The emergence of extracellular vesicles in urology: fertility, cancer, biomarkers and targeted pharmacotherapy.

Extracellular vesicles (EV) are small membrane-bound vesicles enriched in a selective repertoire of mRNA, miRNA, proteins and cell surface receptors from parental cells and are actively involved in the transmission of inter and intracellular signals. Cancer cells produce EV that contain cargo including DNA, mRNA, miRNA and proteins that allow EV to create epigenetic changes in target cells both locally and systemically. Cancer-derived EV play critical roles in tumorigenesis, cancer cell migration, metastasis, evasion of host immune defense, chemoresistance, and they promote a premetastatic niche favourable to micrometastatic seeding.

Regulation of Aspartyl-(Asparaginyl)-β-Hydroxylase Protein Expression and Function by Phosphorylation in Hepatocellular Carcinoma Cells.

Background: Asparaginyl-β-hydroxylase (AAH) promotes cell adhesion, migration, and invasion via Notch activation. AAH's expression is up-regulated by insulin/IGF signaling through PI3K-Akt, but its protein is independently regulated by GSK-3β. The multiple predicted GSK-3β phosphorylation sites suggest post-translational mechanisms may regulate AAH protein expression.

Associations Between Psychiatric Impairment and Sexual Risk Behavior Among Teens in Mental Health Treatment.

Aims: To assess the associations of sexual risk behavior with psychiatric impairment and individual, peer, and partner attitudes among adolescents receiving mental health treatment.

Methods: Adolescents (N=893, 56% female, 67% African American) completed assessments of psychiatric impairment, rejection sensitivity, peer norms, HIV knowledge, perceived vulnerability, self-efficacy and condom use intentions. Two structural equation models were used to test the study hypotheses; one for sexually active youth and one for non-active youth.

Describing directional cell migration with a characteristic directionality time.

Many cell types can bias their direction of locomotion by coupling to external cues. Characteristics such as how fast a cell migrates and the directedness of its migration path can be quantified to provide metrics that determine which biochemical and biomechanical factors affect directional cell migration, and by how much. To be useful, these metrics must be reproducible from one experimental setting to another.

Restoration of Wnt/β-catenin signaling attenuates alcoholic liver disease progression in a rat model.

Background & Aims: Alcoholic liver disease (ALD) is characterized by the development of fatty liver, alcoholic hepatitis, fibrosis and cirrhosis. However, the underlying mechanism(s) associated with progression remains elusive. Pro-inflammatory cytokines have been implicated in ALD progression due to pro-apoptotic effects on hepatocytes.

Aspartate-β-hydroxylase induces epitope-specific T cell responses in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) has a poor prognosis due to high recurrence rate. Aspartate-β-hydroxylase (ASPH) is a highly conserved transmembrane protein, which is over expressed in HCC and promotes a malignant phenotype. The capability of ASPH protein-derived HLA class I and II peptides to generate antigen specific CD4(+) and CD8(+) immune responses is unknown.

Evidence for safe tourniquet use in 500 consecutive upper extremity procedures.

Background: Although pneumatic tourniquets are widely used in upper extremity surgery, further evidence is needed to support their safe use. Excessive pressure and prolonged ischemic time can cause soft-tissue injury. The purpose of this study was to determine the safety of tourniquet use in a yearlong, consecutive series of patients.

Internalizing Symptoms and Safe Sex Intentions among Adolescents in Mental Health Treatment: Personal Factors as Mediators.

Little is known about why some adolescents with internalizing symptoms engage in sexual behaviors that increase their risk for HIV. This study tested a mediation model of internalizing symptoms and safe sex intentions among adolescents receiving mental health treatment. Self-efficacy for HIV prevention, HIV knowledge, and worry about HIV were hypothesized to mediate associations between internalizing symptoms and safe sex intentions among sexually active and non-active adolescents receiving mental health treatment ( = 893, M age = 14.

Finesse in forehead and brow rejuvenation: modern concepts, including endoscopic methods.

Background: The brow and forehead are essential elements of the facial aesthetic architecture. Although frequently overlooked in youth, signs of facial aging are often most noticeable in the upper third of the face. Ptosis and loss of contour in the brows, along with temporal volume loss, sagging of periorbital tissue, and rhytides in the forehead, are common presenting complaints for aesthetic surgery.

Shaking up the system: the role of change in maternal-adolescent communication quality and adolescent weight loss.

Objective: The association between directly observed mother-adolescent weight-related communication quality and adolescent percent overweight within the context of an adolescent weight control study was examined.

Methods: As part of a larger study examining the impact of a behavioral weight control intervention that included attention to parent-adolescent communication (Standard Behavioral Treatment + Enhanced Parenting, SBT + EP) compared with an efficacious Standard Behavioral Treatment (SBT), 38 mother-adolescent dyads participated in a weight-related videotaped discussion. Discussions were taped and collected pre- and postintervention.

HCV epitope, homologous to multiple human protein sequences, induces a regulatory T cell response in infected patients.

Background & Aims: Spontaneous resolution of hepatitis C virus (HCV) infection depends upon a broad T cell response to multiple viral epitopes. However, most patients fail to clear infections spontaneously and develop chronic disease. The elevated number and function of CD3(+)CD4(+)CD25(+)FoxP3(+) regulatory T cells (T(reg)) in HCV-infected patients suggest a role of Treg cells in impaired viral clearance.

Family environment, coping, and mental health in adolescents attending therapeutic day schools.

