Hydrogel Loaded with Components for Therapeutic Applications in Hypertrophic Scars and Keloids.

Hypertrophic scars and keloids are common fibroproliferative diseases following injury. Patients with pathologic scars suffer from impaired quality of life and psychological health due to appearance disfiguration, itch, pain, and movement disorders. Recently, the advancement of hydrogels in biomedical fields has brought a variety of novel materials, methods and therapeutic targets for treating hypertrophic scars and keloids, which exhibit broad prospects. This review has summarized current research on hydrogels and loaded components used in preventing and treating hypertrophic scars and keloids. These hydrogels attenuate keloid and hypertrophic scar formation and progression by loading organic chemicals, drugs, or bioactive molecules (such as growth factors, genes, proteins/peptides, and stem cells/exosomes). Among them, smart hydrogels (a very promising method for loading many types of bioactive components) are currently favoured by researchers. In addition, combining hydrogels and current therapy (such as laser or radiation therapy, etc.) could improve the treatment of hypertrophic scars and keloids. Then, the difficulties and limitations of the current research and possible suggestions for improvement are listed. Moreover, we also propose novel strategies for facilitating the construction of target multifunctional hydrogels in the future.

A bibliometric analysis of m6A methylation in viral infection from 2000 to 2022.

BACKGROUND: N6-methyladenosine (m6A) methylation has become an active research area in viral infection, while little bibliometric analysis has been performed. In this study, we aim to visualize hotspots and trends using bibliometric analysis to provide a comprehensive and objective overview of the current research dynamics in this field. METHODS: The data related to m6A methylation in viral infection were obtained through the Web of Science Core Collection form 2000 to 2022. To reduce bias, the literature search was conducted on December 1, 2022. Bibliometric and visual analyzes were performed using CiteSpace and Bibliometrix package. After screening, 319 qualified records were retrieved. RESULTS: These publications mainly came from 28 countries led by China and the United States (the US), with the US ranking highest in terms of total link strength.The most common keywords were m6A, COVID-19, epitranscriptomics, METTL3, hepatitis B virus, innate immunity and human immunodeficiency virus 1. The thematic map showed that METTL3, plant viruses, cancer progression and type I interferon (IFN-I) reflected a good development trend and might become a research hotspot in the future, while post-transcriptional modification, as an emerging or declining theme, might not develop well. CONCLUSIONS: In conclusion, m6A methylation in viral infection is an increasingly important topic in articles. METTL3, plant viruses, cancer progression and IFN-I may still be research hotspots and trends in the future.

Waste to treasure: Superwetting foam enhanced by bamboo powder for sustainable on-demand oil-water separation.

Low-cost and sustainable superwetting materials are urgently required for oily wastewater treatment. Many poly(vinylidene fluoride) (PVDF)-based materials have been designed for oil-water separation. However, their fabrication processes frequently require toxic organic solvents and high-cost materials (e.g., carbon tubes and graphene). In this study, a highly porous and superhydrophobic bamboo powders (BP)-enhanced PVDF foam (SBPF) was fabricated via an organic solvent-free process. The SBPF exhibits efficient adsorption and recovery for various oils and organic solvents. Moreover, the SBPF shows high adsorption and separation performance under ultraviolet exposure and turbulent environments. It can also be used for water-in-oil emulsions separation, with a high separation efficiency more than 99.3 % under gravity. Interestingly, the amphiphilic PVDF-BP foam (ABPF) shows underwater superoleophobicity and underoil superhydrophobicity after delignification of SBPF. Owing to the conversion of wettability, it presents a high performance in treatment of both surfactant-stabilied water-in-oil and oil-in-water emulsions with the high separation efficiency achieving more than 99.6 % and 99.5 % respectively under gravity. In addition, the ABPF shows a high separation performance even after ten cycles. Hence, this fabricated organic solvent-free foams are promising candidates for sustainable on-demand separation of oils or organic solvents and water in complex environments.

Effect and Mechanism of Cotrimoxazole Against Talaromyces marneffei in vitro.

