Aspirin in Pregnancy.

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.

Excluding pregnancy-associated deep vein thrombosis with whole-leg ultrasound.

Background: Deep vein thrombosis (DVT) is common in pregnancy, yet data are limited on the best diagnostic strategies in pregnant patients suspected of DVT. Objectives: We conducted a prospective cohort study to evaluate the rate of symptomatic DVT in the 90 days after a negative whole-leg compression ultrasound (CUS) in pregnant women presenting with DVT symptoms. Methods: In this prospective cohort study, we enrolled pregnant patients suspected of DVT between 2011 and 2019 who were referred to the vascular imaging laboratory at a tertiary care center and had anticoagulation held after a negative whole-leg CUS. Primary outcome was objectively confirmed DVT or pulmonary embolism or death due to venous thromboembolism (VTE). Results: Whole-leg CUS yielded normal results in 186 patients (97.9%) and identified DVT in 4 (2.1%). The mean age was 30 and 164 were White. Among the 186 patients with a negative, initial whole-leg CUS who did not receive anticoagulation, there were 2 DVT events identified over the 90-day follow-up period, for an overall rate of 1.1% (95% CI: 0.2-3.4%). The study was terminated before full planned accrual for administrative reasons. Conclusion: The rate of symptomatic DVT is low in pregnant patients who have a single, negative whole-leg CUS and did not receive anticoagulation. Adequately powered studies should prospectively assess whole-leg CUS in a larger population alone and in combination with pre-test probability scores and/or D-dimer to determine its role in the evaluation of suspected DVT in pregnancy.

Probing the pressure dependence of sound speed and attenuation in bubbly media: Experimental observations, a theoretical model and numerical calculations.

The problem of attenuation and sound speed of bubbly media has remained partially unsolved. Comprehensive data regarding pressure-dependent changes of the attenuation and sound speed of a bubbly medium are not available. Our theoretical understanding of the problem is limited to linear or semi-linear theoretical models, which are not accurate in the regime of large amplitude bubble oscillations. Here, by controlling the size of the lipid coated bubbles (mean diameter of ≈5.4µm), we report the first time observation and characterization of the simultaneous pressure dependence of sound speed and attenuation in bubbly water below, at and above microbubbles resonance (frequency range between 1-3 MHz). With increasing acoustic pressure (between 12.5-100 kPa), the frequency of the peak attenuation and sound speed decreases while maximum and minimum amplitudes of the sound speed increase. We propose a nonlinear model for the estimation of the pressure dependent sound speed and attenuation with good agreement with the experiments. The model calculations are validated by comparing with the linear and semi-linear models predictions. One of the major challenges of the previously developed models is the significant overestimation of the attenuation at the bubble resonance at higher void fractions (e.g. 0.005). We addressed this problem by incorporating bubble-bubble interactions and comparing the results to experiments. Influence of the bubble-bubble interactions increases with increasing pressure. Within the examined exposure parameters, we numerically show that, even for low void fractions (e.g. 5.1×10-6) with increasing pressure the sound speed may become 4 times higher than the sound speed in the non-bubbly medium.

Prediction and Prevention of Preterm Birth: A Prospective, Randomized Intervention Trial.

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 (NCT03530332). 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..

Effects of genetic selection on activity of corticotropic and thyrotropic axes in modern broiler chickens.

