Feasibility and Preliminary Efficacy of a Physical Activity Counseling Intervention Using Fitbit in People With Knee Osteoarthritis: The TRACK-OA Study Protocol

Background Physical activity (PA) reduces pain and improves functioning in people with knee osteoarthritis (OA), but few people with the condition meet recommended PA guidelines. Successful intervention strategies to increase PA include goal setting, action planning, self-monitoring, and follow-up feedback from a healthcare professional. Recently developed consumer wearable activity trackers allow users to set activity goals, self-monitor daily goal-progress, and provide feedback on goal attainment. It is hypothesized that a multi-component physiotherapist-led intervention that includes a short (40-min) education module, guided goal-setting and action planning, the use of a wristband activity tracker, and weekly follow-up phone calls will lead to increased PA outcomes. Methods/design Thirty-six participants will be recruited from the community for a two-group pilot randomized controlled trial with a stepped-wedge design using an intention-to-treat analysis. Computer-generated block randomization will be performed using varying block sizes and a 1:1 allocation ratio. The 4-week intervention will be delivered immediately (immediate-intervention group) or after a 5-week delay (delayed-intervention group). Outcome measures of pain and disability (Knee Injury and OA Outcome Score), disease self-management ability (Partners in Health Scale), and objective bouted moderate-to-vigorous PA and sedentary time (BodyMedia SenseWear Mini Armband) will be collected at baseline (week 0) and two follow-ups (weeks 5 and 10), for a total study duration of 11 weeks. Feasibility data relating to process, resource, management, and scientific elements of the trial will be collected. Outcome measure and feasibility data will be summarized, and an estimate of intervention efficacy will be obtained by regression model with planned comparisons. The trial began recruiting in February 2015. To date, 34 subjects have been recruited. Discussion This study will evaluate the feasibility and preliminary efficacy of a novel intervention to promote PA in people living with knee OA. The results will provide valuable information to inform a larger randomized trial to assess intervention effectiveness

Dopamine dysregulation in the prefrontal cortex relates to cognitive deficits in the sub-chronic PCP-model for schizophrenia: a preliminary investigation

yesRationale: Dopamine dysregulation in the prefrontal cortex (PFC) plays an important role in cognitive dysfunction in schizophrenia. Sub-chronic phencyclidine (scPCP) treatment produces cognitive impairments in rodents and is a thoroughly validated animal model for cognitive deficits in schizophrenia. The aim of our study was to investigate the role of PFC dopamine in scPCP-induced deficits in a cognitive task of relevance to the disorder, novel object recognition (NOR). Methods: Twelve adult female Lister Hooded rats received scPCP (2 mg/kg) or vehicle via the intraperitoneal route twice daily for seven days, followed by seven days washout. In vivo microdialysis was carried out prior to, during and following the NOR task. Results: Vehicle rats successfully discriminated between novel and familiar objects and this was accompanied by a significant increase in dopamine in the PFC during the retention trial (P<0.01). scPCP produced a significant deficit in NOR (P<0.05 vs. control) and no PFC dopamine increase was observed. Conclusions: These data demonstrate an increase in dopamine during the retention trial in vehicle rats that was not observed in scPCP-treated rats accompanied by cognitive disruption in the scPCP group. This novel finding suggests a mechanism by which cognitive deficits are produced in this animal model and support its use for investigating disorders in which PFC dopamine is central to the pathophysiology

Chemoselective sequential click ligations directed by enhanced reactivity of an aromatic ynamine

Aromatic ynamines or N-alkynylheteroarenes are highly reactive alkyne components in Cu-catalyzed Huisgen [3 +2] cycloaddition (“click”) reactions. This enhanced reactivity enables the chemoselective formation of 1,4-triazoles using the representative aromatic ynamine N-ethynylbenzimidazole in the presence of a competing aliphatic alkyne substrate. The unique chemoselectivity profile of N-ethynylbenzimidazole is further demonstrated by the sequential click ligation of a series of highly functionalized azides using a heterobifunctional diyne, dispelling the need for alkyne protecting groups

The type III secretion system effector SeoC of salmonella enterica subsp. salamae and S. enterica subsp. arizonae ADP-Ribosylates Src and inhibits opsonophagocytosis

