Preliminary Integrated Chronostratigraphy of the AND-1B Core, ANDRILL McMurdo Ice Shelf Project, Antarctica

Chronostratigraphic data available for the preliminary age model for the upper 700 m for the AND-1B drill core include diatom biostratigraphy, magnetostratigraphy, 40Ar/39Ar ages on volcanic material, 87Sr/86Sr ages on calcareous fossil material, and surfaces of erosion identifi ed from physical appearance and facies relationships recognised in the AND-1B drill core. The available age data allow a relatively well-constrained age model to be constructed for the upper 700 m of the drill core. Available diatom biostratigraphic constraints and 40Ar/39Ar ages allow a unique correlation of ~70% of the AND- 1B magnetic polarity stratigraphy with the Geomagnetic Polarity Time Scale (GPTS). Unique correlation is not possible in several coarse diamictite intervals with closely spaced glacial surfaces of erosion and sparse microfl ora. However, the age model indicates relatively rapid (up to 1 m/k.y.) and continuous accumulation of intervening fi ner grained diatomaceous intervals punctuated by several half- to millionyear hiatuses representing more than half of the last 7 m.y. in the AND-1B record. The mid- to late Pleistocene is represented by superimposed diamictite units separated from upper Pliocene alternating diamictites/diatomites by a ~1 m.y. hiatus co-incident with a regionally correlated seismic reflection surface. A c. 100 m-thick diatomite represents a signifi cant portion of the early Pliocene record in the AND-1B drill core. Strata below ~620 m are late Miocene in age; however, biostratigraphic constraints are absent below 586 m and correlation with the GPTS is relatively unconstrained. At the time of writing, the only chronostratigraphic data available below 700 mbsf include three 40Ar/39Ar ages on volcanic clasts from near 1280 mbsf affording a maximum depositional age of 13.57 Ma for the base of the AND-1B drill core

Predicting glycated hemoglobin levels in the non-diabetic general population:Development and validation of the DIRECT-DETECT prediction model - a DIRECT study

AIMS/HYPOTHESIS: To develop a prediction model that can predict HbA1c levels after six years in the non-diabetic general population, including previously used readily available predictors. METHODS: Data from 5,762 initially non-diabetic subjects from three population-based cohorts (Hoorn Study, Inter99, KORA S4/F4) were combined to predict HbA1c levels at six year follow-up. Using backward selection, age, BMI, waist circumference, use of anti-hypertensive medication, current smoking and parental history of diabetes remained in sex-specific linear regression models. To minimize overfitting of coefficients, we performed internal validation using bootstrapping techniques. Explained variance, discrimination and calibration were assessed using R2, classification tables (comparing highest/lowest 50% HbA1c levels) and calibration graphs. The model was externally validated in 2,765 non-diabetic subjects of the population-based cohort METSIM. RESULTS: At baseline, mean HbA1c level was 5.6% (38 mmol/mol). After a mean follow-up of six years, mean HbA1c level was 5.7% (39 mmol/mol). Calibration graphs showed that predicted HbA1c levels were somewhat underestimated in the Inter99 cohort and overestimated in the Hoorn and KORA cohorts, indicating that the model's intercept should be adjusted for each cohort to improve predictions. Sensitivity and specificity (95% CI) were 55.7% (53.9, 57.5) and 56.9% (55.1, 58.7) respectively, for women, and 54.6% (52.7, 56.5) and 54.3% (52.4, 56.2) for men. External validation showed similar performance in the METSIM cohort. CONCLUSIONS/INTERPRETATION: In the non-diabetic population, our DIRECT-DETECT prediction model, including readily available predictors, has a relatively low explained variance and moderate discriminative performance, but can help to distinguish between future highest and lowest HbA1c levels. Absolute HbA1c values are cohort-dependent

DLG5 variants are associated with multiple congenital anomalies including ciliopathy phenotypes

BackgroundCilia are dynamic cellular extensions that generate and sense signals to orchestrate proper development and tissue homeostasis. They rely on the underlying polarisation of cells to participate in signalling. Cilia dysfunction is a well-known cause of several diseases that affect multiple organ systems including the kidneys, brain, heart, respiratory tract, skeleton and retina.MethodsAmong individuals from four unrelated families, we identified variants in discs large 5 (DLG5) that manifested in a variety of pathologies. In our proband, we also examined patient tissues. We depleted dlg5 in Xenopus tropicalis frog embryos to generate a loss-of-function model. Finally, we tested the pathogenicity of DLG5 patient variants through rescue experiments in the frog model.ResultsPatients with variants of DLG5 were found to have a variety of phenotypes including cystic kidneys, nephrotic syndrome, hydrocephalus, limb abnormalities, congenital heart disease and craniofacial malformations. We also observed a loss of cilia in cystic kidney tissue of our proband. Knockdown of dlg5 in Xenopus embryos recapitulated many of these phenotypes and resulted in a loss of cilia in multiple tissues. Unlike introduction of wildtype DLG5 in frog embryos depleted of dlg5, introduction of DLG5 patient variants was largely ineffective in restoring proper ciliation and tissue morphology in the kidney and brain suggesting that the variants were indeed detrimental to function.ConclusionThese findings in both patient tissues and Xenopus shed light on how mutations in DLG5 may lead to tissue-specific manifestations of disease. DLG5 is essential for cilia and many of the patient phenotypes are in the ciliopathy spectrum.</jats:sec

Risks of dengue secondary infective biting associated with aedes aegypti in home environments in Monterrey, Mexico

