3D human skin bioprinting: a view from the bio side

Based on the 3D printing technologies and the concepts developed in tissue engineering during the last decades, 3D bioprinting is emerging as the most innovative and promising technology for the generation of human tissues and organs. In the case of skin bioprinting, thanks to the research process carried out during the last years, interfollicular skin has been printed with a structural and functional quality that paves the way for clinical and industrial applications. This review analyzes the present achievements and the future improvements that this area must bring about if bioprinted skin is to become widely used. We have made an effort to integrate the technological and the biological/biomedical sides of the subject.We thank the Spanish Fundación Ramón Areces for its continuous support. This work was partially supported by grant DPI2014-61887-EXP from the Spanish Ministerio de Economía y Competitividad

Factors associated with crisis pregnancies in Ireland: Findings from three nationally representative sexual health surveys

Background: Findings on the demographic and sexual health characteristics associated with the experience of a crisis pregnancy is important to inform the public health policy of a country, including Ireland. Findings from other jurisdictions have suggested that certain demographic groups are at risk for unintended pregnancies and the disparity between the groups have been growing in recent years. Ireland is a country which experienced much economic and societal change in the first decade of the 21st century, changes which are likely to have affected demographic variables pertaining to sexual health. The current study had two aims: to investigate changes in the socioeconomic characteristics associated with crisis pregnancies over a seven year period [2003 to 2010], and to investigate the recent [2010] socioeconomic risk factors associated with crisis pregnancies in Ireland. Methods: The study compared the results from 18-45 year old women using data from three broadly similar nationally representative Irish sexual health surveys carried out in 2003, 2004-2006 and 2010. Chi square analysis compared of the socioeconomic characteristics across the seven year period and found that a higher proportion of women with two or more children and women for whom religion was not important reported a crisis pregnancy in 2010 compared with earlier years. A logistic regression then investigated the sexual health history and socioeconomic factors associated with the experience of a recent crisis pregnancy using the most recent 2010 data. Results: Receipt of sex education and contraception use at first sex significantly predicted the experiencing of a recent crisis pregnancy. Younger women and those with a lower level of education were more likely to report having experienced a recent crisis pregnancy. Conclusion: Similar demographic groups are at risk for experiencing a crisis pregnancy in Ireland compared with international research, yet the disparities between demographic groups who have experienced a crisis pregnancy appear to be decreasing rather than increasing over a seven year period. Recommendations are made with regard to the provision of continued sex education throughout the lifespan, particularly for those women who are at an increased risk of experiencing a crisis pregnancy

Synthesis and Characterization of Ultrathin Silver Sulfide Nanoplatelets

© 2017 American Chemical Society. We report the synthesis of ultrathin silver sulfide (Ag2S) nanoplatelets (NPLs) synthesized via a one-pot method in ethylene glycol with 3-mercaptopropionic acid serving as both the sulfur precursor and the platelet ligand. The colloidally synthesized nanoplatelets are exceptionally thin, with a thickness of only 3.5 ± 0.2 Å and a 1S exciton Bohr diameter to confinement ratio of ∼12.6. The NPL growth is shown to be quantized by layer thickness using absorption and photoluminescence (PL) spectroscopy. Transmission electron microscopy, atomic force microscopy, and X-ray diffraction analyses of the NPLs show that they correspond to the (202) plane of the β-Ag2S structure. The PL quantum yield of these NPLs is ∼30%, suggesting their potential use in biomedical imaging. Optoelectronic properties were evaluated via sensitized photocurrent spectroscopy with the resulting spectra closely matching the distinctive absorption spectral shape of the Ag2S NPLs

Alteration of Forest Structure Modifies the Distribution of Scale Insect, Stigmacoccus garmilleri, in Mexican Tropical Montane Cloud Forests

