Airway exposure to multi-walled carbon nanotubes disrupts the female reproductive cycle without affecting pregnancy outcomes in mice

Abstract Background The use of multiwalled carbon nanotubes (MWCNT) is increasing due to a growing use in a variety of products across several industries. Thus, occupational exposure is also of increasing concern, particularly since airway exposure to MWCNTs can induce sustained pulmonary acute phase response and inflammation in experimental animals, which may affect female reproduction. This proof-of-principle study therefore aimed to investigate if lung exposure by intratracheal instillation of the MWCNT NM-400 would affect the estrous cycle and reproductive function in female mice. Results Estrous cycle regularity was investigated by comparing vaginal smears before and after exposure to 67 μg of NM-400, whereas reproductive function was analyzed by measuring time to delivery of litters after instillation of 2, 18 or 67 μg of NM-400. Compared to normal estrous cycling determined prior to exposure, exposure to MWCNT significantly prolonged the estrous cycle during which exposure took place, but significantly shortened the estrous cycle immediately after the exposed cycle. No consistent effects were seen on time to delivery of litter or other gestational or litter parameters, such as litter size, sex ratio, implantations and implantation loss. Conclusion Lung exposure to MWCNT interfered with estrous cycling. Effects caused by MWCNTs depended on the time of exposure: the estrous stage was particularly sensitive to exposure, as animals exposed during this stage showed a higher incidence of irregular cycling after exposure. Our data indicates that MWCNT exposure may interfere with events leading to ovulation

Duration of hydrothermal alteration and mineralization of the Don Manuel porphyry copper system, central Chile

The Don Manuel porphyry copper system, located in the Miocene–Pliocene metallogenic belt of central Chile, contains spatially zoned alteration styles common to other porphyry copper deposits including extensive potassic alteration, propylitic alteration, localized sericite-chlorite alteration and argillic alteration but lacks pervasive hydrolytic alteration typical of some deposits. It is one of the youngest porphyry copper deposits in the Andes. Timing of mineralization and the hydrothermal system at Don Manuel are consistent with emplacement of the associated intrusions (ca. 4 and 3.6 Ma). Two molybdenite samples yielded consistent ages of 3.412 ± 0.037 and 3.425 ± 0.037 Ma. 40Ar/39Ar ages on hydrothermal biotites (3.57 ± 0.02, 3.51 ± 0.02, 3.41 ± 0.01, and 3.37 ± 0.01 Ma) are associated with potassic alteration. These ages are younger than the youngest intrusion by ~300 k.y. recording the cooling of the system below 350 °C. Such a time gap can be explained by fluxing of hot magmatic fluids from deeper magmatic sources

Abnormal vital signs are strong predictors for intensive care unit admission and in-hospital mortality in adults triaged in the emergency department - a prospective cohort study

<p>Abstract</p> <p>Background</p> <p>Assessment and treatment of the acutely ill patient have improved by introducing systematic assessment and accelerated protocols for specific patient groups. Triage systems are widely used, but few studies have investigated the ability of the triage systems in predicting outcome in the unselected acute population. The aim of this study was to quantify the association between the main component of the Hillerød Acute Process Triage (HAPT) system and the outcome measures; Admission to Intensive Care Unit (ICU) and in-hospital mortality, and to identify the vital signs, scored and categorized at admission, that are most strongly associated with the outcome measures.</p> <p>Methods</p> <p>The HAPT system is a minor modification of the Swedish Adaptive Process Triage (ADAPT) and ranks patients into five level colour-coded triage categories. Each patient is assigned a triage category for the two main descriptors; vital signs, T_vitals, and presenting complaint, T_complaint. The more urgent of the two determines the final triage category, T_final. We retrieved 6279 unique adult patients admitted through the Emergency Department (ED) from the Acute Admission Database. We performed regression analysis to evaluate the association between the covariates and the outcome measures.</p> <p>Results</p> <p>The covariates, T_vitals, T_complaintand T_finalwere all significantly associated with ICU admission and in-hospital mortality, the odds increasing with the urgency of the triage category. The vital signs best predicting in-hospital mortality were saturation of peripheral oxygen (SpO₂), respiratory rate (RR), systolic blood pressure (BP) and Glasgow Coma Score (GCS). Not only the type, but also the number of abnormal vital signs, were predictive for adverse outcome. The presenting complaints associated with the highest in-hospital mortality were 'dyspnoea' (11.5%) and 'altered level of consciousness' (10.6%). More than half of the patients had a T_complaintmore urgent than T_vitals, the opposite was true in just 6% of the patients.</p> <p>Conclusion</p> <p>The HAPT system is valid in terms of predicting in-hospital mortality and ICU admission in the adult acute population. Abnormal vital signs are strongly associated with adverse outcome, while including the presenting complaint in the triage model may result in over-triage.</p

