Clinician Perspectives on Treating Adolescents with Co-occurring Post-Traumatic Stress Disorder, Substance Use, and Other Problems.

Clinicians (n=138) who treat adolescents with co-occurring posttraumatic stress and substance use disorders (PTSD+SUD) were surveyed about their attitudes and practice behaviors. Most providers were trained in PTSD treatment; fewer were trained in SUD or PTSD+SUD treatments. PTSD+SUD treatment was rated more difficult than treatment of other diagnoses.

Bacterial Replication Rate Modulation in Combination with Antimicrobial Therapy: Turning the Microbe against Itself.

A major clinical challenge for treating infectious diseases is the duration of antimicrobial therapy required to eradicate the pathogen. We hypothesized that modulation of the bacterial replication rate in the context of an antimicrobial exposure is coupled with the rate and extent of bactericidal effects. Herein we describe results from in vitro infection model (one compartment, 24-h model; hollow fiber, 10-day model) studies designed to probe the relationship between the bacterial replication rate and the rate and extent of bactericidal effects in the context of an effective antibiotic exposure.

Hepatitis C virus NS3/4a protease inhibitors.

Hepatitis C virus (HCV) infection is a major health issue around the world and HCV NS3/4a protease inhibitors have been the focus of intensive research for the past 20 years. From the first identification of substrate-derived peptide inhibitors to the complex, macrocyclic compounds, including paritaprevir and grazoprevir, that are currently available, the field has used structure-based design to confront the issues of potency, resistance and pharmacokinetics. Numerous breakthrough structures from a multitude of companies have led to compounds that are now key components of combination therapies with cure rates of >90%.

Contribution of laboratories in the WHO Eastern Mediterranean Region to the selection of candidate seasonal influenza vaccine, 2010-2015.

The World Health Organization (WHO) formulates recommendations for viruses to be included in vaccines for the influenza seasons in the northern and southern hemispheres on the basis of analyses by its collaborating centres (CCs). This report describes the contribution of influenza laboratories and national influenza centres in countries in the WHO Region for the Eastern Mediterranean to the selection process of seasonal and pre-pandemic influenza virus subtypes. Data submitted by 22 countries to FluNet and FluID between September 2010 and June 2015 were analysed.

Medical Spending of the US Elderly.

We use data from the Medicare Current Beneficiary Survey (MCBS) to document the medical spending of Americans aged 65 and older. We find that medical expenses more than double between ages 70 and 90 and that they are very concentrated: the top 10 per cent of all spenders are responsible for 52 per cent of medical spending in a given year. In addition, those currently experiencing either very low or very high medical expenses are likely to find themselves in the same position in the future.

Selection of antigenically advanced variants of seasonal influenza viruses.

Influenza viruses mutate frequently, necessitating constant updates of vaccine viruses. To establish experimental approaches that may complement the current vaccine strain selection process, we selected antigenic variants from human H1N1 and H3N2 influenza virus libraries possessing random mutations in the globular head of the haemagglutinin protein (which includes the antigenic sites) by incubating them with human and/or ferret convalescent sera to human H1N1 and H3N2 viruses. We also selected antigenic escape variants from human viruses treated with convalescent sera and from mice that had been previously immunized against human influenza viruses.

Osteochondral Allograft Transplantation in Patients With Osteochondritis Dissecans of the Knee.

Background: Osteochondritis dissecans (OCD) of the knee can be difficult to treat. Cartilage restoration techniques are often indicated when the lesion or fragment cannot be salvaged and the patient remains symptomatic. Fresh osteochondral allograft (OCA) transplantation can restore both bone and cartilage defects characteristic of OCD.

Role of the B Allele of Influenza A Virus Segment 8 in Setting Mammalian Host Range and Pathogenicity.

Unlabelled: Two alleles of segment 8 (NS) circulate in nonchiropteran influenza A viruses. The A allele is found in avian and mammalian viruses, but the B allele is viewed as being almost exclusively found in avian viruses. This might reflect the fact that one or both of its encoded proteins (NS1 and NEP) are maladapted for replication in mammalian hosts.

