Evaluation of the efficacy and safety of high dose short duration enrofloxacin treatment regimen for uncomplicated urinary tract infections in dogs.

BackgroundUncomplicated urinary tract infections (UTI) in dogs usually are treated with antimicrobial drugs for 10-14 days. Shorter duration antimicrobial regimens have been evaluated in human patients.HypothesisA high dose short duration (HDSD) enrofloxacin protocol administered to dogs with uncomplicated UTI will not be inferior to a 14-day treatment regimen with amoxicillin-clavulanic acid.AnimalsClient-owned adult, otherwise healthy dogs with aerobic bacterial urine culture yielding ≥ 10(3) CFU/mL of bacteria after cystocentesis.MethodsProspective, multicenter, controlled, randomized blinded clinical trial. Enrolled dogs were randomized to group 1 (enrofloxacin 18-20 mg/kg PO q24h for 3 days) or group 2 (amoxicillin-clavulanic acid 13.75-25 mg/kg PO q12h for 14 days). Urine cultures were obtained at days 0, 10, and 21. Microbiologic and clinical cure rates were evaluated 7 days after antimicrobial treatment was discontinued. Lower urinary tract signs and adverse events also were recorded.ResultsThere were 35 dogs in group 1 and 33 in group 2. The microbiologic cure rate was 77.1 and 81.2% for groups 1 and 2, respectively. The clinical cure rate was 88.6 and 87.9% for groups 1 and 2, respectively. Cure rates between groups did not differ according to the selected margin of noninferiority.Conclusions and clinical importanceHDSD enrofloxacin treatment was not inferior to a conventional amoxicillin-clavulanic acid protocol for the treatment of uncomplicated bacterial UTI in dogs. Further research is warranted to determine if this protocol will positively impact owner compliance and decrease the emergence of antimicrobial resistance

A new method for spike extraction using velocity selective recording demonstrated with physiological ENG in Rat

BACKGROUND: This paper describes a series of experiments designed to verify a new method of electroneurogram (ENG) recording that enables the rate of neural firing within prescribed bands of propagation velocity to be determined in real time. Velocity selective recording (VSR) has been proposed as a solution to the problem of increasing the information available from an implantable neural interface (typically with electrodes in circumferential nerve cuffs) and has been successful in transforming compound action potentials into the velocity domain. NEW METHOD: The new method extends VSR to naturally-evoked (physiological) ENG in which the rate of neural firing at particular velocities is required in addition to a knowledge of the velocities present in the recording. RESULTS: The experiments, carried out in rats required individual spikes to be distinct and non-overlapping, which could be achieved by a microchannel or small-bore cuff. In these experiments, strands of rat nerve were laid on ten hook electrodes in oil to demonstrate the principle. COMPARISON WITH EXISTING METHOD: The new method generates a detailed overview of the firing rates of neurons based on their conduction velocity and direction of propagation. In addition it allows real time working in contrast to existing spike sorting methods using statistical pattern processing techniques. CONCLUSIONS: Results show that by isolating neural activity based purely on conduction velocity it was possible to determine the onset of direct cutaneous stimulation of the L5 dermatome

Generating EQ-5D-3L health utility scores from the Edinburgh Postnatal Depression Scale: a perinatal mapping study

