There is uncertainty regarding how long the effects of acupuncture treatment persist after a course of treatment. We aimed to determine the trajectory of pain scores over time after acupuncture, ...using a large individual patient data set from high-quality randomized trials of acupuncture for chronic pain. The available individual patient data set included 29 trials and 17,922 patients. The chronic pain conditions included musculoskeletal pain (low back, neck, and shoulder), osteoarthritis of the knee, and headache/migraine. We used meta-analytic techniques to determine the trajectory of posttreatment pain scores. Data on longer term follow-up were available for 20 trials, including 6376 patients. In trials comparing acupuncture to no acupuncture control (wait-list, usual care, etc), effect sizes diminished by a nonsignificant 0.011 SD per 3 months (95% confidence interval: -0.014 to 0.037, P = 0.4) after treatment ended. The central estimate suggests that approximately 90% of the benefit of acupuncture relative to controls would be sustained at 12 months. For trials comparing acupuncture to sham, we observed a reduction in effect size of 0.025 SD per 3 months (95% confidence interval: 0.000-0.050, P = 0.050), suggesting approximately a 50% diminution at 12 months. The effects of a course of acupuncture treatment for patients with chronic pain do not seem to decrease importantly over 12 months. Patients can generally be reassured that treatment effects persist. Studies of the cost-effectiveness of acupuncture should take our findings into account when considering the time horizon of acupuncture effects. Further research should measure longer term outcomes of acupuncture.
Tumours are comprised of a highly heterogeneous population of cells, of which only a small subset of stem-like cells possess the ability to regenerate tumours in vivo. These cancer stem cells (CSCs) ...represent a significant clinical challenge as they are resistant to conventional cancer therapies and play essential roles in metastasis and tumour relapse. Despite this realization and great interest in CSCs, it has been difficult to develop CSC-targeted treatments due to our limited understanding of CSC biology. Here, we present evidence that specific histone deacetylases (HDACs) play essential roles in the CSC phenotype. Utilizing a novel CSC model, we discovered that the HDACs, HDAC1 and HDAC7, are specifically over-expressed in CSCs when compared to non-stem-tumour-cells (nsTCs). Furthermore, we determine that HDAC1 and HDAC7 are necessary to maintain CSCs, and that over-expression of HDAC7 is sufficient to augment the CSC phenotype. We also demonstrate that clinically available HDAC inhibitors (HDACi) targeting HDAC1 and HDAC7 can be used to preferentially target CSCs. These results provide actionable insights that can be rapidly translated into CSC-specific therapies.
Non-invasively measured brain activity is related to progression-free survival in glioma patients, suggesting its potential as a marker of glioma progression. We therefore assessed the relationship ...between brain activity and increasing tumor volumes on routine clinical magnetic resonance imaging (MRI) in glioma patients. Postoperative magnetoencephalography (MEG) was recorded in 45 diffuse glioma patients. Brain activity was estimated using three measures (absolute broadband power, offset and slope) calculated at three spatial levels: global average, averaged across the peritumoral areas, and averaged across the homologues of these peritumoral areas in the contralateral hemisphere. Tumors were segmented on MRI. Changes in tumor volume between the two scans surrounding the MEG were calculated and correlated with brain activity. Brain activity was compared between patient groups classified into having increasing or stable tumor volume. Results show that brain activity was significantly increased in the tumor hemisphere in general, and in peritumoral regions specifically. However, none of the measures and spatial levels of brain activity correlated with changes in tumor volume, nor did they differ between patients with increasing versus stable tumor volumes. Longitudinal studies in more homogeneous subgroups of glioma patients are necessary to further explore the clinical potential of non-invasively measured brain activity.
We conducted a randomized phase II study to evaluate the impact of adding bevacizumab (B) to 5-fluorouracil (5-FU), hydroxyurea (HU), and radiotherapy (FHX) for intermediate-stage and select T4 head ...and neck squamous cell cancers (HNSCC).
Eligible patients had newly diagnosed HNSCC. Randomization was 2:1 in favor of BFHX. All patients received 500 mg HU p.o. b.i.d., 600 mg/m2/day continuous infusion 5-FU, and b.i.d. radiotherapy with or without bevacizumab 10 mg/kg administered on day 1 of each 14-day cycle. Patients received five cycles consisting of chemoradiotherapy for 5 days followed by 9 days without therapy.
Twenty-six patients were enrolled (19 BFHX and 7 FHX). The study was halted following unexpected locoregional progression. Two-year survival was 68%; 89% treated with FHX and 58% (95% confidence interval 33% to 78%) treated with BFHX. Two-year locoregional control was 80% after chemoradiotherapy and 85% after surgical salvage. All locoregional progression occurred in T4 tumors randomized to BFHX. Two patients receiving BFHX died during therapy, and one died shortly after therapy. No catastrophic bleeding events were seen.
Locoregional progression seen in T4N0-1 tumors treated with BFHX was unexpected and led to study termination. The addition of bevacuzimab to chemoradiotherapy for HNSCC should be limited clinical trials.
