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Background: Pseudogenes are non-functional copies of protein coding genes that typically follow a different molecular evolutionary path as compared to functional genes. The inclusion of pseudogene sequences in DNA barcoding and metabarcoding analysis can lead to misleading results. None of the most widely used bioinformatic pipelines used to process marker gene (metabarcode) high throughput sequencing data specifically accounts for the presence of pseudogenes in protein-coding marker genes. The purpose of this study is to develop a method to screen for nuclear mitochondrial DNA segments (nuMTs) in large COI datasets. We do this by: (1) describing gene and nuMT characteristics from an artificial COI barcode dataset, (2) show the impact of two different pseudogene removal methods on perturbed community datasets with simulated nuMTs, and (3) incorporate a pseudogene filtering step in a bioinformatic pipeline that can be used to process Illumina paired-end COI metabarcode sequences. Open reading frame length and sequence bit scores from hidden Markov model (HMM) profile analysis were used to detect pseudogenes. Results: Our simulations showed that it was more difficult to identify nuMTs from shorter amplicon sequences such as those typically used in metabarcoding compared with full length DNA barcodes that are used in the construction of barcode libraries. It was also more difficult to identify nuMTs in datasets where there is a high percentage of nuMTs. Existing bioinformatic pipelines used to process metabarcode sequences already remove some nuMTs, especially in the rare sequence removal step, but the addition of a pseudogene filtering step can remove up to 5% of sequences even when other filtering steps are in place. Conclusions: Open reading frame length filtering alone or combined with hidden Markov model profile analysis can be used to effectively screen out apparent pseudogenes from large datasets. There is more to learn from COI nuMTs such as their frequency in DNA barcoding and metabarcoding studies, their taxonomic distribution, and evolution. Thus, we encourage the submission of verified COI nuMTs to public databases to facilitate future studies. [ABSTRACT FROM AUTHOR]

In mammals, insulin regulates blood glucose levels and plays a key regulatory role in appetite via the hypothalamus. In contrast, chickens are characterized by atypical glucose homeostasis, with relatively high blood glucose levels, reduced glucose sensitivity of pancreatic beta cells, and large resistance to exogenous insulin. The aim of the present study was to investigate in chickens the effects of 5 h fasting and 5 h insulin immuno-neutralization on hypothalamic mRNA levels of 23 genes associated with food intake, energy balance, and glucose metabolism. We observed that insulin immune-neutralization by administration of antiporcine insulin guinea pig serum (AI) significantly decreased food intake and increased plasma glucose levels in chickens, while 5 h fasting produced a limited and non-significant reduction in plasma glucose. In addition, 5 h fasting increased levels of NPY, TAS1R1, DIO2, LEPR, GLUT1, GLUT3, GLUT8, and GCK mRNA. In contrast, AI had no impact on the levels of any selected mRNA. Therefore, our results demonstrate that in chickens, food intake inhibition or satiety mechanisms induced by insulin immuno-neutralization do not rely on hypothalamic abundance of the 23 transcripts analyzed. The hypothalamic transcripts that were increased in the fasted group are likely components of a mechanism of adaptation to fasting in chickens. [ABSTRACT FROM AUTHOR]

Choosing an evidence-based workup and treatment for recurrent pregnancy loss is imperative to provide best patient care and create a culture that permits rigorous research into potential (not yet evidence-based) tests and therapeutics. As health sciences technologies become more sophisticated, more precise, and less expensive, new tools may be developed that allow better evaluation and treatment of couples with recurrent pregnancy loss. The goal must remain optimizing value and adhering to evidence-based care. [ABSTRACT FROM AUTHOR]

Objective To measure variance in antiphospholipid antibody (aPL) levels during pregnancy and to determine if variation affects pregnancy outcomes. Methods We used data from the PROMISSE (Predictors of Pregnancy Outcome: Biomarkers in Antiphospholipid Antibody Syndrome and Systemic Lupus Erythematosus) study, a multicenter prospective study of pregnant women with aPL and/or systemic lupus erythematosus (SLE). Antiphospholipid antibodies were considered present if any of the following were positive: anticardiolipin (aCL), anti-β2-glycoprotein I (anti-β2GPI) titers ≥40 IgG phospholipid (GPL) or IgM phospholipid (MPL) units, and/or lupus anticoagulant (LAC). Antiphospholipid antibodies were measured every trimester and postpartum. Adverse pregnancy outcomes were defined as fetal/neonatal death, preterm delivery (<36 weeks) due to preeclampsia or placental insufficiency, or growth restriction. Results One hundred fifty-two aPL-positive patients were studied. Fifty-seven percent had clinical antiphospholipid syndrome (APS) and 36% had SLE. IgG aPL levels were significantly lower during the second and third trimesters compared to initial screening, but IgG aCL and anti-β2GPI remained high-positive through pregnancy in 93% of patients during the second trimester, and in 85% of patients during the third trimester. IgM aPL titers were negative in the majority of patients and decreased modestly during pregnancy among patients who were positive. LAC frequency also decreased, but 75% of patients remained positive through the second trimester. Only 4% of patients with aPL at baseline did not have aPL in either the second or third trimesters. Changes in aPL levels or aPL status were not associated with adverse pregnancy outcomes. LAC was the only aPL associated with adverse pregnancy outcomes. Conclusion The aPL in the cohort decreased marginally during pregnancy, and changes were not associated with pregnancy outcomes. Our results suggest that, among women with aPL and/or SLE, measuring aPL early in pregnancy is sufficient to assess risk. Repeat aPL testing through pregnancy is unnecessary. [ABSTRACT FROM AUTHOR]

Preeclampsia is associated with significant perinatal morbidity and mortality. Aspirin has been long purported and extensively studied for prevention of preeclampsia. For this reason, the U.S. Preventive Services Task Force, the American College of Obstetricians and Gynecologists, and the Society for Maternal-Fetal Medicine recommend its use in pregnancy for preeclampsia prevention in those at high risk. Yet, much controversy exists regarding optimal use in pregnancy with guidelines across global organizations varying. In this narrative review, we summarize the published literature related to the safety, optimal dose, and timing and duration of use of aspirin, as well as other indications for which aspirin has been studied in pregnancy. [ABSTRACT FROM AUTHOR]

