Paclitaxel-PHBV nanoparticles and their toxicity to endometrial and primary ovarian cancer cells.

This report is an integrated study to include the molecular simulation, physicochemical characterization and biological analysis of a paclitaxel-loaded PHBV nanoparticle that demonstrates uptake, release and cytotoxicity in cancer cell lines. Taking this nanoparticle one step closer to its use in a clinical setting, we demonstrate that it causes significant cell death in primary cultures of stage IIIc serous ovarian cancer cells isolated from six patients. Molecular simulations revealed a high affinity of paclitaxel for the water-polymer interface, thus the drug is delivered only when the polymer near it is degraded.

Calculating Position-Dependent Diffusivity in Biased Molecular Dynamics Simulations.

Calculating transition rates and other kinetic quantities from molecular simulations requires knowledge not only of the free energy along the relevant coordinate but also the diffusivity as a function of that coordinate. A variety of methods are currently used to map the free-energy landscape in molecular simulations; however, simultaneous calculation of position-dependent diffusivity is complicated by biasing forces applied with many of these methods. Here, we describe a method to calculate position-dependent diffusivities in simulations including known time-dependent biasing forces, which relies on a previously proposed Bayesian inference scheme.

Psychosocial treatment efficacy for disruptive behavior problems in very young children: a meta-analytic examination.

Objective: Service use trends showing increased off-label prescribing in very young children and reduced psychotherapy use raise concerns about quality of care for early disruptive behavior problems. Meta-analysis can empirically clarify best practices and guide clinical decision making by providing a quantitative synthesis of a body of literature, identifying the magnitude of overall effects across studies, and determining systematic factors associated with effect variations.

Method: We used random-effects meta-analytic procedures to empirically evaluate the overall effect of psychosocial treatments on early disruptive behavior problems, as well as potential moderators of treatment response.

Evidence-based psychological treatments: an update and a way forward.

Enormous progress in the field of clinical science has been made over the past 50 years, with advances in our understanding of psychopathology and more sophisticated research methodology leading to the development of more efficacious psychological treatments for a variety of behavioral disorders. Despite these advances, the public health impact of well-established psychological treatments is less than it should be. After an overview of the current status of the field, we identify barriers that must be overcome to maximize the public health impact and propose that to breach these barriers we must (a) augment the efficacy of treatments, (b) broaden the impact of treatments across diagnoses to include temperamental variables, (c) attend more closely to mechanisms of action of treatments, and (d) learn the best methods for disseminating and implementing psychological interventions.

Toward detection of DNA-bound proteins using solid-state nanopores: insights from computer simulations.

Through all-atom molecular dynamics simulations, we explore the use of nanopores in thin synthetic membranes for detection and identification of DNA binding proteins. Reproducing the setup of a typical experiment, we simulate electric field driven transport of DNA-bound proteins through nanopores smaller in diameter than the proteins. As model systems, we use restriction enzymes EcoRI and BamHI specifically and nonspecifically bound to a fragment of dsDNA, and streptavidin and NeutrAvidin proteins bound to dsDNA and ssDNA via a biotin linker.

Seasonal pulses of Marburg virus circulation in juvenile Rousettus aegyptiacus bats coincide with periods of increased risk of human infection.

Marburg virus (family Filoviridae) causes sporadic outbreaks of severe hemorrhagic disease in sub-Saharan Africa. Bats have been implicated as likely natural reservoir hosts based most recently on an investigation of cases among miners infected in 2007 at the Kitaka mine, Uganda, which contained a large population of Marburg virus-infected Rousettus aegyptiacus fruit bats. Described here is an ecologic investigation of Python Cave, Uganda, where an American and a Dutch tourist acquired Marburg virus infection in December 2007 and July 2008.

The reciprocal relationship between alliance and symptom improvement across the treatment of childhood anxiety.

This study examined changes in the therapeutic alliance and in self-reported anxiety over the course of 16 weeks of manual-based family treatment for child anxiety disorders. Eighty-six children (51.3% female; aged 7.

Development of an inhalational Bacillus anthracis exposure therapeutic model in cynomolgus macaques.

Appropriate animal models are required to test medical countermeasures to bioterrorist threats. To that end, we characterized a nonhuman primate (NHP) inhalational anthrax therapeutic model for use in testing anthrax therapeutic medical countermeasures according to the U.S.

Generalized anxiety disorder and the proposed associated symptoms criterion change for DSM-5 in a treatment-seeking sample of anxious youth.

