Developmental energetics: Energy expenditure, budgets and metabolism during animal embryogenesis.

Developing embryos are metabolically active, open systems that constantly exchange matter and energy with their environment. They function out of thermodynamic equilibrium and continuously use metabolic pathways to obtain energy from maternal nutrients, in order to fulfill the energetic requirements of growth and development. While an increasing number of studies highlight the role of metabolism in different developmental contexts, the physicochemical basis of embryogenesis, or how cellular processes use energy and matter to act together and transform a zygote into an adult organism, remains unknown. As we obtain a better understanding of metabolism, and benefit from current technology development, it is a promising time to revisit the energetic cost of development and how energetic principles may govern embryogenesis. Here, we review recent advances in methodology to measure and infer energetic parameters in developing embryos. We highlight a potential common pattern in embryonic energy expenditure and metabolic strategy across animal embryogenesis, and discuss challenges and open questions in developmental energetics.

The Impact of Drosophila Awd/NME1/2 Levels on Notch and Wg Signaling Pathways.

Awd, the Drosophila homologue of NME1/2 metastasis suppressors, plays key roles in many signaling pathways. Mosaic analysis of the null awdJ2A4 allele showed that loss of awd gene function blocks Notch signaling and the expression of its target genes including the Wingless (Wg/Wnt1) morphogen. We also showed that RNA interference (RNAi)-mediated awd silencing (awdi) in larval wing disc leads to chromosomal instability (CIN) and to Jun amino-terminal kinases (JNK)-mediated cell death. Here we show that this cell death is independent of p53 activity. Based on our previous finding showing that forced survival of awdi-CIN cells leads to aneuploidy without the hyperproliferative effect, we investigated the Wg expression in awdi wing disc cells. Interestingly, the Wg protein is expressed in its correct dorso-ventral domain but shows an altered cellular distribution which impairs its signaling. Further, we show that RNAi-mediated knock down of awd in wing discs does not affect Notch signaling. Thus, our analysis of the hypomorphic phenotype arising from awd downregulation uncovers a dose-dependent effect of Awd in Notch and Wg signaling.

Mortality in Patients With Septic Shock by Multidrug Resistant Bacteria: Risk Factors and Impact of Sepsis Treatments.

BACKGROUND:: Patients with septic shock by multidrug resistant (MDR) microorganism maybe considered a specific population of critical patients at very high risk of death in whom the effects of standard sepsis treatment has never been assessed. The objective of this retrospective analysis was to evaluate the risk factors for 30-day mortality and the impact of sepsis management in patients with septic shock caused by MDR bacteria. METHODS:: Patients with septic shock by MDR bacteria admitted to the mixed intensive care unit (ICU) of Modena University Hospital during a 6-year period were studied. The clinical and microbiological characteristics and sepsis treatments provided were analyzed and compared between survivors (S) and nonsurvivors (NS) at 30 days after septic shock appearance. RESULTS:: Ninety-four patients were studied. All therapeutic interventions applied to patients during their ICU stay did not show statistical significance between S and NS groups, except for administration of immunoglobulin M (IgM) preparation which were provided more frequently in S group ( P < .05). At the multivariate adjusted analysis, preexisting cancer (odds ratio [OR] = 2.965) and Acinetobacter baumannii infections (OR = 3.197) were independently correlated with an increased risk of 30-day mortality, whereas treatment with IgM preparation was protective (OR = 0.283). CONCLUSIONS:: This retrospective study showed that in patients with septic shock caused by MDR bacteria, history of cancer and infection sustained by A baumannii increase the risk of mortality and that standard sepsis treatments do not seem to provide any protective effect. Adjunctive therapy with IgM preparation seems to be beneficial, but further appropriate studies are needed to confirm the results observed.

A polydnavirus-encoded ANK protein has a negative impact on steroidogenesis and development.

Polydnaviruses (PDV) are viral symbionts associated with ichneumonid and braconid wasps parasitizing moth larvae, which are able to disrupt the host immune response and development, as well as a number of other physiological pathways. The immunosuppressive role of PDV has been more intensely investigated, while very little is known about the PDV-encoded factors disrupting host development. Here we address this research issue by further expanding the functional analysis of ankyrin genes encoded by the bracovirus associated with Toxoneuron nigriceps (Hymenoptera, Braconidae). In a previous study, using Drosophila melanogaster as experimental model system, we demonstrated the negative impact of TnBVank1 impairing the ecdysone biosynthesis by altering endocytic traffic in prothoracic gland cells. With a similar approach here we demonstrate that another member of the viral ank gene family, TnBVank3, does also contribute to the disruption of ecdysone biosynthesis, but with a completely different mechanism. We show that its expression in Drosophila prothoracic gland (PG) blocks the larval-pupal transition by impairing the expression of steroidogenic genes. Furthermore, we found that TnBVank3 affects the expression of genes involved in the insulin/TOR signaling and the constitutive activation of the insulin pathway in the PG rescues the pupariation impairment. Collectively, our data demonstrate that TnBVANK3 acts as a virulence factor by exerting a synergistic and non-overlapping function with TnBVANK1 to disrupt the ecdysone biosynthesis.

