Control of parasitic infection with ivermectin long-acting injection (IVOMEC® GOLD) and production benefit in first-season grazing cattle facing a high-level larval challenge in Germany.

Gastrointestinal and pulmonary nematode infections are affecting the health and productivity of grazing cattle worldwide. To evaluate the effects of a single treatment with ivermectin long-acting injection (IVM LAI; IVOMEC® GOLD, Merial; 3.15 % ivermectin w/v) in first-grazing season cattle, two studies were conducted under continued stocking conditions for 84 or 100 days in Bavaria, Germany. Each study involved 68 naturally infected, approximately 4- to 6-month-old Brown Swiss bull calves. Animals were blocked based on pretreatment body weights. Within each block of four animals, animals were randomly assigned to treatments: one to saline (control) and three to IVM LAI. Treatments were injected at 1 mL/50 kg body weight subcutaneously in front of the shoulder. Animals in both studies were managed as one herd each grazing together. Cattle were weighed and fecal samples were collected pretreatment and at intervals thereafter for determination of weight gain and treatment efficacy, respectively. Fecal examination including composite fecal culture indicated the presence of nematodes of the genera Cooperia (dominating), Haemonchus, Nematodirus, Ostertagia, Strongyloides, Trichostrongylus, Trichuris, and Dictyocaulus, and Moniezia cestodes in the cattle. Following treatment, IVM LAI-treated cattle did not shed any Dictyocaulus larvae for 84 days while controls continued to pass larvae. Compared to the controls, IVM LAI-treated cattle had significantly (p < 0.01) lower strongylid egg counts at each occasion. Percentage reductions were ≥94 % up to 70 days after treatment and were ≥83.9 and 58.9 % at 84 and 100 days. Over the 84- or 100-day study periods, IVM LAI-treated cattle gained significantly more weight than the controls: 22.7 and 12.4 kg, respectively. The two studies demonstrated a high efficacy of IVM LAI against gastrointestinal and pulmonary nematode infections under field conditions in Germany which was associated with significant benefit as to weight gain.

Multilocus sequence typing of canine Giardia duodenalis from South Eastern European countries.

Giardia duodenalis is a worldwide occurring protozoan that can infect various mammalian hosts. While living conditions are getting closer between pet animals and owners, there is discussion whether dogs may contribute to the transmission of these pathogens to humans. The present study was conducted in order to identify the Giardia assemblages in dogs from South Eastern Europe. For this purpose, 1645 faecal samples of household and shelter dogs from Albania, Bulgaria, Hungary, Macedonia, Romania and Serbia were tested for Giardia coproantigen by enzyme-linked immunosorbent assay (ELISA). A subset of 107 faecal samples demonstrating Giardia cysts by direct immunofluorescence assay (IFA) or microscopy (15-22 per country) plus 26 IFA-positive canine faecal samples from Croatia were used for DNA extraction and multilocus sequence typing with nested PCRs targeting five different gene loci: SSU rRNA, ITS1-5.8S-ITS2, beta giardin (bg), glutamate dehydrogenase (gdh) and triosephosphate isomerase (tpi). One third (33.7%) of the samples tested positive for Giardia antigen in the coproantigen ELISA. Shelter dogs were infected more frequently than household dogs (57.2 vs. 29.7%, p < 0.01). Amplification was obtained in 82.0, 12.8, 11.3, 1.5, and 31.6%, of the investigated samples at the SSU rRNA, bg, gdh and tpi loci and the ITS1-5.8S-ITS2 region, respectively. The dog-specific assemblages C and D were identified in 50 and 68 samples, respectively. The results demonstrate that G. duodenalis should be considered as a common parasite in dogs from South Eastern Europe. However, there was no evidence for zoonotic Giardia assemblages in the investigated canine subpopulation.

Activity of ivermectin long-acting injectable (IVOMEC(®) GOLD) in first-season grazing cattle exposed to natural challenge conditions in Germany.

