Direct-Write Deposition of Thermogels

The use of biocompatible hydrogels has widely extended the potential of additive manufacturing (AM) in the biomedical field leading to the production of 3D tissue and organ analogs for in vitro and in vivo studies. In this work, the direct-write deposition of thermosensitive hydrogels is described as a facile route to obtain 3D cell-laden constructs with controlled 3D structure and stable behavior under physiological conditions

Nm23 expression in endometrial and cervical cancer: inverse correlation with lymph node involvement and myometrial invasion.

The expression of nm23 has been shown to correlate in some solid tumours with their metastatic potential and to be associated with a favourable prognosis in human breast cancer and melanoma. In breast and ovarian cancer nm23 expression is also correlated with lymph node involvement. We analysed the expression of nm23-H1 and -H2 in normal endometrium and in endometrial and cervical cancer by both Northern and Western blotting. Cellular localisation of Nm23-H1 was visualised by immunohistochemistry mostly in the cytoplasm. Both isoforms of Nm23 were present in all the samples analysed, and a clear direct correlation between Nm23-H1 and -H2 levels was evident. Median nm23-H2 levels were higher than than -H1 levels in both tissues. Cervical cancer patients with lymph node involvement were shown to have significantly lower protein levels of Nm23 (P < 0.007 for H1 and P < 0.009 for H2), and a similar trend was also evident in endometrial cancer. Furthermore, the degree of myometrial invasion in endometrial cancer patients was also inversely correlated with Nm23-H1 levels of expression (P < 0.003). Nm23 level may therefore be taken into consideration as a new marker in the prognostic characterisation and in the treatment planning of uterine tumour patients

Response to the 2009 influenza A(H1N1) pandemic in Italy

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Vaccino antinfluenzale stagionale in Italia: misurare l&#8217;efficacia sul campo e la sicurezza : Stagione 2015-2016

In Italia, nella stagione influenzale 2015-2016 sono stati condotti dall\u2019Istituto Superiore di Sanit\ue0 (ISS), con il supporto dell\u2019Agenzia Italiana del Farmaco (AIFA), due studi al fine di stimare l\u2019efficacia sul campo (I-MOVE, Influenza - Monitoring Vaccine Effectiveness) e valutare la sicurezza (SVEVA, Studio sulla Valutazione degli Eventi dopo Vaccinazione Antinfluenzale) del vaccino antinfluenzale. Nel complesso hanno aderito 8 Regioni che corrispondono a oltre met\ue0 della popolazione italiana nel 2015 (non tutte le Regioni hanno aderito a entrambi gli obiettivi di studio). Nello studio I-MOVE sono stati reclutati 1.094 casi di ILI (Influenza-Like Illness), dai 64 medici di medicina generale e pediatri di libera scelta partecipanti (506 casi e 498 controlli). I risultati suggeriscono che il vaccino ha conferito una protezione moderata nei confronti del tipo virale A(H1N1)pdm09 e molto bassa per A(H3N2) e B a causa del sostanziale grado di mismatch antigenico osservato, rispetto al ceppo vaccinale. Nello studio SVEVA sono stati monitorati 3.213 soggetti vaccinati e rilevati 854 (26%) eventi dopo 7 giorni dalla vaccinazione, la maggior parte dei quali di lieve entit\ue0. Al fine di ottenere stime di efficacia pi\uf9 solide e descrivere eventi avversi rari, \ue8 necessario tuttavia raggiungere una numerosit\ue0 campionaria maggiore.In Italy, during the 2015/2016 flu season, the National Institute of Health (ISS), with the support of the Italian Drug Agency (AIFA), conducted two studies to estimate vaccine effectiveness (I-MOVE) and evaluate safety (SVEVA) of the flu vaccine. A total of 8 regions, among 21, participated to the study which can correspond to more than 50% of the Italian population in 2015 (not all regions participated to both objectives of the study). For the I-MOVE study, 1094 cases of ILI (506 cases and 498 controls) were recruited by 64 general practitioners and pediatricians. The results indicate that the vaccine gave moderate protection against the virus type A (H1N1) pdm09 and very low protection for A (H3N2) and B due to the antigenic mismatch that was observed, compared to the vaccine strain. For SVEVA study, 3213 vaccinated cases were monitored and 854 (26%) side effects were notified after 7 days of vaccination, the major part were mild. In order to obtain more solid data regarding vaccine effectiveness, and to describe rare adverse events, it is necessary to increase the sample size of both studies

