Target Attainment and Population Pharmacokinetics of Cefazolin in Patients with Invasive Infections: A Prospective Cohort Study.

This study aimed to determine cefazolin target attainment in patients with invasive () infections and to develop a population pharmacokinetic (PK) model. Adult patients with invasive infections treated with cefazolin bolus infusions were included. Unbound and total trough and mid-dose cefazolin concentrations were measured, and strain-specific MICs were determined.

Li NMR Spectroscopy: A Tool for Determining Dimerization Constants and Averaged Dimerization Constants of the Monomer/Dimer Equilibrium of Hierarchical Helicates.

Li nuclear magnetic resonance (NMR) spectroscopy is an ideal tool to study hierarchically assembled helicates of the form Li[LiLTi]. Internally bound and external lithium ions can be well distinguished by solution- or solid-state NMR spectroscopy and dimerization constants of the monomer/dimer equilibrium can be easily determined in solution. Averaged dimerization constants can be estimated in case of statistical mixtures of helicates formed from mixtures of ligands.

A Copper-Catalyzed Interrupted Domino Reaction for the Synthesis of Fused Triazolyl Benzothiadiazine-1-oxides.

Copper(I)-catalyzed domino reactions of 2-azido sulfoximines with 1-iodoalkynes yield fused triazolyl-containing benzothiadiazine-1-oxides. The protocol features the synthesis of two fused heterocyclic rings in one step with good to excellent yields and a broad functional group tolerance. Detailed mechanistic investigations indicate that a copper π-complex initiates a cycloaddition and oxidative C-N coupling reaction sequence.

Cefepime-Induced Neurotoxicity in the Setting of Acute Kidney Injury: A Case Series and Discussion of Preventive Measures.

Neurotoxicity is a well-described adverse effect of cefepime. Clinical presentation includes mild neurological deficits, aphasia, impairment of consciousness, and even nonconvulsive status epilepticus. Impaired kidney function is considered the most important risk factor for cefepime-induced neurotoxicity (CIN) and frequently occurs during the course of critical diseases with concomitant acute kidney injury (AKI).

Opportunities and Challenges for Adolescent Health Under the Affordable Care Act.

The purpose of this commentary is to highlight some of the key policy changes under the Patient Protection and Affordable Care Act (ACA) that have the potential to improve health care services for adolescents as well as to draw attention to challenges that have yet to be addressed. This commentary stems from our prior policy research, which examined the extent to which the health care needs of adolescents were being considered in the early implementation phases of the ACA. This study was informed by a literature review and interviews with health care administrators, health policy researchers, and adolescent medicine specialists.

Options for assuring access to confidential care for adolescents and young adults in an explanation of benefits environment.

The Affordable Care Act (ACA) has expanded the enrollment of young people in insurance plans and aims to increase access to preventive health services. For adolescents and young adults to fully utilize these services, access to confidential care is critical, especially for sensitive services, like sexual and reproductive health care. With this expansion, the ACA inadvertently exposes more individuals (especially those with private insurance) to confidentiality breaches through routine communications in the form of Explanation of Benefits (EOBs) sent to policyholders (typically the parent).

Dynorphin up-regulation in the dentate granule cell mossy fiber pathway following chronic inhibition of GluN2B-containing NMDAR is associated with increased CREB (Ser 133) phosphorylation, but is independent of BDNF/TrkB signaling pathways.

Emerging evidence suggests that neuronal responses to N-methyl-d-aspartate (NMDAR) activation/inactivation are influenced by subunit composition. For example, activation of synaptic NMDAR (comprised of GluN2A>GluN2B) phosphorylates cAMP-response-element-binding protein (CREB) at Ser 133, induces BDNF expression and promotes neuronal survival. Activation of extrasynaptic NMDAR (comprised of GluN2B>GluN2) dephosphorylates CREB (Ser 133), reduces BDNF expression and triggers neuronal death.

Synaptic plasticity in glutamatergic and GABAergic neurotransmission following chronic memantine treatment in an in vitro model of limbic epileptogenesis.

Chronic N-methyl-D-aspartate receptor (NMDAR) blockade with high affinity competitive and uncompetitive antagonists can lead to seizure exacerbation, presumably due to an imbalance in glutamatergic and GABAergic transmission. Acute administration of the moderate affinity NMDAR antagonist memantine in vivo has been associated with pro- and anticonvulsive properties. Chronic treatment with memantine can exacerbate seizures.

It takes a village: community-based organizations and the availability and utilization of HIV/AIDS-related services in Nigeria.

