1,141 research outputs found
The navigation of homing pigeons: Do they use sun Navigation?
Experiments to determine the dependence of homing pigeons on the sun as a navigational cue are discussed. Various methods were employed to interrupt the circadian rhythms of the pigeons prior to release. It was determined that the sun may serve as a compass, but that topographic features are more important for navigation. The effects of a magnetic field produced by electric equipment carried by the bird were also investigated. It was concluded that magnetic fields may have a small effect on the homing ability. The exact nature of the homing pigeon's navigational ability is still unknown after years of elaborate experimentation
Isolated deep earthquakes beneath the North Island of New Zealand
Seismicity shallows towards the south along the Tonga-Kermadec-Hikurangi margin, deep and intermediate seismicity being absent altogether in the South Island of New Zealand. Beneath the Taranaki region of the North Island the maximum depth of the main seismicity is 250 km, but very rare events occur directly below at 600 km. These could be associated with a detached slab or a vertical, aseismic continuation of the subducted Pacific Plate. Six small events that occurred in the 1990s were recorded extensively by digital instruments of the New Zealand National Network (NZNN) and temporary deployments. We relocate these events by a joint hypocentre determination (JHD) method and find their focal mechanisms using first motions and relative amplitudes of P and S arrivals. The earthquakes relocate to a remarkably uniform depth of 603 +/- 3 kmrelative error (+/- 10 km absolute error) in a line 30- km long orientated 40 NE, roughly parallel to the strike of the intermediate- depth seismicity. The only consistent component of the focal mechanisms is the tension axis: all lie close to horizontal and tend to align with the line of hypocentres. We interpret this deep seismic zone as a detached sliver of plate lying horizontally with the same orientation as the main subducted plate above. Volume change caused by a phase change controlled by the pressure at 600 km and temperature in the sliver produces a pattern of strain that places the sliver under tension along its lengt
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Conflict of Interest in Spine Research Reporting
Background: Medical studies are more likely to report favorable findings when a conflict of interest is declared. We aim to quantify and determine the effect of author disclosure of conflict of interest on scientific reporting. Methods: Abstracts from an international spine research meeting (North American Spine Society 2010) were selected that specifically evaluated a device, biologic, or proprietary procedure. They were then made anonymous to reviewers. An item of interest was established in each of the abstracts in order to standardize evaluation. Next, three blinded reviewers independently rated the abstracts as favorable, neutral, or unfavorable with regard to the item of interest. Additionally, the blinded reviewers attempted to predict whether a related disclosure was made. The meeting disclosure index was used to tabulate the minimum US dollar value attributable to disclosures. Results: Of the 344 total abstracts, 76 met inclusion criteria. In 79%, a related conflict of interest was reported. The amount of the disclosure was incompletely reported in 30% of cases. Where available, it averaged a cumulative minimum of $219,634 USD per abstract. The results of the abstracts were judged to be favorable, neutral, and unfavorable in 63%, 32% and 5% of abstracts, respectively. There was no correlation between the presence of a related disclosure and the findings of the studies (p = 0.81), although interpretation of this is limited by a small sample size and an overall apparent bias to report favorable studies. Additionally, the blinded reviewers were unable to predict whether a related disclosure was made (p = 0.40). Conclusion: No association existed between the presence of a related disclosure and the results of the studies. While the actual compliance with reporting a potential conflict of interest is unable to be determined, the value amount related to the disclosures made was inadequately reported according to meeting guidelines
Etiology of Experimental Osteoarthritis: Early Events and Potential Clinical Implications
Introduction Osteoarthritis (OA) is the most common form of arthritis and accounts for 50% of all chronic conditions in the elderly. One in two adults reported a chronic musculoskeletal condition in 2005, twice the rate of reported chronic heart or respiratory conditions(2). In addition, persons aged 45 to 64 account for an increasingly greater proportion of total musculoskeletal disease treatment costs and lost wages, a trend that will continue for the next several decades(3). Surgical treatment culminating in total joint replacement (TJR) remains the most effective therapy for late stage OA. Current treatment of pre-surgical OA consists of pain relieving medications (i.e. NSAIDs), physical therapy, and mechanical supports (i.e. braces, canes, and walkers). Despite the wealth of clinical data on OA, there is currently no cure for the disease. Our previous work in developing potential disease-modifying osteoarthritis drugs (DMOADs) had yielded promising results, showing a decrease in OA cartilage lesion areas and histological grades (Figure 1). Interestingly, we noted that animals treated for only the first 3 weeks demonstrated near 6-week levels of OA reduction. These differences in treatment responsiveness necessitate a better characterization of the specific cellular phases of OA throughout the natural disease progression. The current study was undertaken to clarify this progression of early OA events.