Objective The study aimed to determine if a program of mid-trimester serum proteomics screening of women at low risk for spontaneous preterm birth (sPTB) and the use of a PTB risk-reduction protocol in those whose results indicated an increased risk of sPTB would reduce the likelihood of sPTB and its sequelae. Study Design Prospective comparison of birth outcomes in singleton pregnancies with mid-trimester cervical length ≥2.5 cm and at otherwise low risk for sPTB randomized to undergo or not undergo mid-trimester serum proteomics screening for increased risk of sPTB (NCT 03530332). Screen-positive women were offered a group of interventions aimed at reducing the risk of spontaneous PTB. The primary outcome was the rate of sPTB <37 weeks, and secondary outcomes were gestational age at delivery, total length of neonatal stay, and NICU length of stay (LOS). Unscreened and screen-negative women received standard care. The adaptive study design targeted a sample size of 3,000 to 10,000 women to detect a reduction in sPTB from 6.4 to 4.7%. Due to limited resources, the trial was stopped early prior to data unblinding. Results A total of 1,191 women were randomized. Screened and unscreened women were demographically similar. sPTB <37 weeks occurred in 2.7% of screened women and 3.5% of controls (p = 0.41). In the screened compared with the unscreened group, there were no between-group differences in the gestational age at delivery, total length of neonatal stay, and NICU LOS. However, the NICU LOS among infants admitted for sPTB was significantly shorter (median = 6.8 days, interquartile range [IQR]: 1.8–8.0 vs. 45.5 days, IQR: 34.6–79.0; p = 0.005). Conclusion Mid-trimester serum proteomics screening of women at low risk for sPTB and the use of a sPTB risk-reduction protocol in screen-positive patients did not significantly reduce the rate of sPTB compared with women not screened, though the trial was underpowered thus limiting the interpretation of negative findings. Infants in the screened group had a significantly shorter NICU LOS, a difference likely due to a reduced number of infants in the screened group that delivered <35 weeks. Key Points Mid-trimester serum proteomics screening of women at low risk for sPTB and the use of a sPTB risk-reduction protocol in screen-positive patients did not significantly reduce the rate of sPTB, though the trial was underpowered. NICU LOS following sPTB was significantly shortened among women who underwent screening and risk-reduction management. The use of serum biomarkers may contribute to a practical strategy to reduce sPTB sequelae. [ABSTRACT FROM AUTHOR]

Highlights: [•] This paper presents a comprehensive review of world-class porphyry systems in central Eurasia. [•] An overview of the tectonics of central Eurasia. [•] Description of key porphyry and related epithermal systems in central Eurasia. [ABSTRACT FROM AUTHOR]

Using infrared, radio, and γ-ray data, we investigate the propagation characteristics of cosmic-ray (CR) electrons and nuclei in the 30 Doradus (30 Dor) star-forming region in the Large Magellanic Cloud (LMC) using a phenomenological model based on the radio-far-infrared correlation within galaxies. Employing a correlation analysis, we derive an average propagation length of ~100-140 pc for ~3 GeV CR electrons resident in 30 Dor from consideration of the radio and infrared data. Assuming that the observed γ-ray emission toward 30 Dor is associated with the star-forming region, and applying the same methodology to the infrared and γ-ray data, we estimate a ~20 GeV propagation length of 200-320 pc for the CR nuclei. This is approximately twice as large as for ~3 GeV CR electrons, corresponding to a spatial diffusion coefficient that is ~4 times higher, scaling as (R/GV)δ with δ ≈ 0.7-0.8 depending on the smearing kernel used in the correlation analysis. This value is in agreement with the results found by extending the correlation analysis to include ~70 GeV CR nuclei traced by the 3-10 GeV γ-ray data (δ ≈ 0.66 ± 0.23). Using the mean age of the stellar populations in 30 Dor and the results from our correlation analysis, we estimate a diffusion coefficient DR ≈ (0.9-1.0) x 1027 (R/GV)0.7 cm² s-1. We compare the values of the CR electron propagation length and surface brightness for 30 Dor and the LMC as a whole with those of entire disk galaxies. We find that the trend of decreasing average CR propagation distance with increasing disk-averaged star formation activity holds for the LMC, and extends down to single star-forming regions, at least for the case of 30 Dor. [ABSTRACT FROM AUTHOR]

The article discusses a study conducted by the U.S. Centers for Disease Control and Prevention (CDC) to evaluate the possible health effects, use of alternative water resources and efficiency of the emergency response on the up to 12 days water interruption in two rural counties in Alabama in January 2010. The Alabama Department of Public Health (ADPH) asked the CDC's help in the probe. Based on the results, there are substantially higher cases of acute gastrointestinal illness (AGI) on households which lost both water service and water pressure.

A total of 49 profiles of growing turkey hens from commercial flocks were used in this study. Three flexible growth functions (von Bertalanffy, Richards, and Morgan) were evaluated with regard to their ability to describe the relationship between BW and age and were compared with the Gompertz equation with its fixed point of inflection, which might result in its overestimation. For each function, 4 ways of analysis were implemented. A basic model was fitted first, followed by implementation of a first-order autoregressive correlation structure. A model that considered only mature BW varied with year and another that considered only the rate coefficient varied with different years were applied. The results showed that the fixed point of inflection of the Gompertz equation can be a limitation and that the relationship between BW and age in turkeys was best described using flexible growth functions. However, the Richards equation failed to converge when fitted to the turkey growth data; therefore, it was not considered further. Inclusion of an autoregressive process of the first order rendered a substantially improved fit to data for the 3 growth functions. The Morgan equation provided the best fit to the data set and was used for characterizing mean growth curves for the 7 yr of production. It was estimated that the maximum growth rate occurred at 3.74, 3.65, 3.99, 4.18, 4.05, 4.01, and 3.77 kg BW for production years from 1997 to 2003, respectively. It is recommended that flexible growth functions should be considered as an alternative to the simpler functions (with a fixed point of inflection) for describing the relationship between BW and age in turkeys because they were easier to fit and very often gave a closer fit to data points because of their flexibility, and therefore a smaller residual MS value, than simpler models. It can also be recommended that studies should consider adding a first-order autoregressive process when analyzing repeated measures data with nonlinear models. [ABSTRACT FROM AUTHOR]

