Sleep-Dependent Consolidation of Rewarded Behavior Is Diminished in Children with Attention Deficit Hyperactivity Disorder and a Comorbid Disorder of Social Behavior.

Children suffering from attention-deficit hyperactivity disorder (ADHD) often also display impaired learning and memory. Previous research has documented aberrant reward processing in ADHD as well as impaired sleep-dependent consolidation of declarative memory. We investigated whether sleep also fosters the consolidation of behavior learned by probabilistic reward and whether ADHD patients with a comorbid disorder of social behavior show deficits in this memory domain, too.

Autologous co-culture of primary human alveolar macrophages and epithelial cells for investigating aerosol medicines. Part I: model characterisation.

The development of new formulations for pulmonary drug delivery is a challenge on its own. New in vitro models which address the lung are aimed at predicting and optimising the quality, efficacy and safety of inhaled drugs, to facilitate the more rapid translation of such products into the clinic. Reducing the complexity of the in vivo situation requires that such models reproducibly reflect essential physiological factors in vitro.

Recombinant herpes simplex virus type 1 strains with targeted mutations relevant for aciclovir susceptibility.

Here, we describe a novel reliable method to assess the significance of individual mutations within the thymidine kinase (TK) gene of herpes simplex virus type 1 (HSV-1) to nucleoside analogue resistance. Eleven defined single nucleotide polymorphisms that occur in the TK gene of clinical HSV-1 isolates and a fluorescence reporter were introduced into the HSV-1 strain 17(+) that had been cloned into a bacterial artificial chromosome. The susceptibility of these different strains to aciclovir, penciclovir, brivudin, and foscarnet was determined with a modified cytopathic effect reduction assay.

Analysis of an echovirus 18 outbreak in Thuringia, Germany: insights into the molecular epidemiology and evolution of several enterovirus species B members.

In October and November 2010, six children and one woman were presented with symptoms of aseptic meningitis in Jena, Thuringia, Germany. Enterovirus RNA was detected in the cerebrospinal fluid of all patients by RT-PCR, and preliminary molecular typing revealed echovirus 18 (E-18) as causative agent. Virus isolates were obtained from stool samples of three patients and several contact persons.

Deep metagenome and metatranscriptome analyses of microbial communities affiliated with an industrial biogas fermenter, a cow rumen, and elephant feces reveal major differences in carbohydrate hydrolysis strategies.

Background: The diverse microbial communities in agricultural biogas fermenters are assumed to be well adapted for the anaerobic transformation of plant biomass to methane. Compared to natural systems, biogas reactors are limited in their hydrolytic potential. The reasons for this are not understood.

Primary Diffuse Large B-Cell Lymphoma of the Liver in a Patient with Sjogren Syndrome.

Sjögren's syndrome (SS) has the highest incidence of malignant lymphoproliferative disorders transformation among autoimmune diseases. We present a case of extranodal high grade lymphoma of the liver in a 52-year-old patient with long history of SS. Lymphoma manifested with sharp significant pain in the right hypochondrium, weakness, and profuse night sweats.

Antigen delivery via hydrophilic PEG-b-PAGE-b-PLGA nanoparticles boosts vaccination induced T cell immunity.

Here, we evaluate the use of hydrophilic PEG-b-PAGE-b-PLGA (PPP) for the preparation of antigen loaded nanoparticles (NPs) as a platform for prophylactic vaccination. To investigate the suitability of PPP-NPs for antigen delivery, we used the double emulsion evaporation technique to prepare NPs of different sizes, antigen-loading efficiencies and -release kinetics for the model antigen Ovalbumin (OVA). Prior to applying the PPP-NPs in biological in vitro or in vivo models, all materials were tested for absence of cytotoxicity and endotoxins.

Loss of spatial organization and destruction of the pericellular matrix in early osteoarthritis in vivo and in a novel in vitro methodology.

Objectives: Current repair procedures for articular cartilage (AC) cannot restore the tissue's original form and function because neither changes in its architectural blueprint throughout life nor the respective biological understanding is fully available. We asked whether two unique elements of human cartilage architecture, the chondrocyte-surrounding pericellular matrix (PCM) and the superficial chondrocyte spatial organization (SCSO) beneath the articular surface (AS) are congenital, stable or dynamic throughout life. We hypothesized that inducing chondrocyte proliferation in vitro impairs organization and PCM and induces an advanced osteoarthritis (OA)-like structural phenotype of human cartilage.

Neural representation of emotion regulation goals.

The use of top-down cognitive control mechanisms to regulate emotional responses as circumstances change is critical for mental and physical health. Several theoretical models of emotion regulation have been postulated; it remains unclear, however, in which brain regions emotion regulation goals (e.g.

Roflumilast for asthma: Efficacy findings in mechanism of action studies.

Background: The efficacy profile of roflumilast, a phosphodiesterase-4 inhibitor used for the treatment of chronic obstructive pulmonary disease (COPD), is well known. In asthma treatment, much less is understood about the role of roflumilast, particularly its mechanism of action and potential bronchodilatory effects.

Aim: To evaluate the therapeutic efficacy and mechanism of action of roflumilast in patients with asthma using data from eight placebo-controlled, double-blind phase I-III studies.

Acute Activation of Oxidative Pentose Phosphate Pathway as First-Line Response to Oxidative Stress in Human Skin Cells.

Integrity of human skin is endangered by exposure to UV irradiation and chemical stressors, which can provoke a toxic production of reactive oxygen species (ROS) and oxidative damage. Since oxidation of proteins and metabolites occurs virtually instantaneously, immediate cellular countermeasures are pivotal to mitigate the negative implications of acute oxidative stress. We investigated the short-term metabolic response in human skin fibroblasts and keratinocytes to H2O2 and UV exposure.

