Use of a Mobile Application to Increase Patient Compliance to a Prescribed Home Exercise Program and Improve Outcomes

Methods: The creator of the app offered free use of their app to a physical therapy clinic. As the app is only compatible with Apple products, the clinic used the app with any patient that had an iPhone. Retrospective review was conducted to determine if differences in patient outcomes were observed. Patients who had access to an iPad or iPhone were considered part of the “app group” and used the mobile app to reference and report PT HEP compliance. Patients without access to an iPad or iPhone were considered part of the “non-app group” and received traditional PT HEP prescription and monitoring. Patient data was extracted from patient medical records, de-identified, and sent to University researchers. An independent t-test was used to analyze age and compliance of the app group and the non-app group. Mann-Whitney U tests were used to analyze number of exercises assigned, global rating of change, functional index score, and pain rating. (See pdf for complete abstract

IR Monitoring of the Microquasar GRS 1915+105: Detection of Orbital and Superhump Signatures

We present the results of seven years of K-band monitoring of the low-mass X-ray binary GRS 1915+105. Positive correlations between the infrared flux and the X-ray flux and X-ray hardness are demonstrated. Analysis of the frequency spectrum shows that the orbital period of the system is $P_{orb}= 30.8 \pm 0.2$ days. The phase and amplitude of the orbital modulation suggests that the modulation is due to the heating of the face of the secondary star. We also report another periodic signature between 31.2 and 31.6 days, most likely due to a superhump resonance. From the superhump period we then obtain a range on the mass ratio of the system, $0.05 < q < 0.12$.Comment: 16 pages, 6 figures; v2: minor change

Tracer Studies Conducted Nearly Two Decades Apart Elucidate Groundwater Movement through a Karst Aquifer in the Frederick Valley of Maryland

A pair of groundwater tracer studies at a single karst test site were completed 18 years apart. The results of these studies have provided evidence of both relatively rapid advective transport via conduits and an extreme capacity for dye storage and retardation. The tracer results, coupled with other subsurface investigation data, are used to develop a conceptual model for groundwater movement through this karst aquifer in the Frederick Valley of Maryland, as well as identify implications for remediation. Three fluorescent tracer dyes used in the initial study were detected in several background monitoring locations established for the second study conducted 18 years later, demonstrating the persistence of these dyes in the aquifer. One of these dyes was not detected during the original study, providing useful information regarding flow and transport in the aquifer. At some of these sampling locations, at least one of the dyes was degraded, and would have gone undetected without the use of activated carbon samplers. Lastly, even though relatively rapid first detections occurred during both studies (as compared to non-karst groundwater systems) the majority of injected dye mass remained in the aquifer after the studies were completed. This suggests that the aquifer has a large capacity to store contaminants and that low levels of contaminants can be expected to persist in groundwater discharged from springs for a long period of time

Thiol-ene Adhesives From Clove Oil Derivatives

This paper reports the synthesis of catechol-functionalized thiol–ene polymer networks as photocurable adhesives, where the adhesive interactions are derived from 4-allylpyrocatechol – a monofunctional alkene readily obtained from natural products of Syzygium aromaticum flower buds (clove). The thiol–ene photopolymerization process enables rapid cure times, low energy input, and solvent-free processing. The resulting polymer networks show improved macroscopic adhesion to a variety of substrates – including glass, marble, aluminum, and steel – by varying the concentration of 4-allylpyrocatechol in the network. Additionally, the effects of the catechol moiety on polymerization kinetics, thermomechanical, and mechanical properties were determined by comparing the synthesized catechol moiety to a series of control monomers such as eugenol (one phenol group) and methyl eugenol (no phenol groups)

The CK1α Activator Pyrvinium Enhances the Catalytic Efficiency (k cat/K m) of CK1α

The serine/threonine protein kinase casein kinase 1α (CK1α) functions as a negative regulator of Wnt signaling, phosphorylating β-catenin at serine 45 (P–S45) to initiate its eventual ubiquitin-mediated degradation. We previously showed that the repurposed, FDA-approved anthelminthic drug pyrvinium potently inhibits Wnt signaling in vitro and in vivo. Moreover, we proposed that pyrvinium’s Wnt inhibitory activity was the result of its function as an activator of CK1α. An understanding of the mechanism by which pyrvinium activates CK1α is important because pyrvinium was given an orphan drug designation by the FDA to treat familial adenomatous polyposis, a precancerous condition driven by constitutive Wnt signaling. In the current study, we show that pyrvinium stimulates the phosphorylation of S45 β-catenin, a known CK1α substrate, in a cell-based assay, and does so in a dose- and time-dependent manner. Alternative splicing of CK1α results in four forms of the protein with distinct biological properties. We evaluated these splice products and identified the CK1α splice variant, CK1αS, as the form that exhibits the most robust response to pyrvinium in cells. Kinetic studies indicate that pyrvinium also stimulates the kinase activity of purified, recombinant CK1αS in vitro, increasing its catalytic efficiency (k cat/K m) toward substrates. These studies provide strong and clear mechanistic evidence that pyrvinium enhances CK1α kinase activity

Differential abundance of CK1α provides selectivity for pharmacological CK1α activators to target WNT-dependent tumors

Constitutive WNT activity drives the growth of various human tumors, including nearly all colorectal cancers (CRCs). Despite this prominence in cancer, no WNT inhibitor is currently approved for use in the clinic largely due to the small number of druggable signaling components in the WNT pathway and the substantial toxicity to normal gastrointestinal tissue. We have shown that pyrvinium, which activates casein kinase 1α (CK1α), is a potent inhibitor of WNT signaling. However, its poor bioavailability limited the ability to test this first-in-class WNT inhibitor in vivo. We characterized a novel small-molecule CK1α activator called SSTC3, which has better pharmacokinetic properties than pyrvinium, and found that it inhibited the growth of CRC xenografts in mice. SSTC3 also attenuated the growth of a patient-derived metastatic CRC xenograft, for which few therapies exist. SSTC3 exhibited minimal gastrointestinal toxicity compared to other classes of WNT inhibitors. Consistent with this observation, we showed that the abundance of the SSTC3 target, CK1α, was decreased in WNT-driven tumors relative to normal gastrointestinal tissue, and knocking down CK1α increased cellular sensitivity to SSTC3. Thus, we propose that distinct CK1α abundance provides an enhanced therapeutic index for pharmacological CK1α activators to target WNT-driven tumors