Background: The prevalence of diagnosed diabetes among different ethnic groups and the influence of deprivation on the prevalence of diabetes among Māori and New Zealand Europeans was investigated. Methods: This was a cross-sectional survey on all patients registered with 10 practices in the Rotorua General Practice Group on 1 July 2007. Patients diagnosed with diabetes were identified though diagnostic codes for diabetes, prescriptions for diabetes medications and laboratory tests for glycosylated haemoglobin (HbA1c). Prevalence of diabetes by ethnicity, age group, gender and NZDep2001 quintiles was calculated. Adjusted ORs for the risk of diabetes were obtained from logistic regression analysis. Results: Of the 45 500 patients registered, 1819 had been diagnosed with diabetes mellitus. In the 40+ age groups, the prevalence of diabetes in Māori and Pacific people was around three times that in Europeans. With increasing deprivation, the age-standardised prevalence of diagnosed diabetes increased among European males (2.7-5.0%) and females (2.1-3.1%). However, the prevalence of diabetes was highest among the least deprived Māori (males 9.7%, females 6.2%). The adjusted risk of diabetes for the most deprived Māori is not significantly different from that for the least deprived Māori. The most deprived Europeans had nearly twice the risk of having diabetes than the least deprived Europeans. Conclusions: Although the rising prevalence of diabetes with increasing deprivation among Europeans shows a similar trend to results from national and international studies, the trend among Māori seems to be different because the least deprived are equally at risk of diabetes. Diabetes interventions aimed at Māori should be tailor-made to include the least deprived groups. [ABSTRACT FROM AUTHOR]

Objective To determine which interventions for managing placenta accreta were associated with reduced maternal morbidity. Design Retrospective cohort study. Setting Two tertiary care teaching hospitals in Utah. Population All identified cases of placenta accreta from 1996 to 2008. Methods Cases of placenta accreta were identified using standard ICD-9 codes for placenta accreta, placenta praevia, and caesarean hysterectomy. Medical records were then abstracted for maternal medical history, hospital course, and maternal and neonatal outcomes. Maternal and neonatal complications were compared according to antenatal suspicion of accreta, indications for delivery, preoperative preparation, attempts at placental removal before hysterectomy, and hypogastric artery ligation. Main outcome measures Early morbidity (prolonged maternal intensive care unit admission, large volume of blood transfusion, coagulopathy, ureteral injury, or early re-operation) and late morbidity (intra-abdominal infection, hospital re-admission, or need for delayed re-operation). Results Seventy-six cases of placenta accreta were identified. When accreta was suspected, scheduled caesarean hysterectomy without attempting placental removal was associated with a significantly reduced rate of early morbidity compared with cases in which placental removal was attempted (67 versus 36%, P = 0.038). Women with preoperative bilateral ureteric stents had a lower incidence of early morbidity compared with women without stents (18 versus 55%, P= 0.018). Hypogastric artery ligation did not reduce maternal morbidity. Conclusions Scheduled caesarean hysterectomy with preoperative ureteric stent placement and avoiding attempted placental removal are associated with reduced maternal morbidity in women with suspected placenta accreta. [ABSTRACT FROM AUTHOR]

Since the sequencing of the genome and the development of high-throughput tools for the exploration of functional elements of the genome, the chicken has reached model organism status. Functional genomics focuses on understanding the function and regulation of genes and gene products on a global or genome-wide scale. Systems biology attempts to integrate functional information derived from multiple high-content data sets into a holistic view of all biological processes within a cell or organism. Generation of a large collection (∼600K) of chicken expressed sequence tags, representing most tissues and developmental stages, has enabled the construction of high-density microarrays for transcriptional profiling. Comprehensive analysis of this large expressed sequence tag collection and a set of ∼20K full-length cDNA sequences indicate that the transcriptome of the chicken represents approximately 20,000 genes. Furthermore, comparative analyses of these sequences have facilitated functional annotation of the genome and the creation of several bioinformatic resources for the chicken. Recently, about 20 papers have been published on transcriptional profiling with DNA microarrays in chicken tissues under various conditions. Proteomics is another powerful high-throughput tool currently used for examining the dynamics of protein expression in chicken tissues and fluids. Computational analyses of the chicken genome are providing new insight into the evolution of gene families in birds and other organisms. Abundant functional genomic resources now support large-scale analyses in the chicken and will facilitate identification of transcriptional mechanisms, gene networks, and metabolic or regulatory pathways that will ultimately determine the phenotype of the bird. New technologies such as marker-assisted selection, transgenics, and RNA interference offer the opportunity to modify the phenotype of the chicken to fit defined production goals. This review focuses on functional genomics in the chicken and provides a road map for large-scale exploration of the chicken genome. [ABSTRACT FROM AUTHOR]

Purpose: To identify the important issues which have an impact on the quality of life (QoL) of men suffering from erectile dysfunction (ED) and to generate a new ED-specific QoL questionnaire ready to undergo further psychometric testing.Methods: QoL issues relating to ED were generated through in-depth qualitative interviews of 29 patients, literature review and consultation with other healthcare professionals. The issues were formulated into a questionnaire, which was piloted using 40 patients with ED and subsequently refined using well-established principles of questionnaire development.Results: The qualitative interviews revealed numerous psychosocial problems associated with ED, which were operationalised into a 40-item questionnaire. Pilot testing allowed the questionnaire to be reduced to a manageable 15-item final questionnaire while maintaining face and content validity and the potential to discriminate between men with varying degrees of affected QoL. This questionnaire had a Cronbach's alpha of 0.94.Conclusions: A new ED-specific QoL measure has been developed using appropriate methodology. Qualitative techniques identified a range of psychosocial morbidity in men with ED, leading to a simple but robust instrument with face and content validity. This questionnaire, Erectile Dysfunction-Effect on quality of life (ED-EQoL), has now undergone psychometric testing for validity and reliability. [ABSTRACT FROM AUTHOR]

Summarizes the literature on the causes of hematuria in asymptomatic patients, and the natural history of the underlying conditions. Patterns of referral and investigation; Assumptions behind the medical investigation of hematuria; Diagnostic procedures; Treatment.

