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.

BackgroundOncogene overexpression in primary cells often triggers the induction of a cellular safeguard response promoting senescence or apoptosis. Secondary cooperating genetic events are generally required for oncogene-induced tumorigenesis to overcome these biologic obstacles. We employed comparative genomic hybridization for eight genetically engineered mouse models of mammary cancer to identify loci that might harbor genes that enhance oncogene-induced tumorigenesis.ResultsUnlike many other mammary tumor models, the MMTV-Myc tumors displayed few copy number variants except for amplification of distal mouse chromosome 11 in 80 % of the tumors (syntenic to human 17q23-qter often amplified in human breast cancer). Analyses of candidate genes located in this region identified JMJD6 as an epigenetic regulatory gene that cooperates with Myc to enhance tumorigenesis. It suppresses Myc-induced apoptosis under varying stress conditions through inhibition of p19ARF messenger RNA (mRNA) and protein, leading to reduced levels of p53. JMJD6 binds to the p19ARF promoter and exerts its inhibitory function through demethylation of H4R3me2a. JMJD6 overexpression in MMTV-Myc cell lines increases tumor burden, induces EMT, and greatly enhances tumor metastasis. Importantly, we demonstrate that co-expression of high levels of JMJD6 and Myc is associated with poor prognosis for human ER+ breast cancer patients.ConclusionsA novel epigenetic mechanism has been identified for how JMJD6 cooperates with Myc during oncogenic transformation. Combined high expression of Myc and JMJD6 confers a more aggressive phenotype in mouse and human tumors. Given the pleiotropic pro-tumorigenic activities of JMJD6, it may be useful as a prognostic factor and a therapeutic target for Myc-driven mammary tumorigenesis.Electronic supplementary materialThe online version of this article (doi:10.1186/s13148-016-0205-6) contains supplementary material, which is available to authorized users.

Objective: To report a single institutional experience with urethroplasty outcomes and success rates at long-term follow up. Methods: A retrospective review was carried out of all urethroplasties performed by a single surgeon from 2000 to 2010. A total of 347 patients underwent urethroplasty during this time period, of which 227 had minimum 1-year follow-up data available. Demographic, clinical, pathological and outcome data were reviewed. Recurrence was defined by patient reported urinary symptoms or need for subsequent intervention. Statistical analyses were carried out using SPSS statistical software. Results: A total of 26% of all patients had a recurrence at a mean follow up of 62 months (range 13-147 months). The recurrence rate after anastomotic urethroplasty was 18%, as compared with 31% after substitution urethroplasty. Mean time to recurrence was 34 months (range 5-87). On univariate analysis, use of abdominal skin graft, history of prior urethroplasty, lichen sclerosus and length of follow up were statistically significant predictors of recurrence. On multivariate analysis, only history of prior urethroplasty and length of follow-up time exceeding 48 months were statistically significant predictors of recurrence. Conclusions: Urethroplasty for urethral stricture is the most durable treatment modality, regardless of surgical approach. However, there is an ongoing risk of recurrence with the passage of time. Patients should be counseled appropriately on the potential for late recurrence of stricture disease after urethroplasty.

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On re-review of surgical specimens we noted a significant incidence of lichen sclerosus in isolated bulbar strictures in men undergoing urethroplasty. The incidence of lichen sclerosus may be higher than reported in isolated bulbar urethral segments without evidence of distal to proximal progressive urethral disease.

The spread of COVID-19 and large-scale travel restrictions has caused serious damage to the global tourism industry. Tourists pay additional attention to public health services and their health during travel, but studies on tourism public health service quality (TPHSQ) are limited. Therefore, this study aims to define TPHSQ and revise and validate its scale. The result of exploratory factor analysis (EFA) indicates that TPHSQ includes two dimensions “overall environmental image” and “public health facilities and management.” And based on 456 valid samples, the relationship among TPHSQ, tourists’ trust, satisfaction, and loyalty was validated using the multiple linear regression models. Results revealed the importance of the TPHSQ in improving tourists’ satisfaction and recovering their trust and loyalty. These results provided several implications for research, practice, and society that can benefit diverse stakeholders, which could accelerate the recovery of the tourism industry.

Background: Mental health problems are common among older people living with HIV and associated with poorer health outcomes. Social capital is an important determinant of mental health problems but under-studied in this population. This study investigated the association between social capital and mental health problems among older people living with HIV in China. Methods: The study was based on the baseline data of a cohort study investigating mental health among older people living with HIV in Sichuan, China during November 2018 to February 2019. Participants were people living with HIV aged ≥50 years living in Sichuan province. Stratified multi-stage cluster sampling was used to recruit participants from 30 communities/towns; 529 out of 556 participants being approached completed the face-to-face interview. Social capital was measured by two validated health-related social capital scales: the Individual and Family scale and the Community and Society scale. Presence of probable depression (CES-D-10 score ≥ 10) and probable anxiety (GAD-7 score ≥ 5) were used as dependent variables. Two-level logistic regression models were applied to examine the association between social capital and probable depression/anxiety. Results: The prevalence of probable depression and probable anxiety was 25.9% (137/529) and 36.3% (192/529), respectively. After adjusting for significant covariates, the individual/family level of social capital was inversely associated with both probable depression (odds ratios (OR): 0.89, 95% CI: 0.84-0.93, p < 0.001) and probable anxiety (OR: 0.90, 95% CI: 0.86-0.95, p < 0.001). The community/society level social capital was associated with probable depression (OR: 0.91, 95% CI: 0.84-0.99, p < 0.001) but not probable anxiety (p > 0.05).

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