Salmonella species utilize type III secretion systems (T3SSs) to translocate effectors into the cytosol of mammalian host cells, subverting cell signaling and facilitating the onset of gastroenteritis. In this study, we compared a draft genome assembly of Salmonella enterica subsp. salamae strain 3588/07 against the genomes of S. enterica subsp. enterica serovar Typhimurium strain LT2 and Salmonella bongori strain 12419. S. enterica subsp. salamae encodes the Salmonella pathogenicity island 1 (SPI-1), SPI-2, and the locus of enterocyte effacement (LEE) T3SSs. Though several key S Typhimurium effector genes are missing (e.g., avrA, sopB, and sseL), S. enterica subsp. salamae invades HeLa cells and contains homologues of S. bongori sboK and sboC, which we named seoC SboC and SeoC are homologues of EspJ from enteropathogenic and enterohemorrhagic Escherichia coli (EPEC and EHEC, respectively), which inhibit Src kinase-dependent phagocytosis by ADP-ribosylation. By screening 73 clinical and environmental Salmonella isolates, we identified EspJ homologues in S. bongori, S. enterica subsp. salamae, and Salmonella enterica subsp. arizonae The β-lactamase TEM-1 reporter system showed that SeoC is translocated by the SPI-1 T3SS. All the Salmonella SeoC/SboC homologues ADP-ribosylate Src E310 in vitro Ectopic expression of SeoC/SboC inhibited phagocytosis of IgG-opsonized beads into Cos-7 cells stably expressing green fluorescent protein (GFP)-FcγRIIa. Concurrently, S. enterica subsp. salamae infection of J774.A1 macrophages inhibited phagocytosis of beads, in a seoC-dependent manner. These results show that S. bongori, S. enterica subsp. salamae, and S. enterica subsp. arizonae share features of the infection strategy of extracellular pathogens EPEC and EHEC and shed light on the complexities of the T3SS effector repertoires of Enterobacteriaceae

Oceanographic Variability in Cumberland Bay, South Georgia, and Its Implications for Glacier Retreat

South Georgia is a heavily glaciated sub-Antarctic island in the Southern Ocean. Cumberland Bay is the largest fjord on the island, split into two arms, each with a large marine-terminating glacier at the head. Although these glaciers have shown markedly different retreat rates over the past century, the underlying drivers of such differential retreat are not yet understood. This study uses observations and a new high-resolution oceanographic model to characterize oceanographic variability in Cumberland Bay and to explore its influence on glacier retreat. While observations indicate a strong seasonal cycle in temperature and salinity, they reveal no clear hydrographic differences that could explain the differential glacier retreat. Model simulations suggest the subglacial outflow plume dynamics and fjord circulation are sensitive to the bathymetry adjacent to the glacier, though this does not provide persuasive reasoning for the asymmetric glacier retreat. The addition of a postulated shallow inner sill in one fjord arm, however, significantly changes the water properties in the resultant inner basin by blocking the intrusion of colder, higher salinity waters at depth. This increase in temperature could significantly increase submarine melting, which is proposed as a possible contribution to the different rates of glacier retreat observed in the two fjord arms. This study represents the first detailed description of the oceanographic variability of a sub-Antarctic island fjord, highlighting the sensitivity of fjord oceanography to bathymetry. Notably, in fjords systems where temperature decreases with depth, the presence of a shallow sill has the potential to accelerate glacier retreat

Versatile poly(diallyl dimethyl ammonium chloride)-layered nanocomposites for removal of cesium in water purification

In this work, we elucidate polymer-layered hollow Prussian blue-coated magnetic nanocomposites as an adsorbent to remove radioactive cesium from environmentally contaminated water. To do this, Fe3O4 nanoparticles prepared using a coprecipitation method were thickly covered with a layer of cationic polymer to attach hollow Prussian blue through a self-assembly process. The as-synthesized adsorbent was confirmed through various analytical techniques. The adsorbent showed a high surface area (166.16 m2/g) with an excellent cesium adsorbent capacity and removal efficiency of 32.8 mg/g and 99.69%, respectively. Moreover, the superparamagnetism allows effective recovery of the adsorbent using an external magnetic field after the adsorption process. Therefore, the magnetic adsorbent with a high adsorption efficiency and convenient recovery is expected to be effectively used for rapid remediation of radioactive contamination

A Changing Hydrological Regime: Trends in Magnitude and Timing of Glacier Ice Melt and Glacier Runoff in a High Latitude Coastal Watershed