Background: A current proposal for the DSM-5 general anxiety disorder (GAD) definition is to remove fatigue, difficulty concentrating, irritability, and sleep disturbance from the list of associated symptoms, and to require the presence of one of two retained symptoms (restlessness or muscle tension) for diagnosis. Relevant evaluations in youth to support such a change are sparse.

Methods: The present study evaluated patterns and correlates of the DSM-IV GAD associated symptoms in a large outpatient sample of anxious youth (N = 650) to empirically consider how the proposed diagnostic change might impact the prevalence and sample composition of GAD in children.

Achieving consistent multiple daily low-dose Bacillus anthracis spore inhalation exposures in the rabbit model.

Repeated low-level exposures to biological agents could occur before or after the remediation of an environmental release. This is especially true for persistent agents such as B. anthracis spores, the causative agent of anthrax.

Characterization of a therapeutic model of inhalational anthrax using an increase in body temperature in New Zealand white rabbits as a trigger for treatment.

The development of an appropriate animal therapeutic model is essential to assess the potential efficacy of therapeutics for use in the event of a Bacillus anthracis exposure. We conducted a natural history study that showed New Zealand White rabbits exhibited a significant increase in body temperature (SIBT), changes in hematologic parameters, and increases in C-reactive protein and succumbed to disease with an average time to death of approximately 73 h following aerosol challenge with B. anthracis Ames spores.

Specifying child anxiety disorders not otherwise specified in the DSM-IV.

Background: Anxiety disorder not otherwise specified (ADNOS) is one of the more common and impairing DSM-IV diagnoses assigned in child practice settings, but it is not clear what percentage of these assignments simply reflect poor diagnostic practices.

Methods: The present study evaluated patterns and correlates of child ADNOS in a large outpatient treatment seeking sample of anxious youth (N = 650), utilizing structured diagnostic interviewing procedures.

Results: Roughly, 15% of youth met diagnostic criteria for ADNOS.

Adapting parent-child interaction therapy to treat anxiety disorders in young children.

Anxiety disorders are prevalent in children 7 years and younger; however, these children generally do not possess developmental skills required in cognitive behavior treatment. Recent efforts have adapted parent-child interaction therapy (PCIT), originally developed for disruptive and noncompliant behavior, for young children with anxiety. This article reviews the principles underlying PCIT and the rationale for adapting it to target anxiety symptoms.

Assessing graphene nanopores for sequencing DNA.

Using all-atom molecular dynamics and atomic-resolution Brownian dynamics, we simulate the translocation of single-stranded DNA through graphene nanopores and characterize the ionic current blockades produced by DNA nucleotides. We find that transport of single DNA strands through graphene nanopores may occur in single nucleotide steps. For certain pore geometries, hydrophobic interactions with the graphene membrane lead to a dramatic reduction in the conformational fluctuations of the nucleotides in the nanopores.

DNA base-calling from a nanopore using a Viterbi algorithm.

Nanopore-based DNA sequencing is the most promising third-generation sequencing method. It has superior read length, speed, and sample requirements compared with state-of-the-art second-generation methods. However, base-calling still presents substantial difficulty because the resolution of the technique is limited compared with the measured signal/noise ratio.

Microscopic Perspective on the Adsorption Isotherm of a Heterogeneous Surface.

Adsorption of dissolved molecules onto solid surfaces can be extremely sensitive to the atomic-scale properties of the solute and surface, causing difficulties for the design of fluidic systems in industrial, medical and technological applications. In this communication, we show that the Langmuir isotherm for adsorption of a small molecule to a realistic, heterogeneous surface can be predicted from atomic structures of the molecule and surface through molecular dynamics (MD) simulations. We highlight the method by studying the adsorption of dimethyl-methylphosphonate (DMMP) to amorphous silica substrates and show that subtle differences in the atomic-scale surface properties can have drastic effects on the Langmuir isotherm.

Predicting the DNA sequence dependence of nanopore ion current using atomic-resolution Brownian dynamics.

It has become possible to distinguish DNA molecules of different nucleotide sequences by measuring ion current passing through a narrow pore containing DNA. To assist experimentalists in interpreting the results of such measurements and to improve the DNA sequence detection method, we have developed a computational approach that has both the atomic-scale accuracy and the computational efficiency required to predict DNA sequence-specific differences in the nanopore ion current. In our Brownian dynamics method, the interaction between the ions and DNA is described by three-dimensional potential of mean force maps determined to a 0.

Optimization of the molecular dynamics method for simulations of DNA and ion transport through biological nanopores.

