Development and validation of a questionnaire to assess owner and canine quality-of-life and treatment satisfaction in canine allergic dermatitis.

BACKGROUND: Animal and owner quality-of-life (QoL) is pivotal in treatment decisions. Accurate measurement of owner-reported QoL and treatment satisfaction (TS) supports disease burden and treatment benefit evaluation. OBJECTIVES: Develop and evaluate an owner-completed canine dermatitis QoL and TS questionnaire (CDQoL-TSQ) in allergic dogs. MATERIALS AND METHODS: The CDQoL-TSQ was drafted following review of existing measures and expert input. Content validity was assessed through interviews with owners of allergic dogs. Psychometric properties of the QoL domains (Canine QoL, Owner QoL) were evaluated. Score interpretation was derived. RESULTS: Twenty dog owners were interviewed. Item wording was amended following the first 10 interviews. Data from 211 owners were used in the psychometric evaluation. The Canine QoL domain demonstrated strong internal consistency (α = 0.89), test-retest reliability (ICC2,1 = 0.844), moderate convergent validity (r = 0.41) and moderate-high known-groups validity (effect size 0.37-0.64). The Owner QoL domain demonstrated strong internal consistency (α = 0.73), high convergent validity (r = 0.63) and moderate-high known-groups validity (0.43-0.63). Test-retest reliability approached moderate strength (ICC2,1 = 0.490). Group-level interpretation analysis showed minimal important difference of 7.0-13.6 points for dogs and 13.0-13.6 for owners. For individual dogs a change of 6.3 or 12.5 points for dogs, and 12.5 or 18.8 for owners indicates a response. CONCLUSIONS AND CLINICAL RELEVANCE: The CDQOL-TSQ is a two-part assessment to evaluate QoL and TS in canine allergic dermatitis. The QoL questionnaire demonstrated validity and reliability, and interpretation of scores was derived, making it suitable for use in research and practice. The TS module is suitable for clinical setting use to improve owner-veterinarian communication.

Medicalisation of vaping in the UK? E-cigarette users' perspectives on the merging of commercial and medical routes to vaping.

BACKGROUND: In the UK, most smokers choosing e-cigarettes to quit smoking will access vaping via commercial routes. In recent years, however, a shift towards medicalisation of vaping has become apparent, with public health guidance supporting e-cigarettes for smoking cessation and increased partnership working between healthcare professionals and the vaping industry. To achieve the UK's Smokefree 2030 target, the UK Government has set out measures to use e-cigarettes in National Health Service (NHS) settings and to move towards streamlining processes to make e-cigarettes available to a million smokers. This article aims to understand acceptability of different approaches by seeking perspectives of people with lived experience of e-cigarette use for smoking cessation. METHODS: Mixed methods data collected between March 2018 and March 2019 as part of a broader study of e-cigarette use trajectories (ECtra study). Data here relate to the views of partnership working and medicalisation of vaping extracted from 136 interviews/extended surveys of people who had used e-cigarettes to try to stop smoking. Qualitative data were thematically analysed. Participant ratings of interventions were presented descriptively, and differences in participant characteristics and ratings were reported. RESULTS: Three qualitative themes were identified: pro-partnership, anti-partnership and medicalisation dissonance. Medicalisation was discussed for its potential to reassure smokers about e-cigarette harms and its potential to reach smokers from disadvantaged backgrounds. Concerns were raised about cost-effectiveness, quality of support, conflicts of interest and limiting product choice. Most participants rated interventions involving partnership working as potentially helpful in switching from smoking to vaping. There were no statistically significant associations between age, gender and socioeconomic status, and helpfulness ratings. CONCLUSION: Both commercial and medical routes to vaping offer perceived benefits to vapers and may complement and reinforce each other to support smoking cessation.

Higher Incidence of Unruptured Intracranial Aneurysms among Black and Hispanic Women on Screening MRA in Large Urban Populations.

