The effects of Zinc-Methionine on glucose metabolism and insulin resistance during late pregnancy in ewes.

This study investigated the effects of dietary supplements of Zinc-Methionine (Zn-Met) on the zinc concentration of the blood and indices such as insulin resistance and glucose tolerance in late-pregnancy ewes to provide a practical solution to prevent metabolic diseases associated with energy status. In this research, 18 Makouei pregnant ewes were selected and randomized into 3 experimental groups: Group 1: Basal diet containing 10.3 mg Zn/kgDM and no zinc supplementation = CTR (Control); Group 2: Basal diet supplemented with low-dose zinc equivalent to the pregnancy requirements (30 mg Zn/kgDM) = LZN; Group 3: Basal diet supplemented with high-dose zinc (300 mg Zn/kgDM) = HZN. Blood samples for insulin resistance and glucose tolerance indices were collected according to standard methods. The results of this study indicated that supplementation of high-dose Zn-Met decreased (P < 0.05) blood glucose and tended (P < 0.1) to reduce the beta-hydroxybutyrate (BHB) concentrations. After intravenous injection of glucose and insulin, none of the glucose tolerance and insulin resistance indices were significant among groups (P > 0.05). However, the intravenous glucose tolerance test (IGTT) showed that the area under the curve (AUC) of serum glucose in the HZN group was numerically lower than that of the LZN and CTR groups. Furthermore, the numerically higher clearance rate (CR) of glucose and more negative glucose AUC following intravenous administration of insulin in Zinc-supplemented groups suggested that the ewes had greater insulin response than control group. The results showed a decrease in blood glucose concentration due to higher zinc intake after insulin injection and supported the evidence for improving insulin sensitivity. In addition, our results showed that ewes receiving zinc supplementation experienced a more favorable state of BHB or NEFA values. In conclusion, Zn-Met supplementation was found to have promising effects in improving energy metabolism in late pregnant ewes. However, further studies are needed to understand the mechanisms involved in regulating lipolysis and energy metabolism.

Association of protein intake with the outcomes of critically ill patients: a post hoc analysis of the PermiT trial.

Background: The optimal amount of protein intake in critically ill patients is uncertain. Objective: In this post hoc analysis of the PermiT (Permissive Underfeeding vs. Target Enteral Feeding in Adult Critically Ill Patients) trial, we tested the hypothesis that higher total protein intake was associated with lower 90-d mortality and improved protein biomarkers in critically ill patients. Design: In this post hoc analysis of the PermiT trial, we included patients who received enteral feeding for ≥3 consecutive days. Using the median protein intake of the cohort as a cutoff, patients were categorized into 2 groups: a higher-protein group (>0.80 g · kg-1 · d-1) and a lower-protein group (≤0.80 g · kg-1 · d-1). We developed a propensity score for receiving higher protein. Primary outcome was 90-d mortality. We also compared serial values of prealbumin, transferrin, 24-h urinary nitrogen, and 24-h nitrogen balance on days 1, 7, and 14. Results: Among the 729 patients included in this analysis, the average protein intake was 0.8 ± 0.3 g · kg-1 · d-1 [1.0 ± 0.2 g · kg-1 · d-1 in the higher-protein group (n = 365) and 0.6 ± 0.2 g · kg-1 · d-1 in the lower-protein group (n = 364); P < 0.0001]. There was no difference in 90-d mortality between the 2 groups [88/364 (24.2%) compared with 94/363 (25.9%), propensity score-adjusted OR: 0.80; 95% CI: 0.56, 1.16; P = 0.24]. Higher protein intake was associated with an increase in 24-h urea nitrogen excretion compared with lower protein intake, but without a significant change in prealbumin, transferrin, or 24-h nitrogen balance. Conclusions: In the PermiT trial, a moderate difference in protein intake was not associated with lower mortality. Higher protein intake was associated with increased nitrogen excretion in the urine without a corresponding change in prealbumin, transferrin, or nitrogen balance. Protein intake needs to be tested in adequately powered randomized controlled trials targeting larger differences in protein intake in high-risk populations.

Relationship among temporary separation, attachment styles, and adjustment in first-grade Iranian children.

If mothers work outside the home, some degree of mother-child separation will be experienced and mother-child attachment will be affected. In this study, regarding the attachment styles, sociobehavioral problems in first-grade children with experience of preschool and in those taught by their mothers at-home are compared. A casual-comparative method was used to compare children in the two groups. A total of 320 first-grade children participated in the study. The study measures included a separation anxiety test, an adaptive behavior scale, and a children's symptom inventory. Data were analyzed using multivariate statistics. Secure attachment in the group with experience of preschool was significantly higher than that in the at-home group. None of the variables, including parents' education and father's income, significantly affected attachment style. Neither father's education, father's income, or attachment significantly influenced adjustment. Father's education significantly influenced children's symptoms. Attachment style and hours of preschool attendance had no effect on Child Symptom Inventory scores. Associations among age at joining preschool, attachment style, and behavioral and adaptive problems in first-grade children were nonlinear and multivariate. By taking into account parents' awareness, sensitivity, and responsiveness, relative welfare, appropriate quality of child-care centers, and having fewer hours of preschool attendance, the risk factors for early parent-child separation and institutional care can be reduced.

