Histological response to injected gluteraldehyde cross-linked bovine collagen based implant in a rat model

BACKGROUND: The aim of present study is to investigate the short and long term histopathological alterations caused by submucosal injection of gluteraldehyde cross-linked bovine collagen based on an experimental rat model. METHODS: Sixty Sprague-Dawley rats were assigned into two groups as group I and II each containing 30 rats. 0.1 ml of saline solution and 0.1 ml of gluteraldehyde cross-linked bovine collagen were injected into the submucosa of bladder of first (control) and second groups, respectively. Both group I and II were further subdivided into 3 other groups as Group IA, IB, IC and Group IIA, IIB, IIC according to the sacrification period. Group IA and IIA, IB and IIB, IC and IIC rats (10 rats for each group) were sacrificed 3, 6, and 12 months after surgical procedure, respectively. Two slides prepared from injection site of the bladder were evaluated completely for each rat by being unaware of the groups and at random by two independent senior pathologists to determine the fibroblast invasion, collagen formation, capillary ingrowth and inflammatory reaction. Additionally, randomized brain sections from each rat were also examined to detect migration of the injection material. The measurements were made using an ocular micrometer at ×10 magnification. The results were assessed using t-tests for paired and independent samples, with p < 0.05 considered to indicate significant differences; all values were presented as the mean (SD). RESULTS: Migration to the brain was not detected in any group. Significant histopathological changes in the gluteraldehyde cross-linked bovine collagen injected groups were fibroblast invasion in 93.3%, collagen formation in 73.3%, capillary ingrowth in 46.6%, inflamatory reaction in 20%. CONCLUSION: We emphasize that the usage of gluteraldehyde cross-linked bovine collagen in children appears to be safe for endoscopic treatment of vesicoureteral reflux

2015 ACVIM Small Animal Consensus Statement on Seizure Management in Dogs

This report represents a scientific and working clinical consensus statement on seizure management in dogs based on current literature and clinical expertise. The goal was to establish guidelines for a predetermined, concise, and logical sequential approach to chronic seizure management starting with seizure identification and diagnosis (not included in this report), reviewing decision‐making, treatment strategies, focusing on issues related to chronic antiepileptic drug treatment response and monitoring, and guidelines to enhance patient response and quality of life. Ultimately, we hope to provide a foundation for ongoing and future clinical epilepsy research in veterinary medicine

A new small-bodied azhdarchoid pterosaur from the Lower Cretaceous of England and its implications for pterosaur anatomy, diversity and phylogeny

BACKGROUND: Pterosaurs have been known from the Cretaceous sediments of the Isle of Wight (southern England, United Kingdom) since 1870. We describe the three-dimensional pelvic girdle and associated vertebrae of a small near-adult pterodactyloid from the Atherfield Clay Formation (lower Aptian, Lower Cretaceous). Despite acknowledged variation in the pterosaur pelvis, previous studies have not adequately sampled or incorporated pelvic characters into phylogenetic analyses. METHODOLOGY/PRINCIPAL FINDINGS: The new specimen represents the new taxon Vectidraco daisymorrisae gen. et sp. nov., diagnosed by the presence of a concavity posterodorsal to the acetabulum and the form of its postacetabular process on the ilium. Several characters suggest that Vectidraco belongs to Azhdarchoidea. We constructed a pelvis-only phylogenetic analysis to test whether the pterosaur pelvis carries a useful phylogenetic signal. Resolution in recovered trees was poor, but they approximately matched trees recovered from analyses of total evidence. We also added Vectidraco and our pelvic characters to an existing total-evidence matrix for pterosaurs. Both analyses recovered Vectidraco within Azhdarchoidea. CONCLUSIONS/ SIGNIFICANCE: The Lower Cretaceous strata of western Europe have yielded members of several pterosaur lineages, but Aptian pterosaurs from western Europe are rare. With a pelvis length of 40 mm, the new animal would have had a total length of c. 350 mm, and a wingspan of c. 750 mm. Barremian and Aptian pterodactyloids from western Europe show that small-bodied azhdarchoids lived alongside ornithocheirids and istiodactylids. This assemblage is similar in terms of which lineages are represented to the coeval beds of Liaoning, China; however, the number of species and specimens present at Liaoning is much higher. While the general phylogenetic composition of western European and Chinese communities appear to have been approximately similar, the differences may be due to different palaeoenvironmental and depositional settings. The western Europe pterodactyloid record may therefore be artificially low in diversity due to preservational factors

Genetic and biochemical analyses of chromosome and plasmid gene homologues encoding ICL and ArCP domains in Vibrioanguillarum strain 775

