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.

Guidelines advocate universal, prompt treatment of hepatitis C (HCV) infection in HIV/HCV co-infected patients, but barriers to uptake of HCV direct-acting antivirals (DAAs) remain unclear in this population. This retrospective study investigated the care cascade from HCV diagnosis to sustained virologic response (SVR) at an urban infectious disease clinic in Saint Louis, Missouri during the first 18 months of interferon-free DAA availability in the United States. Of 1949 HIV patients seen in clinic, 91.9% were screened for HCV and 5.4% (n = 106) had chronic HCV infection with follow-up. Of these 106 co-infected patients, 100 underwent fibrosis testing, 55 were offered DAAs, 38 completed treatment, and 37 achieved SVR. Delayed DAA treatment was associated with no insurance, substance abuse, poor HIV control, and younger age. Providers delayed DAA treatment most commonly for substance abuse, psychiatric disease, and uncontrolled HIV. Mean time to insurance decision from initial prescription was 20.9 ± 29.6 days and mean time to final decision was 29.9 ± 40.1 days. DAAs are highly successful in co-infected patients in this early period but insurance delays and misconceptions from the interferon era can ultimately limit uptake. Addressing these factors in a comprehensive treatment model may bridge disparities and improve real-world SVRs.

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of C. difficile infection in adults 189 point in their lives, if not multiple times. Most of the time, it results in transient, asymptomatic colonization. When C. difficile causes a disease, as in CDI, it can range from mild self-limited diarrhea to fulminant colitis with shock. New cases can be defined by location and timing of symptom onset to aid in epidemiologic studies and prevention efforts (TABLE 1). 3 After the year 2000, CDI-related morbidity, mortality, and costs have increased dramatically. Before 2000, the mortality rate attributable to CDI was less than 1.5%, while after 2000, this increased to between 4.5% and 5.7% during endemic periods and up to 16.7% during epidemic periods. 4 There were also dramatic increases in the incidence of CDI. According to the Centers for Disease Control and Prevention in the United States, close to 500 000 cases were diagnosed in 2011, with about 29 000 associated deaths and an estimated $4.8 billion in unnecessary inpatient costs. 5,6 These changes in CDI epidemiology coincided with the identification of a new predominant strain known as 027/NAP1/BI (the name varies based on the type of molecular typing technique, referred to as ribotype 027 from here onwards). This strain is highly fluoroquinolone

Pneumonia due to cytomegalovirus and herpes simplex virus-1 caused substantial morbidity after hematopoietic cell transplantation before the institution of preventative approaches. End-organ disease from herpesviruses is poorly described after chimeric antigen receptor-modified T-cell immunotherapy. We report 2 cases of cytomegalovirus pneumonia and 1 case of herpes simplex virus-1 gingivostomatitis, esophagitis, and pneumonia after chimeric antigen receptor-modified T-cell immunotherapy for the treatment of hematologic malignancies.