Vemurafenib Limits Influenza A Virus Propagation by Targeting Multiple Signaling Pathways.

Influenza A viruses (IAV) can cause severe global pandemic outbreaks. The currently licensed antiviral drugs are not very effective and prone to viral resistance. Thus, novel effective and broadly active drugs are urgently needed.

Dose-dependent effect of parathyroid hormone on fracture healing and bone formation in mice.

Background: Parathyroid hormone (PTH) is the only clinically approved osteoanabolic drug for osteoporosis treatment. However, PTH is not established for the treatment of fracture healing, and doses of PTH diverge significantly between different studies. We hypothesized that the effect of PTH on promoting fracture healing and bone formation is dose dependent.

The impact of different peripheral suture techniques on the biomechanical stability in flexor tendon repair.

Purpose: Flexor tendon repair consists of circumferential peripheral sutures in combination with core sutures to avoid fraying and reduces the exposure of suture material on tendon surface. The peripheral suture adds up to a tenfold increase of the biomechanical stability compared to the core suture alone. The purpose of our study was to determine the most favourable peripheral repair technique for tendon repair.

Oxidative stress-triggered interactions between the succinyl- and acetyl-proteomes of rice leaves.

Protein lysine acylations, such as succinylation and acetylation, are important post-translational modification (PTM) mechanisms, with key roles in cellular regulation. Antibody-based affinity enrichment, high-resolution liquid chromatography mass spectrometry analysis, and integrated bioinformatics analysis were used to characterize the lysine succinylome (K ) and acetylome (K ) of rice leaves. In total, 2,593 succinylated and 1,024 acetylated proteins were identified, of which 723 were simultaneously acetylated and succinylated.

A Comparison of Wolbachia Infection Frequencies in Varroa With Prevalence of Deformed Wing Virus.

Wolbachia are widely distributed bacterial endosymbionts of arthropods and filarial nematodes. These bacteria can affect host fitness in a variety of ways, such as protecting hosts against viruses and other pathogens. Here, we investigate the possible role of Wolbachia in the prevalence of the deformed wing virus (DWV), a highly virulent pathogen of honey bees (Apis mellifera) that is transmitted by parasitic Varroa mites (Varroa destructor).

Motor outcome measures in Huntington disease clinical trials.

Deficits in motor function are a hallmark of Huntington disease (HD). The Unified Huntington's Disease Rating Scale Total Motor Score (UHDRS-TMS) is a categoric clinical rating scale assessing multiple domains of motor disability in HD. The UHDRS-TMS or subsets of its items have served as primary or secondary endpoints in numerous clinical trials.

The LIM-Only Protein Four and a Half LIM Domain Protein 2 Attenuates Development of Psoriatic Arthritis by Blocking Adam17-Mediated Tumor Necrosis Factor Release.

Four and a half LIM domain protein 2 (Fhl2) is an intracellular adaptor molecule with a high protein-protein interaction capacity. It acts as a modulator of several signaling molecules in the cytosol and as a cofactor of transcription in the nucleus. Recent studies suggest the role of Fhl2 in tissue repair and the anti-inflammatory response.

PARTICLE triplexes cluster in the tumor suppressor WWOX and may extend throughout the human genome.

The long non-coding RNA PARTICLE (Gene PARTICL- 'Promoter of MAT2A-Antisense RadiaTion Induced Circulating LncRNA) partakes in triple helix (triplex) formation, is transiently elevated following low dose irradiation and regulates transcription of its neighbouring gene - Methionine adenosyltransferase 2A. It now emerges that PARTICLE triplex sites are predicted in many different genes across all human chromosomes. In silico analysis identified additional regions for PARTICLE triplexes at >1600 genomic locations.

Long non-coding RNA PARTICLE bridges histone and DNA methylation.

PARTICLE (Gene PARTICL- 'Promoter of MAT2A-Antisense RadiaTion Induced Circulating LncRNA) expression is transiently elevated following low dose irradiation typically encountered in the workplace and from natural sources. This long non-coding RNA recruits epigenetic silencers for cis-acting repression of its neighbouring Methionine adenosyltransferase 2A gene. It now emerges that PARTICLE operates as a trans-acting mediator of DNA and histone lysine methylation.

Addressing sufficiency of the CB1 receptor for endocannabinoid-mediated functions through conditional genetic rescue in forebrain GABAergic neurons.

Genetic inactivation of the cannabinoid CB1 receptor gene in different cell types in the brain has previously revealed necessary functions for distinct synaptic plasticity processes and behaviors. Here, we sought to identify CB1 receptor expression sites that are minimally required to reconstruct normal phenotypes. In a CB1-null background, we re-expressed endogenous CB1 receptors in forebrain GABAergic neurons, thereby assessing the sufficiency of CB1 receptors.

The MEK-inhibitor CI-1040 displays a broad anti-influenza virus activity in vitro and provides a prolonged treatment window compared to standard of care in vivo.

Influenza viruses (IV) continue to pose an imminent threat to human welfare. Yearly re-occurring seasonal epidemic outbreaks and pandemics with high mortality can occur. Besides vaccination against a limited number of viral strains only a few antiviral drugs are available, which are losing their effectiveness as more and more IV strains become resistant.

Directional spread of activity in synaptic networks of the human lateral amygdala.

