many processes in RA and KA are almost identical, one area can benefit from developments in the other

MUCH work has already been carried out on the treatment of mice infected with schistosomes. It has been observed that the worms which normally inhabit the mesenteric veins of animals infected with Schistosoma mansoni are forced to migrate to the liver after treatment with active schistosomicidal drugs1–6. This hepatic shift has usually been observed after a full course of treatment, and where the course had been inadequate, relapses were found to occur owing to the re-migration of the worms back to the mesenteric veins. Standen6observed a hepatic shift as early as one day following two oral doses of 42 mgm./ kgm. sodium antimonyl III gluconate, but after 7 days the worms were completely restored to their normal distribution in the hepatic portal system. In the work reported here we followed up the effect of a single dose of tartar emetic on the worm migration to show that the hepatic shift actually occurs much earlier than had been previously expected

Intravenous thrombolysis with tissue plasminogen activator is the only proven acute therapy for ischemic stroke. This therapy has not been translated into clinical practice in the developing world primarily due to economic constraints. Streptokinase, a lower cost alternative thrombolytic agent, is widely available in developing countries where it is utilized to treat patients with acute coronary syndromes. Although this drug has previously been found to be ineffective in ischemic stroke, the lack of benefit may have been related to a number of factors related to trial design rather than the drug itself. Specific features of prior trial designs that may have adversely affected outcomes include a prolonged treatment window, inclusion of patients with established infarction on computed tomography scan, failure to treat excessive arterial pressures, a fixed dose of streptokinase, and concomitant use of antithrombotic medications. Given the lack of therapeutic alternatives in developing countries, a new trial of streptokinase in acute stroke, utilizing stricter inclusion criteria similar to those in more recent thrombolytic studies, appears warranted.

Metabolic challenges experienced by dairy cows during the transition between pregnancy and lactation (also known as peripartum), are of considerable interest from a nutrigenomic perspective. The mobilization of large amounts of non-esterified fatty acids () leads to an increase in NEFA uptake in the liver, the excess of which can cause hepatic accumulation of lipids and ultimately fatty liver. Interestingly, peripartum NEFA activate the Peroxisome Proliferator-activated Receptor (), a transcriptional regulator with known nutrigenomic properties. The study of PPAR activation in the liver of periparturient dairy cows is thus crucial; however, current models of the bovine liver are inadequate, and the isolation of primary hepatocytes is time consuming, resource intensive, and prone to errors, with the resulting cells losing characteristic phenotypical traits within hours. The objective of the current study was to evaluate the use of precision-cut liver slices () from liver biopsies as a model for PPAR activation in periparturient dairy cows. Three primiparous Jersey cows were enrolled in the experiment, and PCLS from each were prepared prepartum (-8.0 ± 3.6 DIM) and postpartum (+7.7± 1.2 DIM) and treated independently with a variety of PPAR agonists and antagonists: the PPARα agonist WY-14643 and antagonist GW-6471; the PPARδ agonist GW-50156 and antagonist GSK-3787; and the PPARγ agonist rosiglitazone and antagonist GW-9662. Gene expression was assayed through RT-qPCR and RNAseq, and intracellular triacylglycerol (TAG) concentration was measured. PCLS obtained from postpartum cows and treated with a PPARγ agonist displayed upregulation of and while those treated with PPARδ agonist had increased expression of , and . In PCLS from prepartum cows, transcription of was increased by all PPAR agonists and NEFA. TAG concentration tended to be larger in tissue slices treated with PPARδ agonist compared to CTR. Use of PPAR isotype-specific antagonists in PCLS cultivated in autologous blood serum failed to decrease expression of PPAR targets, except for , which was confirmed to be a PPARδ target. Transcriptome sequencing revealed considerable differences in response to PPAR agonists at a false discovery rate-adjusted -value of 0.2, with the most notable effects exerted by the PPARδ and PPARγ agonists. Differentially expressed genes were mainly related to pathways involved with lipid metabolism and the immune response. Among differentially expressed genes, a subset of 91 genes were identified as novel putative PPAR targets in the bovine liver, by cross-referencing our results with a publicly available dataset of predicted PPAR target genes, and supplementing our findings with prior literature. Our results provide important insights on the use of PCLS as a model for assaying PPAR activation in the periparturient dairy cow.

Since 2000, many countries have achieved considerable success in improving child survival, but localized progress remains unclear. To inform efforts towards United Nations Sustainable Development Goal 3.2-to end preventable child deaths by 2030-we need consistently estimated data at the subnational level regarding child mortality rates and trends. Here we quantified, for the period 2000-2017, the subnational variation in mortality rates and number of deaths of neonates, infants and children under 5 years of age within 99 low- and middle-income countries using a geostatistical survival model. We estimated that 32% of children under 5 in these countries lived in districts that had attained rates of 25 or fewer child deaths per 1,000 live births by 2017, and that 58% of child deaths between 2000 and 2017 in these countries could have been averted in the absence of geographical inequality. This study enables the identification of high-mortality clusters, patterns of progress and geographical inequalities to inform appropriate investments and implementations that will help to improve the health of all populations.