Background: Bacterial cancer therapy was first trialled in patients at the end of the nineteenth century. More recently, tumour-targeting bacteria have been harnessed to deliver plasmid-expressed therapeutic interfering RNA to a range of solid tumours. A major limitation to clinical translation of this is the short-term nature of RNA interference in vivo due to plasmid instability.
View Article and Find Full Text PDFMicrobial communities at the airway mucosal barrier are conserved and highly ordered, in likelihood reflecting co-evolution with human host factors. Freed of selection to digest nutrients, the airway microbiome underpins cognate management of mucosal immunity and pathogen resistance. We show here the initial results of systematic culture and whole-genome sequencing of the thoracic airway bacteria, identifying 52 novel species amongst 126 organisms that constitute 75% of commensals typically present in heathy individuals.
View Article and Find Full Text PDFBackground And Aims: Endoscopic therapies have moved to the forefront in the removal of small, well-differentiated duodenal neuroendocrine tumors (NETs). Classic procedures used to address small tumors, especially those less than 1 cm in diameter, are banding without resection, ligation endoscopic mucosal resection, or endoscopic submucosal dissection. Endoscopic full-thickness resection (EFTR) is a procedure developed recently that allows for sealing off of the tissue surrounding the tumor before full-thickness removal.
View Article and Find Full Text PDFObjective: Assess opinions that influence treatment choice for single sided deafness (SSD).
Study Design: Retrospective chart review.
Setting: Tertiary neurotology referral center.
This randomized, controlled trial evaluated whether a brief educational program (ie, Scenario-Tailored Opioid Messaging Program [STOMP]) would improve parental opioid risk knowledge, perceptions, and analgesic efficacy; ensure safe opioid use decisions; and impact prescription opioid use after surgery. Parent-child dyads (n = 604) who were prescribed an opioid for short-term use were randomized to routine instruction (Control) or routine plus STOMP administered preoperatively. Baseline and follow-up surveys assessed parents' awareness and perceived seriousness of adverse opioid effects, and their analgesic efficacy.
View Article and Find Full Text PDFObjective: Comorbid conditions are associated with poor prognosis in COVID-19. Registry data show that patients with cirrhosis may be at high risk. However, outcome comparisons among patients with cirrhosis+COVID-19 versus patients with COVID-19 alone and cirrhosis alone are lacking.
View Article and Find Full Text PDFJ Psychosom Obstet Gynaecol
September 2021
Purpose: Endometriosis is a chronic condition where endometrial-like cells proliferate outside the uterus causing pain and disability. Limited treatments are available but symptom management is essential for social and economic participation. The aim was to compare women's and health professionals' perceptions of quality of endometriosis health care and opportunities for improvements.
View Article and Find Full Text PDFIntroduction: Nutritional status (NS), defined by undernutrition (body mass index [BMI] <5th percentile) or overnutrition (BMI ≥ 85th percentile), is a poor prognostic indicator in pediatric oncology patients. The impact of NS has been primarily studied in hematologic malignancies. This review is intended to summarize literature reporting on the association of NS and treatment-related outcomes in pediatric solid tumors.
View Article and Find Full Text PDFJ Allergy Clin Immunol
March 2017
Background: Patients with asthma and healthy controls differ in bacterial colonization of the respiratory tract. The upper airways have been shown to reflect colonization of the lower airways, the actual site of inflammation in asthma, which is hardly accessible in population studies.
Objective: We sought to characterize the bacterial communities at 2 sites of the upper respiratory tract obtained from children from a rural area and to relate these to asthma.
Objectives: There is a growing body of evidence suggesting a shared genetic susceptibility between many neuropsychiatric disorders, including schizophrenia, autism, intellectual disability (ID) and epilepsy. The sodium channel, voltage-gated type II α subunit gene SCN2A has been shown to exhibit loss-of-function (LoF) mutations in individuals with seizure disorders, ID, autism and schizophrenia. The role of LoF mutations in schizophrenia is still uncertain with only one such mutation identified to date.
View Article and Find Full Text PDFCurrent use of microbes for metabolic engineering suffers from loss of metabolic output due to natural selection. Rather than combat the evolution of bacterial populations, we chose to embrace what makes biological engineering unique among engineering fields - evolving materials. We harnessed bacteria to compute solutions to the biological problem of metabolic pathway optimization.
View Article and Find Full Text PDFInherited alleles account for most of the genetic risk for schizophrenia. However, new (de novo) mutations, in the form of large chromosomal copy number changes, occur in a small fraction of cases and disproportionally disrupt genes encoding postsynaptic proteins. Here we show that small de novo mutations, affecting one or a few nucleotides, are overrepresented among glutamatergic postsynaptic proteins comprising activity-regulated cytoskeleton-associated protein (ARC) and N-methyl-d-aspartate receptor (NMDAR) complexes.
