It should be borne in mind that our study may have had several limitations. First, reporting ailments I-BET-762 ic50 per week instead of per day may have introduced a recall and reporting bias, resulting in an underestimation of the incidence of ailments. Secondly, we only included children and parents who received pre-travel health advice; as a consequence, the incidence rates of ailments may even be higher in children traveling without any form of pre-travel health advice. Skin problems and abdominal problems like diarrhea are frequently reported ailments

in children and their parents and show a high tendency to recur during travel. The majority of these ailments are mild but occasionally interfere with planned activities. Children in

the age group 12 to 18 years are at a greater risk of developing ailments during a stay in a (sub)tropical country and they should be actively 5-FU nmr informed about the health risks of traveling to the tropics. This study was financially supported by an unconditional grant of the Port of Rotterdam. We thank all health professionals at the Travel Clinic in Rotterdam for their co-operation and Henk Koene for his helpful assistance with data management. P.J.J. van Genderen received speaker’s fee and reimbursement from GlaxoSmithKline and Sanofi Pasteur MSD for attending symposia. D.O. received speaker’s fee and reimbursements from GlaxoSmithKline and Crucell and from GlaxoSmithKline for attending symposia. The other authors state they have no conflicts of interest to declare. “
“With the economic recovery gaining momentum, travel experts predict that tourism in all regions will increase in 2010 by an estimated 3% to 4%.1 This increase in travel is forecasted to exceed 5% in Africa, Asia, and the Middle East, where the risk

of acquiring meningococcal disease or becoming a carrier is higher.2 When evaluating the need for vaccination in travelers, particularly for those traveling to developing world countries, it is important to consider not only the incidence rate but also the impact of the respective infection (Figure 1).3 As an example, Exoribonuclease meningococcal disease is rarely reported in travelers, but the impact of this infection can be as devastating for travelers as for any other individual. With its rapid clinical course and narrow window for diagnosis, the potential for negative outcomes from meningococcal disease may be increased particularly in travelers to remote locations where access to adequate health care facilities and antibiotics is limited. There is an additional public health concern with meningococcal infection, as travelers who are carriers may spread the infection in the society back home.

CyaC inclusions were completely dissolved in 8 M urea at 37 °C for 1 h (Fig. 2b, lane 1). A fast removal of urea in the refolding step

using a reciprocal dialysis or a high dilution (10–100-fold) of the unfolded CyaC solution resulted in a large fraction (≥80%) of sediment aggregates. It has been shown Natural Product Library chemical structure that certain aggregation suppressors (e.g. NaCl) added to the refolding solution at an intermediate-denaturant concentration can induce denatured proteins to refold into globular shape favoring a native conformation (Lairez et al., 2003). Herein, one-step reduction of urea to an intermediate concentration (2 M) of the denatured CyaC solution supplemented with 150 mM NaCl was found to recover a high proportion of refolded monomers (Fig. 2b, lane 2) as observed by size-exclusion chromatography. Thus, this cardinal step allowed us finally to obtain the urea-free refolded CyaC protein with ∼90% purity and ∼70% yield recovery

(∼70 mg L−1 of culture) as analyzed by SDS-PAGE (Fig. 2b, lane 3). It should be noted that the 21-kDa purified proteins obtained from both soluble and insoluble fractions were reverified to be CyaC-acyltransferase as their part of trypsin-generated peptide sequence (DWPVHLLARNTLAPIQLGQYILLR) analyzed by LC/MS/MS, perfectly matching the corresponding CyaC sequence (residues Asp35-Arg58). As mentioned earlier, the CyaA-PF fragment (Fig. 1b, lane 2) can be acylated AZD0530 ic50 in vivo by coexpressed CyaC to exhibit hemolytic activity (Powthongchin & Angsuthanasombat, 2008). By this activation analogy, we initially used this fragment as an acylated target for testing the activating activity of CyaC. When the cell lysate containing proCyaA-PF (Fig. 1b, lane 1) was mixed with the purified CyaC protein,

