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Background End-of-day symptom diaries are recommended by drug regulatory authorities to assess treatment response in patients with irritable bowel syndrome. We developed a smartphone app to measure treatment response. Objective Because the employment of an app to measure treatment response in irritable bowel syndrome is relatively new, we aimed to explore patients’ adherence to diary use and characteristics associated with adherence. Methods A smartphone app was developed to serve as a symptom diary. Patients with irritable bowel syndrome (based on Rome IV criteria) were instructed to fill out end-of-day diary questionnaires during an 8-week treatment. Additional online questionnaires assessed demographics, irritable bowel syndrome symptom severity, and psychosocial comorbidities. Adherence rate to the diary was defined as the percentage of days completed out of total days. Adherence to the additional web-based questionnaires was also assessed. Results Overall, 189 patients were included (age: mean 34.0 years, SD 13.3 years; female: 147/189, 77.8%; male: 42/189, 22.2%). The mean adherence rate was 87.9% (SD 9.4%). However, adherence to the diary decreased over time (P99%). Missing data due to technical issues were limited. Conclusions The use of a smartphone app as a symptom diary to assess treatment response resulted in high patient adherence. The data-collection framework described led to standardized data collection with excellent completeness and can be used for future randomized controlled trials. Due to the slight decrease in adherence to diary use throughout the study, this method might be less suitable for longer trials.

Capromorelin is a ghrelin receptor agonist that is FDA approved for appetite stimulation in dogs. The objective of this study was to evaluate the safety of daily oral administration of capromorelin to cats over a range of doses and for an extended period. Two randomized, controlled studies were conducted: in Study 1, cats (n = 6 per group) received placebo or capromorelin at a dose of 9, 15, 30 or 60 mg/kg once daily for 14 days; and in Study 2, cats received capromorelin at 6 mg/kg (n = 8) or placebo (n = 4) once daily for 91 days. Cats were evaluated using clinical observations and clinical pathology test results for both studies, with the addition of postmortem examination in Study 1 and measurements of growth hormone and insulin-like growth factor 1 in Study 2. Abnormal clinical observations were limited to emesis, hypersalivation, lethargy/depression, head shaking and lip smacking, which occurred more frequently in the capromorelin-treated groups than in the placebo group. There were no clinically relevant differences in clinical pathology test results between the capromorelin and placebo groups in either study.

Background Reduced appetite is a common clinical sign in dogs. This study evaluated the effectiveness and safety of capromorelin oral solution, (ENTYCE®, Aratana Therapeutics, Leawood, KS) a new drug that is a ghrelin receptor agonist, for stimulation of appetite in dogs with reduced appetite. Hypothesis/Objectives Capromorelin will increase appetite, as measured by the owner's evaluation, over 4 days. An additional objective was to evaluate the safety of capromorelin at the labeled dose. Animals A total of 244 client‐owned dogs reported by owners to be inappetent for at least 2 days were enrolled, with 177 cases in the effectiveness analysis. Methods In this prospective, randomized, masked, placebo‐controlled study, dogs were treated daily with capromorelin (3 mg/kg) oral solution (n = 121) or placebo oral solution (n = 56). Owners completed an evaluation of appetite at days 0 and 3 ± 1. Success was defined as improvement in appetite at day 3. Safety was evaluated by physical examination, clinical pathology, and monitoring adverse events and owner observations. Results Capromorelin treatment improved appetite compared to placebo (68.6% and 44.6% treatment successes with 95% CI 59.7, 76.3 and 32.2, 57.8, respectively, P = .008). Mean body weight in capromorelin‐treated dogs increased compared to placebo‐treated dogs (1.8% with 95% CI 1.3, 2.3, and 0.1% with 95% CI 0.9, 1.1, respectively, P 5% of either group were diarrhea and vomiting. Conclusions and Clinical Importance Capromorelin oral solution is an effective treatment for stimulation of appetite in dogs and represents the first ghrelin receptor agonist shown to be effective for this indication.

Background Mechanisms linking changes to the environment with changes in physical activity are poorly understood. Insights into mechanisms of interventions can help strengthen causal attribution and improve understanding of divergent response patterns. We examined the causal pathways linking exposure to new transport infrastructure with changes in cycling to work. Methods We used baseline (2009) and follow-up (2012) data (N = 469) from the Commuting and Health in Cambridge natural experimental study (Cambridge, UK). Exposure to new infrastructure in the form of the Cambridgeshire Guided Busway was defined using residential proximity. Mediators studied were changes in perceptions of the route to work, theory of planned behaviour constructs and self-reported use of the new infrastructure. Outcomes were modelled as an increase, decrease or no change in weekly cycle commuting time. We used regression analyses to identify combinations of mediators forming potential pathways between exposure and outcome. We then tested these pathways in a path model and stratified analyses by baseline level of active commuting. Results We identified changes in perceptions of the route to work, and use of the cycle path, as potential mediators. Of these potential mediators, only use of the path significantly explained (85%) the effect of the infrastructure in increasing cycling. Path use also explained a decrease in cycling among more active commuters. Conclusion The findings strengthen the causal argument that changing the environment led to changes in health-related behaviour via use of the new infrastructure, but also show how some commuters may have spent less time cycling as a result., Highlights • Environmental perceptions did not explain effects of new infrastructure on cycling. • Motivational factors did not explain effects of new infrastructure on cycling. • Eighty-five percent of the effect on increasing cycling was explained by use of the infrastructure. • These results strengthen quasi-experimental causal attribution and understanding.