BACKGROUND AND PURPOSE: Intracranial aneurysms have a reported prevalence of 1%-2% in the general population. Currently, only patients with a strong family history or autosomal dominant polycystic kidney disease are screened for intracranial aneurysms using MRA. The purpose of this study was to determine whether there are other specific patient populations at risk that should be offered screening for intracranial aneurysms. MATERIALS AND METHODS: This is a retrospective case-control study of adult patients who underwent a screening MRA of their brain at our comprehensive stroke center from 2011 to 2020. Patients with a history of a known brain aneurysm were excluded. Data were extracted on patient demographics and medical comorbidities. Bivariate analyses were performed, followed by multivariable logistic regression, to identify factors associated with a positive MRA screen for incidental aneurysms. RESULTS: Of 24,397 patients eligible for this study, 2084 screened positive for a possible intracranial aneurysm. On bivariate analysis, significant differences were present in the following categories: age, sex, race and ethnicity, chronic constipation, and hyperlipidemia. On logistic regression analysis, older age (+10 years: OR = 10.01; 95% CI, 10.01-10.02; P = .001), female sex (OR = 1.37; 95% CI, 1.24-1.51; P = .001), non-Hispanic Black (OR = 1.19; 95% CI, 1.02-1.40; P = .031), and Hispanic ethnicity (OR = 1.35; 95% CI, 1.16-1.58; P = .001) versus non-Hispanic White remained significant when adjusted for other factors. CONCLUSIONS: Targeted screening for high-risk elderly women of Black or Hispanic descent will yield higher positive findings for brain aneurysms, which may mitigate the risk of rupture. Whether this is a cost-effective approach has yet to be determined.

Evaluation of a training programme for Pharmacist Independent Prescribers in a care home medicine management intervention.

BACKGROUND: The provision of independent prescribing rights for United Kingdom (UK) pharmacists has enabled them to prescribe within their area of competence. The aim of this study was to evaluate an evidence-based training programme designed to prepare Pharmacist Independent Prescribers (PIPs) to safely and effectively assume responsibility for pharmaceutical care of older people in care homes in the UK, within a randomised controlled trial. METHODS: The training and competency assessment process included two training days, professional development planning against a bespoke competency framework, mentor support, and a viva with an independent General Practitioner (GP). Data on the PIPs' perceptions of the training were collected through evaluation forms immediately after the training days and through online questionnaires and interviews after delivery of the 6-month intervention. Using a mixed method approach each data set was analysed separately then triangulated providing a detailed evaluation of the process. Kaufman's Model of Learning Evaluation guided interpretations. RESULTS: All 25 PIPs who received the training completed an evaluation form (N = 25). Post-intervention questionnaires were completed by 16 PIPs and 14 PIPs took part in interviews. PIPs reported the training days and mentorship enabled them to develop a personalised portfolio of competence in preparation for discussion during a viva with an independent GP. Contact with the mentor reduced as PIPs gained confidence in their role. PIPs applied their new learning throughout the delivery of the intervention leading to perceived improvements in residents' quality of life and medicines management. A few PIPs reported that developing a portfolio of competence was time intensive, and that further training on leadership skills would have been beneficial. CONCLUSIONS: The bespoke training programme was fit for purpose. Mentorship and competency assessment were resource intensive but appropriate. An additional benefit was that many PIPs reported professional growth beyond the requirement of the study. TRIAL REGISTRATION: The definitive RCT was registered with the ISRCTN registry (registration number ISRCTN 17,847,169 ).

Determining of canine position by multiple facial landmarks to achieve natural esthetics in complete denture treatment.

