The future of canine glaucoma therapy

Canine glaucoma is a group of disorders that are generally associated with increased intraocular pressure (IOP) resulting in a characteristic optic neuropathy. Glaucoma is a leading cause of irreversible vision loss in dogs and may be either primary or secondary. Despite the growing spectrum of medical and surgical therapies, there is no cure, and many affected dogs go blind. Often eyes are enucleated because of painfully high, uncontrollable IOP. While progressive vision loss due to primary glaucoma is considered preventable in some humans, this is mostly not true for dogs. There is an urgent need for more effective, affordable treatment options. Because newly developed glaucoma medications are emerging at a very slow rate and may not be effective in dogs, work toward improving surgical options may be the most rewarding approach in the near term. This Viewpoint Article summarizes the discussions and recommended research strategies of both a Think Tank and a Consortium focused on the development of more effective therapies for canine glaucoma; both were organized and funded by the American College of Veterinary Ophthalmologists Vision for Animals Foundation (ACVO‐VAF). The recommendations consist of (a) better understanding of disease mechanisms, (b) early glaucoma diagnosis and disease staging, (c) optimization of IOP‐lowering medical treatment, (d) new surgical therapies to control IOP, and (e) novel treatment strategies, such as gene and stem cell therapies, neuroprotection, and neuroregeneration. In order to address these needs, increases in research funding specifically focused on canine glaucoma are necessary.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/151896/1/vop12678_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151896/2/vop12678.pd

Horizontal DNA transfer mechanisms of bacteria as weapons of intragenomic conflict

Horizontal DNA transfer (HDT) is a pervasive mechanism of diversification in many microbial species, but its primary evolutionary role remains controversial. Much recent research has emphasised the adaptive benefit of acquiring novel DNA, but here we argue instead that intragenomic conflict provides a coherent framework for understanding the evolutionary origins of HDT. To test this hypothesis, we developed a mathematical model of a clonally descended bacterial population undergoing HDT through transmission of mobile genetic elements (MGEs) and genetic transformation. Including the known bias of transformation toward the acquisition of shorter alleles into the model suggested it could be an effective means of counteracting the spread of MGEs. Both constitutive and transient competence for transformation were found to provide an effective defence against parasitic MGEs; transient competence could also be effective at permitting the selective spread of MGEs conferring a benefit on their host bacterium. The coordination of transient competence with cell-cell killing, observed in multiple species, was found to result in synergistic blocking of MGE transmission through releasing genomic DNA for homologous recombination while simultaneously reducing horizontal MGE spread by lowering the local cell density. To evaluate the feasibility of the functions suggested by the modelling analysis, we analysed genomic data from longitudinal sampling of individuals carrying Streptococcus pneumoniae. This revealed the frequent within-host coexistence of clonally descended cells that differed in their MGE infection status, a necessary condition for the proposed mechanism to operate. Additionally, we found multiple examples of MGEs inhibiting transformation through integrative disruption of genes encoding the competence machinery across many species, providing evidence of an ongoing "arms race." Reduced rates of transformation have also been observed in cells infected by MGEs that reduce the concentration of extracellular DNA through secretion of DNases. Simulations predicted that either mechanism of limiting transformation would benefit individual MGEs, but also that this tactic's effectiveness was limited by competition with other MGEs coinfecting the same cell. A further observed behaviour we hypothesised to reduce elimination by transformation was MGE activation when cells become competent. Our model predicted that this response was effective at counteracting transformation independently of competing MGEs. Therefore, this framework is able to explain both common properties of MGEs, and the seemingly paradoxical bacterial behaviours of transformation and cell-cell killing within clonally related populations, as the consequences of intragenomic conflict between self-replicating chromosomes and parasitic MGEs. The antagonistic nature of the different mechanisms of HDT over short timescales means their contribution to bacterial evolution is likely to be substantially greater than previously appreciated

Tracing the dynamic life story of a Bronze Age Female

YesAncient human mobility at the individual level is conventionally studied by the diverse application of suitable techniques (e.g. aDNA, radiogenic strontium isotopes, as well as oxygen and lead isotopes) to either hard and/or soft tissues. However, the limited preservation of coexisting hard and soft human tissues hampers the possibilities of investigating high-resolution diachronic mobility periods in the life of a single individual. Here, we present the results of a multidisciplinary study of an exceptionally well preserved circa 3.400-year old Danish Bronze Age female find, known as the Egtved Girl. We applied biomolecular, biochemical and geochemical analyses to reconstruct her mobility and diet. We demonstrate that she originated from a place outside present day Denmark (the island of Bornholm excluded), and that she travelled back and forth over large distances during the final months of her life, while consuming a terrestrial diet with intervals of reduced protein intake. We also provide evidence that all her garments were made of non-locally produced wool. Our study advocates the huge potential of combining biomolecular and biogeochemical provenance tracer analyses to hard and soft tissues of a single ancient individual for the reconstruction of high-resolution human mobility.The Danish National Research Foundation; The Carlsberg Foundation, L'Oreal Denmark-UNESCO; The ERC agreement no. 26944

