Altered integrity of perisylvian language pathways in schizophrenia: relationship to auditory hallucinations.

Background: Functional neuroimaging supports the hypothesis that auditory verbal hallucinations (AVH) in schizophrenia result from altered functional connectivity between perisylvian language regions, although the extent to which AVH are also associated with an altered tract anatomy is less clear.

Methods: Twenty-eight patients with schizophrenia subdivided into 17 subjects with a history of AVH and 11 without a history of hallucinations and 59 age- and IQ-matched healthy controls were recruited. The number of streamlines, fractional anisotropy (FA), and mean diffusivity were measured along the length of the arcuate fasciculus and its medial and lateral components.

White matter microstructural abnormalities in the frontal lobe of adults with antisocial personality disorder.

Unlabelled: Antisocial personality disorder (ASPD) and psychopathy involve significant interpersonal and behavioural impairments. However, little is known about their underlying neurobiology and in particular, abnormalities in white matter (WM) microstructure. A preliminary diffusion tensor magnetic resonance imaging (DT-MRI) study of adult psychopaths employing tractography revealed abnormalities in the right uncinate fasciculus (UF) (Craig et al.

Higher busulfan dose intensity does not improve outcomes of patients undergoing allogeneic haematopoietic cell transplantation following fludarabine, busulfan-based reduced toxicity conditioning.

We evaluated the impact of busulfan dose intensity in patients undergoing reduced toxicity/intensity conditioning allogeneic transplantation in a multicenter retrospective study of 112 consecutive patients. Seventy-five patients were conditioned with busulfan (0.8 mg/kg/dose IV × 8 doses), fludarabine (30 mg/m(2) /day, days -7 to -3), and 6 mg/kg of ATG [reduced intensity conditioning (RIC) group], while 37 patients received a more-intense conditioning with busulfan (130 mg/m(2) /day IV, days -6 to -3), fludarabine (40 mg/m(2) /day, days -6 to -3) and 6 mg/kg of ATG [reduced toxicity conditioning (RTC) group].

Phase 2 trial of romidepsin in patients with peripheral T-cell lymphoma.

Romidepsin (depsipeptide or FK228) is a histone deacetylase inhibitor, one of a new class of agents active in T-cell lymphoma. A phase 2 trial was conducted in cutaneous (CTCL) and peripheral (PTCL) T-cell lymphoma. Major and durable responses in CTCL supported the approval of romidepsin for CTCL.

A post-marketing evaluation of posaconazole plasma concentrations in neutropenic patients with haematological malignancy receiving posaconazole prophylaxis.

This is one of the first studies to report on therapeutic drug monitoring (TDM) of posaconazole (PCZ) for antifungal prophylaxis in patients with acute myelogenous leukaemia or myelodysplastic syndrome outside of the rigours of clinical licencing trials. A number of factors have been identified or proposed as causing poor oral absorption of PCZ. Putative PCZ concentrations have been recommended for TDM (0.

Management of right ventricular failure in the era of ventricular assist device therapy.

The increasing incidence of patients with advanced heart failure, limited donor availability, and continued advancements in the field of mechanical circulatory support have made implantation of left ventricular assist device therapy (LVAD) an attractive option for patients with end-stage heart failure. Perioperative right ventricular failure (RVF) occurs frequently in patients undergoing LVAD implantation and is associated with significant morbidity and mortality. This review will discuss the pathophysiology of RVF, recent efforts to risk-stratify patients preoperatively, and current preoperative, perioperative, and postoperative management strategies.

VE-cadherin Regulates Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia Sensitivity to Apoptosis.

The mechanisms by which the bone marrow microenvironment regulates tumor cell survival are diverse. This study describes the novel observation that in addition to Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL) cell lines, primary patient cells also express Hypoxia Inducible Factor-2α (HIF-2α) and Vascular Endothelial Cadherin (VE-cadherin), which are regulated by Abl kinase. Tumor expression of the classical endothelial protein, VE-cadherin, has been associated with aggressive phenotype and poor prognosis in other models, but has not been investigated in hematopoietic malignancies.

The evolving role of statins in hematopoietic stem and progenitor cell transplantation.

