Epidemiology, prehospital care and outcomes of patients arriving by ambulance with dyspnoea: An observational study

Background: This study aimed to determine epidemiology and outcome for patients presenting to emergency departments (ED) with shortness of breath who were transported by ambulance. Methods: This was a planned sub-study of a prospective, interrupted time series cohort study conducted at three time points in 2014 and which included consecutive adult patients presenting to the ED with dyspnoea as a main symptom. For this sub-study, additional inclusion criteria were presentation to an ED in Australia or New Zealand and transport by ambulance. The primary outcomes of interest are the epidemiology and outcome of these patients. Analysis was by descriptive statistics and comparisons of proportions. Results: One thousand seven patients met inclusion criteria. Median age was 74 years (IQR 61-68) and 46.1 % were male. There was a high rate of co-morbidity and chronic medication use. The most common ED diagnoses were lower respiratory tract infection (including pneumonia, 22.7 %), cardiac failure (20.5%) and exacerbation of chronic obstructive pulmonary disease (19.7 %). ED disposition was hospital admission (including ICU) for 76.4 %, ICU admission for 5.6 % and death in ED in 0.9 %. Overall in-hospital mortality among admitted patients was 6.5 %. Discussion: Patients transported by ambulance with shortness of breath make up a significant proportion of ambulance caseload and have high comorbidity and high hospital admission rate. In this study, >60 % were accounted for by patients with heart failure, lower respiratory tract infection or COPD, but there were a wide range of diagnoses. This has implications for service planning, models of care and paramedic training. Conclusion: This study shows that patients transported to hospital by ambulance with shortness of breath are a complex and seriously ill group with a broad range of diagnoses. Understanding the characteristics of these patients, the range of diagnoses and their outcome can help inform training and planning of services

Phase-locked mutants of Mycoplasma agalactiae: defining the molecular switch of high-frequency Vpma antigenic variation

Mycoplasma agalactiae, an important pathogen of small ruminants, exhibits antigenic diversity by switching the expression of multiple surface lipoproteins called Vpmas (Variable proteins of M. agalactiae). Although phase variation has been shown to play important roles in many host–pathogen interactions, the biological significance and the mechanism of Vpma oscillations remain largely unclear. Here, we demonstrate that all six Vpma proteins are expressed in the type strain PG2 and all undergo phase variation at an unusually high frequency. Furthermore, targeted gene disruption of the xer1 gene encoding a putative site-specific recombinase adjacent to the vpma locus was accomplished via homologous recombination using a replicon-based vector. Inactivation of xer1 abolished further Vpma switching and the ‘phase-locked’ mutants (PLMs) continued to steadily express only a single Vpma product. Complementation of the wild-type xer1 gene in PLMs restored Vpma phase variation thereby proving that Xer1 is essential for vpma inversions. The study is not only instrumental in enhancing our ability to understand the role of Vpmas in M. agalactiae infections but also provides useful molecular approaches to study potential disease factors in other ‘difficult-to-manipulate’ mycoplasmas

Cell-type specific RNA-Seq reveals novel roles and regulatory programs for terminally differentiated Dictyostelium cells

Abstract Background A major hallmark of multicellular evolution is increasing complexity by the evolution of new specialized cell types. During Dictyostelid evolution novel specialization occurred within taxon group 4. We here aim to retrace the nature and ancestry of the novel “cup” cells by comparing their transcriptome to that of other cell types. Results RNA-Seq was performed on purified mature spore, stalk and cup cells and on vegetative amoebas. Clustering and phylogenetic analyses showed that cup cells were most similar to stalk cells, suggesting that they share a common ancestor. The affinity between cup and stalk cells was also evident from promoter-reporter studies of newly identified cell-type genes, which revealed late expression in cups of many stalk genes. However, GO enrichment analysis reveal the unexpected prominence of GTPase mediated signalling in cup cells, in contrast to enrichment of autophagy and cell wall synthesis related transcripts in stalk cells. Combining the cell type RNA-Seq data with developmental expression profiles revealed complex expression dynamics in each cell type as well as genes exclusively expressed during terminal differentiation. Most notable were nine related hssA-like genes that were highly and exclusively expressed in cup cells. Conclusions This study reveals the unique transcriptomes of the mature cup, stalk and spore cells of D. discoideum and provides insight into the ancestry of cup cells and roles in signalling that were not previously realized. The data presented in this study will serve as an important resource for future studies into the regulation and evolution of cell type specialization

