Novel use of old drug: Anti-rheumatic agent auranofin overcomes imatinib-resistance of chronic myeloid leukemia cells.

Patients with chronic myeloid leukemia (CML) are commonly treated with a specific inhibitor of BCR-ABL tyrosine kinase, imatinib mesylate (IM). Unfortunately, CML patients develop IM-resistance, which has emerged as a significant clinical problem. Somatic mutations, especially T315I mutation, in BCR-ABL kinase domain represent the most common mechanism underlying drug resistance to tyrosine kinase inhibitors (TKI), including imatinib.

Glandular Lesions of the Cervix in Clinical Practice: A Cytology, Histology, and Human Papillomavirus Correlation Study From 2 Institutions.

Context: The Papanicolaou (Pap) test has indisputably decreased cervical cancer mortality, as rates have declined by up to 80% in the United States since its implementation. However, the Pap test is considered less sensitive for detecting glandular lesions than for detecting those of squamous origin. Some studies have even suggested an increasing incidence of cervical adenocarcinoma, which may be a consequence of a relatively reduced ability to detect glandular lesions with cervical cancer screening techniques.

Reliable Quantitative SERS Analysis Facilitated by Core-Shell Nanoparticles with Embedded Internal Standards.

Quantitative analysis is a great challenge in surface-enhanced Raman scattering (SERS). Core-molecule-shell nanoparticles with two components in the molecular layer, a framework molecule to form the shell, and a probe molecule as a Raman internal standard, were rationally designed for quantitative SERS analysis. The signal of the embedded Raman probe provides effective feedback to correct the fluctuation of samples and measuring conditions.

Metaplastic breast cancer in a patient with neurofibromatosis.

Metaplastic breast cancer is a rare malignancy in the breast. Neurofibromatosis Type 1 is an autosomal dominant multisystem disorder associated with multiple neoplasms such as optic gliomas and peripheral nerve sheath tumors. The association of breast cancer with neurofibromatosis is very rare.

Late onset multiple sclerosis: Is it really late onset?

Background: Multiple sclerosis (MS) is the most common demyelinating disease, and onset over the age of 50 years is referred to as late onset MS (LOMS). It has been thought that LOMS patients will be more likely to exhibit a primary progressive (PPMS) clinical course.

Objective: To identify the clinical characteristics of demyelinating disease in patients over the age of 50 years from four different MS centers in the Northern Midwest USA.

Gambogic acid induces apoptosis in diffuse large B-cell lymphoma cells via inducing proteasome inhibition.

Resistance to chemotherapy is a great challenge to improving the survival of patients with diffuse large B-cell lymphoma (DLBCL), especially those with activated B-cell-like DLBCL (ABC-DLBCL). Therefore it is urgent to search for novel agents for the treatment of DLBCL. Gambogic acid (GA), a small molecule derived from Chinese herb gamboges, has been approved for Phase II clinical trial for cancer therapy by Chinese FDA.

Concurrent use of stimulants and second-generation antipsychotics among children with ADHD enrolled in Medicaid.

Objective: This study examined the prevalence of and factors associated with concurrent use of long-acting stimulants (LAS) and second-generation antipsychotic agents among children and adolescents with attention-deficit hyperactivity disorder (ADHD).

Methods: The study involved retrospective longitudinal analysis of 2003-2007 Medicaid data from four states for children and adolescents between the ages of six and 17 years who were diagnosed as having ADHD and initiated LAS treatment. Concurrent use of LAS and second-generation antipsychotic medications was defined as simultaneous receipt of both medications for at least 14 days.

OnabotulinumtoxinA Injections for the Treatment of Cyclic Vomiting Syndrome.

Cyclic vomiting syndrome (CVS) is a disorder characterized by episodes of nausea and vomiting lasting 1 to 5 days, followed by asymptomatic periods. The etiology and pathophysiology of CVS are unknown, but CVS shares similar characteristics to those of migraine headaches. Tricyclic antidepressants have the most evidence and are generally effective for prophylaxis of further episodes in patients with CVS.

