Optimizing Patient Education of Oncology Medications: A Patient Perspective.

The medication information needs of patients with cancer have been primarily studied using quantitative methods and little qualitative research on this topic exists. The purpose of this study was to explore patients' perspectives of optimal oncology medication education provided to patients at the Nova Scotia Health Authority (NSHA). Adult (≥ 18 years) outpatients in medical, gynecological and hematology oncology at NSHA were invited to participate in focus groups, which were audio-recorded, transcribed and analyzed thematically. Three focus groups, including 21 outpatients, were conducted. Four major themes were identified: (1) preparing for what lies ahead consisted of: readiness to receive information, anxiety over the unknown, setting expectations and patients supporting one another; (2) bridging the information gaps was made up of gap in provision of patient education, gap in continuity of patient education, and gap in trustworthy information; (3) understanding the education needs of the patients was comprised of sources of information, education timing and setting, prioritizing information needs, and individuality; and (4) experience within the health care system encompassed: interactions with health care professionals, willingness to ask questions, patient satisfaction, and financial implications. This study identified previously unknown patient education needs and also supported ideas reported in the literature. This data will guide the strategies that will be used to optimize the delivery of oncology medication education at our facility and other health care institutions.

Quorum sensing inhibitors from Leucetta chagosensis Dendy, 1863.

UNLABELLED: Sponges are a rich source for investigation of bioactive small molecules. They have been mostly investigated for the search of new pharmacological models or therapeutic agents for the treatment of human diseases. Micro-organisms can also represent a virulent pathogen for marine invertebrates such as sponges, which need to protect themselves against these microbes. Sponges' self defence mechanisms involving dialogue molecules thus represent a pertinent research track for potent anti-infective and anti-biofilm activities such as quorum sensing inhibitors (QSIs). The investigation of the QSI crude extract of Leucetta chagosensis Dendy, 1863 led to the isolation of three new alkaloids, isonaamine D, di-isonaamidine A and leucettamine D, along with the known isonaamine A and isonaamidine A. Isonaamidine A and isonaamine D were identified as inhibitors of the three quorum sensing pathways of Vibrio harveyi (CAI-1, AI-2 and harveyi auto inducer), but isonaamidine A displayed the strongest activity on AI-2 biosensor. Both compounds are new examples of natural QSIs of V. harveyi. These results outline the importance of these secondary metabolites for their producing organisms themselves in their natural environment, as well as the potential of the marine resource for aquaculture needs. SIGNIFICANCE AND IMPACT OF THE STUDY: A new type of quorum sensing inhibitors was isolated from the sponge Leucetta chagosensis. One of them inhibits strongly the AI-2 channel of Vibrio harveyi, a marine pathogen of special importance in aquaculture. The activity of five different related compounds, including three new natural products discovered there, was investigated leading to structure-activity relationships which are useful for the design of new quorum sensing inhibitors to control marine infectious pathogens.

Lactobacillus reuteri-specific immunoregulatory gene rsiR modulates histamine production and immunomodulation by Lactobacillus reuteri.

Human microbiome-derived strains of Lactobacillus reuteri potently suppress proinflammatory cytokines like human tumor necrosis factor (TNF) by converting the amino acid l-histidine to the biogenic amine histamine. Histamine suppresses mitogen-activated protein (MAP) kinase activation and cytokine production by signaling via histamine receptor type 2 (H2) on myeloid cells. Investigations of the gene expression profiles of immunomodulatory L. reuteri ATCC PTA 6475 highlighted numerous genes that were highly expressed during the stationary phase of growth, when TNF suppression is most potent. One such gene was found to be a regulator of genes involved in histidine-histamine metabolism by this probiotic species. During the course of these studies, this gene was renamed the Lactobacillus reuteri-specific immunoregulatory (rsiR) gene. The rsiR gene is essential for human TNF suppression by L. reuteri and expression of the histidine decarboxylase (hdc) gene cluster on the L. reuteri chromosome. Inactivation of rsiR resulted in diminished TNF suppression in vitro and reduced anti-inflammatory effects in vivo in a trinitrobenzene sulfonic acid (TNBS)-induced mouse model of acute colitis. A L. reuteri strain lacking an intact rsiR gene was unable to suppress colitis and resulted in greater concentrations of serum amyloid A (SAA) in the bloodstream of affected animals. The PhdcAB promoter region targeted by rsiR was defined by reporter gene experiments. These studies support the presence of a regulatory gene, rsiR, which modulates the expression of a gene cluster known to mediate immunoregulation by probiotics at the transcriptional level. These findings may point the way toward new strategies for controlling gene expression in probiotics by dietary interventions or microbiome manipulation.

