This study explores the use of measuring plasma biomarkers at exacerbation of chronic obstructive pulmonary disease (COPD), providing insight into the underlying pathogenesis of these important ...events.
The use of measuring C-reactive protein (CRP) to confirm exacerbation, or to assess exacerbation severity, in COPD is unclear. Furthermore, it is not known whether there may be more useful systemic biomarkers.
To assess the use of plasma biomarkers in confirming exacerbation and predicting exacerbation severity.
We assessed 36 biomarkers in 90 paired baseline and exacerbation plasma samples from 90 patients with COPD. The diagnosis of exacerbation fulfilled both health care use and symptom-based criteria. Biomarker concentrations were related to clinical indices of exacerbation severity. Interrelationships between biomarkers were examined to gain information on mechanisms of systemic inflammation at exacerbation of COPD.
To confirm the diagnosis of exacerbation, the most selective biomarker was CRP. However, this was neither sufficiently sensitive nor specific alone (area under the receiver operating characteristic curve AUC, 0.73; 95% confidence interval, 0.66-0.80). The combination of CRP with any one increased major exacerbation symptom recorded by the patient on that day (dyspnea, sputum volume, or sputum purulence) significantly increased the AUC to 0.88 (95% confidence interval, 0.82-0.93; p<0.0001). There were no significant relationships between biomarker concentrations and clinical indices of exacerbation severity. Interrelationships between biomarkers suggest that the acute-phase response is related, separately, to monocytic and lymphocytic-neutrophilic pathways.
Plasma CRP concentration, in the presence of a major exacerbation symptom, is useful in the confirmation of COPD exacerbation. Systemic biomarkers were not helpful in predicting exacerbation severity. The acute-phase response at exacerbation was most strongly related to indices of monocyte function.
Background and objective
The resorption of alveolar ridge bone and maxillary sinus pneumatization are challenges to implant-supported prosthetic rehabilitation. Bone regeneration using bone ...substitutes and growth factors are alternatives for maxillary sinus augmentation (MSA). Therefore, we sought to evaluate the effects of the association between leukocyte and platelet–rich fibrin (L-PRF) and deproteinized bovine bone mineral (DBBM) in MSA procedures.
Materials and methods
Thirty-six maxillary sinuses from 24 individuals were included in this randomized clinical trial. The maxillary sinuses were randomly grafted with LPRF and DBBM (test group) or grafted only with DBBM (positive control). Dental implants were installed in the test group following two periods of evaluation: after 4 (DBBM+LPRF4) and 8 (DBBM+LPFR8) months of sinus graft healing, while the control group received implants only after 8 months. Cone beam computed tomography (CBCT) was taken 1 week after surgery (T1) and before implant placement (T2). Bone samples were collected during implant placement for histomorphometric and immunohistochemical (IHC) analysis. The primary implant stability was assessed by resonance frequency analysis.
Results
CBCT analysis demonstrated a significant decrease in bone volume from T1 to T2 in all groups without differences among them. Histologically, the test group showed significantly increase in bone neoformation in both periods of evaluation (LPRF+DBBM4: 44.70±14.01%; LPRF+DBBM8: 46.56±12.25%) compared to the control group (32.34±9.49%). The control group showed the highest percentage of residual graft. IHC analysis showed increased staining intensity of osteocalcin (OCN), vascular endothelial growth factor (VEGF), and runt related transcription factor 2 (RUNX-2) in LPRF+DBBM4 group, and osteopontin (OPN) in the L-PRF+DBBM8. Primary implant stability was successfully achieved (above 60 in implant stability quotient) in all the evaluated groups.
Conclusion
Combination of L-PRF and DBBM increased and accelerated new bone formation allowing early implant placement probably due to the higher protein expression of RUNX2, VEGF, OCN, and OPN. These data suggest that the use of L-PRF might be an interesting alternative to use in combination with DBBM for augment the maxillary sinuses allowing the installation of appropriate length implants in shorter period of time.
Clinical relevance
This study showed improvement in bone neoformation and accelerated healing when associating L-PRF and DBBM for maxillary sinus augmentation procedures.
Trial registration
This study was registered before participant recruitment in Brazilian Registry of Clinical Trials (ReBEC - RBR-95m73t).
