Balancing precision versus cohort transcriptomic analysis of acute and recovery phase of viral bronchiolitis.

Viral infections affecting the lower respiratory tract place enormous burdens on hospitals. As neither vaccines nor antiviral agents exist for many viruses, understanding risk factors and outcomes in each patient using minimally invasive analysis, such as blood, can lead to improved health care delivery. A cohort of PAXgene RNA sequencing of infants admitted with moderate or severe acute bronchiolitis and respiratory syncytial virus were compared with case-control statistical analysis and cohort-based outlier mapping for precision transcriptomics.

Gene expression signatures identify paediatric patients with multiple organ dysfunction who require advanced life support in the intensive care unit.

Background: Multiple organ dysfunction syndrome (MODS) occurs in the setting of a variety of pathologies including infection and trauma. Some patients decompensate and require Veno-Arterial extra corporeal membrane oxygenation (ECMO) as a palliating manoeuvre for recovery of cardiopulmonary function. The molecular mechanisms driving progression from MODS to cardiopulmonary collapse remain incompletely understood, and no biomarkers have been defined to identify those MODS patients at highest risk for progression to requiring ECMO support.

Outcomes after completion total gastrectomy for gastric remnant cancer: experience from a Canadian tertiary centre.

Background: There is controversy about the safety and outcomes of completion total gastrectomy (CTG) for gastric adenocarcinoma. We compared a cohort of patients who underwent CTG for gastric remnant cancer (GRC) after partial gastrectomy for benign disease with patients who underwent primary total gastrectomy (PTG) for sporadic gastric cancer.

Methods: We retrospectively reviewed a single-institution, prospectively maintained clinical database of patients who had undergone gastrectomy from 2005 to 2016 for demographic, surgical, clinical and tumour pathology data, as well as postoperative, pathologic and oncologic outcomes including complications, length of stay, disease-free survival and overall survival.

Application of an individualized operative strategy for wedge resection of gastric gastrointestinal stromal tumors: Effectiveness for tumors in difficult locations.

Background: There is some concern that wedge resection of gastric gastrointestinal stromal tumors is not feasible in certain anatomic locations, such as the cardia or antrum. We sought to review our experience with treatment of gastric gastrointestinal stromal tumors with a particular focus on nonanatomic wedge resections in these challenging locations.

Methods: Patients undergoing resection of gastrointestinal stromal tumors from 2000-2014 at the Montreal General Hospital were identified from a prospectively collected database, and outcomes were tabulated.

A 2-amino quinoline, 5-(3-(2-(7-chloroquinolin-2-yl)ethenyl)phenyl)-8-dimethylcarbamyl-4,6-dithiaoctanoic acid, interacts with PfMDR1 and inhibits its drug transport in Plasmodium falciparum.

Malaria is a major disease in the tropics where chemotherapy remains the main mode of treatment and as such the rise and spread of drug-resistant malaria can lead to human tragedy. Two membrane transport proteins, PfMDR1 (Plasmodium falciparum multidrug resistance protein 1) and PfCRT (P. falciparum chloroquine resistance transporter), have been shown to cause resistance to several antimalarials.

Treatment of suspected hyper-reactive malarial splenomegaly (HMS) in pregnancy with mefloquine.

Malaria infections in pregnancy are associated with adverse outcomes for both mother and child. There are few data on hyper-reactive malarial splenomegaly, an aberrant immunological response to chronic or recurrent malaria in pregnancy. This retrospective assessment reviewed the impact of mefloquine treatment on pregnant women with suspected hyper-reactive malarial splenomegaly in an area of low malaria transmission in the 1990s, showing significant reductions in spleen size and anemia and anti-malarial antibody titers without any notable negative effect on treated women or their newborns.

Long-term storage limits PCR-based analyses of malaria parasites in archival dried blood spots.

Background: Blood samples collected in epidemiological and clinical investigations and then stored, often at room temperature, as blood spots dried on a filter paper have become one of the most popular source of material for further molecular analyses of malaria parasites. The dried blood spots are often archived so that they can be used for further retrospective investigations of parasite prevalence, or as new genetic markers come to the fore. However, the suitability of the template obtained from dried blood spots that have been stored for long periods for DNA amplification is not known.

Photoaffinity labeling of the multidrug resistance protein 2 (ABCC2/cMOAT) with a photoreactive analog of LTC(4).

