580 research outputs found

    Mouse skin passage of a Streptococcus pyogenes Tn917 mutant of sagA/pel restores virulence, beta-hemolysis and sagA/pel expression without altering the position or sequence of the transposon

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    BACKGROUND: Streptolysin S (SLS), the oxygen-stable hemolysin of Streptococcus pyogenes, has recently been shown to be encoded by the sagA/pel gene. Mutants lacking expression of this gene were less virulent in a dermonecrotic mouse infection model. Inactivation of the sagA/pel gene affect the expression of a variety of virulence factors in addition to the hemolysin. Insertion of a Tn917 transposon into the promoter region of the sagA/pel gene of S. pyogenes isolate CS101 eliminated expression of SLS, as well as decreased expression of the streptococcal pyrogenic exotoxin B, streptokinase and M protein. RESULTS: In this study a mouse skin air sac model was utilized to analyze the effect of biological pressures on expression of SLS and other sagA/pel regulated gene products. The insertion delayed the lethal effect of S. pyogenes in a mouse skin infection model. Despite this, bacteria could be cultured from the kidneys 72 hours post infection. These kidney-recovered isolates were β-hemolytic despite the transposon being present in its original location and had equivalent virulence to the wild type isolate when re-injected into naive mice. Northern blot analysis of the kidney-recovered isolates confirmed that transcription of sagA/pel was restored; however the expression of all sagA/pel regulated genes was not restored to wild type levels. CONCLUSIONS: These results show that biological pressure present in the mouse can select for variants with altered expression of key virulence factor genes in S. pyogenes

    Exploring the concept of the (future) mobile office

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    This video shows a concept of a future mobile office in a semi-automated vehicle that uses augmented reality. People perform non-driving tasks in current, non-automated vehicles even though that is unsafe. Moreover, even for passengers there is limited space, it is not social, and there can be motion sickness. In future cars, technology such as augmented reality might alleviate some of these issues. Our concept shows how augmented reality can project a remote conversant onto the dashboard. Thereby, the driver can keep an occasional eye on the road while the automated vehicle drives, and might experience less motion sickness. Potentially, this concept might even be used for group calls or for group activities such as karaoke, thereby creating a social setting. We also demonstrate how integration with an intelligent assistant (through speech and gesture analysis) might save the driver from having to grab a calendar to write things down, again allowing them to focus on the road

    Circuit dissection of the role of somatostatin in itch and pain

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    Stimuli that elicit itch are detected by sensory neurons that innervate the skin. This information is processed by the spinal cord; however, the way in which this occurs is still poorly understood. Here we investigated the neuronal pathways for itch neurotransmission, particularly the contribution of the neuropeptide somatostatin. We find that in the periphery, somatostatin is exclusively expressed in Nppb+ neurons, and we demonstrate that Nppb+somatostatin+ cells function as pruriceptors. Employing chemogenetics, pharmacology and cell-specific ablation methods, we demonstrate that somatostatin potentiates itch by inhibiting inhibitory dynorphin neurons, which results in disinhibition of GRPR+ neurons. Furthermore, elimination of somatostatin from primary afferents and/or from spinal interneurons demonstrates differential involvement of the peptide released from these sources in itch and pain. Our results define the neural circuit underlying somatostatin-induced itch and characterize a contrasting antinociceptive role for the peptide

    Genomic-Bioinformatic Analysis of Transcripts Enriched in the Third-Stage Larva of the Parasitic Nematode Ascaris suum