Discovery of MK-8718, an HIV Protease Inhibitor Containing a Novel Morpholine Aspartate Binding Group.

A novel HIV protease inhibitor was designed using a morpholine core as the aspartate binding group. Analysis of the crystal structure of the initial lead bound to HIV protease enabled optimization of enzyme potency and antiviral activity. This afforded a series of potent orally bioavailable inhibitors of which MK-8718 was identified as a compound with a favorable overall profile.

Structures and Rotational Barriers of a Diiodobinorsnoutane: Energetic Preference for Gauche Conformation.

The diiodobinorsnoutane, bi(5-iodopentacyclo[4.3.0.

A Frameshift in CSF2RB Predominant Among Ashkenazi Jews Increases Risk for Crohn's Disease and Reduces Monocyte Signaling via GM-CSF.

Background & Aims: Crohn's disease (CD) has the highest prevalence in Ashkenazi Jewish populations. We sought to identify rare, CD-associated frameshift variants of high functional and statistical effects.

Methods: We performed exome sequencing and array-based genotype analyses of 1477 Ashkenazi Jewish individuals with CD and 2614 Ashkenazi Jewish individuals without CD (controls).

Host genetics determine susceptibility to avian influenza infection and transmission dynamics.

Host-genetic control of influenza virus infection has been the object of little attention. In this study we determined that two inbred lines of chicken differing in their genetic background , Lines 0 and C-B12, were respectively relatively resistant and susceptible to infection with the low pathogenicity influenza virus A/Turkey/England/647/77 as defined by substantial differences in viral shedding trajectories. Resistant birds, although infected, were unable to transmit virus to contact birds, as ultimately only the presence of a sustained cloacal shedding (and not oropharyngeal shedding) was critical for transmission.

GWAS analysis implicates NF-κB-mediated induction of inflammatory T cells in multiple sclerosis.

To identify genes and biologically relevant pathways associated with risk to develop multiple sclerosis (MS), the Genome-Wide Association Studies noise reduction method (GWAS-NR) was applied to MS genotyping data. Regions of association were defined based on the significance of linkage disequilibrium blocks. Candidate genes were cross-referenced based on a review of current literature, with attention to molecular function and directly interacting proteins.

Relationship between Fosfomycin Exposure and Amplification of Escherichia coli Subpopulations with Reduced Susceptibility in a Hollow-Fiber Infection Model.

Understanding the relationship between antibiotic exposure and amplification of bacterial subpopulations with reduced drug susceptibility over time is important for evaluating the adequacy of dosing regimens. We utilized a hollow-fiber infection model to identify the fosfomycin intravenous dosing regimens that prevented the amplification of Escherichia coli bacterial subpopulations with reduced fosfomycin susceptibility. The challenge isolate was E.

Antigenic characterization of influenza viruses produced using synthetic DNA and novel backbones.

The global system for manufacturing seasonal influenza vaccines has been developed to respond to the natural evolution of influenza viruses, but the problem of antigenic mismatch continues to be a challenge in certain years. In some years, mismatches arise naturally due to the antigenic drift of circulating viruses after vaccine strain selection has already been made. In other years, antigenic differences between the vaccine virus and circulating viruses are introduced as part of the current system, which relies on the use of egg-adapted isolates as a starting material for candidate vaccine viruses (CVVs).

Cognitive control and episodic memory in adolescents with autism spectrum disorders.

Introduction: To further investigate manifestations of episodic memory impairments in adolescents, we examined the role of encoding on recognition of stimuli in conditions designed to emphasize their item-specific versus relational characteristics in a group of 12-18 year olds with autism spectrum disorders (ASD). We also examined how strategic learning and memory processes, verbal abilities, attention, and age were associated with recognition in this group.

Materials And Method: Twenty two high functioning adolescents with ASD (mean age=15 years; SD=1.

Parameters affecting the analytical profile of fatty acids in the macroalgal genus Ulva.