Stigmacoccus garmilleri Foldi (Hemiptera: Margarodidae) is an ecologically important honeydew-producing scale insect associated with oak trees (Quercus spp.) in highland forests of Veracruz, Mexico. The honeydew exudates of S. garmilleri serve as a significant nutrient source to many species of birds, insects, and sooty molds. Oak trees found in the forest interior, forest edge, and those scattered in pasture areas support scale insect colonies, though the pattern of insect infestations on trees within these varying landscape types has not been elucidated. This study aims to describe the distribution of scale insect infestation and any distinctions in honeydew production based on tree location. Scale insect density, honeydew volume, and sugar concentration were surveyed throughout a continuous landscape that included both patches of forest and scattered pasture trees. In addition, the anal filament through which the honeydew drop is secreted was also measured and was experimentally removed to test and measure regrowth. Scale insect densities on tree trunks were greatest on pasture trees, while intermediate densities were found on trees at the forest edge, and low densities on interior forest trees, suggesting that trees in disturbed areas are more susceptible to scale insect infestation. Trees with small diameters at breast height had significantly higher insect densities than trees with medium to large diameters. Trunk aspect (North, South, East, and West) was not a significant determinant of scale insect density. In forested areas higher densities of scale insects were found at three meters height in comparison to lower heights. Sugar concentrations and drop volumes of honeydew in forest and pasture areas were not significantly different. However, scale-insect anal tubes/filaments were significantly longer in pasture than they were in forests. Sugar concentrations of honeydew appeared to be positively correlated with temperature and negatively correlated with relative humidity. Experiments indicated that anal filaments could grow approximately 4 mm every 24 hours, and average tube growth was significantly faster in pasture than in forest, suggesting that there may be a physiological effect on the insect due to landscape disturbance. The results obtained in this study describe the increases in scale insect infestation of trees with forest disturbance. The effect of these increased scale insect densities on the host tree physiology is still to be resolved

Catheter ablation vs. thoracoscopic surgical ablation in long-standing persistent atrial fibrillation: CASA-AF randomized controlled trial.

AIMS: Long-standing persistent atrial fibrillation (LSPAF) is challenging to treat with suboptimal catheter ablation (CA) outcomes. Thoracoscopic surgical ablation (SA) has shown promising efficacy in atrial fibrillation (AF). This multicentre randomized controlled trial tested whether SA was superior to CA as the first interventional strategy in de novo LSPAF. METHODS AND RESULTS: We randomized 120 LSPAF patients to SA or CA. All patients underwent predetermined lesion sets and implantable loop recorder insertion. Primary outcome was single procedure freedom from AF/atrial tachycardia (AT) ≥30 s without anti-arrhythmic drugs at 12 months. Secondary outcomes included clinical success (≥75% reduction in AF/AT burden); procedure-related serious adverse events; changes in patients' symptoms and quality-of-life scores; and cost-effectiveness. At 12 months, freedom from AF/AT was recorded in 26% (14/54) of patients in SA vs. 28% (17/60) in the CA group [OR 1.128, 95% CI (0.46-2.83), P = 0.83]. Reduction in AF/AT burden ≥75% was recorded in 67% (36/54) vs. 77% (46/60) [OR 1.13, 95% CI (0.67-4.08), P = 0.3] in SA and CA groups, respectively. Procedure-related serious adverse events within 30 days of intervention were reported in 15% (8/55) of patients in SA vs. 10% (6/60) in CA, P = 0.46. One death was reported after SA. Improvements in AF symptoms were greater following CA. Over 12 months, SA was more expensive and provided fewer quality-adjusted life-years (QALYs) compared with CA (0.78 vs. 0.85, P = 0.02). CONCLUSION: Single procedure thoracoscopic SA is not superior to CA in treating LSPAF. Catheter ablation provided greater improvements in symptoms and accrued significantly more QALYs during follow-up than SA. CLINICAL TRIAL REGISTRATION: ISRCTN18250790 and ClinicalTrials.gov: NCT02755688

Expression of estrogen receptor beta in the breast carcinoma of BRCA1 mutation carriers

