Absence of inspiratory laryngeal constrictor muscle activity during nasal neurally adjusted ventilatory assist in newborn lambs

It has been demonstrated that a progressive increase in nasal pressure support ventilation (nPSV) leads to an active inspiratory glottal closure in non-sedated newborn lambs, which limits lung ventilation (24, 33). Unlike nPSV, the pressure delivered during nasal Neurally Adjusted Ventilatory Assist (nNAVA) is synchronized to the diaphragm electrical activity on inspiration (36). Given the tight neural integration of the glottal dilators and constrictors with diaphragm activity on inspiration and expiration respectively, the aim of the present study was to test the hypothesis that inspiratory glottal closure does not develop during nNAVA. Polysomnographic recordings were performed in eight non-sedated, chronically instrumented lambs, which were ventilated with progressively increasing levels of nPSV and nNAVA, in random order. States of alertness, diaphragm and glottal muscle electrical activity, tracheal pressure, SpO2, tracheal PETCO2 and respiratory inductive plethysmography were continuously recorded. While phasic inspiratory glottal constrictor electrical activity appeared with increasing levels of nPSV in 5 out of 8 lambs, it was never observed at any nNAVA level in any lamb, even at maximal achievable nNAVA levels. In addition, a decrease in arterial PCO2 was neither necessary nor sufficient for the development of phasic inspiratory glottal constrictor activity. In conclusion, nNAVA does not induce active glottal closure in non-sedated newborn lambs at high-pressure levels, in contrast to nPSV

Pentraxins coordinate excitatory synapse maturation and circuit integration of parvalbumin interneurons

This is the author accepted manuscript. The final version is available from the publisher via the DOI in this record.Circuit computation requires precision in the timing, extent, and synchrony of principal cell (PC) firing that is largely enforced by parvalbumin-expressing, fast-spiking interneurons (PVFSIs). To reliably coordinate network activity, PVFSIs exhibit specialized synaptic and membrane properties that promote efficient afferent recruitment such as expression of high-conductance, rapidly gating, GluA4-containing AMPA receptors (AMPARs). We found that PVFSIs upregulate GluA4 during the second postnatal week coincident with increases in the AMPAR clustering proteins NPTX2 and NPTXR. Moreover, GluA4 is dramatically reduced in NPTX2(-/-)/NPTXR(-/-) mice with consequent reductions in PVFSI AMPAR function. Early postnatal NPTX2(-/-)/NPTXR(-/-) mice exhibit delayed circuit maturation with a prolonged critical period permissive for giant depolarizing potentials. Juvenile NPTX2(-/-)/NPTXR(-/-) mice display reduced feedforward inhibition yielding a circuit deficient in rhythmogenesis and prone to epileptiform discharges. Our findings demonstrate an essential role for NPTXs in controlling network dynamics highlighting potential therapeutic targets for disorders with inhibition/excitation imbalances such as schizophrenia.Work supported by a PRAT fellowship to M.S.W., an NICHD intramural award to C.J.M., NIDCD intramural research program funding to R.S.P., an NIMH intramural award to H.A.C., NIH grants (PAR-02-059, NS 039156) to P.F.W., and an NIH grant (EY022730) to M.T.

Transition of plasmodium sporozoites into liver stage-like forms is regulated by the RNA binding protein pumilio

Many eukaryotic developmental and cell fate decisions that are effected post-transcriptionally involve RNA binding proteins as regulators of translation of key mRNAs. In malaria parasites (Plasmodium spp.), the development of round, non-motile and replicating exo-erythrocytic liver stage forms from slender, motile and cell-cycle arrested sporozoites is believed to depend on environmental changes experienced during the transmission of the parasite from the mosquito vector to the vertebrate host. Here we identify a Plasmodium member of the RNA binding protein family PUF as a key regulator of this transformation. In the absence of Pumilio-2 (Puf2) sporozoites initiate EEF development inside mosquito salivary glands independently of the normal transmission-associated environmental cues. Puf2- sporozoites exhibit genome-wide transcriptional changes that result in loss of gliding motility, cell traversal ability and reduction in infectivity, and, moreover, trigger metamorphosis typical of early Plasmodium intra-hepatic development. These data demonstrate that Puf2 is a key player in regulating sporozoite developmental control, and imply that transformation of salivary gland-resident sporozoites into liver stage-like parasites is regulated by a post-transcriptional mechanism

Assessing the association between all-cause mortality and multiple aspects of individual social capital among the older Japanese