From Marx to Gramsci to us: Laboratory to prison, and back

Marx and Gramsci remain two of the most constant presences and inspirations for those on the left. Yet there is a persistent sense that we have still to get them right. Perhaps this indicates that sources like this are now fully classics, to be returned, and returned to. In the case of Marx and Gramsci, a series of major works published in the Brill Historical Materialism series breaks new ground as well as returning to older controversies, both resolved and unresolved. Apart from remaining arguments concerning the status of materials unpublished in their own lifetimes, the major tension that emerges here is that between the task of immanent, contextual philology and the challenge of reading ‘Marx for today’ or ‘Gramsci for today’. The tension between text and context, and the question of what travels, conceptually persists

The mitochondrial genome of the hexactinellid sponge Aphrocallistes vastus: Evidence for programmed translational frameshifting

<p>Abstract</p> <p>Background</p> <p>Mitochondrial genomes (mtDNA) of numerous sponges have been sequenced as part of an ongoing effort to resolve the class-level phylogeny of the Porifera, as well as to place the various lower metazoan groups on the animal-kingdom tree. Most recently, the partial mtDNA of two glass sponges, class Hexactinellida, were reported. While previous phylogenetic estimations based on these data remain uncertain due to insufficient taxon sampling and accelerated rates of evolution, the mtDNA molecules themselves reveal interesting traits that may be unique to hexactinellids. Here we determined the first complete mitochondrial genome of a hexactinellid sponge, <it>Aphrocallistes vastus</it>, and compared it to published poriferan mtDNAs to further describe characteristics specific to hexactinellid and other sponge mitochondrial genomes.</p> <p>Results</p> <p>The <it>A. vastus </it>mtDNA consisted of a 17,427 base pair circular molecule containing thirteen protein-coding genes, divergent large and small subunit ribosomal RNAs, and a reduced set of 18 tRNAs. The <it>A. vastus </it>mtDNA showed a typical hexactinellid nucleotide composition and shared a large synteny with the other sequenced glass sponge mtDNAs. It also contained an unidentified open reading frame and large intergenic space region. Two frameshifts, in the <it>cox3 </it>and <it>nad6 </it>genes, were not corrected by RNA editing, but rather possessed identical shift sites marked by the extremely rare tryptophan codon (UGG) followed by the common glycine codon (GGA) in the +1 frame.</p> <p>Conclusion</p> <p>Hexactinellid mtDNAs have shown similar trends in gene content, nucleotide composition, and codon usage, and have retained a large gene syntenty. Analysis of the mtDNA of <it>A. vastus </it>has provided evidence diagnostic for +1 programmed translational frameshifting, a phenomenon disparately reported throughout the animal kingdom, but present in the hexactinellid mtDNAs that have been sequenced to date.</p

Generation of Antibodies Selectively Recognizing Epitopes in a Formaldehyde-Fixed Cell-Surface Antigen Using Virus-like Particle Display and Hybridoma Technology