Methods OA was induced in the right knees of 10-week-old male 129 S6/SvEv (Taconic) mice via DMM surgery. Mice receiving sham surgery with no destabilization were used as negative controls. Both groups were sacrificed at 4, 8, 12, 16, and 20-day intervals in order to evaluate OA progression. Knees were harvested, processed, and sectioned at 6um intervals. Sections were stained for cartilage composition (Safranin-O) and scored for progression and severity of OA by 3 blinded observers using a 0-5 scale (modified Mankin System)(4). Both ‘mean maximal’ scores (highest scores per knee), and ‘mean summed scores (sum of scores per knee) were generated using this scale. All scores were averaged across observers. Cartilage lesion area, subchondral bone area (sclerosis), and apoptosis (TUNEL method) were measured using a histomorphometric analysis package (ImageJ)(5).
Conclusions Measurable osteoarthritic changes in articular cartilage and underlying bone following meniscal injury occur far earlier than previously described. Some changes are clearly degenerative (OA grade, stage & lesion area), however, some changes (subchondral bone thickening) could be regarded as compensatory supportive mechanisms. Cell death (apoptosis) is an acute event following relatively minor changes to knee biomechanics. Our results suggest an opportunity for intervention early on in OA before the resulting articular changes become irreversible. Specifically, consideration of anti-apoptosis based therapies could prevent much of the subsequent structural changes in articular cartilage.
Future Directions Apoptosis data suggests pursuing an anti-apoptotic therapy strategy in the DMM model of OA Early bone sclerotic events suggest bone tissue as a target for anti-OA therapy. Translationally, preventing or delaying OA due to soft tissue injuries (e.g., sports injuries) may be possible with early medical treatment of OA proximal to the time of injury.
References
(1) International Bone and Joint Decade 2000-2010 Organization, 1999.
(2) National Center for Health Statistics, National Health Interview Survey, 2005.
(3) Kurtz, SM, Lau, E, et al. Future Young Patient Demand for Primary and Revision Joint Replacement: National Projections from 2010 to 2030. Clinical Orthopaedics and Related Research, April 2009.
(4) Kurtz, SM, Ong, K, et. al. Projections of Primary and Revision Hip and Knee Arthroplasty in the United States from 2005 to 2030. The Journal of Bone and Joint Surgery, 2007;89:780-5.
