Influence of structurally related impurities on the crystal nucleation of curcumin

peer-reviewedIn this work, the influence of the structurally related impurities, Demethoxycurcumin (DMC) and Bisdemethoxycurcumin (BDMC) on the primary nucleation of Curcumin (CUR) has been investigated in propan-2-ol. The induction time for nucleation was measured at different CUR driving forces and impurity concentrations 0.10 mmol.dm-3, 0.30 mmol.dm-3 and 0.60 mmol.dm-3 and the results are analysed by the classical nucleation theory (CNT). The nucleation rate for the impure systems was noticeably lower than the nucleation rate of the pure system, and the times of growth to visibility were much longer for the impure systems. The pre-exponential factors are clearly lower for the impure system compared to the pure CUR system, while the increase in the solid-liquid interfacial energy is small. DFT and Metadynamic molecular modelling reveal that the 1:1 bonding between CUR and an impurity molecule is stronger than to another CUR molecule, thus suggesting that the developing CUR nucleus has to overcome a certain energy barrier in order to remove the impurity molecules from their surface, which may explain why nucleation of CUR is more difficult in presence of the structurally related impurities; DMC and BDMC

Evaluating the effectiveness of rosuvastatin in preventing the progression of diastolic dysfunction in aortic stenosis: A substudy of the aortic stenosis progression observation measuring effects of rosuvastatin (ASTRONOMER) study

<p>Abstract</p> <p>Background</p> <p>Tissue Doppler imaging (TDI) is a noninvasive echocardiographic method for the diagnosis of diastolic dysfunction in patients with varying degrees of aortic stenosis (AS). Little is known however, on the utility of TDI in the serial assessment of diastolic abnormalities in AS.</p> <p>Objective</p> <p>The aim of the current proposal was to examine whether treatment with rosuvastatin was successful in improving diastolic abnormalities in patients enrolled in the Aortic Stenosis Progression Observation Measuring Effects of Rosuvastatin (ASTRONOMER) study.</p> <p>Methods</p> <p>Conventional Doppler indices including peak early (E) and late (A) transmitral velocities, and E/A ratio were measured from spectral Doppler. Tissue Doppler measurements including early (E') and late (A') velocities of the lateral annulus were determined, and E/E' was calculated.</p> <p>Results</p> <p>The study population included 168 patients (56 ± 13 years), whose AS severity was categorized based on peak velocity at baseline (Group I: 2.5-3.0 m/s; Group II: 3.1-3.5 m/s; Group III: 3.6-4.0 m/s). Baseline and follow-up hemodynamics, LV dimensions and diastolic functional parameters were evaluated in all three groups. There was increased diastolic dysfunction from baseline to follow-up in each of the placebo and rosuvastatin groups. In patients with increasing severity of AS in Groups I and II, the lateral E' was lower and the E/E' (as an estimate of increased left ventricular end-diastolic pressure) was higher at baseline (p < 0.05). However, treatment with rosuvastatin did not affect the progression of diastolic dysfunction from baseline to 3.5 year follow-up between patients in any of the three predefined groups.</p> <p>Conclusion</p> <p>In patients with mild to moderate asymptomatic AS, rosuvastatin did not attenuate the progression of diastolic dysfunction.</p

Increased Prevalence of Chronic Disease in Back Pain Patients Living in Car-dependent Neighbourhoods in Canada: A Cross-sectional Analysis

Objectives Chronic diseases, including back pain, result in significant patient morbidity and societal burden. Overall improvement in physical fitness is recommended for prevention and treatment. Walking is a convenient modality for achieving initial gains. Our objective was to determine whether neighbourhood walkability, acting as a surrogate measure of physical fitness, was associated with the presence of chronic disease. Methods We conducted a cross-sectional study of prospectively collected data from a prior randomized cohort study of 227 patients referred for tertiary assessment of chronic back pain in Ottawa, ON, Canada. The Charlson Comorbidity Index (CCI) was calculated from patient-completed questionnaires and medical record review. Using patients’ postal codes, neighbourhood walkability was determined using the Walk Score, which awards points based on the distance to the closest amenities, yielding a score from 0 to 100 (0-50: car-dependent; 50-100: walkable). Results Based on the Walk Score, 134 patients lived in car-dependent neighborhoods and 93 lived in walkable neighborhoods. A multivariate logistic regression model, adjusted for age, gender, rural postal code, body mass index, smoking, median household income, percent employment, pain, and disability, demonstrated an adjusted odds ratio of 2.75 (95% confidence interval, 1.16 to 6.53) times higher prevalence for having a chronic disease for patients living in a car-dependent neighborhood. There was also a significant dose-related association (p=0.01; Mantel-Haenszel chi-square=6.4) between living in car-dependent neighbourhoods and more severe CCI scores. Conclusions Our findings suggest that advocating for improved neighbourhood planning to permit greater walkability may help offset the burden of chronic disease

Highly degradable porous melt-derived bioactive glass foam scaffolds for bone regeneration