Efficient induction of target-specific antibodies can be elicited upon immunization with highly immunogenic virus-like particles (VLPs) decorated with desired membrane-anchored target antigens (Ags). However, for example, for diagnostic purposes, monoclonal antibodies (mAbs) are required to enable the histological examination of formaldehyde-fixed paraffin-embedded (FFPE) biopsy tissue samples. Aiming at the generation of FFPE-antigen-specific mAbs and as a proof of concept (POC), we first established a simplified protocol using only formaldehyde and 90 °C heat fixation (FF90) of cells expressing the target Ag nerve growth factor receptor (NGFR). The FF90 procedure was validated using flow cytometric analysis and two mAbs recognizing either the native and FFPE-Ag or exclusively the native Ag. C-terminally truncated NGFR (trNGFR)-displaying native and FF90-treated VLPs derived from HIV-1 did not reveal distinctive changes in particle morphology using transmission electron microscopy (TEM) and dynamic light scattering (DLS) analysis. Mice were subsequently repetitively immunized with trNGFR-decorated FF90-VLPs and hybridoma technology was used to establish mAb-producing cell clones. In multiple screening rounds, nine cell clones were identified producing mAbs distinctively recognizing epitopes in FF90- and FFPE-NGFR. This POC of a new methodology should foster the future generation of mAbs selectively targeting FFPE-fixed cell-surface Ags

Reproducibility of shear wave elastography measuresof the Achilles tendon.

OBJECTIVE To assess the reproducibility of shear wave elastography (SWE) measures in the Achilles tendon (AT) in vivo. MATERIALS AND METHODS Shear wave velocity (SWV) of 14 healthy volunteers [7 males, 7 females; mean age 26.5 ± 3.8 years, mean height 171.6 ± 10.9 cm, mean Victorian Institute of Sports Assessment Achilles questionnaire (VISA-A) score 99.4 ± 1.2] was measured with the foot relaxed and fixed at 90°. Data were collected over five consecutive measures and 5 consecutive days. RESULTS Mean SWV values ranged from 7.91 m/s-9.56 m/s ± 0.27-0.50 m/s. Coefficient of variation (CV), correlations and intra-class correlation coefficient (ICC) scores ranged from 2.9%-6.3%, 0.4-0.7 and 0.54-0.85 respectively. No significant differences were noted for longitudinal or transverse data with respect to protocol or time and no significant differences were noted for foot position in transverse data. Significant differences in SWV values were noted between foot positions for longitudinal scanning (p = <0.05), with a relaxed foot position providing SWV values on average 0.47 m/s faster than a fixed position. Increased reproducibility was obtained with the foot relaxed. ICC between operators was 0.70 for transverse and 0.80 for longitudinal scanning. CONCLUSIONS Reproducible SWE measures were obtained over a 1-h period as well as a period of 5 consecutive days with more reliable measures obtained from a longitudinal plane using a relaxed foot position. SWE also has a high level of agreement between operators making SWE a reproducible technique for quantitatively assessing the mechanical properties of the human AT in vivo

Configuring the PrEP user: Framing Pre-exposure Prophylaxis in UK newsprint 2012 – 2016

Pre-exposure prophylaxis (PrEP) has been hailed as a revolutionary intervention for HIV prevention. PrEP’s controversial status in the UK has generated significant media coverage. It is important to understand what role the media plays in framing PrEP policy issues. We undertook a qualitative analysis of UK newsprint articles between 2012 and 2016 to examine how PrEP was framed as a public health intervention up until a controversial policy decision not to provide PrEP in England. We identified how scientific evidence was deployed to shape two narratives: ir/responsible citizens focused on imagined PrEP users and their capacity to use PrEP effectively; and the public health imperative, which described the need for PrEP. Our analysis demonstrates the particular ways in which scientific evidence contributed to the certainty of PrEP as an effective intervention within UK newsprint. Scientific evidence also played a key role in framing PrEP as an intervention specifically for cis-gendered gay and bisexual men, playing into wider debates about who is a deserving patient and the appropriate use of public resources. Practitioners in the UK and elsewhere should be aware of these constructions of the PrEP user to ensure equitable access to PrEP beyond gay and bisexual men

Long Term Efficacy and Safety of Bronchoscopic Thermal Vapor Ablation in Patients with COPD: A Retrospective Study of 50 Patients