Numerical study on load-bearing capabilities of beam-like lattice structures with three different unit cells

The design and analysis of lattice structures manufactured using Additive Manufacturing (AM) technique is a new approach to create lightweight high-strength components. However, it is difficult for engineers to choose the proper unit cell for a certain function structure and loading case. In this paper, three beam-like lattice structures with triangular prism, square prism and hexagonal prism were designed, manufactured by SLM process using AlSi10Mg and tested. The mechanical performances of lattice structures with equal relative density, equal base area and height, and equal length for all unit cells were conducted by Finite Element Analysis (FEA). It was found that effective Young’s modulus is proportional to relative density, but with different affecting levels. When the lattice structures are designed with the same relative density or the same side lengths, the effective Young’s modulus of lattice structure with triangular prism exhibits the maximum value for both cases. When the lattice structures are designed with the same base areas for all unit cells, the effective Young’s modulus of lattice structures with square prism presents the maximum. FEA results also show that the maximum stress of lattice structures with triangular prisms in each comparison is at the lowest level and the stiffness-to-mass ratio remains at the maximum value, showing the overwhelming advantages in terms of mechanical strength. The excellent agreements between numerical results and experimental tests reveal the validity of FEA methods applied. The results in this work provide an explicit guideline to fabricate beam-like lattice structures with the best tensile and bending capabilities

Selective laser melting–enabled electrospinning: Introducing complexity within electrospun membranes

Additive manufacturing technologies enable the creation of very precise and well-defined structures that can mimic hierarchical features of natural tissues. In this article, we describe the development of a manufacturing technology platform to produce innovative biodegradable membranes that are enhanced with controlled microenvironments produced via a combination of selective laser melting techniques and conventional electrospinning. This work underpins the manufacture of a new generation of biomaterial devices that have significant potential for use as both basic research tools and components of therapeutic implants. The membranes were successfully manufactured and a total of three microenvironment designs (niches) were chosen for thorough characterisation. Scanning electron microscopy analysis demonstrated differences in fibre diameters within different areas of the niche structures as well as differences in fibre density. We also showed the potential of using the microfabricated membranes for supporting mesenchymal stromal cell culture and proliferation. We demonstrated that mesenchymal stromal cells grow and populate the membranes penetrating within the niche-like structures. These findings demonstrate the creation of a very versatile tool that can be used in a variety of tissue regeneration applications including bone healing

Schizophrenia risk conferred by rare protein-truncating variants is conserved across diverse human populations

Schizophrenia (SCZ) is a chronic mental illness and among the most debilitating conditions encountered in medical practice. A recent landmark SCZ study of the protein-coding regions of the genome identified a causal role for ten genes and a concentration of rare variant signals in evolutionarily constrained genes1. This recent study—and most other large-scale human genetics studies—was mainly composed of individuals of European (EUR) ancestry, and the generalizability of the findings in non-EUR populations remains unclear. To address this gap, we designed a custom sequencing panel of 161 genes selected based on the current knowledge of SCZ genetics and sequenced a new cohort of 11,580 SCZ cases and 10,555 controls of diverse ancestries. Replicating earlier work, we found that cases carried a significantly higher burden of rare protein-truncating variants (PTVs) among evolutionarily constrained genes (odds ratio = 1.48; P = 5.4 × 10−6). In meta-analyses with existing datasets totaling up to 35,828 cases and 107,877 controls, this excess burden was largely consistent across five ancestral populations. Two genes (SRRM2 and AKAP11) were newly implicated as SCZ risk genes, and one gene (PCLO) was identified as shared by individuals with SCZ and those with autism. Overall, our results lend robust support to the rare allelic spectrum of the genetic architecture of SCZ being conserved across diverse human populations

