Hypoxaemia as a Mortality Risk Factor in Acute Lower Respiratory Infections in Children in Low and Middle-Income Countries: Systematic Review and Meta-Analysis

Objective

To evaluate the association between hypoxaemia and mortality from acute lower respiratory infections (ALRI) in children in low- and middle-income countries (LMIC).

Design

Systematic review and meta-analysis.

Study Selection

Observational studies reporting on the association between hypoxaemia and death from ALRI in children below five years in LMIC.

Data Sources

Medline, Embase, Global Health Library, Lilacs, and Web of Science to February 2015.

Risk of Bias Assessment

Quality In Prognosis Studies tool with minor adaptations to assess the risk of bias; funnel plots and Egger’s test to evaluate publication bias.

Results

Out of 11,627 papers retrieved, 18 studies from 13 countries on 20,224 children met the inclusion criteria. Twelve (66.6%) studies had either low or moderate risk of bias. Hypoxaemia defined as oxygen saturation rate (SpO2) <90% associated with significantly increased odds of death from ALRI (OR 5.47, 95% CI 3.93 to 7.63) in 12 studies on 13,936 children. An Sp02 <92% associated with a similar increased risk of mortality (OR 3.66, 95% CI 1.42 to 9.47) in 3 studies on 673 children. Sensitivity analyses (excluding studies with high risk of bias and using adjusted OR) and subgroup analyses (by: altitude, definition of ALRI, country income, HIV prevalence) did not affect results. Only one study was performed on children living at high altitude.

Conclusions

The results of this review support the routine evaluation of SpO2 for identifying children with ALRI at increased risk of death. Both a Sp02 value of 92% and 90% equally identify children at increased risk of mortality. More research is needed on children living at high altitude. Policy makers in LMIC should aim at improving the regular use of pulse oximetry and the availability of oxygen in order to decrease mortality from ALRI.     

An Update on Maternal Hydration Strategies for Amniotic Fluid Improvement in Isolated Oligohydramnios and Normohydramnios: Evidence from a Systematic Review of Literature and Meta-Analysis

Objective

Several trials aimed at evaluating the efficacy of maternal hydration (MH) in increasing amniotic-fluid-volume (AFV) in pregnancies with isolated oligohydramnios or normohydramnos have been conducted. Unfortunately, no evidences support this intervention in routine-clinical-practice. The aim of this systematic-literature-review and meta-analysis was to collect all data regarding proposed strategies and their efficacy in relation to each clinical condition for which MH-therapy was performed with the aim of increasing amniotic-fluid (AF) and improving perinatal outcomes.

Materials and Methods

A systematic literature search was conducted in electronic-database MEDLINE, EMBASE, ScienceDirect and the Cochrane-Library in the time interval between 1991 and 2014. Following the identification of eligible trials, we estimated the methodological quality of each study (using QADAS-2) and clustered patients according to the following outcome measures: route of administration (oral versus intravenous versus combined), total daily dose of fluids administered (<2000 versus >2000), duration of hydration therapy: (1 day, >1 day but <1 week, >1 week), type of fluid administered (isotonic versus hypotonic versus combination).

Results

In isolated-oligohydramnios (IO), maternal oral hydration is more effective than intravenous hydration and hypotonic solutions superior to isotonic solutions. The improvement in AFV appears to be time-dependent rather than daily-dose dependent. Regarding normohydramnios pregnancies, all strategies seem equivalent though the administration of hypotonic-fluid appears to have a slightly greater effect than isotonic-fluid. Regarding perinatal outcomes, data is fragmentary and heterogeneous and does not allow us to define the real clinical utility of MH.

Conclusions

Available data suggests that MH may be a safe, well-tolerated and useful strategy to improve AFV especially in cases of IO. In view of the numerous obstetric situations in which a reduced AFV may pose a threat, particularly to the fetus, the possibility of increasing AFV with a simple and inexpensive practice like MH-therapy may have potential clinical applications. Considering the various strategies of maternal hydration implemented in the treatment of IO, better results were observed when treatment was based on a combination of intravenous (for a period of 1 day) and oral (for a period of at least 14 days) hypotonic fluids (≥2000ml).     

PhiC31-mediated cassette exchange into a bacterial artificial chromosome

The use of bacterial artificial chromosomes (BACs) modified via homologous recombination in Escherichia coli has become a powerful tool in the transgenic field. Homologous recombination allows the manipulation of BACs in very different ways. However this process can be cumbersome and problematic when using large targeting constructs containing several repeated elements. In order to address this problem, we have established a phiC31 integrase-mediated cassette exchange into a BAC. As an example of this technique, we have exchanged a cassette previously recombined into a BAC containing the Rosa 26 locus, by a 16.5-kb incoming construct containing several repeated elements. The combination of homologous recombination in E. coli and cassette exchange should expand the tools for manipulating BACs, thus facilitating the generation of constructs with higher complexity.     