BACKGROUND: Talaromyces marneffei (formerly Penicillium marneffei) is an important thermally dimorphic fungus endemic which is characterized by one of the most frequent opportunistic infections in HIV/AIDS patients, mainly prevalent in Southeast Asia, southern China, and northeastern India. Cotrimoxazole(CTX) inhibits folic acid synthesis which is important for the survival of many bacteria, protozoa, and fungi, thereby commonly used to prevent several opportunistic infections among HIV/AIDS patients. In addition to preventing other HIV-associated opportunistic infections, CTX prophylaxis are considered to have the potential to prevent T. marneffei infection in HIV/AIDS patients receiving antiretroviral therapy (ART). However, the effect of cotrimoxazole towards T. marneffei fungus in vitro remains unclear. METHODS: Human THP-1 macrophages were used as cell model in vitro to explore the effect and mechanism of cotrimoxazole resistance towards T. marneffei. Cell viability assay and drug sensitivity colony forming units (CFU) experiments were conducted to determine the minimum inhibitory concentration (MIC) of cotrimoxazole inside and outside THP-1 macrophages respectively. Enzyme-linked immunosorbent assay (Elisa) was used to measure the concentration of Dihydropteroic acid synthetase (DHPS), Dihydrofolate synthetase (DHFS) and Dihydrofolate reductase (DHFR) between T. marneffei adding TMP/SMX and without adding TMP/SMX group respectively. Real-time fluorescence quantitative PCR(qPCR) was performed to detect the mRNA expression levels in Dectin-1 mediated signaling pathway and downstream inflammatory cytokines including IL-6, IL-10, IL-23A, CXCL8 and TNF-α released by T. marneffei-infected macrophages between adding TMP/SMX and without adding TMP/SMX group respectively. RESULTS: Cotrimoxazole can inhibit the proliferation of T. marneffei within safe concentration inside and outside THP-1 macrophages. Drug susceptibility results showed the minimal inhibit concentration(MIC) of 1:5 TMP/SMX was ranging from 14/70 to 68/340 µg/ml. The MIC of SMX was ranging from 100 to 360 µg/ml. The MIC of TMP was ranging from 240 to 400 µg/ml outside macrophages. The MIC of TMP/SMX was ranging from 36/180 to 68/340 µg/ml. The MIC of SMX was ranging from 340 to 360 µg/ml. The MIC of TMP was ranging from 320 to 400 µg/ml inside macrophages. The synergistic interaction of 1:5 TMP/SMX was more effective in inhibiting T. marneffei than separate SMX and TMP. DHPS, DHFS and DHFR can be inhibited by cotrimoxazole within safe and effective concentration. Dectin-1 expression is increased following T. marneffei infection, leading to the increase of IL-6, IL-10, IL-23A and the decrease of CXCL8 and TNF-α. Conversely, cotrimoxazole decrease the levels of Dectin-1, IL-6, IL-10, IL-23A and increase the levels of CXCL8 and TNF-α, thereby enhancing the intracellular killing-T. marneffei capacity of macrophages. CONCLUSIONS: Our findings indicated that cotrimoxazole directly inhibited T. marneffei growth by blocking DHPS, DHFS and DHFR and indirectly inhibited T. marneffei growth perhaps by regulating the Dectin-1 signaling pathway, which may effectively interfere with the defense ability of the host against T. marneffei infection.

Ionic liquid exfoliated Ti3C2Tx MXene nanosheets for photoacoustic imaging and synergistic photothermal/chemotherapy of cancer.

Ti3C2Tx MXene is a new type of two-dimensional material with good biocompatibility and a good photothermal effect, and shows great potential in cancer treatment. In this study, few-layer ionic liquid (IL)-Ti3C2Tx MXene nanosheets were synthesized using IL stripping technology, which have high chemical stability, and allow photoacoustic imaging and synergistic photothermal/chemotherapy of cancer. Under 808 nm laser irradiation, the nanosheets have strong absorption in the near-infrared region, and high photothermal conversion efficiency (∼63.91%). Using DOX as a model drug, the IL-Ti3C2Tx MXene@DOX nanosheets exhibited high drug loading capacity and pH-/photosensitivity, which will further promote the drug release of the nanosheets in an acidic tumor microenvironment and under 808 nm laser irradiation. In vitro and in vivo experiments showed that IL-Ti3C2Tx MXene@DOX has good biological safety, allows remarkable photoacoustic imaging, and can effectively kill cancer cells with synergistic photothermal/chemotherapy. Therefore, IL-Ti3C2Tx MXene nanosheets are expected to provide powerful and useful two-dimensional nanoplatforms for various biomedical applications.

