Opioid Dependent and Pregnant: What Are the Best Options for Mothers and Neonates?

Pregnancy in opioid-dependent women is a major public health issue. Women who are afflicted by opioid addiction are a highly vulnerable group of patients frequently becoming pregnant unplanned and at risk of adverse pregnancy outcomes and peri-natal complications. Opioid agonist maintenance treatment is the best option for the majority of women. Ideally, early and closely monitored treatment in an interdisciplinary team approach including social workers, nurses, psychologists, psychiatrists, gynecologists, anesthesiologists, and pediatricians should be provided. The treatment of comorbid psychiatric conditions, the resolution of financial, legal, and housing issues, and the psychosocial support provided have a significant effect on optimizing pregnancy outcomes. This paper aims to update health professionals in the field of gynecology and obstetrics on the latest optimal treatment approaches for mothers suffering from opioid dependence and their neonates

Effective microRNAs for cell line engineering and cellular mechanisms of action

MicroRNAs (miRNAs) constitute an important class of small non-coding RNAs and are imperative for the regulation of gene expression in mammalian cells. By post-transcriptionally modulating the expression of hundreds of different genes concomitantly, miRNAs are capable of regulating entire cellular pathways to control cellular phenotypes. Thus, miRNAs represent promising tools for cell engineering of biopharmaceutical production cells. By taking advantage of a functional high-content miRNA screening procedure we were able to identify \u3e750 miRNAs significantly affecting protein expression, cell growth, apoptosis and necrosis in CHO cells. Functionality of impactful miRNAs could be successfully validated in secondary screening approaches as well as by stable miRNA overexpression. Furthermore, we demonstrate that identified pro-productive miRNAs were able to substantially increase monoclonal antibody yields of two industrial high-producing CHO cell lines expressing different monoclonal antibodies. To better understand the molecular mechanisms behind this improved phenotype, we analyzed selected pro-productive miRNAs and were able to reveal downstream mRNA targets and underlying cellular mechanisms of action. In this conjunction, we identified the ubiquitin pathway to be involved in enhanced protein production induced by the miR-30 family, miR-2861 was discovered as a potential HDAC5 inhibitor enhancing productivity in CHO cells while maintaining product quality and miR-483 was shown to act as species independent universal enhancer of cellular antibody and viral productivity while mimicking mild hypothermia. These significant findings reveal not only the existence of effective miRNAs for the use in cell line engineering but also shed light on underlying mechanisms of action within the cellular environment supporting the hypothesis that miRNAs regulate diverse and essential cellular pathways important for industrial protein production. Engineering production cell lines using miRNAs therefore constitutes a highly attractive and easy-to-use methodology to substantially enhance cellular productivity

In Situ Observation Reveals Local Detachment Mechanisms and Suction Effects in Micropatterned Adhesives

Fibrillar adhesion pads of insects and geckoes have inspired the design of high-performance adhesives enabling a new generation of handling devices. Despite much progress over the last decade, the current understanding of these adhesives is limited to single contact pillars and the behavior of whole arrays is largely unexplored. In the study reported here, a novel approach is taken to gain insight into the detachment mechanisms of whole micropatterned arrays. Individual contacts are imaged by frustrated total internal reflection, allowing in situ observation of contact formation and separation during adhesion tests. The detachment of arrays is found to be governed by the distributed adhesion strength of individual pillars, but no collaborative effect mediated by elastic interactions can be detected. At the maximal force, about 30% of the mushroom structures are already detached. The adhesive forces decrease with reduced air pressure by 20% for the smooth and by 6% for the rough specimen. These contributions are attributed to a suction effect, whose strength depends critically on interfacial defects controlling the sealing quality of the contact. This dominates the detachment process and the resulting adhesion strength. © 2019 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinhei

Determining the Pace and Magnitude of Lake Level Changes in Southern Ethiopia Over the Last 20,000 Years Using Lake Balance Modeling and SEBAL

The Ethiopian rift is known for its diverse landscape, ranging from arid and semi-arid savannahs to high and humid mountainous regions. Lacustrine sediments and paleo-shorelines indicate water availability fluctuated dramatically from deep fresh water lakes, to shallow highly alkaline lakes, to completely desiccated lakes. To investigate the role lakes have played through time as readily available water sources to humans, an enhanced knowledge of the pace, character and magnitude of these changes is essential. Hydro-balance models are used to calculate paleo-precipitation rates and the potential pace of lake level changes. However, previous models did not consider changes in hydrological connectivity during humid periods in the rift system, which may have led to an overestimation of paleo-precipitation rates. Here we present a comprehensive hydro-balance modeling approach that simulates multiple rift lakes from the southern Ethiopian Rift (lakes Abaya, Chamo, and paleo-lake Chew Bahir) simultaneously, considering their temporal hydrological connectivity during high stands of the African Humid Period (AHP, ~15–5 ka). We further used the Surface Energy Balance Algorithm for Land (SEBAL) to calculate the evaporation of paleo-lake Chew Bahir's catchment. We also considered the possibility of an additional rainy season during the AHP as previously suggested by numerous studies. The results suggest that an increase in precipitation of 20–30% throughout the southern Ethiopian Rift is necessary to fill paleo-lake Chew Bahir to its overflow level. Furthermore, it was demonstrated that paleo-lake Chew Bahir was highly dependent on the water supply from the upper lakes Abaya and Chamo and dries out within ~40 years if the hydrological connection is cut off and the precipitation amount decreases to present day conditions. Several of such rapid lake level fluctuations, from a freshwater to a saline lake, might have occurred during the termination of the AHP, when humid conditions were less stable. Fast changes in fresh water availability requires high adaptability for humans living in the area and might have exerted severe environmental stress on humans in a sub-generational timescale