it showed high hemolytic activity against sheep erythrocytes (∼30%). In contrast, the lysate containing proCyaA-PF alone or the proCyaA-PF-free lysate mixed with CyaC exhibited very weak activity (≤5%) (Table 1). These results indicate that the proCyaA-PF fragment could be acylated by CyaC in vitro. It was also observed that both soluble and refolded CyaC could activate the proCyaA-PF fragment in vitro to show comparable hemolysis of ∼30%, suggesting that the refolded CyaC is likely to exist as an active monomer corresponding to the native-folded protein in soluble fraction. Thus, C59 supplier this hemolytic activity could be inferred as the CyaC capability in transferring acyl group to the proCyaA-PF acceptor. Further attempts were therefore made to assay its catalyzing capability of acyl group, as this has not been characterized thus far for any RTX-acyltransferases. It has been shown that homoserine acyltransferase (Ziegler et al., 2007) and arylamine N-acetyltransferase (Pluvinage et al., 2007) also catalyze a related reaction in vitro– namely, the hydrolysis of oxygen–ester bond of a nonphysiological substrate (i.e. pNPA).

, 2006). Bacteria have developed different mechanisms to confer resistance to copper, which vary significantly among the species. In Pseudomonas species, the well characterized copper resistance system is the plasmid-encoded cop system in Pseudomonas

syringae pv. tomato (Cha & Cooksey, 1991; Cooksey, 1993). In this organism, a 35-kb plasmid pPT23D carries the cop operon, which consists of four structural genes (copABCD) and two regulatory genes (copRS). Recent proteomic analysis of Pseudomonas putida KT2440 in response to copper and cadmium identified that the bacterial isolate is able to survive under copper stress by up-regulation of the expression of copper-binding proteins (CopA and CopR), oxidative stress protective check details proteins and several enzymes involved in the Krebs cycle (Miller et al., 2009). Besides genetic and proteomic studies, the metabolomic approach provides additional information on how the bacteria adapt to various environments (Frimmersdorf et al., 2010). Changes in tricarboxylic acid cycle (TCA) cycle, glycolysis, pyruvate and nicotinate Selleck Z VAD FMK metabolism of Pseudomonas fluorescens planktonic culture in response to copper stress were found using a combined gas chromatography-mass spectrometry (GC-MS) and nuclear

magnetic resonance (NMR) approach (Booth et al., 2011). Pseudomonas sp. TLC6-6.5-4 isolated from Torch Lake sediment contaminated Thalidomide by copper mine tailings shows high resistance with the minimum inhibitory concentration of 5 mM in basic salt medium (BSM) and 6 mM in Luria broth (LB) medium (Li & Ramakrishna, 2011). The bacteria produce indole-3-acetic acid and siderophores and solubilize phosphate, which promotes plant growth. The objective of this study was to investigate how this bacterium adapts to the toxic

levels of copper. We created a transposon insertion library, screened for copper-sensitive mutants and found that the disruption of ATP-dependent clp protease (clpA) gene caused a significant reduction in copper resistance of Pseudomonas sp. TLC6-6.5-4. Further, we performed proteomic and metabolomic analyses to compare the copper-sensitive mutant with the wild type. Bacterial strain Pseudomonas sp. TLC6-6.5-4 was grown in Luria broth (LB) with 4 mM Cu2+ at 30 °C and shaken at 140 r.p.m. until the OD600 mm reached 0.4 (exponential phase). This concentration challenged the bacteria but did not inhibit growth. Bacteria grown in LB medium without copper were used as control. Bacterial cells were stained using a gram staining kit (BD) and observed under an Olympus BX51 microscope (Leeds Precision). In addition, the morphology of the bacterial isolate was examined using a scanning electron microscope (SEM) (JSM-6400, JEOL). Sample preparation was carried out as described by Shi & Xia (2003). The bacterial length was measured using image j software (http://rsb.info.nih.gov/ij).