The pharmacokinetics after oral application of the fluoroquinolones (FQs), enrofloxacin, difloxacin, marbofloxacin and orbifloxacin were compared in independent crossover studies in Beagle dogs. Commercially available tablet formulations were given at common dosage recommended by the manufacturers which were 2.0 mg/kg body weight (bw) for marbofloxacin, 2.5 mg/kg bw for orbifloxacin and 5.0 mg/kg bw for enrofloxacin and difloxacin. Analysis was performed by an agar diffusion assay. Pharmacokinetic parameters were calculated by noncompartmental methods. All FQs were rapidly absorbed and achieved average peak serum concentrations of 1.41, 1.11, 1.47 and 1.37 μg/ mL for enrofloxacin, difloxacin, marbofloxacin and orbifloxacin, respectively. Enrofloxacin was eliminated at a terminal half-life (t 1 /2) of 4.1 h, difloxacin at 6.9 h, orbifloxacin at 7.1 h and marbofloxacin at 9.1 h. While the area under the serum concentration-time curve of the 24-h dosing interval (AUC 0 - 2 4 ) for marbofloxacin and orbifloxacin were similar (approximately 13 μg . h/mL), enrofloxacin attained an AUC 0 - 2 4 of 8.7 and difloxacin of 9.3 μg . h/mL. Because of its favourable pharmacokinetics combined with excellent in vitro activity, enrofloxacin exhibited superior pharmacodynamic predictors of in vivo antimicrobial activity as C m a x /MIC (maximum serum concentration/minimum inhibitory concentration) and AUC 0 - 2 4 /MIC (area under the 24-h serum concentration-time curve/minimum inhibitory concentration) compared with other FQs.

Clinical trials in cattle demonstrated that the IBR marker modified live vaccine based on the gE-deleted IBR strain Difivac is immunogenic and safe for bovines of all ages. Potential effects of the vaccine virus have also been tested in swine and sheep and proved safe for these species as well. For evaluation of other environmental aspects, the spread of the vaccine virus after immunisation was investigated. The data indicated that the vaccine virus may be shed by immunised animals but that it has a limited ability to pass from animal to animal. It was also demonstrated that the attenuated Difivac strain does not revert to virulence during calf passage. Preliminary results indicated that the gE-deleted vaccine virus of the IBR marker vaccine cannot be reactivated after dexamethasone treatment, an important advantage for a vaccine strain. Furthermore, immunisation with the Difivac strain reduced the ability of a superinfecting challenge virus to become latent or to be reactivated.

An inhibition of peripheral conversion of T4 to T3 is thought to be of benefit in the treatment of thyrotoxicosis. Therefore, propylthiouracil (PTU) has been considered to be more effective in the therapy of hyperthyroidism than methimazole, since the former has the additional peripheral effect of decreasing the conversion of T4 to T3, From in vitro studies PTU is known, however, to inhibit the deiodination at the 5' as well as at the 5 position of the iodothyronine molecule. To study if PTU blocks degradation in T3 in vivo as well, the effect of PTU on thyroid hormone concentrations in serum and liver tissue during a constant and high administration of T4 or T3 to rats was followed. It was shown that PTU clearly inhibits T4 and reverse T3 degradation. Moreover, simultaneous treatment of the rats with T3 and PTU resulted in a significantly higher increase of T3 concentration in liver tissue (11.5 ng/g liver vs 5.6 ng/g liver) and serum (615 ng/di vs 345 ng/dl) than with T3 alone. This effect may be explained by an inhibition of the T3 degradation by PTU in vivo as well. Provided the results obtained from these animal experiments can be applied to the situation in man, the inhibition of peripheral deiodination could have an adverse effect at least in the treatment of T3-thyrotoxicosis.

Amniotic epithelium of the rat has been studied during the eight last days of pregnancy, by scanning electron microscope analysis. The cells of this organ progressively become larger and flatter. Changes on their surface have also been observed : density of microvilli increases but single cilia disappear. These changes are related to modifications in the exchange processes.

The ultrastructural study of the unfertilized Rat egg ooplasm has shown that the so-called lamellar structures are in fact filaments constituted of proteins and where no ribonucleic acid can be detected. Thus, they do not represent a particular organization of polyribosomes. These filaments could be considered as protein stockage, maybe from membranous origin, ready for use during segmentation. Several figures suggest that endocytotic vesicles and vacuoli constitute the source of the filamentous material.