Photo-fluorescent and magnetic properties of iron oxide nanoparticles for biomedical applications.

Iron oxide exhibits fascinating physical properties especially in the nanometer range, not only from the standpoint of basic science, but also for a variety of engineering, particularly biomedical applications. For instance, Fe3O4 behaves as superparamagnetic as the particle size is reduced to a few nanometers in the single-domain region depending on the type of the material. The superparamagnetism is an important property for biomedical applications such as magnetic hyperthermia therapy of cancer. In this review article, we report on some of the most recent experimental and theoretical studies on magnetic heating mechanisms under an alternating (AC) magnetic field. The heating mechanisms are interpreted based on Néel and Brownian relaxations, and hysteresis loss. We also report on the recently discovered photoluminescence of Fe3O4 and explain the emission mechanisms in terms of the electronic band structures. Both optical and magnetic properties are correlated to the materials parameters of particle size, distribution, and physical confinement. By adjusting these parameters, both optical and magnetic properties are optimized. An important motivation to study iron oxide is due to its high potential in biomedical applications. Iron oxide nanoparticles can be used for MRI/optical multimodal imaging as well as the therapeutic mediator in cancer treatment. Both magnetic hyperthermia and photothermal effect has been utilized to kill cancer cells and inhibit tumor growth. Once the iron oxide nanoparticles are up taken by the tumor with sufficient concentration, greater localization provides enhanced effects over disseminated delivery while simultaneously requiring less therapeutic mass to elicit an equal response. Multi-modality provides highly beneficial co-localization. For magnetite (Fe3O4) nanoparticles the co-localization of diagnostics and therapeutics is achieved through magnetic based imaging and local hyperthermia generation through magnetic field or photon application. Here, Fe3O4 nanoparticles are shown to provide excellent conjugation bases for entrapment of therapeutic molecules, fluorescent agents, and targeting ligands; enhancement of solid tumor treatment is achieved through co-application of local hyperthermia with chemotherapeutic agents.

Severe neurologic syndrome associated with Middle East respiratory syndrome corona virus (MERS-CoV).

BACKGROUND: Since the identification of the first case of infection with the Middle East respiratory syndrome corona virus (MERS-CoV) in Saudi Arabia in June 2012, the number of laboratory-confirmed cases has exceeded 941 cases globally, of which 347 died. The disease presents as severe respiratory infection often with shock, acute kidney injury, and coagulopathy. Recently, we observed three cases who presented with neurologic symptoms. These are so far the first reported cases of neurologic injury associated with MERS-CoV infection. METHODS: Data was retrospectively collected from three patients admitted with MERS-CoV infection to Intensive Care unit (ICU) at King Abdulaziz Medical City, Riyadh. They were managed separately in three different wards prior to their admission to ICU. FINDING: The three patients presented with severe neurologic syndrome which included altered level of consciousness ranging from confusion to coma, ataxia, and focal motor deficit. Brain MRI revealed striking changes characterized by widespread, bilateral hyperintense lesions on T2-weighted imaging within the white matter and subcortical areas of the frontal, temporal, and parietal lobes, the basal ganglia, and corpus callosum. None of the lesions showed gadolinium enhancement. INTERPRETATION: CNS involvement should be considered in patients with MERS-CoV and progressive neurological disease, and further elucidation of the pathophysiology of this virus is needed.

Photothermal effects and toxicity of Fe3O4 nanoparticles via near infrared laser irradiation for cancer therapy.

The photothermal effect of magnetite (Fe3O4) nanoparticles was characterized by photonic absorption in the near-infrared (NIR) region. Upon laser irradiation at 785 nm, the Fe3O4 nanoparticles generate localized hyperthermia in tumorous lesions, which is an effective strategy for cancer therapy; however, uncoated magnetite possesses an innate toxicity which can lead to drawbacks in the clinical setting. To reduce innate toxicity, a poly(acrylic acid) (PAA) coating on the nanoparticles was investigated in order to determine the alterations to stability and the degree of toxicity in an attempt to create a higher utility vector. It was found that the PAA coating significantly reduced the innate toxicity of the uncoated magnetite. Furthermore, the efficacy of PAA-coated magnetite nanoparticles (PAA-Fe3O4) was investigated for treating MDA-MB-231 (human mammary gland adenocarcinoma) cultures in viable concentration ranges (0.1-0.5mg/ml). An appropriate PAA-Fe3O4 concentration range was then established for inducing significant cell death by hyperthermic ablation, but not through innate toxicity.

Effect of spatial confinement on magnetic hyperthermia via dipolar interactions in Fe3O4 nanoparticles for biomedical applications.

