Neuroimaging safety during pregnancy and lactation: a review.

PURPOSE: Imaging studies are crucial adjuncts when studying acute and chronic diseases, so pregnant and lactating women are as likely to be evaluated with one of the available imaging modalities. Due to the specific condition of the mother and child in this time period it is crucial to make an appropriate selection of imaging studies. METHODS: We review the existing literature and analyse the latest evidence and guidelines regarding neuroimaging safety during pregnancy and lactation, proposing an algorithm of action based on risk/benefits assessment. RESULTS: Choosing the most appropriate neuroimaging modality implicates assessing the pretest pertinence of the study-the possibility of a serious treatable neurologic disease, pondering what is the most useful imaging modality for the diagnosis and evaluating the associated risks. Among physicians (and patients), however, the risk component is perhaps the least well understood, with misperceptions regarding safety and potential hazards. Computed tomography (CT) risks are principally related to ionizing radiation and intravenous (IV) administration of iodinated contrast. However, as very low risks for the mother and foetus have been reported and CT remains the most available tool for initial rapid diagnosis of acute neurological conditions, it should not be withheld in urgent situations. Magnetic resonance imaging (MRI), unlike CT, does not use ionizing radiation or iodinated contrast mediums, having the best anatomical detail possible. However, there are some usage safety concerns regarding the magnetic field strength and gadolinium-based contrast use. CONCLUSION: There are lacking longitudinal and prospective studies to sustain evidence based choices of imaging studies during pregnancy and lactation. Ultimately the decision should be based on the risk/benefit, taking into account the patient's safety, care and outcomes. However, using a specific algorithm can guide decisions in daily clinical practice.

Supporting the improvement of air quality management practices: The "FAIRMODE pilot" activity.

This paper presents the first outcomes of the "FAIRMODE pilot" activity, aiming at improving the way in which air quality models are used in the frame of the European "Air Quality Directive". Member States may use modelling, combined with measurements, to "assess" current levels of air quality and estimate future air quality under different scenarios. In case of current and potential exceedances of the Directive limit values, it is also requested that they "plan" and implement emission reductions measures to avoid future exceedances. In both "assessment" and "planning", air quality models can and should be used; but to do so, the used modelling chain has to be fit-for-purpose and properly checked and verified. FAIRMODE has developed in the recent years a suite of methodologies and tools to check if emission inventories, model performance, source apportionment techniques and planning activities are fit-for-purpose. Within the "FAIRMODE pilot", these tools are used and tested by regional/local authorities, with the two-fold objective of improving management practices at regional/local scale, and providing valuable feedback to the FAIRMODE community. Results and lessons learnt from this activity are presented in this paper, as a showcase that can potentially benefit other authorities in charge of air quality assessment and planning.

Defective expression of apoptosis-related molecules in multiple sclerosis patients is normalized early after autologous haematopoietic stem cell transplantation.

Defective apoptosis might be involved in the pathogenesis of multiple sclerosis (MS). We evaluated apoptosis-related molecules in MS patients before and after autologous haematopoietic stem cell transplantation (AHSCT) using BCNU, Etoposide, AraC and Melphalan (BEAM) or cyclophosphamide (CY)-based conditioning regimens. Patients were followed for clinical and immunological parameters for 2 years after AHSCT. At baseline, MS patients had decreased proapoptotic BAD, BAX and FASL and increased A1 gene expression when compared with healthy counterparts. In the BEAM group, BAK, BIK, BIMEL , FAS, FASL, A1, BCL2, BCLXL , CFLIPL and CIAP2 genes were up-regulated after AHSCT. With the exception of BIK, BIMEL and A1, all genes reached levels similar to controls at day + 720 post-transplantation. Furthermore, in these patients, we observed increased CD8+ Fas+ T cell frequencies after AHSCT when compared to baseline. In the CY group, we observed increased BAX, BCLW, CFLIPL and CIAP1 and decreased BIK and BID gene expressions after transplantation. At day + 720 post-AHSCT, the expression of BAX, FAS, FASL, BCL2, BCLXL and CIAP1 was similar to that of controls. Protein analyses showed increased Bcl-2 expression before transplantation. At 1 year post-AHSCT, expression of Bak, Bim, Bcl-2, Bcl-xL and cFlip-L was decreased when compared to baseline values. In summary, our findings suggest that normalization of apoptosis-related molecules is associated with the early therapeutic effects of AHSCT in MS patients. These mechanisms may be involved in the re-establishment of immune tolerance during the first 2 years post-transplantation.

