Short-course systemic corticosteroids in asthma : striking the balance between efficacy and safety

The authors thank Gillian Lavelle and Claire Twomey (Novartis Product Lifecycle Services, Dublin, Ireland) for providing scientific writing support for this article, which was funded by Novartis Pharma AG (Basel, Switzerland) in accordance with Good Publication Practice (GPP3) guidelines (www.ismpp.org/gpp3).Peer reviewedPublisher PD

Diagnostic accuracy of inferior vena cava evaluation in the diagnosis of acute heart failure among dyspneic patients.

Acute dyspnea is one of the main reasons for admission to the Emergency Department (ED). A rapid and accurate diagnosis can be lifesaving for these patients. Particularly, it is important to differentiate between dyspnea due to acute heart failure (AHF) and dyspnea of pulmonary origin. The aim of this study is to evaluate the real accuracy of the evaluation of diameter and collapsibility of IVC for the diagnosis of AHF among dyspneic patients. We analyzed 155 patients admitted for acute dyspnea to the ED of "Maurizio Bufalini" hospital in Cesena (Italy) and "Antonio Cardarelli" hospital in Naples (Italy) from November 2014 to April 2017. All patients underwent ultrasound of inferior vena cava (IVC) examination with a hand-held device in addition to the traditional pathway. Patients were classified into AHF group or non-AHF group according to the current guidelines. The final diagnosis was AHF in 64 patients and dyspnea of non-cardiac origin in 91 patients. Sensibility and specificity of IVC hypo-collapsibility was 75.81% (95% CI 63.26% to 85.78%) and 67.74% (95% CI 57.25% to 77.07%) for the diagnosis of AHF. Sensibility and specificity of IVC dilatation was 69.35% (95% CI 56.35% to 80.44%) and 74.19% (95%CI 64.08% to 82.71%) for the diagnosis of AHF. AUC was 0.718 (0.635-0.801) for IVC hypo-collapsibility, 0.718 (0.634-0.802) for IVC dilatation. Our study demonstrated that the sonographic assessment of IVC diameter and collapsibility is suboptimal to differentiate acute dyspnea due to AHF or other causes in the emergency setting

Diagnostic Multidisciplinary Investigations for Cultural Heritage at Etna Volcano: A Case Study from the 1669 Eruption in the Mother Church at the Old Settlement of Misterbianco

Misterbianco is located on the southern flank of Mt. Etna (Unesco site), in eastern Sicily (Italy). This site, also known as Monasterium Album, has a long and tormented history linked with volcanic activity of Mt. Etna and regional seismicity. This site received much attention in the 2000s when excavation works brought to light a 14th century church remains below the thick layer of the 1669 lava. This study documents the first diagnostic multidisciplinary survey performed at this site 350 years after the eruption: the investigations were performed by using techniques such as ground-penetrating radar, infrared thermography, a terrestrial laser scanner and a drone survey to analyze the site’s topography, to adequately map the hidden structures inside the building and to identify fractures and deformations in the church. Starting from the site history, we present the results of the multidisciplinary approach aimed at reconstructing the historical events that led to the damage in the church

Diagnostic Multidisciplinary Investigations for Cultural Heritage at Etna Volcano: A Case Study from the 1669 Eruption in the Mother Church at the Old Settlement of Misterbianco

Misterbianco is located on the southern flank of Mt. Etna (Unesco site), in eastern Sicily (Italy). This site, also known as Monasterium Album, has a long and tormented history linked with volcanic activity of Mt. Etna and regional seismicity. This site received much attention in the 2000s when excavation works brought to light a 14th century church remains below the thick layer of the 1669 lava. This study documents the first diagnostic multidisciplinary survey performed at this site 350 years after the eruption: the investigations were performed by using techniques such as ground-penetrating radar, infrared thermography, a terrestrial laser scanner and a drone survey to analyze the site’s topography, to adequately map the hidden structures inside the building and to identify fractures and deformations in the church. Starting from the site history, we present the results of the multidisciplinary approach aimed at reconstructing the historical events that led to the damage in the church

Same riot/demo, different views (guest blog)

By Shakuntala Banaji In riposte to various UK newspapers’ and news channels’ conservative versions of reality, I would like to give an alternative account of what happened on the November 10th NUS and UCU demonstration against student fees and on the break-away part of it at 30 Millbank, the Conservative party HQ