1. The aim of this project was to identify and explore the issues facing men who live with erectile dysfunction (ED), in particular men's' relationships with women partners and men's interactions with the wider world. 2. In order to gain an understanding of their everyday lives, a qualitative research design was used. This is an account of the interpretation and analysis of nine interviews with men living with ED that were carried out during the autumn of 1997. 3. The analysis identified two main themes, 'loss' and 'being alone with it'; with meta-categories 'making sense of it' and 'telling other people', and 'place of sex'. The latter acts as a bridge between the two themes. 4. The implications for nursing practice are considered and recommendations are made for practice, education and research. [ABSTRACT FROM AUTHOR]

A general purpose data acquisition and control system for scanning tunneling microscopy (STM) using Visual Basic is presented. This Windows hosted Visual Basic environment is highly desirable for use in STM image manipulation, storage, and printing, but in its standard form is not suitable for most data acquisition and display applications. Many of the inherent limitations in the Visual Basic language have been overcome by the use of direct calls to the Windows Application Program Interface. In this paper, we describe a general Visual Basic STM user interface and control system, and the extensions to the language using the Windows API needed to implement this system. [ABSTRACT FROM AUTHOR]

Cosmic rays (CRs) interact with the diffuse gas, radiation, and magnetic fields in the interstellar medium (ISM) to produce electromagnetic emissions that are a significant component of the all-sky flux across a broad wavelength range. The Fermi –Large Area Telescope (LAT) has measured these emissions at GeV γ-ray energies with high statistics. Meanwhile, the high-energy stereoscopic system (H.E.S.S.) telescope array has observed large-scale Galactic diffuse emission in the TeV γ-ray energy range. The emissions observed at GeV and TeV energies are connected by the common origin of the CR particles injected by the sources, but the energy dependence of the mixture from the general ISM (true 'diffuse'), those emanating from the relatively nearby interstellar space about the sources, and the sources themselves, is not well understood. In this paper, we investigate predictions of the broad-band emissions using the galprop code over a grid of steady-state 3D models that include variations over CR sources, and other ISM target distributions. We compare, in particular, the model predictions in the very-high energy ( VHE; ≳100 GeV) γ-ray range with the H.E.S.S. Galactic plane survey (HGPS) after carefully subtracting emission from catalogued γ-ray sources. Accounting for the unresolved source contribution, and the systematic uncertainty of the HGPS, we find that the galprop model predictions agree with lower estimates for the HGPS source-subtracted diffuse flux. We discuss the implications of the modelling results for interpretation of data from the next generation Cherenkov Telescope Array (CTA). [ABSTRACT FROM AUTHOR]

The article discusses the impact of extended loss of water service on community health in Alabama in January 2010 based on a household survey conducted by the Alabama Department of Public Health (ADPH) and the U.S. Centers for Disease Control and Prevention (CDC). The survey found that the prevalence of acute gastrointestinal illness (AGI) was higher among residents in areas that lost water service and water pressure. Increased cases of acute respiratory illness (ARI) were found associated with increasing duration of loss of pressure, but not with water service loss. The importance of investing in enhanced drinking water infrastructure to protect public health is tackled. INSET: What is already known on this topic?.

A lipid coated bubble (LCB) oscillator is a very interesting non-smooth oscillator with many important applications ranging from industry and chemistry to medicine. However, due to the complex behavior of the coating intermixed with the nonlinear behavior of the bubble itself, the dynamics of the LCB are not well understood. In this work, lipid coated Definity® microbubbles (MBs) were sonicated with 25 MHz 30 cycle pulses with pressure amplitudes between 70 and 300 kPa. Here, we report higher order subharmonics in the scattered signals of single MBs at low-amplitude high-frequency ultrasound excitations. Experimental observations reveal the generation of period 2, period 3, and two different period 4 oscillations at low excitation amplitudes. Despite the reduced damping of the uncoated bubble system, such enhanced nonlinear oscillations have not been observed and cannot be theoretically explained for the uncoated bubble. To investigate the mechanism of the enhanced non-linearity, the bifurcation structure of the lipid coated MBs is studied for a wide range of MBs sizes and shell parameters. Consistent with the experimental results, we show that this unique oscillator can exhibit chaotic oscillations and higher order subharmonics at excitation amplitudes considerably below those predicted by the uncoated oscillator. Buckling or rupture of the shell and the dynamic variation of the shell elasticity cause the intensified non-linearity at low excitation pressure amplitudes. The simulated scattered pressure by single MBs is in good agreement with the experimental signals. [ABSTRACT FROM AUTHOR]

A simple method of achieving dual scan ranges with a single piezo element in scanning probe microscope instruments is described. Both high-resolution small-scan ranges and low-resolution large-scan areas are obtainable. [ABSTRACT FROM AUTHOR]