Community-based organizations (CBOs) have emerged as a vital part of the response to HIV/AIDs in Nigeria. The evaluation, on which this article is based, conducted in 28 communities in 6 states and the Federal capital Territory in Nigeria, assessed the effects of the CBO engagement on a set of outcomes related to HIV/AIDS knowledge, attitudes, beliefs, and practices, stigma, service availably and utilization and social capital. It consisted of three components: a household survey conducted in all 28 communities, qualitative data collected from CBO staff and key informants (KIs), and a funding allocation study (qualitative interviews and the funding allocation study were conducted in a subset of 14 communities).

GABAergic transmission facilitates ictogenesis and synchrony between CA3, hilus, and dentate gyrus in slices from epileptic rats.

The impact of regional hippocampal interactions and GABAergic transmission on ictogenesis remain unclear. Cortico-hippocampal slices from pilocarpine-treated epileptic rats were compared with controls to investigate associations between seizurelike events (SLE), GABAergic transmission, and neuronal synchrony within and between cortico-hippocampal regions. Multielectrode array recordings revealed more prevalent hippocampal SLE in epileptic tissue when excitatory transmission was enhanced and GABAergic transmission was intact [removal of Mg(2+) (0Mg)] than when GABAergic transmission was blocked [removal of Mg(2+) + bicuculline methiodide (0Mg+BMI)].

Synaptic and extrasynaptic plasticity in glutamatergic circuits involving dentate granule cells following chronic N-methyl-D-aspartate receptor inhibition.

Chronic global N-methyl-d-aspartate receptor (NMDAR) blockade leads to changes in glutamatergic transmission. The impact of more subunit-selective NMDAR inhibition on glutamatergic circuits remains incomplete. To this end, organotypic hippocampal slice cultures were treated for 17-21 days with the high-affinity competitive antagonist d-aminophosphonovaleric acid (d-APV), the allosteric GluN2B-selective antagonist Ro25-6981, or the newer competitive GluN2A-preferring antagonist NVP-AAM077.

Alexithymia and script-driven emotional imagery in healthy female subjects: no support for deficiencies in imagination.

Alexithymia is associated with a limited access to inner emotional processes. Furthermore, alexithymia is assumed to be characterized by a limited ability to use imagination. To evaluate the frequently proposed thesis of a reduced imagination ability in alexithymic persons, 25 high and 24 low alexithymic women self-rated their imagination ability.

Inverse relationship between seizure expression and extrasynaptic NMDAR function following chronic NMDAR inhibition.

We showed previously that electrographic seizures involving dentate granule cells in organotypic hippocampal slice cultures were dramatically reduced following chronic treatment with the NR2B-selective antagonist, Ro25,6981, but were increased following chronic treatment with the high-affinity competitive antagonist, D(-)-2-amino-5-phosphonopentanoic acid (D-APV). To begin to investigate the potential mechanisms underlying the differential effects of N-methyl-D-aspartate receptor (NMDAR) antagonists on seizures, electrophysiologic experiments were conducted in dentate granule cells in hippocampal slice cultures treated for the entire 17-21 day culture period with vehicle, Ro25,6981 or D-APV. Initial experiments revealed a lack of an association between miniature excitatory postsynaptic current (mEPSC) measures and seizures suggesting that shifts in mEPSC were unlikely to account for the differential effects of D-APV and Ro25,6981 on seizures.

Alexithymia as a predictor of outcome of psychodynamically oriented inpatient treatment.

This naturalistic study aimed to determine whether the initial degree of alexithymia can predict treatment outcome of psychodynamically oriented multimodal therapy. The Toronto Alexithymia Scale-26, the Global Severity Index (GSI), and the Depression subscale of the Symptom Checklist-90-Revised were administered at hospital admission and at discharge to 480 inpatients with various psychological disorders. GSI and depressive symptoms decreased significantly during treatment.

Effects of inpatient psychotherapy on the stability of alexithymia characteristics.

Background: Although alexithymia is associated with several psychiatric disorders, there has been little research into the effects of psychodynamic psychotherapies on this condition. Here, the influence of inpatient multimodal psychodynamic psychotherapy on alexithymia and symptom load was evaluated in a large sample of patients.

Methods: Alexithymia [measured with the Toronto Alexithymia Scale (TAS)-26] and psychological stress and depression [measured with the Symptom Checklist 90 Revised (SCL-90-R)] were evaluated at admission and after inpatient multimodal psychotherapy in patients with various psychosomatic and psychiatric disorders admitted to this unit between 2002 and 2005.

S-Citalopram in neuroendocrine challenge-tests: serotonergic responsivity in healthy male and female human participants.