Mapping genomic loci implicates genes and synaptic biology in schizophrenia

Schizophrenia has a heritability of 60-80%1, much of which is attributable to common risk alleles. Here, in a two-stage genome-wide association study of up to 76,755 individuals with schizophrenia and 243,649 control individuals, we report common variant associations at 287 distinct genomic loci. Associations were concentrated in genes that are expressed in excitatory and inhibitory neurons of the central nervous system, but not in other tissues or cell types. Using fine-mapping and functional genomic data, we identify 120 genes (106 protein-coding) that are likely to underpin associations at some of these loci, including 16 genes with credible causal non-synonymous or untranslated region variation. We also implicate fundamental processes related to neuronal function, including synaptic organization, differentiation and transmission. Fine-mapped candidates were enriched for genes associated with rare disruptive coding variants in people with schizophrenia, including the glutamate receptor subunit GRIN2A and transcription factor SP4, and were also enriched for genes implicated by such variants in neurodevelopmental disorders. We identify biological processes relevant to schizophrenia pathophysiology; show convergence of common and rare variant associations in schizophrenia and neurodevelopmental disorders; and provide a resource of prioritized genes and variants to advance mechanistic studies

2015/16 seasonal vaccine effectiveness against hospitalisation with influenza a(H1N1)pdm09 and B among elderly people in Europe: Results from the I-MOVE+ project

We conducted a multicentre test-negative caseâ\u80\u93control study in 27 hospitals of 11 European countries to measure 2015/16 influenza vaccine effectiveness (IVE) against hospitalised influenza A(H1N1)pdm09 and B among people aged â\u89¥ 65 years. Patients swabbed within 7 days after onset of symptoms compatible with severe acute respiratory infection were included. Information on demographics, vaccination and underlying conditions was collected. Using logistic regression, we measured IVE adjusted for potential confounders. We included 355 influenza A(H1N1)pdm09 cases, 110 influenza B cases, and 1,274 controls. Adjusted IVE against influenza A(H1N1)pdm09 was 42% (95% confidence interval (CI): 22 to 57). It was 59% (95% CI: 23 to 78), 48% (95% CI: 5 to 71), 43% (95% CI: 8 to 65) and 39% (95% CI: 7 to 60) in patients with diabetes mellitus, cancer, lung and heart disease, respectively. Adjusted IVE against influenza B was 52% (95% CI: 24 to 70). It was 62% (95% CI: 5 to 85), 60% (95% CI: 18 to 80) and 36% (95% CI: -23 to 67) in patients with diabetes mellitus, lung and heart disease, respectively. 2015/16 IVE estimates against hospitalised influenza in elderly people was moderate against influenza A(H1N1)pdm09 and B, including among those with diabetes mellitus, cancer, lung or heart diseases

Mapping genomic loci prioritises genes and implicates synaptic biology in schizophrenia

Schizophrenia has a heritability of 60–80%1, much of which is attributable to common risk alleles. Here, in a two-stage genome-wide association study of up to 76,755 individuals with schizophrenia and 243,649 control individuals, we report common variant associations at 287 distinct genomic loci. Associations were concentrated in genes that are expressed in excitatory and inhibitory neurons of the central nervous system, but not in other tissues or cell types. Using fine-mapping and functional genomic data, we identify 120 genes (106 protein-coding) that are likely to underpin associations at some of these loci, including 16 genes with credible causal non-synonymous or untranslated region variation. We also implicate fundamental processes related to neuronal function, including synaptic organization, differentiation and transmission. Fine-mapped candidates were enriched for genes associated with rare disruptive coding variants in people with schizophrenia, including the glutamate receptor subunit GRIN2A and transcription factor SP4, and were also enriched for genes implicated by such variants in neurodevelopmental disorders. We identify biological processes relevant to schizophrenia pathophysiology; show convergence of common and rare variant associations in schizophrenia and neurodevelopmental disorders; and provide a resource of prioritized genes and variants to advance mechanistic studies