The Value of Second-Opinion Consultation in Nongynecologic Cytopathology.

Objectives: The value of consultation in pathology has been well documented in surgical pathology, but there are few comprehensive studies of consultation cases in cytopathology. Here we report our experience with cytopathology consultation cases at a large academic center.

Methods: A review of consultation cases at our institution was performed by searching our laboratory information system.

Transcriptional control of subtype switching ensures adaptation and growth of pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDA) is a heterogeneous disease comprised of a basal-like subtype with mesenchymal gene signatures, undifferentiated histopathology and worse prognosis compared to the classical subtype. Despite their prognostic and therapeutic value, the key drivers that establish and control subtype identity remain unknown. Here, we demonstrate that PDA subtypes are not permanently encoded, and identify the GLI2 transcription factor as a master regulator of subtype inter-conversion.

TP53 Status as a Determinant of Pro- vs Anti-Tumorigenic Effects of Estrogen Receptor-Beta in Breast Cancer.

Background: Anti-tumorigenic vs pro-tumorigenic roles of estrogen receptor-beta (ESR2) in breast cancer remain unsettled. We investigated the potential of TP53 status to be a determinant of the bi-faceted role of ESR2 and associated therapeutic implications for triple negative breast cancer (TNBC).

Methods: ESR2-TP53 interaction was analyzed with multiple assays including the in situ proximity ligation assay.

Activity of a novel antimicrobial peptide against Pseudomonas aeruginosa biofilms.

With the increasing recognition of biofilms in human disease, the development of novel antimicrobial therapies is of critical importance. For example, in patients with cystic fibrosis (CF), the acquisition of host-adapted, chronic Pseudomonas aeruginosa infection is associated with a decline in lung function and increased mortality. Our objective was to test the in vitro efficacy of a membrane-active antimicrobial peptide we designed, termed 6K-F17 (sequence: KKKKKK-AAFAAWAAFAA-NH), against multidrug resistant P.

Combined Treatment with Epigenetic, Differentiating, and Chemotherapeutic Agents Cooperatively Targets Tumor-Initiating Cells in Triple-Negative Breast Cancer.

Efforts to induce the differentiation of cancer stem cells through treatment with all-trans retinoic acid (ATRA) have yielded limited success, partially due to the epigenetic silencing of the retinoic acid receptor (RAR)-β The histone deacetylase inhibitor entinostat is emerging as a promising antitumor agent when added to the standard-of-care treatment for breast cancer. However, the combination of epigenetic, cellular differentiation, and chemotherapeutic approaches against triple-negative breast cancer (TNBC) has not been investigated. In this study, we found that combined treatment of TNBC xenografts with entinostat, ATRA, and doxorubicin (EAD) resulted in significant tumor regression and restoration of epigenetically silenced RAR-β expression.

Cytotechnologist Performance for Screening Hürthle Cell Atypia in Indeterminate Thyroid Fine-Needle Aspirates.

Objectives: We have previously shown that specimens diagnosed as containing Hürthle cells have a 12% chance of being malignant if they are classified as atypia of undetermined significance (AUS-HC). The identification of Hürthle cells by cytotechnologists (CTs) during screening can improve cytopathologist efficiency and may prevent diagnostic errors due to the oversights of focal findings. Here, we examine the performance of our institutional CTs when screening for Hürthle cell atypia in thyroid fine-needle aspiration (FNA) specimens.

Cytotechnologist performance for screening microfollicular atypia in indeterminate thyroid fine-needle aspirates.

Introduction: We previously identified a high level of accuracy among our cytotechnologists (CTs) for identifying nuclear atypia in thyroid fine-needle aspiration (FNA) specimens. Herewith, we present our CT performance at screening for microfollicular atypia.

Methods: 8,814 thyroid FNA specimens were identified in our archives, all screened by 1 of 11 CTs and signed out by a cytopathologist.

Cytotechnologist performance for detecting nuclear atypia in indeterminate thyroid fine needle aspirates.

