Ketoprofen gel improves low back pain in addition to IV dexketoprofen: a randomized placebo-controlled trial

Objective Oligoanalgesia is common in emergency departments (EDs), and pain management is of concern for ED physicians. The aim of this study was to reveal the effect of ketoprofen gel in patients presenting with mechanical low back pain to the ED. Method All the study patients received intravenous dexketoprofen additional to study drugs. After dexketoprofen, 2 g of 2.5% ketoprofen gel or placebo was administered to the site with pain and tenderness. Pain relief at 15 and 30 minutes was measured by visual analog scale scores. Rescue drug need and adverse effects were also recorded. Results A total of 140 patients were enrolled into the study. The mean age of the study patients was 35 ± 12, and 56% (n = 79) of them were male. The mean pain reduction at 30 minutes was 52 ± 18 for ketoprofen gel and 37 ± 17 for placebo, and ketoprofen gel was better than placebo at 30 minutes (mean difference, 16 mm; 95% confidence interval, 10-21). Ten patients (14%) in the placebo group and 2 patients (3%) in the ketoprofen gel group needed rescue drug (P = .35). Conclusion Ketoprofen gel improves pain in patients presenting with mechanical low back pain to ED at 30 minutes in addition to intravenous dexketoprofen when compared to placebo. © 2016 Elsevier Inc

Inbred Strain-Specific Response to Biglycan Deficiency in the Cortical Bone of C57BL6/129 and C3H/He Mice

Inbred strain-specific differences in mice exist in bone cross-sectional geometry, mechanical properties, and indices of bone formation. Inbred strain-specific responses to external stimuli also exist, but the role of background strain in response to genetic deletion is not fully understood. Biglycan (bgn) deficiency impacts bone through negative regulation of osteoblasts, resulting in extracellular matrix alterations and decreased mechanical properties. Because osteoblasts from C3H/He (C3H) mice are inherently more active versus osteoblasts from other inbred strains, and the bones of C3H mice are less responsive to other insults, it was hypothesized that C3H mice would be relatively more resistant to changes associated with bgn deficiency compared with C57BL6/129 (B6;129) mice. Changes in mRNA expression, tissue composition, mineral density, bone formation rate, cross-sectional geometry, and mechanical properties were studied at 8 and 11 wk of age in the tibias of male wildtype and bgn-deficient mice bred on B6;129 and C3H background strains. Bgn deficiency altered collagen cross-linking and gene expression and the amount and composition of mineral in vivo. In bgn's absence, changes in collagen were independent of mouse strain. Bgn-deficiency increased the amount of mineral in both strains, but changes in mineral composition, cross-sectional geometry, and mechanical properties were dependent on genetic background. Bgn deficiency influenced the amount and composition of bone in mice from both strains at 8 wk, but C3H mice were better able to maintain properties close to wildtype (WT) levels. By 11 wk, most properties from C3H knockout (KO) bones were equal to or greater than WT levels, whereas phenotypic differences persisted in B6;129 KO mice. This is the first study into mouse strain-specific changes in a small leucine-rich proteoglycan gene disruption model in properties across the bone hierarchy and is also one of the first to relate these changes to mechanical competence. This study supports the importance of genetic factors in determining the response to a gene deletion and defines biglycan's importance to collagen and mineral composition in vivo

Inbred Strain-Specific Effects of Exercise in Wild Type and Biglycan Deficient Mice

Biglycan (bgn)-deficient mice (KO) have defective osteoblasts which lead to changes in the amount and quality of bone. Altered tissue strength in C57BL6/129 (B6;129) KO mice, a property which is independent of tissue quantity, suggests that deficiencies in tissue quality are responsible. However, the response to bgn-deficiency is inbred strain-specific. Mechanical loading influences bone matrix quality in addition to any increase in bone mass or change in bone formation activity. Since many diseases influence the mechanical integrity of bone through altered tissue quality, loading may be a way to prevent and treat extracellular matrix deficiencies. C3H/He (C3H) mice consistently have a less vigorous response to mechanical loading vs. other inbred strains. It was therefore hypothesized that the bones from both wild type (WT) and KO B6;129 mice would be more responsive to exercise than the bones from C3H mice. To test these hypotheses at 11 weeks of age, following 21 consecutive days of exercise, we investigated cross-sectional geometry, mechanical properties, and tissue composition in the tibiae of male mice bred on B6;129 and C3H backgrounds. This study demonstrated inbred strain-specific compositional and mechanical changes following exercise in WT and KO mice, and showed evidence of genotype-specific changes in bone in response to loading in a gene disruption model. This study further shows that exercise can influence bone tissue composition and/or mechanical integrity without changes in bone geometry. Together, these data suggest that exercise may represent a possible means to alter tissue quality and mechanical deficiencies caused by many diseases of bone

Is photobleaching necessary for Raman imaging of bone tissue using a green laser?