Responses of diploid and triploid Pacific oysters Crassostrea gigas to Vibrio infection in relation to their reproductive status.

Several Vibrio species are known to be pathogenic to the Pacific oyster Crassostrea gigas. Survival varies according to pathogen exposure and high mortality events usually occur in summer during gametogenesis. In order to study the effects of gametogenetic status and ploidy (a factor known to affect reproduction allocation in oysters) on vibriosis survival, we conducted two successive experiments. Our results demonstrate that a common bath challenge with pathogenic Vibrio splendidus and Vibrio aestuarianus on a mixture of mature, spawning and non-mature oysters can lead to significant mortality. Previous bath challenges, which were done using only non-mature oysters, had not produced mortality. Immunohistochemical analyses showed the affinity of Vibrio for gonadic tissues, highlighting the importance of sexual maturity for vibriosis infection processes in oysters. Mortality rate results showed poor repeatability between tanks, however, in this bath challenge. We then tested a standardized and repeatable injection protocol using two different doses of the same combination of two Vibrio species on related diploid and triploid oysters at four different times over a year. Statistical analyses of mortality kinetics over a 6-day period after injection revealed that active gametogenesis periods correspond to higher susceptibility to vibriosis and that there is a significant interaction of this seasonal effect with ploidy. However, no significant advantage of triploidy was observed. Triploid oysters even showed lower survival than diploid counterparts in winter. Results are discussed in relation to differing energy allocation patterns between diploid and triploid Pacific oysters.

Dual RNAseq highlights the kinetics of skin microbiome and fish host responsiveness to bacterial infection.

BACKGROUND: Tenacibaculum maritimum is a fish pathogen known for causing serious damage to a broad range of wild and farmed marine fish populations worldwide. The recently sequenced genome of T. maritimum strain NCIMB 2154T provided unprecedented information on the possible molecular mechanisms involved in the virulence of this species. However, little is known about the dynamic of infection in vivo, and information is lacking on both the intrinsic host response (gene expression) and its associated microbiota. Here, we applied complementary omic approaches, including dual RNAseq and 16S rRNA gene metabarcoding sequencing using Nanopore and short-read Illumina technologies to unravel the host-pathogen interplay in an experimental infection system using the tropical fish Platax orbicularis as model. RESULTS: We showed that the infection of the host is characterised by an enhancement of functions associated with antibiotic and glucans catabolism functions but a reduction of sulfate assimilation process in T. maritimum. The fish host concurrently displays a large panel of immune effectors, notably involving innate response and triggering acute inflammatory response. In addition, our results suggest that fish activate an adaptive immune response visible through the stimulation of T-helper cells, Th17, with congruent reduction of Th2 and T-regulatory cells. Fish were, however, largely sensitive to infection, and less than 25% survived after 96 hpi. These surviving fish showed no evidence of stress (cortisol levels) or significant difference in microbiome diversity compared with controls at the same sampling time. The presence of T. maritimum in resistant fish skin and the total absence of any skin lesions suggest that these fish did not escape contact with the pathogen, but rather that some mechanisms prevented pathogens entry. In resistant individuals, we detected up-regulation of specific immune-related genes differentiating resistant individuals from controls at 96 hpi, which suggests a possible genomic basis of resistance, although no genetic variation in coding regions was found. CONCLUSION: Here we focus in detail on the interplay between common fish pathogens and host immune response during experimental infection. We further highlight key actors of defence response, pathogenicity and possible genomic bases of fish resistance to T. maritimum.

Expanding the reach of probiotics through social enterprises.

The rapid rise in microbiome and probiotic science has led to estimates of product creation and sales exceeding $50 billion within five years. However, many people do not have access to affordable products, and regulatory agencies have stifled progress. The objective of a discussion group at the 2017 meeting of the International Scientific Association for Probiotics and Prebiotics was to identify mechanisms to confer the benefits of probiotics to a larger portion of the world's population. Three initiatives, built around fermented food, were discussed with different methods of targeting populations that face enormous challenges of malnutrition, infectious disease, poverty and violent conflict. As new candidate probiotic strains emerge, and the market diversifies towards more personalised interventions, manufacturing processes will need to evolve. Information dissemination through scientific channels and social media is projected to provide consumers and healthcare providers with rapid access to clinical results, and to identify the nearest location of sites making new and affordable probiotic food and supplements. This rapid translation of science to individual well-being will not only expand the beneficiaries of probiotics, but also fuel new social enterprises and economic business models.

