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1.
J Am Coll Surg ; 231(5): 520-526, 2020 11.
Article in English | MEDLINE | ID: mdl-32758533

ABSTRACT

BACKGROUND: Little is known regarding important long-term outcomes after robotic paraesophageal hernia (PEH) repairs, such as symptom relief and recurrence rates. The aim of this study was to evaluate the long-term clinical outcomes in a large series of patients undergoing robotic PEH repair. STUDY DESIGN: This prospective, IRB-approved study analyzed adult patients who underwent robotic PEH repair, from 2010 to 2014, at a high-volume tertiary academic medical center. Detailed information on patient characteristics, perioperative factors, and long-term patient-reported outcomes for up to 5 years postoperatively were collected. Objective long-term outcomes included radiographic evidence of PEH recurrence at 1, 3, and 5 years postoperatively. RESULTS: A total of 233 patients underwent robotic PEH repair during the study period-70% were primary, 30% were revisional. Seventy-eight percent of patients (181) had a type III PEH, 21% (49) had a type IV, and 1% (3) had a type II. At 5 years postoperatively, 62% of patients (145 of 233) were available for follow-up, with a radiographic recurrence rate of 9% (13 of 145). Additionally, there was a significant improvement in the GERD-HRQL score at 5 years postoperatively (preoperative: 25.6 ± 8.7, 5-year postoperative, 4.5 ± 1.7, p < 0.01, 95% CI 19.7 to 22.5). CONCLUSIONS: This study represents one of the largest longitudinal robotic foregut surgical databases to date. Our results demonstrate that robotic PEH repair with an experienced surgical team is a safe and effective alternative to laparoscopic repair, with excellent long-term outcomes, including a very low recurrence rate.


Subject(s)
Hernia, Hiatal/surgery , Herniorrhaphy/methods , Robotic Surgical Procedures , Aged , Female , Humans , Male , Patient Reported Outcome Measures , Prospective Studies , Recurrence , Reoperation
2.
Cancer Res ; 78(13): 3510-3521, 2018 07 01.
Article in English | MEDLINE | ID: mdl-29724719

ABSTRACT

Point mutations in the seed sequence of miR-142-3p are present in a subset of acute myelogenous leukemia (AML) and in several subtypes of B-cell lymphoma. Here, we show that mutations associated with AML result both in loss of miR-142-3p function and in decreased miR-142-5p expression. Mir142 loss altered the hematopoietic differentiation of multipotent hematopoietic progenitors, enhancing their myeloid potential while suppressing their lymphoid potential. During hematopoietic maturation, loss of Mir142 increased ASH1L protein expression and consequently resulted in the aberrant maintenance of Hoxa gene expression in myeloid-committed hematopoietic progenitors. Mir142 loss also enhanced the disease-initiating activity of IDH2-mutant hematopoietic cells in mice. Together these data suggest a novel model in which miR-142, through repression of ASH1L activity, plays a key role in suppressing HOXA9/A10 expression during normal myeloid differentiation. AML-associated loss-of-function mutations of MIR142 disrupt this negative signaling pathway, resulting in sustained HOXA9/A10 expression in myeloid progenitors/myeloblasts and ultimately contributing to leukemic transformation.Significance: These findings provide mechanistic insights into the role of miRNAs in leukemogenesis and hematopoietic stem cell function. Cancer Res; 78(13); 3510-21. ©2018 AACR.


Subject(s)
DNA-Binding Proteins/genetics , Gene Expression Regulation, Leukemic , Histone-Lysine N-Methyltransferase/genetics , Leukemia, Myeloid, Acute/genetics , MicroRNAs/genetics , MicroRNAs/metabolism , Transcription Factors/genetics , Animals , Bone Marrow/pathology , Carcinogenesis/genetics , DNA-Binding Proteins/metabolism , Disease Models, Animal , HEK293 Cells , Hematopoietic Stem Cells/pathology , Histone-Lysine N-Methyltransferase/metabolism , Homeobox A10 Proteins , Homeodomain Proteins/metabolism , Humans , Isocitrate Dehydrogenase/genetics , Leukemia, Myeloid, Acute/pathology , Loss of Function Mutation , Mice , Mice, Inbred C57BL , Mice, Knockout , Point Mutation , Receptor, EphB2 , Signal Transduction/genetics , Transcription Factors/metabolism
3.
Int J Syst Evol Microbiol ; 63(Pt 9): 3280-3286, 2013 Sep.
Article in English | MEDLINE | ID: mdl-23475344