Commercial selection for meat-type (broiler) chickens has produced economically valuable birds with fast growth rates, enhanced muscle mass, and highly efficient feed utilization. The physiological changes that account for this improvement and unintended consequences associated with them remain largely unexplored, despite their potential to guide further advancements in broiler production efficiency. To identify effects of genetic selection on hormonal signaling in the adrenocorticotropic and thyrotropic axes, gene expression in muscle and liver and post-hatch circulating hormone concentrations were measured in legacy [Athens Canadian Random Bred (ACRB)] and modern (Ross 308) male broilers between embryonic days (e) 10 and e18 and post-hatch days (d) 10 and d40. No interactive effects or main effects of line were observed for adrenocorticotropic gene expression during either developmental period, although age effects appeared for corticosteroid-binding globulin in liver during embryogenesis and post-hatch and glucocorticoid receptor in both tissues post-hatch. There was a main line effect for circulating corticosterone, with levels in ACRB greater than those in Ross. Several thyrotropic genes exhibited line-by-age interactions during embryonic or post-hatch development. In liver, embryonic expression of thyroid hormone receptor beta was greater in ACRB on e12, and deiodinase 3 (DIO3) levels were greater in Ross on e14 and e16. In juvenile liver, deiodinase 2 (DIO2) expression was greater in ACRB on d10 but greater in Ross on d20, while DIO3 was higher in ACRB on d30 and d40. Levels of thyroid hormone receptor alpha mRNA exhibited a main line effect, with levels greater in ACRB juvenile breast muscle. Several thyrotropic genes exhibited main age effects, including DIO2 and DIO3 in embryonic breast muscle, thyroid hormone receptor alpha and thyroid hormone receptor beta in post-hatch liver, and DIO2 in post-hatch breast muscle. Circulating triiodothyronine displayed a main line effect, with levels in Ross significantly reduced as compared to ACRB. These findings suggest that in modern broilers, a decrease in levels of hormones that control basal metabolism triiodothyronine and the stress response circulating corticosterone, as well as altered expression of genes regulating thyroid hormone activity, could contribute to lower heat production, reduced stress response, and altered nutrient partitioning, leading to more efficient feed utilization and faster, more productive growth.

Erratum: "Inference of the Local Interstellar Spectra of Cosmic-Ray Nuclei Z ⩽ 28 with the GALPROP-HELMOD Framework" (2020, ApJS, 250, 27).

[This corrects the article PMC8549769.].

The Discovery of a Low-energy Excess in Cosmic-Ray Iron: Evidence of the Past Supernova Activity in the Local Bubble.

Since its launch, the Alpha Magnetic Spectrometer-02 (AMS-02) has delivered outstanding quality measurements of the spectra of cosmic-ray (CR) species ( p ¯ , 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 p ¯ , e -, and nuclei Z ⩽ 28.

The effect of selected in ovo green light photostimulation periods on post-hatch broiler growth and somatotropic axis activity.

Targeted in ovo green light (GL) photostimulation during the last days of broiler egg incubation increases embryonic expression of the somatotropic axis, similar to in ovo green light photostimulation from embryonic day (ED) 0 to the end of incubation. The aim of this study was to examine the effect of selected in ovo GL photostimulation periods on post-hatch broiler growth. Four hundred twenty fertile broiler eggs were divided into 7 treatment groups: the first incubated in the dark (standard conditions) as a negative control; the second incubated under monochromatic GL from ED0-ED20 (positive control); the third group incubated under monochromatic GL light from ED15-ED20; the fourth, fifth and sixth groups were incubated under monochromatic GL on ED16, ED17, and ED18, respectively; and the seventh group was incubated under monochromatic GL from ED18-ED20. All illumination was provided intermittently using LED lamps. After hatch, all chicks were transferred to a controlled room under standard rearing conditions. The group incubated under green light from ED18 until hatch showed similar results to the positive control group in body weights, as well as breast muscle weights (as % of body weights), and an elevation in the somatotropic axis activity during the experiment. We suggest that broiler embryos can be exposed to in ovo GL photostimulation from ED18 until hatch (hatching period), and still exhibit the same performance as obtained by photostimulation from d 0 of incubation.

Profile hidden Markov model sequence analysis can help remove putative pseudogenes from DNA barcoding and metabarcoding datasets.

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.

In ovo green light photostimulation during the late incubation stage affects somatotropic axis activity.

Targeted green light photostimulation during the last stage of broiler incubation increases expression of the somatotropic axis. The purpose of this study was to further shorten the in ovo green light photostimulation and determine the critical age for photostimulation in broilers embryos, as a future strategy for broiler incubation. Fertile broilers eggs (n = 420) were divided into 5 treatment groups. The first group was incubated under standard conditions (in the dark) as the negative control group. The second was incubated under intermittent monochromatic green light using light-emitting diode lamps with an intensity of 0.1 W/m2 at shell level from embryonic day (ED) 0 of incubation until hatch, as a positive control. The third, fourth, and fifth groups were incubated under intermittent monochromatic green light from ED 15, 16, and 18 of incubation, respectively, until hatch. All treatment groups showed elevated somatotropic axis expression compared with the negative control, with the group incubated under monochromatic green light from ED 18 until hatch showing results closest to the positive control. This suggests that broiler embryos can be exposed to in ovo green light photostimulation from a late stage of incubation (when transferring the eggs to the hatchery) and exhibit essentially the same outcome as obtained by photostimulation during the entire incubation period.

