Late Glacial and Holocene Palaeolake History of the Última Esperanza Region of Southern Patagonia

We undertook multi-proxy analyses on two sediment cores from Lago Pato, a small lake basin at 51°S topographically separated from Lago del Toro in Torres del Paine (TdP), to provide insights into glacier dynamics and lake-level change in the TdP and Última Esperanza region over the last ∼30,000 cal a BP (30 ka). Lago Pato is situated in a region overridden by the Southern Patagonian Ice Field during the Last Glacial and in a transitional climatic zone of Southern Patagonia sensitive to seasonal- to millennial-scale changes in the Southern Hemisphere Westerly Winds (SWW). Results show that a deep ice-dammed and enlarged palaeolake encompassed Lago del Toro and Lago Pato c. 30–20 ka after the ice had retreated from local-Last Glacial Maximum (l-LGM) limits at c. 48–34 ka and during the build-up to the global-Last Glacial Maximum (g-LGM), c. 26–19 ka. Gaps in both sediment records between c. 20–13.4 ka and c. 20–10 ka suggest hiatuses in sediment accumulation during the g-LGM and Antarctic Cold Reversal (ACR) readvances and/or removal by lake lowering or flushing during the Late Glacial–early Holocene. The palaeolake level dropped from >100 m a.s.l. to ∼40–50 m a.s.l. towards the end of the ACR c. 13.4–13.0 ka, creating a shallower glaciolacustrine environment dammed by an ice tongue in the Estancia Puerto Consuelo–Última Esperanza fjord. Further lowering of the enlarged palaeolake level occurred when the ice thinned to <40 m a.s.l., eventually isolating Lago Pato from Lago del Toro and glaciogenic sediment input at c. 11.7 ka. After isolation, the ecology and water levels in Lago Pato became sensitive to regional climate shifts. The shallow, stable, and highly anoxic environment that developed after c. 11.7 ka is associated with weaker (or poleward shifted) SWW at 51°S and was replaced at c. 10 ka by an increasingly productive shallow-littoral lake with a variable lake-level and periodic shifts in anoxic-oxic bottom water conditions and ratios of benthic-planktonic diatoms. A more open Nothofagus forest, established at c. 8.6–7.5 ka, and more arid conditions c. 7.5–5.7 cal ka BP are linked to another phase of weaker (or poleward shifted) SWW at 51°S. More persistently wet conditions from c. 5.7 ka, with extensive closed Nothofagus forests and planktonic diatoms dominant, are associated with stronger (or equatorward shifted) SWW over 51°S. The abrupt return of benthic-to-tychoplanktonic diatoms after c. 3 ka reflects enhanced SWW at 51°S. Increasingly stable lacustrine and littoral wetland conditions established in the last ∼500 years reflect weaker SWW and lasted until recent decades

Prevention of ventilator-associated pneumonia with oral antiseptics : a systematic review and meta-analysis

Background: We did a systematic review and random effects meta-analysis of randomised trials to assess the effect of oral care with chlorhexidine or povidone-iodine on the prevalence of ventilator-associated pneumonia versus oral care without these antiseptics in adults. Methods: Studies were identified through PubMed, CINAHL, Web of Science, CENTRAL, and complementary manual searches. Eligible studies were randomised trials of mechanically ventilated adult patients receiving oral care with chlorhexidine or povidone-iodine. Relative risks (RR) and 95% CIs were calculated with the Mantel-Haenszel model and heterogeneity was assessed with the 12 test. Findings: 14 studies were included (2481 patients), 12 investigating the effect of chlorhexidine (2341 patients) and two of povidone-iodine (140 patients). Overall, antiseptic use resulted in a significant risk reduction of ventilator-associated pneumonia (RR 0.67; 95% CI 0.50-0.88; p=0.004). Chlorhexidine application was shown to be effective (RR 0.72; 95% CI 0.55-0.94; p=0.02), whereas the effect resulting from povidone-iodine remains unclear (RR 0.39; 95% CI 0.11-1.36; p=0.14). Heterogeneity was moderate (I(2)=29%; p=0.16) for the trials using chlorhexidine and high (I(2)=67%; p=0.08) for those assessing povidone-iodine use. Favourable effects were more pronounced in subgroup analyses for 2% chlorhexidine (RR 0.53, 95% CI 0.31-0.91), and in cardiosurgical studies (RR 0.41, 95% CI 0.17-0.98). Interpretation: This analysis showed a beneficial effect of oral antiseptic use in prevention of ventilator-associated pneumonia. Clinicians should take these findings into account when providing oral care to intubated patients

Nurses’ Sedation Practices During Weaning of Adults From Mechanical Ventilation in an Intensive Care Unit

Background: Sedation and analgesia have an important impact on the outcome of patients treated with mechanical ventilation. International guidelines recommend use of sedation protocols to ensure best patient care. Objective: To determine the sedation practice of intensive care nurses weaning adults from mechanical ventilation. Methods: A cross-sectional survey with a self-administered questionnaire was used to determine sedation practices of Flemish critical care nurses during weaning. Consensus on content validity was achieved through a Delphi procedure among experts. Data were collected during the 32nd Annual Congress of the Flemish Society of Critical Care Nurses in Ghent, Belgium, December 2014. Results: A total of 342 nurses were included in the study. Of these, 43.7% had a sedation protocol in their unit that was used by 61.8% of the respondents. Sedation protocols were more often available (P<.001) in academic hospitals (72%) than in general hospitals (41.5%). Sedatives were administered via continuous infusion with bolus doses if needed (81%). Level of sedation was assessed every 2 hours (56%), mostly via the Richmond Agitation-Sedation Scale (59.1%). Daily interruption of sedation was used by 16.5% of respondents. The biggest barriers to daily interruption were patient comfort (49.4%) and fear of respiratory worsening (46.6%). Conclusions: A considerable discrepancy exists between international recommendations and actual sedation practices. Standardization of sedation practices across different institutions on a regional and national level may improve the quality of care

Cationic amphiphilic drugs boost the lysosomal escape of small nucleic acid therapeutics in a nanocarrier-dependent manner

Small nucleic acid (NA) therapeutics, such as small interfering RNA (siRNA), are generally formulated in nanoparticles (NPs) to overcome the multiple extra- and intracellular barriers upon in vivo administration. Interaction with target cells typically triggers endocytosis and sequesters the NPs in endosomes, thus hampering the pharmacological activity of the encapsulated siRNAs that occurs in the cytosol. Unfortunately, for most state-of-the-art NPs, endosomal escape is largely inefficient. As a result, the bulk of the endocytosed NA drug is rapidly trafficked toward the degradative lysosomes that are considered as a dead end for siRNA nanomedicines. In contrast to this paradigm, we recently reported that cationic amphiphilic drugs (CADs) could strongly promote functional siRNA delivery from the endolysosomal compartment via transient induction of lysosomal membrane permeabilization. However, many questions still remain regarding the broader applicability of such a CAD adjuvant effect on NA delivery. Here, we report a drug repurposing screen (National Institutes of Health Clinical Collection) that allowed identification of 56 CAD adjuvants. We furthermore demonstrate that the CAD adjuvant effect is dependent on the type of nanocarrier, with NPs that generate an appropriate pool of decomplexed siRNA in the endolysosomal compartment being most susceptible to CAD-promoted gene silencing. Finally, the CAD adjuvant effect was verified on human ovarian cancer cells and for antisense oligonucleotides. In conclusion, this study strongly expands our current knowledge on how CADs increase the cytosolic release of small NAs, providing relevant insights to more rationally combine CAD adjuvants with NA-loaded NPs for future therapeutic applications