Decellularization of human donor aortic and pulmonary valved conduits using low concentration sodium dodecyl sulfate

The clinical use of decellularised cardiac valve allografts is increasing. Long term data will be required to determine whether they outperform conventional cryopreserved allografts. Valves decellularised using different processes may show varied long-term outcomes. It is therefore important to understand the effects of specific decellularisation technologies on the characteristics of donor heart valves. Human cryopreserved aortic and pulmonary valved conduits were decellularised using hypotonic buffer, 0.1% (w/v) SDS and nuclease digestion. The decellularised tissues were compared to cellular cryopreserved valve tissues using histology, immunohistochemistry, quantitation of total DNA, collagen and glycosaminoglycan content, in vitro cytotoxicity assays, uniaxial tensile testing and subcutaneous implantation in mice. The decellularised tissues showed no histological evidence of cells or cell remnants and over 97% DNA removal in all regions (arterial wall, muscle, leaflet and junction). The decellularised tissues retained collagen IV and von Willebrand factor staining with some loss of fibronectin, laminin and chondroitin sulphate staining. There was an absence of MHC Class I staining in decellularised pulmonary valve tissues, with only residual staining in isolated areas of decellularised aortic valve tissues. The collagen content of the tissues was not decreased following decellularisation however the glycosaminoglycan content was reduced. Only moderate changes in the maximum load to failure of the tissues were recorded post-decellularisation. The decellularised tissues were non-cytotoxic in vitro, and were biocompatible in vivo in a mouse subcutaneous implant model. The decellularisation process will now be translated into a GMP compatible process for donor cryopreserved valves with a view to future clinical use

Modeling seizures in the Human Phenotype Ontology according to contemporary ILAE concepts makes big phenotypic data tractable.

OBJECTIVE: The clinical features of epilepsy determine how it is defined, which in turn guides management. Therefore, consideration of the fundamental clinical entities that comprise an epilepsy is essential in the study of causes, trajectories, and treatment responses. The Human Phenotype Ontology (HPO) is used widely in clinical and research genetics for concise communication and modeling of clinical features, allowing extracted data to be harmonized using logical inference. We sought to redesign the HPO seizure subontology to improve its consistency with current epileptological concepts, supporting the use of large clinical data sets in high-throughput clinical and research genomics. METHODS: We created a new HPO seizure subontology based on the 2017 International League Against Epilepsy (ILAE) Operational Classification of Seizure Types, and integrated concepts of status epilepticus, febrile, reflex, and neonatal seizures at different levels of detail. We compared the HPO seizure subontology prior to, and following, our revision, according to the information that could be inferred about the seizures of 791 individuals from three independent cohorts: 2 previously published and 150 newly recruited individuals. Each cohort\u27s data were provided in a different format and harmonized using the two versions of the HPO. RESULTS: The new seizure subontology increased the number of descriptive concepts for seizures 5-fold. The number of seizure descriptors that could be annotated to the cohort increased by 40% and the total amount of information about individuals\u27 seizures increased by 38%. The most important qualitative difference was the relationship of focal to bilateral tonic-clonic seizure to generalized-onset and focal-onset seizures. SIGNIFICANCE: We have generated a detailed contemporary conceptual map for harmonization of clinical seizure data, implemented in the official 2020-12-07 HPO release and freely available at hpo.jax.org. This will help to overcome the phenotypic bottleneck in genomics, facilitate reuse of valuable data, and ultimately improve diagnostics and precision treatment of the epilepsies

No straight lines – young women’s perceptions of their mental health and wellbeing during and after pregnancy: a systematic review and meta-ethnography

Background: Young mothers face mental health challenges during and after pregnancy including increased rates of depression compared to older mothers. While the prevention of teenage pregnancy in countries such as the United States and the United Kingdom has been a focus for policy and research in recent decades, the need to understand young women’s own experiences has been highlighted. The aim of this meta-ethnography was to examine young women’s perceptions of their mental health and wellbeing during and after pregnancy to provide new understandings of those experiences. Methods: A systematic review and meta-ethnographic synthesis of qualitative research was conducted. Seven databases were systematically searched and forward and backward searching conducted. Papers were included if they were from Organisation for Economic Co-operation and Development countries and explored mental health and wellbeing experiences of young mothers (age under 20 in pregnancy; under 25 at time of research) as a primary research question – or where evidence about mental health and wellbeing from participants was foregrounded. Nineteen papers were identified and the Critical Appraisal Skills Programme checklist for qualitative research used to appraise the evidence. Following the seven-step process of meta-ethnography, key constructs were examined within each study and then translated into one another. Results: Seven translated themes were identified forming a new line of argument wherein mental health and wellbeing was analysed as relating to individual bodily experiences; tied into past and present relationships; underpinned by economic insecurity and entangled with feelings of societal surveillance. There were ‘no straight lines’ in young women’s experiences, which were more complex than dominant narratives around overcoming adversity suggest. Conclusions: The synthesis concludes that health and social care professionals need to reflect on the operation of power and stigma in young women’s lives and its impact on wellbeing. It adds to understanding of young women’s mental health and wellbeing during and after pregnancy as located in physical and structural factors rather than individual capacities alone