<p>Abstract</p> <p>Background</p> <p>Few prospective cohort studies have assessed the association between social capital and mortality. The studies were conducted only in Western countries and did not use the same social capital indicators. The present prospective cohort study aimed to examine the relationships between various forms of individual social capital and all-cause mortality in Japan.</p> <p>Methods</p> <p>Self-administered questionnaires were mailed to subjects in the Aichi Gerontological Evaluation Study (AGES) Project in 2003. Mortality data from 2003 to 2008 were analyzed for 14,668 respondents. Both cognitive and structural components of individual social capital were collected: 8 for cognitive social capital (trust, 3; social support, 3; reciprocity, 2) and 9 for structural social capital (social network). Cox proportional hazard models stratified by sex with multiple imputation were used. Age, body mass index, self-rated health, current illness, smoking history, alcohol consumption, exercise, equivalent income and education were used as covariates.</p> <p>Results</p> <p>During 27,571 person-years of follow-up for men and 29,561 person-years of follow-up for women, 790 deaths in men and 424 in women were observed. In the univariate analyses for men, lower social capital was significantly related to higher mortality in one general trust variable, all generalised reciprocity variables and four social network variables. For women, lower social capital was significantly related to higher mortality in all generalised reciprocity and four social network variables. After adjusting for covariates, lower friendship network was significantly associated with higher all-cause mortality among men (meet friends rarely; HR = 1.30, 95%CI = 1.10-1.53) and women (having no friends; HR = 1.81, 95%CI = 1.02-3.23). Among women, lower general trust was significantly related to lower mortality (most people cannot be trusted; HR = 0.65, 95%CI = 0.45-0.96).</p> <p>Conclusions</p> <p>Friendship network was a good predictor for all-cause mortality among older Japanese. In contrast, mistrust was associated with lower mortality among women. Studies with social capital indices considering different culture backgrounds are needed.</p

Clinical characteristics of children with Juvenile Systemic Sclerosis: follow-up of 23 patients in a single tertiary center

© 2007 Russo and Katsicas; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Quantitative analysis of left atrial function in asymptomatic patients with b-thalassemia major using real-time three-dimensional echocardiography

<p>Abstract</p> <p>Background</p> <p>There is strong evidence that left atrial (LA) size is a prognostic marker in a variety of heart diseases. Recently, real-time three-dimensional echocardiography (RT3DE) has been reported as a useful tool for studying the phasic changes of the left atrial volumes. The aim of this study was to investigate the performance of the left atrium in beta-thalassemic patients with preserved left ventricular ejection fraction (EF) and no iron overload, using RT3DE.</p> <p>Methods</p> <p>Twenty-eight asymptomatic b-thalassemic patients (32.2 ± 4.3 years old, 17 men) who were on iron chelating therapy, as well as 20 age- and sex-matched healthy controls underwent transthoracic RT3DE. The patient group had normal echocardiographic systolic and diastolic indices, while there was no myocardial iron disposition according to MRI. Apical full volume data sets were obtained and LA volumes were measured at 3 time points of the cardiac cycle: (1) maximum volume (LAmax) at end-systole, just before mitral valve opening; (2) minimum volume (LAmin) at end-diastole, just before mitral valve closure; and (3) volume before atrial active contraction (LApreA) obtained from the last frame before mitral valve reopening or at time of the P wave on the surface electrocardiogram. From the derived values, left atrial active and passive emptying volumes, as well as the respective emptying fractions were calculated.</p> <p>Results</p> <p>Left ventricular EF (59.2 ± 2.5% patients vs. 60.1 ± 2.1% controls), E/A, E/E' were similar between the two groups. Differences in the LAmax, LAmin and LApreA between b-thalassemic patients and controls were non-significant, LAmax:(35.5 ± 13.4 vs 31.8 ± 9.8)cm³, LAmin:(16.0 ± 6.0 vs. 13.5 ±4.2)cm³, and LApreA:(25.4 ± 9.8 vs. 24.3 ± 7.2)cm³. However, left atrial active emptying fraction was reduced in the patient group as compared to the healthy population (34.3 ± 16.4% vs. 43.2 ± 11.4%, p < 0.05).</p> <p>Conclusion</p> <p>RT3DE may be a novel technique for the evaluation of LA function in asymptomatic patients with b-Thalassemia Major. Among three-dimensional volumes and indices, left atrial active emptying fraction may be an early index of LA dysfunction in the specific patient population.</p

Multimodal discrimination of immune cells using a combination of Raman spectroscopy and digital holographic microscopy

This work was supported by the UK Engineering and Physical Sciences Research Council under grant EP/J01771X/1, A European Union FAMOS project (FP7 ICT, 317744), and the ’BRAINS’ 600th anniversary appeal, and Dr. E. Killick. We would also like to thank The RS Macdonald Charitable Trust for funding support. KD acknowledges support of a Royal Society Leverhulme Trust Senior Fellowship. This work was also supported by the PreDiCT-TB consortium [IMI Joint undertaking grant agreement number 115337, resources of which are composed of financial contribution from the European Union’s Seventh Framework Programme (FP7/2007-2013) and EFPIA companies’ in kind contribution (www.imi.europa.eu)]The ability to identify and characterise individual cells of the immune system under label-free conditions would be a significant advantage in biomedical and clinical studies where untouched and unmodified cells are required. We present a multi-modal system capable of simultaneously acquiring both single point Raman spectra and digital holographic images of single cells. We use this combined approach to identify and discriminate between immune cell populations CD4+ T cells, B cells and monocytes. We investigate several approaches to interpret the phase images including signal intensity histograms and texture analysis. Both modalities are independently able to discriminate between cell subsets and dual-modality may therefore be used a means for validation. We demonstrate here sensitivities achieved in the range of 86.8% to 100%, and specificities in the range of 85.4% to 100%. Additionally each modality provides information not available from the other providing both a molecular and a morphological signature of each cell.Publisher PDFPeer reviewe