Educational and economic returns to cognitive ability in low- and middle-income countries: A systematic review.

There is growing interest to use early cognitive ability to predict schooling and employment outcomes in low- and middle-income countries (LMICs). Rather than using educational attainment and school enrollment as predictors of future economic growth or of improving an individual's earning potential, mounting evidence suggests that cognitive ability may be a better predictor. The relationship between cognitive ability, education, and employment are essential to predict future development in LMICs. We performed a systematic literature review and meta-analysis of the evidence regarding the relationship between cognitive ability and educational outcomes, and between cognitive ability and economic outcomes across LMICs. We searched peer-reviewed studies since 2000 that quantitatively measured these relationships. Based on an initial search of 3,766 records, we identified 14 studies, including 8 studies that examined the cognition-education link and 8 studies that assessed cognition-employment returns in LMICs. Identified studies showed that higher cognitive ability increased the probability of school enrollment, academic achievement, and educational attainment across LMICs. A meta-analysis of returns to wages from cognitive ability suggested that a standard deviation increase in cognitive test scores was associated with a 4.5% (95% CI 2.6%-9.6%) increase in wages. Investments into early cognitive development could play a critical role in improving educational and economic outcomes in LMICs. Further research should focus particularly in low-income countries with the least evidence, and examine the impact on education and economic outcomes by cognitive domains to provide more robust evidence for policy makers to take action.

Murine maternal dietary restriction affects neural Humanin expression and cellular profile.

To understand the cellular basis for the neurodevelopmental effects of intrauterine growth restriction (IUGR), we examined the global and regional expression of various cell types within murine (Mus musculus) fetal brain. Our model employed maternal calorie restriction to 50% daily food intake from gestation day 10-19, producing IUGR offspring. Offspring had smaller head sizes with larger head:body ratios indicating a head sparing IUGR effect. IUGR fetuses at embryonic day 19 (E19) had reduced nestin (progenitors), ß-III tubulin (immature neurons), Glial fibrillary acidic protein (astrocytes), and O4 (oligodendrocytes) cell lineages via immunofluorescence quantification and a 30% reduction in cortical thickness. No difference was found in Bcl-2 or Bax (apoptosis) between controls and IUGR, though qualitatively, immunoreactivity of doublecortin (migration) and Ki67 (proliferation) was decreased. In the interest of examining a potential therapeutic peptide, we next investigated a novel pro-survival peptide, mouse Humanin (mHN). Ontogeny examination revealed highest mHN expression at E19, diminishing by postnatal day 15 (P15), and nearly absent in adult (3 months). Subanalysis by sex at E19 yielded higher mHN expression among males during fetal life, without significant difference between sexes postnatally. Furthermore, female IUGR mice at E19 had a greater increase in cortical mHN versus the male fetus over their respective controls. We conclude that maternal dietary restriction-associated IUGR interferes with neural progenitors differentiating into the various cellular components populating the cerebral cortex, and reduces cerebral cortical size. mHN expression is developmental stage and sex specific, with IUGR, particularly in the females, adaptively increasing its expression toward mediating a pro-survival approach against nutritional adversity.

HX-1171, a Novel Nrf2 Activator, Induces NQO1 and HMOX1 Expression.

HX-1171 (1-O-hexyl-2,3,5-trimethylhydroquinone) is a novel synthesized vitamin E derivative, which reportedly has positive effects on various diseases and conditions, such as liver fibrosis, hepatic cirrhosis, and cancer. In this study, we analyzed the transcriptional activity induced by HX-1171. Results from reverse transcription polymerase chain reaction and promoter assays reveal that HX-1171 increased the expression of NQO1 and HMOX1, encoding antioxidant-related enzymes, in A549 human lung epithelial cells. The activity of nuclear factor-E2-related factor (Nrf2), a key transcriptional factor for antioxidative enzymes, was examined in HX-1171-treated cells. Confocal microscopy and Western blotting showed that HX-1171 effectively induced the nuclear translocation and transcriptional activity of Nrf2. We conclude that HX-1171, a novel Nrf2 activator, may be a promising therapeutic agent for oxidative stress-induced diseases. J. Cell. Biochem. 118: 3372-3380, 2017. © 2017 Wiley Periodicals, Inc.

Improving Delivery Accuracy of Stereotactic Body Radiotherapy to a Moving Tumor Using Simplified Volumetric Modulated Arc Therapy.