The reported prevalence of antiphospholipid antibodies in women with a chief complaint of pregnancy loss varies, as does the risk of adverse outcomes in subsequent pregnancies. Our objectives were to assess the prevalence of antiphospholipid antibodies meeting revised Sapporo thresholds among women presenting with a chief complaint of pregnancy loss and risks in subsequent pregnancies for these women. We examined a retrospective cohort of patients presenting with a chief complaint of pregnancy loss between 2003 and 2012. Antiphospholipid antibodies were assessed at the providers’ discretion, and patients were considered positive if they met the revised Sapporo criteria. Patient data were obtained by review of the medical records. 338/390 women (86.7%) presented with a chief complaint of pregnancy loss and had testing for antiphospholipid antibodies. 19/338 women (5.6%) persistently tested positive for at least one antiphospholipid antibody. Seven women who tested positive had isolated recurrent early pregnancy loss ≤10 weeks, and 12 women who tested positive had venous thromboembolism (VTE), systemic lupus erythematosus (SLE), delivery <34 weeks for pre-eclampsia, and/or placental insufficiency, or fetal demise >10 weeks. Subsequent pregnancy outcomes were available for 13 patients. Compared with women with recurrent early pregnancy loss alone, subsequent obstetric morbidity was significantly more likely in those patients with a history of SLE and/or VTE ( p = 0.048). We conclude that the prevalence of positive antiphospholipid antibodies in women with a chief complaint of pregnancy loss and without autoimmune disease or prior thrombosis is low and that among these women, subsequent pregnancy outcomes are largely favorable. [ABSTRACT FROM AUTHOR]

Aims Type 2 diabetes mellitus ( T2DM) is often associated with cardiovascular ( CV) risk factors such as obesity, hypertension and dyslipidemia. The objective of this analysis was to evaluate potential effects of exenatide once weekly ( ExQW), a GLP-1 receptor agonist, on glycaemic control and CV risk factors. Methods This analysis included 675 Intent-to-Treat patients with T2DM [baseline (mean ± SD) HbA1c, 8.1 ± 1.2%; fasting blood glucose ( FBG), 166 ± 48 mg/ dl; weight, 94.3 ± 19.4 kg; systolic/diastolic blood pressure ( SBP/ DBP), 129 ± 15/78 ± 9 mm Hg; total cholesterol, 178.5 ± 41.9 mg/ dl; low-density lipoprotein ( LDL), 100.1 ± 35.0 mg/ dl; high-density lipoprotein ( HDL), 44.5 ± 11.6 mg/ dl; triglycerides, 155.6 ± 3.3 mg/ dl; alanine aminotransferase ( ALT), 32.1 ± 19.5 U/l] treated with diet and exercise alone or in combination with metformin, sulfonylurea, and/or thiazolidinedione who received 52 weeks of ExQW in four clinical trials. Results At 52 weeks, ExQW significantly improved HbA1c [mean ( SE) change from baseline, −1.3 (0.05)%], FBG [−36.3 (2.02) mg/ dl], body weight [−2.6 (0.19) kg], SBP/ DBP [−3.6 (0.56) mm Hg/−1.2 (0.34) mm Hg], total cholesterol, −4.4 (1.33) mg/ dl; LDL, −2.6 (1.08) mg/ dl; HDL, 1.1 (0.31) mg/ dl; triglycerides, −7 (1.6)%], and ALT [−4.3 (0.71) IU/l] concentrations, with greater improvements in patients with elevated analyte levels at baseline. Improvements were observed across a range of background antihyperglycaemia therapies. Of patients completing 52 weeks, 19% achieved the composite American Diabetes Association goal ( HbA1c < 7.0%, BP < 130/80 mm Hg, LDL < 100 mg/ dl), compared to 1% at baseline. Nearly half (48%) achieved HbA1c < 7.0% without weight gain or major/minor hypoglycaemia. Nausea was the most frequent adverse event and was predominantly mild. Hypoglycaemia was infrequent, and more common with a sulfonylurea. Conclusions With 52 weeks of ExQW, patients experienced sustained improvements in glycaemic control and CV risk factors, with an increased likelihood of achieving both a clinically relevant composite outcome ( HbA1c < 7% without weight gain or increased risk of hypoglycaemia) and a composite of key therapeutic goals ( HbA1c < 7%, BP < 130/80 mm Hg, LDL < 100 mg/ dl). [ABSTRACT FROM AUTHOR]

The subject of obstetric antiphospholipid syndrome (APS) has been reviewed dozens of times, and there is little doubt that the international APS community has done well in bringing APS to the attention of clinicians around the world. However, the evolution of clinical practice, at least in the US, also has convinced us that our field would benefit from further clinical study. For example, the number of women diagnosed with 'APS', but who do not meet the revised Sapporo criteria, seems to have increased. It is now common practice for women with recurrent miscarriage or prior fetal death to be treated with heparin, even in the presence of indeterminate or low titer antiphospholipid antibody (aPL) levels and even after only one positive test. In part, this common practice derives from confusion on the part of many clinicians and patients regarding the diagnosis of APS as well as the clinical and laboratory criteria for the syndrome. In part, this derives from the common practice of so-called 'empiric treatment' in US reproductive medicine, often driven as much by patients as by clinicians. This brief commentary focuses on areas of uncertainty that we see as deserving of new or renewed study for the sake of improving our understanding of APS and best patient care. [ABSTRACT FROM AUTHOR]

