Triple negative breast tumors in African-American and Hispanic/Latina women are high in CD44+, low in CD24+, and have loss of PTEN.

Background: African-American women have higher mortality from breast cancer than other ethnic groups. The association between poor survival and differences with tumor phenotypes is not well understood. The purpose of this study is to assess the clinical significance of (1) Stem cell-like markers CD44 and CD24; (2) PI3K/Akt pathway associated targets PTEN, activation of Akt, and FOXO1; and (3) the Insulin-like growth factor-1 (IGF-I) and IGF binding protein-3 (IGFBP3) in different breast cancer subtypes, and compare the differences between African-American and Hispanic/Latina women who have similar social-economic-status.

The mTOR kinase inhibitors, CC214-1 and CC214-2, preferentially block the growth of EGFRvIII-activated glioblastomas.

Purpose: mTOR pathway hyperactivation occurs in approximately 90% of glioblastomas, but the allosteric mTOR inhibitor rapamycin has failed in the clinic. Here, we examine the efficacy of the newly discovered ATP-competitive mTOR kinase inhibitors CC214-1 and CC214-2 in glioblastoma, identifying molecular determinants of response and mechanisms of resistance, and develop a pharmacologic strategy to overcome it.

Experimental Design: We conducted in vitro and in vivo studies in glioblastoma cell lines and an intracranial model to: determine the potential efficacy of the recently reported mTOR kinase inhibitors CC214-1 (in vitro use) and CC214-2 (in vivo use) at inhibiting rapamycin-resistant signaling and blocking glioblastoma growth and a novel single-cell technology-DNA Encoded Antibody Libraries-was used to identify mechanisms of resistance.

Pharmacokinetics and safety of tenofovir in HIV-infected women during labor and their infants during the first week of life.

Background: Data describing the pharmacokinetics and safety of tenofovir in neonates are lacking.

Methods: The HIV Prevention Trials Network 057 protocol was a phase 1, open-label study of the pharmacokinetics and safety of tenofovir disoproxil fumarate (TDF) in HIV-infected women during labor and their infants during the first week of life with 4 dosing cohorts: maternal 600 mg doses/no infant dosing; no maternal dosing/infant 4 mg/kg doses on days 0, 3, and 5; maternal 900 mg doses/infant 6 mg/kg doses on days 0, 3, and 5; maternal 600 mg doses/infant 6 mg/kg daily for 7 doses. Pharmacokinetic sampling was performed on cohort 1 and 3 mothers and all infants.

Advances in MR imaging for cervical spondylotic myelopathy.

Purpose: To outline the pathogenesis of cervical spondylotic myelopathy (CSM), the correlative abnormalities observed on standard magnetic resonance imaging (MRI), the biological implications and current status of diffusion tensor imaging (DTI), and MR spectroscopy (MRS) as clinical tools, and future directions of MR technology in the management of CSM patients.

Methods: A systematic review of the pathogenesis and current state-of-the-art in MR imaging technology for CSM was performed.

Results: CSM is caused by progressive, degenerative, vertebral column abnormalities that result in spinal cord damage related to both primary mechanical and secondary biological injuries.

Impaired left ventricular filling in COPD and emphysema: is it the heart or the lungs? The Multi-Ethnic Study of Atherosclerosis COPD Study.

Background: COPD and heart failure with preserved ejection fraction overlap clinically, and impaired left ventricular (LV) filling is commonly reported in COPD. The mechanism underlying these observations is uncertain, but may include upstream pulmonary dysfunction causing low LV preload or intrinsic LV dysfunction causing high LV preload. The objective of this study is to determine if COPD and emphysema are associated with reduced pulmonary vein dimensions suggestive of low LV preload.

Neurostimulation for drug-resistant epilepsy.

Purpose Of Review: The purpose of this review is to provide an evidence-based update on the neurostimulation options available for patients with drug-resistant epilepsy in the United States and in European countries.

Recent Findings: The field of neurostimulation for epilepsy has grown dramatically since 1997, when vagus nerve stimulation became the first device to be approved for epilepsy by the US Food and Drug Administration (FDA). New data from recently completed randomized controlled trials are available for deep brain stimulation of the anterior thalamus, responsive neurostimulation, and trigeminal nerve stimulation.

Atypical rearrangement involving 3'-IGH@ and a breakpoint at least 400 Kb upstream of an intact MYC in a CLL patient with an apparently balanced t(8;14)(q24.1;q32) and negative MYC expression.

The t(8;14)(q24.1;q32), the cytogenetic hallmark of Burkitt's lymphoma, is also found, but rarely, in cases of chronic lymphocytic leukemia (CLL). Such translocation typically results in a MYC-IGH@ fusion subsequently deregulating and overexpressing MYC on der 14q32.

A Chronic Myelogenous Leukemia (CML) Case with a Cryptic Insertion of the ABL1 Gene of Chromosome 9 into 22 Resulting in a Fusion Signal on the Derivative 22: 46,XY.ish ins(22;9)(q11.2;q34q34)BCR+,ABL1.

Chronic myelogenous leukemia (CML) is characterized by the specific cytogenetic translocation t(9;22)(q34;q11.2), also called the Philadelphia (Ph) chromosome. We present a case of a cryptic BCR/ABL1 fusion, which was not originally detected by standard karyotyping.