A challenge in using bioactive melt-derived glass in bone regeneration is to produce scaffolds with interconnected pores while maintaining the amorphous nature of the glass and its associated bioactivity. Here we introduce a method for creating porous melt-derived bioactive glass foam scaffolds with low silica content and report in vitro and preliminary in vivo data. The gel-cast foaming process was adapted, employing temperature controlled gelation of gelatin, rather than the in situ acrylic polymerisation used previously. To form a 3D construct from melt derived glasses, particles must be fused via thermal processing, termed sintering. The original Bioglass® 45S5 composition crystallises upon sintering, altering its bioactivity, due to the temperature difference between the glass transition temperature and the crystallisation onset being small. Here, we optimised and compared scaffolds from three glass compositions, ICIE16, PSrBG and 13–93, which were selected due to their widened sintering windows. Amorphous scaffolds with modal pore interconnect diameters between 100–150 µm and porosities of 75% had compressive strengths of 3.4 ± 0.3 MPa, 8.4 ± 0.8 MPa and 15.3 ± 1.8 MPa, for ICIE16, PSrBG and 13–93 respectively. These porosities and compressive strength values are within the range of cancellous bone, and greater than previously reported foamed scaffolds. Dental pulp stem cells attached to the scaffold surfaces during in vitro culture and were viable. In vivo, the scaffolds were found to regenerate bone in a rabbit model according to X-ray micro tomography imaging

A guide to creating design matrices for gene expression experiments.

Differential expression analysis of genomic data types, such as RNA-sequencing experiments, use linear models to determine the size and direction of the changes in gene expression. For RNA-sequencing, there are several established software packages for this purpose accompanied with analysis pipelines that are well described. However, there are two crucial steps in the analysis process that can be a stumbling block for many -- the set up an appropriate model via design matrices and the set up of comparisons of interest via contrast matrices. These steps are particularly troublesome because an extensive catalogue for design and contrast matrices does not currently exist. One would usually search for example case studies across different platforms and mix and match the advice from those sources to suit the dataset they have at hand. This article guides the reader through the basics of how to set up design and contrast matrices. We take a practical approach by providing code and graphical representation of each case study, starting with simpler examples (e.g. models with a single explanatory variable) and move onto more complex ones (e.g. interaction models, mixed effects models, higher order time series and cyclical models). Although our work has been written specifically with a limma-style pipeline in mind, most of it is also applicable to other software packages for differential expression analysis, and the ideas covered can be adapted to data analysis of other high-throughput technologies. Where appropriate, we explain the interpretation and differences between models to aid readers in their own model choices. Unnecessary jargon and theory is omitted where possible so that our work is accessible to a wide audience of readers, from beginners to those with experience in genomics data analysis

Diagnosing the Dermatologic Blues: Systematic Review of the Rare Conundrum, Psychogenic Purpura

BackgroundPsychogenic purpura is an idiopathic psychodermatologic condition of recurrent, painful purpura precipitated by psychological stress, predominantly affecting young females. Little consensus exists on the diagnostic guidelines for this rare condition, often resulting in costly, unnecessary, and stressful investigations as well as prolonged hospital admissions. ObjectiveWith this first up-to-date systematic review of 134 cases of psychogenic purpura in over a decade, we aim to thoroughly investigate the diagnostic strategy and treatment regimens used in the last decade. With a sooner diagnosis, patient stress and nosocomial ecchymoses can be minimized, and treatment can be expedited. MethodsWe conducted a literature review of 4 databases (PubMed, Ovid Embase, Ovid MEDLINE, and Web of Science) on October 5, 2022 that yielded 46 full-text articles, which were reviewed and extracted by 2 independent reviewers. ResultsWe analyzed a total of 134 cases, consisting largely of females (125/134, 93.3%) with purpura on the upper (103/134, 76.9%) or lower limbs (112/134, 83.6%). Apart from a paresthesia prodrome, patients commonly experienced headaches, malaise, and arthralgia or myalgia. Approximately 70% (95/134) of patients reported a physiological or psychological stressor or psychiatric diagnosis before the development of the purpura. Laboratory testing almost always revealed unremarkable results. The intradermal washed autoerythrocyte sensitization test was positive in 98% (42/43) of cases. Histopathology biopsy findings commonly revealed dermal erythrodiapedesis or hemorrhage (n=34) and perivascular inflammatory infiltrates (n=17). Approximately 42% (56/134) of patients received a novel psychiatric diagnosis, with depression being the most common (40/72, 56%). In both patients with and those without a novel psychiatric diagnosis, observation, counseling, treatment with antidepressants (ie, selective serotonin reuptake inhibitors), and psychotherapy (ie, cognitive behavioral therapy) prevailed in the resolution of the purpura. ConclusionsDue to the unclear etiology and infrequent presentation of this condition, it remains a diagnosis of exclusion based on clinical suspicion evaluating the presence of stressors or psychiatric comorbidities and exclusion of systemic conditions. Clinical confirmation can be sought through a positive autoerythrocyte sedimentation test, characteristic histopathology findings, and remission of purpura after psychiatric treatment