Solvent-free processing of eco-friendly magnetic and superhydrophobic absorbent from all-plant-based materials for efficient oil and organic solvent sorption.

The unique features of bioresources such as cellulose and bio-wax include renewability, biodegradability, low cost, and abundance on Earth. Therefore, their efficient use is essential for a sustainable economy. Herein, we report a facile method for the surface modification of pretreated cotton with a bio-wax emulsion in water and Fe3O4 nanoparticles to fabricate a green, durable, magnetic, and superhydrophobic/superoleophilic absorbent for the sorption of oil and organic solvents. Magnetic superhydrophobic cotton (MSC) was successfully prepared via a simple two-step dip-coating method without using any toxic organic reagents. The as-prepared MSC was used to selectively absorb various types of oils and organic solvents up to approximately 20-50 times its own weight. Furthermore, it exhibited a stable magnetic responsivity and high reusability in oil/water separation cycles. In addition, the removal and collection of the absorbed oil/organic solvents were easily achieved with distillation and a vacuum air pump. Moreover, the as-prepared MSC was used in a heavy oil/water gravity-separation filter system and in the continuous collection of a light oil from water surfaces using a pump. The proposed concept may provide a green and sustainable strategy for fabricating superhydrophobic/superoleophilic materials for efficient sorption of oils and organic solvents.

2D MXene Nanomaterials for Versatile Biomedical Applications: Current Trends and Future Prospects.

Research on 2D nanomaterials is still in its early stages. Most studies have focused on elucidating the unique properties of the materials, whereas only few reports have described the biomedical applications of 2D nanomaterials. Recently, important questions about the interaction of 2D MXene nanomaterials with biological components have been raised. 2D MXenes are monolayer atomic nanosheets derived from MAX phase ceramics. As a new type of inorganic nanosystems, they are being widely used in biology and biomedicine. This review introduces the latest developments in 2D MXenes for the most advanced biomedical applications, including preparation and surface modification strategies, treatment modes, drug delivery, antibacterial activity, bioimaging, sensing, and biocompatibility. Besides, this review also discusses the current development trends and prospects of 2D inorganic nanosheets for further clinical applications. These emerging 2D inorganic MXenes will play an important role in next-generation cancer treatments.

Personal exposure to PM2.5-bound heavy metals associated with cardiopulmonary function in general population.

To better understand the cardiopulmonary alterations associated with personal exposed PM2.5-bound heavy meals, we conducted a cross-sectional study in 2018 on 54 general residents. For each subject, PM2.5 exposure filter was collected by a low-volume sampler for 24 h; blood and urine samples were collected subsequently. Heavy metals in PM2.5, blood, and urine samples were determined by inductively coupled plasma mass spectrometry method. PM2.5-bound Mn, Cd, Sb, Pb, and Ni levels were 20.5, 9.27, 9.59, 28.3, and 16.9 ng/m3, respectively. The distribution of these metals followed the order: Pb (33.47%) > Mn (24.24%) > Ni (19.99%) > Sb (11.34%) > Cd (10.96%). The distribution of heavy meals in PM2.5, blood, and urine differed from each other. PM2.5-bound Cd, Pb levels were positively correlated with blood Cd, Pb levels (r = 0.323, r = 0.334, p < 0.05), respectively. PM2.5-bound Cd level was significantly higher in smoking group than non-smoking group (28.8 vs. 7.27 ng/m3, p < 0.01), same as Sb level (12.0 vs. 9.34 ng/m3, p < 0.01). Cd and Pb exposure might interact with cardiovascular function through autonomic regulation. No significant correlation was observed between metal exposure and pulmonary function. In conclusion, our data suggested that personal exposure to specific PM2.5-bound heavy metals might interact with profound cardiovascular alterations.

Stimuli-responsive poly(ionic liquid) nanoparticles for controlled drug delivery.