(5) http://rsbweb.nih.gov/ij
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Socioeconomic Status Correlates with the Prevalence of Advanced Coronary Artery Disease in the United States
Background: Increasingly studies have identified socioeconomic factors adversely affecting healthcare outcomes for a multitude of diseases. To date, however, there has not been a study correlating socioeconomic details from nationwide databases on the prevalence of advanced coronary artery disease. We seek to identify whether socioeconomic factors contribute to advanced coronary artery disease prevalence in the United States. Methods and Findings: State specific prevalence data was queried form the United States Nationwide Inpatient Sample for 2009. Patients undergoing percutaneous coronary angioplasty and coronary artery bypass graft were identified as principal procedures. Non-cardiac related procedures, lung lobectomy and hip replacement (partial and total) were identified and used as control groups. Information regarding prevalence was then merged with data from the Behavioral Risk Factor Surveillance System, the largest, on-going telephone health survey system tracking health conditions and risk behaviors in the United States. Pearson's correlation coefficient was calculated for individual socioeconomic variables including employment status, level of education, and household income. Household income and education level were inversely correlated with the prevalence of percutaneous coronary angioplasty (−0.717; −0.787) and coronary artery bypass graft surgery (−0.541; −0.618). This phenomenon was not seen in the non-cardiac procedure control groups. In multiple linear regression analysis, socioeconomic factors were significant predictors of coronary artery bypass graft and percutaneous transluminal coronary angioplasty (p<0.001 and p = 0.005, respectively). Conclusions: Socioeconomic status is related to the prevalence of advanced coronary artery disease as measured by the prevalence of percutaneous coronary angioplasty and coronary artery bypass graft surgery
The Varus Knee Reveals Differential Expression Patterns of miRNAs in Spared vs. Non-spared Compartments
Introduction MicroRNAs (miRNAs) function by repressing cellular protein levels to provide a sophisticated level of gene regulation that coordinates a broad spectrum of biological processes. MiRNA inhibition of mRNA translation has emerged as an important regulator of chondrogenic and osteogenic development, osteoblast, osteoclast and chondrocyte cell growth and differentiation, and tissue homeostasis in the adult skeleton. MiRNAs control many layers of regulation in adult tissues connected to both normal biological and pathologic cellular activities. The study of miRNAs in skeletal disorders is in its infancy. Osteoarthritis (OA) is a disease that progresses from degeneration of the articular cartilage to remodeling of the underlying subchondral bone over many years. While miRNAs have been identified with the inflammatory pathogenesis of rheumatoid arthritis (RA), only a few studies have been performed on OA tissue (1,2) . Here we performed a systematic analysis of the articular cartilage from varus OA knee replacements, comparing multiple tissue samples from the lateral (spared) and medial (diseased) compartments. Before proceeding to a miRNA profiling, each sample was analyzed for expression of a small set of miRNAs that have been reported in association with RA, OA and cartilage formation. These preliminary findings have identified a spectrum of changes in surface cartilage between control and diseased tissue.
Methods Human tissues: 6 individual articular cartilage samples were harvested from a total of 5 osteoarthritic varus human knees. Cartilage samples were exempt from IRB review as they are discarded materials. Samples were removed with a biopsy punch and were approximately 6 x 2mm (diameter x thickness). Cartilage specimens were harvested from the more normal-appearing lateral (‘spared’) compartments and from the more OA-affected, medial compartments of the knees. This sampling technique allows direct comparison of more significantly OA-affected cartilage samples with those of lower OA grade from the same set of individuals. Knee ages ranged from 53-74 years old and averaged 65 years old.
RNA and miRNA Isolation: Each osteochondral specimen was placed in RNA Later (Sigma) immediately following surgical removal, in order to preserve the integrity of the total RNA. Specimens were transported to the lab where individual samples were removed carefully with RNase-treated tools and were transferred intofresh RNA Later solution and incubated overnight at 4C to allow penetration and maximal inhibition of RNase activity. Samples were then removed from RNA Later, blotted briefly and frozen in liquid N2, and then pulverized using a Bessman tissue pulverizer (Fisher). The pulverized samples were immediately placed into Trizol (InVitrogen) and homogenized using a polytron device. Total RNA was isolated to include small RNAs of \u3e17 nucleotides, according to the manufacturer’s protocol (InVitrogen). Purified RNA was obtained using precipitated total RNAs filtered through glass columns according to the manufacturer’s protocol (Zymo Research). RNAs were reverse-transcribed into DNA using 900ng of each purified RNA sample using the TaqMan microRNA Reverse Transcription Kit (Applied Biosystems). TaqMan qPCR analysis for small RNAs was performed using the following human primer-probe sets from Applied Biosystems: hsa-miRs-: 9, 22, 27a, 29a and 34a. Human U6 was used to normalize all qPCR data and data was plotted as normalized relative values. Normalized relative values were averaged for each of the complement of medial vs. lateral samples.