Optimization of somatic inhibition at critical period onset in mouse visual cortex

Local GABAergic circuits trigger visual cortical plasticity in early postnatal life. How these diverse connections contribute to critical period onset was investigated by nonstationary fluctuation analysis following laser photo-uncaging of GABA onto discrete sites upon individual pyramidal cells in slices of mouse visual cortex. The GABA(A) receptor number decreased on the soma-proximal dendrite (SPD), but not at the axon initial segment, with age and sensory deprivation. Benzodiazepine sensitivity was also higher on the immature SPD. Too many or too few SPD receptors in immature or dark-reared mice, respectively, were adjusted to critical period levels by benzodiazepine treatment in vivo, which engages ocular dominance plasticity in these animal models. Combining GAD65 deletion with dark rearing from birth confirmed that an intermediate number of SPD receptors enable plasticity. Site-specific optimization of perisomatic GABA response may thus trigger experience-dependent development in visual cortex.     

Production of <Emphasis Type="Italic">Cocconeis neothumensis</Emphasis> (Bacillariophyceae) biomass in batch cultures and bioreactors for biotechnological applications: light and nutrient requirements

Cocconeis neothumensis, a benthic diatom living as epiphyte on Posidonia oceanica leaves, was hypothesised to synthesize secondary metabolites inducing apoptosis in the androgenic gland of the protandric shrimp Hippolyte inermis. The optimization of C. neothumensis cultures is a primary aim in order to identify and characterise the active compounds produced by this diatom. Light intensity and concentration of nutrients, such as silicates and selenium, are of major importance in determining the growth rate of diatoms and the maximum produced biomass. Thus, we evaluated the growth performances of C. neothumensis cultures at different light intensities, corresponding to those recorded in Posidonia oceanica meadows in April, when the induction of sexual reversal in Hippolyte inermis occurs; the growth performances were also determined in relation to different selenium and silicate availability in the culture medium and the possible interactions between these two micronutrients were evaluated. Two methods of cultivations were compared: batch cultures in Petri dishes and cultures in a bioreactor with a continuous medium flow in the system. C. neothumensis showed a faster growth at low light intensities, although with a good acclimation capacity in the range from 60 to 140 μmol photons m⁻² s⁻¹. The presence of selenium in the medium improved both the exponential growth rate and the maximum cell density. The same results were evidenced for a silicate concentration double that in Guillard f/2 medium. On the other hand, a simultaneous increase of silicate concentration and the presence of selenium led to a loss of the positive effects detected with single nutrients. This result suggests either a possible antagonism in selenium and silicate uptake or a negative interaction between these two micronutrients in Cocconeis. The yields of the two tested cultivation methods calculated in terms of diethyl ether extract dry weight per unit of substrate area were highest for the bioreactor.     

The Application of the Environmental Product Declaration to Waste Disposal in a Sanitary Landfill - Four Case Studies (10 pp)

Goal, Scope and Background

The aim of the present study is to evaluate, through LCA, the potential environmental impact associated to urban waste dumping in a sanitary landfill for four case studies and to compare different technologies for waste treatment and leachate or biogas management in the framework of the EPD® system. Specific data were collected on the four Italian landfills during a five-year campaign from 2000 to 2004. This work also analyses the comparability of EPD results for different products in the same product category. For this purpose, a critical review of PSR 2003:3, for preparing an EPD on ‘Collection, transfer and disposal service for urban waste in sanitary landfills', is performed.

Methods

PSR 2003:3 defines the requirements, based on environmental parameters, that should be considered in an LCA study for collecting and disposal service of Municipal Solid Waste (MSW) in a sanitary landfill. It defines functional unit, system boundaries towards nature, other technical systems and boundaries in time, cut-off rules, allocation rules and parameters to be declared in the EPD. This PSR is tested on four case studies representing the major landfills located from the farthest west to the farthest east side of the Ligurian Region. Those landfills are managed with different technologies as concerns waste pre-treatment and leachate or biogas treatment. For each landfill, a life cycle assessment study is performed.

Results and Discussion

The comparison of the LCA results is performed separately for the following phases: Transport, Landfill, Leachate and Biogas. The following parameters are considered: Resource use (Use of non-renewable resources with and without energy content, Use of renewable resources with and without energy content, Water consumption); Pollutant emissions expressed as potential environmental impact (Global Warming Potential from biological and fossil sources, Acidification, Ozone depletion, Photochemical oxidant formation, Eutrophication, Land use, Hazardous and other Waste production). The comparison of the LCA results obtained for alternative landfill and biogas management techniques in the case studies investigated shows that the best practicable option that benefits the environment as a whole must be identified and chosen in the LCA context. For example, a strong waste pre-treatment causes a high biological GWP in the Landfill phase, but a low GWP contribution in the Biogas phase, due to the consequent low biogas production, evaluated for 30 years since landfill closure.