Pearl formation: persistence of the graft during the entire process of biomineralization.

Most bivalves species of the genus Pinctada are well known throughout the world for production of white or black pearls of high commercial value. For cultured pearl production, a mantle allograft from a donor is implanted into the gonad of a recipient oyster, together with a small inorganic bead. Because of the dedifferentiation of cells during the first steps of the host oyster's immunological reaction, so far the fate of the graft and its exact role in the process of pearl formation could not be determined via classical histological methods. Here we report the first molecular evidence of the resilience of the graft in the recipient organism by showing that cells containing genome from the donor are still present at the end of pearl formation. These results suggest the existence of a unique biological cooperation leading to the successful biomineralization process of nacreous secretion in pearl formation.

Cloning, sequencing and expression of a cDNA encoding an antigen from the Myxosporean parasite causing the proliferative kidney disease of salmonid fish.

A pool of monoclonal antibodies (MAbs) raised against the unknown organism causing the proliferative kidney disease of salmonid fish (PKX) has been used to screen a cDNA expression library constructed from poly (A+) RNA extracted from PKX infected kidney. Four immunopositive lambda ZapII recombinant phages were selected. Sequencing of the cDNAs revealed identical 3' ends. The longest cDNA clone (2652 nucleotides) had an open reading frame (ORF) of 872 amino acids and encoded a protein with a predicted size of 101 kDa (PKX101). Sequence analysis of PKX101 revealed two leucine zipper motifs, a putative transmembrane region and a microbody targeting signal at its C-terminal end. Three cDNA fragments were subcloned in pET-14b expression vector and the ORF verified by an in vitro transcription/translation procedure. Recombinant clones were expressed in Escherichia coli and the antigenicity of fusion proteins was studied by Western blotting using monoclonal antibodies directed against PKX cells and a pool of serum from preimmune or PKX-infected rainbow trout. Western blotting of enriched PKX cell antigen probed with one MAb or with sera from infected trout revealed a single protein with relative mobility of 13 kDa (PKX13). This discrepancy between PKX101 and PKX13 observed in Western blot suggests post-translational modifications of the full-length PKX antigen.

Identification, expression in E. coli and insect cells of the non-structural protein NS2 encoded by mRNA2 of bovine coronavirus (BCV).

The coding part of mRNA 2 (ORF2) of BCV (F15 strain) was cloned and sequenced. The comparison of our sequence data with the sequence of the same ORF of BCV Quebec strain previously published revealed a major difference in the length of the C-terminal part of the NS2 protein. In vitro transcription and translation of ORF2 resulted in the synthesis of a single protein migrating with a Mr of 31 kDa. The ORF2 was fused in frame with the glutathione S transferase gene (GSH) in the pGEX vector. The fusion protein was synthesized as inclusion bodies which were concentrated and used to raise a monospecific antiserum. Alternatively the fusion protein was solubilized, purified by affinity chromatography and cleaved with Factor Xa to yield pure recombinant NS2. The ORF2 was also expressed in the baculovirus system and the recombinant proteins expressed in pro- and eukaryotic systems were compared on the basis of their size and immunoreactivity. Immunoprecipitation performed with the monospecific antiserum allowed us to identify NS2 in HRT18 infected cells, to follow its kinetic of synthesis, and to ascertain that NS2 was not incorporated in the virion as a minor structural component.

Molecular evidence that the proliferative kidney disease organism unknown (PKX) is a myxosporean.

The proliferative kidney organism unknown (PKX), a serious salmonid fish pathogen, is considered to be a myxosporean on the basis of ultrastructural studies, but its real taxonomic position has never been confirmed. In order to ascertain its position, genomic DNA was extracted from PKX and small subunit (SSU) ribosomal DNA was amplified by PCR, cloned and sequenced. A phylogenetical analysis on SSU rDNA from 76 or 128 eucaryotic species was carried out. Whatever the tree reconstruction methods used, PKX was found to be a sister group of the Myxozoa phylum, providing the first molecular evidence for its membership in this phylum.