Results MiRs were found to be either up- or down-regulated in a manner that suggests a mechanism of de-repression of pro-inflammatory cytokine signaling and repression of pro-inflammatory events in medial vs. lateral varus knee OA cartilage samples, respectively. MiRs 9, 27a, and 29a were found to up-regulated in lateral varus knee cartilage samples vs. medial varus knee cartilage samples (Fig.1. A,C,E,F). Conversely, miRs 22 and 34a were found to upregulated in medial vs. lateral cartilage samples (Fig1, B, D).
Discussion The functional characterization of global gene expression patterns through miRNAs in OA is lacking. Particularly, the roles of miRs in OA disease development, as biomarkers, and in disease outcomes are at question. A few large-scale microarray approaches have previously identified expression signatures of potential OA-involved miRNAs (2). By comparing cartilage samples that derive from more advanced (medial) vs. less advanced (lateral) OA stages in varus human knees, we seek to combine miRNA expression analysis with clinicopathologic features. MiRs -9, -22 and -34a are known to be involved in regulating pro-inflammatory events in OA. Higher levels of miRs, -9, -27a & -140 in less-affected lateral compartment cartilage are consistent with previous reports of reduced TNFa, MMP-13 & ADAMTS-5 expression events, respectively (Fig.1, F, E & A) (3,4,5). MiRs -22 and -34a have been shown to be associated with promoting tissue catabolism by their presence and are here shown to be increased in more affected medial compartment cartilage (Fig.1, B, D) (4). In addition, miR-34a deficiency has been previously shown to inhibit chondrocyte apoptosis, consistent with the lower expression level found in lateral cartilage (Fig.1, D) (6). MiR-29a was found in a previous microarray analysis to be the highest-fold down-regulated miRNA in OA vs. normal cartilage, consistent with our finding of under-expression in medial cartilage samples (Fig.1, C) (1). The goal of these studies is to begin to understand how miRNAs can both contribute to and protect against OA. Here we show that the comparison of cartilage-derived miRNAs in medial and lateral compartment pairs from the same knee may facilitate validation of candidate OA miRNAs.
Significance The aims of this project are to provide an internally-controlled platform of study for the miRNAs of OA using the natural disease differences inherent in spared vs. non-spared cartilage compartments from a varus OA knee. Such efforts may provide an alternative methodology when compared to the significant barrier of obtaining age-matched, non-OA control knee cartilage.
References
1.) Iliopoulus D. PLoS One. 2008;3(11):e3740. Epub 2008 Nov 17.
2.) Goldring MB. Curr Opin Rheumatol. 2011 Jul 22. [Epub].
3.) Yu C. J Int Med Res. 2011;39(1):1-9.
4.) Alcaraz MJ. Biochem Pharmacol. 2010 Jul 1;80(1):13-21.
5.) Miyaki S. Genes Dev. 2010 Jun 1;24(11):1173-85.
6.) Abouheif MM. Rheumatology. 2010 Nov;49(11):2054-60
Botulinum toxin type A in the prophylactic treatment of chronic tension-type headache: A multicentre, double-blind, randomized, placebo-controlled, parallel-group study
We studied the safety and efficacy of 0 U, 50 U, 100 U, 150 U (five sites), 86 Usub and 100 Usub (three sites) botulinum toxin type A (BoNTA; BOTOX); Allergan, Inc., Irvine, CA, USA) for the prophylaxis of chronic tension-type headache (CTTH). Three hundred patients (62.3% female; mean age 42.6 years) enrolled. For the primary endpoint, the mean change from baseline in the number of TTH-free days per month, there was no statistically significant difference between placebo and four BoNTA groups, but a significant difference favouring placebo vs. BoNTA 150 was observed (4.5 vs. 2.8 tension headache-free days/month; P = 0.007). All treatment groups improved at day 60. Although efficacy was not demonstrated for the primary endpoint, at day 90, more patients in three BoNTA groups had \u3eor=50% decrease in tension headache days than did placebo (
Non-edible parts of Solanum stramoniifolium Jacq. - a new potent source of bioactive extracts rich in phenolic compounds for functional foods
