Clinic-Level Predictors of Psychotherapy Dosage in the Military Health System.

Objective: This study aimed to describe the demand for, supply of, and clinic processes associated with behavioral health care delivery in the Military Health System and to examine the clinic-level factors associated with receipt of a minimally adequate dosage of psychotherapy.

Methods: This retrospective study used administrative behavioral health data from eight military treatment facilities (N=25,433 patients; N=241,028 encounters) that were participating in a larger implementation study of evidence-based psychotherapy for posttraumatic stress disorder. Minimally adequate dosage of psychotherapy was defined in two ways: at least three sessions within a 90-day period and at least six sessions within a 90-day period.

Barriers and Potential Solutions to Implementing Evidence-Based PTSD Treatment in Military Treatment Facilities.

Introduction: Prolonged exposure therapy is an effective treatment for posttraumatic stress disorder that is underutilized in health systems, including the military health system. Organizational barriers to prolonged exposure implementation have been hypothesized but not systematically examined. This multisite project sought to identify barriers to increasing the use of prolonged exposure across eight military treatment facilities and describe potential solutions to addressing these barriers.

Ivermectin-induced cell death of cervical cancer cells in vitro a consequence of precipitate formation in culture media.

The anthelmintic ivermectin has been reported to possess anticancer and antiviral efficacy. However, the effective concentrations reported in vitro are near the predicted aqueous solubility limit for this hydrophobic drug. We observed that ivermectin-induced cell death in two cervical cancer cell lines correlated with the formation of solid ivermectin aggregates in both serum-free and serum-supplemented culture media.

K3.1-dependent uptake of the cytotoxic DNA-binding dye Hoechst 33258 into cancerous but not healthy cervical cells.

The poor and nonselective penetration of current chemotherapeutics across the plasma membranes of cancer cells, which is necessary for the targeted disruption of the intracellular machinery, remains a major pharmaceutical challenge. In several cell types, including mast cells and macrophages, exposure to extracellular ATP is known to stimulate passive entry of large and otherwise membrane impermeable cationic dyes, which is usually attributed to conduction through ionotropic P2X receptors. Here, we report that elevations in cytosolic Ca stimulate the rapid uptake and nuclear accumulation of a DNA-binding fluorescent cation, Hoechst 33258 (H33258), in cervical cancer cells.

Targeted Assessment and Context-Tailored Implementation of Change Strategies (TACTICS) to increase evidence based psychotherapy in military behavioral health clinics: Design of a cluster-randomized stepped-wedge implementation study.

Background: Despite efforts by the U.S. Department of Defense to train behavioral health (BH) providers in evidence-based psychotherapies (EBPs) for posttraumatic stress disorder (PTSD), numerous barriers limit EBP implementation.

Establishment and optimization of epithelial cell cultures from human ectocervix, transformation zone, and endocervix optimization of epithelial cell cultures.

Cervical cancer is a major public health problem and research using cell culture models has improved understanding of this disease. The human cervix contains three anatomic regions; ectocervix with stratified squamous epithelium, endocervix with secretory epithelium, and transformation zone (TZ) with metaplastic cells. Most cervical cancers originate within the TZ.

HPV16-Immortalized Cells from Human Transformation Zone and Endocervix are More Dysplastic than Ectocervical Cells in Organotypic Culture.

A major risk factor for cervical cancer is persistent infection with high-risk human papillomaviruses (HPV) which can cause cervical intraepithelial neoplasia. Greater than 90% of cervical cancers develop in the transformation zone (TZ), a small region of metaplastic squamous epithelium at the squamocolumnar junction between endocervix and ectocervix. However, it is unclear why this region is highly susceptible to malignant progression.

Susceptibility of epithelial cells cultured from different regions of human cervix to HPV16-induced immortalization.

Persistent infection with high-risk human papillomavirus (HPV) is a major risk factor for cervical cancer. Greater than 90% of these cancers originate in the cervical transformation zone (TZ), a narrow region of metaplastic squamous epithelium that develops at the squamocolumnar junction between the ectocervix and endocervix. It is unclear why the TZ has high susceptibility to malignant transformation and few studies have specifically examined cells from this region.