Reduced level of arousal and increased mortality in adult acute medical admissions: a systematic review and meta-analysis

Abstract Background Reduced level of arousal is commonly observed in medical admissions and may predict in-hospital mortality. Delirium and reduced level of arousal are closely related. We systematically reviewed and conducted a meta-analysis of studies in adult acute medical patients of the relationship between reduced level of arousal on admission and in-hospital mortality. Methods We conducted a systematic review (PROSPERO: CRD42016022048), searching MEDLINE and EMBASE. We included studies of adult patients admitted with acute medical illness with level of arousal assessed on admission and mortality rates reported. We performed meta-analysis using a random effects model. Results From 23,941 studies we included 21 with 14 included in the meta-analysis. Mean age range was 33.4 - 83.8 years. Studies considered unselected general medical admissions (8 studies, n=13,039) or specific medical conditions (13 studies, n=38,882). Methods of evaluating level of arousal varied. The prevalence of reduced level of arousal was 3.1%-76.9% (median 13.5%). Mortality rates were 1.7%-58% (median 15.9%). Reduced level of arousal was associated with higher in-hospital mortality (pooled OR 5.71; 95% CI 4.21-7.74; low quality evidence: high risk of bias, clinical heterogeneity and possible publication bias). Conclusions Reduced level of arousal on hospital admission may be a strong predictor of in-hospital mortality. Most evidence was of low quality. Reduced level of arousal is highly specific to delirium, better formal detection of hypoactive delirium and implementation of care pathways may improve outcomes. Future studies to assess the impact of interventions on in-hospital mortality should use validated assessments of both level of arousal and delirium

Post-collisional shift from polygenetic to monogenetic volcanism revealed by new 40Ar/39Ar ages in the southern Lesser Caucasus (Armenia)

