Vulnerable periods during the development of the nervous system are sensitive to environmental insults because they are dependent on the temporal and regional emergence of critical developmental ...processes (i.e., proliferation, migration, differentiation, synaptogenesis, myelination, and apoptosis). Evidence from numerous sources demonstrates that neural development extends from the embryonic period through adolescence. In general, the sequence of events is comparable among species, although the time scales are considerably different. Developmental exposure of animals or humans to numerous agents (e.g., X-ray irradiation, methylazoxymethanol, ethanol, lead, methyl mercury, or chlorpyrifos) demonstrates that interference with one or more of these developmental processes can lead to developmental neurotoxicity. Different behavioral domains (e.g., sensory, motor, and various cognitive functions) are subserved by different brain areas. Although there are important differences between the rodent and human brain, analogous structures can be identified. Moreover, the ontogeny of specific behaviors can be used to draw inferences regarding the maturation of specific brain structures or neural circuits in rodents and primates, including humans. Furthermore, various clinical disorders in humans (e.g., schizophrenia, dyslexia, epilepsy, and autism) may also be the result of interference with normal ontogeny of developmental processes in the nervous system. Of critical concern is the possibility that developmental exposure to neurotoxicants may result in an acceleration of age-related decline in function. This concern is compounded by the fact that developmental neurotoxicity that results in small effects can have a profound societal impact when amortized across the entire population and across the life span of humans.
Background
Guidelines and position papers indicate that allergen immunotherapy (AIT) is the only disease‐modifying treatment, including prevention of the onset of new allergen sensitizations. ...However, this preventive effect was shown by only a few observational studies. Our aim was to systematically review the efficacy of AIT in preventing the onset of new allergen sensitizations.
Methods
Computerized bibliographic searches of Medline, EMBASE, and the Cochrane Library (through June 2015) were supplemented with manual searches of reference lists. Observational studies or randomized controlled trials with a long‐term observation period were included. Paired reviewers extracted data about study characteristics and assessed biases. The end point was the risk difference in the onset of new allergen sensitizations between patients treated with AIT and pharmacotherapy. The strength of the evidence was graded based on the risk of bias, consistency, and magnitude of effect, according to the GRADE Working Group's guide.
Results
Eighteen studies (1049 children, 10 057 adults) met the inclusion criteria. The risk of bias was high in all but one study. Low evidence supports the position that AIT prevents the onset of new allergen sensitizations, with 10 of 18 studies reporting a reduction in the onset of new sensitizations in patients treated with AIT vs placebo. Small studies and studies with a shorter follow‐up showed the highest benefit of AIT.
Conclusions
The overall evidence provides a low‐grade level of the evidence supporting the efficacy of AIT in preventing the onset of new allergen sensitizations, but high‐quality studies could change this estimate.
The potential of additive manufacturing to produce optimised and customized polymeric parts is often impaired by poor surface finish, low mechanical properties, and insufficient dimensional accuracy. ...Post-processing treatments are usually adopted to address these issues. Scientific community and industrial actors are engaged in the development and use of post-processing to enhance the performance and widen the range of application of polymeric components manufactured by additive technologies.
The present work aims to provide an exhaustive classification and discussion of the post-processing treatments, as well as an extensive literature review of the approaches proposed within the scientific community. A holistic view of post-processing is provided, including a discussion of the benefits associated with each technique as well as its side effects. This work is intended to support the selection of the most appropriate post-processing by considering multiple aspects such as the material, part geometry, processing time, costs, and treatment specificity.
Current research on underwater 3D imaging methods is mainly addressing long range applications like seafloor mapping or surveys of archeological sites and shipwrecks. Recently, there is an increasing ...need for more accessible and precise close-range 3D acquisition technologies in some application fields like, for example, monitoring the growth of coral reefs or reconstructing underwater archaeological pieces that in most cases cannot be recovered from the seabed. This paper presents the first results of a research project that aims to investigate the possibility of using active optical techniques for the whole-field 3D reconstructions in an underwater environment. In this work we have tested an optical technique, frequently used for in air acquisition, based on the projection of structured lighting patterns acquired by a stereo vision system. We describe the experimental setup used for the underwater tests, which were conducted in a water tank with different turbidity conditions. The tests have evidenced that the quality of 3D reconstruction is acceptable even with high turbidity values, despite the heavy presence of scattering and absorption effects.
