Diagnosis of Ovarian Carcinoma Homologous Recombination DNA Repair Deficiency From Targeted Gene Capture Oncology Assays.

Purpose: Homologous recombination DNA repair deficiency (HRD) is a therapeutic biomarker for sensitivity to platinum and poly(ADP-ribose) polymerase inhibitor therapies in breast and ovarian cancers. Several molecular phenotypes and diagnostic strategies have been developed to assess HRD; however, their clinical implementation remains both technically challenging and methodologically unstandardized.

Methods: We developed and validated an efficient and cost-effective strategy for HRD determination on the basis of calculation of a genome-wide loss of heterozygosity (LOH) score through targeted, hybridization capture and next-generation DNA sequencing augmented with 3,000 common, polymorphic single-nucleotide polymorphism (SNP) sites distributed genome-wide.

Polyclonality, Shared Strains, and Convergent Evolution in Chronic Cystic Fibrosis Airway Infection.

is the most common respiratory pathogen isolated from patients with cystic fibrosis (CF) in the United States. Although modes of acquisition and genetic adaptation have been described for , resulting in improved diagnosis and treatment, these features remain more poorly defined for . To characterize the molecular epidemiology and genetic adaptation of during chronic CF airway infection and in response to antibiotic therapy.

Deep-Structure Adaptations and Culturally Grounded Prevention Interventions for Native Hawaiians: a Systematic Review of the Literature.

Research has shown that Native Hawaiians disproportionately suffer from behavioral disorders and chronic physical diseases, yet they have historically lacked effective and culturally relevant prevention interventions to address their pervasive health disparities. This article systematically reviewed the recent culturally relevant prevention intervention literature focused on Native Hawaiians. In this review, we assessed 14 peer-reviewed articles published between 2015 and 2020 that met inclusion and exclusion criteria pertaining to the development and/or evaluation of prevention interventions for Native Hawaiians.

Occurrence of cross-resistance and β-lactam seesaw effect in glycopeptide-, lipopeptide- and lipoglycopeptide-resistant MRSA correlates with membrane phosphatidylglycerol levels.

Background: Glycopeptides (GPs), lipopeptides (LPs) and lipoglycopeptides (LGPs) are related antimicrobials important for the management of invasive MRSA infections. Cross-resistance among these antibiotics in MRSA is well documented, as is the observation that susceptibility of MRSA to β-lactams increases as susceptibility to GPs and LPs decreases (i.e.

Improved Species-Level Clinical Identification of Enterobacteriaceae through Broad-Range PCR and Sequencing.

represent a diverse and medically important family of bacteria that are difficult to identify to the species level using the standard molecular method of 16S rRNA gene sequencing. Prior work has demonstrated the value of gene sequence analysis in resolving different members of the family. However, existing protocols are not optimized for clinical use and exhibit several limitations in practice.

Genomic Analysis Identifies Novel Pseudomonas aeruginosa Resistance Genes under Selection during Inhaled Aztreonam Therapy .

Inhaled aztreonam is increasingly used for chronic suppression in patients with cystic fibrosis (CF), but the potential for that organism to evolve aztreonam resistance remains incompletely explored. Here, we performed genomic analysis of clonally related pre- and posttreatment CF clinical isolate pairs to identify genes that are under positive selection during aztreonam therapy We identified 16 frequently mutated genes associated with aztreonam resistance, the most prevalent being and , and 13 of which increased aztreonam resistance when introduced as single gene transposon mutants. Several previously implicated aztreonam resistance genes were found to be under positive selection in clinical isolates even in the absence of inhaled aztreonam exposure, indicating that other selective pressures in the cystic fibrosis airway can promote aztreonam resistance.

Gallium disrupts bacterial iron metabolism and has therapeutic effects in mice and humans with lung infections.

The lack of new antibiotics is among the most critical challenges facing medicine. The problem is particularly acute for Gram-negative bacteria. An unconventional antibiotic strategy is to target bacterial nutrition and metabolism.

Evolved Aztreonam Resistance Is Multifactorial and Can Produce Hypervirulence in .

While much attention has been focused on acquired antibiotic resistance genes, chromosomal mutations may be most important in chronic infections where isolated, persistently infecting lineages experience repeated antibiotic exposure. Here, we used experimental evolution and whole-genome sequencing to investigate chromosomally encoded mutations causing aztreonam resistance in and characterized the secondary consequences of resistance development. We identified 19 recurrently mutated genes associated with aztreonam resistance.

Placental IL-10 dysregulation and association with bronchopulmonary dysplasia risk.

Cytokine profiles in amniotic fluid, cord serum, and tracheal aspirate of premature infants suggest a shift toward a proinflammatory state. Cytokines also contribute to the pathogenesis of bronchopulmonary dysplasia (BPD). We hypothesize that the initiating events for BPD are reflected in the placenta and propose that placental expression of cytokines provide a blueprint of events leading to BPD.

Severe umbilical cord inflammation-a predictor of periventricular leukomalacia in very low birth weight infants.

Chorioamnionitis has been associated with periventricular leukomalacia (PVL) in very low birth weight (VLBW) infants. We examined the association between the pathological severity of chorioamnionitis and PVL in VLBW infants. Thirty-four VLBW infants with PVL and 34 control infants matched for gestational age without a diagnosis of PVL or intraventricular hemorrhage were obtained from the Women and Infants' Hospital of Rhode Island's Neonatal Follow-up Clinic database.

Osteogenesis imperfecta.

Osteogenesis imperfecta (OI) is a rare congenital disorder of collagen production that results in brittle bones and affects other body systems containing collagen. This article reviews the current body of knowledge about OI and the management of infants with the disorder. Relieving pain, reducing the incidence of new fractures, establishing adequate follow-up, and connecting parents with community resources are the goals of management during the neonatal period.