Extracts prepared from leaves, roots, and stems of Solanum stramoniifolium Jacq. (Solanaceae) in 80% ethanol have been tested for their in vitro antioxidant, anti-inflammatory, antimicrobial, and cytotoxic activities with an aim to find new sources of substances for functional foods and food additives. The root extract revealed the highest antioxidant activity in all assays exceeding the trolox capacity, and was the only extract that inhibited nitric oxide production in mouse macrophage cells, showing also the capacity to suppress the growth of all tested human tumor cell lines (MCF-7, NCI-H460, HeLa and HepG2). The leaf extract showed the strongest antimicrobial activity inhibiting all tested clinical isolates. To the author's best knowledge it was the first time that all individual parts of this plant were tested for biological activity together with the phenolic compound characterization.Foundation for Science and Technology (FCT, Portugal) [UID/AGR/00690/2013, SFRH/BPD/107855/2015, SFRH/BPD/101413/2014, SFRH/BPD/BPD/68344/2010]; FEDER [UID/AGR/00690/2013, SFRH/BPD/107855/2015, SFRH/BPD/101413/2014, SFRH/BPD/BPD/68344/2010]; FEDER, through POCI-COMPETE [POCI-01-0145-FEDER-006984]; FCT [POCI-01-0145-FEDER-006984]; Internal Grant Agency of Tomas Bata University in Zlin [IGA/FT/2016/003]POCI-01-0145-FEDER-006984, CIMO, Kansainvälisen Liikkuvuuden ja Yhteistyön Keskus; POCI-COMPETE2020, FCT, Fundació Catalana de Trasplantament; SFRH/BPD/101413/2014, CIMO, Kansainvälisen Liikkuvuuden ja Yhteistyön Keskus; SFRH/BPD/107855/2015, CIMO, Kansainvälisen Liikkuvuuden ja Yhteistyön Keskus; SFRH/BPD/BPD/68344/2010, CIMO, Kansainvälisen Liikkuvuuden ja Yhteistyön Keskus; UID/AGR/00690/2013, CIMO, Kansainvälisen Liikkuvuuden ja Yhteistyön Keskus; FEDER, Federación Española de Enfermedades Rara
Tantalum versus Titanium Acetabular Shells in Young Active THR Patients: A Radiostereometric Analysis (RSA) Study
Introduction: In the active THR (total hip replacement) population, acetabular component stability is crucial for preventing implant failure. Titanium fiber metal coating is the most common material used in cementless THR. Trabecular metal, composed of porous tantalum, is designed to improve tissue infiltration and limit migration. It is unknown if tantalum offers an advantage over titanium in the biologic fixation of porous-coated acetabular shells. Radiostereometric analysis (RSA) provides highly precise measurements of micromotion that are otherwise not detectable by routine radiographs.
Methods: In this IRB approved, prospective, randomized, blinded study, 46 patients received a primary THR by a single surgeon. Each patient was randomized to receive a titanium (23) or tantalum (23) uncemented cup. Tantalum RSA markers were implanted around the polyethylene liner and into the patient’s femur and periacetabular bone. Also, patients received either a highly cross-linked (n=25) or a conventional liner (n=21). RSA examinations, Harris Hip, UCLA, WOMAC, SF-12 scores were obtained at 10 days, 6 months, and annually through 5 years.
Results: The randomized groups had comparable mean age, preoperative activity, and average BMI. The tantalum shells demonstrated less median translation than the titanium shells at each time-point, but there was no statistical difference between the two shells. At 6 months median translation of tantalum and titanium was -0.01mm and 0.04mm and remained stable with median translation of -0.02mm and 0.04mm at four years. Mean UCLA, WOMAC, Harris Hip, and SF-12 PCS and MCS scores improved similarly in both groups.
Conclusions: After THR, both patient cohorts had excellent clinical outcomes with statistically significant improvements in function and pain relief. Although tantalum porous-coated acetabular shells demonstrated less y-translation and y-rotation at all time points, there was no statistically significant difference in shell migration and both shells demonstrated excellent stability with minimal micromotion at four years
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