What Is the Best Option for Treating Venous Leg Ulcer Infection? Is It Systemic or Local Antimicrobials or a Combination of Both? A Retrospective Cohort Study

Study aimed to find out best option (systemic or local antimicrobial or combination of both) for treating venous leg ulcer infection. Patients’ files were reviewed retrospectively. Participants were divided into three groups. First group was treated by systemic antibiotics only (SABG). Second group received local antibiotics only (LABG). Third group was treated by combination of both (SLABG). Treatment strategies were compared based on multiple parameters using Pearson chi-squared test & relative risk (RR). 456 participants identified: 153 in SABG, 152 in LABG and 151 in SLABG. It was found that SLABG group was statistically significantly better than other single treatment strategies regarding all parameters (except bacterial resistance): (i) ulcer healing within usual duration (10-14 days) was 2.4 time higher (RR 2.4, 95% CI: 1.84, 3.12), (ii) probability of not recurring ulcer was 2.6 time higher (iii) probability of not getting increased wound size, abscess,cellulites was 5 times higher (iv) probability of not developing septicemia was 40% higher (v) probability of not requiring surgical intervention was 30% higher (vi) fewer patients needed prolonged hospitalization & lower cost was 8 times more likely (vii) patients were 3 times more satisfied during treatment.Probability of bacterial resistance was six times higher with SLABG and 5 times higher with SABG compared to LABG. For RR & CI values for all above parameters, see results below Ultimately, combination of both systemic and local antimicrobials may be best option to treat venous leg ulcer infection with out- weight with emergence of antibiotic-resistance microorganism

A mean square chain rule and its application in solving the random Chebyshev differential equation

[EN] In this paper a new version of the chain rule for calculat- ing the mean square derivative of a second-order stochastic process is proven. This random operational calculus rule is applied to construct a rigorous mean square solution of the random Chebyshev differential equation (r.C.d.e.) assuming mild moment hypotheses on the random variables that appear as coefficients and initial conditions of the cor- responding initial value problem. Such solution is represented through a mean square random power series. Moreover, reliable approximations for the mean and standard deviation functions to the solution stochastic process of the r.C.d.e. are given. Several examples, that illustrate the theoretical results, are included.This work was completed with the support of our TEX-pert.Cortés, J.; Villafuerte, L.; Burgos-Simon, C. (2017). A mean square chain rule and its application in solving the random Chebyshev differential equation. Mediterranean Journal of Mathematics. 14(1):14-35. https://doi.org/10.1007/s00009-017-0853-6S1435141Calbo, G., Cortés, J.C., Jódar, L., Villafuerte, L.: Analytic stochastic process solutions of second-order random differential equations. Appl. Math. Lett. 23(12), 1421–1424 (2010). doi: 10.1016/j.aml.2010.07.011El-Tawil, M.A., El-Sohaly, M.: Mean square numerical methods for initial value random differential equations. Open J. Discret. Math. 1(1), 164–171 (2011). doi: 10.4236/ojdm.2011.12009Khodabin, M., Maleknejad, K., Rostami, K., Nouri, M.: Numerical solution of stochastic differential equations by second order Runge Kutta methods. Math. Comp. Model. 59(9–10), 1910–1920 (2010). doi: 10.1016/j.mcm.2011.01.018Santos, L.T., Dorini, F.A., Cunha, M.C.C.: The probability density function to the random linear transport equation. Appl. Math. Comput. 216(5), 1524–1530 (2010). doi: 10.1016/j.amc.2010.03.001González Parra, G., Chen-Charpentier, B.M., Arenas, A.J.: Polynomial Chaos for random fractional order differential equations. Appl. Math. Comput. 226(1), 123–130 (2014). doi: 10.1016/j.amc.2013.10.51El-Beltagy, M.A., El-Tawil, M.A.: Toward a solution of a class of non-linear stochastic perturbed PDEs using automated WHEP algorithm. Appl. Math. Model. 37(12–13), 7174–7192 (2013). doi: 10.1016/j.apm.2013.01.038Nouri, K., Ranjbar, H.: Mean square convergence of the numerical solution of random differential equations. Mediterran. J. Math. 12(3), 1123–1140 (2015). doi: 10.1007/s00009-014-0452-8Villafuerte, L., Braumann, C.A., Cortés, J.C., Jódar, L.: Random differential operational calculus: theory and applications. Comp. Math. Appl. 59(1), 115–125 (2010). doi: 10.1016/j.camwa.2009.08.061Øksendal, B.: Stochastic differential equations: an introduction with applications, 6th edn. Springer, Berlin (2007)Soong, T.T.: Random differential equations in science and engineering. Academic Press, New York (1973)Wong, B., Hajek, B.: Stochastic processes in engineering systems. Springer Verlag, New York (1985)Arnold, L.: Stochastic differential equations. Theory and applications. John Wiley, New York (1974)Cortés, J.C., Jódar, L., Camacho, J., Villafuerte, L.: Random Airy type differential equations: mean square exact and numerical solutions. Comput. Math. Appl. 60(5), 1237–1244 (2010). doi: 10.1016/j.camwa.2010.05.046Calbo, G., Cortés, J.C., Jódar, L.: Random Hermite differential equations: mean square power series solutions and statistical properties. Appl. Math. Comp. 218(7), 3654–3666 (2011). doi: 10.1016/j.amc.2011.09.008Calbo, G., Cortés, J.C., Jódar, L., Villafuerte, L.: Solving the random Legendre differential equation: Mean square power series solution and its statistical functions. Comp. Math. Appl. 61(9), 2782–2792 (2010). doi: 10.1016/j.camwa.2011.03.045Cortés, J.C., Jódar, L., Company, R., Villafuerte, L.: Laguerre random polynomials: definition, differential and statistical properties. Utilit. Math. 98, 283–293 (2015)Cortés, J.C., Jódar, L., Villafuerte, L.: Mean square solution of Bessel differential equation with uncertainties. J. Comp. Appl. Math. 309, 383–395 (2017). doi: 10.1016/j.cam.2016.01.034Golmankhaneh, A.K., Porghoveh, N.A., Baleanu, D.: Mean square solutions of second-order random differential equations by using homotopy analysis method. Romanian Reports Physics 65(2), 1237–1244 (2013)Khalaf, S.L.: Mean square solutions of second-order random differential equations by using homotopy perturbation method. Int. Math. Forum 6(48), 2361–2370 (2011)Khudair, A.R., Ameen, A.A., Khalaf, S.L.: Mean square solutions of second-order random differential equations by using Adomian decomposition method. Appl. Math. Sci. 5(49), 2521–2535 (2011)Agarwal, R.P., O’Regan, D.: Ordinary and partial differential equations. Springer, New York (2009