A poly(ionic liquid) (PIL) obtained by polymerizing an ionic liquid (IL) monomer exhibits the characteristics of low cost and good biocompatibility, and it retains the excellent properties of the monomer. However, there is still a need to develop PILs for biomedical applications, which has been paid little attention. Herein, an amphiphilic block polymer containing a PIL block is synthesized, which simultaneously includes a targeted ligand, a photo-responsive block, and a pH-responsive block. The resultant amphiphilic block polymer can self-assemble into drug-loaded nanoparticles with a size of ∼80 nm in aqueous solution, and its drug loading capacity is as high as 70%. Moreover, the drug releasing mechanism of these drug-loaded nanoparticles can be triggered by light and pH stimuli. These novel amphiphilic PIL-based drug-loaded nanoparticles show highly effective antitumor effects, providing a promising approach for the delivery and controlled release of chemotherapy drugs in cancer therapy.

Redox-Sensitive Hyaluronic Acid Polymer Prodrug Nanoparticles for Enhancing Intracellular Drug Self-Delivery and Targeted Cancer Therapy.

Currently, available nanoscale anticancer drug delivery systems have low targeting and release efficiency, limiting their therapeutic effects. Thus, tumor-targeting nanocarriers for self-assembly of amphiphilic polymer-drug conjugates are urgently needed to improve drug targeting and treatment efficacy. Here, we report the construction of a stable, reduction-sensitive prodrug conjugate based on hyaluronic acid-grafted pH-sensitive doxorubicin (DOX). The amphiphilic prodrug copolymer self-assembled into spherical nanoparticles in aqueous solution and exhibited an average diameter of 150 nm. Prodrug micelles were stable in a normal physiological environment and achieve selective and rapid release under acidic pH and/or high reduction conditions. Cell Counting Kit-8, flow cytometry, and live cell imaging assays showed that the prodrug had high targeting and antitumor activity against CD44 receptors. Moreover, in vivo pharmacokinetics and biodistribution studies showed that the prodrug had a longer circulation time in BALB/c mice and higher accumulation in 4T1 tumors. Interestingly, the prodrug could effectively treat tumors with few side effects. These results showed that the DOX prodrug micelles developed in this study may have great potential in targeted therapy.

Redox-Sensitive Polymer Micelles Based on CD44 and Folic Acid Receptor for Intracellular Drug Delivery and Drug Controlled Release in Cancer Therapy.

Redox-responsive ferrocene (Fc)-grafted supramolecular block copolymers functionalized with hyaluronic acid (HA-g-ß-CD/Fc-polymers or HAP) or folic acid (FA-g-ß-CD/Fc-polymers or FAP) were synthesized by host-guest interaction. The copolymer structures were characterized by Fourier transform infrared spectroscopy, nuclear magnetic resonance, and gel permeation chromatography. The block copolymers self-assemble into spherical micellar aggregates in aqueous solution, and exhibit reversible redox characteristics in the presence of an oxidant and reductant. The tunable redox response was evaluated by transmission electron microscopy, ultraviolet-visible spectroscopy, cyclic voltammetry and dynamic light scattering. The micelles rapidly release DOX under oxidative and acidic condition in vitro. Furthermore, presence of HA and FA on the micelles enabled effective uptake by the CD44 and FA receptor-overexpressing cancer cells. Taken together, the redox responsive Fc-block copolymer micelles have good biocompatibility, biodegradability, low toxicity, and high selectivity, and are a highly promising drug delivery system for cancer therapy.

Sulforaphane protects MLE-12 lung epithelial cells against oxidative damage caused by ambient air particulate matter.

Ambient air particulate matter with aerodynamic diameters ≤2.5 µm (PM2.5) can cause pulmonary injury. Oxidative stress is thought to be an important mechanism of PM2.5-mediated toxicity. Sulforaphane (SFN), a compound derived from cruciferous vegetables, is a well-known potent antioxidant; however, its protective effect on lung epithelial cells exposed to PM2.5 is unclear. The results showed that SFN pre-treatment markedly inhibited PM2.5-induced apoptosis of the type II alveolar epithelial cell line MLE-12 by elevating glutathione S-transferase levels and decreasing reactive oxygen species. SFN pre-treatment down-regulated the expression of the pro-apoptotic proteins Bax and Bad, and reduced the activity of caspase-3, while it up-regulated the expression of the anti-apoptotic protein Bcl-2. Moreover, SFN induced the activation of the Akt and ERK pathways, and up-regulated the expression of Nrf2 and its downstream antioxidant genes NQO-1 and HO-1. This is the first study to demonstrate that SFN could protect MLE-12 cells against PM2.5-induced oxidative damage via activation of the Nrf2 pathway and inhibition of the mitochondrial apoptotic pathway; therefore, SFN may be a promising compound for preventing PM2.5-triggered pulmonary cell damage.