Background: Perinatal depression (PND) describes depression experienced by parents during pregnancy or in the first year after a baby is born. The EQ-5D instrument (a generic measure of health status) is not often collected in perinatal research, however disease-specific measures, such as the Edinburgh Postnatal Depression Scale (EPDS) are widely used. Mapping can be used to estimate generic health utility index values from disease-specific measures like the EPDS. Objective: To develop a mapping algorithm to estimate EQ-5D utility index values from the EPDS. Methods: Patient-level data from the BaBY PaNDA study (English observational cohort study) provided 1068 observations with paired EPDS and EQ-5D (3-level version; EQ-5D-3L) responses. We compared the performance of six alternative regression model types, each with four specifications of covariates (EPDS score and age: base, squared, and cubed). Model performance (ability to predict utility values) was assessed by ranking mean error, mean absolute error, and root mean square error. Algorithm performance in 3 external datasets was also evaluated. Results: There was moderate correlation between EPDS score and utility values (coefficient: – 0.42). The best performing model type was a two-part model, followed by ordinary least squared. Inclusion of squared and cubed covariates improved model performance. Based on graphs of observed and predicted utility values, the algorithm performed better when utility was above 0.6. Conclusions: This direct mapping algorithm allows the estimation of health utility values from EPDS scores. The algorithm has good external validity but is likely to perform better in samples with higher health status

Orthodontic treatment needs in the western region of Saudi Arabia: a research report

BACKGROUND: Evaluation of self perceived and actual need for orthodontic treatment helps in planning orthodontic services and estimating the required resources and man power. In the present study, the perceptive need as evaluated by patients and the actual need to orthodontic treatment, as assessed by orthodontists, were evaluated at two types of dental practices in the city of Jeddah using the Index of Orthodontic Treatment Need (IOTN). METHODS: A consecutive sample of 743 adults seeking orthodontic treatment at two different types of dental practices in Jeddah; King Abdulaziz University, Faculty of Dentistry (KAAU) (Free treatment) and two private dental polyclinics (PDP) (Paid treatment), was examined for orthodontic treatment need using the dental health component (DHC) of the IOTN. The self-perceived need for orthodontic treatment was also determined using the aesthetic component (AC) of the IOTN. The IOTN score and the incidence of each variable were calculated statistically. AC and DHC categories were compared using the Chi-Square and a correlation between them was assessed using Spearman's correlation test. AC and DHC were also compared between the two types of dental practices using the Chi-Square. RESULTS: The results revealed that among the 743 patients studied, 60.6% expressed no or slight need for treatment, 23.3% expressed moderate to borderline need and only16.1% thought they needed orthodontic treatment. Comparing these estimates to professional judgments, only 15.2% conformed to little or no need for treatment, 13.2% were assessed as in borderline need and 71.6% were assessed as in need for treatment (p < 0.001). Spearman's correlation test proved no correlation (r = -.045) between the two components. Comparing the AC and the DHC between the KAAU group and PDP group showed significant differences between the two groups (p < 0.001). CONCLUSION: Patient's perception to orthodontic treatment does not always correlate with professional assessment. The IOTN is a valid screening tool that should be used in orthodontic clinics for better services especially, in health centers that provide free treatment

Chaos around Holographic Regge Trajectories

Using methods of Hamiltonian dynamical systems, we show analytically that a dynamical system connected to the classical spinning string solution holographically dual to the principal Regge trajectory is non-integrable. The Regge trajectories themselves form an integrable island in the total phase space of the dynamical system. Our argument applies to any gravity background dual to confining field theories and we verify it explicitly in various supergravity backgrounds: Klebanov-Strassler, Maldacena-Nunez, Witten QCD and the AdS soliton. Having established non-integrability for this general class of supergravity backgrounds, we show explicitly by direct computation of the Poincare sections and the largest Lyapunov exponent, that such strings have chaotic motion.Comment: 28 pages, 5 figures. V3: Minor changes complying to referee's suggestions. Typos correcte

A randomized open-label trial on the use of budesonide/formoterol (Symbicort®) as an alternative reliever medication for mild to moderate asthmatic attacks