The stimuli were presented on video once every 2.3–6.2 s. As a control, we presented two horizontal black bars moving with the same time

courses and the same extent as the eyelids in the blink video. Both types of blinks and bars elicited clear responses peaking at about 200 ms in the occipital areas, with no systematic differences between hemispheres. For the bars, these main responses were (as expected) weaker Talazoparib in vitro (by 24%) and later (by 33 ms) to slow-motion than normal-speed stimuli. For blinks, however, the responses to both normal-speed and slow-motion stimuli were of the same amplitude and latency. Our results demonstrate that the brain not only responds to other persons’ eye blinks, but that the responses are as fast and of equal size even when the blinks are considerably slowed down. We interpret this finding to reflect the increased social salience of the slowed-down blinks that counteracted www.selleckchem.com/products/VX-809.html the general tendency of the brain

to react more weakly and more slowly to slowly- vs. quickly-changing stimuli. This finding may relate to the social importance of facial gestures, including eye blinks. “
“Rodent models are a key factor in the process of translating psychiatric genetics and genomics findings, allowing us to shed light on how risk-genes confer changes in neurobiology by merging different types of data across fields, from behavioural neuroscience to the burgeoning omics (e.g. genomics, epigenomics, proteomics, etc.). Moreover, they also provide an indispensable first step for drug discovery. However, recent evidence from both clinical and genetic studies highlights possible limitations in the current methods for classifying psychiatric illness, as both symptomology and underlying genetic risk are found to increasingly overlap across disorder diagnoses. Meanwhile, integration of data from animal models across disorders is currently limited. Here, we argue that behavioural neuroscience is in danger of missing

informative data because of the practice of trying to ‘diagnose’ an animal model with a psychiatric illness. What is needed is a shift in emphasis, from seeking to ally an animal model to a specific disorder, to one focused on a more systematic assessment of Alanine-glyoxylate transaminase the neurobiological and behavioural outcomes of any given genetic or environmental manipulation. “
“A major side effect of carbamazepine (CBZ), a drug used to treat neurological and neuropsychiatric disorders, is drowsiness, a state characterized by increased slow-wave oscillations with the emergence of sleep spindles in the electroencephalogram (EEG). We conducted cortical EEG and thalamic cellular recordings in freely moving or lightly anesthetized rats to explore the impact of CBZ within the intact corticothalamic (CT)–thalamocortical (TC) network, more specifically on CT 5–9-Hz and TC spindle (10–16-Hz) oscillations.

Easterly winds prevailed in the northern region (78±13°) and north-easterly winds in the south (46.1±12°). During 25–28 January, a major dust deposition event occurred, while the ship was in the southwest of the region, making the sky brown and covering the ship in a layer of red-brown dust. The dust cloud was clearly visible in satellite images and back trajectories for these dates show that

the air mass came from the Sahara region. Seawater samples were collected using a trace metal clean technique from 20 m depth, to minimize iron contamination from the ship’s hull, using a rosette of 20-L Niskin bottles mounted on a titanium frame with a CTD profiler (Sea-Bird Electronics) in polyoxymethylene plastic and titanium casing. Samples were decanted learn more into 1-L HCl-cleaned polycarbonate bottles. The experiments commenced within an hour of sampling. Dust samples were collected daily, at sea, onto polypropylene filters (47 mm, 0.45 μm, Sterlitech). Rotary vein vacuum pumps filtered aerosol at 25–30 L min−1 for periods of typically 24 h, although this was reduced to 4–6 h during the major dust event on 25–28 January. The instantaneous dissolution of metals and nutrients was simulated

Bcl-2 inhibitor by quickly passing 100 mL of deionized water (milli-Q) through the dust-loaded filter (Buck et al., 2006) and the leachate was subsampled into sterile 2-mL polypropylene vials. The bacterioplankton response to dust and leachate additions was determined by time-course sampling during incubations lasting 24 h. Four incubations were performed, two in the southwest of the region and two in the north (Fig.

