritization. Structured phenotypes, prioritized variants, and pedigrees were stored in PhenoTips database, with data sharing through controlled access the database of Genotypes and Phenotypes. RESULTS: Diagnostic rates ranged from 11% in patients with prior negative genetic testing to 34.5% in naive patients. Incorporating SVs from genome sequencing added up to 13% of new diagnoses in previously unsolved cases. HiFi-GS yielded increased discovery rate with >4-fold more rare coding SVs compared with srGS. Variants and genes of unknown significance remain the most common finding (58% of nondiagnostic cases). CONCLUSION: Computational prioritization is efficient for diagnostic SNVs. Thorough identification of non-SNVs remains challenging and is partly mitigated using HiFi-GS sequencing. Importantly, community research is supported by sharing real-time data to accelerate gene validation and by providing HiFi variant (SNV/SV) resources from >1000 human alleles to facilitate implementation of new sequencing platforms for rare disease diagnoses.

ACG Clinical Report and Recommendations on Transition of Care in Children and Adolescents With Hereditary Polyposis Syndromes.

Transition of care (TOC) in adolescents and young adults (AYAs) with chronic gastrointestinal disorders has received increased attention, especially in those with inflammatory bowel disease. AYAs with hereditary polyposis syndromes are a heterogeneous group of patients with overlapping and complex medical needs. These patients are particularly vulnerable because of the risk of loss of continuity of care and subsequent poor disease outcomes. The Pediatric Committee of the American College of Gastroenterology commissioned a report with recommendations on TOC in AYAs with hereditary polyposis syndromes. This report aims at achieving best practice by both pediatric and adult gastroenterologists despite the paucity of published evidence in this population reflected in the included PRISMA report. Therefore, the group extrapolated findings from the literature related to other chronic gastrointestinal disorders, and a high degree of expert consensus was scored for all recommendations. The report addresses TOC through identifying shared domains followed by specific recommendations in disease management, including models of care, providers and patient and socioeconomic factors relevant to TOC. Areas of strong emphasis include the need for early planning, flexibility in the transition process to maintain continuity during major surgical procedures, patient and family psychological readiness, liaison among team members addressing transition, and changing insurance coverage in this population.

PTEN Hamartoma Syndrome in a Child Presenting With Malrotation, Panintestinal Polyps, Severe Anemia, and Protein-Losing Enteropathy.

PTEN hamartoma syndrome (PTEN-HS) is a rare syndrome including neurologic, neurodevelopmental, integumentary, endocrine, and gastrointestinal manifestations. Eosinophilic disorders of the gastrointestinal system are diverse group of disorders reported to be more common in PTEN-HS. Our patient had malrotation and obstruction in infancy and subsequently developed macrocephaly and a lipoma. She presented at 4 years of age with both iron deficiency anemia and hypoalbuminemia from protein-losing enteropathy. She went on to endoscopy, colonoscopy, and video capsule endoscopy showing gastric, small intestinal, and colonic polyps but with histology including both a mixed histologic characterization of the polyps as expected with PTEN-HS, along with eosinophilic esophagitis, gastric, duodenal, colonic and polyp eosinophilia. She improved with enteral nutritional support and budesonide. Intestinal malrotation is a previously unrecognized feature of PTEN-HS, in our patient protein-losing enteropathy may have resulted from polyposis or eosinophilic gastrointestinal disorder. Albeit rare, PTEN-HS represents an elusive differential diagnosis with a broad spectrum including gastrointestinal symptomatology. Our case report illustrates the overlap of clinical, endoscopic, and histologic findings that can complicate PTEN-HS.

Heat stress decreases the diversity, abundance and functional potential of coral gas emissions.