Electronic properties of nickel-doped TiO₂ anatase.

Atomistic details of electron transfer in semiconductor materials are characterized for TiO2 thin film surfaces doped with nickel. A periodic slab model of eight atomic layers exposes the (1 0 0) crystallographic surface and is covered with a monolayer of water. The density of states, absorption spectra, partial charge densities, molecular dynamics, and non-adiabatic couplings are compared between doped and undoped models.

Priming the proteasome by protein kinase G: a novel cardioprotective mechanism of sildenafil.

The proteasome mediates the degradation of most cellular proteins including misfolded proteins, pivotal to intracellular protein hemostasis. Proteasome functional insufficiency is implicated in a large subset of human failing hearts. Experimental studies have established proteasome functional insufficiency as a major pathogenic factor, rationalizing proteasome enhancement as a potentially new therapeutic strategy for congestive heart failure.

Effective treatment of dyssynergic defecation using sacral neuromodulation in a patient with cerebral palsy.

Background: Dyssynergic defecation is a complex bowel problem that leads to chronic constipation and abdominal pain. Management is often challenging owing to the incoordination of multiple pelvic floor muscles involved in normal defecation.

Case: We report a case of dyssynergic defecatory dysfunction in a patient with cerebral palsy treated with sacral neuromodulation.

Plasma phospholipids, non-esterified plasma polyunsaturated fatty acids and oxylipids are associated with BMI.

The obese lipid profile is associated with increased free fatty acids and triacylglycerides. Currently, little is known about the plasma lipid species associated with obesity. In this study, we compared plasma lipid fatty acid (FA) profiles as a function of BMI.

Epigenetics in pediatrics.

Epigenetic mechanisms are external modifications of DNA that cause changes in gene function and are involved in many diseases. Specific examples of pediatric diseases with a known or suspected epigenetic component include Beckwith-Wiedemann syndrome, childhood leukemia, allergies, asthma, fetal alcohol spectrum disorders, childhood obesity, and type 2 diabetes mellitus. Currently, epigenetically active treatments are being used to treat childhood leukemia.

Surface modification of CoCr alloy using varying concentrations of phosphoric and phosphonoacetic acids: albumin and fibrinogen adsorption, platelet adhesion, activation, and aggregation studies.

CoCr alloy is commonly used in various cardiovascular medical devices for its excellent physical and mechanical properties. However, the formation of blood clots on the alloy surfaces is a serious concern. This research is focused on the surface modification of CoCr alloy using varying concentrations (1, 25, 50, 75, and 100 mM) of phosphoric acid (PA) and phosphonoacetic acid (PAA) to generate various surfaces with different wettability, chemistry, and roughness.

Inactivation of the Rgg2 transcriptional regulator ablates the virulence of Streptococcus pyogenes.

Streptococcus pyogenes adapts to different niches encountered in the human host via the activity of numerous regulatory proteins including the Rgg family of transcriptional regulators. The S. pyogenes chromosome encodes four Rgg paralogues designated Rgg1 (RopB), Rgg2 (MutR), Rgg3, and Rgg4 (ComR).

Nonsense-mediated decay in genetic disease: friend or foe?

Eukaryotic cells utilize various RNA quality control mechanisms to ensure high fidelity of gene expression, thus protecting against the accumulation of nonfunctional RNA and the subsequent production of abnormal peptides. Messenger RNAs (mRNAs) are largely responsible for protein production, and mRNA quality control is particularly important for protecting the cell against the downstream effects of genetic mutations. Nonsense-mediated decay (NMD) is an evolutionarily conserved mRNA quality control system in all eukaryotes that degrades transcripts containing premature termination codons (PTCs).

Prevalence and characteristics of fetal alcohol spectrum disorders.

Objectives: To determine the prevalence and characteristics of fetal alcohol spectrum disorders (FASD) among first grade students (6- to 7-year-olds) in a representative Midwestern US community.

