AR negative triple negative or "quadruple negative" breast cancers in African American women have an enriched basal and immune signature.

There is increasing evidence that Androgen Receptor (AR) expression has prognostic usefulness in Triple negative breast cancer (TNBC), where tumors that lack AR expression are considered "Quadruple negative" Breast Cancers ("QNBC"). However, a comprehensive analysis of AR expression within all breast cancer subtypes or stratified by race has not been reported. We assessed AR mRNA expression in 925 tumors from The Cancer Genome Atlas (TCGA), and 136 tumors in 2 confirmation sets.

Traditional and systems biology based drug discovery for the rare tumor syndrome neurofibromatosis type 2.

Neurofibromatosis 2 (NF2) is a rare tumor suppressor syndrome that manifests with multiple schwannomas and meningiomas. There are no effective drug therapies for these benign tumors and conventional therapies have limited efficacy. Various model systems have been created and several drug targets have been implicated in NF2-driven tumorigenesis based on known effects of the absence of merlin, the product of the NF2 gene.

Prevalence of Obstructive Sleep Apnea (OSA) in Spontaneous Cerebrospinal Fluid (CSF) Leaks: A Prospective Cohort Study.

Objective: To determine the prevalence of obstructive sleep apnea (OSA) in a prospective cohort of patients with spontaneous CSF (sCSF) leaks of the temporal bone.

Study Design: Prospective cohort study.

Setting: Tertiary referral center.

"…Not Intended to Diagnose, Treat, Cure or Prevent Any Disease." 25 Years of Botanical Dietary Supplement Research and the Lessons Learned.

Botanical dietary supplements (BDS) are complex mixtures of phytochemicals exhibiting complex pharmacology and posing complex research challenges. For 25 years, clinical pharmacologists researching BDS have confronted a litany of issues unlike those encountered with conventional medications. Foundational to these concerns is the Dietary Supplement Health and Education Act of 1994, which exempted BDS from premarket safety and efficacy trials.

Current Therapeutic Strategies for Adipose Tissue Defects/Repair Using Engineered Biomaterials and Biomolecule Formulations.

Tissue engineered scaffolds for adipose restoration/repair has significantly evolved in recent years. Patients requiring soft tissue reconstruction, caused by defects or pathology, require biomaterials that will restore void volume with new functional tissue. The gold standard of autologous fat grafting (AFG) is not a reliable option.

Real-time super-resolved 3D in turbid water using a fast range-gated CMOS camera.

We present a range-gated camera system designed for real-time (10 Hz) 3D estimation underwater. The system uses a fast-shutter CMOS sensor (1280×1024) customized to facilitate gating with 1.67 ns (18.

VT-1598 inhibits the in vitro growth of mucosal Candida strains and protects against fluconazole-susceptible and -resistant oral candidiasis in IL-17 signalling-deficient mice.

Background: Chronic mucocutaneous candidiasis (CMC) treatment often induces drug resistance, posing long-term challenges. A novel broad-spectrum fungal CYP51 inhibitor, VT-1598, specifically targets fungal CYP51, but not human CYP enzymes.

Objectives: To determine the efficacy of VT-1598 in the treatment of oral Candida infection caused by fluconazole-susceptible and -resistant clinical isolates.

The TP53-Induced Glycolysis and Apoptosis Regulator mediates cooperation between HTLV-1 p30 and the retroviral oncoproteins Tax and HBZ and is highly expressed in an in vivo xenograft model of HTLV-1-induced lymphoma.

The human T-cell leukemia virus type-1 (HTLV-1) is an oncoretrovirus that infects and transforms CD4+ T-cells and causes adult T-cell leukemia/lymphoma (ATLL) -an aggressive lymphoproliferative disease that is highly refractive to most anticancer therapies. The HTLV-1 proviral genome encodes several regulatory products within a conserved 3' nucleotide sequence, known as pX; however, it remains unclear how these factors might cooperate or dynamically interact in virus-infected cells. Here we demonstrate that the HTLV-1 latency-maintenance factor p30 induces the TP53-induced glycolysis and apoptosis regulator (TIGAR) and counters the oxidative stress, mitochondrial damage, and cytotoxicity caused by the viral oncoproteins Tax and HBZ.