Rapid and sensitive PCR detection of Vibrio penaeicida, the putative etiological agent of syndrome 93 in New Caledonia.

Experimental infections of Penaeus (Litopenaeus) stylirostris were performed with a Vibrio penaeicida strain (AM101) isolated in New Caledonia from Syndrome 93 diseased shrimp. Cumulative mortalities resulting from intramuscular injection or immersion of shrimp in bacterial suspensions demonstrated high virulence for this bacterial strain and suggested that V. penaeicida could be the etiological agent of Syndrome 93. The median lethal dose (LD50) for AM101 was 1.3 x 10(4) CFU (colony forming units) ml-1 by immersion and less than 5 CFU shrimp-1 by intramuscular challenge, with mortality outbreaks at 48 and 22 h after challenge, respectively. A polymerase chain reaction (PCR) detection assay using a primer set designed from the 16S ribosomal RNA gene of V. penaeicida was developed. It gave an expected amplicon of approximately 310 bp in ethidium bromide-stained agarose gels. The specificity of these primers was assessed with different Vibrio species. Furthermore, DNA extracted by the Chelex method could be used to detect fewer than 20 cultured Vibrio cells in sea-water or shrimp hemolymph by this assay. It appears to be a reliable screening method for detecting V. penaeicida in shrimp and from the aquatic environment.

[Repetitive screams]. / Les cris répétitifs.

Nurses are challenged by the repetitive shouting of the cognitively-impaired elderly. The author reflects on the known causes of this behavior and how it affects staff members. She suggests nursing actions to discourage shouting and encourages nurses to explore new ways to cope. One way is to modify staff behavior by correcting attitudes that stereotype the elderly.

Detection of early effects of a single herbicide (diuron) and a mix of herbicides and pharmaceuticals (diuron, isoproturon, ibuprofen) on immunological parameters of Pacific oyster (Crassostrea gigas) spat.

In the context of massive summer mortality events of the Pacific oyster Crassostrea gigas, the aim of this study was to investigate the early effects on genes, enzymes and haemocyte parameters implicated in immune defence mechanisms in C. gigas oysters exposed to a potentially hostile environment, i.e. to an herbicide alone or within a mixture. Following 2 h of exposure to the herbicide diuron at 1 µg L(-1), the repression of different genes implicated in immune defence mechanisms in the haemocytes and the inhibition of enzyme activities, such as laccase-type phenoloxidase (PO) in the plasma, were observed. The inhibition of superoxide dismutase (SOD) activity in the plasma was also observed after 6 and 24 h of exposure. In the mixture with the herbicides diuron and isoproturon, and the pharmaceutical ibuprofen, catecholase-type PO activity in the plasma and the percentage of phagocytosis in the haemocytes were reduced after 6 h of exposure. Our results showed that early effects on molecular, biochemical and cellular parameters can be detected in the presence of diuron alone or within a mixture, giving an insight of its potential effect in situations that can be found in natural environments, i.e. relatively high concentrations for short periods of time.

Experimental ostreid herpesvirus 1 infection of the Pacific oyster Crassostrea gigas: kinetics of virus DNA detection by q-PCR in seawater and in oyster samples.

Herpes- and herpes-like viruses are known to infect a wide range of bivalve mollusc species throughout the world. Abnormal summer mortalities associated to the detection of ostreid herpesvirus 1 (OsHV-1) have been currently reported in France among larvae and spat of the Pacific cupped oyster Crassostrea gigas. In the present work, we have developed an experimental protocol of horizontal transmission based on the cohabitation between healthy and experimentally infected oysters. Through a cohabitation trial, the kinetics of OsHV-1 detection in different oyster organs and seawater samples were investigated and characterized for the first time using real time quantitative PCR.

Characterization of actin genes in Bonamia ostreae and their application to phylogeny of the Haplosporidia.

Bonamia ostreae is a protozoan parasite that infects the European flat oyster Ostrea edulis, causing systemic infections and resulting in massive mortalities in populations of this valuable bivalve species. In this work, we have characterized B. ostreae actin genes and used their sequences for a phylogenetic analysis. Design of different primer sets was necessary to amplify the central coding region of actin genes of B. ostreae. Characterization of the sequences and their amplification in different samples demonstrated the presence of 2 intragenomic actin genes in B. ostreae, without any intron. The phylogenetic analysis placed B. ostreae in a clade with Minchinia tapetis, Minchinia teredinis and Haplosporidium costale as its closest relatives, and demonstrated that the paralogous actin genes found in Bonamia resulted from a duplication of the original actin gene after the Bonamia origin.