Composition of Bacterial Communities Associated with Aurelia aurita Changes with Compartment, Life Stage, and Population.

The scyphozoan Aurelia aurita is recognized as a key player in marine ecosystems and a driver of ecosystem change. It is thus intensely studied to address ecological questions, although its associations with microorganisms remain so far undescribed. In the present study, the microbiota associated with A.

Applicability of the one-step DVS method for the determination of amorphous amounts for further different hydrophilic and hydrophobic drugs.

In a former publication the authors showed that low amounts of amorphous content (LOQ of 0.5%) in a hydrophobic model API (Ciclesonide) can be measured with an individually adjusted one-step dynamic organic vapor sorption (DVS). In this investigation the applicability is tested on various APIs which differ in lipophilicity (poor water solubility) and hygroscopicity (absorption of water).

Measurement of low amounts of amorphous content in hydrophobic active pharmaceutical ingredients with dynamic organic vapor sorption.

Today, a variety of devices for dry powder inhalers (DPIs) is available and many different formulations for optimized deposition in the lung are developed. However, during the production of powder inhalers, processing steps may induce changes to both, the carrier and active pharmaceutical ingredients (APIs). It is well known that standard pharmaceutical operations may lead to structural changes, crystal defects and amorphous regions.

Influence of small amorphous amounts in hydrophilic and hydrophobic APIs on storage stability of dry powder inhalation products.

The effects of different manufacturing methods to induce formation of amorphous content, changes of physico-chemical characteristics of powder blends and changes of aerodynamic properties over storage time (6months) analyzed with the Next Generation Impactor (NGI) are investigated. Earlier studies have shown that standard pharmaceutical operations lead to structural disorders which may influence drug delivery and product stability. In this investigation, fully amorphous drug samples produced by spray-drying (SD) and ball-milling (BM) as well as semi-crystalline samples (produced by blending and micronization) are studied and compared to fully crystalline starting material.

Changes in Effective Connectivity Between Dorsal and Ventral Prefrontal Regions Moderate Emotion Regulation.

Reappraisal, the cognitive reevaluation of a potentially emotionally arousing event, has been proposed to be based upon top-down appraisal systems within the prefrontal cortex (PFC). It still remains unclear, however, how different prefrontal regions interact to control and regulate emotional responses. We used fMRI and dynamic causal modeling (DCM) to characterize the functional interrelationships among dorsal and ventral PFC regions involved in reappraisal.

Biomechanical and antibacterial properties of Tobramycin loaded hydroxyapatite coated fixation pins.

The present study investigates the use of nanoporous, biomimetic hydroxyapatite (HA) coatings deposited on TiO₂ coated fixation pins as functional implant surfaces for the local release of Tobramycin in order to prevent bacterial colonization. The impact of HA-coating thickness, coating morphology and biomechanical forces during insertion into synthetic bone on the drug loading and release properties are analyzed. The coatings are shown to exhibit bactericidal effects against Staphylococcus aureus in agar medium for a duration of 6 days after loading by adsorption with Tobramycin for only 5 min at elevated temperature and pressure.

Relationship between personality traits and brain reward responses when playing on a team.

Cooperation is an integral part of human social life and we often build teams to achieve certain goals. However, very little is currently understood about emotions with regard to cooperation. Here, we investigated the impact of social context (playing alone versus playing on a team) on emotions while winning or losing a game.

SPINK9 stimulates metalloprotease/EGFR-dependent keratinocyte migration via purinergic receptor activation.

Serine protease inhibitors of the Kazal-type 9 (SPINK9) is a keratinocyte-derived cationic peptide that is found most abundantly in the upper layers of the palmar-plantar epidermis. In vitro, the peptide displays the capacity to inhibit specifically kallikrein-related peptidase 5 (KLK5). Here, we report that cells expressing SPINK9 secrete the peptide constitutively.

Soil C and N availability determine the priming effect: microbial N mining and stoichiometric decomposition theories.

The increasing input of anthropogenically derived nitrogen (N) to ecosystems raises a crucial question: how does available N modify the decomposer community and thus affects the mineralization of soil organic matter (SOM). Moreover, N input modifies the priming effect (PE), that is, the effect of fresh organics on the microbial decomposition of SOM. We studied the interactive effects of C and N on SOM mineralization (by natural (13) C labelling adding C4 -sucrose or C4 -maize straw to C3 -soil) in relation to microbial growth kinetics and to the activities of five hydrolytic enzymes.

Locally enhanced early bone formation of zoledronic acid incorporated into a bone cement plug in vivo.

Objectives: The aim of the study was to gain experience about the short-term effects of zoledronic acid (ZOL) on bone-implant contact (BIC), bone regeneration and bone area (BA).

Methods: In this in-vivo study, ZOL was released locally from a drug-loaded pre-shaped calcium phosphate bone cement plug which was implanted into a bone defect in the proximal tibia of rats. At 1 and 3 weeks post implantation, tissue reactions as well as bone regeneration capabilities at the implant site were investigated.

Pore-forming bacterial toxins and antimicrobial peptides as modulators of ADAM function.

Membrane-perturbating proteins and peptides are widespread agents in biology. Pore-forming bacterial toxins represent major virulence factors of pathogenic microorganisms. Membrane-damaging peptides constitute important antimicrobial effectors of innate immunity.

Delivery of antigens used for vaccination: recent advances and challenges.

Pasteur's principle 'isolate, inactivate, inject' was the starting point for the successful development of many vaccines, but now, new ways for antigen discovery and vaccine administration present a challenge. Whereas vaccines against polio, measles and influenza are common for many parts of the world, the development of thermostable vaccines not being injected would ease vaccine distribution in developing countries. This review summarizes the general principles of vaccination and looks at common and novel vaccination targets.