BACKGROUND Conventionally, a nebulized short-acting β-2 agonist like salbutamol is often used as the reliever in acute exacerbations of asthma. However, recent worldwide respiratory outbreaks discourage routine use of nebulization. Previous studies have shown that combined budesonide/formoterol (Symbicort®, AstraZeneca) is effective as both a maintenance and reliever anti-asthmatic medication. METHODS We performed a randomized, open-label study from March until August 2011 to compare the bronchodilatory effects of Symbicort® vs. nebulized salbutamol in acute exacerbation of mild to moderate asthmatic attack in an emergency department. Initial objective parameters measured include the oxygen saturation, peak expiratory flow rate (PEFR) and respiratory rate. During clinical reassessment, subjective parameters [i.e., Visual Analog Scale (VAS) and 5-point Likert scale of breathlessness] and the second reading of the objective parameters were measured. For the 5-point Likert scale, the patients were asked to describe their symptom relief as 1, much worse; 2, a little worse; 3, no change; 4, a little better; 5, much better. RESULTS Out of the total of 32 patients enrolled, 17 patients (53%) were randomized to receive nebulized salbutamol and 15 (47%) to receive Symbicort®. For both treatment arms, by using paired t- and Wilcoxon signed rank tests, it was shown that there were statistically significant improvements in oxygen saturation, PEFR and respiratory rate within the individual treatment groups (pre- vs. post-treatment). Comparing the effects of Symbicort® vs. nebulized salbutamol, the average improvement of oxygen saturation was 1% in both treatment arms (p = 0.464), PEFR 78.67 l/min vs. 89.41 l/min, respectively (p = 0.507), and respiratory rate 2/min vs. 2/min (p = 0.890). For subjective evaluation, all patients reported improvement in the VAS (average 2.45 cm vs. 2.20 cm), respectively (p = 0.765). All patients in both treatment arms reported either "a little better" or "much better" on the 5-point Likert scale, with none reporting "no change" or getting worse. CONCLUSION This study suggests that there is no statistical difference between using Symbicort® vs. nebulized salbutamol as the reliever for the first 15 min post-intervention

Microparticles from patients with metabolic syndrome induce vascular hypo-reactivity via Fas/Fas-ligand pathway in mice

Peer reviewedPublisher PD

Design of a prospective cohort study to assess ethnic inequalities in patient safety in hospital care using mixed methods

<p>Abstract</p> <p>Background</p> <p>While US studies show a higher risk of adverse events (AEs) for ethnic minorities in hospital care, in Europe ethnic inequalities in patient safety have never been analysed. Based on existing literature and exploratory research, our research group developed a conceptual model and empirical study to increase our understanding of the role ethnicity plays in patient safety. Our study is designed to (1) assess the risk of AEs for hospitalised patients of non-Western ethnic origin in comparison to ethnic Dutch patients; (2) analyse what patient-related determinants affect the risk of AEs; (3) explore the mechanisms of patient-provider interactions that may increase the risk of AEs; and (4) explore possible strategies to prevent inequalities in patient safety.</p> <p>Methods</p> <p>We are conducting a prospective mixed methods cohort study in four Dutch hospitals, which began in 2010 and is running until 2013. 2000 patients (1000 ethnic Dutch and 1000 of non-Western ethnic origin, ranging in age from 45-75 years) are included. Survey data are collected to capture patients’ explanatory variables (e.g., Dutch language proficiency, health literacy, socio-economic status (SES)-indicators, and religion) during hospital admission. After discharge, a two-stage medical record review using a standardized instrument is conducted by experienced reviewers to determine the incidence of AEs. Data will be analysed using multilevel multivariable logistic regression. Qualitative interviews with providers and patients will provide insight into the mechanisms of AEs and potential prevention strategies.</p> <p>Conclusion</p> <p>This study uses a robust study plan to quantify the risk difference of AEs between ethnic minority and Dutch patients in hospital care. In addition we are developing an in-depth description of the mechanisms of excess risk for some groups compared to others, while identifying opportunities for more equitable distributions of patient safety for all.</p