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    Differential transcription in Ascaris suum was investigated using a genomic-bioinformatic approach. A cDNA archive enriched for molecules in the infective third-stage larva (L3) of A. suum was constructed by suppressive-subtractive hybridization (SSH), and a subset of cDNAs from 3075 clones subjected to microarray analysis using cDNA probes derived from RNA from different developmental stages of A. suum. The cDNAs (n = 498) shown by microarray analysis to be enriched in the L3 were sequenced and subjected to bioinformatic analyses using a semi-automated pipeline (ESTExplorer). Using gene ontology (GO), 235 of these molecules were assigned to ‘biological process’ (n = 68), ‘cellular component’ (n = 50), or ‘molecular function’ (n = 117). Of the 91 clusters assembled, 56 molecules (61.5%) had homologues/orthologues in the free-living nematodes Caenorhabditis elegans and C. briggsae and/or other organisms, whereas 35 (38.5%) had no significant similarity to any sequences available in current gene databases. Transcripts encoding protein kinases, protein phosphatases (and their precursors), and enolases were abundantly represented in the L3 of A. suum, as were molecules involved in cellular processes, such as ubiquitination and proteasome function, gene transcription, protein–protein interactions, and function. In silico analyses inferred the C. elegans orthologues/homologues (n = 50) to be involved in apoptosis and insulin signaling (2%), ATP synthesis (2%), carbon metabolism (6%), fatty acid biosynthesis (2%), gap junction (2%), glucose metabolism (6%), or porphyrin metabolism (2%), although 34 (68%) of them could not be mapped to a specific metabolic pathway. Small numbers of these 50 molecules were predicted to be secreted (10%), anchored (2%), and/or transmembrane (12%) proteins. Functionally, 17 (34%) of them were predicted to be associated with (non-wild-type) RNAi phenotypes in C. elegans, the majority being embryonic lethality (Emb) (13 types; 58.8%), larval arrest (Lva) (23.5%) and larval lethality (Lvl) (47%). A genetic interaction network was predicted for these 17 C. elegans orthologues, revealing highly significant interactions for nine molecules associated with embryonic and larval development (66.9%), information storage and processing (5.1%), cellular processing and signaling (15.2%), metabolism (6.1%), and unknown function (6.7%). The potential roles of these molecules in development are discussed in relation to the known roles of their homologues/orthologues in C. elegans and some other nematodes. The results of the present study provide a basis for future functional genomic studies to elucidate molecular aspects governing larval developmental processes in A. suum and/or the transition to parasitism

    Smaller self-inflating bags produce greater guideline consistent ventilation in simulated cardiopulmonary resuscitation

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    <p>Abstract</p> <p>Background</p> <p>Suboptimal bag ventilation in cardiopulmonary resuscitation (CPR) has demonstrated detrimental physiological outcomes for cardiac arrest patients. In light of recent guideline changes for resuscitation, there is a need to identify the efficacy of bag ventilation by prehospital care providers. The objective of this study was to evaluate bag ventilation in relation to operator ability to achieve guideline consistent ventilation rate, tidal volume and minute volume when using two different capacity self-inflating bags in an undergraduate paramedic cohort.</p> <p>Methods</p> <p>An experimental study using a mechanical lung model and a simulated adult cardiac arrest to assess the ventilation ability of third year Monash University undergraduate paramedic students. Participants were instructed to ventilate using 1600 ml and 1000 ml bags for a length of two minutes at the correct rate and tidal volume for a patient undergoing CPR with an advanced airway. Ventilation rate and tidal volume were recorded using an analogue scale with mean values calculated. Ethics approval was granted.</p> <p>Results</p> <p>Suboptimal ventilation with the use of conventional 1600 ml bag was common, with 77% and 97% of participants unable to achieve guideline consistent ventilation rates and tidal volumes respectively. Reduced levels of suboptimal ventilation arouse from the use of the smaller bag with a 27% reduction in suboptimal tidal volumes (p = 0.015) and 23% reduction in suboptimal minute volumes (p = 0.045).</p> <p>Conclusion</p> <p>Smaller self-inflating bags reduce the incidence of suboptimal tidal volumes and minute volumes and produce greater guideline consistent results for cardiac arrest patients.</p

    Status and perspectives of hospital mortality in a public urban Hellenic hospital, based on a five-year review