Terrestrial ecosystems emit large quantities of biogenic volatile organic compounds (BVOCs), many of which play important roles in abiotic stress responses, pathogen and grazing defences, inter- and intra-species communications, and climate regulation. Conversely, comparatively little is known about the diversity and functional potential of BVOCs produced in the marine environment, especially in highly productive coral reefs. Here we describe the first 'volatilomes' of two common reef-building corals, Acropora intermedia and Pocillopora damicornis, and how the functional potential of their gaseous emissions is altered by heat stress events that are driving rapid deterioration of coral reef ecosystems worldwide. A total of 87 BVOCs were detected from the two species and the chemical richness of both coral volatilomes-particularly the chemical classes of alkanes and carboxylic acids-decreased during heat stress by 41% and 62% in A. intermedia and P. damicornis, respectively. Across both coral species, the abundance of individual compounds changed significantly during heat stress, with the majority (>86%) significantly decreasing compared to control conditions. Additionally, almost 60% of the coral volatilome (or 52 BVOCs) could be assigned to four key functional groups based on their activities in other species or systems, including stress response, chemical signalling, climate regulation and antimicrobial activity. The total number of compounds assigned to these functions decreased significantly under heat stress for both A. intermedia (by 35%) and P. damicornis (by 64%), with most dramatic losses found for climatically active BVOCs in P. damicornis and antimicrobial BVOCs in A. intermedia. Together, our observations suggest that future heat stress events predicted for coral reefs will reduce the diversity, quantity and functional potential of BVOCs emitted by reef-building corals, potentially further compromising the healthy functioning of these ecosystems.

Pathogenic variants in TNRC6B cause a genetic disorder characterised by developmental delay/intellectual disability and a spectrum of neurobehavioural phenotypes including autism and ADHD.

BACKGROUND: Rare variants in hundreds of genes have been implicated in developmental delay (DD), intellectual disability (ID) and neurobehavioural phenotypes. TNRC6B encodes a protein important for RNA silencing. Heterozygous truncating variants have been reported in three patients from large cohorts with autism, but no full phenotypic characterisation was described. METHODS: Clinical and molecular characterisation was performed on 17 patients with TNRC6B variants. Clinical data were obtained by retrospective chart review, parent interviews, direct patient interaction with providers and formal neuropsychological evaluation. RESULTS: Clinical findings included DD/ID (17/17) (speech delay in 94% (16/17), fine motor delay in 82% (14/17) and gross motor delay in 71% (12/17) of subjects), autism or autistic traits (13/17), attention deficit and hyperactivity disorder (ADHD) (11/17), other behavioural problems (7/17) and musculoskeletal findings (12/17). Other congenital malformations or clinical findings were occasionally documented. The majority of patients exhibited some dysmorphic features but no recognisable gestalt was identified. 17 heterozygous TNRC6B variants were identified in 12 male and five female unrelated subjects by exome sequencing (14), a targeted panel (2) and a chromosomal microarray (1). The variants were nonsense (7), frameshift (5), splice site (2), intragenic deletions (2) and missense (1). CONCLUSIONS: Variants in TNRC6B cause a novel genetic disorder characterised by recurrent neurocognitive and behavioural phenotypes featuring DD/ID, autism, ADHD and other behavioural abnormalities. Our data highly suggest that haploinsufficiency is the most likely pathogenic mechanism. TNRC6B should be added to the growing list of genes of the RNA-induced silencing complex associated with ID/DD, autism and ADHD.

Extrachromosomal Genetic Engineering of the Marine Diatom Phaeodactylum tricornutum Enables the Heterologous Production of Monoterpenoids.

