Afamitresgene autoleucel for advanced synovial sarcoma and myxoid round cell liposarcoma (SPEARHEAD-1): an international, open-label, phase 2 trial.

Background: Afamitresgene autoleucel (afami-cel) showed acceptable safety and promising efficacy in a phase 1 trial (NCT03132922). The aim of this study was to further evaluate the efficacy of afami-cel for the treatment of patients with HLA-A*02 and MAGE-A4-expressing advanced synovial sarcoma or myxoid round cell liposarcoma.

Methods: SPEARHEAD-1 was an open-label, non-randomised, phase 2 trial done across 23 sites in Canada, the USA, and Europe.

Teenage dating abuse, rape, and violence: The dermatologist's role.

Teenage dating abuse, rape, and violence are considered major public health problems that affect the lives of millions of teenagers in the United States. Dermatologists have traditionally become involved in these cases when confronted with patients who have unexplained bruising or other skin injuries and/or sexually transmitted diseases that raise the possibility that they could be victims of sexual abuse and violence. This contribution explores the role of the dermatologist in the diagnosis and management of teen dating abuse.

Single surgeon versus co-surgeon bilateral mastectomy: Comparing outcomes and costs based on health economic modeling from the perspective of the hospital system.

Introduction: Co-surgeon approach for bilateral mastectomy may lead to shorter operative times and improved outcomes compared with single-surgeon approach, but cost differences remain unclear. Economic models were applied to determine whether either approach offered a lower cost opportunity.

Methods: A retrospective review of 409 patients undergoing single-surgeon or co-surgeon bilateral mastectomy between January 1, 2010 through April 30, 2016 was conducted.

Dominant effect of gap junction communication in wound-induced calcium-wave, NFAT activation and wound closure in keratinocytes.

Wounding induces a calcium wave and disrupts the calcium gradient across the epidermis but mechanisms mediating calcium and downstream signalling, and longer-term wound healing responses are incompletely understood. As expected, live-cell confocal imaging of Fluo-4-loaded normal human keratinocytes showed an immediate increase in [Ca ] at the wound edge that spread as a calcium wave (8.3 µm/s) away from the wound edge with gradually diminishing rate of rise and amplitude.

Domestic violence in the coronavirus disease 2019 era: Insights from a survivor.

Amid the coronavirus disease 2019 (COVID-19) pandemic, there has been an alarming rise in domestic violence worldwide. Factors believed to be fueling this escalation in domestic violence include increasing social confinement at home during lockdowns and mounting stress levels from unemployment that have resulted from the economic uncertainties of these times. This contribution explores some of the challenges faced by physicians in clinically assessing victims of domestic violence during the COVID-19 era.

Radiographic Surveillance of Patients with Non-BRCA1/2 Pathogenic Variants.

Introduction: The National Comprehensive Cancer Network (NCCN) developed clinical practice guidelines for germline pathogenic variants in highly penetrant genes, such as TP53 and PTEN, and in moderately penetrant genes, such as CHEK2, ATM and PALB2. Whether the practice of radiographic surveillance of patients with pathogenic variants in genes other than BRCA1/2 complies with current NCCN guidelines remains unclear.

Methods: Retrospective review of patients identified with pathogenic variants in genes other than BRCA1/2 from 2007 through 2017 to determine if radiographic surveillance was in accordance with NCCN guidelines for mammography and consideration of magnetic resonance imaging (MRI).

Individual and combined effects of the infrared, visible, and ultraviolet light components of solar radiation on damage biomarkers in human skin cells.

The ability of solar ultraviolet (UV) to induce skin cancer and photoaging is well recognized. The effect of the infrared (IR) and visible light (Vis) components of solar radiation on skin and their interaction with UV is less well known. This study compared the effects of physiologically relevant doses of complete (UV + Vis + IR) solar-simulated light and its individual components on matched primary dermal fibroblasts and epidermal keratinocytes from human donors on three biomarkers of cellular damage (reactive oxygen species (ROS) generation, mitochondrial DNA (mtDNA), and nuclear DNA (nDNA) damage).

Who Gets What? Describing the Non-supervisory Training and Supports Received by Home Visiting Staff Members and its Relationship with Turnover.

The early childhood home visiting field lacks a basic understanding of home visiting program staff members' receipt of on-the-job training from experts outside of their programs who are not their immediate colleagues or supervisors. To address this gap, we created a unique dataset by asking program leaders to log the external technical assistance (TA) that staff members received, and we collected a survey from 288 of the same staff members. We performed descriptive analyses to learn how many hours of TA staff members were receiving, what topics the TA most commonly addressed, and what formats (e.

