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  • 1
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    Drosophila Muller F Elements Maintain a Distinct Set of Genomic Properties Over 40 Million Years of Evolution
    Oxford University Press (OUP) ; 2015
    In:  G3 Genes|Genomes|Genetics Vol. 5, No. 5 ( 2015-05-01), p. 719-740
    Details
    In: G3 Genes|Genomes|Genetics, Oxford University Press (OUP), Vol. 5, No. 5 ( 2015-05-01), p. 719-740
    Abstract: The Muller F element (4.2 Mb, ~80 protein-coding genes) is an unusual autosome of Drosophila melanogaster; it is mostly heterochromatic with a low recombination rate. To investigate how these properties impact the evolution of repeats and genes, we manually improved the sequence and annotated the genes on the D. erecta, D. mojavensis, and D. grimshawi F elements and euchromatic domains from the Muller D element. We find that F elements have greater transposon density (25–50%) than euchromatic reference regions (3–11%). Among the F elements, D. grimshawi has the lowest transposon density (particularly DINE-1: 2% vs. 11–27%). F element genes have larger coding spans, more coding exons, larger introns, and lower codon bias. Comparison of the Effective Number of Codons with the Codon Adaptation Index shows that, in contrast to the other species, codon bias in D. grimshawi F element genes can be attributed primarily to selection instead of mutational biases, suggesting that density and types of transposons affect the degree of local heterochromatin formation. F element genes have lower estimated DNA melting temperatures than D element genes, potentially facilitating transcription through heterochromatin. Most F element genes (~90%) have remained on that element, but the F element has smaller syntenic blocks than genome averages (3.4–3.6 vs. 8.4–8.8 genes per block), indicating greater rates of inversion despite lower rates of recombination. Overall, the F element has maintained characteristics that are distinct from other autosomes in the Drosophila lineage, illuminating the constraints imposed by a heterochromatic milieu.
    Type of Medium: Online Resource
    ISSN: 2160-1836
    URL: Article
    DOI: 10.1534/g3.114.015966
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2015
    detail.hit.zdb_id: 2629978-1
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  • 2
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    Transmission of Mycobacterium tuberculosis to Healthcare Personnel Resulting From Contaminated Bone Graft Material, United States, June 2021–August 2022
    Oxford University Press (OUP) ; 2023
    In:  Clinical Infectious Diseases Vol. 76, No. 10 ( 2023-05-24), p. 1847-1849
    Details
    In: Clinical Infectious Diseases, Oxford University Press (OUP), Vol. 76, No. 10 ( 2023-05-24), p. 1847-1849
    Abstract: A nationwide tuberculosis outbreak linked to a viable bone allograft product contaminated with Mycobacterium tuberculosis was identified in June 2021. Our subsequent investigation identified 73 healthcare personnel with new latent tuberculosis infection following exposure to the contaminated product, product recipients, surgical instruments, or medical waste.
