Osteomyelitis associated with periprosthetic joint infection (PJI) signals a chronic infection and the need for revision surgery. An osteomyelitic bone exhibits distinct morphological features, ...including evidence for osteolysis and an accelerated bone remodelling into poorly organised, poor-quality bone. In addition to immune cells, various bone cell-types have been implicated in the pathology. The present study sought to determine the types of bone-cell activities in human PJI bones. Acetabular biopsies from peri-implant bone from patients undergoing revision total hip replacement (THR) for chronic PJI (with several identified pathogens) as well as control bone from the same patients and from patients undergoing primary THR were analysed. Histological analysis confirmed that PJI bone presented increased osteoclastic activity compared to control bone. Analysis of osteocyte parameters showed no differences in osteocyte lacunar area between the acetabular bone taken from PJI patients or primary THR controls. Analysis of bone matrix composition using Masson's trichrome staining and second-harmonic generation microscopy revealed widespread lack of mature collagen, commonly surrounding osteocytes, in PJI bone. Increased expression of known collagenases, such as matrix metallopeptidase (MMP) 13, MMP1 and cathepsin K (CTSK), was measured in infected bone compared to non-infected bone. Human bone and cultured osteocyte-like cells experimentally exposed to Staphylococcus aureus exhibited strongly upregulated expression of MMP1, MMP3 and MMP13 compared to non-exposed controls. In conclusion, the study identified previously unrecognised bone-matrix changes in PJI caused by multiple organisms deriving from osteocytes. Histological examination of bone collagen composition may provide a useful adjunct diagnostic measure of PJI.
Pulmonary rehabilitation (PR) is a core component of Chronic Obstructive Pulmonary Disease (COPD) management with well recognized benefits. While suggestions for educational content within pulmonary ...rehabilitation have been detailed in clinical guidance, it is unclear what educational content is delivered as part of pulmonary rehabilitation, who delivers it, and how it is delivered.
A systematic review was conducted to identify what educational content is delivered as part of pulmonary rehabilitation, how is this delivered and who delivers it. Databases were searched from 1981 to 2017 using multiple search terms related to “pulmonary rehabilitation” and “education”.
Fourteen studies were identified. This included 6 survey studies, 5 quasi-experimental studies and 3 RCTs. Five key topics that were consistently included within PR programmes were identified as:
1) Anxiety/depression and stress management.
2) Early recognition of signs of infection.
3) Dyspnea and symptom management.
4) Nutrition.
5) Techniques using inhalers and nebulizers.
Broader topics such as welfare/benefits, sexuality, and advance care directives did not frequently feature. Only four studies used tools to measure knowledge or learning pre and post rehabilitation in an attempt to evaluate the effectiveness of the education delivered as part of PR.
The delivery of education in PR programmes is variable and does not follow suggested educational topics. Education needs to take a patient centered motivational approach to ensure effective delivery. Further research into appropriate educational outcome measures are needed, in order to evaluate the changes in behaviour associated with education.
•Pulmonary rehabilitation is an effective intervention which improves outcomes in COPD.•This systematic review has shown that delivery of education in pulmonary rehabilitation is often poorly described in published papers.•The delivery of education in pulmonary rehabilitation is variable and often does not cover suggested topic areas.•Education needs to take a patient centered motivational approach to ensure effective delivery.•Appropriate educational outcome measures are needed to evaluate changes in behaviour before and after pulmonary rehabilitation.
The treatment of deep dental decay has traditionally involved removal of all the soft demineralised dentine before a filling is placed. However this has been challenged in three groups of studies ...which involve sealing soft caries into the tooth. The three main groups either remove no caries and seal the decay into the tooth, remove minimal (ultraconservative) caries at the entrance to a cavity and seal the remaining caries in, or remove caries in stages over two visits some months apart to allow the pulp time to lay down reparative dentine (the stepwise excavation technique).
To test the null hypothesis of no difference in the incidence of damage or disease of the nerve of the tooth (pulp), progression of decay and longevity of restorations irrespective of whether the removal of decay had been minimal (ultraconservative) or complete.
The Cochrane Oral Health Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, PubMed and EMBASE databases were searched. The reference lists in relevant papers were checked.
Randomised controlled trials and controlled clinical trials comparing minimal (ultraconservative) caries removal with complete caries removal in unrestored permanent and deciduous teeth.
Outcome measures recorded were exposure of the nerve of the tooth (pulp) during caries removal, patient experience of symptoms of pulpal inflammation or necrosis, progression of caries under the filling, time until the filling was lost or replaced. Due to the heterogeneity of the included studies the overall estimate of effect was calculated using a random-effects model.
Four studies met the inclusion criteria; two stepwise excavation studies and two ultraconservative caries removal studies. Partial caries removal in symptomless, primary or permanent teeth reduces the risk of pulp exposure. We found no detriment to the patient in terms of pulpal symptoms in this procedure and no reported premature loss or deterioration of the restoration.