Characterization of airborne particles generated from metal active gas welding process.

This study is focused on the characterization of particles emitted in the metal active gas welding of carbon steel using mixture of Ar + CO2, and intends to analyze which are the main process parameters that influence the emission itself. It was found that the amount of emitted particles (measured by particle number and alveolar deposited surface area) are clearly dependent on the distance to the welding front and also on the main welding parameters, namely the current intensity and heat input in the welding process. The emission of airborne fine particles seems to increase with the current intensity as fume-formation rate does. When comparing the tested gas mixtures, higher emissions are observed for more oxidant mixtures, that is, mixtures with higher CO2 content, which result in higher arc stability. These mixtures originate higher concentrations of fine particles (as measured by number of particles by cm(3) of air) and higher values of alveolar deposited surface area of particles, thus resulting in a more severe worker's exposure.

Coccolith-calcite Sr/Ca as a proxy for transient export production related to Saharan dust deposition in the tropical North Atlantic.

Atmospheric dust deposition can modulate the earth's climate and atmospheric CO2 through fertilising the ocean (nutrient source) and by accelerating the biological carbon pump through fuelling the ballasting process. To distinguish the biogeochemical effects of Saharan dust with respect to fertilization and ballasting, and to gain a broader perspective on the coccolith calcite Sr/Ca in relation to the drivers of coccolith export production, we determined the coccolith-Sr/Ca from a one-year (2012-2013) time-series sediment trap record in the western tropical North Atlantic (M4-49°N/12°W). High Sr/Ca were linked to enhanced export production in the upper part of the photic zone, most notably under windier, dry, and dustier conditions during spring. Attenuated Sr/Ca in the autumn probably reflect a combination of lower Sr-incorporation by dominant but small-size placolith-bearing species and the presence of "aged" coccoliths rapidly scavenged during a highly productive and usually fast export event, likely added by (wet) dust ballasting. Higher Sr/Ca observed in the large coccolith size fractions support the existing notion that larger-sized coccolithophores incorporate more Sr during calcification under the same environmental conditions. The presence of the abnormally Sr-rich species Scyphosphaera apsteinii is also shown in the separated large fraction of our Sr/Ca seasonal data.

Early abdominal pregnancy with an unexpected and misleading location. The ultrasonographic interpretation.

Abdominal pregnancy is a rare condition defined as an ectopic pregnancy that implants in the peritoneal cavity and is associated with important morbidity and mortality. We report a case of a 35-year-old woman with an ultrasonographic diagnosis of a left extrauterine pregnancy located proximally in the isthmus or distally in the interstitial region. In the exploratory laparotomy a gestational sac implanted anteriorly on the uterine serosa was found, with no signs of uterine perforation or tubal abortion. The pathologic examination confirmed the diagnosis of an early first trimester abdominal pregnancy. This case illustrates the importance of an early sonography in the diagnosis of an abdominal pregnancy as well as a high index of suspicion.

Structures of synthetic O-antigen fragments from serotype 2a Shigella flexneri in complex with a protective monoclonal antibody.

The anti-LPS IgG mAb F22-4, raised against Shigella flexneri serotype 2a bacteria, protects against homologous, but not heterologous, challenge in an experimental animal model. We report the crystal structures of complexes formed between Fab F22-4 and two synthetic oligosaccharides, a decasaccharide and a pentadecasaccharide that were previously shown to be both immunogenic and antigenic mimics of the S. flexneri serotype 2a O-antigen. F22-4 binds to an epitope contained within two consecutive 2a serotype pentasaccharide repeat units (RU). Six sugar residues from a contiguous nine-residue segment make direct contacts with the antibody, including the nonreducing rhamnose and both branching glucosyl residues from the two RUs. The glucosyl residue, whose position of attachment to the tetrasaccharide backbone of the RU defines the serotype 2a O-antigen, is critical for recognition by F22-4. Although the complete decasaccharide is visible in the electron density maps, the last four pentadecasaccharide residues from the reducing end, which do not contact the antibody, could not be traced. Although considerable mobility in the free oligosaccharides can thus be expected, the conformational similarity between the individual RUs, both within and between the two complexes, suggests that short-range transient ordering to a helical conformation might occur in solution. Although the observed epitope includes the terminal nonreducing residue, binding to internal epitopes within the polysaccharide chain is not precluded. Our results have implications for vaccine development because they suggest that a minimum of two RUs of synthetic serotype 2a oligosaccharide is required for optimal mimicry of O-Ag epitopes.