Methods: From a consented sample of 70.5% of all first graders enrolled in public and private schools, an oversample of small children (≤ 25th percentile on height, weight, and head circumference) and randomly selected control candidates were examined for physical growth, development, dysmorphology, cognition, and behavior.

Vulnerability of the medial frontal corticospinal projection accompanies combined lateral frontal and parietal cortex injury in rhesus monkey.

Concurrent damage to the lateral frontal and parietal cortex is common following middle cerebral artery infarction, leading to upper extremity paresis, paresthesia, and sensory loss. Motor recovery is often poor, and the mechanisms that support or impede this process are unclear. Since the medial wall of the cerebral hemisphere is commonly spared following stroke, we investigated the spontaneous long-term (6 and 12 month) effects of lateral frontoparietal injury (F2P2 lesion) on the terminal distribution of the corticospinal projection (CSP) from intact, ipsilesional supplementary motor cortex (M2) at spinal levels C5 to T1.

Ormeloxifene efficiently inhibits ovarian cancer growth.

Ovarian cancer continues to be a leading cause of cancer related deaths for women. Anticancer agents effective against chemo-resistant cells are greatly needed for ovarian cancer treatment. Repurposing drugs currently in human use is an attractive strategy for developing novel cancer treatments with expedited translation into clinical trials.

Mechanisms by which low glucose enhances the cytotoxicity of metformin to cancer cells both in vitro and in vivo.

Different cancer cells exhibit altered sensitivity to metformin treatment. Recent studies suggest these findings may be due in part to the common cell culture practice of utilizing high glucose, and when glucose is lowered, metformin becomes increasingly cytotoxic to cancer cells. In low glucose conditions ranging from 0 to 5 mM, metformin was cytotoxic to breast cancer cell lines MCF7, MDAMB231 and SKBR3, and ovarian cancer cell lines OVCAR3, and PA-1.

A comparison of the direct cost of care in an open-bay and single-family room NICU.

Objective: This research examined the proposition that the direct costs of care were no different in an open-bay (OPBY) as compared with a single-family room (SFR) neonatal intensive care (NICU) environment.

Study Design: This was a sequential cohort study.

Result: General linear models were implemented using clinical and cost data for all neonates admitted to the two cohorts studied.

Antiprogestins in gynecological diseases.

Antiprogestins constitute a group of compounds, developed since the early 1980s, that bind progesterone receptors with different affinities. The first clinical uses for antiprogestins were in reproductive medicine, e.g.

Multicenter cohort study on association of genotypes with prospective sports concussion: methods, lessons learned, and recommendations.

Background: Approximately 3.8 million sports related TBIs occur per year. Genetic variation may affect both TBI risk and post-TBI clinical outcome.

Serotonin in the ventral hippocampus modulates anxiety-like behavior during amphetamine withdrawal.

Withdrawal from amphetamine is associated with increased anxiety and sensitivity to stressors which are thought to contribute to relapse. Rats undergoing amphetamine withdrawal fail to exhibit stress-induced increases in serotonin (5-HT) release in the ventral hippocampus and show heightened anxiety-like behaviors. Therefore, we tested the hypothesis that reducing 5-HT levels in the ventral hippocampus is a causal mechanism in increasing anxiety-like behaviors during amphetamine withdrawal.

Central CRF2 receptor antagonism reduces anxiety states during amphetamine withdrawal.

Increased depressive and anxiety-like behaviors are exhibited by rats and humans during withdrawal from psychostimulants. Anxiety-like behaviors observed during amphetamine withdrawal are mediated by increased expression and activity of corticotropin releasing factor type 2 (CRF2) receptors in the dorsal raphe nucleus (dRN). Anxiety-like behavior of rats during withdrawal can be reversed by CRF2 receptor antagonism in the dRN, but the efficacy of global central CRF2 receptor antagonism is unknown.