Bad air gets under your skin.

Air pollution is increasing beyond previous estimates and is viewed as the world's largest environmental health risk factor. Numerous clinical and epidemiological studies have highlighted the adverse effects of environmental pollutants on health. Although there is comparatively less research investigating the cutaneous effects of ambient pollution, there is growing recognition of the adverse effects on skin.

Leukocyte Ig-Like Receptors - A Model for MHC Class I Disease Associations.

MHC class I (MHC-I) polymorphisms are associated with the outcome of some viral infections and autoimmune diseases. MHC-I proteins present antigenic peptides and are recognized by receptors on natural killer cells and cytotoxic T lymphocytes, thus enabling the immune system to detect self-antigens and eliminate targets lacking self or expressing foreign antigens. Recognition of MHC-I, however, extends beyond receptors on cytotoxic leukocytes.

Mitochondrial damage and ageing using skin as a model organ.

Ageing describes the progressive functional decline of an organism over time, leading to an increase in susceptibility to age-related diseases and eventually to death, and it is a phenomenon observed across a wide range of organisms. Despite a vast repertoire of ageing studies performed over the past century, the exact causes of ageing remain unknown. For over 50 years it has been speculated that mitochondria play a key role in the ageing process, due mainly to correlative data showing an increase in mitochondrial dysfunction, mitochondrial DNA (mtDNA) damage, and reactive oxygen species (ROS) with age.

Aberrant phenotype in human endothelial cells of diabetic origin: implications for saphenous vein graft failure?

Type 2 diabetes (T2DM) confers increased risk of endothelial dysfunction, coronary heart disease, and vulnerability to vein graft failure after bypass grafting, despite glycaemic control. This study explored the concept that endothelial cells (EC) cultured from T2DM and nondiabetic (ND) patients are phenotypically and functionally distinct. Cultured human saphenous vein- (SV-) EC were compared between T2DM and ND patients in parallel.

Soybean seeds: a practical host for the production of functional subunit vaccines.

Soybean seeds possess several inherent qualities that make them an ideal host for the production of biopharmaceuticals when compared with other plant-based and non-plant-based recombinant expression systems (e.g., low cost of production, high protein to biomass ratio, long-term stability of seed proteins under ambient conditions, etc.

Family history of dilated cardiomyopathy among patients with heart failure from the HF-ACTION genetic ancillary study.

Background: The value of family history (FH) is well established, but its sensitivity to detect familial dilated cardiomyopathy (FDC) has been infrequently examined.

Methods: A genetic ancillary study was created as a component of the HF-ACTION trial, a multicenter, prospective, randomized clinical trial of exercise in patients with heart failure and an ejection fraction <35%. A FH-based study using a structured questionnaire mailed to all consenting individuals was incorporated into the genetic ancillary.

Assessment of the protective effect of Imvamune and Acam2000 vaccines against aerosolized monkeypox virus in cynomolgus macaques.

To support the licensure of a new and safer vaccine to protect people against smallpox, a monkeypox model of infection in cynomolgus macaques, which simulates smallpox in humans, was used to evaluate two vaccines, Acam2000 and Imvamune, for protection against disease. Animals vaccinated with a single immunization of Imvamune were not protected completely from severe and/or lethal infection, whereas those receiving either a prime and boost of Imvamune or a single immunization with Acam2000 were protected completely. Additional parameters, including clinical observations, radiographs, viral load in blood, throat swabs, and selected tissues, vaccinia virus-specific antibody responses, immunophenotyping, extracellular cytokine levels, and histopathology were assessed.

Sublethal staphylococcal enterotoxin B challenge model in pigs to evaluate protection following immunization with a soybean-derived vaccine.

In an effort to develop a sustainable platform for manufacturing protein-based vaccine candidates, we expressed a triple mutant of staphylococcal enterotoxin B carrying the L45R, Y89A, and Y94A modifications in transgenic soybean seeds (soy-mSEB). Soy-mSEB possessed no detectable superantigen activity in vitro. We found that this soybean-derived, nontoxic mutant of SEB could be stably expressed, stored in seeds for extended periods at room temperature without degradation, and easily purified from contaminating soy proteins.

1 or 2 cm margins of excision for T2 melanomas: do they impact recurrence or survival?

Background: NCCN guidelines recommend 1 or 2 cm margins for melanomas 1-2 mm (T2 melanomas) in depth; however, no head-to-head comparison has been performed. We hypothesized 1- or 2-cm margins would have similar local recurrence (LR) and overall survival (OS).