Swept-source optical coherence tomography (SS-OCT) shows potential for the in vivo quantitative evaluation of micro-structural enamel surface phenomena occurring during early erosive ...demineralization. This randomized controlled single-blind cross-over clinical study aimed to evaluate the use of SS-OCT for detecting optical changes in the enamel of 30 healthy volunteers subjected to orange juice rinsing (erosive challenge) in comparison to mineral water rinsing (control), according to wiped and non-wiped enamel surface states. Participants were randomly allocated to 60 min of orange juice rinsing (pH 3.8) followed by 60 min of water rinsing (pH 6.7) and vice versa, with a 2-week wash-out period. In addition, the labial surfaces of the right or left maxillary incisors were wiped prior to SS-OCT imaging. An automated ImageJ algorithm was designed to analyse the back-scattered OCT signal intensity (D) after orange juice rinsing compared to after water rinsing. D was quantified as the OCT signal scattering from the 33 µm sub-surface enamel, normalised by the total OCT signal intensity entering the enamel. The back-scattered OCT signal intensity increased by 3.1% (95% CI 1.1-5.1%) in the wiped incisors and by 3.5% (95% CI 1.5-5.5%) in the unwiped incisors (p < 0.0001). Wiping reduced the back-scattered OCT signal intensity by 1.7% (95% CI -3.2 to -0.3%; p = 0.02) in comparison to the unwiped enamel surfaces for both rinsing solutions (p = 0.2). SS-OCT detected OCT signal changes in the superficial sub-surface enamel of maxillary central incisor teeth of healthy volunteers after orange juice rinsing.
Abstract Objectives To investigate the dentine occlusion and acid resistance of dentifrices developed to treat dentine hypersensitivity. Methods This was a single centre, single blind, randomised, ...split mouth, four treatments, two period crossover, in situ study in healthy subjects. Subjects wore buccal intra-oral appliances each fitted with four dentine samples over four consecutive days with one study product applied per appliance; 8% strontium acetate in silica base, 1040 ppm sodium fluoride (Sensodyne® Rapid Relief), 8% arginine, calcium carbonate, 1450 ppm sodium monofluorophosphate (Colgate Sensitive Pro-Relief® ), 1450 ppm sodium fluoride (control paste) and water. On days 3 and 4, two agitated grapefruit juice challenges (ex vivo) occurred for 1 min. At the end of each treatment day 1 dentine sample was removed from each appliance for scanning electron microscopy (SEM). The extent of tubule occlusion was measured using an examiner-based visual scoring index (three trained examiners). Results In total, 28 subjects ((12 males and 16 females with a mean age of 34.7 years (SD 8.41 years)) completed the study. On day 2, both test dentifrices demonstrated significantly better dentine tubule occlusion than water ( p < 0.0001) and control paste (8% strontium p = 0.0003 and 8% arginine p = 0.0019). After 3 and 4 days of twice daily brushing with acid challenges on days 3 and 4 the strontium-based dentifrice demonstrated significantly better dentine occlusion than all other treatments ( p < 0.0001). Conclusions Strontium acetate and arginine-based dentifrice result in statistically significant dentine tubular occlusion compared to controls, but the arginine-based dentifrice is more susceptible to acid challenge. Clinical significance Erosive beverages are an important aetiology in DH by exposing dentine tubules. Their consumption has increased significantly over the past decade in the UK. This 4-day in situ study investigated the properties of commercially available dentifrices designed to occlude dentine tubules and their resistance to an agitated acid challenge.
Of 18 sites that participated in an implementation study of the Xpert® MTB/RIF assay in India, we selected five microscopy centres and two reference laboratories.
To obtain unit costs of diagnostic ...tests for tuberculosis (TB) and drug-resistant TB.
Laboratories were purposely selected to capture regional variations and different laboratory types. Both bottom-up and the top-down methods were used to estimate unit costs.