The persistent activity of ivermectin long-acting injection (IVM LAI; IVOMEC® GOLD, Merial; 3.15% ivermectin w/v) against nematode infections of cattle was evaluated under natural challenge conditions. Seventy nematode-free Brown Swiss calves were blocked by pre-treatment bodyweight and allocated randomly to seven groups of 10 animals each: saline (control) at 1 mL/50 kg bodyweight once on day 0 or IVM LAI at 1 mL/50 kg bodyweight (630 mcg IVM/kg) on either days 0, 7, 14, 21, 28, or 35. After housing until day 35, calves were grazed as one herd on a naturally contaminated pasture for 42 days. Calves were then weighed and housed for 4 weeks before being necropsied for parasite counting. Treatment with IVM LAI prevented the establishment (>90%, p < 0.05) of Dictyocaulus viviparus (100%), Bunostomum phlebotomum (100 %), Haemonchus contortus (98.6%), Ostertagia ostertagi/lyrata (94.9%), and Oesophagostomum radiatum (93.3%) for at least 77 days; Ostertagia leptospicularis (99.1%) for 63 days; Cooperia punctata (97.7%), Trichostrongylus axei (96.5%), and Ostertagia spp. inhibited larvae 4 (93.3%) for 56 days; Cooperia oncophora/surnabada (96.9%), Trichuris discolor (93.6%), and Cooperia spp. inhibited larvae 4 (98.8%); and Nematodirus spp. inhibited larvae 4 (97.1%) for 42 days. Calves of groups treated with IVM LAI had significantly (p < 0.001) higher days 0 to 77 weight gains than the saline-treated controls (28.40-39.25 vs 2.60 kg); the weight gains of the IVM LAI-treated groups, however, were not different from one another (p > 0.3). This study demonstrated a very high efficacy of IVOMEC® GOLD in preventing the establishment of a wide range of bovine nematodes for extended periods of time which was associated with a significant benefit to productivity in terms of weight gain.

Measures of user experience in a streptococcal pharyngitis and pneumonia clinical decision support tools.

OBJECTIVE: To understand clinician adoption of CDS tools as this may provide important insights for the implementation and dissemination of future CDS tools. MATERIALS AND METHODS: Clinicians (n=168) at a large academic center were randomized into intervention and control arms to assess the impact of strep and pneumonia CDS tools. Intervention arm data were analyzed to examine provider adoption and clinical workflow. Electronic health record data were collected on trigger location, the use of each component and whether an antibiotic, other medication or test was ordered. Frequencies were tabulated and regression analyses were used to determine the association of tool component use and physician orders. RESULTS: The CDS tool was triggered 586 times over the study period. Diagnosis was the most frequent workflow trigger of the CDS tool (57%) as compared to chief complaint (30%) and diagnosis/antibiotic combinations (13%). Conversely, chief complaint was associated with the highest rate (83%) of triggers leading to an initiation of the CDS tool (opening the risk prediction calculator). Similar patterns were noted for initiation of the CDS bundled ordered set and completion of the entire CDS tool pathway. Completion of risk prediction and bundled order set components were associated with lower rates of antibiotic prescribing (OR 0.5; CI 0.2-1.2 and OR 0.5; CI 0.3-0.9, respectively). DISCUSSION: Different CDS trigger points in the clinician user workflow lead to substantial variation in downstream use of the CDS tool components. These variations were important as they were associated with significant differences in antibiotic ordering. CONCLUSIONS: These results highlight the importance of workflow integration and flexibility for CDS success.

Efficacy of a novel topical combination of fipronil, (S)-methoprene, eprinomectin, and praziquantel, against the ticks, Ixodes ricinus and Ixodes scapularis, on cats.

Five controlled, blinded and randomized studies were conducted to examine the efficacy of a single topical application of a combination of fipronil, (S)-methoprene, eprinomectin, and praziquantel (BROADLINE(®), Merial) against induced infestations with Ixodes ticks on cats. Three studies investigated the efficacy against Ixodes ricinus and two against Ixodes scapularis. In each study, purpose-bred cats were assigned at random to an untreated group or to a treated group. For the studies using I. ricinus, cats were infested with 50 female ticks and a similar number of males 2 days before treatment application, and weekly afterwards on between four and six occasions. For the studies using I. scapularis, cats were infested with a total of 50 ticks (approximately 25 females and 25 males) according to the same schedule as for I. ricinus. Tick counts for the evaluation of efficacy were performed 48 h after treatment and 48 h after the subsequent weekly infestations. Weekly attachment rates to untreated cats of at least 29% for I. ricinus and at least 30% for I. scapularis demonstrated consistently that the ticks were vigorous and that the attachment rates were adequate for efficacy evaluation. In the I. ricinus studies, an efficacy of at least 93% was demonstrated for up to 37 days after the treatment. In the I. scapularis studies, the efficacy level was at least 95% 30 days after the treatment. The product was well tolerated and caused no adverse reaction.

Characterization of glycans in the developmental stages of Myxobolus cerebralis (Myxozoa), the causative agent of whirling disease.