Geraniol is a commercially relevant plant-derived monoterpenoid that is a main component of rose essential oil and used as insect repellent. Geraniol is also a key intermediate compound in the biosynthesis of the monoterpenoid indole alkaloids (MIAs), a group of over 2000 compounds that include high-value pharmaceuticals. As plants naturally produce extremely small amounts of these molecules and their chemical synthesis is complex, industrially sourcing these compounds is costly and inefficient. Hence, microbial hosts suitable to produce MIA precursors through synthetic biology and metabolic engineering are currently being sought. Here, we evaluated the suitability of a eukaryotic microalga, the marine diatom Phaeodactylum tricornutum, for the heterologous production of monoterpenoids. Profiling of endogenous metabolism revealed that P. tricornutum, unlike other microbes employed for industrial production of terpenoids, accumulates free pools of the precursor geranyl diphosphate. To evaluate the potential for larger synthetic biology applications, we engineered P. tricornutum through extrachromosomal, episome-based expression, for the heterologous biosynthesis of the MIA intermediate geraniol. By profiling the production of geraniol resulting from various genetic and cultivation arrangements, P. tricornutum reached the maximum geraniol titer of 0.309 mg/L in phototrophic conditions. This work provides (i) a detailed analysis of P. tricornutum endogenous terpenoid metabolism, (ii) a successful demonstration of extrachromosomal expression for metabolic pathway engineering with potential gene-stacking applications, and (iii) a convincing proof-of-concept of the suitability of P. tricornutum as a novel production platform for heterologous monoterpenoids, with potential for complex pathway engineering aimed at the heterologous production of MIAs.

Revealing changes in the microbiome of Symbiodiniaceae under thermal stress.

Symbiodiniaceae are a diverse family of marine dinoflagellates, well known as coral endosymbionts. Isolation and in vitro culture of Symbiodiniaceae strains for physiological studies is a widely adopted tool, especially in the context of understanding how environmental stress perturbs Symbiodiniaceae cell functioning. While the bacterial microbiomes of corals often correlate with coral health, the bacterial communities co-cultured with Symbiodiniaceae isolates have been largely overlooked, despite the potential of bacteria to significantly influence the emergent physiological properties of Symbiodiniaceae cultures. We examined the physiological response to heat stress by Symbiodiniaceae isolates (spanning three genera) with well-described thermal tolerances, and combined these observations with matched changes in bacterial composition and abundance through 16S rRNA metabarcoding. Under thermal stress, there were Symbiodiniaceae strain-specific changes in maximum quantum yield of photosystem II (proxy for health) and growth rates that were accompanied by changes in the relative abundance of multiple Symbiodiniaceae-specific bacteria. However, there were no Symbiodiniaceae-independent signatures of bacterial community reorganisation under heat stress. Notably, the thermally tolerant Durusdinium trenchii (ITS2 major profile D1a) had the most stable bacterial community under heat stress. Ultimately, this study highlights the complexity of Symbiodiniaceae-bacteria interactions and provides a first step towards uncoupling their relative contributions towards Symbiodiniaceae physiological functioning.

Coral endosymbionts (Symbiodiniaceae) emit species-specific volatilomes that shift when exposed to thermal stress.

Biogenic volatile organic compounds (BVOCs) influence organism fitness by promoting stress resistance and regulating trophic interactions. Studies examining BVOC emissions have predominantly focussed on terrestrial ecosystems and atmospheric chemistry - surprisingly, highly productive marine ecosystems remain largely overlooked. Here we examined the volatilome (total BVOCs) of the microalgal endosymbionts of reef invertebrates, Symbiodiniaceae. We used GC-MS to characterise five species (Symbiodinium linucheae, Breviolum psygmophilum, Durusdinium trenchii, Effrenium voratum, Fugacium kawagutii) under steady-state growth. A diverse range of 32 BVOCs were detected (from 12 in D. trenchii to 27 in S. linucheae) with halogenated hydrocarbons, alkanes and esters the most common chemical functional groups. A thermal stress experiment on thermally-sensitive Cladocopium goreaui and thermally-tolerant D. trenchii significantly affected the volatilomes of both species. More BVOCs were detected in D. trenchii following thermal stress (32 °C), while fewer BVOCs were recorded in stressed C. goreaui. The onset of stress caused dramatic increases of dimethyl-disulfide (98.52%) in C. goreaui and nonanoic acid (99.85%) in D. trenchii. This first volatilome analysis of Symbiodiniaceae reveals that both species-specificity and environmental factors govern the composition of BVOC emissions among the Symbiodiniaceae, which potentially have, as yet unexplored, physiological and ecological importance in shaping coral reef community functioning.