Conclusion

The analysis of four case studies showed that, through the EPD tool, it is possible to make a comparison among different declarations for the same product category only with some modification and integration to existent PSR 2003:3. Results showed that different products have different performances for phases and impact categories. It is not possible to identify the \best product\ from an environmental point of view, but it is possible to identify the product (or service) with the lowest impact on the environment for each impact category and resource use.

Recommendation and Perspective

In consequences of the verification of the comprehensiveness of existent PSR 2003:3 for the comparability of EPD, some modifications and integration to existent rules are suggested.

     

Triterpenes in the hexane extract of leaves of Olea europaea L.: analysis using 13C-NMR spectroscopy

Two neutral triterpenes and a triterpene acid were identified and quantified directly, in the absence of any purification steps, in a precipitate obtained during the industrial extraction of the leaves of Olea europaea L. using 13C-NMR spectroscopy (spectrometer operating at 4.7 T equipped with a 10 mm probe). The method was optimised in order to reduce the duration of analysis with a routine NMR spectrometer. Together with long-chain linear compounds, erythrodiol, uvaol and oleanolic acid accounted for 27.3, 18.3 and 12.5% of the precipitate, respectively.     

Gain-of-glycosylation mutations

Disease-causing missense (and other in-frame) mutations can exert their deleterious effects at the cellular level through multiple mechanisms. A pathogenic mechanism involves the addition of a novel N-linked glycan. Up to 1.4% of known disease-causing missense mutations are predicted to give rise to gains-of-glycosylation. For some of these mutations, the novel glycans have been shown to be both necessary and sufficient to account for the deleterious impact of the mutation. The chemical complementation of cells from patients in vitro with various modifiers of glycosylation has been demonstrated and raises the possibility of specific chemical treatments for patients bearing gain-of-glycosylation mutations.     

Structural bases for substrate recognition and activity in Meaban virus nucleoside-2'-O-methyltransferase

Viral methyltransferases are involved in the mRNA capping process, resulting in the transfer of a methyl group from S-adenosyl-L-methionine to capped RNA. Two groups of methyltransferases (MTases) are known: (guanine-N7)-methyltransferases (N7MTases), adding a methyl group onto the N7 atom of guanine, and (nucleoside-2'-O-)-methyltransferases (2'OMTases), adding a methyl group to a ribose hydroxyl. We have expressed and purified two constructs of Meaban virus (MV; genus Flavivirus) NS5 protein MTase domain (residues 1-265 and 1-293, respectively). We report here the three-dimensional structure of the shorter MTase construct in complex with the cofactor S-adenosyl-L-methionine, at 2.9 angstroms resolution. Inspection of the refined crystal structure, which highlights structural conservation of specific active site residues, together with sequence analysis and structural comparison with Dengue virus 2'OMTase, suggests that the crystallized enzyme belongs to the 2'OMTase subgroup. Enzymatic assays show that the short MV MTase construct is inactive, but the longer construct expressed can transfer a methyl group to the ribose 2'O atom of a short GpppAC(5) substrate. West Nile virus MTase domain has been recently shown to display both N7 and 2'O MTase activity on a capped RNA substrate comprising the 5'-terminal 190 nt of the West Nile virus genome. The lack of N7 MTase activity here reported for MV MTase may be related either to the small size of the capped RNA substrate, to its sequence, or to different structural properties of the C-terminal regions of West Nile virus and MV MTase-domains.     

Early Cambrian origin of modern food webs: evidence from predator arrow worms

Although palaeontological evidence from exceptional biota demonstrates the existence of diverse marine communities in the Early Cambrian (approx. 540-520 Myr ago), little is known concerning the functioning of the marine ecosystem, especially its trophic structure and the full range of ecological niches colonized by the fauna. The presence of a diverse zooplankton in Early Cambrian oceans is still an open issue. Here we provide compelling evidence that chaetognaths, an important element of modern zooplankton, were present in the Early Cambrian Chengjiang biota with morphologies almost identical to Recent forms. New information obtained from the lowermost Cambrian of China added to previous studies provide convincing evidence that protoconodont-bearing animals also belonged to chaetognaths. Chaetognaths were probably widespread and diverse in the earliest Cambrian. The obvious raptorial function of their circumoral apparatuses (grasping spines) places them among the earliest active predator metazoans. Morphology, body ratios and distribution suggest that the ancestral chaetognaths were planktonic with possible ecological preferences for hyperbenthic niches close to the sea bottom. Our results point to the early introduction of prey-predator relationships into the pelagic realm, and to the increase of trophic complexity (three-level structure) during the Precambrian-Cambrian transition, thus laying the foundations of present-day marine food chains.