Fortunella margarita Transcriptional Reprogramming Triggered by Xanthomonas citri subsp. citri

<p>Abstract</p> <p>Background</p> <p>Citrus canker disease caused by the bacterial pathogen <it>Xanthomonas citri </it>subsp. <it>citri (</it>Xcc) <it>has </it>become endemic in areas where high temperature, rain, humidity, and windy conditions provide a favourable environment for the dissemination of the bacterium. Xcc is pathogenic on many commercial citrus varieties but appears to elicit an incompatible reaction on the citrus relative <it>Fortunella margarita </it>Swing (kumquat), in the form of a very distinct delayed necrotic response. We have developed subtractive libraries enriched in sequences expressed in kumquat leaves during both early and late stages of the disease. The isolated differentially expressed transcripts were subsequently sequenced. Our results demonstrate how the use of microarray expression profiling can help assign roles to previously uncharacterized genes and elucidate plant pathogenesis-response related mechanisms. This can be considered to be a case study in a citrus relative where high throughput technologies were utilized to understand defence mechanisms in <it>Fortunella </it>and citrus at the molecular level.</p> <p>Results</p> <p><b>cDNAs from sequenced kumquat libraries (ESTs) made from subtracted RNA populations, healthy vs. infected, were used to make this microarray</b>. Of 2054 selected genes on a customized array, 317 were differentially expressed (P < 0.05) in Xcc challenged kumquat plants compared to mock-inoculated ones. This study identified components of the incompatible interaction such as reactive oxygen species (ROS) and programmed cell death (PCD). Common defence mechanisms and a number of resistance genes were also identified. In addition, there were a considerable number of differentially regulated genes that had no homologues in the databases. This could be an indication of either a specialized set of genes employed by kumquat in response to canker disease or new defence mechanisms in citrus.</p> <p>Conclusion</p> <p>Functional categorization of kumquat Xcc-responsive genes revealed an enhanced defence-related metabolism as well as a number of resistant response-specific genes in the kumquat transcriptome in response to Xcc inoculation. Gene expression profile(s) were analyzed to assemble a comprehensive and inclusive image of the molecular interaction in the kumquat/Xcc system. This was done in order to elucidate molecular mechanisms associated with the development of the hypersensitive response phenotype in kumquat leaves. These data will be used to perform comparisons among citrus species to evaluate means to enhance the host immune responses against bacterial diseases.</p