Background: Recombinant human bone morphogenetic proteins (rhBMPs) are being tested in clinical studies for their capacity to elicit bone formation. Biomaterials used in delivery systems also play a critical role in supporting the osteoinductive activity of BMPs, attributable to the controlled presentation of the BMPs to target cells. Despite extensive preclinical studies, the factors contributing to local rhBMP pharmacokinetics remain to be elucidated. Methods: The rhBMP pharmacokinetics were studied in a rat subcutaneous implant and in an intramuscular injection model. In situ levels of rhBMPs were quantitated with use of 125I-labeled tracers. The effects of protein structural features and the nature of the biomaterial implant were explored. Osteoinduction by biomaterial+rhBMP combinations was assessed by a semiquantitative, histology-based bone score. Results: With the use of rhBMP-2, rhBMP-4, and an N-truncated rhBMP-2, the protein isoelectric point was found critical for the initial retention of rhBMPs in an implant. Osteoinduction studies carried out in parallel indicated that rhBMPs with a higher implant retention elicited more bone formation. In the clinically used collagen+rhBMP-2 device, collagen crosslinking and sterilization were most influential in rhBMP-2 retention. To increase retention at an application site, thermoreversible polymers were engineered and shown to enhance local rhBMP-2 retention, especially by injectable delivery. Conclusions: Two critical components of an osteoinductive device--namely, the biomaterial and the rhBMP--were shown to influence local protein pharmacokinetics and osteoinductive activity of the device. Designer biomaterials can provide an additional mechanism to modulate local protein pharmacokinetics. Clinical Relevance: These studies form the foundation of next-generation osteoinductive devices with improved potency at sites of desired bone regeneration and reduced side effects at other sites. [ABSTRACT FROM AUTHOR]

Intravenous injections or infusions of perfluorocarbon-exposed sonicated dextrose albumin microbubbles were given 2.4 +/- 1.6 days following acute myocardial infarction to 45 consecutive patients. Patients were divided into 3 groups: patients with Thrombolysis In Myocardial Infarction (TIMI) grade 3 angiographic flow but persistent myocardial contrast defects by echocardiography (no reflow), patients with TIMI 3 flow and myocardial contrast enhancement (reflow), and patients with TIMI grade 0 to 2 flow in the infarct vessel. Thirty-five patients had TIMI 3 flow at the time of contrast study. Of these, 25 had evidence of reflow with intravenous contrast, whereas 10 (29%) still had contrast defects. At follow-up, end-systolic volume index decreased significantly in patients who exhibited reflow (21 +/- 8 ml/m2 at baseline to 18 +/- 8 ml/m2 at follow-up; p = 0.04), whereas those with no reflow had a significant increase (26 +/- 9 ml/m2 at baseline to 32 +/- 9 ml/m2 at follow-up; p = 0.006). A persistent contrast defect in the infarct zone demonstrated with intravenous ultrasound contrast following restoration of TIMI grade 3 flow in the infarct vessel identified patients likely to have deterioration in both regional and global systolic function. [ABSTRACT FROM AUTHOR]

Since its launch, the Alpha Magnetic Spectrometer—02 (AMS-02) has delivered outstanding quality measurements of the spectra of cosmic-ray (CR) species (, e±, and nuclei, 1H–8O, 10Ne, 12Mg, 14Si) which resulted in a number of breakthroughs. One of the latest long-awaited surprises is the spectrum of 26Fe just published by AMS-02. Because of the large fragmentation cross section and large ionization energy losses, most of CR iron at low energies is local and may harbor some features associated with relatively recent supernova (SN) activity in the solar neighborhood. Our analysis of the new AMS-02 results, together with Voyager 1 and ACE-CRIS data, reveals an unexpected bump in the iron spectrum and in the Fe/He, Fe/O, and Fe/Si ratios at 1–2 GV, while a similar feature in the spectra of He, O, and Si and in their ratios is absent, hinting at a local source of low-energy CRs. The found excess extends the recent discoveries of radioactive 60Fe deposits in terrestrial and lunar samples and in CRs. We provide an updated local interstellar spectrum (LIS) of iron in the energy range from 1 MeV nucleon−1 to ∼10 TeV nucleon−1. Our calculations employ the GalProp – HelMod framework, which has proved to be a reliable tool in deriving the LIS of CR , e−, and nuclei Z ≤ 28. [ABSTRACT FROM AUTHOR]

p53, The tumour suppressor protein encoded by P53 gene, is the most commonly altered protein in the human malignancies. MDM2 controls the p53 activity through an autoregulatory feedback loop. p53 activates the expression of MDM2 and in return, MDM2 blocks the p53 activity through various mechanisms. Nutlins, including nutlin-3, are a new class of small molecules that bind to MDM2 and prevent its interaction with p53. This antagonism results in increased p53 activity and can also re-activates the p53 pathway and resensitize the glioblastoma cells to apoptosis. Here we used nutlin-3 in combination with another potent anticancer drug, doxorubicin, to investigate the synergism between these drugs. We encapsulated both water-insoluble drugs in the PEG-PE-based micellar nanocarriers efficiently and evaluate their efficacy against U87MG cells in 2 D and 3 D models. These nanomedicine formulations successfully re-activated the p53 levels in cells, increased the apoptosis and showed strong synergistic cytotoxic effect. [ABSTRACT FROM AUTHOR]

Previous studies demonstrated that inovo photostimulation with monochromatic green light increased the somatotropic axis expression in broilers embryos. The objective of the current study was to detect the critical period for in-ovo GL photostimulation, in order to find the optimal targeted photostimulation period during the incubation process. Three hundred thirty-six fertile broiler eggs were divided into 4 groups. The first group was incubated under dark conditions as a negative control. The second incubated under intermittent monochromatic green light using lightemitting diode (LED) lamps with an intensity of 0.1 W\m2 at shell level from d 0 of the incubation as a positive control. The third group incubated under intermittent monochromatic green light from d 10 of the incubation. The last group incubated under intermittent monochromatic green light from d 15 of the incubation. In-ovo green light photostimulation from embryonic d 0 (ED0) increased plasma growth hormone (GH), as well as hypothalamic growth hormone releasing hormone (GHRH) and liver growth hormone receptor (GHR) and insulin-like growth factor-1 (IGF-1) mRNA levels. In-ovo green light photostimulation from ED10 increased the GH plasma levels compared to the negative control group, without affecting somatotropic axis mRNA genes expressions of GHRH, GHR, and IGF-1. In-ovo green light photostimulation from ED15 caused an increase in both the plasma GH levels and the somatotropic axis mRNA genes expressions of GHRH, GHR, and IGF-1, compared to the negative control group. These results suggest that the critical period of somatotropic axis acceleration by GL photostimulation start at 15 d of incubation. [ABSTRACT FROM AUTHOR]