STATEMENT OF PROBLEM: Anterior tooth selection is an important step in complete denture treatment as it plays a pivotal role not only in esthetics but also in mastication and pronunciation. However, conventional methods for tooth selection are not well established and rely on facial measurements and proportions, which vary among different ethnicities. PURPOSE: The purpose of this clinical study was to investigate the relationship between interalar width and intercanine distance and to compare different clinical methods for determining the position of the canine tooth. MATERIAL AND METHODS: Two hundred Thai participants (100 men and 100 women) aged 18 to 25 years with 6 full maxillary anterior teeth were enrolled in this study. The interalar width and intercanine distance were measured with digital vernier calipers and compared by using the paired-samples t test. To determine the canine position, 2 reference lines-the alar line (A line) and the inner canthus of the eye to alar line (IA line)-were drawn through the canine on both sides. The horizontal distances from each reference line to the canine cusp tip and distal contact point were evaluated and then analyzed using the 1-sample t test. RESULTS: All measurements were significantly different between men and women (P<.01). Interalar width was greater than intercanine distance in both sexes. In men, the A line coincided with the canine distal contact point (P>.05). In contrast, the IA line was distal to the canine distal contact point by 3.5 ±3.6 mm on the left side and by 3.9 ±3.4 mm on the right side. In women, the A line was situated between the canine cusp tip and distal contact point. It was mesial to the distal contact point by 2.0 ±2.0 mm on the left side and by 1.8 ±2.0 mm on the right side. The IA line was distal to the canine distal contact point by 1.2 ±2.6 mm on the left side and by 1.6 ±2.7 mm on the right side. CONCLUSIONS: The interalar width is greater than the intercanine distance in both sexes. The A line is more clinically relevant than the IA line for predicting canine position. The A line can directly determine the distal contact point of the canine in edentulous male patients. However, in women, a distance of approximately 2 mm should be added distal to the A line to locate the distal contact point of the canine on both sides.

Long-term cost-effectiveness of screening for fracture risk in a UK primary care setting: the SCOOP study.

Community-based screening and treatment of women aged 70-85 years at high fracture risk reduced fractures; moreover, the screening programme was cost-saving. The results support a case for a screening programme of fracture risk in older women in the UK. INTRODUCTION: The SCOOP (screening for prevention of fractures in older women) randomized controlled trial investigated whether community-based screening could reduce fractures in women aged 70-85 years. The objective of this study was to estimate the long-term cost-effectiveness of screening for fracture risk in a UK primary care setting compared with usual management, based on the SCOOP study. METHODS: A health economic Markov model was used to predict the life-time consequences in terms of costs and quality of life of the screening programme compared with the control arm. The model was populated with costs related to drugs, administration and screening intervention derived from the SCOOP study. Fracture risk reduction in the screening arm compared with the usual management arm was derived from SCOOP. Modelled fracture risk corresponded to the risk observed in SCOOP. RESULTS: Screening of 1000 patients saved 9 hip fractures and 20 non-hip fractures over the remaining lifetime (mean 14 years) compared with usual management. In total, the screening arm saved costs (£286) and gained 0.015 QALYs/patient in comparison with usual management arm. CONCLUSIONS: This analysis suggests that a screening programme of fracture risk in older women in the UK would gain quality of life and life years, and reduce fracture costs to more than offset the cost of running the programme.

Screening for high hip fracture risk does not impact on falls risk: a post hoc analysis from the SCOOP study.

A reduction in hip fracture incidence following population screening might reflect the effectiveness of anti-osteoporosis therapy, behaviour change to reduce falls, or both. This post hoc analysis demonstrates that identifying high hip fracture risk by FRAX was not associated with any alteration in falls risk. INTRODUCTION: To investigate whether effectiveness of an osteoporosis screening programme to reduce hip fractures was mediated by modification of falls risk in the screening arm. METHODS: The SCOOP study recruited 12,483 women aged 70-85 years, individually randomised to a control (n = 6250) or screening (n = 6233) arm; in the latter, osteoporosis treatment was recommended to women at high risk of hip fracture, while the control arm received usual care. Falls were captured by self-reported questionnaire. We determined the influence of baseline risk factors on future falls, and then examined for differences in falls risk between the randomisation groups, particularly in those at high fracture risk. RESULTS: Women sustaining one or more falls were slightly older at baseline than those remaining falls free during follow-up (mean difference 0.70 years, 95%CI 0.55-0.85, p < 0.001). A higher FRAX 10-year probability of hip fracture was associated with increased likelihood of falling, with fall risk increasing by 1-2% for every 1% increase in hip fracture probability. However, falls risk factors were well balanced between the study arms and, importantly, there was no evidence of a difference in falls occurrence. In particular, there was no evidence of interaction (p = 0.18) between baseline FRAX hip fracture probabilities and falls risk in the two arms, consistent with no impact of screening on falls in women informed to be at high risk of hip fracture. CONCLUSION: Effectiveness of screening for high FRAX hip fracture probability to reduce hip fracture risk was not mediated by a reduction in falls.

