Balancing Trained Immunity with Persistent Immune Activation and the Risk of Simian Immunodeficiency Virus Infection in Infant Macaques Vaccinated with Attenuated Mycobacterium tuberculosis or Mycobacterium bovis BCG Vaccine.

Our goal is to develop a pediatric combination vaccine to protect the vulnerable infant population against human immunodeficiency virus type 1 (HIV-1) and tuberculosis (TB) infections. The vaccine consists of an auxotroph Mycobacterium tuberculosis strain that coexpresses HIV antigens. Utilizing an infant rhesus macaque model, we have previously shown that this attenuated M.

Assessing Injury and Violence Prevention in North Carolina's Local Health Departments.

Background: Injury and violence-related morbidity and mortality present a major public health problem in North Carolina. However, the extent to which local health departments (LHDs) engage in injury and violence prevention (IVP) has not been well described.

Objectives: One objective of the current study is to provide a baseline assessment of IVP in the state's LHDs, describing capacity, priorities, challenges, and the degree to which programs are data-driven and evidence-based.

JQ1 suppresses tumor growth via PTEN/PI3K/AKT pathway in endometrial cancer.

Overexpression of c-Myc is associated with worse outcomes in endometrial cancer, indicating that c-Myc may be a promising target for endometrial cancer therapy. A novel small molecule, JQ1, has been shown to block BRD4 resulting in inhibition of c-Myc expression and tumor growth. Thus, we investigated whether JQ1 can inhibit endometrial cancer growth in cell culture and xenograft models.

LOVTRAP: an optogenetic system for photoinduced protein dissociation.

LOVTRAP is an optogenetic approach for reversible light-induced protein dissociation using protein A fragments that bind to the LOV domain only in the dark, with tunable kinetics and a >150-fold change in the dissociation constant (Kd). By reversibly sequestering proteins at mitochondria, we precisely modulated the proteins' access to the cell edge, demonstrating a naturally occurring 3-mHz cell-edge oscillation driven by interactions of Vav2, Rac1, and PI3K proteins.

Association Between Variants in Arsenic (+3 Oxidation State) Methyltranserase (AS3MT) and Urinary Metabolites of Inorganic Arsenic: Role of Exposure Level.

Variants in AS3MT, the gene encoding arsenic (+3 oxidation state) methyltranserase, have been shown to influence patterns of inorganic arsenic (iAs) metabolism. Several studies have suggested that capacity to metabolize iAs may vary depending on levels of iAs exposure. However, it is not known whether the influence of variants in AS3MT on iAs metabolism also vary by level of exposure.

Vaccine-Elicited Mucosal and Systemic Antibody Responses Are Associated with Reduced Simian Immunodeficiency Viremia in Infant Rhesus Macaques.

Unlabelled: Despite significant progress in reducing peripartum mother-to-child transmission (MTCT) of human immunodeficiency virus (HIV) with antiretroviral therapy (ART), continued access to ART throughout the breastfeeding period is still a limiting factor, and breast milk exposure to HIV accounts for up to 44% of MTCT. As abstinence from breastfeeding is not recommended, alternative means are needed to prevent MTCT of HIV. We have previously shown that oral vaccination at birth with live attenuated Mycobacterium tuberculosis strains expressing simian immunodeficiency virus (SIV) genes safely induces persistent SIV-specific cellular and humoral immune responses both systemically and at the oral and intestinal mucosa.

The state of melanoma: challenges and opportunities.

The Melanoma Research Foundation (MRF) has charted a comprehensive assessment of the current state of melanoma research and care. Intensive discussions among members of the MRF Scientific Advisory Council and Breakthrough Consortium, a group that included clinicians and scientists, focused on four thematic areas - diagnosis/early detection, prevention, tumor cell dormancy (including metastasis), and therapy (response and resistance). These discussions extended over the course of 2015 and culminated at the Society of Melanoma Research 2015 International Congress in November.

Demographic Disparities in Late-Stage Diagnosis of Breast and Colorectal Cancers Across the USA.

Background: We determined whether there were disparities in the likelihood of being diagnosed at a late stage for breast cancer (BC) or colorectal cancer (CRC) in each of 40 states, using the recently available US Cancer Statistics (USCS) database.