The results of this systematic review reject the null hypothesis of no difference in the incidence of damage or disease of the nerve of the tooth (pulp) irrespective of whether the removal of decay had been minimal (ultraconservative) or complete and accepts the null hypothesis of no difference in the progression of decay and longevity of restorations. However, the number of included studies is small and differ considerably. Partial caries removal is therefore preferable to complete caries removal in the deep lesion, in order to reduce the risk of carious exposure. However, there is insufficient evidence to know whether it is necessary to re-enter and excavate further but studies that have not re-entered do not report adverse consequences.
The polymorphic inversion on 17q21, sometimes called the microtubular associated protein tau (MAPT) inversion, is an ∼900 kb inversion found primarily in Europeans and Southwest Asians. We have ...identified 21 SNPs that act as markers of the inverted, i.e., H2, haplotype. The inversion is found at the highest frequencies in Southwest Asia and Southern Europe (frequencies of ∼30%); elsewhere in Europe, frequencies vary from < 5%, in Finns, to 28%, in Orcadians. The H2 inversion haplotype also occurs at low frequencies in Africa, Central Asia, East Asia, and the Americas, though the East Asian and Amerindian alleles may be due to recent gene flow from Europe. Molecular evolution analyses indicate that the H2 haplotype originally arose in Africa or Southwest Asia. Though the H2 inversion has many fixed differences across the ∼900 kb, short tandem repeat polymorphism data indicate a very recent date for the most recent common ancestor, with dates ranging from 13,600 to 108,400 years, depending on assumptions and estimation methods. This estimate range is much more recent than the 3 million year age estimated by Stefansson et al. in 2005.1
Highlights • The patient activation measure is a useful tool to measure readiness to engage. • PAM scores can help tailor support for those with long term conditions. • The PAM tool should not be ...used without clinical and sociodemographic information. • Further work is needed to monitor PAM through the patient journey.
Near‐Earth asteroid (101955) Bennu is an active asteroid experiencing mass loss in the form of ejection events emitting up to hundreds of millimeter‐ to centimeter‐scale particles. The close ...proximity of the Origins, Spectral Interpretations, Resource Identification, and Security–Regolith Explorer spacecraft enabled monitoring of particles for a 10‐month period encompassing Bennu's perihelion and aphelion. We found 18 multiparticle ejection events, with masses ranging from near zero to hundreds of grams (or thousands with uncertainties) and translational kinetic energies ranging from near zero to tens of millijoules (or hundreds with uncertainties). We estimate that Bennu ejects ~104 g per orbit. The largest event took place on 6 January 2019 and consisted of ~200 particles. The observed mass and translational kinetic energy of the event were between 459 and 528 g and 62 and 77 mJ, respectively. Hundreds of particles not associated with the multiparticle ejections were also observed. Photometry of the best‐observed particles, measured at phase angles between ~70° and 120°, was used to derive a linear phase coefficient of 0.013 ± 0.005 magnitudes per degree of phase angle. Ground‐based data back to 1999 show no evidence of past activity for Bennu; however, the currently observed activity is orders of magnitude lower than observed at other active asteroids and too low be observed remotely. There appears to be a gentle decrease in activity with distance from the Sun, suggestive of ejection processes such as meteoroid impacts and thermal fracturing, although observational bias may be a factor.
Plain Language Summary
We measured the brightness of pebble‐sized particles in the vicinity of near‐Earth asteroid Bennu to better understand their physical characteristics and the events that launched them from Bennu's surface. Our measurements spanned 10 months, encompassing Bennu's closest and farthest distances from the Sun, so that we could assess how the level of ejection activity changes with solar distance. We observed 18 multiparticle ejection events containing anywhere from a few to 200+ particles. Individual particles ranged from millimeters to centimeters in diameter. The energy of the events and a possible decrease in activity with larger distances from the Sun suggest that meteoroid impacts, fracturing of surface boulders due to solar heating, or both may be responsible for ejecting the particles. We estimate that Bennu releases ~10,000 g of material over one orbit or 1.2 years. Although mass loss has been remotely observed for other asteroids, the comparatively low level of particle ejection activity at Bennu was only observable thanks to the close proximity of the Origins, Spectral Interpretations, Resource Identification, and Security–Regolith Explorer spacecraft.