A Genome-Wide Linkage and Association Scan Reveals Novel Loci for Hypertension and Blood Pressure Traits

Hypertension is caused by the interaction of environmental and genetic factors. The condition which is very common, with about 18% of the adult Hong Kong Chinese population and over 50% of older individuals affected, is responsible for considerable morbidity and mortality. To identify genes influencing hypertension and blood pressure, we conducted a combined linkage and association study using over 500,000 single nucleotide polymorphisms (SNPs) genotyped in 328 individuals comprising 111 hypertensive probands and their siblings. Using a family-based association test, we found an association with SNPs on chromosome 5q31.1 (rs6596140; P<9×10−8) for hypertension. One candidate gene, PDC, was replicated, with rs3817586 on 1q31.1 attaining P = 2.5×10−4 and 2.9×10−5 in the within-family tests for DBP and MAP, respectively. We also identified regions of significant linkage for systolic and diastolic blood pressure on chromosomes 2q22 and 5p13, respectively. Further family-based association analysis of the linkage peak on chromosome 5 yielded a significant association (rs1605685, P<7×10−5) for DBP. This is the first combined linkage and association study of hypertension and its related quantitative traits with Chinese ancestry. The associations reported here account for the action of common variants whereas the discovery of linkage regions may point to novel targets for rare variant screening

Glycerol treatment as recovery procedure for cryopreserved human skin allografts positive for bacteria and fungi

Human donor skin allografts are suitable and much used temporary biological (burn) wound dressings. They prepare the excised wound bed for final autografting and form an excellent substrate for revascularisation and for the formation of granulation tissue. Two preservation methods, glycerol preservation and cryopreservation, are commonly used by tissue banks for the long-term storage of skin grafts. The burn surgeons of the Queen Astrid Military Hospital preferentially use partly viable cryopreserved skin allografts. After mandatory 14-day bacterial and mycological culture, however, approximately 15% of the cryopreserved skin allografts cannot be released from quarantine because of positive culture. To maximize the use of our scarce and precious donor skin, we developed a glycerolisation-based recovery method for these culture positive cryopreserved allografts. The inactivation and preservation method, described in this paper, allowed for an efficient inactivation of the colonising bacteria and fungi, with the exception of spore-formers, and did not influence the structural and functional aspects of the skin allografts

Phylogenetics and taxonomy of the N ew W orld leafy spurges, E uphorbia section T ithymalus ( E uphorbiaceae)

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/107503/1/boj12167-sup-0002-fs2.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/107503/2/boj12167-sup-0003-fs3.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/107503/3/boj12167-sup-0004-fs4.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/107503/4/boj12167.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/107503/5/boj12167-sup-0001-fs1.pd

Alien Invasive Slider Turtle in Unpredicted Habitat: A Matter of Niche Shift or of Predictors Studied?

BACKGROUND: Species Distribution Models (SDMs) aim on the characterization of a species' ecological niche and project it into geographic space. The result is a map of the species' potential distribution, which is, for instance, helpful to predict the capability of alien invasive species. With regard to alien invasive species, recently several authors observed a mismatch between potential distributions of native and invasive ranges derived from SDMs and, as an explanation, ecological niche shift during biological invasion has been suggested. We studied the physiologically well known Slider turtle from North America which today is widely distributed over the globe and address the issue of ecological niche shift versus choice of ecological predictors used for model building, i.e., by deriving SDMs using multiple sets of climatic predictor. PRINCIPAL FINDINGS: In one SDM, predictors were used aiming to mirror the physiological limits of the Slider turtle. It was compared to numerous other models based on various sets of ecological predictors or predictors aiming at comprehensiveness. The SDM focusing on the study species' physiological limits depicts the target species' worldwide potential distribution better than any of the other approaches. CONCLUSION: These results suggest that a natural history-driven understanding is crucial in developing statistical models of ecological niches (as SDMs) while "comprehensive" or "standard" sets of ecological predictors may be of limited use