AbstractRaman microspectroscopy is widely used for musculoskeletal tissues studies. But the fluorescence background obscures prominent Raman bands of mineral and matrix components of bone tissue. A 532-nm laser irradiation has been used efficiently to remove the fluorescence background from Raman spectra of cortical bone. Photochemical bleaching reduces over 80% of the fluorescence background after 2 h and is found to be nondestructive within 40 min. The use of electron multiplying couple charge detector (EMCCD) enables to acquire Raman spectra of bone tissues within 1–5 s range and to obtain Raman images less than in 10 min

Estimating the number of pure chemical components in a mixture by maximum likelihood

This paper addresses the problem of determining the number of pure chemical components in a mixture by applying the maximum likelihood estimator (MLE) of intrinsic dimension. The application here is to Raman spectroscopy data, although the method is general and can be applied to any type of data from a chemical mixture. We show that the MLE produces superior results compared to other methods on both simulated and real chemical mixtures, and is accurate even when minor components are present. Even if the signal-to-noise (SN) ratio is very low, accurate estimates can still be obtained by smoothing the data before applying the estimator, this approach is illustrated on two real datasets with high noise levels. Since the MLE is computed locally at every data point, we also show how the local estimates can be used for other applications, such as segmenting the specimen into homogeneous regions. Copyright © 2007 John Wiley & Sons, Ltd.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/56074/1/1027_ftp.pd

Bringing to light the physiological and pathological firing patterns of human induced pluripotent stem cell-derived neurons using optical recordings

Human induced pluripotent stem cells (hiPSCs) are a promising approach to study neurological and neuropsychiatric diseases. Most methods to record the activity of these cells have major drawbacks as they are invasive or they do not allow single cell resolution. Genetically encoded voltage indicators (GEVIs) open the path to high throughput visualization of undisturbed neuronal activity. However, conventional GEVIs perturb membrane integrity through inserting multiple copies of transmembrane domains into the plasma membrane. To circumvent large add-ons to the plasma membrane, we used a minimally invasive novel hybrid dark quencher GEVI to record the physiological and pathological firing patterns of hiPSCs-derived sensory neurons from patients with inherited erythromelalgia, a chronic pain condition associated with recurrent attacks of redness and swelling in the distal extremities. We observed considerable differences in action potential firing patterns between patient and control neurons that were previously overlooked with other recording methods. Our system also performed well in hiPSC-derived forebrain neurons where it detected spontaneous synchronous bursting behavior, thus opening the path to future applications in other cell types and disease models including Parkinson’s disease, Alzheimer’s disease, epilepsy, and schizophrenia, conditions associated with disturbances of neuronal activity and synchrony

AMERICAN JOURNAL OF EMERGENCY MEDICINE

Objective: This study aims to compare serum pregnancy-associated plasma protein A (PAPP-A) levels in surviving and nonsurviving elderly patients with community-acquired pneumonia (CAP), investigating whether PAPP-A is correlated with CAP prediction scores and whether PAPP-A can successfully predict 28-day mortality rates in elderly patients. Methods: This prospective, observational, single-center, cross-sectional study was conducted at the emergency department (ED) of Celal Bayar University Hospital in Manisa, Turkey, between January and September 2014. All patients underwent follow-up evaluations 28 days after admission. The end point was defined as all-cause mortality. Results: A total of 100 elderly patients (mean age, 77.3 +/- 7.6 years [range, 65-94 years]); 60% men) with CAP were enrolled in this study. All-cause mortality at the 28-day follow-up evaluation was 22%. Admission PAPP-A levels were significantly higher in nonsurvivors compared with 28-day survivors (10.3 +/- 4.5 vs 3.8 +/- 2.6 ng/mL, P < .001). A significant and positive correlation between admission PAPP-A levels and pneumonia severity index; confusion, oxygen saturation, respiratory rate, blood pressure, and age 75 years or older; and confusion, urea, respiratory rate, blood pressure, and age older than 65 years scores was found (r = .440, P < .001; r = .395, P < .001; and r = .359, P < .001, respectively). Moreover, we determined that the optimal PAPP-A cutoff for predicting 28-day mortality at the time of ED admission was 5.1 ng/mL, with 77.3% sensitivity and 77.9% specificity. Conclusions: Serum PAPP-A level is valuable for predicting mortality and the severity of the disease among elderly patients with CAP at ED admission. Thus, PAPP-A might play a further role in the clinical assessment of the severity of CAP. (C) 2015 Elsevier Inc. All rights reserved