Systematic screening using FRAX® leads to increased use of, and adherence to, anti-osteoporosis medications: an analysis of the UK SCOOP trial.

In the large community-based SCOOP trial, systematic fracture risk screening using FRAX® led to greater use of AOM and greater adherence, in women at high fracture risk, compared with usual care. INTRODUCTION: In the SCreening of Older wOmen for Prevention of fracture (SCOOP) trial, we investigated the effect of the screening intervention on subsequent long-term self-reported adherence to anti-osteoporosis medications (AOM). METHODS: SCOOP was a primary care-based UK multicentre trial of screening for fracture risk. A total of 12,483 women (70-85 years) were randomised to either usual NHS care, or assessment using the FRAX® tool ± dual-energy X-ray absorptiometry (DXA), with medication recommended for those found to be at high risk of hip fracture. Self-reported AOM use was obtained by postal questionnaires at 6, 12, 24, 36, 48 and 60 months. Analysis was limited to those who initiated AOM during follow-up. Logistic regression was used to explore baseline determinants of adherence (good ≥ 80%; poor < 80%). RESULTS: The mean (SD) age of participants was 75.6 (4.2) years, with 6233 randomised to screening and 6250 to the control group. Of those participants identified at high fracture risk in the screening group, 38.2% of those on treatment at 6 months were still treated at 60 months, whereas the corresponding figure for the control group was 21.6%. Older age was associated with poorer adherence (OR per year increase in age 0.96 [95% CI 0.93, 0.99], p = 0.01), whereas history of parental hip fracture was associated with greater rate adherence (OR 1.67 [95% CI 1.23, 2.26], p < 0.01). CONCLUSIONS: Systematic fracture risk screening using FRAX® leads to greater use of AOM and greater adherence, in women at high fracture risk, compared with usual care.

Inflammatory microglia are glycolytic and iron retentive and typify the microglia in APP/PS1 mice.

Microglia, like macrophages, can adopt inflammatory and anti-inflammatory phenotypes depending on the stimulus. In macrophages, the evidence indicates that these phenotypes have different metabolic profiles with lipopolysaccharide (LPS)- or interferon-γ (IFNγ)-stimulated inflammatory cells switching to glycolysis as their main source of ATP and interleukin-4 (IL-4)-stimulated cells utilizing oxidative phosphorylation. There is a paucity of information regarding the metabolic signatures of inflammatory and anti-inflammatory microglia. Here, we polarized primary microglia with IFNγ and show that the characteristic increases in tumor necrosis factor-α (TNFα) and nitric oxide synthase 2 (NOS2) were accompanied by increased glycolysis and an increase in the expression of 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase (PFKFB)3, an enzyme that plays a significant role in driving glycolysis. These changes were associated with increased expression of ferritin and retention of iron in microglia. Significantly, retention of iron in microglia increased TNFα expression and also increased glycolysis suggesting that increased intracellular iron concentration may drive the metabolic and/or inflammatory changes. Analysis of microglia prepared from wildtype mice and from transgenic mice that overexpress amyloid precursor protein (APP) and presenilin 1 (PS1; APP/PS1) revealed genotype-related increases in glycolysis, accompanied by increased PFKFB3, and an increase in the expression of ferritin. The data indicate a distinct metabolic signature of inflammatory microglia from APP/PS1 mice that are also distinguishable by their iron handling profiles.

Study protocol for a randomised pragmatic trial comparing the clinical and cost effectiveness of lithium and quetiapine augmentation in treatment resistant depression (the LQD study).

