Loss of anion transport without increased sodium absorption characterizes newborn porcine cystic fibrosis airway epithelia

Defective transepithelial electrolyte transport is thought to initiate cystic fibrosis (CF) lung disease. Yet, how loss of CFTR affects electrolyte transport remains uncertain. CFTR -/- pigs spontaneously develop lung disease resembling human CF. At birth, their airways exhibit a bacterial host defense defect, but are not inflamed. Therefore, we studied ion transport in newborn nasal and tracheal/bronchial epithelia in tissues, cultures, and in vivo. CFTR -/- epithelia showed markedly reduced Cl - and HCO 3 - transport. However, in contrast to a widely held view, lack of CFTR did not increase transepithelial Na + or liquid absorption or reduce periciliary liquid depth. Like human CF, CFTR -/- pigs showed increased amiloride-sensitive voltage and current, but lack of apical Cl - conductance caused the change, not increased Na + transport. These results indicate that CFTR provides the predominant transcellular pathway for Cl - and HCO 3 - in porcine airway epithelia, and reduced anion permeability may initiate CF airway disease. © 2010 Elsevier Inc.published_or_final_versio

Antiepileptic drugs’ tolerability and safety – a systematic review and meta-analysis of adverse effects in dogs

<p>Various anti-epileptic drugs (AEDs) are used for the management of idiopathic epilepsy (IE) in dogs. Their safety profile is an important consideration for regulatory bodies, owners and prescribing clinicians. However, information on their adverse effects still remains limited with most of it derived from non-blinded non-randomized uncontrolled trials and case reports.</p><p><span>This poster won third place, which was presented at the Veterinary Evidence Today conference, Edinburgh November 1-3, 2016. </span></p><br /> <img src="https://www.veterinaryevidence.org/rcvskmod/icons/oa-icon.jpg" alt="Open Access" /

Photo-antagonism of the GABAA receptor

Neurotransmitter receptor trafficking is fundamentally important for synaptic transmission and neural network activity. GABAA receptors and inhibitory synapses are vital components of brain function, yet much of our knowledge regarding receptor mobility and function at inhibitory synapses is derived indirectly from using recombinant receptors, antibody-tagged native receptors and pharmacological treatments. Here we describe the use of a set of research tools that can irreversibly bind to and affect the function of recombinant and neuronal GABAA receptors following ultraviolet photoactivation. These compounds are based on the competitive antagonist gabazine and incorporate a variety of photoactive groups. By using site-directed mutagenesis and ligand-docking studies, they reveal new areas of the GABA binding site at the interface between receptor β and α subunits. These compounds enable the selected inactivation of native GABAA receptor populations providing new insight into the function of inhibitory synapses and extrasynaptic receptors in controlling neuronal excitation

Distortions of Subjective Time Perception Within and Across Senses

Background: The ability to estimate the passage of time is of fundamental importance for perceptual and cognitive processes. One experience of time is the perception of duration, which is not isomorphic to physical duration and can be distorted by a number of factors. Yet, the critical features generating these perceptual shifts in subjective duration are not understood. Methodology/Findings: We used prospective duration judgments within and across sensory modalities to examine the effect of stimulus predictability and feature change on the perception of duration. First, we found robust distortions of perceived duration in auditory, visual and auditory-visual presentations despite the predictability of the feature changes in the stimuli. For example, a looming disc embedded in a series of steady discs led to time dilation, whereas a steady disc embedded in a series of looming discs led to time compression. Second, we addressed whether visual (auditory) inputs could alter the perception of duration of auditory (visual) inputs. When participants were presented with incongruent audio-visual stimuli, the perceived duration of auditory events could be shortened or lengthened by the presence of conflicting visual information; however, the perceived duration of visual events was seldom distorted by the presence of auditory information and was never perceived shorter than their actual durations. Conclusions/Significance: These results support the existence of multisensory interactions in the perception of duration and, importantly, suggest that vision can modify auditory temporal perception in a pure timing task. Insofar as distortions in subjective duration can neither be accounted for by the unpredictability of an auditory, visual or auditory-visual event, we propose that it is the intrinsic features of the stimulus that critically affect subjective time distortions

Emplacement of inflated Pāhoehoe flows in the Naude’s Nek Pass, Lesotho remnant, Karoo continental flood basalt province: use of flow-lobe tumuli in understanding flood basalt emplacement