Methods: An institutional database was queried for patients with 1.

Services for adults with an autism spectrum disorder.

The need for useful evidence about services is increasing as larger numbers of children identified with an autism spectrum disorder (ASD) age toward adulthood. The objective of this review was to characterize the topical and methodological aspects of research on services for supporting success in work, education, and social participation among adults with an ASD and to propose recommendations for moving this area of research forward. We reviewed the literature published in English from 2000 to 2010 and found that the evidence base about services for adults with an ASD is underdeveloped and can be considered a field of inquiry that is relatively unformed.

Recombinant expression of homodimeric 660 kDa human thyroglobulin in soybean seeds: an alternative source of human thyroglobulin.

Soybean seeds possess many qualities that make them ideal targets for the production of recombinant proteins. However, one quality often overlooked is their ability to stockpile large amounts of complex storage proteins. Because of this characteristic, we hypothesized that soybean seeds would support recombinant expression of large and complex proteins that are currently difficult or impossible to express using traditional plant and non-plant-based host systems.

Universal surfactant for water, oils, and CO2.

A trichain anionic surfactant sodium 1,4-bis(neopentyloxy)-3-(neopentyloxycarbonyl)-1,4-dioxobutane-2-sulfonate (TC14) is shown to aggregate in three different types of solvent: water, heptane, and liquid CO(2). Small-angle neutron scattering (SANS) has been used to characterize the surfactant aggregates in water, heptane, and dense CO(2). Surface tension measurements, and analyses, show that the addition of a third branched chain to the surfactant structural template is critical for sufficiently lowering the surface energy, tipping the balance between a CO(2)-incompatible surfactant (AOT) and CO(2)-philic compounds that will aggregate to form micelles in dense CO(2) (TC14).

Oral vaccine formulations stimulate mucosal and systemic antibody responses against staphylococcal enterotoxin B in a piglet model.

Despite the potential for its use as an agent of biowarfare or bioterrorism, no approved vaccine against staphylococcal enterotoxin B (SEB) exists. Nontoxic, mutant forms of SEB have been developed; however, it has been difficult to determine the efficacy of such subunit vaccine candidates due to the lack of superantigen activity of native SEB in rodents and due to the limitations of primate models. Since pigs respond to SEB in a manner similar to that of human subjects, we utilized this relevant animal model to investigate the safety and immunogenicity of a triple mutant of SEB carrying the amino acid changes L45R, Y89A, and Y94A.

Expression of the NS3 protease of cytopathogenic bovine viral diarrhea virus results in the induction of apoptosis but does not block activation of the beta interferon promoter.

Bovine viral diarrhea virus (BVDV; genus Pestivirus) can exist as two biotypes, cytopathogenic (CP) and non-cytopathogenic (NCP). The CP form differs from NCP by the continual expression of free non-structural protein 3 (NS3). CP BVDV infection of cultured cells induces apoptosis, whereas NCP BVDV infection has been reported to block the induction of beta interferon (IFN-beta).

Fluorocarbon-hydrocarbon incompatibility in micellar polymerizations.

A new approach to micellar polymerization is described. It is well known that hydrocarbons and fluorocarbons exhibit local phase segregation (demixing) owing to mutual antipathy; here this effect is employed in monomer swollen micelles with appropriate combinations of hydrocarbon and fluorocarbon monomers and surfactants. A matrix of these hydro- and fluorocarbon components has been investigated to delineate the effects of H-F antipathy on the outcomes of polymerization reactions to generate nanolatices of different size (and possibly morphology).

Escape from HLA-B*08-restricted CD8 T cells by hepatitis C virus is associated with fitness costs.

The inherent sequence diversity of the hepatitis C virus (HCV) represents a major hurdle for the adaptive immune system to control viral replication. Mutational escape within targeted CD8 epitopes during acute HCV infection has been well documented and is one possible mechanism for T-cell failure. HLA-B*08 was recently identified as one HLA class I allele associated with spontaneous clearance of HCV replication.

Conventional and PCR Detection of Aphelenchoides fragariae in Diverse Ornamental Host Plant Species.

A PCR-based diagnostic assay was developed for early detection and identification of Aphelenchoides fragariae directly in host plant tissues using the species-specific primers AFragFl and AFragRl that amplify a 169-bp fragment in the internal transcribed spacer (ITS1) region of ribosomal DNA. These species-specific primers did not amplify DNA from Aphelenchoides besseyi or Aphelenchoides ritzemabosi. The PCR assay was sensitive, detecting a single nematode in a background of plant tissue extract.