1). Seawater samples (34 mL) were incubated in HCl-cleaned 35-mL PTFE bottles with dust, leachate or no (control) additions. Dust was added with the polypropylene filter onto which it was collected; additions were calculated postcruise to be 0.3 mg L−1 (incubation 1), 1.5 mg L−1 (incubation 2) or 4.7 mg L−1 (incubations 3 and 4). A further control of a blank polypropylene filter was used to ensure that the bacterioplankton response was due to the dust and not the filter. Leachate additions of 700 μL supplied 100 nM inorganic N and 10 nM P to all incubations. Bottles were placed in Protein kinase N1 on-deck incubators screened to allow 20% surface irradiance and cooled to in situ temperature. The uptake rate of 35S-methionine (35S-Met) was measured at t=0, 2, 4, 6 and 24 h to determine the bacterioplankton community metabolic response to treatments (+Leachate or +Dust) as compared with controls. Two incubations were also sampled at t=8 h. At t=0 and 6 h, samples were taken to measure cellular uptake by sorted bacterioplankton groups. A further eight t=0 h samples were collected throughout the cruise to measure the cellular uptake in response to natural dust deposition in the ocean.

We would like to thank Prof. Anne O. Summers (The University of Georgia, Athens, USA) for

providing the original E. casseliflavus 664.1H1 isolate and Dr Carla Novais (Fernando Pessoa University, Oporto, Portugal) for critically reading the manuscript. “
“Ramoplanin is a lipoglycodepsipeptide antimicrobial active against clinically important Gram-positive bacteria signaling pathway including methicillin-resistant Staphylococcus aureus. To proactively examine ramoplanin resistance, we subjected S. aureus NCTC 8325-4 to serial passage in the presence of increasing concentrations of ramoplanin, generating the markedly resistant strain RRSA16. Susceptibility testing of RRSA16 revealed the unanticipated acquisition of cross-resistance to vancomycin and nisin. RRSA16 displayed Selleckchem Enzalutamide phenotypes, including a thickened cell wall and reduced susceptibility to Triton X-100-induced autolysis, which are associated with vancomycin intermediate-resistant S. aureus strains. Passage of RRSA16 for 18 days in a drug-free medium yielded strain R16-18d with restored antibiotic susceptibility. The RRSA16 isolate may be used to identify the genetic and biochemical basis for ramoplanin resistance and to further our understanding of the evolution of antibiotic cross-resistance mechanisms

in S. aureus. Staphylococcus aureus is the frequent causative agent of hospital- and community-acquired infections. In 2005, there were an estimated 94 360 invasive methicillin-resistant Nintedanib (BIBF 1120) S. aureus (MRSA) cases and an estimated 18 650 deaths in the United States due to these infections (Klevens et al., 2007). Most alarming is the observation that in 2005, the number of deaths in the United States attributed to

MRSA infections exceeded the total number of US deaths attributable to HIV/AIDS (Bancroft, 2007; Klevens et al., 2007). Ramoplanin is a lipoglycodepsipeptide antibiotic active against clinically important Gram-positive bacteria including vancomycin-resistant Enterococcus sp., MRSA and vancomycin intermediate-resistant Clostridium difficile (Neu & Neu, 1986; Jones & Barry, 1989; Biavasco et al., 1991; Johnson et al., 1992; Mobarakai et al., 1994; Ristow et al., 1995; Rolston et al., 1996; Finegold et al., 2004; Pelaez et al., 2005). Preclinical studies have demonstrated that ramoplanin exerted a rapid bactericidal effect on S. aureus biofilms (Opperman et al., 2003) and that a clinical vancomycin-resistant S. aureus strain containing the vanA gene was susceptible to ramoplanin (Bozdogan et al., 2003). In the immediate past, ramoplanin was evaluated as a possible treatment for infection from these microorganisms, and in Asia, the structurally related antibiotic enduracidin has been in use as a growth-promoting feed additive for livestock (McCafferty et al., 2002). Treatment options for MRSA infections are limited as many MRSA strains are resistant to multiple antimicrobial agents (Ayliffe, 1997).