    Type of Medium: Online Resource
    ISSN: 1058-4838 , 1537-6591
    URL: Article
    DOI: 10.1093/cid/ciad029
    RVK:
    XA 10000
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 2002229-3
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  • 3
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    Life-Threatening Complications of Influenza vs Coronavirus Disease 2019 (COVID-19) in US Children
    Oxford University Press (OUP) ; 2023
    In:  Clinical Infectious Diseases Vol. 76, No. 3 ( 2023-02-08), p. e280-e290
    Details
    In: Clinical Infectious Diseases, Oxford University Press (OUP), Vol. 76, No. 3 ( 2023-02-08), p. e280-e290
    Abstract: Clinical differences between critical illness from influenza infection vs coronavirus disease 2019 (COVID-19) have not been well characterized in pediatric patients. Methods We compared demographics, clinical characteristics, and outcomes of US children (aged 8 months to 17 years) admitted to the intensive care or high-acuity unit with influenza or COVID-19. Using mixed-effects models, we assessed the odds of death or requiring life support for influenza vs COVID-19 after adjustment for age, sex, race and Hispanic origin, and underlying conditions including obesity. Results Children with influenza (n = 179) were younger than those with COVID-19 (n = 381; median, 5.2 years vs 13.8 years), less likely to be non-Hispanic Black (14.5% vs 27.6%) or Hispanic (24.0% vs 36.2%), and less likely to have ≥1 underlying condition (66.4% vs 78.5%) or be obese (21.4% vs 42.2%), and a shorter hospital stay (median, 5 days vs 7 days). They were similarly likely to require invasive mechanical ventilation (both 30.2%), vasopressor support (19.6% and 19.9%), or extracorporeal membrane oxygenation (2.2% and 2.9%). Four children with influenza (2.2%) and 11 children with COVID-19 (2.9%) died. The odds of death or requiring life support in children with influenza vs COVID-19 were similar (adjusted odds ratio, 1.30; 95% confidence interval, .78–2.15; P = .32). Conclusions Despite differences in demographics and clinical characteristics of children with influenza or COVID-19, the frequency of life-threatening complications was similar. Our findings highlight the importance of implementing prevention measures to reduce transmission and disease severity of influenza and COVID-19.
    Type of Medium: Online Resource
    ISSN: 1058-4838 , 1537-6591
    URL: Article
    DOI: 10.1093/cid/ciac477
    RVK:
    XA 10000
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
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  • 4
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    Pre-existing Immunocompromising Conditions and Outcomes of Acute COVID-19 Patients Admitted for Pediatric Intensive Care
    Oxford University Press (OUP) ; 2024
    In:  Clinical Infectious Diseases ( 2024-03-11)
    Details
    In: Clinical Infectious Diseases, Oxford University Press (OUP), ( 2024-03-11)
    Abstract: We aimed to determine if pre-existing immunocompromising conditions (ICCs) were associated with the presentation or outcome of patients with acute coronavirus disease 2019 (COVID-19) admitted for pediatric intensive care. Methods 55 hospitals in 30 U.S. states reported cases through the Overcoming COVID-19 public health surveillance registry. Patients & lt;21 years admitted March 12, 2020–December 30, 2021 to the pediatric intensive care unit (PICU) or high acuity unit for acute COVID-19 were included Results Of 1,274 patients, 105 (8.2%) had an ICC including 33 (31.4%) hematologic malignancies, 24 (22.9%) primary immunodeficiencies and disorders of hematopoietic cells, 19 (18.1%) nonmalignant organ failure with solid organ transplantation, 16 (15.2%) solid tumors and 13 (12.4%) autoimmune disorders. Patients with ICCs were older, had more underlying renal conditions, and had lower white blood cell and platelet counts than those without ICCs, but had similar clinical disease severity upon admission. In-hospital mortality from COVID-19 was higher (11.4% vs. 4.6%, p = 0.005) and hospitalization was longer (p = 0.01) in patients with ICCs. New major morbidities upon discharge were not different between those with and without ICC (10.5% vs 13.9%, p = 0.40). In patients with ICC, bacterial co-infection was more common in those with life-threatening COVID-19. Conclusions In this national case series of patients & lt;21 years of age with acute COVID-19 admitted for intensive care, existence of a prior ICCs were associated with worse clinical outcomes. Reassuringly, most patients with ICCs hospitalized in the PICU for severe acute COVID-19 survived and were discharged home without new severe morbidities.