Anguibactin, the siderophore produced by Vibrio anguillarum 775 is synthesized from 2,3-dihydroxybenzoic acid (DHBA), cysteine and hydroxyhistamine via a nonribosomal peptide synthetase (NRPS) mechanism. Most of the genes encoding anguibactin biosynthetic proteins are harbored by the pJM1 plasmid. In this work we report the identification of a homologue of the plasmid-encoded angB on the chromosome of strain 775. The product of both genes harbor an isochorismate lyase (ICL) domain that converts isochorismic acid to 2,3-dihydro-2,3-dihydroxybenzoic acid, one of the steps of DHBA synthesis. We show in this work that both ICL domains are functional in the production of DHBA in V. anguillarum as well as in E. coli. Substitution by alanine of the aspartic acid residue in the active site of both ICL domains completely abolishes their isochorismate lyase activity in vivo. The two proteins also carry an aryl carrier protein (ArCP) domain. In contrast with the ICL domains only the plasmid encoded ArCP can participate in anguibactin production as determined by complementation analyses and site-directed mutagenesis in the active site of the plasmid encoded protein, S248A. The site-directed mutants, D37A in the ICL domain and S248A in the ArCP domain of the plasmid encoded AngB were also tested in vitro and clearly show the importance of each residue for the domain function and that each domain operates independently.

Does offering an incentive payment improve recruitment to clinical trials and increase the proportion of socially deprived and elderly participants?

BACKGROUND: Patient recruitment into clinical trials is a major challenge, and the elderly, socially deprived and those with multiple comorbidities are often underrepresented. The idea of paying patients an incentive to participate in research is controversial, and evidence is needed to evaluate this as a recruitment strategy. METHOD: In this study, we sought to assess the impact on clinical trial recruitment of a £100 incentive payment and whether the offer of this payment attracted more elderly and socially deprived patients. A total of 1,015 potential patients for five clinical trials (SCOT, FAST and PATHWAY 1, 2 and 3) were randomised to receive either a standard trial invitation letter or a trial invitation letter containing an incentive offer of £100. To receive payment, patients had to attend a screening visit and consent to be screened (that is, sign a consent form). To maintain equality, eventually all patients who signed a consent form were paid £100. RESULTS: The £100 incentive offer increased positive response to the first invitation letter from 24.7% to 31.6%, an increase of 6.9% (P < 0.05). The incentive offer increased the number of patients signing a consent form by 5.1% (P < 0.05). The mean age of patients who responded positively to the invitation letter was 66.5 ± 8.7 years, whereas those who responded negatively were significantly older, with a mean age of 68.9 ± 9.0 years. The incentive offer did not influence the age of patients responding. The incentive offer did not improve response in the most socially deprived areas, and the response from patients in these areas was significantly lower overall. CONCLUSION: A £100 incentive payment offer led to small but significant improvements in both patient response to a clinical trial invitation letter and in the number of patients who consented to be screened. The incentive payment did not attract elderly or more socially deprived patients. TRIAL REGISTRATIONS: Standard care versus Celecoxib Outcome Trial (SCOT) (ClinicalTrials.gov identifier: NCT00447759). Febuxostat versus Allopurinol Streamlined Trial (FAST) (EudraCT number: 2011-001883-23). Prevention and Treatment of Hypertension with Algorithm Guided Therapy (British Heart Foundation funded trials) (PATHWAY) 1: Monotherapy versus dual therapy for initiating treatment (EudraCT number: 2008-007749-29). PATHWAY 2: Optimal treatment of drug-resistant hypertension (EudraCT number: 2008-007149-30). PATHWAY 3: Comparison of single and combination diuretics in low-renin hypertension (EudraCT number: 2009-010068-41). ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13063-015-0582-8) contains supplementary material, which is available to authorized users

Sources of Community Health Worker Motivation: A Qualitative Study in Morogoro Region, Tanzania.