<p>Abstract</p> <p>Background</p> <p>Breast cancers (BC) in women carrying mutations in BRCA1 gene are more frequently estrogen receptor negative than the nonhereditary BC. Nevertheless, tamoxifen has been found to have a protective effect in preventing contralateral tumors in BRCA1 mutation carriers. The identification of the second human estrogen receptor, ERβ, raised a question of its role in hereditary breast cancer. The aim of this study was to assess the frequency of ERα, ERβ, PgR (progesterone receptor) and HER-2 expression in breast cancer patients with mutated <it>BRCA1 </it>gene and in the control group.</p> <p>Methods</p> <p>The study group consisted of 48 women with <it>BRCA1 </it>gene mutations confirmed by multiplex PCR assay. The patients were tested for three most common mutations of BRCA1 affecting the Polish population (5382insC, C61G, 4153delA). Immunostaining for ERα, ERβ and PgR (progesterone receptor) was performed using monoclonal antibodies against ERα, PgR (DakoCytomation), and polyclonal antibody against ERβ (Chemicon). The EnVision detection system was applied. The study population comprised a control group of 120 BC operated successively during the years 1998–99.</p> <p>Results</p> <p>The results of our investigation showed that <it>BRCA1 </it>mutation carriers were more likely to have ERα-negative breast cancer than those in the control group. Only 14.5% of <it>BRCA1</it>-related cancers were ERα-positive compared with 57.5% in the control group (<it>P </it>< 0.0001). On the contrary, the expression of ERβ protein was observed in 42% of <it>BRCA1</it>-related tumors and in 55% of the control group. An interesting finding was that most hereditary cancers (75% of the whole group) were triple-negative: ERα(-)/PgR(-)/HER-2(-) but almost half of this group (44.4%) showed the expression of ERβ.</p> <p>Conclusion</p> <p>In the case of <it>BRCA1</it>-associated tumors the expression of ERβ was significantly higher than the expression of ERα. This may explain the effectiveness of tamoxifen in preventing contralateral breast cancer development in <it>BRCA1 </it>mutation carriers.</p

Association of oestrogen receptor beta 2 (ERβ2/ERβcx) with outcome of adjuvant endocrine treatment for primary breast cancer – a retrospective study

<p>Abstract</p> <p>Background</p> <p>Oestrogen receptor beta (ERβ) modulates ERα activity; wild type ERβ (ERβ1) and its splice variants may therefore impact on hormone responsiveness of breast cancer. ERβ2/ERβcx acts as a dominant negative inhibitor of ERα and expression of ERβ2 mRNA has been proposed as a candidate marker for outcome in primary breast cancer following adjuvant endocrine therapy. We therefore now assess ERβ2 protein by immunostaining and mRNA by quantitative RT-PCR in relation to treatment outcome.</p> <p>Methods</p> <p>ERβ2-specific immunostaining was quantified in 141 primary breast cancer cases receiving adjuvant endocrine therapy, but no neoadjuvant therapy or adjuvant chemotherapy. The expression of mRNA for ERβ2/ERβcx was measured in 100 cases by quantitative RT-PCR. Statistical analysis of breast cancer relapse and breast cancer survival was performed using Kaplan Meier log-rank tests and Cox's univariate and multivariate survival analysis.</p> <p>Results</p> <p>High ERβ2 immunostaining (Allred score >5) and high ERβ2 mRNA levels were independently associated with significantly better outcome across the whole cohort, including both ERα positive and negative cases (Log-Rank P < 0.05). However, only ERβ2 mRNA levels were significantly associated with better outcome in the ERα + subgroup (Log-Rank P = 0.01) and this was independent of grade, size, nodal status and progesterone receptor status (Cox hazard ratio 0.31 P = 0.02 for relapse; 0.17 P = 0.01 for survival). High ERβ2 mRNA was also associated with better outcome in node negative cases (Log Rank P < 0.001).</p> <p>ERβ2 protein levels were greater in ERα positive cases (T-test P = 0.00001), possibly explaining the association with better outcome. Levels of ERβ2 protein did not correlate ERβ2 mRNA levels, but 34% of cases had both high mRNA and protein and had a significantly better outcome (Log-Rank relapse P < 0.005).</p> <p>Conclusion</p> <p>High ERβ2 protein levels were associated with ERα expression. Although most cases with high ERβ2 mRNA had strong ERβ2 immunostaining, mRNA levels but not protein levels were independently predictive of outcome in tamoxifen-treated ERα + tumours. Post-transcriptional control needs to be considered when assessing the biological or clinical importance of ERβ proteins.</p