Molecular dynamics (MD) simulations have become a standard method for the rational design and interpretation of experimental studies of DNA translocation through nanopores. The MD method, however, offers a multitude of algorithms, parameters, and other protocol choices that can affect the accuracy of the resulting data as well as computational efficiency. In this chapter, we examine the most popular choices offered by the MD method, seeking an optimal set of parameters that enable the most computationally efficient and accurate simulations of DNA and ion transport through biological nanopores.

Characterization of Nipah virus from outbreaks in Bangladesh, 2008-2010.

Nipah virus (NiV) is a highly pathogenic paramyxovirus that causes fatal encephalitis in humans. The initial outbreak of NiV infection occurred in Malaysia and Singapore in 1998-1999; relatively small, sporadic outbreaks among humans have occurred in Bangladesh since 2001. We characterized the complete genomic sequences of identical NiV isolates from 2 patients in 2008 and partial genomic sequences of throat swab samples from 3 patients in 2010, all from Bangladesh.

Developmental changes and individual differences in young children's moral judgments.

Developmental trajectories and individual differences in 70 American middle-income 2½- to 4-year olds' moral judgments were examined 3 times across 1 year using latent growth modeling. At Wave 1, children distinguished hypothetical moral from conventional transgressions on all criteria, but only older preschoolers did so when rating deserved punishment. Children's understanding of moral transgressions as wrong independent of authority grew over time.

Ancient ancestry of KFDV and AHFV revealed by complete genome analyses of viruses isolated from ticks and mammalian hosts.

Background: Alkhurma hemorrhagic fever virus (AHFV) and Kyasanur forest disease virus (KFDV) cause significant human disease and mortality in Saudi Arabia and India, respectively. Despite their distinct geographic ranges, AHFV and KFDV share a remarkably high sequence identity. Given its emergence decades after KFDV, AHFV has since been considered a variant of KFDV and thought to have arisen from an introduction of KFDV to Saudi Arabia from India.

Atoms-to-microns model for small solute transport through sticky nanochannels.

Modeling the transport of solutes through fluidic systems that have adsorbing surfaces is challenging due to the range of length and time scales involved. The components of such systems typically have dimensions from hundreds of nanometres to microns, whereas adsorption of solutes is sensitive to the atomic-scale structure of the solutes and surfaces. Here, we describe an atomic-resolution Brownian dynamics method for modeling the transport of solutes through sticky nanofluidic channels.

Date palm sap linked to Nipah virus outbreak in Bangladesh, 2008.

Introduction: We investigated a cluster of patients with encephalitis in the Manikgonj and Rajbari Districts of Bangladesh in February 2008 to determine the etiology and risk factors for disease.

Methods: We classified persons as confirmed Nipah cases by the presence of immunoglobulin M antibodies against Nipah virus (NiV), or by the presence of NiV RNA or by isolation of NiV from cerebrospinal fluid or throat swabs who had onset of symptoms between February 6 and March 10, 2008. We classified persons as probable cases if they reported fever with convulsions or altered mental status, who resided in the outbreak areas during that period, and who died before serum samples were collected.

A pilot feasibility evaluation of the CALM Program for anxiety disorders in early childhood.

As many as 9% of preschoolers suffer from an anxiety disorder, and earlier onset of disorder is associated with more intractable forms of psychopathology in later life. At present there is a relative dearth of empirical work examining the development of evidence-based treatments for anxiety disorders presenting in early childhood. Building on previous work supporting extensions of PCIT for separation anxiety disorder, the present study examines the preliminary feasibility and efficacy of an anxiety-based modification of PCIT (The CALM Program; Coaching Approach behavior and Leading by Modeling) for the treatment of youth between the ages of three and eight presenting with separation anxiety disorder, social anxiety disorder, generalized anxiety disorder, and/or specific phobias (N=9; M(age)=5.

National trends in the antipsychotic treatment of psychiatric outpatients with anxiety disorders.

Objective: The purpose of the present study was to examine patterns and recent trends in the antipsychotic medication treatment of anxiety disorders among visits to office-based psychiatrists in the United States.

Method: Annual data from the 1996-2007 National Ambulatory Medical Care Survey were analyzed to examine the patterns and trends in antipsychotic medication treatment within a nationally representative sample of 4,166 visits to office-based psychiatrists in which an anxiety disorder was diagnosed.

Results: Across the 12-year period, antipsychotic prescriptions in visits for anxiety disorders increased from 10.