Developing risk prediction models for type 2 diabetes: a systematic review of methodology and reporting

<p>Abstract</p> <p>Background</p> <p>The World Health Organisation estimates that by 2030 there will be approximately 350 million people with type 2 diabetes. Associated with renal complications, heart disease, stroke and peripheral vascular disease, early identification of patients with undiagnosed type 2 diabetes or those at an increased risk of developing type 2 diabetes is an important challenge. We sought to systematically review and critically assess the conduct and reporting of methods used to develop risk prediction models for predicting the risk of having undiagnosed (prevalent) or future risk of developing (incident) type 2 diabetes in adults.</p> <p>Methods</p> <p>We conducted a systematic search of PubMed and EMBASE databases to identify studies published before May 2011 that describe the development of models combining two or more variables to predict the risk of prevalent or incident type 2 diabetes. We extracted key information that describes aspects of developing a prediction model including study design, sample size and number of events, outcome definition, risk predictor selection and coding, missing data, model-building strategies and aspects of performance.</p> <p>Results</p> <p>Thirty-nine studies comprising 43 risk prediction models were included. Seventeen studies (44%) reported the development of models to predict incident type 2 diabetes, whilst 15 studies (38%) described the derivation of models to predict prevalent type 2 diabetes. In nine studies (23%), the number of events per variable was less than ten, whilst in fourteen studies there was insufficient information reported for this measure to be calculated. The number of candidate risk predictors ranged from four to sixty-four, and in seven studies it was unclear how many risk predictors were considered. A method, not recommended to select risk predictors for inclusion in the multivariate model, using statistical significance from univariate screening was carried out in eight studies (21%), whilst the selection procedure was unclear in ten studies (26%). Twenty-one risk prediction models (49%) were developed by categorising all continuous risk predictors. The treatment and handling of missing data were not reported in 16 studies (41%).</p> <p>Conclusions</p> <p>We found widespread use of poor methods that could jeopardise model development, including univariate pre-screening of variables, categorisation of continuous risk predictors and poor handling of missing data. The use of poor methods affects the reliability of the prediction model and ultimately compromises the accuracy of the probability estimates of having undiagnosed type 2 diabetes or the predicted risk of developing type 2 diabetes. In addition, many studies were characterised by a generally poor level of reporting, with many key details to objectively judge the usefulness of the models often omitted.</p

Polyamide-Scorpion Cyclam Lexitropsins Selectively Bind AT-Rich DNA Independently of the Nature of the Coordinated Metal

Cyclam was attached to 1-, 2- and 3-pyrrole lexitropsins for the first time through a synthetically facile copper-catalyzed “click” reaction. The corresponding copper and zinc complexes were synthesized and characterized. The ligand and its complexes bound AT-rich DNA selectively over GC-rich DNA, and the thermodynamic profile of the binding was evaluated by isothermal titration calorimetry. The metal, encapsulated in a scorpion azamacrocyclic complex, did not affect the binding, which was dominated by the organic tail

Systematic Review of Potential Health Risks Posed by Pharmaceutical, Occupational and Consumer Exposures to Metallic and Nanoscale Aluminum, Aluminum Oxides, Aluminum Hydroxide and Its Soluble Salts