In this work, the effect of nanoparticle confinement on the magnetic relaxation of iron oxide (Fe3O4) nanoparticles (NP) was investigated by measuring the hyperthermia heating behavior in high frequency alternating magnetic field. Three different Fe3O4 nanoparticle systems having distinct nanoparticle configurations were studied in terms of magnetic hyperthermia heating rate and DC magnetization. All magnetic nanoparticle (MNP) systems were constructed using equivalent ~10nm diameter NP that were structured differently in terms of configuration, physical confinement, and interparticle spacing. The spatial confinement was achieved by embedding the Fe3O4 nanoparticles in the matrices of the polystyrene spheres of 100 nm, while the unconfined was the free Fe3O4 nanoparticles well-dispersed in the liquid via PAA surface coating. Assuming the identical core MNPs in each system, the heating behavior was analyzed in terms of particle freedom (or confinement), interparticle spacing, and magnetic coupling (or dipole-dipole interaction). DC magnetization data were correlated to the heating behavior with different material properties. Analysis of DC magnetization measurements showed deviation from classical Langevin behavior near saturation due to dipole interaction modification of the MNPs resulting in a high magnetic anisotropy. It was found that the Specific Absorption Rate (SAR) of the unconfined nanoparticle systems were significantly higher than those of confined (the MNPs embedded in the polystyrene matrix). This increase of SAR was found to be attributable to high Néel relaxation rate and hysteresis loss of the unconfined MNPs. It was also found that the dipole-dipole interactions can significantly reduce the global magnetic response of the MNPs and thereby decrease the SAR of the nanoparticle systems.

Retroviral vector integration in post-transplant hematopoiesis in mice conditioned with either submyeloablative or ablative irradiation.

X-linked chronic granulomatous disease (X-CGD) is an inherited immunodeficiency with absent phagocyte NADPH-oxidase activity caused by defects in the gene-encoding gp91(phox). Here, we evaluated strategies for less intensive conditioning for gene therapy of genetic blood disorders without selective advantage for gene correction, such as might be used in a human X-CGD protocol. We compared submyeloablative with ablative irradiation as conditioning in murine X-CGD, examining engraftment, oxidase activity and vector integration in mice transplanted with marrow transduced with a gamma-retroviral vector for gp91(phox) expression. The frequency of oxidase-positive neutrophils in the donor population was unexpectedly higher in many 300 cGy-conditioned mice compared with lethally irradiated recipients, as was the fraction of vector-marked donor secondary CFU-S12. Vector integration sites in marrow, spleen and secondary CFU-S12 DNA from primary recipients were enriched for cancer-associated genes, including Evi1, and integrations in or near cancer-associated genes were more frequent in marrow and secondary CFU-S12 from 300 cGy-conditioned mice compared with fully ablated mice. These findings support the concept that vector integration can confer a selection bias, and suggest that the intensity of the conditioning regimen may further influence the effects of vector integration on clonal selection in post-transplant engraftment and hematopoiesis.

GATA-3 represses gp91phox gene expression in eosinophil-committed HL-60-C15 cells.

To study the regulatory mechanism of gp91phox gene expression in eosinophils, we transiently transfected eosinophil-committed HL-60-C15 cells with gp91phox promoter constructs, and identified a negative element from bp -267 to -246 of the gp91phox gene, the deletion of which caused an 83% increase in promoter activity. Electrophoresis mobility shift assays demonstrated GATA-3 binds to the GATA consensus site from bp -256 to -250. An 81% increment in promoter activity was obtained when a mutation was introduced in the GATA-3 binding site of the bp -267 to +12 construct, which is comparable to that of the bp -245 to +12 construct. We therefore conclude that GATA-3 specifically binding to the GATA site negatively regulates the expression of the gene in HL-60-C15 cells.

PU.1 as an essential activator for the expression of gp91(phox) gene in human peripheral neutrophils, monocytes, and B lymphocytes.

We have reported a deficiency of a 91-kDa glycoprotein component of the phagocyte NADPH oxidase (gp91(phox)) in neutrophils, monocytes, and B lymphocytes of a patient with X chromosome-linked chronic granulomatous disease. Sequence analysis of his gp91(phox) gene revealed a single-base mutation (C --> T) at position -53. Electrophoresis mobility-shift assays showed that both PU.1 and hematopoietic-associated factor 1 (HAF-1) bound to the inverted PU.1 consensus sequence centered at position -53 of the gp91(phox) promoter, and the mutation at position -53 strongly inhibited the binding of both factors. It was also indicated that a mutation at position -50 strongly inhibited PU.1 binding but hardly inhibited HAF-1 binding, and a mutation at position -56 had an opposite binding specificity for these factors. In transient expression assay using HEL cells, which express PU.1 and HAF-1, the mutations at positions -53 and -50 significantly reduced the gp91(phox) promoter activity; however, the mutation at position -56 did not affect the promoter activity. In transient cotransfection study, PU.1 dramatically activated the gp91(phox) promoter in Jurkat T cells, which originally contained HAF-1 but not PU.1. In addition, the single-base mutation (C --> T) at position -52 that was identified in a patient with chronic granulomatous disease inhibited the binding of PU.1 to the promoter. We therefore conclude that PU.1 is an essential activator for the expression of gp91(phox) gene in human neutrophils, monocytes, and B lymphocytes.