Patterns of Betel Quid, Cigarette, and Alcohol Use, and Their Correlates With Betel Quid Cessation in a Male Inmate Population.

BACKGROUND: There are few published studies addressing multiple substance uses and their effects on subsequent cessation of betel quid (BQ) chewing in the Asia Pacific region. OBJECTIVES: This study aims to investigate the usage patterns of BQ chewing, cigarette smoking, and alcohol drinking, and their correlates with subsequent BQ cessation among a male inmate population. METHODS: Data from 473 male inmates with a history of BQ use who were incarcerated in Taiwan Kaohsiung Prison was used for this analysis. Participants were asked to report their lifetime usage patterns of cigarette, alcohol, and BQ, and their cessation status of each substance. A stepwise logistic regression analysis was performed to identify predictors of voluntary BQ cessation. RESULTS: Seventy-five percent of all participants reported habitual use of all three substances. A total of 185 (39%) participants reported voluntary cessation of BQ prior to incarceration, and 288 (61%) reported cessation because of incarceration. Inmates who quit smoking before incarceration were more likely to voluntarily quit BQ. Inmates who had drinking habits were less likely to quit BQ, but those who quit drinking before incarceration were more likely to quit BQ. Inmates who preferred the type of BQ known as lao-hwa quid were more likely to quit BQ, and a longer chewing history correlated with a lower likelihood of quitting BQ. CONCLUSIONS IMPORTANCE: Our data suggest that coexisting habitual use of cigarette, alcohol, and BQ is very common in this inmate population. BQ cessation is significantly associated with not only inmates' usage patterns of cigarette and alcohol, but also their cessation status of these substances.

Prevalence and concordance of human papillomavirus infection at multiple anatomic sites among HIV-infected women from Chennai, India.

Human papillomavirus (HPV) infection at the cervix, anus and oropharynx has been rarely concurrently estimated among HIV-infected women. Using multiplex polymerase chain reaction testing, we prospectively evaluated HPV genotype distribution across three anatomic sites among 50 eligible HIV-infected women from Chennai, India, who provided biological specimens and answered a sexual behaviour questionnaire. We also assessed clinical and behavioural factors related to HPV prevalence. Oncogenic HPV prevalence was comparable between the anus and cervix at 52.2% and 52.0% and lower at the oropharynx at 13.2%; 78% of women with a cervical HPV infection had the same type in the anus. Newly acquired oncogenic HPV infections were lower at cervix (24%) than anus (35%) at three months. 'Any type' cervical HPV prevalence was higher among women with low education and less than five years since HIV diagnosis. CD4+ count and antiretroviral therapy status were not associated with HPV prevalence at the three anatomic sites; however, enrolment cervical HPV16 prevalence was elevated among women with nadir CD4+ <200 cells/µL and enrolment CD4+ <350 cells/µL. Regular cervical screening is essential in HIV-infected Indian women irrespective of CD4+ count and antiretroviral therapy status. Additional research clarifying the natural history of anal HPV infection is also needed in this population.

An analysis of HPV infection incidence and clearance by genotype and age in men: The HPV Infection in Men (HIM) Study.

OBJECTIVES: Genital HPV infection in men causes benign and cancerous lesions, the incidence of which differs by age. The goal of this work was to comprehensively evaluate incidence and clearance of individual HPV genotypes among men by age group. METHODS: HIV-negative men ages 18-70 with no history of anogenital cancer were recruited for the HPV Infection in Men (HIM) Study. Participants completed clinical exams and questionnaires every six months for up to ~4 years. Genital specimens underwent HPV genotyping, with associations between age and HPV assessed using Cox analyses. RESULTS: 4085 men were followed for a median of 48.6 months (range: 0.3-94.0). Significantly lower HPV incidence rates were observed among the oldest age group (55-70 years) for grouped high-risk (incidence rate ratio [IRR]=0.71), HPV16 (IRR=0.54), grouped low-risk (IRR=0.74), and HPV6 (IRR=0.57) infections compared to men ages 18-24. However, incidence of the grouped 9-valent HPV vaccine types remained constant across the lifespan. Likelihood of HPV6 and HPV16 clearance remained constant until age 54, then increased significantly for men ages 55-70 (adjusted hazard ratio [AHR]=1.92 and 1.65, respectively). CONCLUSIONS: Men remain susceptible to HPV infections throughout their lifespan, highlighting the need for prevention efforts with long-lasting duration.