The fatty acids (FA) of Ulva have potential to contribute to nutrition. However the large variability of FA profiles of Ulva species; thus the quality and quantity of FA in relation to nutrition is poorly defined. Herein we investigate the FA profile of 74 cultured Ulva samples crossing five culture regimes, six extraction regimes and four post-harvesting processes.

Cadmium Accumulation in Periphyton from an Abandoned Mining District in the Buffalo National River, Arkansas.

The Rush Mining District along the Buffalo River in Arkansas has a significant history of zinc and lead mining operations. The tails and spoils of these operations deposit heavy amounts of raw ore into streams. One element commonly found in the earth's crust that becomes a minor constituent of the deposition is cadmium.

Potent, selective and orally bioavailable leucine-rich repeat kinase 2 (LRRK2) inhibitors.

Familial Parkinson's disease cases have recently been associated with the leucine rich repeat kinase 2 (LRRK2) gene. It has been hypothesized that inhibition of the LRRK2 protein may have the potential to alter disease pathogenesis. A dihydrobenzothiophene series of potent, selective, orally bioavailable LRRK2 inhibitors were identified from a high-throughput screen of the internal Merck sample collection.

Identification of Low- and High-Impact Hemagglutinin Amino Acid Substitutions That Drive Antigenic Drift of Influenza A(H1N1) Viruses.

Determining phenotype from genetic data is a fundamental challenge. Identification of emerging antigenic variants among circulating influenza viruses is critical to the vaccine virus selection process, with vaccine effectiveness maximized when constituents are antigenically similar to circulating viruses. Hemagglutination inhibition (HI) assay data are commonly used to assess influenza antigenicity.

Dental opioid prescribing and multiple opioid prescriptions among dental patients: Administrative data from the South Carolina prescription drug monitoring program.

Background: Despite increased attention to dentists' roles in curbing opioid misuse, abuse, and diversion, information regarding prescribing practices and the frequency of multiple concurrent opioid prescriptions among dental patients is limited.

Methods: The authors reviewed South Carolina prescription drug monitoring program data representing dispensed medication for patients prescribed at least 1 opioid by a dentist during the most recently available 2-year time frame (2012-2013). The authors used descriptive analyses to examine the types and frequency of dental opioid prescriptions and the frequency of existing multiple concurrent opioid prescriptions among dental patients.

Colorectal Tumors From Different Racial and Ethnic Minorities Have Similar Rates of Mismatch Repair Deficiency.

Background & Aims: Microsatellite instability (MSI) in colorectal cancer cells results from deficient mismatch repair (MMR) protein function, either acquired or from germline alterations such as in patients with Lynch syndrome. Universal screening initiatives for Lynch syndrome have been encouraged. However, little is known about the true prevalence of MMR deficiency and MSI in colorectal tumors among individuals from different racial and ethnic subgroups or their clinical effects in these populations.

Power estimation for non-standardized multisite studies.

A concern for researchers planning multisite studies is that scanner and T1-weighted sequence-related biases on regional volumes could overshadow true effects, especially for studies with a heterogeneous set of scanners and sequences. Current approaches attempt to harmonize data by standardizing hardware, pulse sequences, and protocols, or by calibrating across sites using phantom-based corrections to ensure the same raw image intensities. We propose to avoid harmonization and phantom-based correction entirely.

Preclinical pharmacology and pharmacokinetics of CERC-301, a GluN2B-selective N-methyl-D-aspartate receptor antagonist.

The preclinical pharmacodynamic and pharmacokinetic properties of 4-methylbenzyl (3S, 4R)-3-fluoro-4-[(Pyrimidin-2-ylamino) methyl] piperidine-1-carboxylate (CERC-301), an orally bioavailable selective N-methyl-D-aspartate (NMDA) receptor subunit 2B (GluN2B) antagonist, were characterized to develop a translational approach based on receptor occupancy (RO) to guide CERC-301 dose selection in clinical trials of major depressive disorder. CERC-301 demonstrated high-binding affinity (K i, 8.1 nmol L(-1)) specific to GluN2B with an IC 50 of 3.