Nanoreactors based on DNAzyme-functionalized magnetic nanoparticles activated by magnetic field.

A new biomimetic nanoreactor design, MaBiDz, is presented based on a copolymer brush in combination with superparamagnetic nanoparticles. This cellular nanoreactor features two species of magnetic particles, each functionalized with two components of a binary deoxyribozyme system. In the presence of a target mRNA analyte and a magnetic field, the nanoreactor is assembled to form a biocompartment enclosed by the polymeric brush that enables catalytic function of the binary deoxyribozyme with enhanced kinetics.

Magnetic Field-Activated Sensing of mRNA in Living Cells.

Detection of specific mRNA in living cells has attracted significant attention in the past decade. Probes that can be easily delivered into cells and activated at the desired time can contribute to understanding translation, trafficking and degradation of mRNA. Here we report a new strategy termed magnetic field-activated binary deoxyribozyme (MaBiDZ) sensor that enables both efficient delivery and temporal control of mRNA sensing by magnetic field.

Towards early detection of cervical cancer: Fractal dimension of AFM images of human cervical epithelial cells at different stages of progression to cancer.

Unlabelled: We used AFM HarmoniX modality to analyse the surface of individual human cervical epithelial cells at three stages of progression to cancer, normal, immortal (pre-malignant) and carcinoma cells. Primary cells from 6 normal strains, 6 cancer, and 6 immortalized lines (derived by plasmid DNA-HPV-16 transfection of cells from 6 healthy individuals) were tested. This cell model allowed for good control of the cell phenotype down to the single cell level, which is impractical to attain in clinical screening tests (ex-vivo).

Selective permeabilization of cervical cancer cells to an ionic DNA-binding cytotoxin by activation of P2Y receptors.

Extracellular ATP is known to permeabilize certain cell types to polyatomic cations like YO-PRO1. Here, we report that extracellularly applied ATP stimulated rapid uptake and accumulation of an otherwise weakly membrane permeable fluorescent DNA-binding cytotoxin, Hoechst 33258, into cervical cancer cells. While ATP stimulated Hoechst 33258 uptake in 20-70% of cells from seven cervical cancer cell lines, it stimulated uptake in less than 8% of cervical epithelial cells obtained from the normal transformation zone and ectocervix tissue of 11 patients.

Recovery of aging-related size increase of skin epithelial cells: in vivo mouse and in vitro human study.

The size increase of skin epithelial cells during aging is well-known. Here we demonstrate that treatment of aging cells with cytochalasin B substantially decreases cell size. This decrease was demonstrated on a mouse model and on human skin cells in vitro.

Relationship of Sensory Modality to Retention of Episodic Memory.

This study investigated the difference between episodic memory for verbal information presented in an oral format versus equivalent material presented in a written format. The study utilized the Logical Memory subtest of the Wechsler Memory Scales-Fourth Edition and the recently validated Morris Revision-IV Paragraphs. In a sample of 97 normal participants, auditory and visual memory performances were found to be significantly correlated (r = .

Fabrication, nanomechanical characterization, and cytocompatibility of gold-reinforced chitosan bio-nanocomposites.

Chitosan, a naturally derived polymer represents one of the most technologically important classes of active materials with applications in a variety of industrial and biomedical fields. Gold nanoparticles (~32 nm) were synthesized via a citrate reduction method from chloroauric acid and incorporated in Chitosan matrix. Bio-nanocomposite films with varying concentrations of gold nanoparticles were prepared through solution casting process.

Development of alternate paragraphs for the Logical Memory subtest of the Wechsler Memory Scale-IV.

The purpose of the two studies included in this article was to validate an alternate form, the Morris Revision-Fourth Edition (MR-IV), to the Logical Memory paragraphs of the Wechsler Memory Scale-Fourth Edition (LM-IV) for use when retesting of individuals is desired. Study I demonstrated high correlation with the LM-IV paragraphs. Study II was a replication that again demonstrated high correlation between the original LM-IV and the new MR-IV paragraphs.