Transparent and removable aligners represent an effective solution to correct various orthodontic malocclusions through minimally invasive procedures. An aligner‐based treatment requires patients to ...sequentially wear dentition‐mating shells obtained by thermoforming polymeric disks on reference dental models. An aligner is shaped introducing a geometrical mismatch with respect to the actual tooth positions to induce a loading system, which moves the target teeth toward the correct positions. The common practice is based on selecting the aligner features (material, thickness, and auxiliary elements) by only considering clinician's subjective assessments.
In this article, a computational design and engineering methodology has been developed to reconstruct anatomical tissues, to model parametric aligner shapes, to simulate orthodontic movements, and to enhance the aligner design. The proposed approach integrates computer‐aided technologies, from tomographic imaging to optical scanning, from parametric modeling to finite element analyses, within a 3‐dimensional digital framework.
The anatomical modeling provides anatomies, including teeth (roots and crowns), jaw bones, and periodontal ligaments, which are the references for the down streaming parametric aligner shaping. The biomechanical interactions between anatomical models and aligner geometries are virtually reproduced using a finite element analysis software. The methodology allows numerical simulations of patient‐specific conditions and the comparative analyses of different aligner configurations.
In this article, the digital framework has been used to study the influence of various auxiliary elements on the loading system delivered to a maxillary and a mandibular central incisor during an orthodontic tipping movement. Numerical simulations have shown a high dependency of the orthodontic tooth movement on the auxiliary element configuration, which should then be accurately selected to maximize the aligner's effectiveness.
This article presents a digital methodology to study patient‐specific orthodontic treatments based on the use of polymeric aligners. The approach integrates computer‐aided technologies, from tomographic imaging to optical scanning, from parametric modeling to finite element analyses. Numerical analyses proved to be a powerful tool to study different aligner's configurations evidencing how auxiliary elements features might affect the loading system delivered by the aligner. For instance, results pointed out that the loads elicited by divot geometries are higher than those provided by using attachment geometries.
In radiocarbon applied research, both in Cultural Heritage and environmental contexts, minimising the invasiveness of the analysis is of fundamental importance. For this reason, at INFN-LABEC in ...Florence, the CHNet_Lilliput experiment aimed at reducing the graphite sample masses down to a few tens of μg of carbon, while the typical masses collected at the end of our “standard” preparation process are about 700 μg.
Here we discuss the necessary hardware upgrades done on the experimental set-up and the results of the first tests with samples of about 50 μg. Reproducibility of radiocarbon concentrations in NIST Oxalic Acid II samples was satisfying, as well as the comparison of concentrations measured in standard reference materials with their certified values. Background resulted to be slightly worse than the typical one measured for larger samples, as somehow expected, even though some improvements are looked-for thanks to a more careful handling of samples.
Is the microRNA (miRNA) expression pattern of cumulus oophorus cells (COCs) in women undergoing medically assisted reproduction (MAR) procedures differentially modulated according to patient age and ...gonadotropin treatment strategy?
Maternal age is an independent factor impacting miRNA expression in COCs while gonadotropin treatment may affect follicular miRNA expression and IVF efficacy.
Epigenetic mechanisms in female infertility are complex and poorly studied. DNA methylation, histone modifications, miRNAs and nucleosome positioning influence cellular machinery through positive and negative feedback mechanisms either alone or interactively. miRNAs are important regulators during oogenesis, spermatogenesis and early embryogenesis, and are reported to play a role in regulating crosstalk between the oocyte and COCs. Although miRNome analysis has been performed in female human reproductive tissues (endometrium, myometrium, cervix and ovaries), epigenetic modifications in women with infertility have not been explored in detail. In addition, the impact of gonadotropin treatments during MAR on miRNA expression in COCs has not been fully investigated.
