Who and when should we screen for prostate cancer? Interviews with key opinion leaders

Prostate cancer screening using prostate-specific antigen (PSA) is highly controversial. In this Q & A, Guest Editors for BMC Medicine's 'Spotlight on Prostate Cancer' article collection, Sigrid Carlsson and Andrew Vickers, invite some of the world's key opinion leaders to discuss who, and when, to screen for prostate cancer. In response to the points of view from the invited experts, the Guest Editors summarize the experts' views and give their own personal opinions on PSA screening

Synthesis, Characterization, and Direct Intracellular Imaging of Ultrasmall and Uniform Glutathione‐Coated Gold Nanoparticles

Gold nanoparticles (AuNPs) with core sizes below 2 nm and compact ligand shells constitute versatile platforms for the development of novel reagents in nanomedicine. Due to their ultrasmall size, these AuNPs are especially attractive in applications requiring delivery to crowded intracellular spaces in the cytosol and nucleus. For eventual use in vivo, ultrasmall AuNPs should ideally be monodisperse, since small variations in size may affect how they interact with cells and how they behave in the body. Here we report the synthesis of ultrasmall, uniform 144‐atom AuNPs protected by p ‐mercaptobenzoic acid followed by ligand exchange with glutathione (GSH). Quantitative scanning transmission electron microscopy (STEM) reveals that the resulting GSH‐coated nanoparticles (Au(GSH)) have a uniform mass distribution with cores that contain 134 gold atoms on average. Particle size dispersity is analyzed by analytical ultracentrifugation, giving a narrow distribution of apparent hydrodynamic diameter of 4.0 ± 0.6 nm. To evaluate the nanoparticles’ intracellular fate, the cell‐penetrating peptide TAT is attached noncovalently to Au(GSH), which is confirmed by fluorescence quenching and isothermal titration calorimetry. HeLa cells are then incubated with both Au(GSH) and the Au(GSH)‐TAT complex, and imaged without silver enhancement of the AuNPs in unstained thin sections by STEM. This imaging approach enables unbiased detection and quantification of individual ultrasmall nanoparticles and aggregates in the cytoplasm and nucleus of the cells. The synthesis and characterization of an ultrasmall and uniform glutathione‐coated gold nanoparticle is reported. It is also shown that scanning transmission electron microscopy (STEM) enables the visualization and quantification of individual gold nanoparticles as well as small aggregates in the cytoplasm and nucleus of HeLa cells.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/92372/1/2277_ftp.pd

Online medical crowdfunding in the United States: a cross-sectional analysis of gendered cancer campaign outcomes

This cross-sectional analysis examined online US crowdfunding campaigns from 2010–2018. Campaigns including prostate, breast, bladder, kidney, cervical, uterine, ovarian, testicular, oral, and thyroid cancers were included. Multivariable modeling was utilized to examine predictive factors for successful campaigns. A total of 1830 online cancer campaigns were included in the final analysis. Breast cancer was estimated to be the most frequent online campaign type (n = 3682), followed by cervical (n = 492), kidney (n = 475), ovarian (n = 460), and prostate cancers (n = 382). Breast cancer campaigns generated the most total funding ($15.3 million). In adjusted models, breast cancers generated significantly more donations per campaign than any other cancer. There was no difference in the average amount of funds raised per campaign by most cancer types, except for thyroid (19.4% less than breast, p < 0.001). Friend-authored campaigns generated more funding than self- and family-authored. Male cancers are under-represented, and breast cancer campaigns are disproportionately over-represented in online medical crowdfunding and generate more donations than many other cancers. Gendered differences in cancer crowdfunding are likely multifactorial and may be influenced by social networks and public health campaigns

Targeting Antibody Responses to the Membrane Proximal External Region of the Envelope Glycoprotein of Human Immunodeficiency Virus

Although human immunodeficiency type 1 (HIV-1) infection induces strong antibody responses to the viral envelope glycoprotein (Env) only a few of these antibodies possess the capacity to neutralize a broad range of strains. The induction of such antibodies represents an important goal in the development of a preventive vaccine against the infection. Among the broadly neutralizing monoclonal antibodies discovered so far, three (2F5, Z13 and 4E10) target the short and hidden membrane proximal external region (MPER) of the gp41 transmembrane protein. Antibody responses to MPER are rarely observed in HIV-infected individuals or after immunization with Env immunogens. To initiate antibody responses to MPER in its membrane-embedded native conformation, we generated expression plasmids encoding the membrane-anchored ectodomain of gp41 with N-terminal deletions of various sizes. Following transfection of these plasmids, the MPER domains are displayed on the cell surface and incorporated into HIV virus like particles (VLP). Transfected cells displaying MPER mutants bound as efficiently to both 2F5 and 4E10 as cells transfected with a plasmid encoding full-length Env. Mice immunized with VLPs containing the MPER mutants produced MPER-specific antibodies, the levels of which could be increased by the trimerization of the displayed proteins as well as by a DNA prime-VLP boost immunization strategy. Although 2F5 competed for binding to MPER with antibodies in sera of some of the immunized mice, neutralizing activity could not be detected. Whether this is due to inefficient binding of the induced antibodies to MPER in the context of wild type Env or whether the overall MPER-specific antibody response induced by the MPER display mutants is too low to reveal neutralizing activity, remains to be determined