At the microscopy centres, mean bottom-up unit costs were respectively US$0.83 (range US$0.60-US$1.10) and US$12.29 (US$11.61-US$12.89) for sputum smear microscopy and Xpert. At the reference laboratories, mean unit costs were US$1.69 for the decontamination procedure, US$9.83 for a solid culture, US$11.06 for a liquid culture, US$29.88 for a drug susceptibility test, and US$18.18 for a line-probe assay. Top-down mean unit cost estimates were higher for all tests, and for sputum smear microscopy and Xpert these increased to respectively US$1.51 and US$13.58. The difference between bottom-up and top-down estimates was greatest for tests performed at the reference laboratories.
These unit costs for TB diagnostics can be used to estimate resource requirements and cost-effectiveness in India, taking into account geographical location, laboratory type and capacity utilisation.
What is already known about this subject
• Forced expiratory voume in 1 s (FEV1) is the standard measurement used to measure drug effects in chronic obstructive pulmonary disease (COPD) clinical ...trials.
• Having previously shown that specific airway conductance (sGaw) measured using body plethysmography and impulse oscillometry (IOS) are more sensitive than FEV1 for assessing short‐acting bronchodilator effects in patients with COPD, we conducted the first randomized, placebo‐controlled study to compare long‐acting bronchodilators in COPD patients using these techniques.
What this study adds
• sGaw and IOS sensitively differentiated between the effects of tiotropium and salmeterol when FEV1 measurements were similar.
• sGaw and IOS measurements are better than FEV1 for sensitively assessing bronchodilator pharmacology and differentiating between treatments in COPD clinical trials.
Aims
Assessment of bronchodilator pharmacology in chronic obstructive pulmonary disease (COPD) may be improved by using more sensitive methods than spirometry, such as impulse oscillometry (IOS) and body plethysmography. We sought to compare salmeterol (S) and tiotropium (Tio) using these methods.
Methods
In this double‐blind, randomized, four‐way crossover study, 32 COPD patients received single doses of Tio (18 µg), S (50 and 100 µg) or placebo. Specific airway conductance (sGaw), forced expiratory volume in 1 s (FEV1) and IOS were measured pre‐ and up to 26 h postdose. Comparisons between treatments were analysed by weighted means (WM) between 0 and 12 (WM 0–12 h) and 12–24 h (WM 12–24 h) postdose. Data are expressed as mean difference (or geometric ratio for nonparametric data) with 95% confidence intervals.
Results
Tio and S100 significantly improved FEV1, sGaw and IOS parameters up to 26 h and S50 up to 16 h. WM analysis showed no difference between Tio and S100 in FEV1 for 0–12 h or 12–24 h. Maximum mid‐expiratory flow (−0.06; −0.11, −0.01) and R35 (0.02; 0.01, 0.03) demonstrated superiority of S100 compared with Tio for WM 0–12 h sGaw (1.12; 1.02, 1.23), R5 (−0.06; −0.09, −0.02), R15 (−0.03; −0.05, −0.01), and resonant frequency (RF) (−2.30; −3.83, −0.77) showed superiority of Tio compared with S100 for WM 12–24 h. At 26 h, sGaw, R5, R15, X5 and RF also showed superiority of Tio compared with S100.
Conclusions
sGaw and IOS parameters sensitively differentiated between the effects of Tio and S when FEV1 measurements were similar. Clinical trials in patients with COPD should use IOS and sGaw to assess comprehensively bronchodilator pharmacology.
Every year, from December to April, anthropogenic haze spreads over most of the North Indian Ocean, and South and Southeast Asia. The Indian Ocean Experiment (INDOEX) documented this Indo‐Asian haze ...at scales ranging from individual particles to its contribution to the regional climate forcing. This study integrates the multiplatform observations (satellites, aircraft, ships, surface stations, and balloons) with one‐ and four‐dimensional models to derive the regional aerosol forcing resulting from the direct, the semidirect and the two indirect effects. The haze particles consisted of several inorganic and carbonaceous species, including absorbing black carbon clusters, fly ash, and mineral dust. The most striking result was the large loading of aerosols over most of the South Asian region and the North Indian Ocean. The January to March 1999 visible optical depths were about 0.5 over most of the continent and reached values as large as 0.2 over the equatorial Indian ocean due to long‐range transport. The aerosol layer extended as high as 3 km. Black carbon contributed about 14% to the fine particle mass and 11% to the visible optical depth. The single‐scattering albedo estimated by several independent methods was consistently around 0.9 both inland and over the open ocean. Anthropogenic sources contributed as much as 80% (±10%) to the aerosol loading and the optical depth. The in situ data, which clearly support the existence of the first indirect effect (increased aerosol concentration producing more cloud drops with smaller effective radii), are used to develop a composite indirect effect scheme. The Indo‐Asian aerosols impact the radiative forcing through a complex set of heating (positive forcing) and cooling (negative forcing) processes. Clouds and black carbon emerge as the major players. The dominant factor, however, is the large negative forcing (‐20±4 W m−2) at the surface and the comparably large atmospheric heating. Regionally, the absorbing haze decreased the surface solar radiation by an amount comparable to 50% of the total ocean heat flux and nearly doubled the lower tropospheric solar heating. We demonstrate with a general circulation model how this additional heating significantly perturbs the tropical rainfall patterns and the hydrological cycle with implications to global climate.