Background: Decades of intensive genetic selection in the domestic chicken (Gallus gallus domesticus) have enabled the remarkable rapid growth of today's broiler (meat-type) chickens. However, this enhanced growth rate was accompanied by several unfavorable traits (i.e., increased visceral fatness, leg weakness, and disorders of metabolism and reproduction). The present descriptive analysis of the abdominal fat transcriptome aimed to identify functional genes and biological pathways that likely contribute to an extreme difference in visceral fatness of divergently selected broiler chickens. Methods: We used the Del-Mar 14 K Chicken Integrated Systems microarray to take time-course snapshots of global gene transcription in abdominal fat of juvenile [1-11 weeks of age (wk)] chickens divergently selected on bodyweight at two ages (8 and 36 wk). Further, a RNA sequencing analysis was completed on the same abdominal fat samples taken from high-growth (HG) and low-growth (LG) cockerels at 7 wk, the age with the greatest divergence in body weight (3.2-fold) and visceral fatness (19.6-fold). Results: Time-course microarray analysis revealed 312 differentially expressed genes (FDR ≤ 0.05) as the main effect of genotype (HG versus LG), 718 genes in the interaction of age and genotype, and 2918 genes as the main effect of age. The RNA sequencing analysis identified 2410 differentially expressed genes in abdominal fat of HG versus LG chickens at 7 wk. The HG chickens are fatter and over-express numerous genes that support higher rates of visceral adipogenesis and lipogenesis. In abdominal fat of LG chickens, we found higher expression of many genes involved in hemostasis, energy catabolism and endocrine signaling, which likely contribute to their leaner phenotype and slower growth. Many transcription factors and their direct target genes identified in HG and LG chickens could be involved in their divergence in adiposity and growth rate. Conclusions: The present analyses of the visceral fat transcriptome in chickens divergently selected for a large difference in growth rate and abdominal fatness clearly demonstrate that abdominal fat is a very dynamic metabolic and endocrine organ in the chicken. The HG chickens overexpress many transcription factors and their direct target genes, which should enhance in situ lipogenesis and ultimately adiposity. Our observation of enhanced expression of hemostasis and endocrine-signaling genes in diminished abdominal fat of LG cockerels provides insight into genetic mechanisms involved in divergence of abdominal fatness and somatic growth in avian and perhaps mammalian species, including humans. [ABSTRACT FROM AUTHOR]

The vast bacteriophage population harbors an immense reservoir of genetic information. Almost 2000 phage genomes have been sequenced from phages infecting hosts in the phylum Actinobacteria, and analysis of these genomes reveals substantial diversity, pervasive mosaicism, and novel mechanisms for phage replication and lysogeny. Here, we describe the isolation and genomic characterization of 46 phages from environmental samples at various geographic locations in the U.S. infecting a single Arthrobacter sp. strain. These phages include representatives of all three virion morphologies, and Jasmine is the first sequenced podovirus of an actinobacterial host. The phages also span considerable sequence diversity, and can be grouped into 10 clusters according to their nucleotide diversity, and two singletons each with no close relatives. However, the clusters/singletons appear to be genomically well separated from each other, and relatively few genes are shared between clusters. Genome size varies from among the smallest of siphoviral phages (15,319 bp) to over 70 kbp, and G+C contents range from 45–68%, compared to 63.4% for the host genome. Although temperate phages are common among other actinobacterial hosts, these Arthrobacter phages are primarily lytic, and only the singleton Galaxy is likely temperate. [ABSTRACT FROM AUTHOR]

Previous studies demonstrated that in ovo photostimulation with monochromatic green light increases body weight and accelerates muscle development in broilers. The mechanism in which in ovo photostimulation accelerates growth and muscle development is not clearly understood. The objective of the current study was to define development of the somatotropic axis in the broiler embryo associated with in ovo green light photostimulation. Two-hundred-forty fertile broiler eggs were divided into 2 groups. The first group was incubated under intermittent monochromatic green light using light-emitting diode (LED) lamps with an intensity of 0.1 W\m2 at shell level, and the second group was incubated under dark conditions and served as control. In ovo green light photostimulation increased plasma growth hormone (GH) and prolactin (PRL) levels, as well as hypothalamic growth hormone releasing hormone (GHRH), liver growth hormone receptor (GHR), and insulin-like growth factor-1 (IGF-1) mRNA levels. The in ovo photostimulation did not, however, increase embryo's body weight, breast muscle weight, or liver weight. The results of this study suggest that stimulation with monochromatic green light during incubation increases somatotropic axis expression, as well as plasma prolactin levels, during embryonic development. [ABSTRACT FROM AUTHOR]

Heat stress (HS) is devastating to poultry production worldwide, yet its biology and molecular responses are not well defined. Although advances in management strategy have partially alleviated the negative impact of HS, productivity still continues to decline when the ambient temperature rises. Therefore, identifying mechanism-based approaches to decrease HS susceptibility while improving production traits is critical. Recently, we made a breakthrough by applying a surface wetting strategy and showing that it improves growth performance compared with the current conventional cooling system. In the present study, we aimed to further define molecular mechanisms associated with surface wetting in ameliorating HS productivity loss in broilers. Five-week-old broiler chickens were exposed to acute HS (35°C for 2 h) alone or in combination with surface wetting. A control group was maintained at thermoneutral conditions (25°C). Core body temperature (BT) and feed intake were recorded. Blood was collected and hypothalamic tissues (main site involved in the regulation of energy homeostasis) wereed to determine the expression profile of stress- and metabolic-related genes. Surface wetting prevents HS from increasing BT and plasma corticosterone levels (P < 0.05) and improves feeding and drinking behaviors. At molecular levels, surface wetting blocks the activation of hypothalamic heat shock protein and adenosine monophosphate-activated protein-induced by HS and significantly modulates the expression of feeding-related hypothalamic neuropeptides (agouti-related protein, proopiomelanocortin, orexin, orexin receptor, and leptin receptor). Taken together, our data represent the first evidence that surface wetting alleviates systemic and intracellular stress induced by HS and preserves the intracellular energy status, which, in turn, may result in improved broiler well-being and growth performance. [ABSTRACT FROM AUTHOR]

A foreword to "Clinical Obstetrics & Gynecology" is presented.

