Storage of prescription veterinary medicines on UK dairy farms: A cross-sectional study

This is the final version. Available on open access from BMJ Publishing Group via the DOI in this recordPrescription veterinary medicine (PVM) use in the UK is an area of increasing focus for the veterinary profession. While many studies measure antimicrobial use on dairy farms, none report the quantity of antimicrobials stored on farms, nor the ways in which they are stored. The majority of PVM treatments occur in the absence of the prescribing veterinarian, yet there is an identifiable knowledge gap surrounding PVM use and farmer decision making. To provide an evidence base for future work on PVM use, data were collected from 27 dairy farms in England and Wales in Autumn 2016. The number of different PVMs stored on farms ranged from 9 to 35, with antimicrobials being the most common therapeutic group stored. Injectable antimicrobials comprised the greatest weight of active ingredient found, while intramammary antimicrobials were the most frequent unit of medicine stored. Antimicrobials classed by the European Medicines Agency as critically important to human health were present on most farms, and the presence of expired medicines and medicines not licensed for use in dairy cattle was also common. The medicine resources available to farmers are likely to influence their treatment decisions; therefore, evidence of the PVM stored on farms can help inform understanding of medicine use.Langford Trust for Animal Health and Welfar

Monorail/Foxa2 regulates floorplate differentiation and specification of oligodendrocytes, serotonergic raphe neurones and cranial motoneurones

In this study, we elucidate the roles of the winged-helix transcription factor Foxa2 in ventral CNS development in zebrafish. Through cloning of monorail (mol), which we find encodes the transcription factor Foxa2, and phenotypic analysis of mol(-/-) embryos, we show that floorplate is induced in the absence of Foxa2 function but fails to further differentiate. In mol(-/-) mutants, expression of Foxa and Hh family genes is not maintained in floorplate cells and lateral expansion of the floorplate fails to occur. Our results suggest that this is due to defects both in the regulation of Hh activity in medial floorplate cells as well as cell-autonomous requirements for Foxa2 in the prospective laterally positioned floorplate cells themselves. Foxa2 is also required for induction and/or patterning of several distinct cell types in the ventral CNS. Serotonergic neurones of the raphe nucleus and the trochlear motor nucleus are absent in mol(-/-) embryos, and oculomotor and facial motoneurones ectopically occupy ventral CNS midline positions in the midbrain and hindbrain. There is also a severe reduction of prospective oligodendrocytes in the midbrain and hindbrain. Finally, in the absence of Foxa2, at least two likely Hh pathway target genes are ectopically expressed in more dorsal regions of the midbrain and hindbrain ventricular neuroepithelium, raising the possibility that Foxa2 activity may normally be required to limit the range of action of secreted Hh proteins

The gait profile score characterises walking performance impairments in young stroke survivors

Background: The Gait Profile Score (GPS) provides a composite measure of the quality of joint movement during walking, but the relationship between this measure and metabolic cost, temporal (e.g. walking speed) and spatial (e.g. stride length) parameters in stroke survivors has not been reported. Research Question: The aims of this study were to compare the GPS (paretic, non-paretic, and overall score) of young stroke survivors to the healthy able-bodied control and determine the relationship between the GPS and metabolic cost, temporal (walking speed, stance time asymmetry) and spatial (stride length, stride width, step length asymmetry) parameters in young stroke survivors to understand whether the quality of walking affects walking performance in stroke survivors. Methods: Thirty-nine young stroke survivors aged between 18 and 65years and 15 healthy age-matched able-bodied controls were recruited from six hospital sites in Wales, UK. Joint range of motion at the pelvis, hip, knee and ankle, and temporal and spatial parameters were measured during walking on level ground at self-selected speed with calculation of the Gait Variable Score and then the GPS. Results: GPS for the paretic leg (9.40° (8.60–10.21) p < 0.001), non-paretic leg (11.42° (10.20–12.63) p < 0.001) and overall score (11.18° (10.26–12.09) p < 0.001)) for stroke survivors were significantly higher than the control (4.25° (3.40–5.10), 5.92° (5.11 (6.73)). All parameters with the exception of step length symmetry ratio correlated moderate to highly with the GPS for the paretic, non-paretic, and/or overall score (ρ = <−0.732 (p < 0.001)). Significance: The quality of joint movement during walking measured via the GPS is directly related to the speed and efficiency of walking, temporal (stance time symmetry) and spatial (stride length, stride width) parameters in young stroke survivors

Early onset obesity and adrenal insufficiency associated with a homozygous POMC mutation

