This study comprehensively investigates the changing biodistribution of fluorescent-labelled polystyrene latex bead nanoparticles in a mouse model of inflammation. Since inflammation alters systemic ...circulatory properties, increases vessel permeability and modulates the immune system, we theorised that systemic inflammation would alter nanoparticle distribution within the body. This has implications for prospective nanocarrier-based therapies targeting inflammatory diseases. Low dose lipopolysaccharide (LPS), a bacterial endotoxin, was used to induce an inflammatory response, and 20 nm, 100 nm or 500 nm polystyrene nanoparticles were administered after 16 hours. HPLC analysis was used to accurately quantify nanoparticle retention by each vital organ, and tissue sections revealed the precise locations of nanoparticle deposition within key tissues. During inflammation, nanoparticles of all sizes redistributed, particularly to the marginal zones of the spleen. We found that LPS-induced inflammation induces splenic macrophage polarisation and alters leukocyte uptake of nanoparticles, with size-dependent effects. In addition, spleen vasculature becomes significantly more permeable following LPS treatment. We conclude that systemic inflammation affects nanoparticle distribution by multiple mechanisms, in a size dependent manner.
Cell refractive index is a key biophysical parameter, which has been extensively studied. It is correlated with other cell biophysical properties including mechanical, electrical and optical ...properties, and not only represents the intracellular mass and concentration of a cell, but also provides important insight for various biological models. Measurement techniques developed earlier only measure the effective refractive index of a cell or a cell suspension, providing only limited information on cell refractive index and hence hindering its in-depth analysis and correlation. Recently, the emergence of microfluidic, photonic and imaging technologies has enabled the manipulation of a single cell and the 3D refractive index of a single cell down to sub-micron resolution, providing powerful tools to study cells based on refractive index. In this review, we provide an overview of cell refractive index models and measurement techniques including microfluidic chip-based techniques for the last 50 years, present the applications and significance of cell refractive index in cell biology, hematology, and pathology, and discuss future research trends in the field, including 3D imaging methods, integration with microfluidics and potential applications in new and breakthrough research areas.
Fracture liaison services (FLS) have been demonstrated to improve outcomes following osteoporotic fracture. The aim of this systematic literature review (SLR) was to determine the characteristics of ...an FLS that lead to improved patient outcomes. We conducted a SLR, including articles published between 2000 and February 2017, using global (Medline, EMBASE, PubMed and Cochrane Library) and local databases. Studies including patients aged ≥ 50 years with osteoporotic fractures enrolled in an FLS were assessed. Information extracted from each article included key person coordinating the FLS (physician, nurse or other healthcare professional), setting (hospital vs community), intensity (single vs multiple), duration (long vs short term), fracture type and gender. A meta-analysis of randomised controlled trials was conducted based on the key person coordinating the FLS. Out of 7236 articles, 57 were considered to be high quality and identified for further analysis. The SLR identified several components which contributed to FLS success, including multidisciplinary involvement, driven by a dedicated case manager, regular assessment and follow-up, multifaceted interventions and patient education. Meta-analytic data confirm the effectiveness of an FLS following an osteoporotic fracture: approximate 27% increase in the likelihood of BMD testing and up to 21% increase in the likelihood of treatment initiation compared with usual care. The balance of evidence indicates that the multifaceted FLS and dedicated coordination are important success factors that contribute to effective FLS interventions which reduce fracture-related morbidity and mortality.
Particle trapping and binding in optical potential wells provide a versatile platform for various biomedical applications. However, implementation systems to study multi-particle contact interactions ...in an optical lattice remain rare. By configuring an optofluidic lattice, we demonstrate the precise control of particle interactions and functions such as controlling aggregation and multi-hopping. The mean residence time of a single particle is found considerably reduced from 7 s, as predicted by Kramer's theory, to 0.6 s, owing to the mechanical interactions among aggregated particles. The optofluidic lattice also enables single-bacteria-level screening of biological binding agents such as antibodies through particle-enabled bacteria hopping. The binding efficiency of antibodies could be determined directly, selectively, quantitatively and efficiently. This work enriches the fundamental mechanisms of particle kinetics and offers new possibilities for probing and utilising unprecedented biomolecule interactions at single-bacteria level.