    Type of Medium: Online Resource
    ISSN: 1058-4838 , 1537-6591
    URL: Article
    DOI: 10.1093/cid/ciae133
    RVK:
    XA 10000
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2024
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  • 5
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    Hyperactivation of the Silencing Proteins, Sir2p and Sir3p, Causes Chromosome Loss
    Oxford University Press (OUP) ; 1997
    In:  Genetics Vol. 145, No. 3 ( 1997-03-01), p. 605-614
    Details
    In: Genetics, Oxford University Press (OUP), Vol. 145, No. 3 ( 1997-03-01), p. 605-614
    Abstract: The SIR gene products maintain transcriptional repression at the silent mating type loci and telomeres in Saccharomyces cerevisiae, although no enzymatic or structural activity has been assigned to any of the Sir proteins nor has the role of any of these proteins in transcriptional silencing been clearly defined. We have investigated the functions and interactions of the Sir2, Sir3, and Sir4 proteins by overexpressing them in yeast cells. We find that Sir2p and Sir3p are toxic when overexpressed, while high Sir4p levels have no toxic effect. Epistasis experiments indicate that Sir2p-induced toxicity is diminished in strains lacking the SIR3 gene, while both Sir2p and Sir4p are required for Sir3p to manifest its full toxic effect. In addition, the effects of Sir2 or Sir3 overexpression are exacerbated by specific mutations in the N-terminus of the histone H4 gene. These results are consistent with a model in which Sir2p, Sir3p and Sir4p function as a complex and interact with histones to modify chromatin structure. We find no evidence that toxicity from high levels of the Sir proteins results from widespread repression of transcription. Instead, we find that high levels of Sir2p and/or Sir3p cause a profound decrease in chromosome stability. These results can be appreciated in the context of the effects of Sir2p in histone acetylation and of chromatin structure on chromosome stability.
    Type of Medium: Online Resource
    ISSN: 1943-2631
    URL: Article
    DOI: 10.1093/genetics/145.3.605
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 1997
    detail.hit.zdb_id: 1477228-0
    SSG: 12
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  • 6
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    Open Chromatin Profiling in Adipose Tissue Marks Genomic Regions with Functional Roles in Cardiometabolic Traits
    Oxford University Press (OUP) ; 2019
    In:  G3 Genes|Genomes|Genetics Vol. 9, No. 8 ( 2019-08-01), p. 2521-2533
    Details
    In: G3 Genes|Genomes|Genetics, Oxford University Press (OUP), Vol. 9, No. 8 ( 2019-08-01), p. 2521-2533
    Abstract: Identifying the regulatory mechanisms of genome-wide association study (GWAS) loci affecting adipose tissue has been restricted due to limited characterization of adipose transcriptional regulatory elements. We profiled chromatin accessibility in three frozen human subcutaneous adipose tissue needle biopsies and preadipocytes and adipocytes from the Simpson Golabi-Behmel Syndrome (SGBS) cell strain using an assay for transposase-accessible chromatin (ATAC-seq). We identified 68,571 representative accessible chromatin regions (peaks) across adipose tissue samples (FDR & lt; 5%). GWAS loci for eight cardiometabolic traits were enriched in these peaks (P & lt; 0.005), with the strongest enrichment for waist-hip ratio. Of 110 recently described cardiometabolic GWAS loci colocalized with adipose tissue eQTLs, 59 loci had one or more variants overlapping an adipose tissue peak. Annotated variants at the SNX10 waist-hip ratio locus and the ATP2A1-SH2B1 body mass index locus showed allelic differences in regulatory assays. These adipose tissue accessible chromatin regions elucidate genetic variants that may alter adipose tissue function to impact cardiometabolic traits.