Selbstermächtigung und Selbstorganisation als Schlüssel für nachhaltige Lern- und Transformationsprozesse in der Region Römerland Carnuntum

The region Römerland Carnuntum (Lower Austria) is located between the metropolitan areas of Vienna andBratislava and benefits from dynamic demographic and economic development. However, these processes ofgrowth and rapid change are accompanied by specific challenges that are controversial and much-discussed within the region. The question comes up, how a high level of quality of life can be secured in the future and how a transformation towards sustainability can be initiated and established. Since traditional instruments of spatial planning, structural policy, and regional development increasingly show deficits in the face of such complex, multidimensional challenges, the region has set itself the goal of breaking new ground in cooperation, self-organisation, and self-empowerment, within the framework of which the actors in the region become self-organized, collaborative and long-term carriers of sustainable learning and transformation processes in the region. This article describes the structure of the project and highlights, in particular,challenges related to the committee 'Zukunftsrat Römerland Carnuntum', as a basis for self-empowerment, self-organisation and transformative learning as well as to the start-up phase of the transdisciplinary collaboration.First insights after almost one year of project runtime show, that therepresentative composition of the Zukunftsrat, and especially the random selection of citizens proved to be difficult. Nevertheless, the projekt benefits from outstanding commitment and a high willingness to participate on the part of the regional population

Spatio-temporal variations of climate along possible African-Arabian routes of H. sapiens expansion

Eastern Africa and Arabia were major hominin hotspots and critical crossroads for migrating towards Asia during the late Pleistocene. To decipher the role of spatiotemporal environmental change on human occupation and migration patterns, we remeasured the marine core from Meteor Site KL 15 in the Gulf of Aden and reanalyzed its data together with the aridity index from ICDP Site Chew Bahir in eastern Africa and the wet-dry index from ODP Site 967 in the eastern Mediterranean Sea using linear and nonlinear time series analysis. These analyses show major changes in the spatiotemporal paleoclimate dynamics at 400 and 150 ka BP (thousand years before 1950), presumably driven by changes in the amplitude of the orbital eccentricity. From 400 to 150 ka BP, eastern Africa and Arabia show synchronized wet-dry shifts, which changed drastically at 150 ka BP. After 150 ka BP, an overall trend to dry climate states is observable, and the hydroclimate dynamics between eastern Africa and Arabia are negatively correlated. Those spatio-temporal variations and interrelationships of climate potentially influenced the availability of spatial links for human expansion along those vertices. We observe positively correlated network links during the supposed out-of-Africa migration phases of H. sapiens. Furthermore, our data do not suggest hominin occupation phases during specific time intervals of humid or stable climates but provide evidence of the so far underestimated potential role of climate predictability as an important factor of hominin ecological competitiveness

Dynamic and static circulating cancer microRNA biomarkers : a validation study

For cancers and other pathologies, early diagnosis remains the most promising path to survival. Profiling of longitudinal cohorts facilitates insights into trajectories of biomarkers. We measured microRNA expression in 240 serum samples from patients with colon, lung, and breast cancer and from cancerfree controls. Each patient provided at least two serum samples, one prior to diagnosis and one following diagnosis. The median time interval between the samples was 11.6 years. Using computational models, we evaluated the circulating profiles of 21 microRNAs. The analysis yielded two sets of biomarkers, static ones that show an absolute difference between certain cancer types and controls and dynamic ones where the level over time provided higher diagnostic information content. In the first group, miR-99a-5p stands out for all three cancer types. In the second group, miR-155-5p allows to predict lung cancers and colon cancers. Classification in samples from cancer and non-cancer patients using gradient boosted trees reached an average accuracy of 79.9%. The results suggest that individual change over time or an absolute value at one time point may predict a disease with high specificity and sensitivity

A phytolith supported biosphere-hydrosphere predictive model for Southern Ethiopia:Insights into paleoenvironmental changes and human landscape preferences since the last glacial maximum

During the past 25 ka, southern Ethiopia has undergone tremendous climatic changes, from dry and relatively cold during the Last Glacial Maximum (LGM, 25–18 ka) to the African Humid Period (AHP, 15–5 ka), and back to present-day dry conditions. As a contribution to better understand the effects of climate change on vegetation and lakes, we here present a new Predictive Vegetation Model that is linked with a Lake Balance Model and available vegetation-proxy records from southern Ethiopia including a new phytolith record from the Chew Bahir basin. We constructed a detailed paleo-landcover map of southern Ethiopia during the LGM, AHP (with and without influence of the Congo Air Boundary) and the modern-day potential natural landcover. Compared to today, we observe a 15–20% reduction in moisture availability during the LGM with widespread open landscapes and only few remaining forest refugia. We identify 25–40% increased moisture availability during the AHP with prevailing forests in the mid-altitudes and indications that modern anthropogenic landcover change has affected the water balance. In comparison with existing archaeological records, we find that human occupations tend to correspond with open landscapes during the late Pleistocene and Holocene in southern Ethiopia