BACKGROUND: Approximately 30-50% of patients with major depressive disorder can be classed as treatment resistant, widely defined as a failure to respond to two or more adequate trials of antidepressants in the current episode. Treatment resistant depression is associated with a poorer prognosis and higher mortality rates. One treatment option is to augment an existing antidepressant with a second agent. Lithium and the atypical antipsychotic quetiapine are two such add-on therapies and are currently recommended as first line options for treatment resistant depression. However, whilst neither treatment has been established as superior to the other in short-term studies, they have yet to be compared head-to-head in longer term studies, or with a superiority design in this patient group. METHODS: The Lithium versus Quetiapine in Depression (LQD) study is a parallel group, multi-centre, pragmatic, open-label, patient randomised clinical trial designed to address this gap in knowledge. The study will compare the clinical and cost effectiveness of the decision to prescribe lithium or quetiapine add-on therapy to antidepressant medication for patients with treatment resistant depression. Patients will be randomised 1:1 and followed up over 12 months, with the hypothesis being that quetiapine will be superior to lithium. The primary outcomes will be: (1) time to all-cause treatment discontinuation over one year, and (2) self-rated depression symptoms rated weekly for one year via the Quick Inventory of Depressive Symptomatology. Other outcomes will include between group differences in response and remission rates, quality of life, social functioning, cost-effectiveness and the frequency of serious adverse events and side effects. DISCUSSION: The trial aims to help shape the treatment pathway for patients with treatment resistant depression, by determining whether the decision to prescribe quetiapine is superior to lithium. Strengths of the study include its pragmatic superiority design, broad inclusion criteria (external validity) and longer follow up than previous studies. TRIAL REGISTRATION: ISRCTN registry: ISRCTN16387615 , registered 28 February 2016. ClinicalTrials.gov: NCT03004521 , registered 17 November 2016.

Supervised pharmacy student-led medication review in primary care for patients with type 2 diabetes: a randomised controlled pilot study.

OBJECTIVE: To pilot and feasibility-test supervised final year undergraduate pharmacy student-led medication reviews for patients with diabetes to enable definitive trial design. METHOD: Third year pharmacy students were recruited from one UK School of Pharmacy and trained to review patient's medical records and provide face-to-face consultations under supervision while situated within the patient's medical practice. Patients with type 2 diabetes were recruited by postal invitation letter from their medical practice and randomised via automated system to intervention or usual care. Diabetes-related clinical data, quality of life, patient reported beliefs, adherence and satisfaction with medicines information were collected with validated tools at baseline and 6 months postintervention. The process for collecting resource utilisation data was tested. Stakeholder meetings were held before and after intervention to develop study design and learn from its implementation. Recruitment and attrition rates were determined plus the quality of the outcome data. Power calculations for a definitive trial were performed on the different outcome measures to identify the most appropriate primary outcome measure. RESULTS: 792 patients were identified as eligible from five medical practices. 133 (16.8%) were recruited and randomised to control (n=66) or usual care (n=67). 32 students provided the complete intervention to 58 patients. Initial data analysis showed potential for impact in the right direction for some outcomes measured including glycated haemoglobin, quality of life and patient satisfaction with information about medicines. The intervention was found to be feasible and acceptable to patients. The pilot and feasibility study enabled the design of a future full randomised controlled trial. CONCLUSIONS: Student and patient recruitment are possible. The intervention was well received and demonstrated some potential benefits. While the intervention was relatively inexpensive and provided an experiential learning opportunity for pharmacy students, its cost-effectiveness remains to be determined. TRIAL REGISTRATION NUMBER: ISRCTN26445805; Results.

A cohort study of influences, health outcomes and costs of patients' health-seeking behaviour for minor ailments from primary and emergency care settings.