LIM and SH3 Protein -1 Modulates CXCR2-Mediated Cell Migration

BACKGROUND: The chemokine receptor CXCR2 plays a pivotal role in migration of neutrophils, macrophages and endothelial cells, modulating several biological responses such as angiogenesis, wound healing and acute inflammation. CXCR2 is also involved in pathogenesis of chronic inflammation, sepsis and atherosclerosis. The ability of CXCR2 to associate with a variety of proteins dynamically is responsible for its effects on directed cell migration or chemotaxis. The dynamic network of such CXCR2 binding proteins is termed as "CXCR2 chemosynapse". Proteomic analysis of proteins that co-immunoprecipitated with CXCR2 in neutrophil-like dHL-60 cells revealed a novel protein, LIM and SH3 protein 1 (LASP-1), binds CXCR2 under both basal and ligand activated conditions. LASP-1 is an actin binding cytoskeletal protein, involved in the cell migration. METHODOLOGY/PRINCIPAL FINDINGS: We demonstrate that CXCR2 and LASP-1 co-immunoprecipitate and co-localize at the leading edge of migrating cells. The LIM domain of LASP-1 directly binds to the carboxy-terminal domain (CTD) of CXCR2. Moreover, LASP-1 also directly binds the CTD of CXCR1, CXCR3 and CXCR4. Using a site-directed and deletion mutagenesis approach, Iso323-Leu324 of the conserved LKIL motif on CXCR2-CTD was identified as the binding site for LASP-1. Interruption of the interaction between CXCR2-CTD and LIM domain of LASP-1 by dominant negative and knock down approaches inhibited CXCR2-mediated chemotaxis. Analysis for the mechanism for inhibition of CXCR2-mediated chemotaxis indicated that LASP-1/CXCR2 interaction is essential for cell motility and focal adhesion turnover involving activation of Src, paxillin, PAK1, p130CAS and ERK1/2. CONCLUSIONS/SIGNIFICANCE: We demonstrate here for the first time that LASP-1 is a key component of the "CXCR2 chemosynapse" and LASP-1 interaction with CXCR2 is critical for CXCR2-mediated chemotaxis. Furthermore, LASP-1 also directly binds the CTD of CXCR1, CXCR3 and CXCR4, suggesting that LASP-1 is a general mediator of CXC chemokine mediated chemotaxis. Thus, LASP-1 may serve as a new link coordinating the flow of information between chemokine receptors and nascent focal adhesions, especially at the leading edge. Thus the association between the chemokine receptors and LASP-1 suggests to the presence of a CXC chemokine receptor-LASP-1 pro-migratory module in cells governing the cell migration

Societal Learning in Epidemics: Intervention Effectiveness during the 2003 SARS Outbreak in Singapore

BACKGROUND: Rapid response to outbreaks of emerging infectious diseases is impeded by uncertain diagnoses and delayed communication. Understanding the effect of inefficient response is a potentially important contribution of epidemic theory. To develop this understanding we studied societal learning during emerging outbreaks wherein patient removal accelerates as information is gathered and disseminated. METHODS AND FINDINGS: We developed an extension of a standard outbreak model, the simple stochastic epidemic, which accounts for societal learning. We obtained expressions for the expected outbreak size and the distribution of epidemic duration. We found that rapid learning noticeably affects the final outbreak size even when learning exhibits diminishing returns (relaxation). As an example, we estimated the learning rate for the 2003 outbreak of severe acute respiratory syndrome (SARS) in Singapore. Evidence for relaxation during the first eight weeks of the outbreak was inconclusive. We estimated that if societal learning had occurred at half the actual rate, the expected final size of the outbreak would have reached nearly 800 cases, more than three times the observed number of infections. By contrast, the expected outbreak size for societal learning twice as effective was 116 cases. CONCLUSION: These results show that the rate of societal learning can greatly affect the final size of disease outbreaks, justifying investment in early warning systems and attentiveness to disease outbreak by both government authorities and the public. We submit that the burden of emerging infections, including the risk of a global pandemic, could be efficiently reduced by improving procedures for rapid detection of outbreaks, alerting public health officials, and aggressively educating the public at the start of an outbreak