The post-collisional Syunik and Vardenis volcanic highlands, located in the southern Lesser Caucasus mountains (part of the Arabia-Eurasia collision zone) are host to over 200 monogenetic volcanoes, as well as 2 large Quaternary polygenetic volcanoes in the Syunik highland. The latter are overlain by lavas from the monogenetic volcanoes, suggesting there was a transition in the style of volcanic activity from large-volume central vent eruptions to dispersed small-volume eruptions. 12 new high quality 40Ar/39Ar ages are presented here, with 11 ages calculated by step-heating experiments on groundmass separates, and the final age obtained from total fusions of a population of sanidines. All the ages were younger than 1.5 Ma, except for one ignimbrite deposit whose sanidines gave an age of 6 Ma. While the bulk of the exposed products of post-collisional volcanism relate to Pleistocene activity, it is clear there has been active volcanism in the region since at least the late Miocene. All ages for monogenetic volcanoes in the Syunik highland are younger than 1 Ma, but to the north in Vardenis there is geochronological evidence of monogenetic volcanism at 1.4 and 1.3 Ma. An age of 1.3 Ma is determined for a lava flow from one of the polygenetic volcanoes- Tskhouk, and when combined with other ages helps constrain the timing of the polygenetic to monogenetic transition to around 1 Ma. The new ages illustrate a degree of spatio-temporal coupling in the formation of new vents, which could be related to pull-apart basins focussing ascending magmas. This coupling means that future eruptions are particularly likely to occur close to the sites of the most recent Holocene activity. The polygenetic to monogenetic transition is argued to be the result of a decreasing magma supply based on: (i) volume estimates for Holocene eruptions and for all monogenetic volcanoes and their lava flows in Syunik; and (ii) the volcanic stratigraphy of the Lesser Caucasus region which shows late Pliocene- early Pleistocene continental flood basalts being succeeded by a few large andesite-dacite volcanoes and then the most recent deposits consisting of small-volume scoria cones. The Syunik highland has the highest density of monogenetic centres in the Lesser Caucasus, which is taken to indicate this region has the highest magma flux, and was therefore the last location to transition to monogenetic volcanism, which is why the transition is most clearly seen there. There is no evidence from Sr-Nd-B isotope measurements for the exhaustion of fusible slab components in the mantle source, showing that an inherited slab signature can survive for millions of years after the end of subduction. Although volcanism in the Lesser Caucasus is currently waning, a future pulse of activity is possible

Pulmonary toxicity of synthetic amorphous silica–effects of porosity and copper oxide doping

Materials can be modified for improved functionality. Our aim was to test whether pulmonary toxicity of silica nanomaterials is increased by the introduction of: a) porosity; and b) surface doping with CuO; and whether c) these modifications act synergistically. Mice were exposed by intratracheal instillation and for some doses also oropharyngeal aspiration to: 1) solid silica 100 nm; 2) porous silica 100 nm; 3) porous silica 100 nm with CuO doping; 4) solid silica 300 nm; 5) porous silica 300 nm; 6) solid silica 300 nm with CuO doping; 7) porous silica 300 nm with CuO doping; 8) CuO nanoparticles 9.8 nm; or 9) carbon black Printex 90 as benchmark. Based on a pilot study, dose levels were between 0.5 and 162 µg/mouse (0.2 and 8.1 mg/kg bw). Endpoints included pulmonary inflammation (neutrophil numbers in bronchoalveolar fluid), acute phase response, histopathology, and genotoxicity assessed by the comet assay, micronucleus test, and the gamma-H2AX assay. The porous silica materials induced greater pulmonary inflammation than their solid counterparts. A similar pattern was seen for acute phase response induction and histologic changes. This could be explained by a higher specific surface area per mass unit for the most toxic particles. CuO doping further increased the acute phase response normalized according to the deposited surface area. We identified no consistent evidence of synergism between surface area and CuO doping. In conclusion, porosity and CuO doping each increased the toxicity of silica nanomaterials and there was no indication of synergy when the modifications co-occurred

In vitro selection of RNA aptamers against a conserved region of the Plasmodium falciparum erythrocyte membrane protein 1

The var-gene encoding Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) is known to play a major role in the pathogenicity of the P. falciparum parasite. The protein enables the parasite to adhere to the endothelial linings of small blood vessels (cytoadherence) as well as to non-infected erythrocytes (rosetting), thus preventing clearance from the bloodstream. The development and spread of resistance towards most anti-malarial drugs used for treatment and prevention of the most severe form of malaria truly emphasise the importance of a continuous research and development of new drugs. In this study we use Systematic Evolution of Ligands by EXponential enrichment (SELEX) methodology to isolate high-affinity ligands (aptamers). To validate the results from the SELEX in vitro selection, different aptamers have been selected against PfEMP1 in a live cell assay of P. falciparum strain FCR3S1.2, a highly rosetting strain. We have been able to show the rosette disrupting capacity of these SELEX-aptamers at concentrations of 33 nM and with 100% disruption at 387 nM. The described results show that RNA aptamers are promising candidates for adjunct therapy in severe malaria