Vibrio gigantis sp. nov., isolated from the haemolymph of cultured oysters (Crassostrea gigas).

Polyphasic analysis of four new Vibrio isolates originating from the haemolymph of diseased cultured oysters is described. The new isolates were closely related to Vibrio splendidus, having 98 % 16S rRNA gene sequence similarity. Phylogenetic analysis based on DNA gyrase subunit B (gyrB), RNA polymerase sigma70 factor (rpoD), replication origin-binding protein (rctB) and transmembrane regulatory protein (toxR) genes, fluorescent amplified fragment length polymorphism and DNA-DNA hybridization experiments clearly showed that the new isolates form a tight genomic group that is different from the currently known Vibrio species. It is proposed that these new isolates should be accommodated in a novel species, Vibrio gigantis sp. nov. Phenotypic features that differentiate V. gigantis from other known Vibrio species include arginine dihydrolase, gelatinase and beta-galactosidase activities, NO(2) production, growth at 35 degrees C, and utilization of sucrose, melibiose, amygdalin, glycerol, galactose, starch and glycogen. The type strain is LGP 13T (=LMG 22741T=CIP 108656T).

Immunomodulatory effects in vivo of recombinant porcine interferon gamma on leukocyte functions of immunosuppressed pigs.

Immunological parameters of porcine peripheral blood mononuclear cells after in vivo injections of recombinant porcine interferon gamma (rPoIFN gamma) were studied in pigs immunosuppressed by dexamethasone (6 mg/kg body weight in a single injection). A 2-d period of rPoIFN gamma injected alone and intramuscularly at a dose of 1 microgram/kg body weight increased interleukin 1 (IL1) production (P less than 0.05). Recombinant porcine IFN gamma also reversed the immunosuppressive effects of dexamethasone on: i), lymphocyte responsiveness to mitogens: PHA (P less than 0.03), ConA (P less than 0.053); ii), IL1 production; and iii), IL2 production (P less than 0.05). However, rPoIFN gamma had no effect on neutrophilia induced by dexamethasone. These data show that rPoIFN gamma modulates leukocyte functions of pigs in vivo.

[Evaluation of the test for detecting trypanosoma circulating antigens using monoclonal antibodies. Experimental and natural infections]. / Evaluation du test de détection des antigènes circulants de trypanosomes à l'aide d'anticorps monoclonaux. Infections expérimentales et naturelles.

An antigen detection ELISA for the diagnosis of trypanosomes was recently proposed by Nantulya and Lindqvist (1989). Based on species-specific monoclonal antibodies, this test could be used to diagnose a current infection and to identify the causing trypanosomes. The test was evaluated at CRTA during experimental infections in small ruminants and with sera from naturally infected cattle, thanks to reagents supplied by the International Laboratory for Research on Animal Diseases (ILRAD). Sera from cattle sampled in France were also tested. Cattle sera from France gave optical densities (OD) from 0.007 to 0.009 with three monoclonal antibodies against T. congolense, T. vivax and T. brucei. These OD values were well below 0.050, which is considered as a positive threshold OD reading. In the small ruminant experimental infections, the sensitivity of the test was 63.2% for T. congolense-infected animals and 9.9% for T. vivax-infected animals. The sensitivity of parasitological tests was 55.1 and 48.6%, respectively. The combination of the antigen- and parasite-detection tests increased the sensitivity to 82.4 and 52.8%, respectively. Means of OD values, with the naturally infected cattle sera, were 0.116 +/- 0.030 for T. congolense, and 0.011 +/- 0.028 for T. vivax-infected animals. Sixteen out of 20 T. congolense-infected sera (sensitivity of 80%) and one out of 20 T. vivax-infected sera (sensitivity of 5%) gave an OD value exceeding 0.050. The determination of a threshold OD reading lower than 0.050 would greatly improve the sensitivity of the test. This determination could either be done by studying the preinfection sera or a local population of animals living in an area free from trypanosomosis.(ABSTRACT TRUNCATED AT 250 WORDS)