Aluminum (Al) is a ubiquitous substance encountered both naturally (as the third most abundant element) and intentionally (used in water, foods, pharmaceuticals, and vaccines); it is also present in ambient and occupational airborne particulates. Existing data underscore the importance of Al physical and chemical forms in relation to its uptake, accumulation, and systemic bioavailability. The present review represents a systematic examination of the peer-reviewed literature on the adverse health effects of Al materials published since a previous critical evaluation compiled by Krewski et al. (2007). Challenges encountered in carrying out the present review reflected the experimental use of different physical and chemical Al forms, different routes of administration, and different target organs in relation to the magnitude, frequency, and duration of exposure. Wide variations in diet can result in Al intakes that are often higher than the World Health Organization provisional tolerable weekly intake (PTWI), which is based on studies with Al citrate. Comparing daily dietary Al exposures on the basis of “total Al”assumes that gastrointestinal bioavailability for all dietary Al forms is equivalent to that for Al citrate, an approach that requires validation. Current occupational exposure limits (OELs) for identical Al substances vary as much as 15-fold. The toxicity of different Al forms depends in large measure on their physical behavior and relative solubility in water. The toxicity of soluble Al forms depends upon the delivered dose of Al+ 3 to target tissues. Trivalent Al reacts with water to produce bidentate superoxide coordination spheres [Al(O2)(H2O4)+ 2 and Al(H2O)6 + 3] that after complexation with O2•−, generate Al superoxides [Al(O2•)](H2O5)]+ 2. Semireduced AlO2• radicals deplete mitochondrial Fe and promote generation of H2O2, O2 • − and OH•. Thus, it is the Al+ 3-induced formation of oxygen radicals that accounts for the oxidative damage that leads to intrinsic apoptosis. In contrast, the toxicity of the insoluble Al oxides depends primarily on their behavior as particulates. Aluminum has been held responsible for human morbidity and mortality, but there is no consistent and convincing evidence to associate the Al found in food and drinking water at the doses and chemical forms presently consumed by people living in North America and Western Europe with increased risk for Alzheimer\u27s disease (AD). Neither is there clear evidence to show use of Al-containing underarm antiperspirants or cosmetics increases the risk of AD or breast cancer. Metallic Al, its oxides, and common Al salts have not been shown to be either genotoxic or carcinogenic. Aluminum exposures during neonatal and pediatric parenteral nutrition (PN) can impair bone mineralization and delay neurological development. Adverse effects to vaccines with Al adjuvants have occurred; however, recent controlled trials found that the immunologic response to certain vaccines with Al adjuvants was no greater, and in some cases less than, that after identical vaccination without Al adjuvants. The scientific literature on the adverse health effects of Al is extensive. Health risk assessments for Al must take into account individual co-factors (e.g., age, renal function, diet, gastric pH). Conclusions from the current review point to the need for refinement of the PTWI, reduction of Al contamination in PN solutions, justification for routine addition of Al to vaccines, and harmonization of OELs for Al substances

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency–Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research

The Greek-Orthodox version of the Brief Religious Coping (B-RCOPE) instrument: psychometric properties in three samples and associations with mental disorders, suicidality, illness perceptions, and quality of life

Background: The B-RCOPE is a brief measure assessing religious coping. We aimed to assess the psychometric properties of its Greek version in people with and without long-term conditions (LTCs). Associations between religious coping and mental illness, suicidality, illness perceptions, and quality of life were also investigated. Methods: The B-RCOPE was administered to 351 patients with diabetes, chronic pulmonary obstructive disease (COPD), and rheumatic diseases attending either the emergency department (N = 74) or specialty clinics (N = 302) and 127 people without LTCs. Diagnosis of mental disorders was established by the MINI. Associations with depressive symptom severity (PHQ-9), suicidal risk (RASS), illness perceptions (B-IPQ), and health-related quality of life (WHOQOL-BREF) were also investigated. Results: The Greek version of B-RCOPE showed a coherent two-dimensional factor structure with remarkable stability across the three samples corresponding to the positive (PRC) and negative (NRC) religious coping dimensions. Cronbach’s alphas were 0.91–0.96 and 0.77–0.92 for the PRC and NRC dimensions, respectively. Furthermore, NRC was associated with poorer mental health, greater depressive symptom severity and suicidality, and impaired HRQoL. In patients with LTCs, PRC correlated with lower perceived illness timeline, while NRC was associated with greater perceived illness consequences, lower perceived treatment control, greater illness concern, and lower illness comprehensibility. Conclusions: These findings indicate that the Greek-Orthodox B-RCOPE version may reliably assess religious coping. In addition, negative religious coping (i.e., religious struggle) is associated with adverse illness perceptions, and thus may detrimentally impact adaptation to medical illness. These findings deserve replication in prospective studies