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    <p>Abstract</p> <p>Background</p> <p>Analysis of hospital mortality helps to assess the standards of health-care delivery.</p> <p>Methods</p> <p>This is a retrospective cohort study evaluating the causes of deaths which occurred during the years 1995–1999 in a single hospital. The causes of death were classified according to the International Statistical Classification of Diseases (ICD-10).</p> <p>Results</p> <p>Of the 149,896 patients who were discharged the 5836 (3.4%) died. Males constituted 55% and females 45%. The median age was 75.1 years (1 day – 100 years).</p> <p>The seven most common ICD-10 chapters IX, II, IV, XI, XX, X, XIV included 92% of the total 5836 deaths.</p> <p>The most common contributors of non-neoplasmatic causes of death were cerebrovascular diseases (I60–I69) at 15.8%, ischemic heart disease (I20–I25) at 10.3%, cardiac failure (I50.0–I50.9) at 7.9%, diseases of the digestive system (K00–K93) at 6.7%, diabetes mellitus (E10–E14) at 6.6%, external causes of morbidity and mortality (V01–Y98) at 6.2%, renal failure (N17–N19) at 4.5%, influenza and pneumonia (J10–J18) at 4.1% and certain infectious and parasitic diseases (A00–B99) at 3.2%, accounting for 65.3% of the total 5836 deaths.</p> <p>Neoplasms (C00–D48) caused 17.7% (n = 1027) of the total 5836 deaths, with leading forms being the malignant neoplasms of bronchus and lung (C34) at 3.5% and the malignant neoplasms of large intestine (C18–21.2) at 1.5%. The highest death rates occurred in the intensive care unit (23.3%), general medicine (10.7%), cardiology (6.5%) and nephrology (5.5%).</p> <p>Key problems related to certification of death were identified. Nearly half of the deaths (49.3%: n = 2879) occurred by the completion of the third day, which indicates the time limits for investigation and treatment. On the other hand, 6% (n = 356) died between the 29<sup>th </sup>and 262<sup>nd </sup>days after admission.</p> <p>Inadequacies of the emergency care service, infection control, medical oncology, rehabilitation, chronic and terminal care facilities, as well as lack of regional targets for reducing mortality related to diabetes, recruitment of organ donors, provision for the aging population and lack of prevention programs were substantiated.</p> <p>Conclusion</p> <p>Several important issues were raised. Disease specific characteristics, as well as functional and infrastructural inadequacies were identified and provided evidence for defining priorities and strategies for improving the standards of care. Effective transformation can promise better prospects.</p

    Dynamic displacement of normal and detached semicircular canal cupula

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    © 2009 The Authors. This is an open-access article distributed under the terms of the Creative Commons Attribution Noncommercial License. The definitive version was published in JARO - Journal of the Association for Research in Otolaryngology 10 (2009): 497-509, doi:10.1007/s10162-009-0174-y.The dynamic displacement of the semicircular canal cupula and modulation of afferent nerve discharge were measured simultaneously in response to physiological stimuli in vivo. The adaptation time constant(s) of normal cupulae in response to step stimuli averaged 36 s, corresponding to a mechanical lower corner frequency for sinusoidal stimuli of 0.0044 Hz. For stimuli equivalent to 40–200 deg/s of angular head velocity, the displacement gain of the central region of the cupula averaged 53 nm per deg/s. Afferents adapted more rapidly than the cupula, demonstrating the presence of a relaxation process that contributes significantly to the neural representation of angular head motions by the discharge patterns of canal afferent neurons. We also investigated changes in time constants of the cupula and afferents following detachment of the cupula at its apex—mechanical detachment that occurs in response to excessive transcupular endolymph pressure. Detached cupulae exhibited sharply reduced adaptation time constants (300 ms–3 s, n = 3) and can be explained by endolymph flowing rapidly over the apex of the cupula. Partially detached cupulae reattached and normal afferent discharge patterns were recovered 5–7 h following detachment. This regeneration process may have relevance to the recovery of semicircular canal function following head trauma.Financial support was provided by the NIDCD R01 DC06685 (Rabbitt) and NASA GSRP 56000135 & NSF IGERT DGE- 9987616 (Breneman)
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