Allogeneic hematopoietic stem cell transplantation is the sole curative modality for a variety of malignant and benign hematological disorders. Despite advances in supportive care and transplant conditioning regimens graft-versus-host disease (GVHD), infectious complications and end organ toxicity remain the leading causes of transplant related mortality (TRM). Development of safe and effective strategies to mitigate these significant complications associated with HSCT, are urgently needed.

Autism in adults. New biologicial findings and their translational implications to the cost of clinical services.

There is increasing evidence that children with autism spectrum disorder (ASD) have differences in brain growth trajectory. However, the neurobiological basis of ASD in adults is poorly understood. We report evidence that brain anatomy and aging in people with ASD is significantly different as compared to controls-so that in adulthood they no longer have a significantly larger overall brain volume, but they do have anatomical and functional abnormalities in frontal lobe, basal ganglia and the limbic system.

Estrogen therapy and Alzheimer's dementia.

Previous studies in postmenopausal women have reported that estrogen treatment (ET) modulates the risk for developing Alzheimer's disease (AD). It has recently been hypothesized that there may be a "critical period" around the time of menopause during which the prescription of ET may reduce the risk of developing AD in later life. This effect may be most significant in women under 49 years old.

Control of plasma uric acid in adults at risk for tumor Lysis syndrome: efficacy and safety of rasburicase alone and rasburicase followed by allopurinol compared with allopurinol alone--results of a multicenter phase III study.

Purpose: Rasburicase is effective in controlling plasma uric acid in pediatric patients with hematologic malignancies. This study in adults evaluated safety of and compared efficacy of rasburicase alone with rasburicase followed by oral allopurinol and with allopurinol alone in controlling plasma uric acid.

Patients And Methods: Adults with hematologic malignancies at risk for hyperuricemia and tumor lysis syndrome (TLS) were randomly assigned to rasburicase (0.

In vivo brain anatomy of adult males with Fragile X syndrome: an MRI study.

Fragile X Syndrome (FraX) is caused by the expansion of a single trinucleotide gene sequence (CGG) on the X chromosome, and is a leading cause of learning disability (mental retardation) worldwide. Relatively few studies, however, have examined the neuroanatomical abnormalities associated with FraX. Of those that are available many included mixed gender populations, combined FraX children and adults into one sample, and employed manual tracing techniques which measures bulk volume of particular regions.

Sexually segregated housing results in improved early larval survival in zebrafish.

Large-scale aquaculture facilities require highly optimized husbandry protocols that maximize fecundity and embryo health while minimizing cost and effort. Although zebrafish are being increasingly used for preclinical drug screens, functional genomic research and toxicological and behavioral studies, many of the basic husbandry procedures that are used for these fish have not been thoroughly tested. In this study, the authors compared the breeding success of zebrafish housed in sex-separated and those housed in mixed-gender arrangements.

VE-cadherin and PECAM-1 enhance ALL migration across brain microvascular endothelial cell monolayers.

Objective: Infiltration of the central nervous system (CNS) by leukemia is a problematic disease manifestation of acute lymphoblastic leukemia (ALL). The mechanisms by which leukocytes interact with human brain-derived microvasculature endothelial cells (HBMEC) and enter the CNS are largely derived from models of inflammation. However, our data indicate that ALL cells do not elicit an inflammatory phenotype by HBMEC.

Effects of acute tryptophan depletion on neural processing of facial expressions of emotion in humans.

Introduction: Acute tryptophan depletion (ATD) temporarily lowers brain serotonin (5-HT) synthesis, and behavioral studies have shown that this alters the processing of facial expressions of emotion.

Materials And Methods: The neural basis for these alterations is not known. Therefore, we employed ATD and event-related functional magnetic resonance imaging (fMRI) to examine neural responses during incidental processing of fearful, happy, sad, and disgusted facial expressions.

Neurotrophins regulate bone marrow stromal cell IL-6 expression through the MAPK pathway.

Background: The host's response to infection is characterized by altered levels of neurotrophins and an influx of inflammatory cells to sites of injured tissue. Progenitor cells that give rise to the differentiated cellular mediators of inflammation are derived from bone marrow progenitor cells where their development is regulated, in part, by cues from bone marrow stromal cells (BMSC). As such, alteration of BMSC function in response to elevated systemic mediators has the potential to alter their function in biologically relevant ways, including downstream alteration of cytokine production that influences hematopoietic development.