ABSTRACT

Strain IK-1(T) was isolated from decaying tissues of the shrub Wikstroemia oahuensis collected on O'ahu, Hawai'i. Cells were rods that stained Gram-negative. Gliding motility was not observed. The strain was oxidase-negative and catalase-positive. Zeaxanthin was the major carotenoid. Flexirubin-type pigments were not detected. The most abundant fatty acids in whole cells of IK-1(T) grown on R2A were iso-C(15:0) and one or both of C(16:1)ω7c and C(16:1)ω6c. Based on comparisons of the nucleotide sequence of the 16S rRNA gene, the closest neighbouring type strains were Flavobacterium rivuli WB 3.3-2(T) and Flavobacterium subsaxonicum WB 4.1-42(T), with which IK-1(T) shares 93.84 and 93.67% identity, respectively. The G+C content of the genomic DNA was 44.2 mol%. On the basis of distance from its nearest phylogenetic neighbours and phenotypic differences, the species Flavobacterium akiainvivens sp. nov. is proposed to accommodate strain IK-1(T) ( =ATCC BAA-2412(T) =CIP 110358(T)) as the type strain. The description of the genus Flavobacterium is emended to reflect the DNA G+C contents of Flavobacterium akiainvivens IK-1(T) and other species of the genus Flavobacterium described since the original description of the genus.


Subject(s)
Flavobacterium/classification , Phylogeny , Wikstroemia/microbiology , Wood/microbiology , Base Composition , DNA, Bacterial/genetics , Fatty Acids/analysis , Flavobacterium/genetics , Flavobacterium/isolation & purification , Hawaii , Molecular Sequence Data , RNA, Ribosomal, 16S/genetics , Sequence Analysis, DNA , Xanthophylls/analysis , Zeaxanthins
4.
J Speech Lang Hear Res ; 54(6): 1628-43, 2011 Dec.
Article in English | MEDLINE | ID: mdl-21930616

ABSTRACT

PURPOSE: To demonstrate that early childhood speech sound disorders (SSD) and later school-age reading, written expression, and spelling skills are influenced by shared endophenotypes that may be in part genetic. METHOD: Children with SSD and their siblings were assessed at early childhood (ages 4-6 years) and followed at school age (7-12 years). The relationship of shared endophenotypes with early childhood SSD and school-age outcomes and the shared genetic influences on these outcomes were examined. RESULTS: Structural equation modeling demonstrated that oral motor skills, phonological awareness, phonological memory, vocabulary, and speeded naming have varying influences on reading decoding, spelling, spoken language, and written expression at school age. Genetic linkage studies demonstrated linkage for reading, spelling, and written expression measures to regions on chromosomes 1, 3, 6, and 15 that were previously linked to oral motor skills, articulation, phonological memory, and vocabulary at early childhood testing. CONCLUSIONS: Endophenotypes predict school-age literacy outcomes over and above that predicted by clinical diagnoses of SSD or language impairment. Findings suggest that these shared endophenotypes and common genetic influences affect early childhood SSD and later school-age reading, spelling, spoken language, and written expression skills.


Subject(s)
Articulation Disorders/genetics , Endophenotypes , Genetic Linkage , Phonetics , Reading , Speech Disorders/genetics , Articulation Disorders/epidemiology , Articulation Disorders/rehabilitation , Child , Child, Preschool , Dyslexia/epidemiology , Dyslexia/genetics , Dyslexia/rehabilitation , Education , Female , Genetic Predisposition to Disease/epidemiology , Genetic Predisposition to Disease/genetics , Humans , Male , Memory/physiology , Motor Skills/physiology , Risk Factors , Siblings , Speech/physiology , Speech Disorders/epidemiology , Speech Disorders/rehabilitation , Speech Production Measurement
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