Methods: We extracted 981,457 BC cases and 558,568 CRC cases diagnosed in 2004-2009. Separate multilevel regressions were run for each state and each cancer type.

New developments in microextraction techniques in bioanalysis. A review.

In recent years, the interest in new extraction methods with lower sample volume requirements, simpler equipment and handling, and lower reagent consumption, has led to the development of a series of microextraction methods based on extraction phases in the microliter order. Nowadays, many references can be found for several of these methods, which imply a wide range of applications referred to both the analyte and the sample nature. In this paper, recent developments in both well-established microextraction techniques (solid phase microextraction, hollow-fiber liquid phase microextraction, dispersive liquid-liquid microextraction, etc.

Adjuvant Treatment and Clinical Trials in Elderly Patients With Endometrial Cancer: A Time for Change?

Objectives: The aim of the study were to evaluate the gap between recommended and received adjuvant therapy in elderly patients with endometrial cancer (EC) and to determine the percent of women 70 years and older who would meet enrollment criteria for representative Gynecologic Oncology Group (GOG) trials.

Methods And Materials: An institutional review board approved retrospective chart review of all EC cases from a tertiary care institution from 2005 to 2010 was performed. Clinical, surgical, and pathologic data were abstracted from electronic medical records.

Two-stage design for phase II oncology trials with relaxed futility stopping.

Many oncology phase II trials are single arm studies designed to screen novel treatments based on efficacy outcome. Efficacy is often assessed as an ordinal variable based on a level of response of solid tumors with four categories: complete response, partial response, stable disease and progression. We describe a two-stage design for a single-arm phase II trial where the primary objective is to test the rate of tumor response defined as complete plus partial response, and the secondary objective is to estimate the rate of disease control defined as tumor response plus stable disease.

Serial Activation of the Inducible Caspase 9 Safety Switch After Human Stem Cell Transplantation.

Activation of the inducible caspase 9 (iC9) safety gene by a dimerizing drug (chemical inducer of dimerization (CID) AP1903) effectively resolves the symptoms and signs of graft-versus-host disease (GvHD) in haploidentical stem cell transplant (HSCT) recipients. However, after CID treatment, 1% of iC9-T cells remain and can regrow over time; although these resurgent T cells do not cause recurrent GvHD, it remains unclear whether repeat CID treatments are a safe and feasible way to further deplete residual gene-modified T cells should any other adverse effects associated with them occur. Here, we report a patient who received an infusion of haploidentical iC9-T cells after HSCT and subsequently received three treatments with AP1903.

Clonal Dynamics In Vivo of Virus Integration Sites of T Cells Expressing a Safety Switch.

Safety switches are becoming relevant for the clinical translation of T-cell-based immunotherapies. In patients receiving an allogeneic hematopoietic stem cell transplant, the inducible caspase-9 gene (iC9) safety switch expressed by donor-derived T lymphocytes efficiently controls acute graft versus host disease (GvHD). However, in vivo elimination of iC9-T cells by the chemical inducer of dimerization (CID) that activates the iC9 protein is incomplete.

Postmenopausal Female Hormone Use and Estrogen Receptor-Positive and -Negative Breast Cancer in African American Women.

Background: Use of estrogen with progestin (combination therapy) is associated with increased incidence of estrogen receptor-positive (ER+) breast cancer in observational studies and randomized trials among postmenopausal white women. Whether this is also the case among African American women is not established.

Methods: Using data from the AMBER consortium collected from 1993 to 2013, we assessed use of estrogen alone and of combination therapy in relation to ER+ and ER-negative (ER-) breast cancer risk in postmenopausal African American women, based on 1132 ER+ case patients, 512 ER- case patients, and 6693 control patients.

Medication-Taking Practices of Patients on Antiretroviral HIV Therapy: Control, Power, and Intentionality.

Among people living with HIV (PLWH), adherence to antiretroviral therapy (ART) is crucial for health, but patients face numerous challenges achieving sustained lifetime adherence. We conducted six focus groups with 56 PLWH regarding ART adherence barriers and collected sociodemographics and ART histories. Participants were recruited through clinics and AIDS service organizations in North Carolina.

"Error Bars" in Medical Imaging: Stealth and Treacherous.