Modeling persistence of motion in a crowded environment: The diffusive limit of excluding velocity-jump processes.

Persistence of motion is the tendency of an object to maintain motion in a direction for short time scales without necessarily being biased in any direction in the long term. One of the most appropriate mathematical tools to study this behavior is an agent-based velocity-jump process. In the absence of agent-agent interaction, the mean-field continuum limit of the agent-based model (ABM) gives rise to the well known hyperbolic telegraph equation.

Increasing Cardiomyocyte Atrogin-1 Reduces Aging-Associated Fibrosis and Regulates Remodeling in Vivo.

The muscle-specific ubiquitin ligase atrogin-1 (MAFbx) has been identified as a critical regulator of pathologic and physiological cardiac hypertrophy; it regulates these processes by ubiquitinating transcription factors [nuclear factor of activated T-cells and forkhead box O (FoxO) 1/3]. However, the role of atrogin-1 in regulating transcription factors in aging has not previously been described. Atrogin-1 cardiomyocyte-specific transgenic (Tg) adult mice (α-major histocompatibility complex promoter driven) have normal cardiac function and size.

Transcriptional repressor Kaiso promotes epithelial to mesenchymal transition and metastasis in prostate cancer through direct regulation of miR-200c.

The loss of miR-200 family, through DNA methylation, results in cancer cells undergoing an epithelial to mesenchymal transition (EMT), and metastasis. In this study, we established that the transcriptional repressor Kaiso directly binds methylated regions of the miR-200 family, and this is reversed with 5-aza treatment. sh-Kaiso PC-3 cells display increased miR-200-a/b/c, miR-141, and miR-429 expression, with miR-200c demonstrating the most significant increase.

Outbreak of invasive group A streptococcus: investigations using agar settle plates detect perineal shedding from a healthcare worker.

Background: Outbreaks of group A streptococcus (GAS) infections may occur in healthcare settings. Transmission to patients is sometimes linked to colonized healthcare workers (HCWs) and/or a contaminated environment.

Aim: To describe the investigation and control of an outbreak of healthcare-associated GAS on an elderly care medical ward, over six months.

Difficulties in cerebrospinal fluid βhCG interpretation in a patient with an infundibular lesion.

Unlabelled: A variety of neoplastic, inflammatory and congenital conditions can cause pituitary stalk thickening. Differentiating between these causes is important as targeted treatment may be offered. Diagnostic work-up consists of a thorough history, examination, biochemical analysis and imaging.

Spatially extended hybrid methods: a review.

Many biological and physical systems exhibit behaviour at multiple spatial, temporal or population scales. Multiscale processes provide challenges when they are to be simulated using numerical techniques. While coarser methods such as partial differential equations are typically fast to simulate, they lack the individual-level detail that may be required in regions of low concentration or small spatial scale.

Demographic and genetic viability of a medium-sized ground-dwelling mammal in a fire prone, rapidly urbanizing landscape.

The rapid and large-scale urbanization of peri-urban areas poses major and complex challenges for wildlife conservation. We used population viability analysis (PVA) to evaluate the influence of urban encroachment, fire, and fauna crossing structures, with and without accounting for inbreeding effects, on the metapopulation viability of a medium-sized ground-dwelling mammal, the southern brown bandicoot (Isoodon obesulus), in the rapidly expanding city of Perth, Australia. We surveyed two metapopulations over one and a half years, and parameterized the PVA models using largely field-collected data.

Genome-Wide Association Study in African Americans with Acute Respiratory Distress Syndrome Identifies the Selectin P Ligand Gene as a Risk Factor.