Physical volcanological features are presented for a 710-m-thick section, of the Naude’s Nek Pass, within the lower part of the Lesotho remnant of the Karoo Large Igneous Province. The section consists of inflated pāhoehoe lava with thin, impersistent sedimentary interbeds towards the base. There are seven discreet packages of compound and hummocky pāhoehoe lobes containing flow-lobe tumuli, making up approximately 50% of the section. Approximately 45% of the sequence consists of 14 sheet lobes, between 10 and 52-m-thick. The majority of the sheet lobes are in two packages indicating prolonged periods of lava supply capable of producing thick sheet lobes. The other sheet lobes are as individual lobes or pairs, within compound flows, suggesting brief increases in lava supply rate. We suggest, contrary to current belief, that there is no evidence that compound flows are proximal to source and sheet lobes (simple flows) are distal to source and we propose that the presence of flow-lobe tumuli in compound flows could be an indicator that a flow is distal to source. We use detailed, previously published, studies of the Thakurvadi Formation (Deccan Traps) as an example. We show that the length of a lobe and therefore the sections that are ‘medial or distal to source’ are specific to each individual lobe and are dependent on the lava supply of each eruptive event, and as such flow lobe tumuli can be used as an indicator of relative distance from source

Endobronchial Ultrasound-guided Transbronchial Needle Biopsy for Diagnosis of Mediastinal Lymphadenopathy in Patients with Extrathoracic Malignancy

Mediastinal lymphadenopathy associated with extrathoracic malignancy or a metastasis of unknown origin (MUO) requires pathological verification. Surgical exploration or endoscopic ultrasound-guided fine needle aspiration is limited to application. We investigated the effectiveness of endobronchial ultrasound-guided transbronchial needle biopsy (EBUS-TBNA) for evaluating mediastinal lymphadenopathy in patients with an extrathoracic malignancy. We retrospectively analyzed data from 59 patients who underwent EBUS-TBNA with a core biopsy because of a suspected mediastinal metastasis between September 2008 and August 2010. All patients had previously been diagnosed with an extrathoracic malignancy (n = 39, 66.1%) or a suspected MUO without a thoracic lesion (n = 20, 33.9%). A total of 88 lymph nodes was analyzed. EBUS-TBNA findings indicated malignancies in 34 patients (57.6%). The EBUS-TBNA sensitivity and specificity for the detection of mediastinal malignancy in patients with a previous extrathoracic malignancy were 96.3% and 100%, respectively. For MUO patients without a thoracic lesion, the sensitivity and specificity were 61.5% and 100%, respectively. The overall sensitivity and specificity were 81.0% and 100%, respectively (P = 0.053). EBUS-TBNA is a safe and effective modality for evaluating mediastinal lymphadenopathy in patients with a previous extrathoracic malignancy or a MUO without a thoracic lesion. The application of this diagnostic tool is likely to have significant clinical implications

Investigation of the association of Apgar score with maternal socio-economic and biological factors: an analysis of German perinatal statistics

PURPOSE: To examine the relationship of 5-min Apgar score with maternal socio-economic and biological factors. METHODS: We analyzed data from 465,964 singleton pregnancies (37–41 weeks’ gestation) from the German perinatal statistics of 1998–2000. Using a logistic regression model we analyzed the incidence of low (0–6) 5-min Apgar scores in relation to these maternal factors: body mass index (BMI), age, previous live births, country of origin, occupation, single mother status, working during pregnancy, and smoking. RESULTS: A low Apgar score was more common in overweight [adjusted odds ratio (OR) 1.24; 95% confidence interval (CI) 1.10–1.40; P &lt; 0.001] and obese [OR 1.92 (95% CI 1.67–2.20); P &lt; 0.001] compared to normal weight women. A low Apgar score was also more common for women aged &gt;35 years compared to those aged 20–35 years [OR 1.35 (95% CI 1.16–1.58); P &lt; 0.001]. Furthermore, odds of a low Apgar score were higher for women with no previous live births compared to those with one or more previous live births [OR 1.52 (95% CI 1.37–1.70); P &lt; 0.001]. Socio-economic factors did not convincingly influence Apgar scores. CONCLUSIONS: There was an influence of the biological maternal factors age, BMI, and parity on the 5-min Apgar score. There was no convincing effect of socio-economic factors on Apgar score in our study population. Possible reasons for this are discussed