Given the critical role that diagnostic radiology has in patient care, it is important for providers and patients to understand the level of certainty associated with imaging. Over-reliance on imaging and failure to appreciate its limitations can lead to unforeseen consequences. Further, there are uncertainties and inconsistencies in the manner in which imaging-based information is considered, communicated, and applied.

Dual loss of the SWI/SNF complex ATPases SMARCA4/BRG1 and SMARCA2/BRM is highly sensitive and specific for small cell carcinoma of the ovary, hypercalcaemic type.

Small cell carcinoma of the ovary, hypercalcaemic type (SCCOHT) is a lethal and sometimes familial ovarian tumour of young women and children. We and others recently discovered that over 90% of SCCOHTs harbour inactivating mutations in the chromatin remodelling gene SMARCA4 with concomitant loss of its encoded protein SMARCA4 (BRG1), one of two mutually exclusive ATPases of the SWI/SNF chromatin remodelling complex. To determine the specificity of SMARCA4 loss for SCCOHT, we examined the expression of SMARCA4 by immunohistochemistry in more than 3000 primary gynaecological tumours.

Community Member and Stakeholder Perspectives on a Healthy Environment Initiative in North Carolina.

Introduction: The North Carolina Community Transformation Grant Project (NC-CTG) aimed to implement policy, system, and environmental strategies to promote healthy eating, active living, tobacco-free living, and clinical and community preventive services to advance health equity and reduce health disparities for the state's most vulnerable communities. This article presents findings from the Health Equity Collaborative Evaluation and Implementation Project, which assessed community and stakeholder perceptions of health equity for 3 NC-CTG strategies: farmers markets, shared use, and smoke-free multiunit housing.

Methods: In a triangulated qualitative evaluation, 6 photo elicitation (PE) sessions among 45 community members in 1 urban and 3 rural counties and key informant interviews among 22 stakeholders were conducted.

Brief Report: Significant Decreases in Both Total and Unbound Lopinavir and Amprenavir Exposures During Coadministration: ACTG Protocol A5143/A5147s Results.

This secondary analysis explored changes in protein-unbound concentrations of lopinavir and amprenavir when coadministered in HIV-infected subjects. Total and unbound pharmacokinetic parameters were calculated and compared between subjects receiving each agent alone and coadministration. When coadministered, unbound and total concentrations decrease.

Body Mass Index, PAM50 Subtype, and Outcomes in Node-Positive Breast Cancer: CALGB 9741 (Alliance).

Background: Obesity at diagnosis is associated with poor prognosis in women with breast cancer, but few reports have been adjusted for treatment factors.

Methods: CALGB 9741 was a randomized trial of dose density and sequence of chemotherapy for node-positive breast cancer. All patients received doxorubicin, cyclophosphamide, and paclitaxel, dosed by actual body weight.

Important Role of Menarche in Development of Estrogen Receptor-Negative Breast Cancer in African American Women.

Background: Menarche is a critical time point for diverging fates of mammary cells of origin. African American women have young age at menarche, which could be associated with their high rates of estrogen receptor-negative (ER-) breast cancer.

Methods: In the AMBER Consortium, using harmonized data from 4426 African American women with breast cancer and 17 474 controls, we used polytomous logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for ages at menarche and first live birth (FLB), and the interval between, in relation to ER+ and ER- breast cancer.

F-actin bundles direct the initiation and orientation of lamellipodia through adhesion-based signaling.

Mesenchymal cells such as fibroblasts are weakly polarized and reorient directionality by a lamellipodial branching mechanism that is stabilized by phosphoinositide 3-kinase (PI3K) signaling. However, the mechanisms by which new lamellipodia are initiated and directed are unknown. Using total internal reflection fluorescence microscopy to monitor cytoskeletal and signaling dynamics in migrating cells, we show that peripheral F-actin bundles/filopodia containing fascin-1 serve as templates for formation and orientation of lamellipodia.

Therapeutic insights from genomic studies of head and neck squamous cell carcinomas.

Large and comprehensive genomic surveys of head and neck squamous cell carcinomas (HNSCC) are now greatly increasing our understanding of the diversity of this disease and the key genomic changes that drive these tumors. The results from these studies are beginning to inform the introduction of novel therapies for patients with HNSCCs. Here, we review some of the key findings from recent genomic studies of head and neck cancers, including the most comprehensive study to date from The Cancer Genome Atlas Network.