Isolated hypocortisolism due to ACTH deficiency is a rare condition that can be caused by homozygous or compound heterozygous mutations in the gene encoding proopiomelanocortin (POMC). Loss of function mutations of POMC gene typically results in adrenal insufficiency, obesity and red hair. We describe an 18 month old Hispanic female with congenital adrenal insufficiency, a novel POMC mutation and atypical clinical features. The patient presented at the age of 9 months with hypoglycemia and the endocrine evaluation resulted in a diagnosis of ACTH deficiency. She developed extreme weight gain prompting sequence analysis of POMC, which revealed a homozygous c.231C > A change which is predicted to result in a premature termination codon. The case we report had obesity, hypocortisolism but lacked red hair which is typical for subjects with POMC mutations. Mutations of POMC should be considered in individuals with severe early onset obesity and adrenal insufficiency even when they lack the typical pigmentary phenotype

Anatomical heterogeneity of tendon: Fascicular and interfascicular tendon compartments have distinct proteomic composition

This study was funded by the BBSRC (BB/K008412/1)

The prevalence and experience of Australian naturopaths and Western herbalists working within community pharmacies

<p>Abstract</p> <p>Background</p> <p>Naturopaths and Western herbal medicine (WHM) practitioners were surveyed to identify their extent, experience and roles within the community pharmacy setting and to explore their attitudes to integration of complementary medicine (CM) practitioners within the pharmacy setting.</p> <p>Method</p> <p>Practising naturopaths and WHM practitioners were invited to participate in an anonymous, self-administered, on-line survey. Participants were recruited using the mailing lists and websites of CM manufacturers and professional associations.</p> <p>Results</p> <p>479 practitioners participated. 24% of respondents (n = 111) reported they had worked in community pharmacy, three-quarters for less than 5 years. Whilst in this role 74% conducted specialist CMs sales, 62% short customer consultations, 52% long consultations in a private room and 51% staff education. This was generally described as a positive learning experience and many appreciated the opportunity to utilise their specialist knowledge in the service of both customers and pharmacy staff. 14% (n = 15) did not enjoy the experience of working in pharmacy at all and suggested pharmacist attitude largely influenced whether the experience was positive or not. Few practitioners were satisfied with the remuneration received. 44% of the total sample provided comment on the issue of integration into pharmacy, with the main concern being the perceived incommensurate paradigms of practice between pharmacy and naturopathy. Of the total sample, 38% reported that they would consider working as a practitioner in retail pharmacy in future.</p> <p>Conclusions</p> <p>The level of integration of CM into pharmacy is extending beyond the mere stocking of supplements. Naturopaths and Western Herbalists are becoming utilised in pharmacies</p

Influence of oxygen tension on myocardial performance. Evaluation by tissue Doppler imaging

BACKGROUND: Low O(2 )tension dilates coronary arteries and high O(2 )tension is a coronary vasoconstrictor but reports on O(2)-dependent effects on ventricular performance diverge. Yet oxygen supplementation remains first line treatment in cardiovascular disease. We hypothesized that hypoxia improves and hyperoxia worsens myocardial performance. METHODS: Seven male volunteers (mean age 38 ± 3 years) were examined with echocardiography at respiratory equilibrium during: 1) normoxia (≈21% O(2), 79% N(2)), 2) while inhaling a hypoxic gas mixture (≈11% O(2), 89% N(2)), and 3) while inhaling 100% O(2). Tissue Doppler recordings were acquired in the apical 4-chamber, 2-chamber, and long-axis views. Strain rate and tissue tracking displacement analyses were carried out in each segment of the 16-segment left ventricular model and in the basal, middle and apical portions of the right ventricle. RESULTS: Heart rate increased with hypoxia (68 ± 4 bpm at normoxia vs. 79 ± 5 bpm, P < 0.001) and decreased with hyperoxia (59 ± 5 bpm, P < 0.001 vs. normoxia). Hypoxia increased strain rate in four left ventricular segments and global systolic contraction amplitude was increased (normoxia: 9.76 ± 0.41 vs hypoxia: 10.87 ± 0.42, P < 0.001). Tissue tracking displacement was reduced in the right ventricular segments and tricuspid regurgitation increased with hypoxia (7.5 ± 1.9 mmHg vs. 33.5 ± 1.8 mmHg, P < 0.001). The TEI index and E/E' did not change with hypoxia. Hyperoxia reduced strain rate in 10 left ventricular segments, global systolic contraction amplitude was decreased (8.83 ± 0.38, P < 0.001 vs. normoxia) while right ventricular function was unchanged. The spectral and tissue Doppler TEI indexes were significantly increased but E/E' did not change with hyperoxia. CONCLUSION: Hypoxia improves and hyperoxia worsens systolic myocardial performance in healthy male volunteers. Tissue Doppler measures of diastolic function are unaffected by hypoxia/hyperoxia which support that the changes in myocardial performance are secondary to changes in vascular tone. It remains to be settled whether oxygen therapy to patients with heart disease is a consistent rational treatment