Protein Oxidation Implicated as the Primary Determinant of Bacterial Radioresistance

In the hierarchy of cellular targets damaged by ionizing radiation (IR), classical models of radiation toxicity place DNA at the top. Yet, many prokaryotes are killed by doses of IR that cause little DNA damage. Here we have probed the nature of Mn-facilitated IR resistance in Deinococcus radiodurans, which together with other extremely IR-resistant bacteria have high intracellular Mn/Fe concentration ratios compared to IR-sensitive bacteria. For in vitro and in vivo irradiation, we demonstrate a mechanistic link between Mn(II) ions and protection of proteins from oxidative modifications that introduce carbonyl groups. Conditions that inhibited Mn accumulation or Mn redox cycling rendered D. radiodurans radiation sensitive and highly susceptible to protein oxidation. X-ray fluorescence microprobe analysis showed that Mn is globally distributed in D. radiodurans, but Fe is sequestered in a region between dividing cells. For a group of phylogenetically diverse IR-resistant and IR-sensitive wild-type bacteria, our findings support the idea that the degree of resistance is determined by the level of oxidative protein damage caused during irradiation. We present the case that protein, rather than DNA, is the principal target of the biological action of IR in sensitive bacteria, and extreme resistance in Mn-accumulating bacteria is based on protein protection

Incidence of circumcision among insured adults in the United States

PurposeAlthough circumcision is the most commonly performed surgery in males, less is known about the incidence and indications of adult circumcision. In this study, we aim to present the incidence of adult circumcision across the United States.MethodsUsing IBM MarketScan® Commercial Database from 2015 to 2018, we obtained claims for circumcision in men between 18 and 64 years of age. We calculated the incidence of adult circumcision over the study period and across the United States. We also collected data on indications for surgery using International Classification of Diseases codes.ResultsWe identified a total of 12,298 claims for adult circumcisions. The mean age was 39 (±12.9) years. The average incidence rates remained relatively constant from 98.1 per 100,000 person-years in 2015 to 98.2 per 100,000 person-years in 2018 (Δ+0.1%). The age-standardized incidence rates varied significantly across the United States (from 0 to 194.8 per 100,000 person-years) with South Dakota having the highest rate. The most common indications for adult circumcision were phimosis (52.5%), routine/ritual circumcision (28.7%), phimosis + balanitis/balanoposthitis (6.8%), balanitis (3.8%) and balanoposthitis (2.6%), and significantly varied by age groups.ConclusionThis study suggested a wide geographic variation in rates of adult circumcision between states with highest incidences in the Northeast United States. Future studies can identify the underlying causes for the observed variations

Access to telehealth services for colorectal cancer patients in the United States during the COVID-19 pandemic.

BackgroundThe COVID-19 pandemic yielded rapid telehealth deployment to improve healthcare access, including for surgical patients.MethodsWe conducted a secret shopper study to assess telehealth availability for new patient and follow-up colorectal cancer care visits in a random national sample of Commission on Cancer accredited hospitals and investigated predictive facility-level factors.ResultsOf 397 hospitals, 302 (76%) offered telehealth for colorectal cancer patients (75% for follow-up, 42% for new patients). For new patients, NCI-designated Cancer Programs offered telehealth more frequently than Integrated Network (OR: 0.20, p&nbsp;=&nbsp;0.01), Academic Comprehensive (OR: 0.18, p&nbsp;=&nbsp;0.001), Comprehensive Community (OR: 0.10, p&nbsp;&lt;&nbsp;0.001), and Community (OR: 0.11, p&nbsp;&lt;&nbsp;0.001) Cancer Programs. For follow-up, above average timeliness of care hospitals offered telehealth more frequently than average hospitals (OR: 2.87, p&nbsp;=&nbsp;0.04).ConclusionsWe identified access disparities and predictive factors for telehealth availability for colorectal cancer care during the COVID-19 pandemic. These factors should be considered when constructing telehealth policies

Online medical crowdfunding in the United States: a cross-sectional analysis of gendered cancer campaign outcomes

This cross-sectional analysis examined online US crowdfunding campaigns from 2010–2018. Campaigns including prostate, breast, bladder, kidney, cervical, uterine, ovarian, testicular, oral, and thyroid cancers were included. Multivariable modeling was utilized to examine predictive factors for successful campaigns. A total of 1830 online cancer campaigns were included in the final analysis. Breast cancer was estimated to be the most frequent online campaign type (n = 3682), followed by cervical (n = 492), kidney (n = 475), ovarian (n = 460), and prostate cancers (n = 382). Breast cancer campaigns generated the most total funding ($15.3 million). In adjusted models, breast cancers generated significantly more donations per campaign than any other cancer. There was no difference in the average amount of funds raised per campaign by most cancer types, except for thyroid (19.4% less than breast, p &lt; 0.001). Friend-authored campaigns generated more funding than self- and family-authored. Male cancers are under-represented, and breast cancer campaigns are disproportionately over-represented in online medical crowdfunding and generate more donations than many other cancers. Gendered differences in cancer crowdfunding are likely multifactorial and may be influenced by social networks and public health campaigns