Observations indicate that nearly all galaxies contain supermassive black holes at their centers. When galaxies merge, their component black holes form SMBH binaries (SMBHBs), which emit ...low-frequency gravitational waves (GWs) that can be detected by pulsar timing arrays. We have searched the North American Nanohertz Observatory for Gravitational Waves 11 yr data set for GWs from individual SMBHBs in circular orbits. As we did not find strong evidence for GWs in our data, we placed 95% upper limits on the strength of GWs from such sources. At = 8 nHz, we placed a sky-averaged upper limit of h0 < 7.3(3) × 10−15. We also developed a technique to determine the significance of a particular signal in each pulsar using "dropout" parameters as a way of identifying spurious signals. From these upper limits, we ruled out SMBHBs emitting GWs with = 8 nHz within 120 Mpc for , and within 5.5 Gpc for at our most sensitive sky location. We also determined that there are no SMBHBs with emitting GWs with = 2.8-317.8 nHz in the Virgo Cluster. Finally, we compared our strain upper limits to simulated populations of SMBHBs, based on galaxies in the Two Micron All-Sky Survey and merger rates from the Illustris cosmological simulation project, and found that only 34 out of 75,000 realizations of the local universe contained a detectable source.
Aquifer storage and recovery systems using multiple partially penetrating wells (MPPW-ASR) can form a viable solution to the problem of freshwater buoyancy when using brackish aquifers for freshwater ...storage. This study presents the result of a series of laboratory experiments that aimed at visualizing the shape of freshwater bodies injected into a brackish aquifer and determining the effect on the recovery efficiency (RE) of several MPPW-ASR operational variables. A model aquifer was built in a Plexiglas tank using glass beads and water was injected and abstracted through point and vertical wells, which were operated in various combinations. Numerical models were used to support the interpretation of the time-lapse photographs, and showed that three-dimensional flow effects had to be considered for a correct interpretation of the visible dye patterns. Upward migration of both fresh (during injection) and brackish water (during recovery) along the vertical wells was observed, indicating that the role of well infrastructure as conduits is a critical design criterion for real-world systems. Gravitational instabilities formed when freshwater did not extend all the way to the top of the aquifer, and this negatively impacted the RE by causing greater mixing. The positive freshwater buoyancy led to freshwater bodies that became narrower with depth, and the formation of thin, elongated buffer zones along the aquifer top in multicycle experiments. Up-coning below abstraction wells resulted in lower RE values, reinforcing the potential of scavenger wells to enhance MPPW-ASR system performance.
•7 galectin genes were identified in in soil-transmitted intestinal nematode Strongyloides ratti, 4 are excreted/secreted from the parasite.•These 4 galectin genes are differentially expressed in ...Strongyloides stages.•Sr-Gal-3 of intestine-dwellimg parasitic females binds β-galactoside glycans, while Sr-Gal-1 of free-living females did not bind to the glycans.•Sr-Gal-3 and at low degree Sr-Gal-1 induced type 2 cytokines IL-22 and TSLP in 3D co-cultures of intestinal epithelial cells with dendritic cells.•Sr-Gal-1 and Sr-Gal-3 can promote cell migration of intestinal cells compatible with influencing wound healing process.
Helminths are complex pathogens that ensure their long-term survival by influencing the immune responses of their host. Excretory/secretory products (ESP) can exert immunoregulatory effects which foster parasite survival. Galectins represent a widespread group of β-galactoside-binding proteins which are involved in a multitude of biological processes operative in parasite-host interaction. We had earlier identified seven galectins in Strongyloides ratti, four of them detected in the ESP of distinct developmental stages of the parasite. In the present report, we focused on the characterization of two of them, Sr-galectin-1 (Sr-Gal-1) and Sr-galectin-3 (Sr-Gal-3). While Sr-Gal-3 expression was strongest in parasitic females, Sr-Gal-1 was predominantly expressed in free-living females. Both proteins were cloned and recombinantly expressed in an E. coli expression system. Their glycan-binding activity was verified by haemagglutination and glycan array analysis. Furthermore, primary immunological activities of the Sr-galectins were initially investigated by the application of an in vitro mucosal 3D-culture model, comprising of mucosa-associated epithelial and dendritic cells. The Sr-galectins stimulated preferentially the release of the type 2 cytokines thymic stromal lymphopoietin and IL-22, a first indication for immunoregulatory activity. In addition, the Sr-galectins dose-dependently fostered cell migration. Our results confirm the importance of these carbohydrate-binding proteins in host-parasite-interaction by indicating possible interaction with the host mucosa-associated cells.
Atmospheric mercury deposition by wet and dry processes contributes mercury to terrestrial and aquatic systems. Factors influencing the amount of mercury deposited to boreal forests were identified ...in this study. Throughfall and open canopy precipitation samples were collected in 2005 and 2006 using passive precipitation collectors from pristine sites located across the Superior National Forest in northern Minnesota, USA. Samples were collected approximately every 2 weeks and analyzed for total (THg) and methyl mercury (MeHg). Forest canopy type and density were the primary influences on THg and MeHg deposition. Highest THg and MeHg concentrations were measured beneath conifer canopies (THg mean = 19.02 ng L
−1
; MeHg mean = 0.28 ng L
−1
) followed by deciduous throughfall (THg mean = 12.53 ng L
−1
; MeHg mean = 0.19 ng L
−1
) then open precipitation (THg mean = 8.19 ng L
−1
; MeHg mean = 0.12 ng L
−1
). The greater efficiency of conifers at scavenging THg and MeHg from the atmosphere may increase the risk of mercury related water quality issues in conifer-dominated systems.
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