Long-term prognostic value of stress myocardial perfusion echocardiography in patients with coronary artery disease: a meta-analysis.

AIMS: To evaluate the prognostic value of myocardial perfusion (MP) imaging during contrast stress echocardiography (cSE) in patients with known or suspected coronary artery disease (CAD). METHODS AND RESULTS: A search in PubMed, Embase databases, and the Cochrane library was conducted through May 2019. The Cochran Q statistic and the I2 statistic were used to assess heterogeneity, and the results were analysed by RevMan V5.3 and Stata V15.1 software. Twelve studies (seven dipyridamole and five exercise/dobutamine) without evidence of patient overlap (same institution publishing results over a similar time period) enrolling 5953 subjects (47% female, 8-80 months of follow-up) were included in the analysis. In all studies, total adverse cardiovascular events were defined as either cardiac death, non-fatal myocardial infarction (NFMI), or need for urgent revascularization. Hazard ratios (HRs) revealed that a MP abnormality [pooled HR 4.75; 95% confidence interval (CI) 2.47-9.14] was a higher independent predictor of total events than abnormal wall motion (WM, pooled HR 2.39; 95% CI 1.58-3.61) and resting left ventricular ejection fraction (LVEF, pooled HR 1.92; 95% CI 1.44-2.55) with significant subgroup differences (P = 0.002 compared with abnormal WM and 0.01 compared with abnormal LVEF). Abnormal MP was associated with higher risks for death [Risk ratio (RR) 5.24; 95% CI 2.91-9.43], NFMI (RR 3.09; 95% CI 1.84-5.21), and need for coronary revascularization (RR 16.44; 95% CI 6.14-43.99). CONCLUSION: MP analysis during stress echocardiography is an effective prognostic tool in patients with known or suspected CAD and provides incremental value over LVEF and WM in predicting clinical outcomes.

Sonothrombolysis in the ambulance for ST-elevation myocardial infarction: rationale and protocol.

BACKGROUND: Treatment of ST-elevation myocardial infarction (STEMI) has improved over the years. Current challenges in the management of STEMI are achievement of early reperfusion and the prevention of microvascular injury. Sonothrombolysis has emerged as a potential treatment for acute myocardial infarction, both for epicardial recanalisation as well as improving microvascular perfusion. This study aims to determine safety and feasibility of sonothrombolysis application in STEMI patients in the ambulance. METHODS: Ten patients with STEMI will be included and treated with sonothrombolysis in the ambulance during transfer to the PCI centre. Safety will be assessed by the occurrence of ventricular arrhythmias and shock during sonothrombolysis intervention. Feasibility will be assessed by the extent of protocol completion and myocardial visibility. Efficacy will be determined by angiographic patency rate, ST-elevation resolution, infarct size and left ventricular volumes, and function measured with cardiovascular magnetic resonance imaging, and contrast and strain echocardiography. A comparison will be made with matched controls using an existing STEMI database. DISCUSSION: Sonothrombolysis is a novel technique for the treatment of cardiovascular thromboembolic disease. The first clinical trials on its use for STEMI have demonstrated promising results. This study will be the first to examine the feasibility of in-ambulance sonothrombolysis for STEMI. TRIAL REGISTRATION: EU Clinical Trials Register (identifier: 2019-001883-31), registered 2020-02-25.

An Update on Biologic Agents During Pregnancy.

Most biological agents are safe to use in pregnancy. Biologic agents may be divided into 4 risk categories: minimal, uncertain, moderate, and high. Treatment options should be individualized to each patient's disease activity, response to medication, and adverse effects. Hydroxychloroquine, sulfasalazine, azathioprine, cyclosporine A, and low-dose aspirin are considered safe. Glucocorticoids may increase the risk of gestational diabetes and gestational hypertension/preeclampsia. Nonsteroidal medication should only be used during the first trimester and for a short period during the second trimester. Limited experience with tumor necrosis factor-α inhibitor medications suggests minimal risk. Methotrexate, mycophenolate, and leflunomide are contraindicated during pregnancy.