PURPOSE: To develop a simplified volumetric modulated arc therapy (VMAT) technique for more accurate dose delivery in thoracic stereotactic body radiation therapy (SBRT). METHODS AND MATERIALS: For each of the 22 lung SBRT cases treated with respiratory-gated VMAT, a dose rate modulated arc therapy (DrMAT) plan was retrospectively generated. A dynamic conformal arc therapy plan with 33 adjoining coplanar arcs was designed and their beam weights were optimized by an inverse planning process. All sub-arc beams were converted into a series of control points with varying MLC segment and dose rates and merged into an arc beam for a DrMAT plan. The plan quality of original VMAT and DrMAT was compared in terms of target coverage, compactness of dose distribution, and dose sparing of organs at risk. To assess the delivery accuracy, the VMAT and DrMAT plans were delivered to a motion phantom programmed with the corresponding patients' respiratory signal; results were compared using film dosimetry with gamma analysis. RESULTS: The plan quality of DrMAT was equivalent to that of VMAT in terms of target coverage, dose compactness, and dose sparing for the normal lung. In dose sparing for other critical organs, DrMAT was less effective than VMAT for the spinal cord, heart, and esophagus while being well within the limits specified by the Radiation Therapy Oncology Group. Delivery accuracy of DrMAT to a moving target was similar to that of VMAT using a gamma criterion of 2%/2mm but was significantly better using a 2%/1mm criterion, implying the superiority of DrMAT over VMAT in SBRT for thoracic/abdominal tumors with respiratory movement. CONCLUSION: We developed a DrMAT technique for SBRT that produces plans of a quality similar to that achieved with VMAT but with better delivery accuracy. This technique is well-suited for small tumors with motion uncertainty.

Ingenane-type diterpene compounds from Euphorbia kansui modulate IFN-γ production through NF-κB activation.

BACKGROUND: Euphorbia kansui, a traditional medical herb, has been shown to have anti-tumour and anti-viral activities. Previously, we have reported that E. kansui increases interferon-gamma (IFN-γ) production in natural killer (NK) cells. However, it is not clear how E. kansui regulates IFN-γ secretion by NK cells. RESULTS: In this study, E. kansui was separated into six individual compounds from the same chloroform fraction so that the activity of each compound could be compared. E. kansui compounds induced IFN-γ secretion through the phosphorylation of protein kinase D and IκB kinase pathways. Furthermore, E. kansui compounds activated the translocation of p65, a sub-unit of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), to the nucleus and induced NF-κB at the transcriptional level. CONCLUSION: These findings suggest that E. kansui enhances IFN-γ secretion through the NF-κB pathway in NK cells. © 2015 Society of Chemical Industry.

1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol (EC-18) Modulates Th2 Immunity through Attenuation of IL-4 Expression.

Controlling balance between T-helper type 1 (Th1) and T-helper type 2 (Th2) plays a pivotal role in maintaining the biological rhythm of Th1/Th2 and circumventing diseases caused by Th1/Th2 imbalance. Interleukin 4 (IL-4) is a Th2-type cytokine and often associated with hypersensitivity-related diseases such as atopic dermatitis and allergies when overexpressed. In this study, we have tried to elucidate the function of 1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol (EC-18) as an essential modulator of Th1/Th2 balance. EC-18 has showed an inhibitory effect on the production of IL-4 in a dose-dependent manner. RT-PCR analysis has proved EC-18 affect the transcription of IL-4. By analyzing the phosphorylation status of Signal transducer and activator of transcription 6 (STAT6), which is a transcriptional activator of IL-4 expression, we discovered that EC-18 induced the decrease of STAT6 activity in several stimulated cell lines, which was also showed in STAT6 reporter analysis. Co-treatment of EC-18 significantly weakened atopy-like phenotypes in mice treated with an allergen. Collectively, our results suggest that EC-18 is a potent Th2 modulating factor by regulating the transcription of IL-4 via STAT6 modulation, and could be developed for immune-modulatory therapeutics.

The effect of 4α,5α-epoxy-10α,14-dihydro-inuviscolide, a novel immunosuppressant isolated from Carpesium abrotanoides, on the cytokine profile in vitro and in vivo.

The plant Carpesium abrotanoides (CA) is used in Asian herbal medicines as an insecticide and to treat bruises. However, the effect of single compounds from CA blooms and the mechanism of its immunosuppressive effect remain poorly understood. The aim of this study was to investigate the mechanism of the immunosuppressive effect in the three kinds of immune cells, and the immunosuppressive effect of CA bloom extract (CAE) in acute inflammation models (LPS and ConA-induced inflammation). Interleukin-6, IL-4, IL-13, IFNγ, and IL-10-but not TNFα-were significantly reduced in a dose-dependent manner by 4α,5α-epoxy-10α,14-dihydro-inuviscolide (INV). Furthermore, INV inhibited NF-κB transcriptional activation and IL-10 promoter activity in the same manner as for Bay11. Meanwhile, treatment with dexamethasone reduced the levels of IFNγ, but not IL-10, and resulted in no change in NF-κB transcriptional activation or the IL-10 promoter. INV did not affect PMA-induced IκB kinase complex phosphorylation, IκB degradation, or MAPK and the nuclear translocation of p65, as with DEX. The in vivo, CAE has an immunosuppressive effect on the LPS-induced inflammation response model by inhibiting the plasma level of IFNγ and IL-6 levels. CAE treatment also tends to attenuate the plasma level of IFNγ, IL-4, and IL-6 in ConA-induced inflammation. These findings indicate that INV causes the reduction of the cytokine profile by blocking the NF-κB transcription factor activation and the molecular mechanism by which INV operates could provide new insights into the unique mechanisms responsible for NF-κB inhibition, in contrast to established immunosuppressants, as a therapeutic agent for immunopathological treatment.