With a unique biogeophysical signature relative to other freshwater sources, meltwater from glaciers plays a crucial role in the hydrological and ecological regime of high latitude coastal areas. Today, as glaciers worldwide exhibit persistent negative mass balance, glacier runoff is changing in both magnitude and timing, with potential downstream impacts on infrastructure, ecosystems, and ecosystem resources. However, runoff trends may be difficult to detect in coastal systems with large precipitation variability. Here, we use the coupled energy balance and water routing model SnowModel-HydroFlow to examine changes in timing and magnitude of runoff from the western Juneau Icefield in Southeast Alaska between 1980 and 2016. We find that under sustained glacier mass loss (−0.57 ± 0.12 m w. e. a−1), several hydrological variables related to runoff show increasing trends. This includes annual and spring glacier ice melt volumes (+10% and +16% decade−1) which, because of higher proportions of precipitation, translate to smaller increases in glacier runoff (+3% and +7% decade−1) and total watershed runoff (+1.4% and +3% decade−1). These results suggest that the western Juneau Icefield watersheds are still in an increasing glacier runoff period prior to reaching “peak water.” In terms of timing, we find that maximum glacier ice melt is occurring earlier (2.5 days decade−1), indicating a change in the source and quality of freshwater being delivered downstream in the early summer. Our findings highlight that even in maritime climates with large precipitation variability, high latitude coastal watersheds are experiencing hydrological regime change driven by ongoing glacier mass loss.The authors would like to thank W. P. Dryer, C. McNeil, S. Candela, and J. Pierce for help in the field. R. Crumley and C. Cosgrove assisted with SnowModel initialization. The Juneau Icefield Research Program (JIRP) provided field data and logistical support. E. Berthier provided geodetic data, F. Ziemen contributed model results, and C. McNeil provided assistance with datasets on behalf of both USGS and JIRP. The authors thank three anonymous reviewers for suggestions that have greatly improved the manuscript. This work was supported by a Department of Interior Alaska Climate Adaptation Science Center graduate fellowship awarded under Cooperative Agreement G17AC00213, by NASA under award NASANNX16AQ88G, by the National Science Foundation under award OIA-1208927 and by the State of Alaska (Experimental Program for Stimulating Competitive Research–Alaska Adapting to Changing Environments award), and by the University of Alaska Fairbanks Resilience and Adaptation Program. The authors acknowledge that field work was conducted on the traditional and unceded lands of the Lingit Aani (Tlingit), Michif Piyii (Métis), and Dënéndeh nations.Ye

Deep Chandra X-ray Imaging of a Nearby Radio Galaxy 4C+29.30: X-ray/Radio Connection

We report results from our deep Chandra X-ray observations of a nearby radio galaxy, 4C+29.30 (z=0.0647). The Chandra image resolves structures on sub-arcsec to arcsec scales, revealing complex X-ray morphology and detecting the main radio features: the nucleus, a jet, hotspots, and lobes. The nucleus is absorbed (N(H)=3.95 (+0.27/-0.33)x10^23 atoms/cm^2) with an unabsorbed luminosity of L(2-10 keV) ~ (5.08 +/-0.52) 10^43 erg/s characteristic of Type 2 AGN. Regions of soft (<2 keV) X-ray emission that trace the hot interstellar medium (ISM) are correlated with radio structures along the main radio axis indicating a strong relation between the two. The X-ray emission beyond the radio source correlates with the morphology of optical line-emitting regions. We measured the ISM temperature in several regions across the galaxy to be kT ~ 0.5 with slightly higher temperatures (of a few keV) in the center and in the vicinity of the radio hotspots. Assuming these regions were heated by weak shocks driven by the expanding radio source, we estimated the corresponding Mach number of 1.6 in the southern regions. The thermal pressure of the X-ray emitting gas in the outermost regions suggest the hot ISM is slightly under-pressured with respect to the cold optical-line emitting gas and radio-emitting plasma, which both seem to be in a rough pressure equilibrium. We conclude that 4C+29.30 displays a complex view of interactions between the jet-driven radio outflow and host galaxy environment, signaling feedback processes closely associated with the central active nucleus.Comment: ApJ in pres

Somatic mutations in facial skin from countries of contrasting skin cancer risk

The incidence of keratinocyte cancer (basal cell and squamous cell carcinomas of the skin) is 17-fold lower in Singapore than the UK1-3, despite Singapore receiving 2-3 times more ultraviolet (UV) radiation4,5. Aging skin contains somatic mutant clones from which such cancers develop6,7. We hypothesized that differences in keratinocyte cancer incidence may be reflected in the normal skin mutational landscape. Here we show that, compared to Singapore, aging facial skin from populations in the UK has a fourfold greater mutational burden, a predominant UV mutational signature, increased copy number aberrations and increased mutant TP53 selection. These features are shared by keratinocyte cancers from high-incidence and low-incidence populations8-13. In Singaporean skin, most mutations result from cell-intrinsic processes; mutant NOTCH1 and NOTCH2 are more strongly selected than in the UK. Aging skin in a high-incidence country has multiple features convergent with cancer that are not found in a low-risk country. These differences may reflect germline variation in UV-protective genes