Introduction: The thyroid gland is arguably the fastest growing anatomic site for fine needle aspiration (FNA). With the increase of thyroid cases, a reevaluation of cytotechnologist screening quality metrics in terms of thyroid FNA is called for. We present our institutional cytotechnologist performance at screening for nuclear atypia by applying established quality metrics.

Patient report: autism spectrum disorder treated with camel milk.

This patient report is about my son, who was diagnosed with autism spectrum disorder (ASD) at 3 years of age, and the effects I observed when he began drinking camel milk daily. Beginning at age 9, he drank one half cup of raw camel milk a day and experienced overnight an improvement in his symptoms. His continued regular consumption of camel milk was associated with sustained symptom improvements for 6 consecutive years (2007-2013).

Inhibitors of the aminoglycoside 6'-N-acetyltransferase type Ib [AAC(6')-Ib] identified by in silico molecular docking.

AAC(6')-Ib is an important aminoglycoside resistance enzyme to target with enzymatic inhibitors. An in silico screening approach was used to identify potential inhibitors from the ChemBridge library. Several compounds were identified, of which two of them, 4-[(2-{[1-(3-methylphenyl)-4,6-dioxo-2-thioxotetrahydro-5(2H)-pyrimidinylidene]methyl}phenoxy)methyl]benzoic acid and 2-{5-[(4,6-dioxo-1,3-diphenyl-2-thioxotetrahydro-5(2H)-pyrimidinylidene)methyl]-2-furyl}benzoic acid, showed micromolar activity in inhibiting acetylation of kanamycin A.

Cyclin-dependent kinase 2 phosphorylates s/t-p sites in the hepadnavirus core protein C-terminal domain and is incorporated into viral capsids.

Phosphorylation of the hepadnavirus core protein C-terminal domain (CTD) is important for viral RNA packaging, reverse transcription, and subcellular localization. Hepadnavirus capsids also package a cellular kinase. The identity of the host kinase that phosphorylates the core CTD or gets packaged remains to be resolved.

Achromobacter xylosoxidans: an emerging pathogen carrying different elements involved in horizontal genetic transfer.

In the last few years, numerous cases of multidrug-resistant Achromobacter xylosoxidans infections have been documented in immunocompromised and cystic fibrosis patients. To gain insights into the molecular mechanisms and mobile elements related to multidrug resistance in this bacterium, we studied 24 non-epidemiological A. xylosoxidans clinical isolates from Argentina.

TP-RT domain interactions of duck hepatitis B virus reverse transcriptase in cis and in trans during protein-primed initiation of DNA synthesis in vitro.

The hepadnavirus reverse transcriptase (RT) has the unique ability to initiate viral DNA synthesis using RT itself as a protein primer. Protein priming requires complex interactions between the N-terminal TP (terminal protein) domain, where the primer (a specific Y residue) resides, and the central RT domain, which harbors the polymerase active site. While it normally utilizes the cis-linked TP to prime DNA synthesis (cis-priming), we found that the duck hepatitis B virus (DHBV) RT domain, in the context of the full-length RT protein or a mini-RT construct containing only truncated TP and RT domains, could additionally use a separate TP or RT domain in trans as a primer (trans-priming).

Phosphorylation state-dependent interactions of hepadnavirus core protein with host factors.

Dynamic phosphorylation and dephosphorylation of the hepadnavirus core protein C-terminal domain (CTD) are required for multiple steps of the viral life cycle. It remains unknown how the CTD phosphorylation state may modulate core protein functions but phosphorylation state-dependent viral or host interactions may play a role. In an attempt to identify host factors that may interact differentially with the core protein depending on its CTD phosphorylation state, pulldown assays were performed using the CTD of the duck hepatitis B virus (DHBV) and human hepatitis B virus (HBV) core protein, either with wild type (WT) sequences or with alanine or aspartic acid substitutions at the phosphorylation sites.

Virtual cerebral ventricular system: an MR-based three-dimensional computer model.

The inherent spatial complexity of the human cerebral ventricular system, coupled with its deep position within the brain, poses a problem for conceptualizing its anatomy. Cadaveric dissection, while considered the gold standard of anatomical learning, may be inadequate for learning the anatomy of the cerebral ventricular system; even with intricate dissection, ventricular structures remain difficult to observe. Three-dimensional (3D) computer reconstruction of the ventricular system offers a solution to this problem.