The aim of the present study was to assess the usefulness of the selective serotonin-reuptake-inhibitor S-Citalopram as a serotonergic challenge probe in 24 healthy male and 24 healthy female participants. The participants received a single oral dose of 10 and 20mg of S-Citalopram in a placebo-controlled double blind crossover design. In female subjects phases of the menstrual cycle were controlled.

Potential roles for hyaluronan and CD44 in kainic acid-induced mossy fiber sprouting in organotypic hippocampal slice cultures.

The most well-documented synaptic rearrangement associated with temporal lobe epilepsy is mossy fiber sprouting (MFS). MFS is a pronounced expansion of granule cell mossy fiber axons into the inner dentate molecular layer. The recurrent excitatory network formed by MFS is hypothesized to play a critical role in epileptogenesis, which is the transformation of the normal brain into one that is prone to recurrent spontaneous seizures.

Plasticity of both excitatory and inhibitory synapses is associated with seizures induced by removal of chronic blockade of activity in cultured hippocampus.

One factor common to many neurological insults that can lead to acquired epilepsy is a loss of afferent neuronal input. Neuronal activity is one cellular mechanism implicated in transducing deafferentation into epileptogenesis. Therefore the effects of chronic activity blockade on seizure susceptibility and its underlying mechanisms were examined in organotypic hippocampal slice cultures treated chronically with the sodium channel blocker, tetrodotoxin (TTX), or the N-methyl-D-aspartate receptor (NMDAR) antagonist, D-2-amino-5-phosphonovaleric acid (D-APV).

Axonal sprouting of GABAergic interneurons in temporal lobe epilepsy.

Temporal lobe epilepsy is one of the most common forms of epilepsy. Numerous contributing factors and compensatory mechanisms have been associated with temporal lobe epilepsy. One feature found in both humans and animal models is sprouting of hippocampal principal cell axons, which suggests that axonal sprouting may be a general phenomenon associated with temporal lobe epilepsy.

Interactions of the N-terminal domain of ribosomal protein L11 with thiostrepton and rRNA.

Ribosomal protein L11 has two domains: the C-terminal domain (L11-C76) binds rRNA, whereas the N-terminal domain (L11-NTD) may variously interact with elongation factor G, the antibiotic thiostrepton, and rRNA. To begin to quantitate these interactions, L11 from Bacillus stearothermophilus has been overexpressed and its properties compared with those of L11-C76 alone in a fluorescence assay for protein-rRNA binding. The assay relies on 2'-amino-butyryl-pyrene-uridine incorporated in a 58-nucleotide rRNA fragment, which gives approximately 15-fold enhancement when L11 or L11-C76 is bound.

The delta opioid receptor agonist, SNC80, has complex, dose-dependent effects on pilocarpine-induced seizures in Sprague-Dawley rats.

Delta opioid receptor (DOR) selective agonists hold promise clinically as analgesics, but their effects on seizures remain controversial. In this study we examined the effects of the DOR agonist, (+)-4-[(alpha R)-alpha-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]-N,N-diethyl-benzamide (SNC80), on behavioral seizures and hippocampal histopathology in the pilocarpine model of temporal lobe epilepsy. Systemic administration of SNC80 (30 or 60 mg/kg) alone elicited brief seizures within minutes of injection in about half of all rats.

Effects of distinct classes of N-methyl-D-aspartate receptor antagonists on seizures, axonal sprouting and neuronal loss in vitro: suppression by NR2B-selective antagonists.

Chronic treatment with high-affinity, competitive N-methyl-D-aspartate receptor (NMDAR) antagonists can promote axonal sprouting, induce neuronal loss and exacerbate seizures associated with temporal lobe epilepsy. Whether moderate-affinity uncompetitive and NR2B subunit-selective NMDAR antagonists elicit similar responses remains largely unexplored. We directly compared the effects of distinct classes of NMDAR antagonists on electrographic seizures, axonal sprouting and neuronal survival using electrophysiological recordings and histology in hippocampal slice cultures treated chronically with vehicle, D-APV (high-affinity competitive), Ro 25-6981 or ifenprodil (NR2B-selective), or memantine (moderate-affinity uncompetitive).

Contributions of mossy fiber and CA1 pyramidal cell sprouting to dentate granule cell hyperexcitability in kainic acid-treated hippocampal slice cultures.

Axonal sprouting like that of the mossy fibers is commonly associated with temporal lobe epilepsy, but its significance remains uncertain. To investigate the functional consequences of sprouting of mossy fibers and alternative pathways, kainic acid (KA) was used to induce robust mossy fiber sprouting in hippocampal slice cultures. Physiological comparisons documented many similarities in granule cell responses between KA- and vehicle-treated cultures, including: seizures, epileptiform bursts, and spontaneous excitatory postsynaptic currents (sEPSCs) >600 pA.