The Role of Adjunctive Therapies in Septic Shock by Gram Negative MDR/XDR Infections.

Patients with septic shock by multidrug resistant microorganisms (MDR) are a specific sepsis population with a high mortality risk. The exposure to an initial inappropriate empiric antibiotic therapy has been considered responsible for the increased mortality, although other factors such as immune-paralysis seem to play a pivotal role. Therefore, beyond conventional early antibiotic therapy and fluid resuscitation, this population may benefit from the use of alternative strategies aimed at supporting the immune system. In this review we present an overview of the relationship between MDR infections and immune response and focus on the rationale and the clinical data available on the possible adjunctive immunotherapies, including blood purification techniques and different pharmacological approaches.

Effect of performance improvement programs on compliance with sepsis bundles and mortality: a systematic review and meta-analysis of observational studies.

BACKGROUND: Several reports suggest that implementation of the Surviving Sepsis Campaign (SSC) guidelines is associated with mortality reduction in sepsis. However, adherence to the guideline-based resuscitation and management sepsis bundles is still poor. OBJECTIVE: To perform a systematic review of studies evaluating the impact of performance improvement programs on compliance with Surviving Sepsis Campaign (SSC) guideline-based bundles and/or mortality. DATA SOURCES: Medline (PubMed), Scopus and Intercollegiate Studies Institute Web of Knowledge databases from 2004 (first publication of the SSC guidelines) to October 2014. STUDY SELECTION: Studies on adult patients with sepsis, severe sepsis or septic shock that evaluated changes in compliance to individual/combined bundle targets and/or mortality following the implementation of performance improvement programs. Interventions may consist of educational programs, process changes or both. DATA EXTRACTION: Data from the included studies were extracted independently by two authors. Unadjusted binary data were collected in order to calculate odds ratios (OR) for compliance to individual/combined bundle targets. Adjusted (if available) or unadjusted data of mortality were collected. Random-effects models were used for the data synthesis. RESULTS: Fifty observational studies were selected. Despite high inconsistency across studies, performance improvement programs were associated with increased compliance with the complete 6-hour bundle (OR = 4.12 [95% confidence interval 2.95-5.76], I(2) = 87.72%, k = 25, N = 50,081) and the complete 24-hour bundle (OR = 2.57 [1.74-3.77], I(2) = 85.22%, k = 11, N = 45,846) and with a reduction in mortality (OR = 0.66 [0.61-0.72], I(2) = 87.93%, k = 48, N = 434,447). Funnel plots showed asymmetry. CONCLUSIONS: Performance improvement programs are associated with increased adherence to resuscitation and management sepsis bundles and with reduced mortality in patients with sepsis, severe sepsis or septic shock.

Early therapy with IgM-enriched polyclonal immunoglobulin in patients with septic shock.

PURPOSE: To determine whether there was an association between adjunctive therapy with IgM-enriched immunoglobulin (IgM) and the 30-day mortality rate in patients with septic shock. METHODS: In 2008 we introduced IgM as a possible adjunctive therapy to be provided within 24 h after shock onset in the management protocol for patients with septic shock. In this retrospective study we included the adult patients suitable for IgM therapy admitted to our ICU from January 2008 to December 2011. An unadjusted comparison between patients who did or did not receive IgM therapy, a multivariate logistic model adjusted for confounders and propensity score-based matching were used to evaluate the association between early IgM treatment and mortality. RESULTS: One hundred and sixty-eight patients were included in the study. Of these, 92 (54.8%) received IgM therapy. Patients who did or did not receive IgM were similar with regards to infection characteristics, severity scores and sepsis treatment bundle compliance. Patients who received IgM were more likely to have blood cultures before antibiotics and to attain a plateau inspiratory pressure less than 30 cmH2O (p < 0.05). The 30-day mortality rate was reduced by 21.1% (p < 0.05) in the group that received IgM compared to the group that did not. The multivariate adjusted regression model (OR 0.17; CI 95% 0.06-0.49; p = 0.001) and the propensity score-based analysis (OR 0.35; CI 95% 0.14-0.85; p = 0.021) confirmed that IgM therapy was associated with reduced mortality at 30 days after the onset of septic shock. CONCLUSIONS: Our experience indicates that early adjunctive treatment with IgM may be associated with a survival benefit in patients with septic shock. However, additional studies are needed to better evaluate the role of IgM therapy in the early phases of septic shock.