S1). In our previous work, we developed the ‘CRS cassette method’ to construct and combine markerless deletion mutations

(Hashimoto et al., 2005). The CRS cassette has a positive-selection marker (CmR) and two negative-selection markers (sacB+ and rpsL+) (Hashimoto et al., 2005; Kato & Hashimoto, 2008). First, the chromosome region to be deleted was replaced with the CRS cassette using a positive-selection marker and lambda red homologous recombination (Murphy, 1998). Next, the CRS cassette was removed using negative-selection markers and red recombination (Hashimoto et al., 2005). Two types of deletion mutants with and without the CRS cassette were constructed and transferred to recipient cells by transduction Metabolism inhibitor with P1 phage. To avoid creating strains with synthetic growth defects and circumvent the complications associated with the use of a long CRS cassette fragment, a convenient method (ApR-415S Sm system) for introducing the new deletions was developed (Fig. 1). First, the ApR deletion units were constructed by replacing them with an ApR fragment that was shorter than the CRS cassette. After confirming that there was no synthetic growth defect, the ApR fragment was removed using ‘the 415S Sm system’ (Kato & Hashimoto, 2008), in which www.selleckchem.com/products/nutlin-3a.html the chromosomal regions flanking the region to be deleted were cloned into a ts replication plasmid 415S Sm to yield ‘the deletion plasmid.’ The 415S Sm plasmid was constructed by inserting

a negative-selection marker, the wild-type rpsL allele, into the ts plasmid pHSG415S that harbored a positive-selection Adenosine marker CmR (Hashimoto-Gotoh et al., 1981). The deletion plasmid was then introduced into the

rpsL (SmR) mutant with an ApR deletion unit and the CmR transformants were selected at 42 °C. The transformants were incubated at 30 °C to obtain the SmR ApS strains. It was sometimes difficult to isolate ApS strains from the SmR strains using the ApR-415S Sm system. To make this easier, the FRT4 system was used (Fig. 2), in which a CmR fragment containing an FRT site, a recombination site for the FLP site-specific recombinase, was replaced with the deleted region to construct the CmR–FRT deletion unit. The deletion plasmid was constructed by inserting the fragment with the wild-type rpsL allele and the joined chromosomal regions that flanked the deleted regions into the plasmid pSG76A (ApR), which is an R6k derivative plasmid that lacks the pir gene required for replication (Posfai et al., 1997; Kato & Hashimoto, 2008). The deletion plasmid was introduced into the rpsL (SmR) mutant that harbored a CmR–FRT deletion unit and ApR transformants were selected. The FLP-containing plasmid was introduced into the ApR recombinant and, after adding tetracycline to the culture media to induce FLP recombinase, SmR strains were obtained (Posfai et al., 1997). Previously, a series of large-scale chromosome deletion mutants (Δ1–Δ16) were constructed.

marimammalium, we propose that group M strains should be classified as a new species (Stackebrandt et al., 2002). DNA relatedness among the group M strains was>73.1%. Thus, these three strains were confirmed to be the same species. Group M strain PAGU1330 from a human subject was located within the Mitis group with Streptococcus infantis being the closest species in the phylogenetic analysis (16S rRNA gene sequence similarity, 98.7%). The group M strains of canine origin were Gram-positive cocci and occurred in pairs or short chains. These organisms were facultatively