"T-cell prolymphocytic leukemia (T-PLL), a heterogeneous disease exemplified by two cases and the important role of cytogenetics: a multidisciplinary approach".

T-cell prolymphocytic leukemia (T-PLL) is a rare form of leukemia composed of mature T-cells that usually presents in older people with a median age of 65. Most cases of T-PLL will harbor chromosomal abnormalities involving 14q11.2 (TCR alpha/delta), 14q32 (TCL1) or Xq28 (MTCP-1), abnormalities of chromosome 8, 12p and deletions of the long arm of chromosomes 5, 6, 11 and 13.

HOT models in flux: mitochondrial glucose oxidation fuels glioblastoma growth.

Cancer cells in culture obtain ATP and biosynthetic precursors primarily by aerobic glycolysis, not by mitochondrial glucose oxidation. In this issue of Cell Metabolism, Marin-Valencia et al. (2012) demonstrate that glioblastoma, an aggressive and, in culture, highly glycolytic cancer, primarily uses glucose oxidation to meet energetic and biosynthetic demands in vivo.

Infant outcomes after maternal antiretroviral exposure in resource-limited settings.

Background And Objective: The impact of maternal antiretrovirals (ARVs) during pregnancy, labor, and postpartum on infant outcomes is unclear.

Methods: Infants born to HIV-infected mothers in ARV studies were followed for 18 months.

Results: Between June 2006 and December 2008, 236 infants enrolled from Africa (n = 36), India (n = 47), Thailand (n = 152), and Brazil (n = 1).

SMRT compounds correct nonsense mutations in primary immunodeficiency and other genetic models.

Within less than 10 years after the realization of the double helix of DNA, the ability of aminoglycosides to influence the misreading or readthrough of premature termination codons was discovered. It took another three decades to clone and sequence disease genes and appreciate the similarity of mutation spectra for most inborn errors. Nonsense mutations once again have become the target of readthrough compounds.

Thoracic Surgery Workforce: report of STS/AATS Thoracic Surgery Practice and Access Task Force--Snapshot 2010.

Background: The Society of Thoracic Surgeons (STS) and the American Association for Thoracic Surgery (AATS) have intermittently surveyed their combined membership. These manpower surveys have provided snapshots of thoracic surgery, documenting practice changes over time. At this critical time in US health care reform the physician workforce is of critical importance.

Thoracic surgery workforce: report of STS/AATS Thoracic Surgery Practice and Access Task Force--snapshot 2010.

Background: The Society of Thoracic Surgeons (STS) and the American Association for Thoracic Surgery (AATS) have intermittently surveyed their combined membership. These manpower surveys have provided snapshots of thoracic surgery, documenting practice changes over time. At this critical time in US health care reform the physician workforce is of critical importance.

State of the Art Review: Emerging Therapies: The Use of Insulin Sensitizers in the Treatment of Adolescents with Polycystic Ovary Syndrome (PCOS).

PCOS, a heterogeneous disorder characterized by cystic ovarian morphology, androgen excess, and/or irregular periods, emerges during or shortly after puberty. Peri- and post-pubertal obesity, insulin resistance and consequent hyperinsulinemia are highly prevalent co-morbidities of PCOS and promote an ongoing state of excess androgen. Given the relationship of insulin to androgen excess, reduction of insulin secretion and/or improvement of its action at target tissues offer the possibility of improving the physical stigmata of androgen excess by correction of the reproductive dysfunction and preventing metabolic derangements from becoming entrenched.

Shoulder arthrodesis for treatment of flail shoulder in children with polio.

Background: Poliomyelitis in children can cause paralysis of shoulder girdle muscles leading to a flail shoulder. Shoulder arthrodesis is indicated as a possible treatment for these children in order to stabilize the shoulder. This retrospective study reviewed all shoulder arthrodesis surgeries owing to complications of polio performed at a major medical institution between 1981 and 1996 to assess position of fusion, radiographic evidence of fusion, complications, and patient satisfaction.

Determining outcomes, adverse events, and predictors of success after sacral neuromodulation for lower urinary disorders in women.

Introduction And Hypothesis: The objective of this study was to determine the predictors of successful treatment of lower urinary tract disorders with sacral nerve stimulation (SNS) and the rate of adverse events and reoperations.

Methods: A retrospective case series of patients who underwent SNS at a single institution was analyzed.

Results: Seventy-six patients underwent stage I trial of SNS.

New strategies in the molecular targeting of glioblastoma: how do you hit a moving target?

Cancer is a molecularly complex, genomically unstable disease. Selection for drug-resistant mutations, activation of feedback loops, and upregulation of cross-talk pathways provide escape routes by which cancer cells maintain signal flux through critical downstream effectors to promote therapeutic resistance. Attempts to target signal transduction pathways in cancer may therefore require investigators to aim at a moving target.

Extended antenatal antiretroviral use correlates with improved infant outcomes throughout the first year of life.

Objectives: To evaluate the effect of extended antenatal triple antiretroviral therapy (ART) on infant outcomes.

Design: Retrospective cohort study using pooled data from health clinics in Malawi and Mozambique from July 2005 to December 2009.

Methods: Computerized records of 3273 HIV-infected pregnant women accessing Drug Resource Enhancement Against AIDS and Malnutrition centers were reviewed.