This study was carried out in 53 COC samples obtained from mature metaphase II (MII) oocytes in 53 women undergoing MAR treatment. A total of 38 samples for assay development were pooled by maternal age and gonadotropin treatment into four predetermined subgroups: ≥36 years and recombinant human FSH (r-hFSH), n = 10; ≥36 years and r-hFSH+ recombinant human-luteinizing hormone (r-hLH), n = 10; ≤35 years and r-hFSH, n = 9; ≤35 years and r-hFSH+r-hLH, n = 9. miRNome profiles were determined and compared between subgroups. Expression of defined miRNAs was validated in the remaining fifteen samples, representative of each subgroup, by quantitative polymerase chain reaction (PCR).
COCs were processed for miRNA-enriched total RNA extraction and pooled in homogeneous subgroups to obtain a sufficient amount and quality of starting material to perform the analysis. Each pooled sample underwent miRNA profiling using PCR assay system to examine expression of 752 human miRNAs without pre-amplification. Data were analyzed using the delta-delta Ct method for relative quantitation and prediction of target genes (with at least four algorithms predicting the same miRNA-gene interaction pair (HIT)>4). The miRSystem database provided functional annotation enrichment (raw P-value <0.05) of co-expressed miRNAs.
We found distinctive miRNA expression profiles in each subgroup correlating with age and MAR stimulation. In addition, a number of selective and co-expressed miRNAs were revealed by comparative analysis. A cluster of 37 miRNAs were commonly but differentially expressed in all four pools. Significant differences were observed in expression regulation of 37 miRNAs between age groups (≤35 or ≥36) in women receiving r-hFSH+r-hLH compared to those receiving r-hFSH alone. Higher concentrations and increased numbers of miRNAs were recorded in younger than in older patients, regardless of treatment. Functional and expression studies performed to retrieve common miRNome profiles revealed an enrichment of biological functions in oocyte growth and maturation, embryo development, steroidogenesis, ovarian hyperstimulation, apoptosis and cell survival, glucagon and lipid metabolism, and cell trafficking. The highest scored pathways of target genes of the 37 common miRNAs were associated with mitogen-activated protein kinase (MAPK) signaling pathways, G alpha signaling, transcription regulation, tight junctions, RNA polymerase I and III, and mitochondrial transcription. We identified a potential age- and MAR stimulation-dependent signature in the miRNA landscape of COCs.
We cannot rule out the possibility that other unknown individual genetic or clinical factors may have interfered with the reported results. Since miRNA profiling was conducted with a predefined array of target probes, other miRNA molecules, potentially modulated by age and hormonal stimulation, may have been missed in this study.
miRNA expression in COCs is modulated by gonadotropin treatment and correlates strongly with age. A better understanding of the expression patterns and functions of miRNAs may lead to the development of novel therapeutics to treat ovarian dysfunction and improve fertility in older women.
This study was funded by Merck KGaA, Darmstadt, Germany. All authors declared no competing interest, except SL and TD who are fully employed by Merck KGaA.
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Ocrelizumab is a novel humanized anti-CD20 antibody used for treatment of relapsing remitting and primary progressive multiple sclerosis with evidence of inflammatory activity. Guidelines suggest ...assessing vaccination status and eventually vaccinate patients with multiple sclerosis before new disease modifying therapy initiation. However, there are not any specific recommendations about vaccinal immunity reassessment after ocrelizumab injection. We describe the case of a patient who loss varicella zoster vaccinal immunity after the first ocrelizumab infusion. It is advisable to reassess vaccinal immunity to isolate non-immune patients and to adopt suitable preventive measures, including close contacts vaccination and avoidance of contacts with active infection.
•Vaccination should be updated before any DMT.•Live-attenuated vaccines are contraindicated during immunosuppression and, of course, during anti-CD20 treatment.•Immunization decreases over age.•Cocooning strategy should be recommended in case of contraindication for updating vaccinations in negative patients.•Anti CD-20 treatment decreases vaccines efficacy.
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