Enzalutamide mw anaerobic and catalase negative. The colonies that they formed were generally small and translucent on blood agar. In the biochemical test, these strains with group M antigens closely resembled each other. β-Galactosidase activity and utilization of glycogen could distinguish them from the closely related species (Table 2). The G+C content of the DNA of PAGU 653 was determined to be 38.4±0.3 (mean±SD) mol%, which is within the characteristic range of the genus Streptococcus Androgen Receptor activity (34–46 mol%) (Spellerberg & Brandt, 2007). This value is similar to those of other close phylogenetic relatives (e.g. S. marimammalium, 38.0 mol%; S. phocae, 38.6 mol%; Streptococcus castreus, 37.4 mol%) (Skaar et al., 1994; Lawson et al.,

2005a, b). The group M streptococci was established by Fry in 1941 (personal communication cited from Wilson & Miles, 1955). Only the β-hemolytic group M strains isolated from the animal Nintedanib (BIBF 1120) (the tonsil of the dog) were recognized until 1955 (Wilson & Miles, 1955). However in 1959, Skadhauge & Perch (1959) reported the α-hemolytic human strains of group M isolated from the gingival mucosa of healthy persons or from the blood of patients suffering from subacute bacterial endocarditis. They proposed the three biovars within the group M streptococci; biovar-I consists of α-hemolytic human strains that

fail to hydrolyze arginine and have a final pH in glucose broth of 4.6–5.2. Biovar-II strains are of animal origin, β-hemolytic, hydrolyze arginine and attain a final pH of 6.3–7.2. Biovar-III strains are also of animal origin, β-hemolytic, hydrolyze arginine but produce more acid from glucose (final pH 5.9–6.7). Broome et al. (1976) also report many group M α-hemolytic human strains, isolated from the patients of endocarditis, or septicemia from a sternal abscess. In this study, we used only one human isolate called ‘Lindstrøm’ (=PAGU 1330), which was stated as a group M biovar-I strain (Skadhauge & Perch, 1959). The phylogenetic position of the strain was located within the Mitis group and not with the canine, β-hemolytic strains (Fig. 1). Colman (1968) stated that some strains of group M resembled ‘Streptococcus viridans’ or Streptococcus mitis, which would indicate the biovar-I strain group, namely α-hemolytic human group M strains. Additional experiments to determine the accurate phylogenetic and taxonomic position of the biovar-I strain group are required.

2a) decreased substantially with time, from 60% in 2000 to 43% in 2010. Smoking prevalence was lower

Selleck DAPT in participants in the care of private physicians. Observed patterns were very different among the HIV transmission group categories (Fig. 2b). In the year 2000, the prevalence of smoking at the Zurich SHCS centre (64%) was higher than at all other centres (61%), or among participants in the care of private physicians (55%), and it decreased in all care settings, with a more pronounced decrease at the Zurich centre (–22.5%) than in other centres (–16.5%) or in private practices (–14.5%) (Fig. 2a). Smoking prevalence among HIV-positive persons has always been higher than in the general population in Switzerland (Fig. 2c) [30, 31]. Some of these differences may be attributable to differences in age distributions, with older persons, who are less likely to smoke, being underrepresented in the SHCS. For example, in 2009 only 14% of SHCS participants were aged 55 years or above, compared with 40% in the general Swiss population [31]. www.selleckchem.com/products/CAL-101.html Smoking cessation was observed 2019 times during 29 541 person-years for 5805 SHCS participants; and smoking relapses occurred 1390 times during 12 055 person-years

for 1953 participants from 2000 to 2010. The resulting incidences were 6.8 [95% confidence interval (CI) 6.5–7.1] per 100 patient-years for smoking cessation, and 11.5 (95% CI 10.9–12.2) per 100 patient-years for relapses. Incidences varied considerably