Multiphoton absorption in amyloid protein fibres

Fibrillization of peptides leads to the formation of amyloid fibres, which, when in large aggregates, are responsible for diseases such as Alzheimer's and Parkinson's. Here, we show that amyloids have strong nonlinear optical absorption, which is not present in native non-fibrillized protein. Z-scan and pump-probe experiments indicate that insulin and lysozyme β-amyloids, as well as α-synuclein fibres, exhibit either two-photon, three-photon or higher multiphoton absorption processes, depending on the wavelength of light. We propose that the enhanced multiphoton absorption is due to a cooperative mechanism involving through-space dipolar coupling between excited states of aromatic amino acids densely packed in the fibrous structures. This finding will provide the opportunity to develop nonlinear optical techniques to detect and study amyloid structures and also suggests that new protein-based materials with sizable multiphoton absorption could be designed for specific applications in nanotechnology, photonics and optoelectronics

Vaccination with hemagglutinin or neuraminidase DNA protects BALB/c mice against influenza virus infection in presence of maternal antibody

<p>Abstract</p> <p>Background</p> <p>Maternal antibody is the major form of protection against disease in early life; however, its presence interferes with active immunization of offspring. In order to overcome the immunosuppression caused by maternal antibody, several immune strategies were explored in this paper using mouse model and influenza vaccines.</p> <p>Results</p> <p>The results showed that: i) when the offspring were immunized with the same vaccine as their mothers, whether inactivated or DNA vaccine, the presence of maternal antibody inhibited offspring immune response and the offspring could not be protected from a lethal influenza virus infection; ii) when the offspring, born to mothers immunized with inactivated vaccine, were immunized with NA DNA vaccine, the interference of maternal antibody were overcome and the offspring could survive a lethal virus challenge; iii) when the offspring were immunized with different DNA vaccine from that for their mothers, the interference of maternal antibody were also overcome. In addition, high-dose inactivated vaccine in maternal immunization caused partial inhibition in offspring when the offspring were immunized with HA DNA vaccine, while lower dose caused no significant immunosuppression.</p> <p>Conclusion</p> <p>To avoid the interference of maternal antibody in influenza vaccination of offspring, mothers and their offspring shall not be immunized with the same vaccine. If mothers are immunized with inactivated vaccine, NA DNA vaccine for the offspring shall be effective; and if mothers are immunized with HA (NA) DNA, NA (HA) DNA for the offspring shall be effective.</p

Task-Related Effects on the Temporal and Spatial Dynamics of Resting-State Functional Connectivity in the Default Network

Recent evidence points to two potentially fundamental aspects of the default network (DN), which have been relatively understudied. One is the temporal nature of the functional interactions among nodes of the network in the resting-state, usually assumed to be static. The second is possible influences of previous brain states on the spatial patterns (i.e., the brain regions involved) of functional connectivity (FC) in the DN at rest. The goal of the current study was to investigate modulations in both the spatial and temporal domains. We compared the resting-state FC of the DN in two runs that were separated by a 45 minute interval containing cognitive task execution. We used partial least squares (PLS), which allowed us to identify FC spatiotemporal patterns in the two runs and to determine differences between them. Our results revealed two primary modes of FC, assessed using a posterior cingulate seed – a robust correlation among DN regions that is stable both spatially and temporally, and a second pattern that is reduced in spatial extent and more variable temporally after cognitive tasks, showing switching between connectivity with certain DN regions and connectivity with other areas, including some task-related regions. Therefore, the DN seems to exhibit two simultaneous FC dynamics at rest. The first is spatially invariant and insensitive to previous brain states, suggesting that the DN maintains some temporally stable functional connections. The second dynamic is more variable and is seen more strongly when the resting-state follows a period of task execution, suggesting an after-effect of the cognitive activity engaged during task that carries over into resting-state periods