Several studies have shown that the multidrug resistant protein MRP2 mediates the transport of chemotherapeutic drugs and normal cell metabolites, including Leukotriene C (LTC(4)); however direct binding of the LTC(4) to MRP2 has not been demonstrated. In this study, a photoreactive analog of LTC(4) (IAALTC(4)) was used to demonstrate its direct binding to MRP2. Our results show specific photoaffinity labeling of MRP2 with IAALTC(4) in plasma membranes from MDCKII(MRP2) cells.

Chloroquine resistant vivax malaria in a pregnant woman on the western border of Thailand.

Chloroquine (CQ) resistant vivax malaria is spreading. In this case, Plasmodium vivax infections during pregnancy and in the postpartum period were not satisfactorily cleared by CQ, despite adequate drug concentrations. A growth restricted infant was delivered.

Methotrexate is highly potent against pyrimethamine-resistant Plasmodium vivax.

Resistance of vivax malaria to treatment with antifolates, such as pyrimethamine (Pyr), is spreading as mutations in the dihydrofolatereductase (dhfr) genes are selected and disseminated. We tested the antitumor drug methotrexate (MTX), a potent competitive inhibitor of dhfr, against 11 Plasmodium vivax isolates ex vivo, 10 of which had multiple dhfr mutations associated with Pyr resistance. Despite high-grade resistance to Pyr (median 50% inhibitory concentration [IC₅₀], 13,345 nM), these parasites were all highly susceptible to MTX (median IC₅₀, 2.

Effective and cheap removal of leukocytes and platelets from Plasmodium vivax infected blood.

Background: Investigations of Plasmodium vivax are restricted to samples collected from infected persons or primates, because this parasite cannot be maintained in in vitro cultures. Contamination of P. vivax isolates with host leukocytes and platelets is detrimental to a range of ex vivo and molecular investigations.

Autofluorescence of condensed heme aggregates in malaria pigment and its synthetic equivalent hematin anhydride (beta-hematin).

The condensed crystalline phase of iron(III) protoporphyrin IX either isolated from parasite culture as malaria pigment (hemozoin) or synthetic equivalent hematin anhydride exhibits a solid-state autofluorescence characterized by an excitation maximum of 555 nm and an emission maximum of 577 nm. The excitation spectrum maximum at 555 nm corresponds to the Q(0,0) band in the absorption spectrum which represents the lowest singlet of the material. This suggests that the fluorescent emission is due to the heme condensed phase.

Sensitive detection of malaria infection by third harmonic generation imaging.

Malaria remains a major health concern worldwide, with 350-500 million cases reported annually in endemic countries. In this study, we report a novel and highly sensitive optical-based detection of malaria-infected blood cells by third harmonic generation (THG) imaging of hemozoin pigment that is naturally deposited by the parasite during its lifecycle. The THG signal from the hemozoin was greater than we have observed in any cell type with signal/noise ratios that reach 1000:1.

Modulation of GSH levels in ABCC1 expressing tumor cells triggers apoptosis through oxidative stress.

The over-expression of ABCC1 transmembrane protein has been shown to cause multidrug resistance in tumor cell lines. ABCC1 is a member of the ABC transmembrane proteins that function as efflux pumps with diverse substrate specificity. Several endogenous cell metabolites, including the leukotriene C4 (LTC(4)) and glutathione (GSH) are substrates for ABCC1 protein.

ABCG2 membrane transporter in mature human erythrocytes is exclusively homodimer.

The human ABCG2 protein, a member of ABC transporter family, was shown to transport anti-cancer drugs and normal cell metabolites. Earlier studies have demonstrated the expression of ABCG2 in hematopoietic stem cells and erythroid cells; however little is known about the expression and activity of ABCG2 in mature erythrocytes. In this report, we show that ABCG2 in mature human erythrocytes migrates with an apparent molecular mass of 140 kDa, under reducing conditions, on Fairbanks SDS gel system.

Lupeol long-chain fatty acid esters with antimalarial activity from Holarrhena floribunda.

An ethnopharmacological investigation was conducted among the Baka pygmies of Dja biosphere reserve (Cameroon) to collect information on the antimalarial plants used in their daily life. Holarrhena floribunda is one of those plants. Extracts of the stem barks of H.