Reliability of a tool for measuring theory of planned behaviour constructs for use in evaluating research use in policymaking

<p>Abstract</p> <p>Background</p> <p>Although measures of knowledge translation and exchange (KTE) effectiveness based on the theory of planned behavior (TPB) have been used among patients and providers, no measure has been developed for use among health system policymakers and stakeholders. A tool that measures the intention to use research evidence in policymaking could assist researchers in evaluating the effectiveness of KTE strategies that aim to support evidence-informed health system decision-making. Therefore, we developed a 15-item tool to measure four TPB constructs (intention, attitude, subjective norm and perceived control) and assessed its face validity through key informant interviews.</p> <p>Methods</p> <p>We carried out a reliability study to assess the tool's internal consistency and test-retest reliability. Our study sample consisted of 62 policymakers and stakeholders that participated in deliberative dialogues. We assessed internal consistency using Cronbach's alpha and generalizability (G) coefficients, and we assessed test-retest reliability by calculating Pearson correlation coefficients (<it>r</it>) and G coefficients for each construct and the tool overall.</p> <p>Results</p> <p>The internal consistency of items within each construct was good with alpha ranging from 0.68 to alpha = 0.89. G-coefficients were lower for a single administration (G = 0.34 to G = 0.73) than for the average of two administrations (G = 0.79 to G = 0.89). Test-retest reliability coefficients for the constructs ranged from <it>r </it>= 0.26 to <it>r </it>= 0.77 and from G = 0.31 to G = 0.62 for a single administration, and from G = 0.47 to G = 0.86 for the average of two administrations. Test-retest reliability of the tool using G theory was moderate (G = 0.5) when we generalized across a single observation, but became strong (G = 0.9) when we averaged across both administrations.</p> <p>Conclusion</p> <p>This study provides preliminary evidence for the reliability of a tool that can be used to measure TPB constructs in relation to research use in policymaking. Our findings suggest that the tool should be administered on more than one occasion when the intervention promotes an initial 'spike' in enthusiasm for using research evidence (as it seemed to do in this case with deliberative dialogues). The findings from this study will be used to modify the tool and inform further psychometric testing following different KTE interventions.</p

Dvegrajski zbornik, br. 4, zbornik radova znanstvenih skupova "Crtice uz povijesti Kanfanarštine" 2016. i 2017., gl. urednik Marko Jelenić, Kanfanar: Općina Kanfanar / Udruga za očuvanje i promociju nasljeđa - Dvegrajci, 2018., 287 str.

Antibiotic resistance forms a serious threat to the health of hospitalised patients, rendering otherwise treatable bacterial infections potentially life-threatening. A thorough understanding of the mechanisms by which resistance spreads between patients in different hospitals is required in order to design effective control strategies. We measured the differences between bacterial populations of 52 hospitals in the United Kingdom and Ireland, using whole-genome sequences from 1085 MRSA clonal complex 22 isolates collected between 1998 and 2012. The genetic differences between bacterial populations were compared with the number of patients transferred between hospitals and their regional structure. The MRSA populations within single hospitals, regions and countries were genetically distinct from the rest of the bacterial population at each of these levels. Hospitals from the same patient referral regions showed more similar MRSA populations, as did hospitals sharing many patients. Furthermore, the bacterial populations from different time-periods within the same hospital were generally more similar to each other than contemporaneous bacterial populations from different hospitals. We conclude that, while a large part of the dispersal and expansion of MRSA takes place among patients seeking care in single hospitals, inter-hospital spread of resistant bacteria is by no means a rare occurrence. Hospitals are exposed to constant introductions of MRSA on a number of levels: (1) most MRSA is received from hospitals that directly transfer large numbers of patients, while (2) fewer introductions happen between regions or (3) across national borders, reflecting lower numbers of transferred patients. A joint coordinated control effort between hospitals, is therefore paramount for the national control of MRSA, antibiotic-resistant bacteria and other hospital-associated pathogens

Target Deletion of the Cytoskeleton-Associated Protein Palladin Does Not Impair Neurite Outgrowth in Mice

Palladin is an actin cytoskeleton–associated protein which is crucial for cell morphogenesis and motility. Previous studies have shown that palladin is localized to the axonal growth cone in neurons and may play an important role in axonal extension. Previously, we have generated palladin knockout mice which display cranial neural tube closure defect and embryonic lethality before embryonic day 15.5 (E15.5). To further study the role of palladin in the developing nervous system, we examined the innervation of palladin-deficient mouse embryos since the 200 kd, 140 kd, 90–92 kd and 50 kd palladin isoforms were undetectable in the mutant mouse embryo brain. Contrary to the results of previous studies, we found no inhibition of the axonal extension in palladin-deficient mouse embryos. The cortical neurons derived from palladin-deficient mice also showed no significant difference in neurite outgrowth as compared with those from wild-type mice. Moreover, no difference was found in neurite outgrowth of neural stem cell derived-neurons between palladin-deficient mice and wild-type mice. In conclusion, these results suggest that palladin is dispensable for normal neurite outgrowth in mice

Using Vignettes in Qualitative Research to Explore Barriers and Facilitating Factors to the Uptake of Prevention of Mother-to-Child Transmission Services in Rural Tanzania: A Critical Analysis.