Fracture resistance of roots prosthetically restored with intra-radicular posts of different lengths.

The purpose of this study was to assess the fracture resistance of roots that were prosthetically restored with intra-radicular posts of different lengths. Forty-five bovine incisors were sectioned 17 mm from their apices, endodontically treated and randomly divided into three experimental groups: GI, fibreglass posts luted at a depth of 12 mm; GII, 8 mm and GIII, 4 mm. All posts were luted with dual resin cement. Resin composite cores were prepared with standardized measurements, and all teeth were restored with metal crowns. The samples were submitted to the fracture resistance test in a universal testing machine, at an angle of 135 degrees and speed of 0.5 mm min(-1), until fracture occurred. The data, in MPa, were submitted to the analysis of variance (anova) followed by Tukey's test (alpha = 0.01). No statistically significant difference (P > 0.01) was found between GI (129.72 +/- 12.14) and GII (154.3 +/- 12.08), which presented the highest fracture resistance values. Group GIII (100.5 +/- 8.07) showed lower fracture resistance (P < 0.01) when compared with GI and GII. Within the limitations of this study, it was concluded that the post lengths influenced the fracture resistance of prosthetically restored roots. These results suggest that it is not necessary to perform excessive intra-radicular post-space preparation to improve the fracture resistance of roots.

Source apportionment to support air quality planning: Strengths and weaknesses of existing approaches.

Information on the origin of pollution constitutes an essential step of air quality management as it helps identifying measures to control air pollution. In this work, we review the most widely used source-apportionment methods for air quality management. Using theoretical and real-case datasets we study the differences among these methods and explain why they result in very different conclusions to support air quality planning. These differences are a consequence of the intrinsic assumptions that underpin the different methodologies and determine/limit their range of applicability. We show that ignoring their underlying assumptions is a risk for efficient/successful air quality management as these methods are sometimes used beyond their scope and range of applicability. The simplest approach based on increments (incremental approach) is often not suitable to support air quality planning. Contributions obtained through mass-transfer methods (receptor models or tagging approaches built in air quality models) are appropriate to support planning but only for specific pollutants. Impacts obtained via "brute-force" methods are the best suited but it is important to assess carefully their application range to make sure they reproduce correctly the prevailing chemical regimes.

Acyclic phosphonate nucleotides and human adenylate kinases: impact of a borano group on alpha-P position.

Adenylate kinases are involved in the activation of antiviral drugs such as the acyclic phosphonates analogs PMEA and (R)PMPA. We examine the in vitro phosphorylation of PMEA and PMPA bearing a borano- or a H- group on the phosphorus atom. The alpha-borano or alpha-H on PMEA and PMPA were detrimental to the activity of recombinant human AMP kinases 1 and 2. Docking PMEA to the active site of AMP kinase 1 indicated that the borano group may prevent two conserved critical Arg interactions with the alpha-phosphate, resulting in substrate bad positioning.

Role of a family 11 carbohydrate-binding module in the function of a recombinant cellulase used to supplement a barley-based diet for broiler chickens.

1. Cellulases and xylanases display a modular architecture that comprises a catalytic module linked to one or more non-catalytic carbohydrate-binding modules (CBMs). CBMs have been classified into 52 different families, based on primary structure similarity. These non-catalytic modules mediate a prolonged and intimate contact of the enzyme with the target substrate eliciting efficient hydrolysis of the target polysaccharides. 2. A study was undertaken to investigate the importance of a family 11 CBM, displaying high affinities for barley beta-glucans, in the function of recombinant derivatives of cellulase CtLic26A-Cel5E of Clostridium thermocellum used to supplement a barley-based diet for broiler chicken. 3. The results showed that birds fed on diets containing the recombinant CtLic26A-Cel5E modular derivatives or the commercial enzyme mixture Rovabio Excel AP displayed improved performance when compared with birds fed on diets not supplemented with exogenous enzymes. 4. It is suggested that the enzyme dosage used in this study (30 U/kg of basal diet), was probably too high for the efficacy of the family 11 CBM to be noticed. It remains to be established if the targeting effect resulting from the incorporation of CBMs in plant cell wall hydrolases may be effective at lower exogenous enzyme dosages.

