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1.
JACC Case Rep ; 4(17): 1080-1085, 2022 Sep 07.
Article in English | MEDLINE | ID: mdl-36124144

ABSTRACT

A 22-year-old avid cyclist presented with 1 month of right lower extremity pain and associated swelling. Subsequent imaging demonstrated an extensive acute deep vein thrombosis (DVT) in the setting of right iliac vein compression from psoas muscle hypertrophy. We present an unusual risk factor for DVT among cyclists. (Level of Difficulty: Intermediate.).

2.
J Am Coll Cardiol ; 79(20): 2037-2057, 2022 05 24.
Article in English | MEDLINE | ID: mdl-35589166

ABSTRACT

The incidence of injection drug use-associated infective endocarditis has been increasing rapidly over the last decade. Patients with drug use-associated infective endocarditis present an increasingly common clinical challenge with poor long-term outcomes and high reinfection and readmission rates. Their care raises issues unique to this population, including antibiotic selection and administration, indications for and ethical issues surrounding surgical intervention, and importantly management of the underlying substance use disorder to minimize the risk of reinfection. Successful treatment of these patients requires a broad understanding of these concerns. A multidisciplinary, collaborative approach providing a holistic approach to treating both the acute infection along with effectively addressing substance use disorder is needed to improve short-term and longer-term outcomes.


Subject(s)
Drug Users , Endocarditis, Bacterial , Endocarditis , Substance Abuse, Intravenous , Endocarditis/diagnosis , Endocarditis/drug therapy , Endocarditis/etiology , Endocarditis, Bacterial/diagnosis , Endocarditis, Bacterial/drug therapy , Endocarditis, Bacterial/etiology , Humans , Pharmaceutical Preparations , Reinfection , Retrospective Studies , Substance Abuse, Intravenous/complications , Substance Abuse, Intravenous/epidemiology
4.
Oncoscience ; 2(1): 1-2, 2015.
Article in English | MEDLINE | ID: mdl-25821839

ABSTRACT

[This corrects the article on p. 360 in vol. 1, PMID: 25594030.].

5.
DNA Repair (Amst) ; 26: 44-53, 2015 Feb.
Article in English | MEDLINE | ID: mdl-25547252

ABSTRACT

Efficient DNA double-strand break (DSB) repair is a critical determinant of cell survival in response to DNA damaging agents, and it plays a key role in the maintenance of genomic integrity. Homologous recombination (HR) and non-homologous end-joining (NHEJ) represent the two major pathways by which DSBs are repaired in mammalian cells. We now understand that HR and NHEJ repair are composed of multiple sub-pathways, some of which still remain poorly understood. As such, there is great interest in the development of novel assays to interrogate these key pathways, which could lead to the development of novel therapeutics, and a better understanding of how DSBs are repaired. Furthermore, assays which can measure repair specifically at endogenous chromosomal loci are of particular interest, because of an emerging understanding that chromatin interactions heavily influence DSB repair pathway choice. Here, we present the design and validation of a novel, next-generation sequencing-based approach to study DSB repair at chromosomal loci in cells. We demonstrate that NHEJ repair "fingerprints" can be identified using our assay, which are dependent on the status of key DSB repair proteins. In addition, we have validated that our system can be used to detect dynamic shifts in DSB repair activity in response to specific perturbations. This approach represents a unique alternative to many currently available DSB repair assays, which typical rely on the expression of reporter genes as an indirect read-out for repair. As such, we believe this tool will be useful for DNA repair researchers to study NHEJ repair in a high-throughput and sensitive manner, with the capacity to detect subtle changes in DSB repair patterns that was not possible previously.