OBJECTIVES: To compare health-related and cost-related outcomes of consultations for symptoms suggestive of minor ailments in emergency departments (EDs), general practices and community pharmacies. DESIGN: Observational study; prospective cohort design. SETTING: EDs (n=2), general practices (n=6) and community pharmacies (n=10) in a mix of rural/urban and deprived/affluent areas across North East Scotland and East Anglia. Participants Adults (≥18 years) presenting between 09:00 and 18:00 (Monday-Friday) in general practices and 09:00-18:00 (Monday-Saturday) in pharmacies and EDs with ≥1 of the following: musculoskeletal pain; eye discomfort; gastrointestinal disturbance; or upper respiratory tract-related symptoms. INTERVENTIONS: Participants completed three questionnaires: baseline (prior to index consultation); satisfaction with index consultation and follow-up (2 weeks after index consultation). MAIN OUTCOME MEASURES: Symptom resolution, quality of life, costs, satisfaction and influences on care-seeking behaviour. RESULTS: 377 patients participated, recruited from EDs (81), general practices (162) and community pharmacies (134). The 2-week response rate was 70% (264/377). Symptom resolution was similar across all three settings: ED (37.3%), general practice (35.7%) and pharmacy (44.3%). Mean overall costs per consultation were significantly lower for pharmacy (£29.30 (95% CI £21.60 to £37.00)) compared with general practice (£82.34 (95% CI £63.10 to £101.58)) and ED (£147.09 (95% CI £125.32 to £168.85)). Satisfaction varied across settings and by measure used. Compared with pharmacy and general practice use, ED use was significantly (p<0.001) associated with first episode and short duration of symptom(s), as well as higher levels of perceived seriousness and urgency for seeking care. Convenience of location was the most common reason for choice of consultation setting. CONCLUSIONS: These results suggest similar health-related outcomes and substantially lower costs with pharmacy consultations for minor ailments. Effective strategies are now needed to shift demand for minor ailment management away from EDs and general practices to the community pharmacy setting.

Spatio-temporal modelling of disease incidence with missing covariate values.

The search for an association between disease incidence and possible risk factors using surveillance data needs to account for possible spatial and temporal correlations in underlying risk. This can be especially difficult if there are missing values for some important covariates. We present a case study to show how this problem can be overcome in a Bayesian analysis framework by adding to the usual spatio-temporal model a component for modelling the missing data.

Comprehensive dietary education in treated gout patients does not further improve serum urate.

BACKGROUND/AIM: This study aims to investigate the influence of dietary education in patients with gout on a stable dose of urate-lowering therapy (ULT). METHODS: Males and females aged >18 years with a history of gout, receiving an appropriate and stable dose of ULT, were recruited from two tertiary hospitals and randomised into two groups. The control group received basic advice regarding the importance of compliance with therapy and the benefit of weight loss. The intervention group received comprehensive dietary advice based on the British Society of Rheumatology Guidelines. Both groups received education at baseline and 3 months. Serum urate was measured at baseline, 3 months and 6 months, and a questionnaire was completed at baseline and at 6 months. The primary outcome of the study was to compare the change in serum urate between groups. RESULTS: Thirty patients were recruited into the study. There was no difference in serum urate between the control and intervention group at 6 months (0.29 mmol/L vs 0.29 mmol/L at baseline and 0.27 mmol/L vs 0.30 mmol/L at 6 months). The intervention group showed a statistically significant improvement in knowledge (8/13 in control group at baseline to 9/13 at 6 months vs 8/13 in intervention group at baseline to 12/13 at 6 months, P < 0.05) and self-reported dietary modification (1 in control vs 7 in intervention P < 0.05) at 6 months. CONCLUSION: This randomised controlled trial shows that in patients on ULT, providing education on diet does not lead to any clinically significant difference in serum urate at 6 months.

Does medical futility matter in 'do not attempt CPR' decision-making?

The current demographical trend towards an increasingly elderly population combined with advances in end of life care calls for a deeper understanding and common terminology about the concept of futility and additional influences on the resuscitation decision-making process. Such improved understanding of medical futility and other contributing factors when making DNACPR orders would help to ensure that clinicians make appropriate and thoughtful decisions on whether to recommend resuscitation in a patient. When estimating medical futility a physician should consider the chance of survival over different time periods and balance this against the chance of adverse outcomes. This information can then be offered to the patient (or the relatives) so that the patient's views about what is acceptable for the survival chance, length and type of survival can be factored into the eventual decision. Given the lack of evidence in this area and the poor level of patient knowledge and the emotive nature of the topic, it is not surprising that clinicians find such discussions hard.