Glycans and sugar-binding molecules (lectins) form an interactive recognition system, which may enable parasitic organisms to adhere to host cells and migrate into target tissues. The aim of the present study was to analyse surface-associated glycans in the developmental stages of Myxobolus cerebralis (Hofer), the causative agent of whirling disease. A panel of biotin-labelled plant lectins was used to detect a broad spectrum of glycan motifs with high specificity. Binding sites were detected histochemically in the tissue sections of infected rainbow trout, Oncorhynchus mykiss (Walbaum), and infected Tubifex tubifex (Müller), and were characterized by light, fluorescence and transmission electron microscopy. With mannose-specific lectins [Lens culinaris agglutinin, Pisum sativum agglutinin, Canavalia ensiformis agglutinin (LCA, PSA, CanA)] mannose-containing glycans were detected in all the developmental stages and host tissues. No binding sites for galactose-specific lectins were present in M. cerebralis spores but reactivity with host tissues occurred. Diversity in glycans was detected by N-acetyl-D-galactosamine-specific lectins in sporoplasm cells of M. cerebralis and triactinomyxon spores. In the group of lectins with monosaccharide-specificity for N-acetyl-D-glucosamine (GlcNAc), the reactivity of Datura stramonium agglutinin (DSA), Lycopersicon esculentum agglutinin (LEA) and Solanum tuberosum agglutinin (STA) was restricted to polar capsules whereas Griffonia simplicifolia agglutinin II (GSA II) also bound to sporoplasm cells of stages in the fish host but not in those present in infected T. tubifex. Moreover, Triticum vulgaris (wheat germ) agglutinin (WGA) and succinylated WGA indicated the presence of N-acetyl-D-glucosamine polymers in polar capsules. No specificity for spores was observed concerning 'bisected'N-glycans and no reactivity in parasitic stages was observed with the fucose-binding lectin Ulex europaeus agglutinin (UEA) I, Sambucus nigra agglutinin (SNA) (specific for alpha2,6-sialylated glycans) and Maackia amurensis agglutinin (MAAI) (specific for alpha2,3-sialylated glycans). Arachis hypogaea (peanut) agglutinin (PNA), Erythrina cristagalli agglutinin (ECA), GSA I, Sophora japonica agglutinin (SJA), Dolichos biflorus agglutinin (DBA) and GSA II detected reactive sites solely confined to the developmental stages of M. cerebralis and were not reactive in the fish host. These parasite-specific glycans may play a role in the adhesion process of the parasite to fish epidermis prior to infection, but may provide protection to the host by activating the complement system, or stimulating an adaptive immune response as putative antigens.

A novel potential effector of M-Ras and p21 Ras negatively regulates p21 Ras-mediated gene induction and cell growth.

Here, we report the identification and characterization of a new member of the RalGDS-family, which is widely expressed and interacts strongly and selectively with the GTP-bound forms of M-Ras and p21 Ras. This Ras pathway modulator (RPM), also termed RGL3, exhibited Ras-binding and catalytic domains typical of the RalGDS-family of guanine nucleotide exchange factors, and was most similar to Rlf (RalGDS-like factor), but was distinguished by a unique proline-rich region with multiple candidate SH3-domain binding sites. RPM/RGL3 resembled AF-6 and Nore1 in interacting strongly with constitutively active M-Ras and p21 Ras. In contrast to Rlf, transiently expressed RPM/RGL3 did not activate an Elk-1-inducible reporter gene alone or in combination with activated p21 Ras, but strongly inhibited induction of this reporter gene by co-expression of activated H-Ras or MEKK-1. This inhibitory effect was independent of the Ras binding domain and required a second signal provided by p21 Ras or MEKK-1, but not Raf-1 or M-Ras. Expression of RPM/RGL3 also strongly inhibited cell growth of fibroblasts transformed by an activated Src Y527F. Thus, RPM/RGL3 is a novel potential effector of both p21 Ras and M-Ras with the novel function of negatively regulating Elk-1-dependent gene induction downstream of p21 Ras or MEKK-1.

Plasma lipids, lipoproteins, and familial breast cancer.

We have examined the relationship between plasma lipids, lipoproteins, and a family history of breast cancer. We measured the plasma lipids and lipoproteins in unaffected female members of the nuclear family of women with familial breast cancer and compared them with those of the female members of the nuclear family of women with sporadic breast cancer. A mean number of 3.3 relatives of mean age 35 years were studied in 23 pairs of familial and sporadic breast cancer families. After adjustment in multivariate analysis for variables that either differed between high and low risk families, or were significantly associated with plasma levels or lipoproteins, statistically significant differences were found in plasma levels of total cholesterol, low density lipoprotein cholesterol, and apoprotein B, all of which were lower in familial breast cancer than in sporadic breast cancer families. These data suggest that inherited factors associated with breast cancer risk may play a role in determining plasma lipid and lipoprotein levels and that lipid regulatory genes should be considered in this context.