Key Points
Asteroid (101955) Bennu is active from perihelion through aphelion with a possible decrease in activity further from the Sun
Bennu's activity is less than that detected by telescope for other active asteroids and is only observable up close
The particles' shallow phase functions resemble those of similarly sized individual rocks rather than those of ensemble asteroid surfaces
We have characterized the effects of the antimitotic drug paclitaxel (TaxolTM) on the Ca2+ signaling cascade of terminally differentiated mouse pancreatic acinar cells. Using single cell fluorescence ...techniques and whole-cell patch clamping to record cytosolic Ca2+ and plasma membrane Ca2+-dependent Cl−currents, we find that paclitaxel abolishes cytosolic Ca2+oscillations and in more than half of the cells it also induces a rapid, transient cytosolic Ca2+ response. This response is not affected by removal of extracellular Ca2+ indicating that paclitaxel releases Ca2+ from an intracellular Ca2+ store. Using saponin-permeabilized cells, we show that paclitaxel does not affect Ca2+ release from an inositol trisphosphate-sensitive store. Furthermore, up to 15 min after paclitaxel application, there is no significant effect on either microtubule organization or on endoplasmic reticulum organization. The data suggest a non-endoplasmic reticulum source for the intracellular Ca2+ response. Using the mitochondrial fluorescent dyes, JC-1 and Rhod-2, we show that paclitaxel evoked a rapid decline in the mitochondrial membrane potential and a loss of mitochondrial Ca2+. Cyclosporin A, a blocker of the mitochondrial permeability transition pore, blocked both the paclitaxel-induced loss of mitochondrial Ca2+ and the effect on Ca2+spikes. We conclude that paclitaxel exerts rapid effects on the cytosolic Ca2+ signal via the opening of the mitochondrial permeability transition pore. This work indicates that some of the more rapidly developing side effects of chemotherapy might be due to an action of antimitotic drugs on mitochondrial function and an interference with the Ca2+ signal cascade.
Tourette's syndrome (TS) is a developmental disorder that has one of the highest familial recurrence rates among neuropsychiatric diseases with complex inheritance. However, the identification of ...definitive TS susceptibility genes remains elusive. Here, we report the first genome-wide association study (GWAS) of TS in 1285 cases and 4964 ancestry-matched controls of European ancestry, including two European-derived population isolates, Ashkenazi Jews from North America and Israel and French Canadians from Quebec, Canada. In a primary meta-analysis of GWAS data from these European ancestry samples, no markers achieved a genome-wide threshold of significance (P<5 × 10(-8)); the top signal was found in rs7868992 on chromosome 9q32 within COL27A1 (P=1.85 × 10(-6)). A secondary analysis including an additional 211 cases and 285 controls from two closely related Latin American population isolates from the Central Valley of Costa Rica and Antioquia, Colombia also identified rs7868992 as the top signal (P=3.6 × 10(-7) for the combined sample of 1496 cases and 5249 controls following imputation with 1000 Genomes data). This study lays the groundwork for the eventual identification of common TS susceptibility variants in larger cohorts and helps to provide a more complete understanding of the full genetic architecture of this disorder.
The OSIRIS‐REx Asteroid Sample Return Mission is the third mission in National Aeronautics and Space Administration (NASA)'s New Frontiers Program and is the first U.S. mission to return samples from ...an asteroid to Earth. The most important decision ahead of the OSIRIS‐REx team is the selection of a prime sample‐site on the surface of asteroid (101955) Bennu. Mission success hinges on identifying a site that is safe and has regolith that can readily be ingested by the spacecraft's sampling mechanism. To inform this mission‐critical decision, the surface of Bennu is mapped using the OSIRIS‐REx Camera Suite and the images are used to develop several foundational data products. Acquiring the necessary inputs to these data products requires observational strategies that are defined specifically to overcome the challenges associated with mapping a small irregular body. We present these strategies in the context of assessing candidate sample sites at Bennu according to a framework of decisions regarding the relative safety, sampleability, and scientific value across the asteroid's surface. To create data products that aid these assessments, we describe the best practices developed by the OSIRIS‐REx team for image‐based mapping of irregular small bodies. We emphasize the importance of using 3‐D shape models and the ability to work in body‐fixed rectangular coordinates when dealing with planetary surfaces that cannot be uniquely addressed by body‐fixed latitude and longitude.
Plain Language Summary
The OSIRIS‐REx Asteroid Sample Return Mission must map asteroid (101955) Bennu using the OSIRIS‐REx Camera Suite. Here we present the techniques that are established to accomplish this goal. Mapping helps us find the best place on the surface of Bennu from which to gather a sample. Because asteroids are small bodies with weak gravitational fields, maneuvering a spacecraft around them can be challenging. Considering these complexities, we have found ways to gather images of Bennu needed for creating maps. Additionally, due to the irregular shape of many asteroids, producing 2‐D maps in terms of latitude and longitude may be insufficient for describing their surface geography. To that end, we have developed software that is capable of creating and displaying image maps in 3‐D.
Key Points
The OSIRIS‐REx Asteroid Sample Return Mission performs image‐based mapping of (101955) Bennu to aid in the selection of a sample‐site
We develop observational strategies to perform mapping to address the challenges associated with surveying a small body
We identify pitfalls and best practices for mapping images of small bodies with large concavities, elongated axes, or overhanging terrain
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