Catalytic enantioselective Minisci reactions have recently been developed but all instances so far utilize α‐amino radical coupling partners. We report a substantial evolution of the enantioselective ...Minisci reaction that enables α‐hydroxy radicals to be used, providing valuable enantioenriched secondary alcohol products. This is achieved through the direct oxidative coupling of two C−H bonds on simple alcohol and pyridine partners through a hydrogen atom transfer (HAT)‐driven approach: a challenging process to achieve due to the numerous side reactions that can occur. Our approach is highly regioselective as well as highly enantioselective. Dicumyl peroxide, upon irradiation with 390 nm light, serves as both HAT reagent and oxidant whilst selectivity is controlled by use of a chiral phosphoric acid catalyst. Computational and experimental evidence provide mechanistic insight as to the origin of selectivity, revealing a stereodetermining deprotonation step distinct from the analogous reaction of amide‐containing substrates.
An enantioselective Minisci reaction between pyridines and prochiral α‐hydroxy radicals has been developed. Hydrogen atom transfer is used to generate the latter from simple alcohols and the reaction formally constitutes the couple of two C−H bonds to form a new C−C bond in a process that is highly enantioselective and regioselective. Computational studies provide insight into the origins of selectivity.
To evaluate the in vitro accuracy of digital impressions for three-dimensional (3D) volumetric measurement of residual coronal tooth structure postendodontic cavity preparation, with reference to ...micro-computed tomography (μCT).
Quantification of the accuracy and precision of the intraoral digital scanner (3M True Definition Scanner - IOS) was performed using a metrology gauge block and a profilometric calibration model. Thirty-four human extracted molars with endodontic access cavities were scanned using both intraoral scanning (test scanner) in high-resolution mode, and µCT (reference scanner: GE Locus SP μCT scanner) in high- (HiResCT) and low- (LoResCT) resolution modes. Comparisons of volumetric accuracy and 3D profilometric deviations were performed using surface metrology software. One-way repeated measures analysis of variance (ANOVA), in combination with the Bonferroni post hoc test, was implemented to compare the differences in volume measurements between scanning methods.
Digital scanning revealed smaller volume measurements by 1.36% and 0.68% compared to HiResCT and LoResCT, respectively. There was a statistically significant difference in the volumetric measurements obtained from the IOS scanner and both HiResCT and LoResCT scans (P < 0.001). Analysis of the mean 3D profilometric deviations revealed that the IOS displayed greater surface deviation (± 27/33 μm) vs HiResCT and LoResCT (± 16/32 μm).
Although volumetric measurements of endodontically accessed teeth were up to 1.36% smaller in comparison to µCT, the digital scanner was able to reliably measure the extra- and intracoronal aspect of the endodontically accessed tooth.
We describe a system for the isolation, concentration, separation, and recovery of human osteoblast-like cells from a heterogeneous population using dielectrophoretic ring traps. Cells flowing in a ...microfluidic channel are immobilized inside an electric field cage using negative dielectrophoresis. A planar ring electrode creates a closed trap while repelling surrounding cells. Target cells are identified by fluorescent labeling, and are trapped as they pass across a ring electrode by an automated system. We demonstrate recovery of small populations of human osteoblast-like cells with a purity of 100%, which in turn demonstrates the potential of such a device for cell selection from a heterogeneous population.
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