Barak Pertzov,1– 4 Merav Ben Avraham,1,2 Eldar Priel,3– 5 Lev Freidkin,1,2 Dror Rosengarten,1,2 Mordechai Reuven Kramer1,2 1Pulmonary Division, Rabin Medical Center, Petach Tikva, Israel; 2Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; 3Firestone Institute for Respiratory Health, St Joseph’s Healthcare, Hamilton, ON, Canada; 4Department of Medicine, McMaster University, Hamilton, ON, Canada; 5Division of Thoracic Surgery, St. Joseph’s Healthcare, Hamilton, ON, CanadaCorrespondence: Barak Pertzov, Pulmonary Division, Rabin Medical Center, Beilinson Campus, 39 Jabotinski St, Petach Tikva, 4941492, Israel, Tel +972-3-9377221/3, Fax +972-3-9242091, Email [email protected]: Bronchoscopic Thermal Vapor Ablation (BTVA) has demonstrated improvements in FEV1 and quality of life in clinical trials. However, the long-term benefits and overall efficacy of this procedure remain uncertain and are not yet fully established.Methods: We conducted a retrospective observational study of all patients who underwent BTVA at Rabin Medical Center, Israel. The primary outcome was the change in FEV₁ from baseline. Secondary outcomes included other pulmonary function parameters and procedural adverse events.Results: A total of 50 patients were included in the study. The mean FEV1 values at baseline, 6 months, and 12 months post-procedure (n=31) were 0.74± 0.21 L, 0.93± 0.32 L, and 0.85± 0.25 L, respectively (overall P&lt; 0.001; pairwise comparisons: baseline to 6 months, P&lt; 0.001; baseline to 12 months, P=0.016). The mean FVC values at baseline, 6 months, and 12 months post-procedure (n=31) were 1.97± 0.56 L, 2.27± 0.71 L, and 2.14± 0.68 L, respectively (overall P=0.003; pairwise comparisons: baseline to 6 months, P=0.002; baseline to 12 months, P=0.125). Post-procedural complications included pneumonia in 5 patients (11%), of whom 3 developed necrotizing pneumonia and subsequently died, resulting in a 6% post-procedural mortality rate in the entire cohort. Hemoptysis was reported in 1 patient (2%).Conclusion: Bronchoscopic thermal vapor ablation is a minimally invasive bronchoscopic intervention for lung volume reduction. The procedure was associated with significant improvements in FEV₁ at 6 to 12 months and in FVC at 6 months, followed by a gradual decline over 12 to 24 months. Further research is warranted to optimize patient selection, enhance procedural safety, and assess long-term efficacy.Plain Language Summary: COPD is a disease that damages lung tissue. The damaged areas become hyperinflated, compressing healthier parts of the lung and reducing their function. Bronchoscopic Thermal Vapor Ablation (BTVA) is a minimally invasive treatment that uses heated water vapor to target and shrink these damaged areas. During the procedure, a thin tube with a camera (bronchoscope) is inserted into the lungs to deliver vapor directly to diseased regions. The vapor causes controlled injury, leading to shrinkage of the targeted tissue and allowing healthier lung areas to expand and function more effectively. BTVA can be repeated by treating different regions over time, potentially maintaining its benefits.In this study, we evaluated the effectiveness and safety of BTVA in patients with advanced COPD. Lung function improved significantly at 6 and 12 months compared to baseline. Between 12 and 24 months, the benefits gradually declined but remained above baseline.Side effects were primarily pneumonia and temporary coughing up of blood, which resolved in most cases. However, three patients developed severe pneumonia and died, highlighting the need for further research.In conclusion, BTVA improved lung function, but careful selection of treatment areas and energy levels is important to reduce complications and enhance safety.Keywords: COPD, emphysema, BLVR, BTVA, vapor, FEV1, safet

Rethinking the Poverty-disease Nexus: the Case of HIV/AIDS in South Africa

While it is well-established that poverty and disease are intimately connected, the nature of this connection and the role of poverty in disease causation remains contested in scientific and social studies of disease. Using the case of HIV/AIDS in South Africa and drawing on a theoretically grounded analysis, this paper reconceptualises disease and poverty as ontologically entangled. In the context of the South African HIV epidemic, this rethinking of the poverty-disease dynamic enables an account of how social forces such as poverty become embodied in the very substance of disease to produce ontologies of HIV/AIDS unique to South Africa