Nonlinear power loss in the oscillations of coated and uncoated bubbles: Role of thermal, radiation and encapsulating shell damping at various excitation pressures.

This study presents the fundamental equations governing the pressure dependent disipation mechanisms in the oscillations of coated bubbles. A simple generalized model (GM) for coated bubbles accounting for the effect of compressibility of the liquid is presented. The GM was then coupled with nonlinear ODEs that account for the thermal effects. Starting with mass and momentum conservation equations for a bubbly liquid and using the GM, nonlinear pressure dependent terms were derived for power dissipation due to thermal damping (Td), radiation damping (Rd) and dissipation due to the viscosity of liquid (Ld) and coating (Cd). The pressure dependence of the dissipation mechanisms of the coated bubble have been analyzed. The dissipated energies were solved for uncoated and coated 2-20 µm in bubbles over a frequency range of 0.25fr-2.5fr (fr is the bubble resonance) and for various acoustic pressures (1 kPa-300 kPa). Thermal effects were examined for air and C3F8 gas cores. In the case of air bubbles, as pressure increases, the linear thermal model looses accuracy and accurate modeling requires inclusion of the full thermal model. However, for coated C3F8 bubbles of diameter 1-8 µm, which are typically used in medical ultrasound, thermal effects maybe neglected even at higher pressures. For uncoated bubbles, when pressure increases, the contributions of Rd grow faster and become the dominant damping mechanism for pressure dependent resonance frequencies (e.g. fundamental and super harmonic resonances). For coated bubbles, Cd is the strongest damping mechanism. As pressure increases, Rd contributes more to damping compared to Ld and Td. For coated bubbles, the often neglected compressibility of the liquid has a strong effect on the oscillations and should be incorporated in models. We show that the scattering to damping ratio (STDR), a measure of the effectiveness of the bubble as contrast agent, is pressure dependent and can be maximized for specific frequency ranges and pressures.

Deciphering the Local Interstellar Spectra of Secondary Nuclei with the Galprop/Helmod Framework and a Hint for Primary Lithium in Cosmic Rays.

Local interstellar spectra (LIS) of secondary cosmic-ray (CR) nuclei, lithium, beryllium, boron, and partially secondary nitrogen, are derived in the rigidity range from 10 MV to ~200 TV using the most recent experimental results combined with state-of-the-art models for CR propagation in the Galaxy and in the heliosphere. The lithium spectrum appears somewhat flatter at high energies compared to other secondary species, which may imply a primary lithium component. Two propagation packages, GALPROP and HelMod, are combined to provide a single framework that is run to reproduce direct measurements of CR species at different modulation levels, and at both polarities of the solar magnetic field. An iterative maximum-likelihood method is developed that uses GALPROP-predicted LIS as input to HelMod, which provides the modulated spectra for specific time periods of the selected experiments for the model-data comparison. The proposed LIS accommodates the low-energy interstellar spectra measured by Voyager 1, the High Energy Astrophysics Observatory-3 (HEAO-3), and the Cosmic Ray Isotope Spectrometer on board of the Advanced Composition Explorer (ACE/CRIS), as well as the high-energy observations by the Payload for Antimatter Matter Exploration and Light-nuclei Astrophysics (PAMELA), Alpha Magnetic Spectrometer-02 (AMS-02), and earlier experiments that are made deep in the heliosphere. The interstellar and heliospheric propagation parameters derived in this study are consistent with our earlier results for propagation of CR protons, helium, carbon, oxygen, antiprotons, and electrons.

Inference of the Local Interstellar Spectra of Cosmic-Ray Nuclei Z ⩽ 28 with the GalProp-HelMod Framework.