Human papillomavirus type 16 E6 and E 7 proteins alter NF-kB in cultured cervical epithelial cells and inhibition of NF-kB promotes cell growth and immortalization.

The NF-kB family of transcription factors regulates important biological functions including cell growth, survival and the immune response. We found that Human Papillomavirus type 16 (HPV-16) E7 and E6/E7 proteins inhibited basal and TNF-alpha-inducible NF-kB activity in human epithelial cells cultured from the cervical transformation zone, the anatomic region where most cervical cancers develop. In contrast, HPV-16 E6 regulated NF-kB in a cell type- and cell growth-dependent manner.

Inhibition of the epidermal growth factor receptor by erlotinib prevents immortalization of human cervical cells by Human Papillomavirus type 16.

The Human Papillomavirus type-16 (HPV-16) E6 and E7 oncogenes are selectively retained and expressed in cervical carcinomas, and expression of E6 and E7 is sufficient to immortalize human cervical epithelial cells. Expression of the epidermal growth factor receptor (EGFR) is often increased in cervical dysplasia and carcinoma, and HPV oncoproteins stimulate cell growth via the EGFR pathway. We found that erlotinib, a specific inhibitor of EGFR tyrosine kinase activity, prevented immortalization of cultured human cervical epithelial cells by the complete HPV-16 genome or the E6/E7 oncogenes.

Detection of cancerous cervical cells using physical adhesion of fluorescent silica particles and centripetal force.

Here we describe a non-traditional method to identify cancerous human cervical epithelial cells in a culture dish based on physical adhesion between silica beads and cells. It is a simple optical fluorescence-based technique which detects the relative difference in the amount of fluorescent silica beads physically adherent to surfaces of cancerous and normal cervical cells. The method utilizes the centripetal force gradient that occurs in a rotating culture dish.

Towards nonspecific detection of malignant cervical cells with fluorescent silica beads.

To date, the methods for detection of cancer cells are mostly based on traditional techniques used in biology, such as visual identification of malignant changes, cell-growth analysis, specific ligand-receptor labeling, or genetic tests. Despite being well developed, these methods are either insufficiently accurate or require a lengthy complicated analysis. A search for alternative methods for the detection of cancer cells may be a fruitful approach.

Fundamental differences in cell cycle deregulation in human papillomavirus-positive and human papillomavirus-negative head/neck and cervical cancers.

Human papillomaviruses (HPV) are associated with nearly all cervical cancers, 20% to 30% of head and neck cancers (HNC), and other cancers. Because HNCs also arise in HPV-negative patients, this type of cancer provides unique opportunities to define similarities and differences of HPV-positive versus HPV-negative cancers arising in the same tissue. Here, we describe genome-wide expression profiling of 84 HNCs, cervical cancers, and site-matched normal epithelial samples in which we used laser capture microdissection to enrich samples for tumor-derived versus normal epithelial cells.

Recovery of elasticity of aged human epithelial cells in vitro.

We recently found a considerable increase in rigidity of human epithelial cells during aging in vitro. This is important because the loss in elasticity of epithelial tissues with aging contributes to many human diseases. We also found that cultured cells had three distinct regions of rigidity and that the increase in rigidity correlated with an increase in density of cytoskeletal fibers.

Inhibition of the epidermal growth factor receptor increases expression of genes that stimulate inflammation, apoptosis, and cell attachment.

The epidermal growth factor receptor (EGFR) is overexpressed in several types of human cancer, and inhibition of EGFR function is a promising strategy for cancer therapy. We used cDNA microarrays to examine alterations in gene expression after treatment of carcinoma cells with PD153035, a specific and reversible inhibitor of EGFR function. When human cervical carcinoma cells were grown on a collagen substrate in three-dimensional organotypic culture, untreated cells expressed high levels of EGFR RNA and invaded the underlying collagen.

Human epithelial cells increase their rigidity with ageing in vitro: direct measurements.

The decrease in elasticity of epithelial tissues with ageing contributes to many human diseases. This change was previously attributed to increased crosslinking of extracellular matrix proteins. Here we show that individual human epithelial cells also become significantly more rigid during ageing in vitro.