A family 11 carbohydrate-binding module (CBM) improves the efficacy of a recombinant cellulase used to supplement barley-based diets for broilers at lower dosage rates.

1. Exogenous microbial beta-1,3-1,4-glucanases and hemicellulases contribute to improving the nutritive value of cereals rich in soluble non-starch polysaccharides for poultry. 2. In general, plant cell wall hydrolases display a modular structure comprising a catalytic module linked to one or more non-catalytic carbohydrate-binding modules (CBMs). Based on primary structure similarity, CBMs have been classified in 50 different families. CBMs anchor cellulases and hemicellulases into their target substrates, therefore eliciting efficient hydrolysis of recalcitrant polysaccharides. 3. A study was undertaken to investigate the effects of a family 11 beta-glucan-binding domain in the function of recombinant derivatives of cellulase CtLic26A-Cel5E of Clostridium thermocellum that were used to supplement a barley-based diet at lower dosage rates. 4. The results showed that birds fed on diets supplemented with the recombinant CtLic26A-Cel5E modular derivative containing the family 11 CBM or the commercial enzyme mixture Rovabio Excel AP tended to display improved performance when compared to birds fed diets not supplemented with exogenous enzymes. 5. It is suggested that at lower than previously reported enzyme dosage (10 U/kg vs 30 U/kg of basal diet), the beta-glucan-binding domain also elicits the function of the recombinant CtLic26A-Cel5E derivatives. 6. Finally, the data suggest that exogenous enzymes added to barley-based diets act primarily in the proximal section of the gastrointestinal tract.

Crop beta-glucanase activity limits the effectiveness of a recombinant cellulase used to supplement a barley-based feed for free-range broilers.

1. The supplementation of diets rich in soluble polysaccharides with microbial cellulases and hemicellulases decreases digesta viscosity and promotes broiler performance. 2. In contrast, recent experiments suggest that polysaccharidases are ineffective for improving the nutritive value of pasture biomass used by free-range broilers. However, the feasibility of using cellulases and hemicellulases to improve the utilisation of cereal-based feeds by pastured poultry remains to be established. 3. A study was undertaken to investigate the capacity of a recombinant cellulase from Clostridium thermocellum to improve the nutritive value of a barley-based feed for free-range pastured broilers of the RedBro Cou Nu x RedBro M genotype. 4. The results show that supplementation of a barley-based diet with a recombinant beta-glucanase had no effect on the performance of free-range broilers, foraging in legume-based diets from d 28 to 56. In addition, the results confirm that the lack of effect of the recombinant enzyme in improving the nutritive value of the barley-based feed does not result from enzyme proteolysis or inhibition in the gastrointestinal tract. 5. Significantly, beta-glucanase activity was identified in the crop of non-supplemented animals. The data suggest that endogenous cellulases originated both from the barley-based feed and from the crop microflora. 6. The results presented here suggest that in older birds of slow-growing genotypes associated with free-range production systems, previously unknown sources of beta-glucanases, such as the feed and microbial symbiotic microflora, can affect the effectiveness of exogenous enzymes added to the feed.

Benzo(a)pyrene in Europe: Ambient air concentrations, population exposure and health effects.

This study estimated current benzo(a)pyrene (BaP) concentration levels, population exposure and potential health impacts of exposure to ambient air BaP in Europe. These estimates were done by combining the best available information from observations and chemical transport models through the use of spatial interpolation methods. Results show large exceedances of the European target value for BaP in 2012 over large areas, particularly in central-eastern Europe. Results also show large uncertainties in the concentration estimates in regions with a few or no measurement stations. The estimation of the population exposure to BaP concentrations and its health impacts was limited to 60% of the European population, covering only the modelled areas which met the data quality requirement for modelling of BaP concentrations set by the European directive 2004/107/EC. The population exposure estimate shows that 20% of the European population is exposed to BaP background ambient concentrations above the EU target value and only 7% live in areas with concentrations under the estimated acceptable risk level of 0.12 ng m(-3). This exposure leads to an estimated 370 lung cancer incidences per year, for the 60% of the European population included in the estimation. Emissions of BaP have increased in the last decade with the increase in emissions from household combustion of biomass. At the same time, climate mitigation policies are promoting the use of biomass burning for domestic heating. The current study shows that there is a need for more BaP measurements in areas of low measurement density, particularly where high concentrations are expected, e.g. in Romania, Bulgaria, and other Balkan states. Furthermore, this study shows that the health risk posed by PAH exposure calls for better coordination between air quality and climate mitigation policies in Europe.