Ibudilast, a phosphodiesterase inhibitor with anti-inflammatory activity, protects against ischemic brain injury in rats.

Ibudilast, a non-selective phosphodiesterase inhibitor, is clinically used in patients with stroke or dizziness. However, whether the compound exerts a beneficial effect on acute ischemic stroke remains to be established. We used a rat model of transient focal cerebral ischemia using middle cerebral artery occlusion (MCAO) and reperfusion, and explored the effects of ibudilast on infarction size, brain edema, atrophy, and nerve cell death. Neurological outcomes (behavior and mortality) of rats were also assessed. An intravenous administration of ibudilast attenuated the size of cerebral infarction in a dose-dependent manner, with the most significant reduction achieved at the dose of 10mg/kg. Ibudilast induced a significant reduction in infarct size when administered 30min before MCAO or 0-2h after reperfusion, with the largest reduction observed at 30min before MCAO and 1h after reperfusion. Ibudilast significantly attenuated brain edema formation, cerebral atrophy and apoptosis of nerve cells preferentially in the cortical penumbra area, and also significantly reduced mortality and improved neurological outcomes. Expression of various inflammatory mediator molecules in both hemispheres was markedly suppressed by ibudilast. We conclude that ibudilast exerts beneficial effects against acute brain ischemia in an animal model.

Mechanism of glutathione depletion during simulated ischemia-reperfusion of H9c2 cardiac myocytes.

It has been reported that myocardial glutathione content is decreased during ischemia-reperfusion, but the mechanism of glutathione depletion has remained unclear. The present study tested whether osmotic stress is involved in the glutathione depletion during ischemia. Six hours of hypoxic acidosis with either high CO(2) tension or low HCO(3)(-) concentration, which simulates the ischemic condition, resulted in a significant decrease of glutathione content and the glutathione depletion was prevented by hyperosmolarity. High-CO(2) acidosis alone without hypoxia induced a similar degree of glutathione depletion. Intracellular pH was lowered by high-CO(2) acidosis to 6.41 ± 0.03 in 15 min. Meanwhile, the cell size gradually increased and reached ∼110% in 10 min and the increased cell size was maintained for at least 30 min, which was also prevented by hyperosmolarity. Subsequent experiments observed the effects of simulated reperfusion on the glutathione content. Measured in 1 h after the hypoxic acidotic reperfusion, the glutathione content was further decreased compared to the level at the end of ischemia, which was not suppressed by increasing the osmolarity of reperfusion solution. The degree of glutathione depletion during hypoxic reperfusion with normal pH was similar to the hypoxic acidotic reperfusion group. On the other hand, normoxic reperfusion was not accompanied by further depletion of glutathione content. Based on these results, it was concluded that ischemia induces the glutathione depletion via osmotic stress, which results from intracellular acidification, and the glutathione content is further decreased during reperfusion through a mechanism other than oxygen toxicity.

Osmotic stress induces loss of glutathione and increases the sensitivity to oxidative stress in H9c2 cardiac myocytes.

It has been observed that H9c2 cardiac cells cultured in physiologic solutions exhibit delayed cell death after repeated medium replacements, of which the cause was the relatively mild osmotic challenges during the renewal of the culture medium. Interestingly, the cell damage was associated with altered intracellular GSH homeostasis. Therefore, this study attempted to elucidate the effects of osmotic stress on GSH metabolism. In cells subjected to osmotic stress by lowering the NaCl concentration of the medium, the cell swelling was rapidly counterbalanced, but the intracellular GSH content was significantly lower in 3 h. Meanwhile, the ratio of GSH-to-GSSG was not affected. As expected, osmotic stress also increased the sensitivity to H(2)O(2), which was attributable to the decrease of GSH content. The decrease of GSH content was similarly evident when the synthetic pathways of GSH were blocked by BSO or acivicin. It was concluded that osmotic stress induced the decrease of intracellular GSH content by increased consumption and this loss of GSH rendered the cells susceptible to a subsequent oxidative stress.

Immobilization effect of air-injected blanket (AIB) for abdomen fixation.

A new device for reducing the amplitude of breathing motion by pressing a patient's abdomen using an air-injected blanket (AIB) for external beam radiation treatments has been designed and tested. The blanket has two layers sealed in all four sides similar to an empty pillow made of urethane. The blanket is spread over the patient's abdomen with both ends of the blanket fixed to the sides of the treatment couch or a baseboard. The inner side, or patient side, of the blanket is thinner and expands more than the outer side. When inflated, the blanket balloons and effectively puts an even pressure on the patient's abdomen. Fluoroscopic observation was performed to verify the usefulness of AIB for patients with lung, breast cancer, or abdominal cancers. Internal organ movement due to breathing was monitored and measured with and without AIB. With the help of AIB, the average range of diaphragm motion was reduced from 2.6 to 0.7 cm in the anterior-to-posterior direction and from 2.7 to 1.3 cm in the superior-to-inferior direction. The motion range in the right-to-left direction was negligible, for it was less than 0.5 cm. These initial testing demonstrated that AIB is useful for reducing patients' breathing motion in the thoracic and abdominal regions comfortably and consistently.