Objective: This study examined associations among family environment, coping, and emotional and conduct problems in adolescents attending therapeutic day schools due to mental health problems.

Methods: Adolescents (N = 417; 30.2% female) ages 13-20 (M = 15.

Dendritic cell-mediated, DNA-based vaccination against hepatitis C induces the multi-epitope-specific response of humanized, HLA transgenic mice.

Hepatitis C virus (HCV) is the etiologic agent of chronic liver disease, hepatitis C. Spontaneous resolution of viral infection is associated with vigorous HLA class I- and class II-restricted T cell responses to multiple viral epitopes. Unfortunately, only 20% of patients clear infection spontaneously, most develop chronic disease and require therapy.

The G protein-coupled estrogen receptor-1, GPER-1, promotes fibrillogenesis via a Shc-dependent pathway resulting in anchorage-independent growth.

The G protein-coupled estrogen receptor-1, GPER-1, coordinates fibronectin (FN) matrix assembly and release of heparan-bound epidermal growth factor (HB-EGF). This mechanism of action results in the recruitment of FN-engaged integrin α5β1 to fibrillar adhesions and the formation of integrin α5β1-Shc adaptor protein complexes. Here, we show that GPER-1 stimulation of murine 4 T1 or human SKBR3 breast cancer cells with 17β-estradiol (E2β) promotes the formation of focal adhesions and actin stress fibers and results in increased cellular adhesion and haptotaxis on FN, but not collagen.

Type 3 diabetes is sporadic Alzheimer׳s disease: mini-review.

Alzheimer׳s disease (AD) is the most common cause of dementia in North America. Growing evidence supports the concept that AD is a metabolic disease mediated by impairments in brain insulin responsiveness, glucose utilization, and energy metabolism, which lead to increased oxidative stress, inflammation, and worsening of insulin resistance. In addition, metabolic derangements directly contribute to the structural, functional, molecular, and biochemical abnormalities that characterize AD, including neuronal loss, synaptic disconnection, tau hyperphosphorylation, and amyloid-beta accumulation.

A cell-surface β-hydroxylase is a biomarker and therapeutic target for hepatocellular carcinoma.

Unlabelled: Hepatocellular carcinoma (HCC) has a poor prognosis as a result of widespread intra- and extrahepatic metastases. There is an urgent need to understand signaling cascades that promote disease progression. Aspartyl-(asparaginyl)-β-hydroxylase (ASPH) is a cell-surface enzyme that generates enhanced cell motility, migration, invasion, and metastatic spread in HCC.

Intravenous ghrelin administration increases alcohol craving in alcohol-dependent heavy drinkers: a preliminary investigation.

Background: There is a need to identify novel pharmacologic targets to treat alcoholism. Animal and human studies suggest a role for ghrelin in the neurobiology of alcohol dependence and craving. Here, we were the first to test the hypothesis that intravenous administration of exogenous ghrelin acutely increases alcohol craving.

Peptide-pulsed dendritic cells induce the hepatitis C viral epitope-specific responses of naïve human T cells.

Hepatitis C virus (HCV) is a major cause of liver disease. Spontaneous resolution of infection is associated with broad, MHC class I- (CD8(+)) and class II-restricted (CD4(+)) T cell responses to multiple viral epitopes. Only 20% of patients clear infection spontaneously, however, most develop chronic disease.

Adolescents' emotions prior to sexual activity and associations with sexual risk factors.

The present study examined the link between the emotional context of sexual situations and sexual risk, specifically by examining the relationship of teens' recall of their affective states prior to sex with their sexual risk behaviors and attitudes. Adolescents (ages 13-19) attending therapeutic schools due to emotional and behavioral difficulties (n = 247) completed audio computer-assisted self-interviews regarding sexual behavior, including ratings of their emotions prior to last sexual activity. Positive emotions were most commonly endorsed (43-57 % of participants), however, significant proportions (8-23 %) also endorsed negative emotions prior to last sex.

New diagnostic and therapeutic possibilities for diastolic heart failure.

Despite the fact that up to half of all heart failure occurs in patients without evidence of systolic cardiac dysfunction, there are no universally accepted diagnostic markers and no approved therapies for heart failure with preserved ejection fraction (HFpEF). HFpEF, otherwise known as diastolic heart failure, has nearly the same grim prognosis as systolic heart failure, and diastolic heart failure is increasing in incidence and prevalence. Major trials have shown that many of the treatments that are salutary in systolic heart failure have no beneficial effects in diastolic heart failure, suggesting different underlying mechanisms for these two disorders.

Therapeutic reversal of chronic alcohol-related steatohepatitis with the ceramide inhibitor myriocin.

Alcohol-related liver disease (ALD) is associated with steatohepatitis and insulin resistance. Insulin resistance impairs growth and disrupts lipid metabolism in hepatocytes. Dysregulated lipid metabolism promotes ceramide accumulation and oxidative stress, leading to lipotoxic states that activate endoplasmic reticulum (ER) stress pathways and worsen inflammation and insulin resistance.

Main and Interactive Effects of Distress Tolerance and Negative Affect Intensity in Relation to PTSD Symptoms among Trauma-Exposed Adults.

The present investigation evaluated the main and interactive effects of distress tolerance and negative affect intensity in relation to posttraumatic stress disorder (PTSD) symptom severity and symptom cluster severity. Participants were 190 trauma-exposed adults (52.6 % women; =25.