Objective: To characterize tocolytic use and examine perinatal outcomes among women presenting very preterm with spontaneous labor and cervical dilation 4 cm or greater.Methods: This was a retrospective cohort study. Data from January 2000 to June 2011 in a single health care system were reviewed. Women with singleton, nonanomalous fetuses and preterm labor with intact membranes between 23 and 32 weeks of gestation who had cervical dilation 4 cm or greater and less than 8 cm at admission were included. Women receiving one or more tocolytics (magnesium sulfate, indomethacin, or nifedipine) were compared with those who did not receive tocolysis. The primary outcome was composite major neonatal morbidity.Results: Two hundred ninety-seven women were included; 233 (78.5%) received at least one tocolytic. Women receiving tocolysis were slightly less dilated (median 5 compared with 6 cm, P<.001) at presentation and were more likely to receive at least a partial course of corticosteroids (88.4% compared with 56.3%, P<.001). Initial composite severe neonatal morbidity rates were similar (41.6% compared with 43.8%, P=.761) regardless of tocolytic administration. Those receiving tocolysis were significantly more likely to be pregnant at least 48 hours after admission (23.6% compared with 7.8%, P=.005), but a similar proportion delivered within 7 days of admission (94.8% compared with 95.3%, P>.99), and delivery gestational ages were similar (28.9 compared with 29.2 weeks, P=.408). The incidence of chorioamnionitis and postpartum endometritis was similar between groups.Conclusion: The majority of women presenting very preterm with advanced cervical dilation received tocolysis. Although tocolysis administration increased the likelihood of achieving at least 48 hours of latency, initial neonatal outcomes were similar.Level Of Evidence: II. [ABSTRACT FROM AUTHOR]

Background: Because systemic lupus erythematosus (SLE) affects women of reproductive age, pregnancy is a major concern. Objective: To identify predictors of adverse pregnancy outcomes (APOs) in patients with inactive or stable active SLE. Design: Prospective cohort. Setting: Multicenter. Patients: 385 patients (49% non-Hispanic white; 31% with prior nephritis) with SLE in the PROMISSE (Predictors of Pregnancy Outcome: Biomarkers in Antiphospholipid Antibody Syndrome and Systemic Lupus Erythematosus) study. Exclusion criteria were urinary protein–creatinine ratio greater than 1000 mg/g, creatinine level greater than 1.2 mg/dL, prednisone use greater than 20 mg/d, and multifetal pregnancy. Measurements: APOs included fetal or neonatal death; birth before 36 weeks due to placental insufficiency, hypertension, or preeclampsia; and small-for-gestational-age (SGA) neonate (birthweight below the fifth percentile). Disease activity was assessed with the Systemic Lupus Erythematosus Pregnancy Disease Activity Index and the Physician's Global Assessment (PGA). Results: APOs occurred in 19.0% (95% CI, 15.2% to 23.2%) of pregnancies; fetal death occurred in 4%, neonatal death occurred in 1%, preterm delivery occurred in 9%, and SGA neonate occurred in 10%. Severe flares in the second and third trimesters occurred in 2.5% and 3.0%, respectively. Baseline predictors of APOs included presence of lupus anticoagulant (LAC) (odds ratio [OR], 8.32 [CI, 3.59 to 19.26]), antihypertensive use (OR, 7.05 [CI, 3.05 to 16.31]), PGA score greater than 1 (OR, 4.02 [CI, 1.84 to 8.82]), and low platelet count (OR, 1.33 [CI, 1.09 to 1.63] per decrease of 50 × 109 cells/L). Non-Hispanic white race was protective (OR, 0.45 [CI, 0.24 to 0.84]). Maternal flares, higher disease activity, and smaller increases in C3 level later in pregnancy also predicted APOs. Among women without baseline risk factors, the APO rate was 7.8%. For those who either were LAC-positive or were LAC-negative but nonwhite or Hispanic and using antihypertensives, the APO rate was 58.0% and fetal or neonatal mortality was 22.0%. Limitation: Patients with high disease activity were excluded. Conclusion: In pregnant patients with inactive or stable mild/ moderate SLE, severe flares are infrequent and, absent specific risk factors, outcomes are favorable. [ABSTRACT FROM AUTHOR]

Abstract: Pregnancy morbidity is one of the clinical manifestations used for classification criteria of antiphospholipid syndrome (APS). During the 14th International Congress on Antiphospholipid Antibodies (aPL), a Task Force with internationally-known experts was created to carry out a critical appraisal of the literature available regarding the association of aPL with obstetric manifestations present in actual classification criteria (recurrent early miscarriage, fetal death, preeclampsia and placental insufficiency) and the quality of the evidence that treatment(s) provide benefit in terms of avoiding recurrent adverse obstetric outcomes. The association of infertility with aPL and the effectiveness of the treatment of patients with infertility and positive aPL was also investigated. This report presents current knowledge and limitations of published studies regarding pregnancy morbidity, infertility and aPL, identifying areas that need better investigative efforts and proposing how critical flaws could be avoided in future studies, as suggested by participants of the Task Force. Except for fetal death, there are limitations in the quality of the data supporting the association of aPL with obstetric complications included in the current APS classification criteria. Recommended treatments for all pregnancy morbidity associated to APS also lack well-designed studies to confirm its efficacy. APL does not seem to be associated with infertility and treatment does not improve the outcomes in infertile patients with aPL. In another section of the Task Force, Dr. Jane Salmon reviewed complement-mediated inflammation in reproductive failure in APS, considering new therapeutic targets to obstetric APS (Ob APS). [Copyright &y& Elsevier]