Polymorphisms in CYP2C9 and VKORC1 have been shown to be associated with warfarin dose requirements and could be used to predict warfarin dose. We conducted a prospective study in which warfarin dose ...was prescribed based on CYP2C9 and VKORC1 polymorphisms in 108 Han‐Chinese patients without prior warfarin treatments. Using the genotype‐based dosing, 83% of patients reached stable, therapeutic international normalized ratio (INR) within 2 weeks of treatment initiation and none of the patients developed clinical bleeding or thromboembolic event. Ten percent (11) of patients with INR >4 and no clinical bleeding were detected during this study. At 12 weeks, 69% of the patients' maintenance doses matched the prediction. Dosing algorithms incorporating genetic factors, age, and body surface area were developed, which could explain up to 62% of the total variation (R2 of 0.62). This study demonstrated that pharmacogenetics‐based dosing could improve time to stable, therapeutic INR, reduce adverse events, and achieve high sensitivity.
Clinical Pharmacology & Therapeutics (2008); 84, 1, 83–89 doi:10.1038/sj.clpt.6100453
Mechanisms of the development of abnormal metabolic phenotypes among obese population are not yet clear. In this study, we aimed to screen metabolomes of both healthy and subjects with abnormal ...obesity to identify potential metabolic pathways that may regulate the different metabolic characteristics of obesity.
We recruited subjects with body mass index (BMI) over 25 from the weight-loss clinic of a central hospital in Taiwan. Metabolic healthy obesity (MHO) is defined as without having any form of hyperglycemia, hypertension and dyslipidemia, while metabolic abnormal obesity (MAO) is defined as having one or more abnormal metabolic indexes. Serum-based metabolomic profiling using both liquid chromatography-mass spectrometry and gas chromatography-mass spectrometry of 34 MHO and MAO individuals with matching age, sex and BMI was performed. Conditional logistic regression and partial least squares discriminant analysis were applied to identify significant metabolites between the two groups. Pathway enrichment and topology analyses were conducted to evaluate the regulated pathways.
A differential metabolite panel was identified to be significantly differed in MHO and MAO groups, including L-kynurenine, glycerophosphocholine (GPC), glycerol 1-phosphate, glycolic acid, tagatose, methyl palmitate and uric acid. Moreover, several metabolic pathways were relevant in distinguishing MHO from MAO groups, including fatty acid biosynthesis, phenylalanine metabolism, propanoate metabolism, and valine, leucine and isoleucine degradation.
Different metabolomic profiles and metabolic pathways are important for distinguishing between MHO and MAO groups. We have identified and discussed the key metabolites and pathways that may prove important in the regulation of metabolic traits among the obese, which could provide useful clues to study the underlying mechanisms of the development of abnormal metabolic phenotypes.
Background
Combined esophageal high‐resolution impedance manometry (HRIM) measures multiple pressures and bolus transit simultaneously, facilitating detailed assessment of esophageal motility. ...Currently, normative values for water‐perfused HRIM systems for Chinese populations are lacking.
Methods
Healthy volunteers were enrolled for comprehensive anthropometric measures, blood biochemistry tests, and an HRIM study using 22 water‐perfused pressure sensors and 12 impedance channels. Ten 5‐mL liquid swallows of saline at 30‐second intervals were conducted. The following parameters were calculated: distal contractile integral (DCI), distal latency (DL), lower esophageal sphincter (LES) basal pressure, 4‐second integrated relaxation pressure (IRP‐4s), and complete bolus transit percentage. Normal values were established based on the 5th and 95th percentiles.