Intercellular connections exist between germinal center cells especially between lymphoid cells and follicular dendritic cells (FDC). Even after isolation, FDC remain associated to lymphocytes and are able, in a cell suspension, to establish new connections with others. Using human tonsillar cells or mouse lymph node cells we analysed these connections which were shown to be species-specific. Low temperature as well as absence of Ca++ and Mg++ in the culture medium reduced the adherence of fluorochrome-labeled lymphoid cells to FDC. Colchicine treatment did not impair the adherence, whereas cytochalasin B dit it; this was the first observation underlining the importance of microfibrils in FDC. Antibodies directed towards integrin molecules (LFA-1 alpha or beta chain, CD11a and CD18 respectively) reduced the adherence, others (anti-CR3 or anti-gp 150/95, CD11b and c respectively) did not influence it. Antibodies directed against MHC class II exerted no inhibitory action on the lymphoid cell adhesion to FDC. As, at ultrastructural level, gold-labeled immune complexes can be found between FDC and lymphoid cells, we examined the effect on cell adhesion of the addition of immune complexes to the cell suspensions. It only impaired the lymphoid cell adhesion when complement components were present. IgM complexes were then more inhibitory than IgG complexes. When antibodies against Fc IgG receptors (CD16) were added, the adhesion was strongly reduced whereas antibodies to Fc IgE (CD23) receptors had no influence. The antibody DRC1, specifically recognizing an antigen on human FDC reduced the attachment of cells to FDC. This antigen thus seems to play a role in the intercellular contacts; this is the first function ascribed to this FDC specific antigen.

The pattern of the amniotic epithelium during the eight last days of pregnancy is described with the aid of scanning and transmission microscopy. A flattening of the cells appears near the term. Their area becomes progressively greater increasing their contact surface with the amniotic fluid. Simultaneaously, their microvilli become more numerous. During the 20th, the 21st and the 22nd days of pregnancy, we observed cytoplasmic processes emanating from the base of the cell interrupting the basal membrane and entering the underlying connective substance. No evidence of cell degeneration was seen.

In order to check whether the serum free T4 as obtained with commercially available kits can substitute for total T4 measurements in the routine diagnosis of thyroid disorders, serum FT4 was simultaneously assayed using 5 different methods (Amerlex; GammaCoat; Immo-Phase; LiquiSol; T4/TBG) in 152 subjects. Overt hyper- and hypothyroidism were readily distinguished from euthyroidism with each method. Discrepant FT4 results, however, were obtained with these assays in clinically euthyroid subjects exhibiting various extrathyroidal disorders (TBG-deficiency or -excess, late pregnancy, serious illness, T4 administration). Since it is as yet impossible to decide which of the commercial kits will yield methodologically and physiologically reliable results, a substitution of total T4 measurements by FT4 cannot yet be recommended in the laboratory diagnosis of thyroid disease.

When injected into the peritoneal cavity, ethidium bromide can strongly inhibit the multiplication of mouse Ehrlich ascites tumour cells. This antitumour effect is increased when ethidium bromide is linked to DNA and also injected into the peritoneal cavity. The cellular alterations are identical after a treatment with E.B. either free or bound to DNA. However, when the cells are treated with E.B.-DNA they contain E.B. for a longer period than after a treatment with E.B.

With the aid of scanning electron microscopy the normal pattern of both faces of amnion and visceral yolk sac were described. The inner face of the amnion turned towards the amniotic cavity is overlaid by large pavimentous cells bearing numerous microvilli. The opposite face, which delimits the exocoelome, consists of flattened fibroblasts separated by a fundamental connective substance. The two faces of the visceral yolk sac also show very different patterns. The exocoelomic face is covered by pavimentous cells ; these are smaller and bear less microvilli than amniotic cells. The yolk sac endoderm appears built up with prismatic or cubic cells, whose apical part is bulging and possesses a dense covering of microvilli. Amniocentesis effects are then reported. This intervention seems to provoke fetal membrane modifications only after 15 hours. These modifications essentially concern the visceral yolk sac whose exocoelomic cells are covered by more numerous microvilli which may show an intensification of a secretory process.

Recently, we suggested that the cell coat of the surface epithelial cells of the palatal shelves and especially its sialyl groups are implied in the adhesion process which initiates the constitution of the secondary palate. In this work, use of cationized ferritin which interacts with anionic receptors of the plasma membrane give us the possibility to render these sialic acids visible. After five minutes incubation in presence of cationized ferritin, the labeling particles are distributed in monolayer over the plasmalemma of epithelial cells. Subsequent incubation in cationized ferritin free medium results in clustering of the marker followed by the detachment of the labeled patches. Otherwise, incubation in the presence of neuraminidase from Clostridium perfringens before the polycationic ligand contact prevents labeling. We think that lateral migration modifications of the anionic receptor could be associated with changes of the shelves capacity to adhere.