Abstract. Secondary dengue virus infections are a major risk for developing dengue hemorrhagic fever. Recent exposure to infectious bites of Aedes aegypti (L.) females in previously diagnosed dengue cases fulfills the epidemiological model of dengue hemorrhagic fever. A study was comprised of 357 (89.2%) dengue and 43 (10.8%) dengue hemorrhagic fever cases confirmed by laboratory tests and clinical manifestations. An entomological survey was done in homes and backyards. Concurrently, a questionnaire was used to assess the impact of healthpromotion campaigns through knowledge of the vector and its epidemiological role. Seventy-six (28.4%) of the 268 (67.0%) total wet or dry oviposition sites were positive for the presence of larvae or pupae, while adult Ae. aegypti were found in 32 (8.0%). One hundred thirty-two (33%) householders who formerly had dengue fever or dengue hemorrhagic fever had knowledge of either larval or adult dengue vector stages. According to gender distribution, 145 (36.2%) and 14 (3.5%) of the males confirmed with cases of dengue and dengue hemorrhagic fever lived in houses with 17.9 and 2% of the Ae. aegypti larval and pupal habitats. Houses with females who had dengue and dengue hemorrhagic fever were 212 (53%) and 29 (7.3%), with containers with immature Ae. aegypti in 19.4 and 7%, respectively. Lack of sustainability of government-targeted health education campaigns is the major problem for involving communities in prevention and control of dengu

Research priorities in pediatric parenteral nutrition: a consensus and perspective from ESPGHAN/ESPEN/ESPR/CSPEN

Parenteral nutrition is used to treat children that cannot be fully fed by the enteral route. While the revised ESPGHAN/ESPEN/ESPR/CSPEN pediatric parenteral nutrition guidelines provide clear guidance on the use of parenteral nutrition in neonates, infants, and children based on current available evidence, they have helped to crystallize areas where research is lacking or more studies are needed in order to refine recommendations. This paper collates and discusses the research gaps identified by the authors of each section of the guidelines and considers each nutrient or group of nutrients in turn, together with aspects around delivery and organization. The 99 research priorities identified were then ranked in order of importance by clinicians and researchers working in the field using a survey methodology. The highest ranked priority was the need to understand the relationship between total energy intake, rapid catch-up growth, later metabolic function, and neurocognitive outcomes. Research into the optimal intakes of macronutrients needed in order to achieve optimal outcomes also featured prominently. Identifying research priorities in PN should enable research to be focussed on addressing key issues. Multicentre trials, better definition of exposure and outcome variables, and long-term metabolic and developmental follow-up will be key to achieving this. Impact: The recent ESPGHAN/ESPEN/ESPR/CSPEN guidelines for pediatric parenteral nutrition provided updated guidance for providing parenteral nutrition to infants and children, including recommendations for practice.However, in several areas there was a lack of evidence to guide practice, or research questions that remained unanswered. This paper summarizes the key priorities for research in pediatric parenteral nutrition, and ranks them in order of importance according to expert opinion

Epigenetic Regulation of Learning and Memory by Drosophila EHMT/G9a

Behavioral phenotyping and genome-wide profiling of the histone modifier EHMT in Drosophila reveals a mechanism through which an epigenetic writer may control cognition

Heme Oxygenase-1 Accelerates Cutaneous Wound Healing in Mice

Heme oxygenase-1 (HO-1), a cytoprotective, pro-angiogenic and anti-inflammatory enzyme, is strongly induced in injured tissues. Our aim was to clarify its role in cutaneous wound healing. In wild type mice, maximal expression of HO-1 in the skin was observed on the 2nd and 3rd days after wounding. Inhibition of HO-1 by tin protoporphyrin-IX resulted in retardation of wound closure. Healing was also delayed in HO-1 deficient mice, where lack of HO-1 could lead to complete suppression of reepithelialization and to formation of extensive skin lesions, accompanied by impaired neovascularization. Experiments performed in transgenic mice bearing HO-1 under control of keratin 14 promoter showed that increased level of HO-1 in keratinocytes is enough to improve the neovascularization and hasten the closure of wounds. Importantly, induction of HO-1 in wounded skin was relatively weak and delayed in diabetic (db/db) mice, in which also angiogenesis and wound closure were impaired. In such animals local delivery of HO-1 transgene using adenoviral vectors accelerated the wound healing and increased the vascularization. In summary, induction of HO-1 is necessary for efficient wound closure and neovascularization. Impaired wound healing in diabetic mice may be associated with delayed HO-1 upregulation and can be improved by HO-1 gene transfer

Systematic Review of Medicine-Related Problems in Adult Patients with Atrial Fibrillation on Direct Oral Anticoagulants

New oral anticoagulant agents continue to emerge on the market and their safety requires assessment to provide evidence of their suitability for clinical use. There-fore, we searched standard databases to summarize the English language literature on medicine-related problems (MRPs) of direct oral anticoagulants DOACs (dabigtran, rivaroxban, apixban, and edoxban) in the treatment of adults with atri-al fibrillation. Electronic databases including Medline, Embase, International Pharmaceutical Abstract (IPA), Scopus, CINAHL, the Web of Science and Cochrane were searched from 2008 through 2016 for original articles. Studies pub-lished in English reporting MRPs of DOACs in adult patients with AF were in-cluded. Seventeen studies were identified using standardized protocols, and two reviewers serially abstracted data from each article. Most articles were inconclusive on major safety end points including major bleeding. Data on major safety end points were combined with efficacy. Most studies inconsistently reported adverse drug reactions and not adverse events or medication error, and no definitions were consistent across studies. Some harmful drug effects were not assessed in studies and may have been overlooked. Little evidence is provided on MRPs of DOACs in patients with AF and, therefore, further studies are needed to establish the safety of DOACs in real-life clinical practice