Six-month outcomes after individualized nutritional support during the hospital stay in medical patients at nutritional risk: Secondary analysis of a prospective randomized trial.

BACKGROUND Among medical inpatients at risk of malnutrition, the use of individualized nutritional support during the hospital stay was found to reduce complications and improve mortality at short-term. We evaluated clinical outcomes at 6-months follow-up. METHODS We randomly assigned 2028 patients to receive protocol-guided individualized nutritional support to reach protein and energy goals (intervention group) or hospital food as usual (control group) during the hospital stay. The intervention was discontinued at hospital discharge and further nutritional support was based on the discretion of the treating team. We had complete follow-up information of 1995 patients (98%), which were included in the final analysis. The primary endpoint was all-cause mortality at 6-months. Prespecified secondary end points included non-elective hospital readmissions, functional outcome and quality of life. RESULTS At 6-month, 231 of 994 (23.2%) intervention group patients had died compared to 246 of 999 (24.6%) control group patients, resulting in a hazard ratio for death of 0.90 (95%CI 0.76 to 1.08, p = 0.277). Compared to control patients, intervention group patients had similar rates of hospital readmission (27.3% vs. 27.6%, HR 1.00 (95%CI 0.84 to 1.18), p = 0.974), falls (11.2% vs. 10.9%, HR 0.96 (95%CI 0.72 to 1.27), p = 0.773) and similar quality of life and activities of daily living scores. INTERPRETATION While individualized nutritional support during the hospital stay significantly reduced short-term mortality, there was no legacy effect on longer term outcomes. Future trials should investigate whether continuation of nutritional support after hospital discharge reduces the high malnutrition-associated mortality rates in this vulnerable patient population. TRIAL REGISTRATION ClinicalTrials.gov number, NCT02517476

microRNA-122 stimulates translation of hepatitis C virus RNA

Hepatitis C virus (HCV) is a positive strand RNA virus that propagates primarily in the liver. We show here that the liver-specific microRNA-122 (miR-122), a member of a class of small cellular RNAs that mediate post-transcriptional gene regulation usually by repressing the translation of mRNAs through interaction with their 3′-untranslated regions (UTRs), stimulates the translation of HCV. Sequestration of miR-122 in liver cell lines strongly reduces HCV translation, whereas addition of miR-122 stimulates HCV translation in liver cell lines as well as in the non-liver HeLa cells and in rabbit reticulocyte lysate. The stimulation is conferred by direct interaction of miR-122 with two target sites in the 5′-UTR of the HCV genome. With a replication-defective NS5B polymerase mutant genome, we show that the translation stimulation is independent of viral RNA synthesis. miR-122 stimulates HCV translation by enhancing the association of ribosomes with the viral RNA at an early initiation stage. In conclusion, the liver-specific miR-122 may contribute to HCV liver tropism at the level of translation

The safety and applicability of synthetic pyrethroid insecticides for aircraft disinsection: A systematic review

BACKGROUND Air travel contributes to the global spread of vectors and vector-borne infections. Although WHO provides guidance on methods for disinsection of aircraft, there is currently no harmonized or standardized decision-making process to decide when disinsection of an aircraft should be conducted. It is however compulsory for flights arriving in certain countries. Concerns have been expressed about the usefulness of disinsection for preventing the international spread of vectors and vector-borne diseases via air travel and possible toxicity for passengers and flight crew. METHODS We performed a systematic literature review using the databases PubMed, Embase, Medline, Scopus and CINAHL to evaluate all research findings about the applicability and safety of chemical-based, aircraft disinsection. Official reports from the WHO were also screened. This systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and meta-analysis (PRISMA) statement. The literature search strategy included "disinsection, airplane/plane/aviation/aircraft" and several other search items including d-phenothrin, permethrin, insecticide. Papers in English, French and German were reviewed. Reports of adverse events attributed to the disinsection of aircraft were also searched. AMP and PS screened all papers of relevance and agreed on a final selection. RESULTS Our search resulted in 440 papers of possible relevance. After screening, we included a total of 25 papers in this systematic review. Ten papers reported possible human toxicity and 17 papers addressed the applicability of disinsection and 2 papers addressed both topics. Chemical disinsection at recommended insecticide concentrations was found to be highly effective against a broad range of arthropods. Three papers reported passenger or crew illness possibly associated with insecticide spraying in passenger cabins - one describing a single passenger, the other two papers describing occupational illness of 12 and 33 aircrew members respectively, possibly due to aircraft disinsection. Another paper evaluating exposure of flight attendants to permethrin found higher levels of urinary metabolites in those working in planes that had recently been sprayed but this could not be linked to adverse health outcomes. CONCLUSION Our analysis confirmed that disease vectors are carried on international flights and can pose a threat particularly to island populations and certain airport hub areas. Disinsection with permethrin or d-phenothrin was shown to be highly effective against vectors. Despite several hundred million passenger and crew exposures to chemical disinsection, very few proven cases of toxicity have been reported. There is limited evidence linking exposure to insecticide spraying with negative health impact

Correction: microRNA-122 Dependent Binding of Ago2 Protein to Hepatitis C Virus RNA Is Associated with Enhanced RNA Stability and Translation Stimulation.

[This corrects the article DOI: 10.1371/journal.pone.0056272.]

Concern for fairness and incentives in water negotiations

This paper focuses on transboundary water resources and investigates the presence of incentives to cooperate in investment projects for improving water availability. Investments over transboundary water cannot be always protected by suitable contractual arrangements because countries’ actions cannot be monitored and enforced by a third party. In such a case, the traditional literature predicts that cooperation rarely emerges due to the risk of ex-post opportunistic behaviours by the parties. This prediction does not provide a satisfactory representation of many real-world situations in which riparian countries have demonstrated a remarkable ability to cooperate over their shared water resources. This paper shows that it is possible to reconcile the empirical evidence with the theoretical approach if one assumes that countries display some concern for ‘fairness’ when negotiating, which depends on their initial level of investment. Within the proposed framework, the incentives to cooperate turn out to be higher than traditional literature predicts because, by engaging in the investment project, countries do not only increase the amount of water effectively available, but also—through their concern for fairness—the share of water obtainable at the bargaining table

microRNA-122 Dependent Binding of Ago2 Protein to Hepatitis C Virus RNA Is Associated with Enhanced RNA Stability and Translation Stimulation

<div><p>Translation of Hepatitis C Virus (HCV) RNA is directed by an internal ribosome entry site (IRES) in the 5′-untranslated region (5′-UTR). HCV translation is stimulated by the liver-specific microRNA-122 (miR-122) that binds to two binding sites between the stem-loops I and II near the 5′-end of the 5′-UTR. Here, we show that Argonaute (Ago) 2 protein binds to the HCV 5′-UTR in a miR-122-dependent manner, whereas the HCV 3′-UTR does not bind Ago2. miR-122 also recruits Ago1 to the HCV 5’-UTR. Only miRNA duplex precursors of the correct length stimulate HCV translation, indicating that the duplex miR-122 precursors are unwound by a complex that measures their length. Insertions in the 5′-UTR between the miR-122 binding sites and the IRES only slightly decrease translation stimulation by miR-122. In contrast, partially masking the miR-122 binding sites in a stem-loop structure impairs Ago2 binding and translation stimulation by miR-122. In an RNA decay assay, also miR-122-mediated RNA stability contributes to HCV translation stimulation. These results suggest that Ago2 protein is directly involved in loading miR-122 to the HCV RNA and mediating RNA stability and translation stimulation.</p> </div