    Type of Medium: Online Resource
    ISSN: 2160-1836
    URL: Article
    DOI: 10.1534/g3.119.400294
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2019
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  • 7
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    Community-Onset Bacterial Coinfection in Children Critically Ill With Severe Acute Respiratory Syndrome Coronavirus 2 Infection
    Oxford University Press (OUP) ; 2023
    In:  Open Forum Infectious Diseases Vol. 10, No. 3 ( 2023-03-03)
    Details
    In: Open Forum Infectious Diseases, Oxford University Press (OUP), Vol. 10, No. 3 ( 2023-03-03)
    Abstract: Community-onset bacterial coinfection in adults hospitalized with coronavirus disease 2019 (COVID-19) is reportedly uncommon, though empiric antibiotic use has been high. However, data regarding empiric antibiotic use and bacterial coinfection in children with critical illness from COVID-19 are scarce. Methods We evaluated children and adolescents aged & lt;19 years admitted to a pediatric intensive care or high-acuity unit for COVID-19 between March and December 2020. Based on qualifying microbiology results from the first 3 days of admission, we adjudicated whether patients had community-onset bacterial coinfection. We compared demographic and clinical characteristics of those who did and did not (1) receive antibiotics and (2) have bacterial coinfection early in admission. Using Poisson regression models, we assessed factors associated with these outcomes. Results Of the 532 patients, 63.3% received empiric antibiotics, but only 7.1% had bacterial coinfection, and only 3.0% had respiratory bacterial coinfection. In multivariable analyses, empiric antibiotics were more likely to be prescribed for immunocompromised patients (adjusted relative risk [aRR], 1.34 [95% confidence interval {CI}, 1.01–1.79] ), those requiring any respiratory support except mechanical ventilation (aRR, 1.41 [95% CI, 1.05–1.90]), or those requiring invasive mechanical ventilation (aRR, 1.83 [95% CI, 1.36–2.47] ) (compared with no respiratory support). The presence of a pulmonary comorbidity other than asthma (aRR, 2.31 [95% CI, 1.15–4.62]) was associated with bacterial coinfection. Conclusions Community-onset bacterial coinfection in children with critical COVID-19 is infrequent, but empiric antibiotics are commonly prescribed. These findings inform antimicrobial use and support rapid de-escalation when evaluation shows coinfection is unlikely.
    Type of Medium: Online Resource
    ISSN: 2328-8957
    URL: Article
    DOI: 10.1093/ofid/ofad122
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 2757767-3
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  • 8
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    Increasing pneumococcal vaccination rates among adults with cystic fibrosis
    Oxford University Press (OUP) ; 2004
    In:  American Journal of Health-System Pharmacy Vol. 61, No. 14 ( 2004-07-15), p. 1490-1493
    Details
    In: American Journal of Health-System Pharmacy, Oxford University Press (OUP), Vol. 61, No. 14 ( 2004-07-15), p. 1490-1493
    Type of Medium: Online Resource
    ISSN: 1079-2082 , 1535-2900
    URL: Article
    DOI: 10.1093/ajhp/61.14.1490
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2004
    SSG: 15,3
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  • 9
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    Bloodstream Infection Due to Vancomycin-resistant Enterococcus Is Associated With Increased Mortality After Hematopoietic Cell Transplantation for Acute Leukemia and Myelodysplastic Syndrome: A Multicenter, Retrospective Cohort Study
    Oxford University Press (OUP) ; 2019
    In:  Clinical Infectious Diseases Vol. 69, No. 10 ( 2019-10-30), p. 1771-1779
    Details
    In: Clinical Infectious Diseases, Oxford University Press (OUP), Vol. 69, No. 10 ( 2019-10-30), p. 1771-1779
    Abstract: We examined the impact of vancomycin-resistant Enterococcus (VRE) bloodstream infection (BSI) on outcomes of allogeneic hematopoietic cell transplantation (HCT) utilizing the Center for International Blood and Marrow Transplant Research database. Methods Adult and pediatric patients (N = 7128) who underwent first HCT for acute leukemia or myelodysplastic syndrome from 2008 through 2012 were analyzed as 3 groups—VRE BSI, non-VRE BSI, without BSI—according to BSI status at 100 days (D100) after allogeneic HCT. Multivariable models examined the effect of VRE BSI for overall survival (OS) and nonrelapse mortality (NRM) at 1 year. Results Of 7128 patients, 258 (3.2%) had VRE BSI, 2398 (33.6%) had non-VRE BSI, and 4472 (63%) had no BSI. The median time to VRE BSI and non-VRE BSI were D11 and D15, respectively. Compared with non-VRE BSI patients, VRE BSI patients were older, had advanced-stage acute leukemia, and received umbilical cord blood (UCB) allografts. In multivariable models, VRE BSI was associated with lower OS (relative risk [RR], 2.9;(99% confidence interval [CI] , 2.2–3.7) and increased NRM (RR, 4.7; 99% CI, 3.6–6.2) (P & lt; .0001) for both. Other predictors for worse OS and increased NRM were non-VRE BSI, older age, advanced disease stage, UCB allograft, – mismatch, comorbidity index ≥3, and cytomegalovirus seropositivity (P & lt; .001 for all variables). Conclusions VRE BSI is associated with lowest OS and highest NRM compared with patients without BSI or non-VRE BSI. Novel interventions that address the pathophysiology of VRE BSI have the potential of improving survival after HCT.