Quantitative Deep Sequencing Reveals Dynamic HIV-1 Escape and Large Population Shifts during CCR5 Antagonist Therapy In Vivo

High-throughput sequencing platforms provide an approach for detecting rare HIV-1 variants and documenting more fully quasispecies diversity. We applied this technology to the V3 loop-coding region of env in samples collected from 4 chronically HIV-infected subjects in whom CCR5 antagonist (vicriviroc [VVC]) therapy failed. Between 25,000–140,000 amplified sequences were obtained per sample. Profound baseline V3 loop sequence heterogeneity existed; predicted CXCR4-using populations were identified in a largely CCR5-using population. The V3 loop forms associated with subsequent virologic failure, either through CXCR4 use or the emergence of high-level VVC resistance, were present as minor variants at 0.8–2.8% of baseline samples. Extreme, rapid shifts in population frequencies toward these forms occurred, and deep sequencing provided a detailed view of the rapid evolutionary impact of VVC selection. Greater V3 diversity was observed post-selection. This previously unreported degree of V3 loop sequence diversity has implications for viral pathogenesis, vaccine design, and the optimal use of HIV-1 CCR5 antagonists

Climatic predictors of species distributions neglect biophysiologically meaningful variables

This is the final version. Available on open access from Wiley via the DOI in this record.Aim: Species distribution models (SDMs) have played a pivotal role in predicting how species might respond to climate change. To generate reliable and realistic predictions from these models requires the use of climate variables that adequately capture physiological responses of species to climate and therefore provide a proximal link between climate and their distributions. Here, we examine whether the climate variables used in plant SDMs are different from those known to influence directly plant physiology. Location: Global. Methods: We carry out an extensive, systematic review of the climate variables used to model the distributions of plant species and provide comparison to the climate variables identified as important in the plant physiology literature. We calculate the top ten SDM and physiology variables at 2.5 degree spatial resolution for the globe and use principal component analyses and multiple regression to assess similarity between the climatic variation described by both variable sets. Results: We find that the most commonly used SDM variables do not reflect the most important physiological variables and differ in two main ways: (i) SDM variables rely on seasonal or annual rainfall as simple proxies of water available to plants and neglect more direct measures such as soil water content; and (ii) SDM variables are typically averaged across seasons or years and overlook the importance of climatic events within the critical growth period of plants. We identify notable differences in their spatial gradients globally and show where distal variables may be less reliable proxies for the variables to which species are known to respond. Main conclusions: There is a growing need for the development of accessible, fine-resolution global climate surfaces of physiological variables. This would provide a means to improve the reliability of future range predictions from SDMs and support efforts to conserve biodiversity in a changing climate

Etoricoxib - preemptive and postoperative analgesia (EPPA) in patients with laparotomy or thoracotomy - design and protocols

<p>Abstract</p> <p>Background and Objective</p> <p>Our objective was to report on the design and essentials of the <it>Etoricoxib </it>protocol<it>- Preemptive and Postoperative Analgesia (EPPA) </it>Trial, investigating whether preemptive analgesia with cox-2 inhibitors is more efficacious than placebo in patients who receive either laparotomy or thoracotomy.</p> <p>Design and Methods</p> <p>The study is a 2 × 2 factorial armed, double blinded, bicentric, randomised placebo-controlled trial comparing (a) etoricoxib and (b) placebo in a pre- and postoperative setting. The total observation period is 6 months. According to a power analysis, 120 patients scheduled for abdominal or thoracic surgery will randomly be allocated to either the preemptive or the postoperative treatment group. These two groups are each divided into two arms. Preemptive group patients receive etoricoxib prior to surgery and either etoricoxib again or placebo postoperatively. Postoperative group patients receive placebo prior to surgery and either placebo again or etoricoxib after surgery (2 × 2 factorial study design). The Main Outcome Measure is the cumulative use of morphine within the first 48 hours after surgery (measured by patient controlled analgesia PCA). Secondary outcome parameters include a broad range of tests including sensoric perception and genetic polymorphisms.</p> <p>Discussion</p> <p>The results of this study will provide information on the analgesic effectiveness of etoricoxib in preemptive analgesia and will give hints on possible preventive effects of persistent pain.</p> <p>Trial registration</p> <p>NCT00716833</p