Biomarkers: refining diagnosis and expediting drug development - reality, aspiration and the role of open innovation.

In the last decade, there have been intensive efforts to invent, qualify and use novel biomarkers as a means to improve success rates in drug discovery and development. The biomarkers field is maturing and this article considers whether these research efforts have brought about the expected benefits. The characteristics of a clinically useful biomarker are described and the impact this area of research has had is evaluated by reviewing a few, key examples of emerging biomarkers. There is evidence that the impact has been genuine and is increasing in both the drug and the diagnostic discovery and development processes. Beneficial impact on patient health outcomes seems relatively limited thus far, with the greatest impact in oncology (again, both in terms of novel drugs and in terms of more refined diagnoses and therefore more individualized treatment). However, the momentum of research would indicate that patient benefits are likely to increase substantially and to broaden across multiple therapeutic areas. Even though this research was originally driven by a desire to improve the drug discovery and development process, and was therefore funded with this aim in mind, it seems likely that the largest impact may actually come from more refined diagnosis. Refined diagnosis will facilitate both better allocation of healthcare resources and the use of treatment regimens which are optimized for the individual patient. This article also briefly reviews emerging technological approaches and how they relate to the challenges inherent in biomarker discovery and validation, and discusses the role of public/private partnerships in innovative biomarker research.

Encapsulation and delivery of plasmid DNA by virus-like nanoparticles engineered from Macrobrachium rosenbergii nodavirus.

Virus-like particles (VLPs) are potential candidates in developing biological containers for packaging therapeutic or biologically active agents. Here, we expressed Macrobrachium rosenbergii nodavirus (MrNv) capsid protein (encoding amino acids M1-N371 with 6 histidine residuals) in an Escherichia coli BL21(DE3). These easily purified capsid protein self-assembled into VLPs, and disassembly/reassembly could be controlled in a calcium-dependent manner. Physically, MrNv VLPs resisted to digestive enzymes, a property that should be advantageous for protection of active compounds against harsh conditions. We also proved that MrNv VLPs were capable of encapsulating plasmid DNA in the range of 0.035-0.042 mol ratio (DNA/protein) or 2-3 plasmids/VLP (assuming that MrNV VLPs is T=1, i made up of 60 capsid monomers). These VLPs interacted with cultured insect cells and delivered loaded plasmid DNA into the cells as shown by green fluorescent protein (GFP) reporter. With many advantageous properties including self-encapsulation, MrNv VLPs are good candidates for delivery of therapeutic agents.

Wrinkle reduction in post-menopausal women consuming a novel oral supplement: a double-blind placebo-controlled randomized study.

OBJECTIVE: The maintenance of youthful skin appearance is strongly desired by a large proportion of the world's population. The aim of the present study was therefore to evaluate the effect on skin wrinkling, of a combination of ingredients reported to influence key factors involved in skin ageing, namely inflammation, collagen synthesis and oxidative/UV stress. A supplemented drink was developed containing soy isoflavones, lycopene, vitamin C and vitamin E and given to post-menopausal women with a capsule containing fish oil. METHOD: We have performed a double-blind randomized controlled human clinical study to assess whether this cocktail of dietary ingredients can significantly improve the appearance of facial wrinkles. RESULTS: We have shown that this unique combination of micronutrients can significantly reduce the depth of facial wrinkles and that this improvement is associated with increased deposition of new collagen fibres in the dermis. CONCLUSION: This study demonstrates that consumption of a mixture of soy isoflavones, lycopene, vitamin C, vitamin E and fish oil is able to induce a clinically measureable improvement in the depth of facial wrinkles following long-term use. We have also shown, for the first time with an oral product, that the improvement is associated with increased deposition of new collagen fibres in the dermis.

Distribution of Xylella fastidiosa in Blueberry Stem and Root Sections in Relation to Disease Severity in the Field.