    Type of Medium: Online Resource
    ISSN: 1058-4838 , 1537-6591
    URL: Article
    DOI: 10.1093/cid/ciz031
    RVK:
    XA 10000
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2019
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  • 10
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    95. CAUTI and CLABSI in Hospitalized COVID-19 Patients
    Oxford University Press (OUP) ; 2020
    In:  Open Forum Infectious Diseases Vol. 7, No. Supplement_1 ( 2020-12-31), p. S178-S178
    Details
    In: Open Forum Infectious Diseases, Oxford University Press (OUP), Vol. 7, No. Supplement_1 ( 2020-12-31), p. S178-S178
    Abstract: Patients hospitalized for suspected or confirmed COVID-19 often require high levels of support, including supplemental oxygen or ventilation, intravenous fluids and pressors, prone positioning, and strict input/output monitoring. Increased utilization of invasive devices such as indwelling urinary catheters and central venous catheters may be needed in this population. Staff minimize contact time with COVID-19 patients. We hypothesized higher rates of device infection in patients with COVID-19. Table 1 Methods This is a retrospective cohort study at a 555-bed safety net hospital. 4 units (125 beds) primarily cared for patients with confirmed infection. Other units did not accept patients until COVID status was deemed negative, except Labor & Delivery and a designated mixed unit. Indwelling urinary catheter and central venous catheter (CVC) device days are tracked in all inpatient areas. CLABSI and CAUTI surveillance is performed using NHSN definitions. The first hospitalized COVID-19 case at our hospital occurred late March 2020. April - May 2020 was considered the initial pandemic phase for our institution. Device utilization for the 6 months prior (October 2019 – March 2020) was compared to initial pandemic phase. Device infection rates were also compared. Within the initial pandemic phase, utilization and infection rates were stratified by COVID-19 vs non-COVID-19 areas. Results Median indwelling urinary catheter usage increased during the initial pandemic period by 36% (998 to 1355 catheter days, p=0.13); CVC usage increased 25% (997 to 1246 CVC days, p=0.13). Hospital-wide, median CAUTI rates remained constant (2.9 and 2.7 infections/1000 catheter days, p=1.00). CLABSI rates increased significantly (0.0 and 1.6 infections/1000 CVC days, p=0.008). CAUTI rates were 83% higher, and CLABSI rates were 65% higher in COVID-19 areas compared to non-COVID-19 areas (Table 1). Urine culture and blood culture ordering were 69% higher and 73% higher in COVID-19 areas, respectively. Conclusion Utilization of both indwelling urinary catheters and CVC increased during the initial phase of the pandemic. Hospitalized COVID-19 patients appear to be at higher risk of both CAUTI and CLABSI. Patient care protocols, device utilization and culture ordering all require further investigation. Disclosures All Authors: No reported disclosures
    Type of Medium: Online Resource
    ISSN: 2328-8957
    URL: Article
    DOI: 10.1093/ofid/ofaa439.405
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
    detail.hit.zdb_id: 2757767-3
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