Vignettes are short stories about a hypothetical person, traditionally used within research (quantitative or qualitative) on sensitive topics in the developed world. Studies using vignettes in the developing world are emerging, but with no critical examination of their usefulness in such settings. We describe the development and application of vignettes to a qualitative investigation of barriers to uptake of prevention of mother-to-child transmission (PMTCT) HIV services in rural Tanzania in 2012, and critique the successes and challenges of using the technique in this setting. Participatory Learning and Action (PLA) group activities (3 male; 3 female groups from Kisesa, north-west Tanzania) were used to develop a vignette representing realistic experiences of an HIV-infected pregnant woman in the community. The vignette was discussed during in-depth interviews with 16 HIV-positive women, 3 partners/relatives, and 5 HIV-negative women who had given birth recently. A critical analysis was applied to assess the development, implementation and usefulness of the vignette. The majority of in-depth interviewees understood the concept of the vignette and felt the story was realistic, although the story or questions needed repeating in some cases. In-depth interviewers generally applied the vignette as intended, though occasionally were unsure whether to steer the conversation back to the vignette character when participants segued into personal experiences. Interviewees were occasionally confused by questions and responded with what the character should do rather than would do; also confusing fieldworkers and presenting difficulties for researchers in interpretation. Use of the vignette achieved the main objectives, putting most participants at ease and generating data on barriers to PMTCT service uptake. Participants' responses to the vignette often reflected their own experience (revealed later in the interviews). Participatory group research is an effective method for developing vignettes. A vignette was incorporated into qualitative interview discussion guides and used successfully in rural Africa to draw out barriers to PMTCT service use; vignettes may also be valuable in HIV, health service use and drug adherence research in this setting. Application of this technique can prove challenging for fieldworkers, so thorough training should be provided prior to its use

The context of HIV risk behaviours among HIV-positive injection drug users in Viet Nam: Moving toward effective harm reduction

<p>Abstract</p> <p>Background</p> <p>Injection drug users represent the largest proportion of all HIV reported cases in Viet Nam. This study aimed to explore the perceptions of risk and risk behaviours among HIV-positive injection drug users, and their experiences related to safe injection and safe sex practices.</p> <p>Methods</p> <p>This study used multiple qualitative methods in data collection including in-depth interviews, focus group discussions and participant observation with HIV-positive injection drug users.</p> <p>Results</p> <p>The informants described a change in the sharing practices among injection drug users towards more precautions and what was considered 'low risk sharing', like sharing among seroconcordant partners and borrowing rather than lending. However risky practices like re-use of injection equipment and 'syringe pulling' i.e. the use of left-over drugs in particular, were frequently described and observed. Needle and syringe distribution programmes were in place but carrying needles and syringes and particularly drugs could result in being arrested and fined. Fear of rejection and of loss of intimacy made disclosure difficult and was perceived as a major obstacle for condom use among recently diagnosed HIV infected individuals.</p> <p>Conclusion</p> <p>HIV-positive injection drug users continue to practice HIV risk behaviours. The anti-drug law and the police crack-down policy appeared as critical factors hampering ongoing prevention efforts with needle and syringe distribution programmes in Viet Nam. Drastic policy measures are needed to reduce the very high HIV prevalence among injection drug users.</p

Study of Radiologic Technologists’ Perceptions of Picture Archiving and Communication System (PACS) Competence and Educational Issues in Western Australia

Although the implementation of picture archiving and communication system (PACS) could increase productivity of radiology departments, this depends on factors such as the PACS competence of radiologic technologists (RTs). The purpose of this study was to investigate the RTs’ perceptions of PACS competence and educational issues in Western Australia (WA). A hardcopy questionnaire was distributed to WA RTs for obtaining their perceptions of PACS competence and educational issues. Descriptive (percentage of frequency, mean and standard deviation) and inferential statistics (t test and analysis of variance) were used to analyze the responses of the multiple choice and five-point scale questions from the returned questionnaires. The questionnaire response rate was 57.7 % (173 out of 300). The mean values of all PACS competence questions except questions 2e–g are in the range of 3.9–4.9, i.e., around competent to very competent. Participants indicated they received adequate PACS training (mean 3.8). Statistically significant variables influencing RTs’ perceptions of their PACS competence and educational issues including the age (p < 0.01), gender (p < 0.05), years of practice (p < 0.005–0.05), primary duty (p < 0.05), medical imaging qualification (p < 0.001), general computer skills (p < 0.001), and type of PACS education received (p < 0.001–0.05). The WA RTs indicated that they were competent in using the modality workstation, PACS and radiology information system, and received adequate training. However, future PACS education programs should be tailored to different RTs’ groups. For example, multiple training modules might be necessary to support the PACS competence development of older RTs and those with lower general computer literacy