Xylella fastidiosa causes bacterial leaf scorch, a new disease of southern highbush blueberry in the southeastern United States. Infections occlude the xylem of affected plants, causing drought-like symptoms and, eventually, plant death. To assess the likelihood of mitigation of bacterial leaf scorch through cultural practices such as pruning or hedging of affected plants, we determined the localization and population density of X. fastidiosa in naturally infected blueberry plants with varying levels of bacterial leaf scorch severity. Stem segments were sampled from the current season's growth down to the base of the plant, as were root segments on plants that were either asymptomatic or had light, moderate, or severe symptoms in three plantings affected by the disease. Stem sap was extracted from each segment and population densities of X. fastidiosa were determined using real-time polymerase chain reaction with species-specific primers. Detection frequencies were lowest (but non-zero) in sap from asymptomatic plants and highest in plants with severe symptoms. In asymptomatic plants, detection was generally least frequent (0 to 20.0%) in top and root sections and highest (4.6 to 55.6%) in middle and base stem sections. As disease severity increased, detection frequencies in roots increased to >80% in two plantings and to 60% in the third planting. Overall, detection frequencies were highest (>80%) in middle and base stem sections of plants from the moderate and severe disease classes. The lowest bacterial titers (averaging 0 to 2.1 × 101 CFU per 50 µl of sap) were observed in top and root sections of asymptomatic plants, whereas the highest titers (generally between 104 and 105 CFU per 50 µl of sap) were obtained from middle, base, and root sections of plants from the moderate and severe classes. The presence of the bacterium in middle and base stem sections at low disease severity indicates rapid distribution of X. fastidiosa in affected plants. Because the pathogen accumulates in the roots at moderate and high disease severity levels, management strategies such as pruning and mowing are unlikely to be effective in curing affected plants from bacterial leaf scorch.

Estimating the comparative clinical and economic consequences of tulathromycin for treatment of present or anticipated outbreaks of bovine respiratory disease in feedlot cattle in the United States.

The goal of this study was to determine the clinical and economic impact of using tulathromycin as first line treatment for bovine respiratory disease (BRD) compared with other commonly used antimicrobials. Two decision trees were developed simulating the consequences of treating cattle at high risk of developing BRD [control model (CM)] or cattle with first clinical BRD episode [treatment model (TM)]. As comparators florfenicol and tilmicosin were considered in both models whereas enrofloxacin was included in the TM because it was only labeled for treatment of BRD at the time of development of the calculators. A total of 5 (CM) and 10 (TM) comparative clinical studies that reported efficacy data for the selected drugs and indications were identified as suitable for model population. The following outcomes were considered: first treatment success, number of subsequent BRD treatments, chronics, and mortalities. Cost parameters were considered from the perspective of the producer and included treatment costs (first treatment and retreatments) and costs of chronics and deaths derived from published sources for 2010 (default). The models allowed the estimation of clinical and economic consequences according to each individual trial outcomes. Treatment with tulathromycin resulted in more first treatment successes and fewer removals (chronics and deaths) in all comparisons. The average total number of antimicrobial treatments required for the management of BRD was also least with tulathromycin as first treatment option. Because of better efficacy, total costs over the entire study periods were always lowest with tulathromycin. Depending on the study selected as the basis for the efficacy evaluation, cost savings with tulathromycin were calculated in the CM between US$21.00 and $47.86 (vs. florfenicol) and $11.37 and $72.64 (vs. tilmicosin); cost savings in the TM ranged between $28.47 and $143.87 (vs. florfenicol) and $7.75 and $84.91 (vs. tilmicosin) as well as between $23.22 and $47.82 (vs. enrofloxacin), with the ranges reflecting a variety of settings in different trials. Thus, the higher drug costs of tulathromycin were more than offset by reduced BRD treatments, chronics, and mortalities in the herd. Fewer BRD episodes in cattle treated with tulathromycin not only contributes to overall savings in BRD management but also reduces the necessity of repeated antibiotic treatment, supporting prudent use of antimicrobials in livestock.