Rationale: Genetic factors are involved in acute respiratory distress syndrome (ARDS) susceptibility. Identification of novel candidate genes associated with increased risk and severity will improve our understanding of ARDS pathophysiology and enhance efforts to develop novel preventive and therapeutic approaches.

Objectives: To identify genetic susceptibility targets for ARDS.

Chemopreventative celecoxib fails to prevent schwannoma formation or sensorineural hearing loss in genetically engineered murine model of neurofibromatosis type 2.

Mutations in the tumor suppressor gene lead to Neurofibromatosis type 2 (NF2), a tumor predisposition syndrome characterized by the development of schwannomas, including bilateral vestibular schwannomas with complete penetrance. Recent work has implicated the importance of COX-2 in schwannoma growth. Using a genetically engineered murine model of NF2, we demonstrate that selective inhibition of COX-2 with celecoxib fails to prevent the spontaneous development of schwannomas or sensorineural hearing loss , despite elevated expression levels of COX-2 in -deficient tumor tissue.

Acute recreational drug toxicity: Comparison of self-reports and results of immunoassay and additional analytical methods in a multicenter European case series.

The aim of the study was to compare self-reported and analytically confirmed substance use in cases of acute recreational drug toxicity.We performed a retrospective analysis of emergency department presentations of acute recreational drug toxicity over 2 years (October 2013 to September 2015) within the European Drug Emergencies Network Plus project.Among the 10,956 cases of acute recreational drug toxicity during the study period, 831 could be included.

Outpatient management of cholesteatoma with canal wall reconstruction tympanomastoidectomy.

Objectives: The postoperative wound infection rate for canal wall reconstruction (CWR) tympanomastoidectomy with mastoid obliteration in the treatment of chronic otitis media with cholesteatoma has been reported to be 3.6%. Postoperative administration of 24-48 hours of intravenous antibiotics has been recommended.

Neuroligin 4X overexpression in human breast cancer is associated with poor relapse-free survival.

The molecular mechanisms involved in breast cancer progression and metastasis still remain unclear to date. It is a heterogeneous disease featuring several different phenotypes with consistently different biological characteristics. Neuroligins are neural cell adhesion molecules that have been implicated in heterotopic cell adhesion.

A review of structural brain abnormalities in Pallister-Killian syndrome.

Background: Pallister-Killian syndrome (PKS) is a rare multisystem developmental syndrome usually caused by mosaic tetrasomy of chromosome 12p that is known to be associated with neurological defects.

Methods: We describe two patients with PKS, one of whom has bilateral perisylvian polymicrogyria (PMG), the other with macrocephaly, enlarged lateral ventricles and hypogenesis of the corpus callosum. We have also summarized the current literature describing brain abnormalities in PKS.

Polycystin-1 interacts with TAZ to stimulate osteoblastogenesis and inhibit adipogenesis.

The molecular mechanisms that transduce the osteoblast response to physical forces in the bone microenvironment are poorly understood. Here, we used genetic and pharmacological experiments to determine whether the polycystins PC1 and PC2 (encoded by Pkd1 and Pkd2) and the transcriptional coactivator TAZ form a mechanosensing complex in osteoblasts. Compound-heterozygous mice lacking 1 copy of Pkd1 and Taz exhibited additive decrements in bone mass, impaired osteoblast-mediated bone formation, and enhanced bone marrow fat accumulation.

Fungal-specific Cyp51 inhibitor VT-1598 demonstrates in vitro activity against Candida and Cryptococcus species, endemic fungi, including Coccidioides species, Aspergillus species and Rhizopus arrhizus.

Background: Invasive fungal infections, including those caused by yeasts, moulds and endemic organisms, can be significant causes of morbidity and mortality in immunocompromised hosts, those with multiple comorbidities and occasionally immunocompetent hosts. Current antifungal agents are often limited by drug toxicities, drug interactions or the development of resistance. VT-1598 is a novel tetrazole that has greater specificity for fungal Cyp51 than currently available triazoles and thus the potential for clinically significant drug interactions is reduced.