There is a renewed interest in community health workers (CHWs) in Tanzania, but also a concern that low motivation of CHWs may decrease the benefits of investments in CHW programs. This study aimed to explore sources of CHW motivation to inform programs in Tanzania and similar contexts. We conducted semi-structured interviews with 20 CHWs in Morogoro Region, Tanzania. Interviews were digitally recorded, transcribed, and coded prior to translation and thematic analysis. The authors then conducted a literature review on CHW motivation and a framework that aligned with our findings was modified to guide the presentation of results. Sources of CHW motivation were identified at the individual, family, community, and organizational levels. At the individual level, CHWs are predisposed to volunteer work and apply knowledge gained to their own problems and those of their families and communities. Families and communities supplement other sources of motivation by providing moral, financial, and material support, including service fees, supplies, money for transportation, and help with farm work and CHW tasks. Resistance to CHW work exhibited by families and community members is limited. The organizational level (the government and its development partners) provides motivation in the form of stipends, potential employment, materials, training, and supervision, but inadequate remuneration and supplies discourage CHWs. Supervision can also be dis-incentivizing if perceived as a sign of poor performance. Tanzanian CHWs who work despite not receiving a salary have an intrinsic desire to volunteer, and their motivation often derives from support received from their families when other sources of motivation are insufficient. Policy-makers and program managers should consider the burden that a lack of remuneration imposes on the families of CHWs. In addition, CHWs' intrinsic desire to volunteer does not preclude a desire for external rewards. Rather, adequate and formal financial incentives and in-kind alternatives would allow already-motivated CHWs to increase their commitment to their work

International Veterinary Epilepsy Task Force consensus proposal: Medical treatment of canine epilepsy in Europe

In Europe, the number of antiepileptic drugs (AEDs) licensed for dogs has grown considerably over the last years. Nevertheless, the same questions remain, which include, 1) when to start treatment, 2) which drug is best used initially, 3) which adjunctive AED can be advised if treatment with the initial drug is unsatisfactory, and 4) when treatment changes should be considered. In this consensus proposal, an overview is given on the aim of AED treatment, when to start long-term treatment in canine epilepsy and which veterinary AEDs are currently in use for dogs. The consensus proposal for drug treatment protocols, 1) is based on current published evidence-based literature, 2) considers the current legal framework of the cascade regulation for the prescription of veterinary drugs in Europe, and 3) reflects the authors’ experience. With this paper it is aimed to provide a consensus for the management of canine idiopathic epilepsy. Furthermore, for the management of structural epilepsy AEDs are inevitable in addition to treating the underlying cause, if possible

Quantification of cAMP and cGMP analogs in intact cells: pitfalls in enzyme immunoassays for cyclic nucleotides

Immunoassays are routinely used as research tools to measure intracellular cAMP and cGMP concentrations. Ideally, this application requires antibodies with high sensitivity and specificity. The present work evaluates the cross-reactivity of commercially available cyclic nucleotide analogs with two non-radioactive and one radioactive cAMP and cGMP immunoassay. Most of the tested cyclic nucleotide analogs showed low degree competition with the antibodies; however, with Rp-cAMPS, 8-Br-cGMP and 8-pCPT-cGMP, a strong cross-reactivity with the corresponding cAMP and cGMP, respectively, immunoassays was observed. The determined EIA-binding constants enabled the measurement of the intracellular cyclic nucleotide concentrations and revealed a time- and lipophilicity-dependent cell membrane permeability of the compounds in the range of 10–30% of the extracellular applied concentration, thus allowing a more accurate prediction of the intracellular analog levels in a given experiment

Radical SAM enzyme QueE defines a new minimal core fold and metal-dependent mechanism

7-carboxy-7-deazaguanine synthase (QueE) catalyzes a key S-adenosyl-L-methionine (AdoMet)- and Mg[superscript 2+]-dependent radical-mediated ring contraction step, which is common to the biosynthetic pathways of all deazapurine-containing compounds. QueE is a member of the AdoMet radical superfamily, which employs the 5′-deoxyadenosyl radical from reductive cleavage of AdoMet to initiate chemistry. To provide a mechanistic rationale for this elaborate transformation, we present the crystal structure of a QueE along with structures of pre- and post-turnover states. We find that substrate binds perpendicular to the [4Fe-4S]-bound AdoMet, exposing its C6 hydrogen atom for abstraction and generating the binding site for Mg[superscript 2+], which coordinates directly to the substrate. The Burkholderia multivorans structure reported here varies from all other previously characterized members of the AdoMet radical superfamily in that it contains a hypermodified ([β [subscript 6] over α [subscript 3]]) protein core and an expanded cluster-binding motif, CX[subscript 14]CX[subscript 2]C.United States. Dept. of Energy. Office of Biological and Environmental ResearchUnited States. Dept. of Energy. Office of Basic Energy SciencesNational Center for Research Resources (U.S.) (P41RR012408)National Institute of General Medical Sciences (U.S.) (P41GM103473)National Center for Research Resources (U.S.) (5P41RR015301-10)National Institute of General Medical Sciences (U.S.) (8 P41 GM 103403-10)United States. Dept. of Energy (Contract DE-AC02-06CH11357