[Screening active components in compound danshen based on PXR-CYP3A4: an experimental study].

OBJECTIVE: To screen active components in Compound Danshen (CD) based on pregnane X receptor-cytochrome P450 3A4 (PXR-CYP3A4). METHODS: By using PXR-CYP3A stable transfection human hepatoblastoma G2 (HepG2) cell lines engineering cell strain combined reporter genes technology, active components that induce or inhibit PXR-CYP3A4 paths in CD were screened, and confirmed at the level of enzymic activities. The experiment was divided into the positive control group (RIF 10 micro mol/L), the DMSO group (DMSO 0.1%), each dose of treatment groups (ginsenoside Rc, Rf, Rb2, Rg2, F2, F1, tanshinone I , isoborneol 5, 10, 25, 50, 100, and 200 micro mol/L; each with six duplicates). Cells medium was removed 36, 48, and 60 h after treatment. The activity of CYP3A4 was then determined in the supernant and the fold induction was calculated. RESULTS: Compared with the DMSO group, the fold induction increased when ginsenoside Rc, Rf, Rb2, Rg2, F2, F1, tanshinone I , and isoborneol 50 and 100 micro mol/L was respectively intervened for 36, 48, and 60 h (P <0.05). When cells were treated with isoborneol 200 micro mol/L for 48 and 60 h,the fold induction of ginsenoside Rb2, Rg2, and F1 was significantly higher than that of the RIF group (P <0.05). Enzymic activity results showed that ginsenoside Rc, Rf, Rb2, F2, and F1 could increase the enzyme activity of CYP3A4 at 48 h (P <0.05). CONCLUSION: Ginsenoside Rc, Rf, Rb2, F2, F1, tanshinone I, and isoborneol in DC could induce CYP3A4 enzymes.

Male circumcision and the incidence and clearance of genital human papillomavirus (HPV) infection in men: the HPV Infection in men (HIM) cohort study.

BACKGROUND: Reported associations of male circumcision (MC) with human papillomavirus (HPV) infection in men have been inconsistent. METHODS: 4,033 healthy men were examined every six months for a median of 17.5 months. In each study visit, exfoliated cell specimens from the coronal sulcus/glans penis, penile shaft, and scrotum were collected and combined into one sample per person for HPV DNA detection. Samples were tested for 37 HPV types. Cox proportional hazards models were used to evaluate the association between MC and the incidence and clearance of HPV infections and specific genotypes. RESULTS: The overall incidence of new HPV infections did not differ by MC status (for any HPV, adjusted hazard ratio (aHR) 1.08, 95% confidence interval (CI) 0.91-1.27). However, incidence was significantly lower among circumcised versus uncircumcised men for HPV types 58 (p = 0.01), 68 (p < 0.001), 42 (p = 0.01), 61 (p < 0.001), 71 (p < 0.001), 81 (p = 0.04), and IS39 (p = 0.01), and higher for HPV types 39 (p = 0.01) and 51 (p = 0.02). Despite the lack of an overall association in the risk of HPV clearance by MC (for any HPV, aHR 0.95, 95% CI 0.88-1.02), median times to clearance were significantly shorter among circumcised than uncircumcised men for HPV types 33 (p = 0.02) and 64 (p = 0.04), and longer for HPV types 6 (p < 0.001), 16 (p < 0.001), and 51 (p = 0.02). CONCLUSIONS: MC is not associated with the incidence and clearance of genital HPV detection, except for certain HPV types. The use of a single combined sample from the penis and scrotum for HPV DNA detection likely limited our ability to identify a true effect of MC at the distal penis.

The role of monogamy and duration of heterosexual relationships in human papillomavirus transmission.