Subject(s)
DNA Breaks, Double-Stranded , DNA End-Joining Repair , DNA Mutational Analysis/methods , High-Throughput Nucleotide Sequencing/methods , Animals , Chromatin/metabolism , DNA/metabolism , DNA-Binding Proteins/metabolism , Genetic Loci , Humans , INDEL Mutation , Mammals , Recombinational DNA Repair
6.
Cell Cycle ; 13(22): 3465-6, 2014.
Article in English | MEDLINE | ID: mdl-25493409
7.
Oncoscience ; 1(5): 360-6, 2014.
Article in English | MEDLINE | ID: mdl-25594030

ABSTRACT

The molecular abnormalities leading to sporadic parathyroid adenomas, a common type of human endocrine neoplasm, are heterogeneous and incompletely understood. Using whole exome and direct sequencing of parathyroid adenoma DNA samples, we identified recurrent somatic mutations in the ZFX gene. ZFX is a member of Krueppel C2H2 type zinc finger protein family, was initially described as a homolog of ZFY, and has been implicated as a transcription factor regulating embryonic stem cell renewal. The ZFX mutations we identified were strikingly specific, focused in each tumor on one encoded residue in a hotspot of two consecutive highly conserved arginine residues (R786/787; arginine to glutamine, threonine or leucine) in a zinc finger domain near the C-terminus of the protein. The intragenic specificity of these recurrently selected mutations, their confirmed expression within the tumors, the absence of loss of heterozygosity, and the absence of these mutations among over 4000 ZFX alleles in the dbSNP137 database, strongly suggest a novel role for ZFX as a human proto-oncogene. Further, these observations highlight the mutated zinc-finger domain as a new focal point for understanding ZFX's normal and tumorigenic functions, and for development of molecularly-targeted therapeutics.

8.
Horm Cancer ; 4(5): 301-7, 2013 Oct.
Article in English | MEDLINE | ID: mdl-23715670

ABSTRACT

The molecular pathogenesis of sporadic parathyroid adenomas is incompletely understood. The possible role of cyclin-dependent kinase inhibitor (CDKI) genes was raised by recognition of cyclin D1 as a parathyroid oncogene, identification of rare germline mutations in CDKI genes in patients with multiple endocrine neoplasia type 1; that in rodents, mutation in Cdkn1b caused parathyroid tumors; and subsequently through identification of rare predisposing germline sequence variants and somatic mutation of CDKN1B, encoding p27(kip1), in sporadic human parathyroid adenoma. We therefore sought to determine whether mutations/variants in the other six CDKI genes CDKN1A, CDKN1C, CDKN2A, CDKN2B, CDKN2C, and CDKN2D, encoding p21, p57, p14(ARF)/p16, p15, p18, and p19, respectively, contribute to the development of typical parathyroid adenomas. In a series of 85 sporadic parathyroid adenomas, direct DNA sequencing identified alterations in five adenomas (6 %): Two contained distinct heterozygous changes in CDKN1A, one germline and one of undetermined germline status; one had a CDKN2B germline alteration, accompanied by loss of the normal allele in the tumor (LOH); two had variants of CDKN2C, one somatic and one germline with LOH. Abnormalities of three of the mutant proteins were readily demonstrable in vitro. Thus, germline mutations/rare variants in CDKN1A, CDKN2B, and CDKN2C likely contribute to the development of a significant subgroup of common sporadic parathyroid adenomas, and somatic mutation in CDKN2C further suggests a direct role for CDKI alteration in conferring a selective growth advantage to parathyroid cells, providing novel support for the concept that multiple CDKIs can play primary roles in human neoplasia.


Subject(s)
Adenoma/genetics , Cyclin-Dependent Kinase Inhibitor Proteins/genetics , Germ-Line Mutation , Mutation, Missense , Parathyroid Neoplasms/genetics , Adenoma/metabolism , Aged , Aged, 80 and over , Base Sequence , Cell Culture Techniques , Cyclin-Dependent Kinase Inhibitor Proteins/metabolism , Cyclin-Dependent Kinase Inhibitor p15/genetics , Cyclin-Dependent Kinase Inhibitor p15/metabolism , Cyclin-Dependent Kinase Inhibitor p18/genetics , Cyclin-Dependent Kinase Inhibitor p18/metabolism , Cyclin-Dependent Kinase Inhibitor p21/genetics , Cyclin-Dependent Kinase Inhibitor p21/metabolism , HEK293 Cells , Humans , Hyperparathyroidism, Primary/genetics , Hyperparathyroidism, Primary/metabolism , Hyperparathyroidism, Primary/surgery , Middle Aged , Parathyroid Neoplasms/metabolism
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