View Article and Find Full Text PDFPsychotic experiences are not uncommon in general population samples, but no studies have examined to what extent confirmed risk variants for schizophrenia are associated with such experiences. A total of 3483 children in a birth cohort study participated in semistructured interviews for psychotic experiences at ages 12 and 18. We examined whether (1) a composite measure of risk for schizophrenia conferred by common alleles (polygenic score) was associated with psychotic experiences, (2) variants with genome-wide evidence for association with schizophrenia were associated with psychotic experiences, and (3) we could identify genetic variants for psychotic experiences using a genome-wide association (GWA) approach.
View Article and Find Full Text PDFAm J Med Genet B Neuropsychiatr Genet
December 2011
Large collaborative Genome-wide Association studies of schizophrenia have identified genes and genomic regions that are associated with the disorder at highly stringent levels of statistical significance. Among these, transcription factor 4 (TCF4) is one of the best supported although the associated SNP (rs9960767) is located within intron 3 and has no obvious function. Seeking the mechanism at TCF responsible for the association, we examined TCF4 for coding variants, and for cis regulated variation in TCF4 gene expression correlated with the associated SNP using an assay to detect differential allelic expression.
View Article and Find Full Text PDFAm J Med Genet B Neuropsychiatr Genet
December 2011
We sought to investigate the contribution of extended runs of homozygosity in a genome-wide association dataset of 1,955 Alzheimer's disease cases and 955 elderly screened controls genotyped for 529,205 autosomal single nucleotide polymorphisms. Tracts of homozygosity may mark regions inherited from a common ancestor and could reflect disease loci if observed more frequently in cases than controls. We found no excess of homozygous tracts in Alzheimer's disease cases compared to controls and no individual run of homozygosity showed association to Alzheimer's disease.
View Article and Find Full Text PDFA recent study reported a genome-wide significant association between schizophrenia and rs12807809-a SNP located approximately 3 kbp upstream of the neurogranin gene (NRGN). We sought to determine if (a) NRGN contains common exonic variants or variants affecting expression (eQTLs) that could account for the association with rs12807809 and (b) there exist rare non-synonymous highly penetrant variants that could potentially confer high risk of schizophrenia. We sequenced all four exons of NRGN in a screening set of 14 individuals but found no novel common polymorphisms.
View Article and Find Full Text PDFRecent findings from genetic epidemiology and from genome-wide association studies point strongly to a partial overlap in the genes that contribute susceptibility to schizophrenia and bipolar disorder (BD). Previous data have also directly implicated one of the best supported schizophrenia-associated loci, zinc finger binding protein 804A (ZNF804A), as showing trans-disorder effects, and the same is true for one of the best supported bipolar loci, calcium channel, voltage-dependent, L type, alpha 1C subunit (CACNA1C) which has also been associated with schizophrenia. We have undertaken a cross-phenotype study based upon the remaining variants that show genome-wide evidence for association in large schizophrenia and BD meta-analyses.
View Article and Find Full Text PDFContext: The Zinc Finger Protein 804A gene (ZNF804A) has been implicated in schizophrenia susceptibility by several genome-wide association studies. ZNF804A is brain expressed but of unknown function.
Objective: To investigate whether the identified risk allele at the disease-associated single nucleotide polymorphism rs1344706 is associated with variation in neuropsychological performance in patients and controls.
We carried out a genome-wide association study of schizophrenia (479 cases, 2,937 controls) and tested loci with P < 10(-5) in up to 16,726 additional subjects. Of 12 loci followed up, 3 had strong independent support (P < 5 x 10(-4)), and the overall pattern of replication was unlikely to occur by chance (P = 9 x 10(-8)). Meta-analysis provided strongest evidence for association around ZNF804A (P = 1.
View Article and Find Full Text PDFA large-scale population trial using the Triple P-Positive Parenting Program (TPS) was evaluated. The target population was all parents of 4- to 7-year-old children residing in ten geographical catchment areas in Brisbane (intervention communities) and ten sociodemographically matched catchment areas from Sydney (5) and Melbourne (5), care as usual (CAU) comparison communities. All five levels of the Triple P multilevel system of intervention were employed; including a local mass media strategy, a primary care strategy, and three more intensive levels of parenting intervention delivered by a range of service providers (e.
View Article and Find Full Text PDFAKT1 (V-akt murine thyoma viral oncogene homolog 1) is involved in intracellular signalling pathways postulated as of aetiological importance in schizophrenia. Markers in the AKT1 gene have also recently been associated with schizophrenia in two samples of European origin and in Japanese and Iranian samples. Aiming to replicate these findings, we examined ten SNPs spanning AKT1 in a UK case-control sample (schizophrenia cases n=673, controls n=716).
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