GABA(A)-current rundown of temporal lobe epilepsy is associated with repetitive activation of GABA(A) "phasic" receptors

A study was made of the "rundown" of GABA(A) receptors, microtransplanted to Xenopus oocytes from surgically resected brain tissues of patients afflicted with drug-resistant human mesial temporal lobe epilepsy (mTLE). Cell membranes, isolated from mTLE neocortex specimens, were injected into frog oocytes that rapidly incorporated functional GABA(A) receptors. Upon repetitive activation with GABA (1 mM), "epileptic" GABA(A) receptors exhibited a GABA(A)-current (I(GABA)) rundown that was significantly enhanced by Zn(2+) (</=250 microM), and practically abolished by the high-affinity GABA(A) receptor inverse agonist SR95531 (gabazine; 2.5-25 microM). Conversely, I(GABA) generated by "control" GABA(A) receptors microtransplanted from nonepileptic temporal lobe, lesional TLE, or authoptic disease-free tissues remained stable during repetitive stimulation, even in oocytes treated with Zn(2+). We conclude that rundown of mTLE epileptic receptors depends on the presence of "phasic GABA(A) receptors" that have low sensitivity to antagonism by Zn(2+). Additionally, we found that GABA(A) receptors, microtransplanted from the cerebral cortex of adult rats exhibiting recurrent seizures, caused by pilocarpine-induced status epilepticus, showed greater rundown than control tissue, an event also occurring in patch-clamped rat pyramidal neurons. Rundown of epileptic rat receptors resembled that of human mTLE receptors, being enhanced by Zn(2+) (40 microM) and sensitive to the antiepileptic agent levetiracetam, the neurotrophin brain-derived neurotrophic factor, and the phosphatase blocker okadaic acid. Our findings point to the rundown of GABA(A) receptors as a hallmark of TLE and suggest that modulating tonic and phasic mTLE GABA(A) receptor activity may represent a useful therapeutic approach to the disease

GABAA-current rundown of temporal lobe epilepsy is associated with repetitive activation of GABAA “phasic” receptors

A study was made of the “rundown” of GABAA receptors, microtransplanted to Xenopus oocytes from surgically resected brain tissues of patients afflicted with drug-resistant human mesial temporal lobe epilepsy (mTLE). Cell membranes, isolated from mTLE neocortex specimens, were injected into frog oocytes that rapidly incorporated functional GABAA receptors. Upon repetitive activation with GABA (1 mM), “epileptic” GABAA receptors exhibited a GABAA-current (IGABA) rundown that was significantly enhanced by Zn2+ (≤250 μM), and practically abolished by the high-affinity GABAA receptor inverse agonist SR95531 (gabazine; 2.5–25 μM). Conversely, IGABA generated by “control” GABAA receptors microtransplanted from nonepileptic temporal lobe, lesional TLE, or authoptic disease-free tissues remained stable during repetitive stimulation, even in oocytes treated with Zn2+. We conclude that rundown of mTLE epileptic receptors depends on the presence of “phasic GABAA receptors” that have low sensitivity to antagonism by Zn2+. Additionally, we found that GABAA receptors, microtransplanted from the cerebral cortex of adult rats exhibiting recurrent seizures, caused by pilocarpine-induced status epilepticus, showed greater rundown than control tissue, an event also occurring in patch-clamped rat pyramidal neurons. Rundown of epileptic rat receptors resembled that of human mTLE receptors, being enhanced by Zn2+ (40 μM) and sensitive to the antiepileptic agent levetiracetam, the neurotrophin brain-derived neurotrophic factor, and the phosphatase blocker okadaic acid. Our findings point to the rundown of GABAA receptors as a hallmark of TLE and suggest that modulating tonic and phasic mTLE GABAA receptor activity may represent a useful therapeutic approach to the disease

LAV-BPIFB4 isoform modulates eNOS signaling through Ca2+/PKC-alpha dependent mechanism

Aging is associated with impairment of endothelial nitric oxide synthase (eNOS) and progressive reduction in endothelial function. A genetic study on long-living individuals - who are characterized by delays in aging and in the onset of cardiovascular disease - previously revealed I229V ( rs2070325 ) in BPIFB4 as a longevity-associated variant (LAV); the LAV protein enhanced endothelial NO production and vasorelaxation through a PERK/14-3-3/HSP90 signal. Here, we further characterize the molecular mechanisms underlying LAV-BPIFB4-dependent enhancement of vascular function