Phase II study of clofarabine monotherapy in previously untreated older adults with acute myeloid leukemia and unfavorable prognostic factors.

Purpose: This phase II study assessed clofarabine monotherapy in older adults (>or= 60 years of age) with untreated acute myeloid leukemia (AML) and at least one unfavorable baseline prognostic factor.

Patients And Methods: Clofarabine was administered intravenously for 5 days at 30 mg/m(2)/d during induction and 20 mg/m(2)/d during reinduction/consolidation (six cycles maximum). The primary end point was overall remission rate (ORR; ie, complete remission [CR] plus CR with incomplete platelet recovery [CRp]).

Microstructural organization of cerebellar tracts in schizophrenia.

Background: Dysconnectivity theories of schizophrenia would suggest that the connectivity of the cerebellum is impaired and that the impairment may be restricted to certain tracts. Attempts to examine the structural connectivity of the cerebellum using diffusion tensor imaging have yielded conflicting results. However, previous studies have employed region-of-interest approaches or have used small or unmatched samples, with a consequent risk of type II error.

Characterization and performance of nucleic acid nanoparticles combined with protamine and gold.

Macromolecular nucleic acids such as DNA vaccines, siRNA, and splice-site switching oligomers (SSO) have vast chemotherapeutic potential. Nanoparticulate biomaterials hold promise for DNA and RNA delivery when a means for binding is identified that retains structure-function and provides stabilization by the nanoparticles. In order to provide these benefits of binding, we combined DNA and RNA with protamine-demonstrating association to gold microparticles by electrophoretic, gel shot, fluorescence, and dynamic laser light spectroscopy (DLLS).

Proteomic and functional analysis of NCS-1 binding proteins reveals novel signaling pathways required for inner ear development in zebrafish.

Background: The semicircular canals, a subdivision of the vestibular system of the vertebrate inner ear, function as sensors of angular acceleration. Little is currently known, however, regarding the underlying molecular mechanisms that govern the development of this intricate structure. Zebrafish represent a particularly tractable model system for the study of inner ear development.

Cytotoxicity effects of different surfactant molecules conjugated to carbon nanotubes on human astrocytoma cells.

Phase contrast and epifluorescence microscopy were utilized to monitor morphological changes in human astrocytoma cells during a time-course exposure to single-walled carbon nanotube (SWCNT) conjugates with different surfactants and to investigate sub-cellular distribution of the nanotube conjugates, respectively. Experimental results demonstrate that cytotoxicity of the nanotube/surfactant conjugates is related to the toxicity of surfactant molecules attached on the nanotube surfaces. Both sodium dodecyl sulfate (SDS) and sodium dodecylbenzene sulfonate (SDBS) are toxic to cells.

Towards biosensors based on conducting polymer nanowires.

We report the electrochemical deposition of poly(pyrrolepropylic acid) nanowires, their covalent modification with antibodies and their conversion into potential functional sensor devices. The nanowires and the devices were characterised by optical microscopy, fluorescence microscopy, electron microscopy and electrical measurements. Fluorescence images, current-voltage (I-V) profiles and real-time sensing measurements demonstrated a rapid and highly sensitive and selective detection of human serum albumin (HSA), a substance that has been used to diagnose incipient renal disease.

Alzheimer's disease in women.

Women have a significantly higher risk of developing Alzheimer's disease (AD) than men. This has contributed to the hypothesis that the menopause may contribute to the cascade of pathological processes leading to AD. Studies into the role of oestrogen therapy (OT) on the prevention and treatment of AD have led to equivocal findings.

Reversibility of the effects of acute ovarian hormone suppression on verbal memory and prefrontal function in pre-menopausal women.

Background: Whilst acute loss of ovarian function is associated with memory deficits, the biological basis of this is poorly understood. We have previously reported that acute loss of function during Gonadotropin Hormone Releasing Hormone agonists (GnRHa) treatment is associated with impaired verbal memory and a disruption of corresponding left inferior frontal gyrus (LIFG) during the encoding stage. In the current study, we provide a critical extension to this work by determining whether this memory deficit is reversible following normalization of ovarian function.