Purpose Testosterone replacement therapy in men with prostate cancer is controversial, with concern that testosterone can stimulate cancer growth. We evaluated the safety and efficacy of testosterone in hypogonadal men with prostate cancer treated with radical prostatectomy. Materials and Methods We performed a review of 103 hypogonadal men with prostate cancer treated with testosterone after prostatectomy (treatment group) and 49 nonhypogonadal men with cancer treated with prostatectomy (reference group). There were 77 men with low/intermediate (nonhigh) risk cancer and 26 with high risk cancer included in the analysis. All men were treated with transdermal testosterone, and serum hormone, hemoglobin, hematocrit and prostate specific antigen were evaluated for more than 36 months. Results Median (IQR) patient age in the treatment group was 61.0 years (55.0–67.0), and initial laboratory results included testosterone 261.0 ng/dl (213.0–302.0), prostate specific antigen 0.004 ng/ml (0.002–0.007), hemoglobin 14.7 gm/dl (13.3–15.5) and hematocrit 45.2% (40.4–46.1). Median followup was 27.5 months, at which time a significant increase in testosterone was observed in the treatment group. A significant increase in prostate specific antigen was observed in the high risk and nonhigh risk treatment groups with no increase in the reference group. Overall 4 and 8 cases of cancer recurrence were observed in treatment and reference groups, respectively. Conclusions Thus, testosterone therapy is effective and, while followed by an increase in prostate specific antigen, does not appear to increase cancer recurrence rates, even in men with high risk prostate cancer. However, given the retrospective nature of this and prior studies, testosterone therapy in men with history of prostate cancer should be performed with a vigorous surveillance protocol.

Several immunodeficiencies are associated with high susceptibility to persistent and progressive human papillomavirus (HPV) infection leading to a wide range of cutaneous and mucosal lesions. However, the HPV types most commonly associated with such clinical manifestations in these patients have not been systematically defined. Here, we used virion enrichment, rolling circle amplification, and deep sequencing to identify circular DNA viruses present in skin swabs and/or wart biopsy samples from 48 patients with rare genetic immunodeficiencies, including patients with warts, hypogammaglobulinemia, infections, myelokathexis (WHIM) syndrome, or epidermodysplasia verruciformis (EV). Their profiles were compared with the profiles of swabs from 14 healthy adults and warts from 6 immunologically normal children. Individual patients were typically infected with multiple HPV types; up to 26 different types were isolated from a single patient (multiple anatomical sites, one time point). Among these, we identified the complete genomes of 83 previously unknown HPV types and 35 incomplete genomes representing possible additional new types. HPV types in the genusGammapapillomaviruswere common in WHIM patients, whereas EV patients mainly shed HPVs from the genusBetapapillomavirus.Preliminary evidence based on three WHIM patients treated with plerixafor, a leukocyte mobilizing agent, suggest that longer-term therapy may correlate with decreased HPV diversity and increased predominance of HPV types associated with childhood skin warts.IMPORTANCEAlthough some members of the viral familyPapillomaviridaecause benign skin warts (papillomas), many human papillomavirus (HPV) infections are not associated with visible symptoms. For example, most healthy adults chronically shedGammapapillomavirus(Gamma) virions from apparently healthy skin surfaces. To further explore the diversity of papillomaviruses, we performed viromic surveys on immunodeficient individuals suffering from florid skin warts. Our results nearly double the number of knownGammaHPV types and suggest that WHIM syndrome patients are uniquely susceptible toGammaHPV-associated skin warts. Preliminary results suggest that treatment with the drug plerixafor may promote resolution of the unusualGammaHPV skin warts observed in WHIM patients.

Canonical translation initiation in eukaryotes begins with the Eukaryotic Initiation Factor 4F (eIF4F) complex, made up of eIF4E, which recognizes the 7-methylguanosine cap of messenger RNA, and eIF4G, which serves as a scaffold to recruit other translation initiation factors that ultimately assemble the 80S ribosome. Many eukaryotes have secondary EIF4E genes with divergent properties. The model plant Arabidopsis (Arabidopsis thaliana) encodes two such genes in tandem loci on chromosome 1, EIF4E1B (At1g29550) and EIF4E1C (At1g29590). This work identifies EIF4E1B/EIF4E1C-type genes as a Brassicaceae-specific diverged form of EIF4E. There is little evidence for EIF4E1C gene expression; however, the EIF4E1B gene appears to be expressed at low levels in most tissues, though microarray and RNA Sequencing data support enrichment in reproductive tissue. Purified recombinant eIF4E1b and eIF4E1c proteins retain cap-binding ability and form functional complexes in vitro with eIF4G. The eIF4E1b/eIF4E1c-type proteins support translation in yeast (Saccharomyces cerevisiae) but promote translation initiation in vitro at a lower rate compared with eIF4E. Findings from surface plasmon resonance studies indicate that eIF4E1b and eIF4E1c are unlikely to bind eIF4G in vivo when in competition with eIF4E. This study concludes that eIF4E1b/eIF4E1c-type proteins, although bona fide cap-binding proteins, have divergent properties and, based on apparent limited tissue distribution in Arabidopsis, should be considered functionally distinct from the canonical plant eIF4E involved in translation initiation.

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Subcutaneous testosterone (T) pellets are a viable treatment modality for hypogonadism. Optimal dosing, frequency of reimplantation, and long-term safety of T pellets remain incompletely elucidated parameters. A retrospective review of 273 patients treated for hypogonadism using subcutaneous T pellets was performed. Serum total T (TT), free T (FT), and estradiol (E2) levels were analyzed as a function of time from implantation, number of pellets implanted (6-9 or 10-12), body mass index (BMI; ,25 or $25 kg/m 2 ), number of implantations (#4 rounds, 501 insertions), and preimplantation T levels (,300 or $300 ng/dL). T decay was determined using linear regression and TT levels immediately postimplantation and the time for TT levels to reach 300 ng/dL extrapolated for all variables. Mean patient age 6 SD was 56 6 12.6 years. Baseline TT level was 328 6 202 ng/dL, FT 9.49 6 27.8 pg/mL, and E2 25.1 6 17.3 pg/mL. Extrapolated TT and FT peaks were lower in men receiving 6 to 9 pellets than men receiving 10 to 12, although decay rates differed insignificantly. E2 levels rose significantly in men receiving 10 to 12 but not 6 to 9 pellets. Men with BMI $25 kg/m 2 attained lower TT peaks with slower decay than men with BMI ,25 kg/m 2 receiving 10 to 12 pellets, although 300 ng/dL TT levels were reached at approximately 100 days in both groups. No differences were seen in decay rates for men with multiple implant rounds, and no differences in T peaks or decay rates were seen in men with preimplant T level ,300 or $300 ng/dL. One patient developed erythrocytosis, and no prostate-specific antigen recurrences were observed in men with prostate cancer treated with T pellets. Men with BMI ,25 kg/m 2 should receive fewer pellets, and reimplantation for all men should occur 100 to 120 days after prior implantation. Men receiving 10 to 12 pellets have higher E2 levels, potentially reflecting increased aromatization of T. Reimplantation and preimplantation TT levels do not affect pellet decay kinetics.