Ventilator-induced lung injury: historical perspectives and clinical implications

Mechanical ventilation can produce lung physiological and morphological alterations termed ventilator-induced lung injury (VILI). Early experimental studies demonstrated that the main determinant of VILI is lung end-inspiratory volume. The clinical relevance of these experimental findings received resounding confirmation with the results of the acute respiratory distress syndrome (ARDS) Network study, which showed a 22% reduction in mortality in patients with the acute respiratory distress syndrome through a simple reduction in tidal volume. In contrast, the clinical relevance of low lung volume injury remains debated and the application of high positive end-expiratory pressure levels can contribute to lung overdistension and thus be deleterious. The significance of inflammatory alterations observed during VILI is debated and has not translated into clinical application. This review examines seminal experimental studies that led to our current understanding of VILI and contributed to the current recommendations in the respiratory support of ARDS patients

An epidemiological study of pleuropulmonary paragonimiasis among pupils in the peri-urban zone of Kumba town, Meme Division, Cameroon

BACKGROUND: Paragonimiasis have previously been reported in two zones of the Southwest Province of Cameroon including the Kupe mountain and Mundani foci. The aim of this study was to investigate the presence and epidemiology of paragonimiasis in the peri-urban zone of Kumba, Meme Division, located about 50 km away from the Kupe mountain focus. METHODS: Pupils of several government primary schools in 5 villages around Kumba underwent both parasitologic and clinical investigations in search of signs and symptoms of paragonimiasis. Mycobacterium tuberculosis was also searched for in the differential diagnosis.Freshwater crabs from neighbouring streams in the five villages were dissected in search of paragonimus metacercariae. RESULTS: Out of a total of 1482 pupils examined in all five villages, 309 individuals (147 males and 162 females) were recruited for this study based on the presence of one or more signs or symptoms of paragonimiasis. Eggs of Paragonimus africanus were found in stools and/or sputum of pupils from all five villages, giving an overall paragonimus prevalence of 2.56%. There was no significant difference in the disease prevalence between the villages (X(2 )= 8.36, P = 0.08). The prevalence of Paragonimus africanus eggs amongst pupils with symptoms of paragonimiasis was 12.3% (38 of 309). Males were infected more than females (17.0% versus 8.0%), but the difference was not significant (X(2 )= 5.76, P = 0.16). All the 38 paragonimus egg positive subjects presented with cough, 23 (60.53%) complained of chest pain while 16 (42.11%) had haemoptysis. Stool examinations also detected some intestinal parasites including Ascaris lumbricoides (29.45%), Trichuris trichiura (6.47%), Necator americanus (2.27%), Strongyloides stercoralis (1.62%), Enterobius vermicularis (0.65%), and Entamoeba histolytica (4.53%). No case of M. tuberculosis was noted. Out of a total of 85 dissected crabs (Sudanonautes africanus), 6.02 % were infected with paragonimus metacercariae. CONCLUSION: In addition to the two previously described paragonimiasis foci of Kupe mountain and Mundani, the identification of autochthonous cases of paragonimiasis in the peri-urban zone of Kumba town, makes the South West Province the most endemic zone of paragonimiasis in Cameroon at present

Comparative Analysis of mRNA Targets for Human PUF-Family Proteins Suggests Extensive Interaction with the miRNA Regulatory System

Genome-wide identification of mRNAs regulated by RNA-binding proteins is crucial to uncover post-transcriptional gene regulatory systems. The conserved PUF family RNA-binding proteins repress gene expression post-transcriptionally by binding to sequence elements in 3′-UTRs of mRNAs. Despite their well-studied implications for development and neurogenesis in metazoa, the mammalian PUF family members are only poorly characterized and mRNA targets are largely unknown. We have systematically identified the mRNAs associated with the two human PUF proteins, PUM1 and PUM2, by the recovery of endogenously formed ribonucleoprotein complexes and the analysis of associated RNAs with DNA microarrays. A largely overlapping set comprised of hundreds of mRNAs were reproducibly associated with the paralogous PUM proteins, many of them encoding functionally related proteins. A characteristic PUF-binding motif was highly enriched among PUM bound messages and validated with RNA pull-down experiments. Moreover, PUF motifs as well as surrounding sequences exhibit higher conservation in PUM bound messages as opposed to transcripts that were not found to be associated, suggesting that PUM function may be modulated by other factors that bind conserved elements. Strikingly, we found that PUF motifs are enriched around predicted miRNA binding sites and that high-confidence miRNA binding sites are significantly enriched in the 3′-UTRs of experimentally determined PUM1 and PUM2 targets, strongly suggesting an interaction of human PUM proteins with the miRNA regulatory system. Our work suggests extensive connections between the RBP and miRNA post-transcriptional regulatory systems and provides a framework for deciphering the molecular mechanism by which PUF proteins regulate their target mRNAs