Secretion of genome-free hepatitis B virus--single strand blocking model for virion morphogenesis of para-retrovirus.

As a para-retrovirus, hepatitis B virus (HBV) is an enveloped virus with a double-stranded (DS) DNA genome that is replicated by reverse transcription of an RNA intermediate, the pregenomic RNA or pgRNA. HBV assembly begins with the formation of an "immature" nucleocapsid (NC) incorporating pgRNA, which is converted via reverse transcription within the maturing NC to the DS DNA genome. Only the mature, DS DNA-containing NCs are enveloped and secreted as virions whereas immature NCs containing RNA or single-stranded (SS) DNA are not enveloped.

EGFR and KRAS mutations in metastatic lung adenocarcinomas.

In primary lung adenocarcinoma, EGFR and KRAS mutations are found in approximately 10% to 20% and 20% to 30%, respectively. Few studies have investigated these mutations in metastases. Patients with EGFR mutations have a 70% to 80% response rate to tyrosine-kinase inhibitors therapy and a longer progression-free survival rate in contrast to patients with KRAS mutations that are associated with virtually no response tyrosine-kinase inhibitors.

Volitional nonadherence in pediatric asthma: parental report of motivating factors.

Volitional nonadherence is thought to be common among patients with chronic health conditions, including pediatric asthma. To date, no data have been published on the extent to which, and reasons why, families purposefully adjust their child's asthma regimen. This study provides descriptive data for parental report of volitional nonadherence in a sample of 101 children (ages 1-17 years) with asthma.

Social perceptions and preferences of youth with asthma.

Peers are a primary source of psychosocial support in youth. Chronic disease such as asthma can make youth feel different and impinge on their adherence to treatment. We investigated factors that make the asthmatic adolescent feel different from peers, and explore their willingness to belong to a peer social-group such as an asthma club.

Adherence in young children with asthma.

Purpose Of Review: To discuss the unique challenges of managing asthma in young children and to review the literature over the past year with regard to regimen adherence in this relatively understudied population.

Recent Findings: Young children and their families face unique challenges in dealing with asthma and these have the potential to affect regimen adherence. They include the time and effort required by asthma-management activities (e.

Child and caregiver psychosocial functioning in pediatric immunodeficiency disorders.

Background: Children with chronic illness have been found to be at an increased risk of behavioral and emotional difficulties. To date, children with pediatric immunodeficiency disorders (PIDDs) and their families have not been the focus of extensive published psychosocial research.

Objective: To determine if children with PIDDs and their caregivers have altered psychosocial function and whether the severity of the PIDD was associated with such difficulties.

Learning preferences of caregivers of asthmatic children.

Background: People learn in different ways: visually, aurally, by reading/writing, and kinesthetically. In our clinic, we use color-coded Asthma Action Cards to educate our patients and their caregivers on asthma management. Our teaching is largely aural based, with the cards providing reading and visual stimulation and hands-on practice with devices offering kinesthetic stimulation.

Percutaneous translumbar spinal cord compression injury in dogs from an angioplasty balloon: MR and histopathologic changes with balloon sizes and compression times.

Background And Purpose: Our previous model of spinal cord injury (SCI) included six dogs undergoing 30-minute compression with a balloon in the subarachnoid space. We determined whether various balloon sizes and compression times creates a gradation of injuries.

Methods: In 17 dogs (including our original six), angioplasty balloons 2, 4, or 7 mm in diameter (2 cm long) were inflated at T6 for 30, 120, or 240 minutes.

Pediatric asthma: a look at adherence from the patient and family perspective.

Although extensive research has been done in an effort to understand and promote adherence in pediatric asthma, little progress has been made in reducing the prevalence of nonadherence. Some researchers argue that a paradigm shift is necessary to advance the adherence field. Despite the recent trend for increasing the role of families in determining treatment plans, a patient-centered approach has been lacking in adherence to a daily regimen.