Composition and spectra of Galactic cosmic rays (CRs) are vital for studies of high-energy processes in a variety of environments and on different scales, for interpretation of γ-ray and microwave observations, for disentangling possible signatures of new phenomena, and for understanding of our local Galactic neighborhood. Since its launch, AMS-02 has delivered outstanding-quality measurements of the spectra of p ¯ , e ±, and nuclei: 1H-8O, 10Ne, 12Mg, 14Si. These measurements resulted in a number of breakthroughs; however, spectra of heavier nuclei and especially low-abundance nuclei are not expected until later in the mission. Meanwhile, a comparison of published AMS-02 results with earlier data from HEAO-3-C2 indicates that HEAO-3-C2 data may be affected by undocumented systematic errors. Utilizing such data to compensate for the lack of AMS-02 measurements could result in significant errors. In this paper we show that a fraction of HEAO-3-C2 data match available AMS-02 measurements quite well and can be used together with Voyager 1 and ACE-CRIS data to make predictions for the local interstellar spectra (LIS) of nuclei that are not yet released by AMS-02. We are also updating our already-published LIS to provide a complete set from 1H-28Ni in the energy range from 1 MeV nucleon-1 to ~100-500 TeV nucleon-1, thus covering 8-9 orders of magnitude in energy. Our calculations employ the GalProp-HelMod framework, which has proved to be a reliable tool in deriving the LIS of CR p ¯ , e -, and nuclei 1H-8O.

Longitudinal profiling of human blood transcriptome in healthy and lupus pregnancy.

Systemic lupus erythematosus carries an increased risk of pregnancy complications, including preeclampsia and fetal adverse outcomes. To identify the underlying molecular mechanisms, we longitudinally profiled the blood transcriptome of 92 lupus patients and 43 healthy women during pregnancy and postpartum and performed multicolor flow cytometry in a subset of them. We also profiled 25 healthy women undergoing assisted reproductive technology to monitor transcriptional changes around embryo implantation. Sustained down-regulation of multiple immune signatures, including interferon and plasma cells, was observed during healthy pregnancy. These changes appeared early after embryo implantation and were mirrored in uncomplicated lupus pregnancies. Patients with preeclampsia displayed early up-regulation of neutrophil signatures that correlated with expansion of immature neutrophils. Lupus pregnancies with fetal complications carried the highest interferon and plasma cell signatures as well as activated CD4+ T cell counts. Thus, blood immunomonitoring reveals that both healthy and uncomplicated lupus pregnancies exhibit early and sustained transcriptional modulation of lupus-related signatures, and a lack thereof associates with adverse outcomes.

MDM2 antagonist-loaded targeted micelles in combination with doxorubicin: effective synergism against human glioblastoma via p53 re-activation.

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.

Deciphering Residual Emissions: Time-dependent Models for the Nonthermal Interstellar Radiation from the Milky Way.

Cosmic rays (CRs) in the Galaxy are an important dynamical component of the interstellar medium (ISM) that interact with the other major components (interstellar gas and magnetic and radiation fields) to produce broadband interstellar emissions that span the electromagnetic spectrum. The standard modeling of CR propagation and production of the associated emissions is based on a steady-state assumption, where the CR source spatial density is described using a smoothly varying function of position that does not evolve with time. While this is a convenient approximation, reality is otherwise, where primary CRs are produced in and about highly localized regions, e.g., supernova remnants, which have finite lifetimes. In this paper, we use the latest version of the galprop CR propagation code to model time-dependent CR injection and propagation through the ISM from a realistic 3D discretized CR source density distribution, together with full 3D models for the other major ISM components, and make predictions of the associated broadband nonthermal emissions. We compare the predictions for the discretized and equivalent steady-state model, finding that the former predicts novel features in the broadband nonthermal emissions that are absent for the steady-state case. Some of the features predicted by the discretized model may be observable in all-sky observations made by WMAP and Planck, the recently launched eROSITA, the Fermi-LAT, and ground-based observations by HESS, HAWC, and the forthcoming CTA. The nonthermal emissions predicted by the discretized model may also provide explanations of puzzling anomalies in high-energy γ-ray data, such as the Fermi-LAT north/south asymmetry and residuals like the so-called "Fermi bubbles."

In-ovo green light photostimulation during different embryonic stages affect somatotropic axis.

Previous studies demonstrated that in-ovo 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 light-emitting 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.