Spontaneous epileptiform activity has previously been observed in lateral amygdala (LA) slices derived from patients with intractable-temporal lobe epilepsy. The present study aimed to characterize intranuclear LA synaptic connectivity and to test the hypothesis that differences in the spread of flow of neuronal activity may relate to spontaneous epileptiform activity occurrence. Electrical activity was evoked through electrical microstimulation in acute human brain slices containing the LA, signals were recorded as local field potentials combined with fast optical imaging of voltage-sensitive dye fluorescence.

Giant Left Atrial Myxoma: Cause for Position-Dependent Nocturnal Dyspnea and Cardiac Murmur.

Primary tumors of the heart are rare. The majority of them are benign, the left atrial myxoma being the most frequent one. Clinical appearance varies from unapparent to life-threatening complications such as stroke, acute heart failure, or even sudden death.

Mitogen-activated protein kinases (MAPKs) regulate IL-6 over-production during concomitant influenza virus and Staphylococcus aureus infection.

Bacterial super-infections are a major complication of influenza virus (IV) infections and often lead to severe pneumonia. One hallmark of IV-associated Staphylococcus aureus (S. aureus) infection is rapid progression to a serious disease outcome.

Targeting a metabolic pathway to fight the flu.

Our antiviral arsenal to fight influenza viruses is limited and we need novel anti-flu drugs. Recently, cellular drug targets came into focus and omics analysis were instrumental to suggest candidate factors. In this issue of The FEBS Journal, Kainov and colleagues used transcriptome data to investigate virus-induced changes in tryptophan metabolism that may serve as immunomodulatory approach against viruses.

Effect of training and structured medication review on medication appropriateness in nursing home residents and on cooperation between health care professionals: the InTherAKT study protocol.

Background: Pharmacotherapy in residents of nursing homes is critical due to the special vulnerability of this population. Medical care and interprofessional communication in nursing homes are often uncoordinated. As a consequence, polypharmacy and inappropriate medication use are common and may lead to hospitalizations and health hazards.

Redo Operation of Recurrent Giant Coronary Artery Aneurysm: Optimizing Surgical Strategy.

 Giant coronary artery aneurysms (GCAA) are extremely rare, but they can cause life-threatening complications. Indications for surgical intervention are the occurrence of complications such as fistulas, compression, embolization, or rapid enlargement. The optimal therapeutic approach is still under debate.

Minimally Invasive Implantation of HeartWare Assist Device and Simultaneous Tricuspid Valve Reconstruction Through Partial Upper Sternotomy.

Left ventricular assist device (LVAD) implantation is a well-established therapy to support patients with end-stage heart failure. However, the operative procedure is associated with severe trauma. Third generation LVADs like the HeartWare assist device (HeartWare, Inc.

Early outcomes in re-do operation after acute type A aortic dissection: results from the multicenter REAAD database.

This study provides early results of re-operations after the prior surgical treatment of acute type A aortic dissection (AAD) and identifies risk factors for mortality. Between May 2003 and January 2014, 117 aortic re-operations after an initial operation for AAD (a mean time from the first procedure was 3.98 years, with a range of 0.

Acute transfusion-related abdominal injury in trauma patients: a case report.

Background: Secondary abdominal compartment syndrome is well known as a life-threatening complication in critically ill patients in an intensive care unit. Massive crystalloid fluid resuscitation has been identified as the most important risk factor. The time interval from hospital admittance to the development of manifest abdominal compartment syndrome is usually greater than 24 hours.

Discontinuation of long-term adalimumab treatment in patients with juvenile idiopathic arthritis-associated uveitis.

Purpose: The purpose of this study was to evaluate the discontinuation of adalimumab (ADA) treatment in patients with juvenile idiopathic arthritis-associated uveitis (JIAU).

Methods: Patients in whom ADA treatment was initiated for JIAU were included in this retrospective analysis. Reasons for discontinuing ADA treatment in patients with primary treatment response were analysed.

Post-invasion events after infection with Staphylococcus aureus are strongly dependent on both the host cell type and the infecting S. aureus strain.

Host cell invasion is a major feature of Staphylococcus aureus and contributes to infection development. The intracellular metabolically active bacteria can induce host cell activation and death but they can also persist for long time periods. In this study a comparative analysis was performed of different well-characterized S.

Influenza A viruses suppress cyclooxygenase-2 expression by affecting its mRNA stability.

Infection with influenza A viruses (IAV) provokes activation of cellular defence mechanisms contributing to the innate immune and inflammatory response. In this process the cyclooxygenase-2 (COX-2) plays an important role in the induction of prostaglandin-dependent inflammation. While it has been reported that COX-2 is induced upon IAV infection, in the present study we observed a down-regulation at later stages of infection suggesting a tight regulation of COX-2 by IAV.

Priority Setting and Influential Factors on Acceptance of Pharmaceutical Recommendations in Collaborative Medication Reviews in an Ambulatory Care Setting - Analysis of a Cluster Randomized Controlled Trial (WestGem-Study).

Background: Medication reviews are recognized services to increase quality of therapy and reduce medication risks. The selection of eligible patients with potential to receive a major benefit is based on assumptions rather than on factual data. Acceptance of interprofessional collaboration is crucial to increase the quality of medication therapy.

Digital Carotid Compression: A Simple Method to Reduce Solid Cerebral Emboli During Cardiac Surgery.

Objectives: Serious neurologic injury can be attributed to embolization of solid particles into cerebral vessels during cardiac surgery. Previous studies using transcranial Doppler (TCD) identified arterial cannulation and aortic declamping to be associated with cerebral embolization. The purpose of this study was to investigate the impact of transient compression of the carotid arteries during these maneuvers on the embolic load during cardiac surgery with cardiopulmonary bypass.