Key Results
All 66 participants (34 male, 32 female, aged 21‐64 years) completed the study and tolerated the HRIM procedure well. The upper normal limit (95th percentile) of IRP‐4 second was 20 mmHg. The 5th‐95th percentile range for DCI, DL, and complete bolus transit was 99‐2186 mmHg●s●cm, 6.2‐11.3 second, and 50%‐100%, respectively. Age was negatively correlated with DL. Females had significantly higher upper limits for IRP‐4s and median DCI than males. Multivariate analyses confirmed that IRP‐4s was higher in females, and that higher body mass index and waist circumference were associated with reduced DL and better bolus transit, respectively.
Conclusions and Inferences
We established normative values for the water‐perfused HRIM system for a Chinese population. Gender and anthropometric factors may affect various major HRIM parameters and should be taken into account when interpreting HRIM results in clinical practice.
The present study provides the first normative dataset for water‐perfused HRIM systems for the Chinese population, and confirms the importance of establishing respective normative datasets for different HRM/HRIM systems and populations. Moreover, we show that various demographic factors, especially gender, may affect the major parameters of esophageal motility that are obtained using HRIM. These factors may need to be accounted for when interpreting HRIM results in clinical practice.
Objective
To examine the associations between personality traits and suicidal ideation (SI) and attempt (SA) in mood disorder patients and community controls.
Method
We recruited 365 bipolar, 296 ...major depressive disorder patients, and 315 community controls to assess their lifetime suicidality. Participants filled out self‐reported personality questionnaires to collect data of personality traits, including novelty seeking (NS), harm avoidance (HA), extraversion (E), and neuroticism (N). We used logistic regression models adjusted for diagnoses to analyze combinational effects of personality traits on the risk of suicide. Additionally, radar charts display personality profiles for suicidal behaviours by groups.
Results
All personality traits were associated with the risk of suicidality with various effect size, except for E that showed protective effect. High N or HA had prominent and independent risk effects on SI and SA. Combinations of high N and low E, or high HA and NS were the risk personality profiles for suicidality. Higher N scores further distinguished SA from SI in mood disorder patients.
Conclusion
Introvert personality traits showed independent risk effects on suicidality regardless of diagnosis status. Among high‐risk individuals with suicidal thoughts, higher neuroticism tendency is further associated with increased risk of suicide attempt.
Success Criteria in Implant Dentistry Papaspyridakos, P.; Chen, C.-J.; Singh, M. ...
Journal of dental research,
03/2012, Letnik:
91, Številka:
3
Journal Article
Recenzirano
The purpose of this study was to examine the most frequently used criteria to define treatment success in implant dentistry. An electronic MEDLINE/PubMED search was conducted to identify randomized ...controlled trials and prospective studies reporting on outcomes of implant dentistry. Only studies conducted with roughened surface implants and at least five-year follow-up were included. Data were analyzed for success at the implant level, peri-implant soft tissue, prosthetics, and patient satisfaction. Most frequently reported criteria for success at the implant level were mobility, pain, radiolucency, and peri-implant bone loss (> 1.5 mm), and for success at the peri-implant soft-tissue level, suppuration, and bleeding. The criteria for success at the prosthetic level were the occurrence of technical complications/prosthetic maintenance, adequate function, and esthetics during the five-year period. The criteria at patient satisfaction level were discomfort and paresthesia, satisfaction with appearance, and ability to chew/taste. Success in implant dentistry should ideally evaluate a long-term primary outcome of an implant-prosthetic complex as a whole.
We investigate, for two water models displaying a liquid-liquid critical point, the relation between changes in dynamic and ther-modynamic anomalies arising from the presence of the liquid-liquid ...critical point. We find a correlation between the dynamic crossover and the locus of specific heat maxima$C_{P}^{max}$("Widom line") emanating from the critical point. Our findings are consistent with a possible relation between the previously hypothesized liquid-liquid phase transition and the transition in the dynamics recently observed in neutron scattering experiments on confined water. More generally, we argue that this connection between$C_{P}^{max}$and dynamic crossover is not limited to the case of water, a hydrogen bond network-forming liquid, but is a more general feature of crossing the Widom line. Specifically, we also study the Jagla potential, a spherically symmetric two-scale potential known to possess a liquid-liquid critical point, in which the competition between two liquid structures is generated by repulsive and attractive ramp interactions.
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