across settings and over time: values for smoking cessation in 2004, 2007 (just prior to the intervention) and 2010 (after 3 years of the intervention) were 5.0 (95% CI 3.6–6.9), 6.1 (95% CI 4.6–8.1) and 10.8 (95% CI 7.9–14.6) per 100 patient-years at the Zurich centre, 5.2 (95% CI 4.2–6.6), 4.4 (95% CI 3.5–5.5) and 6.2 (95% CI 4.7–8.2) at other centres, and 5.4 (95% CI 4.2–7.0), 7.5 (95% CI 6.1–9.2) and 7.6 (95% CI 5.7–10.1) for private practices, respectively. Values for cessation relapses in 2004, 2007 and 2010 were 11.2 (95% CI 7.7–16.2), 8.7 (95% CI 6.1–12.4) and 2.9 (95% CI 1.3–6.5) per 100 patient-years at the Zurich centre, whereas incidences Astemizole were 10.5 (95% CI 7.8–14.2), 10.9 (95% CI 8.4–14.1) and 9.2 (95% CI 6.6–12.9) for other centres, and 10.8 (95% CI 8.1–14.4), 10.6 (95% CI 8.4–13.5) and 7.3 (95% CI 4.7–11.4) for private practices, respectively. Results from marginal logistic regression models are displayed in Table 3 for smoking cessation and Table 4 for relapses. Although the models for cessation events and relapse events include partly different person groups, effect estimates for the different covariables are very symmetrical across all models (i.e. factors which are negatively associated with cessation events were positively associated with relapse events). Therefore, only the models for cessation events are described in more detail.

92% (n = 80) of respondents identified at selleck kinase inhibitor least one appropriate ethical issue related to the vignette. Non-maleficence, or doing no harm, was the most recognised ethical principle, identified by 23% (n = 20) of respondents. Beneficence was recognised by 21% (n = 18) of respondents and patient autonomy by 15% (n = 13). The principle of justice was clearly stated by 11% (n = 10) of respondents. Maintaining

patient privacy, confidentiality and obtaining patient consent were recognised by 83% (n = 72) of respondents as important to the clinical scenario. Identified by 47% (n = 41) of respondents, an overall theme was the importance of considering the quality use of medicines and their impact on patient care. The majority of fourth year pharmacy

students were able to identify at least one relevant ethical principle involved in the vignette, demonstrating ethical sensitivity. It is important that students’ ethical sensitivity be carried forward into practice as pharmacists’ inability to identify ethical issues has been labeled ‘ethical inattention’ and has been considered by researchers as the first indication of ‘ethical passivity’ in the profession.1 This research was conducted on pharmacy students in their final year and it would be valuable to similarly evaluate ethical sensitivity of students across all years of a pharmacy program to DNA/RNA Synthesis inhibitor determine if there was increasing and evolving sensitivity, or a decline

in later years, as found in medical students.2 While uncomplicated the scenario encompassed all four ethical principles. Blended learning clinical vignettes are a useful way through which to evaluate pharmacy students’ ethical sensitivity. 1. Cooper R, Bissell P, Wingfield J. Ethical decision-making, passivity and pharmacy. Journal of medical ethics. 2008; 34: 441–445. 2. Hébert PC, Meslin EM, Dunn EV. Measuring the ethical sensitivity of medical students: a study at the University of Toronto. Journal of medical ethics. 1992; 18: 142–147. Kate Jenkins1, Paul Deslandes1,2, Kath Haines1, Lck Tessa Lewis1 1All Wales Therapeutics and Toxicology Centre, Cardiff, UK, 2Cardiff University School of Pharmacy and Pharmaceutical Sciences, Cardiff, UK Advice outlining the risks associated with dosulepin use resulted in its inclusion as a National Prescribing Indicator (NPI) in Wales in April 2011. Change in dosulepin prescribing in primary care was measured to examine the impact of the NPI. The rate of dosulepin usage in Wales reduced significantly following introduction of the NPI. Inclusion of dosulepin prescribing as an NPI led to a greater reduction in its use compared to the impact of previous advice. In December 2007, an MHRA Drug Safety Update highlighted the high risk of fatality associated with dosulepin overdose and made recommendations to minimise this risk1.