BACKGROUND: Published data are equivocal about the relative rates of male-to-female and female-to-male human papillomavirus (HPV) transmission. Our objective was to estimate genital HPV incidence among heterosexual partners from a broad age range and to investigate the effects of monogamy and relationship duration on incidence. METHODS: HPV genotyping was conducted for heterosexual partners, aged 18-70 years, from Tampa, Florida, who provided genital exfoliated cell specimens at semiannual visits during a 2-year study. The rate of incident HPV detection was assessed for 99 couples, and transmission incidence was estimated among a subset of 65 discordant couples. We also evaluated the effect of monogamy and relationship duration on transmission incidence. RESULTS: Couples were followed up for a median of 25 months and had a mean age of 33 years for both sexes. The HPV type-specific transmission incidence rate was 12.3 (95% confidence interval, 7.1-19.6) per 1000 person-months for female-to-male transmission and 7.3 (95% confidence interval, 3.5-13.5) per 1000 person-months for male-to-female transmission. Regardless of monogamy status or relationship duration, there was a similar pattern of increased incident HPV detection among men compared with women. CONCLUSIONS: HPV may be transmitted more often from women to men than from men to women, suggesting a need for prevention interventions, such as vaccination, for men.

A comparison of calibration data from full field digital mammography units for breast density measurements.

BACKGROUND: Breast density is a significant breast cancer risk factor measured from mammograms. The most appropriate method for measuring breast density for risk applications is still under investigation. Calibration standardizes mammograms to account for acquisition technique differences prior to making breast density measurements. We evaluated whether a calibration methodology developed for an indirect x-ray conversion full field digital mammography (FFDM) technology applies to direct x-ray conversion FFDM systems. METHODS: Breast tissue equivalent (BTE) phantom images were used to establish calibration datasets for three similar direct x-ray conversion FFDM systems. The calibration dataset for each unit is a function of the target/filter combination, x-ray tube voltage, current × time (mAs), phantom height, and two detector fields of view (FOVs). Methods were investigated to reduce the amount of calibration data by restricting the height, mAs, and FOV sampling. Calibration accuracy was evaluated with mixture phantoms. We also compared both intra- and inter-system calibration characteristics and accuracy. RESULTS: Calibration methods developed previously apply to direct x-ray conversion systems with modification. Calibration accuracy was largely within the acceptable range of ± 4 standardized units from the ideal value over the entire acquisition parameter space for the direct conversion units. Acceptable calibration accuracy was maintained with a cubic-spline height interpolation, representing a modification to previous work. Calibration data is unit specific, can be acquired with the large FOV, and requires a minimum of one reference mAs sample. The mAs sampling, calibration accuracy, and the necessity for machine specific calibration data are common characteristics and in agreement with our previous work. CONCLUSION: The generality of our calibration approach was established under ideal conditions. Evaluation with patient data using breast cancer status as the endpoint is required to demonstrate that the approach produces a breast density measure associated with breast cancer.

Cutaneous human papillomavirus types detected on the surface of male external genital lesions: a case series within the HPV Infection in Men Study.

BACKGROUND: Cutaneous human papillomaviruses (HPVs) may be associated with cutaneous epithelial lesions and non-melanoma skin cancers. No study has systematically evaluated the presence of genus beta [ß]-HPV in male genital skin or external genital lesions (EGLs) OBJECTIVES: To examine cutaneous ß-HPV types detected on the surface of EGLs in men and describe their presence prior to EGL development. STUDY DESIGN: A retrospective case series was conducted among 69 men with pathologically confirmed EGLs (n=72) who participated in the HPV Infection in Men Study. Archived exfoliated cells collected from the surface of each EGL and normal genital skin specimens 6-12 months preceding EGL development were tested for ß-HPV DNA using a type-specific multiplex genotyping assay. RESULTS: ß-HPV DNA was detected on 61.1% of all EGLs, with types 38 (16.7%), 5 (15.3%), and 12 (12.5%) most commonly identified. HPV prevalence differed across pathological diagnoses, with the largest number of ß-HPV types detected on condylomas. Most ß-HPV types were detected on normal genital skin prior to EGL development, though the prevalence was lower on EGLs compared to preceding normal genital skin. CONCLUSIONS: EGLs and the normal genital skin of men harbor a large number of ß-HPV types; however, it appears that ß-HPVs are unrelated to EGL development in men. Despite evidence to support a causal role in skin carcinogenesis at UVR-exposed sites, cutaneous HPV appears unlikely to cause disease at the UVR-unexposed genitals.