Seizure outcome and hippocampal atrophy in familial mesial temporal lobe epilepsy.

OBJECTIVE: To describe the clinical, genetic and MR characteristics of patients with familial mesial temporal lobe epilepsy (MTLE). DESIGN/METHODS: The familial occurrence of MTLE was identified by a systematic search of family history of seizures in patients followed in the authors' epilepsy clinic. All probands and, whenever possible, other affected family members underwent EEG and MR investigations. RESULTS: Twenty-two unrelated families with at least two individuals with MTLE were identified by clinical and EEG findings. Ninety-eight individuals with history of seizures were evaluated. Sixty-eight patients fulfilled the diagnostic criteria for MTLE. MRI was performed in 84 patients, and showed hippocampal atrophy with increased T2 signal in 48 (57%). The distribution of hippocampal atrophy according to the seizure outcome groups was 6 of 13 patients (46%) with seizure remission, 16 of 31 (51%) with good seizure control under medication, and all 16 patients with refractory MTLE. Hippocampal atrophy was found also in patients that did not fulfill the criteria for MTLE: 3 of 10 (30%) patients with febrile seizure alone, 6 of 10 (60%) patients with recurrent generalized tonic-clonic seizures, and 1 of 4 (25%) patients with a single partial seizure. CONCLUSION: Familial MTLE is a clinically heterogeneous syndrome. Hippocampal atrophy was observed in 57% of patients, including those with benign course or seizure remission, indicating that the relationship between hippocampal atrophy and severity of epilepsy might be more complex than previously suspected. In addition, these findings indicate the presence of a strong genetic component determining the development of mesial temporal sclerosis in these families.

A double-blind controlled clinical trial of oxcarbazepine versus phenytoin in adults with previously untreated epilepsy.

In the last 5 years oxcarbazepine (OXC) has been registered in many countries for use as first-line and add-on treatment for partial seizures with or without secondarily generalized seizures (PS) and generalized tonic-clonic seizures without partial onset (GTCS). Its use as monotherapy in adults with newly diagnosed epilepsy was investigated in this double-blind, randomized, parallel-group comparison with phenytoin (PHT). A total of 287 adult patients, with either PS or GTCS, were randomized. After retrospective baseline assessment, patients were randomized to OXC or PHT in a 1:1 ratio. The double-blind treatment phase was divided into two periods: a flexible titration period of 8 weeks, followed by 48 weeks of maintenance treatment. In the efficacy analyses, no statistically significant differences were found between the treatment groups. Seventy patients (59.3%) in the OXC group and 69 (58.0%) in the PHT group were seizure-free during the maintenance period. A total of 56 of the patients in the OXC group discontinued treatment prematurely (five because of tolerability reasons) compared to 61 in the PHT group (16 for tolerability reasons). The number of premature discontinuations due to adverse experiences showed a statistically significant difference in favour of OXC. There was no statistically significant difference between the groups with respect to the total number of premature discontinuations. This trial provides further support for the efficacy and safety of OXC as first-line treatment in adults with PS and GTCS. In addition, the results show that OXC has significant advantages over PHT in terms of tolerability.

Vigabatrin in refractory childhood epilepsy. The Brazilian Multicenter Study.

Children, 47, with various types of severe drug-resistant epilepsy were entered into a prospective, add-on, open trial with vigabatrin. Patients with West syndrome and idiopathic generalized epilepsies were excluded. Seven children had the drug withdrawn, five because of increase in seizure frequency and two because of adverse effects. Drug efficacy, measured according to seizure type, showed a 100% decrease in seizure frequency in 18.6% of partial seizures and 17.3% of the generalized seizures. There was a higher than 50% decrease in 39.5% of partial and 60.8% of generalized seizures, and less than 50% decrease or increase in seizure frequency in 41.8% and 21.8% of partial and generalized seizures, respectively. Vigabatrin mean dosage during phase 3 was 63.6 mg/kg per day (S.D. = 30.5), ranging from 19.3 to 110.5 mg/kg per day. Parametric statistical analysis (Student's t-test) of seizure frequency between phases 1 and 3 showed a significant decrease in seizure frequency for partial (P = 0.022), and generalized seizures (P < 0.0001). Drug-related adverse effects were observed in 18/47 cases (38.3%), consisting mainly of irritability, hyperactivity, dizziness, somnolence and gastrointestinal symptoms.