Conjugation of Functionalized SPIONs with Transferrin for Targeting and Imaging Brain Glial Tumors in Rat Model

Currently, effective and specific diagnostic imaging of brain glioma is a major challenge. Nanomedicine plays an essential role by delivering the contrast agent in a targeted manner to specific tumor cells, leading to improvement in accurate diagnosis by good visualization and specific demonstration of tumor cells. This study investigated the preparation and characterization of a targeted MR contrast agent, transferrin-conjugated superparamagnetic iron oxide nanoparticles (Tf-SPIONs), for brain glioma detection. MR imaging showed the obvious contrast change of brain glioma before and after administration of Tf-SPIONs in C6 glioma rat model in vivo on T2 weighted imaging. Significant contrast enhancement of brain glioma could still be clearly seen even 48 h post injection, due to the retention of Tf-SPIONs in cytoplasm of tumor cells which was proved by Prussian blue staining. Thus, these results suggest that Tf-SPIONs could be a potential targeting MR contrast agent for the brain glioma

From L-Dopa to Dihydroxyphenylacetaldehyde: A Toxic Biochemical Pathway Plays a Vital Physiological Function in Insects

One protein in Aedes aegypti, classified into the aromatic amino acid decarboxylase (AAAD) family based on extremely high sequence homology (∼70%) with dopa decarboxylase (Ddc), was biochemically investigated. Our data revealed that this predicted AAAD protein use L-dopa as a substrate, as does Ddc, but it catalyzes the production of 3,4-dihydroxylphenylacetaldehyde (DHPAA) directly from L-dopa and apparently has nothing to do with the production of any aromatic amine. The protein is therefore named DHPAA synthase. This subsequently led to the identification of the same enzyme in Drosophila melanogaster, Anopheles gambiae and Culex quinquefasciatus by an initial prediction of putative DHPAA synthase based on sequence homology and subsequent verification of DHPAA synthase identity through protein expression and activity assays. DHPAA is highly toxic because its aldehyde group readily reacts with the primary amino groups of proteins, leading to protein crosslinking and inactivation. It has previously been demonstrated by several research groups that Drosophila DHPAA synthase was expressed in tissues that produce cuticle materials and apparent defects in regions of colorless, flexible cuticular structures have been observed in its gene mutants. The presence of free amino groups in proteins, the high reactivity of DHPAA with the free amino groups, and the genetically ascertained function of the Drosophila DHPAA synthase in the formation of colorless, flexible cuticle, when taken together, suggest that mosquito and Drosophila DHPAA synthases are involved in the formation of flexible cuticle through their reactive DHPAA-mediated protein crosslinking reactions. Our data illustrate how a seemingly highly toxic pathway can serve for an important physiological function in insects

Fewer invited talks by women in evolutionary biology symposia.

Lower visibility of female scientists, compared to male scientists, is a potential reason for the under-representation of women among senior academic ranks. Visibility in the scientific community stems partly from presenting research as an invited speaker at organized meetings. We analysed the sex ratio of presenters at the European Society for Evolutionary Biology (ESEB) Congress 2011, where all abstract submissions were accepted for presentation. Women were under-represented among invited speakers at symposia (15% women) compared to all presenters (46%), regular oral presenters (41%) and plenary speakers (25%). At the ESEB congresses in 2001-2011, 9-23% of invited speakers were women. This under-representation of women is partly attributable to a larger proportion of women, than men, declining invitations: in 2011, 50% of women declined an invitation to speak compared to 26% of men. We expect invited speakers to be scientists from top ranked institutions or authors of recent papers in high-impact journals. Considering all invited speakers (including declined invitations), 23% were women. This was lower than the baseline sex ratios of early-mid career stage scientists, but was similar to senior scientists and authors that have published in high-impact journals. High-quality science by women therefore has low exposure at international meetings, which will constrain Evolutionary Biology from reaching its full potential. We wish to highlight the wider implications of turning down invitations to speak, and encourage conference organizers to implement steps to increase acceptance rates of invited talks