Comparison of the demographic characteristics of pediatric and adult colorectal cancer patients: a national inpatient sample based analysis.

BACKGROUND: Colorectal cancer in children is rare, but characterized by late presentation, unfavorable histology and poor prognosis. Risk factors for colorectal cancer in children overlap with those for adults with greater influence of hereditary syndromes. The epidemiology of colon cancer in children is poorly understood; the aim of this study was to characterize and compare the demographics and relevant clinical characteristics of pediatric and adult colon cancer, using a national inpatient sample. METHODS: The AHRQ online resource HCUPnet/KID database was queried for children, under the age of 18 admitted with ICD 9 CM diagnoses relating to colorectal cancer, at the time of discharge. For comparison, the corresponding diagnoses in adult patients were queried for each successive year. Patient demographics including residential type and median income by zip-code, tumor localization; if recorded, and mean hospital charges were all accrued and analyzed. RESULTS: Inpatient admissions for pediatric colorectal cancer were more likely male (54%), in the 15-17 years age bracket (57%). They were significantly more likely from Southwestern regions of the Unites States, and were significantly more likely from residential zip-codes identified as at or below the lowest income quartile than adult CRC patients or pediatric patients as a whole. Hospital charges have more than quadrupled over the time period studied (1997-2012). CONCLUSIONS: Pediatric colorectal cancer is the most common primary gastrointestinal malignancy in children. Better understanding associated risk factors including those associated with gender, geographic region and social economic status may contribute to future prevention or early detection strategies.

Defining the core microbiome of the symbiotic dinoflagellate, Symbiodinium.

Dinoflagellates of the genus Symbiodinium underpin the survival and ecological success of corals. The use of cultured strains has been particularly important to disentangle the complex life history of Symbiodinium and their contribution to coral host physiology. However, these cultures typically harbour abundant bacterial communities which likely play important, but currently unknown, roles in Symbiodinium biology. We characterized the bacterial communities living in association with a wide phylogenetic diversity of Symbiodinium cultures (18 types spanning 5 clades) to define the core Symbiodinium microbiome. Similar to other systems, bacteria were nearly two orders of magnitude more numerically abundant than Symbiodinium cells and we identified three operational taxonomic units (OTUs) which were present in all cultures. These represented the α-proteobacterium Labrenzia and the γ-proteobacteria Marinobacter and Chromatiaceae. Based on the abundance and functional potential of bacteria harboured in these cultures, their contribution to Symbiodinium physiology can no longer be ignored.

Genetic Counselor Practices Involving Pediatric Patients with FAP: an Investigation of their Self-Reported Strategies for Genetic Testing and Hepatoblastoma Screening.

Familial adenomatous polyposis (FAP) is a cancer predisposition syndrome that causes early-onset polyposis and is associated with an increased risk for hepatoblastoma. There is currently a lack of consensus on when to order APC (adenomatous polyposis coli) gene testing or implement surveillance for hepatoblastoma. An online questionnaire was completed by 62 genetic counselors to capture their current practices regarding these questions. Extracolonic findings associated with FAP that were most likely to prompt APC testing in an otherwise asymptomatic 10 year-old child with a negative family history were multiple desmoid tumors, congenital hypertrophy of the retinal pigment epithelium (CHRPE), jaw osteomas, and hepatoblastoma. For hepatoblastoma screening, the majority did recommend this in children less than age five years with known APC mutations. An interval of every 3-6 months was most commonly suggested; however, responses extended to screening on a less than annual basis. These results highlight the need for further investigation into why some genetic counselors do not recommend APC testing in young at-risk children and what factors influence views about the ideal age and indication for APC testing. Studies of these issues would help to define the best clinical practice model for genetic testing and hepatoblastoma screening in pediatric patients with FAP.