User Engagement and Assessment of Treatment Effectiveness in Patients Using a Novel Digital mHealth App During Spinal Cord Stimulation Screening Trials.

BACKGROUND: Patient outcomes and experience during a Spinal Cord Stimulation (SCS) screening trial can have a significant effect on whether to proceed with long-term, permanent implantation of an SCS device for the treatment of chronic pain. Enhancing the ability to track and assess patients during this initial trial evaluation offers the potential for improved understanding regarding the suitability of permanent device implantation as well as identification of the SCS-based neurostimulative modalities and parameters that may provide substantial analgesia in a patient-specific manner. OBJECTIVE: In this report, we aimed to describe a preliminary, real-world assessment of a new, real time tracking, smart, device-based digital app used by patients with chronic pain undergoing trial screening for SCS therapy. METHODS: This is a real-world, retrospective evaluation of 13,331 patients diagnosed with chronic pain who used the new "mySCS" mobile app during an SCS screening trial. The app design is health insurance portability and accountability act (HIPAA)-compliant and compatible with most commercially available smartphones (eg, Apple, iPhone, and Android). The app enables tracking of user-inputted health-related responses (ie, pain relief, activity level, and sleep quality) in addition to personal trial goals and a summary of overall experience during the SCS trial. A deidentified, aggregate analysis of user engagement, user-submitted responses, and overall trial success was conducted. RESULTS: When provided the opportunity, the percentage of users who engaged with the tracking app for ≥50% of the time during their trial was found to be 64.43% (n=8589). Among the 13,331 patients who used the app, 58.24% (n=7764) entered a trial goal. Most patients underwent SCS screening with a trial duration of at least 7 days (n=7739, 58.05%). Of those patients who undertook a 7-day SCS trial, 62.30% (n=3456) engaged the app for 4 days or more. In addition, among all who submitted descriptive responses using the app, health-related improvements were reported by 77.84% (n=10,377) of patients who reached day 3 of the screening phase assessment and by 83.04% (n=11,070) of those who reached trial completion. A trial success rate of 91% was determined for those who used the app (versus 85% success rate for nonusers). CONCLUSIONS: Data from this initial, real-world examination of a mobile, digital-health-based tracking app ("mySCS"), as used during the SCS screening phase, demonstrate that substantial patient engagement can be achieved while also providing for the acquisition of more real time patient-outcome measures that may help facilitate improved SCS trial success.

Vestigial-like 3 is an inhibitor of adipocyte differentiation.

Adipose differentiation is a complex process controlled by a network of transcription factors and co-regulators. We compared the global gene expression patterns of adipogenic and nonadipogenic clones of 3T3-F442A preadipocytes and identified the transcriptional cofactor, vestigial-like 3 (Vgll3), as an inhibitor of adipogenesis. Vgll3 expression is down-regulated during terminal adipocyte differentiation in vitro and negatively correlates with weight and total fat mass in vivo. Furthermore, enforced Vgll3 expression inhibits the differentiation of preadipocytes in vitro, whereas shRNA-mediated knockdown of Vgll3 expression promotes differentiation. Expression of Vgll3 promoted the expression of genes associated with bone and chondrocyte formation, suggesting that Vgll3 participates in the decision of mesenchymal cells to proceed down the adipocyte, bone, or cartilage lineages. The elucidation of factors involved in specification of the adipocyte phenotype may aid in the identification of new strategies for the treatment of metabolic disease.

Before they were fat: adipocyte progenitors.

Adipose tissue mass can expand throughout adult life. Therefore, proliferative adipocyte precursor cells must stand at the ready to respond to increased demand for energy storage. Recent provocative studies have identified discrete immature cell populations from which brown and white adipocytes are derived. This work not only brings fundamental insight into adipose tissue formation but also provides new tools to study how adipogenesis is regulated in pathological conditions such as obesity and diabetes.

Imexon activates an intrinsic apoptosis pathway in RPMI8226 myeloma cells.

Imexon is a new antitumor agent with high activity in multiple myeloma. This drug induces apoptosis, oxidative stress and mitochondrial alterations. However, it was unknown whether imexon activates an intrinsic apoptotic pathway that is associated with activation of caspase-9 or an extrinsic pathway that is induced by receptor-mediated signals such as Fas ligand characterized by caspase-8 activation. In addition, we wanted to investigate the effect of imexon on Bcl-2 family proteins. In RPMI8226 myeloma cells, imexon activated caspase-9 and -3 in a time- and concentration-dependent manner. In contrast, cleavage of procaspase-8 was observed late and only after exposure to very high concentrations of imexon. Confocal microscopy confirmed that caspase-3 is also activated after treatment with imexon. High imexon concentrations activated caspase-3 and -9 at 12 h, while caspase-8 activation occurred only at 48 h. Imexon cytotoxicity was unchanged in three RPMI8226 cell lines with different levels (low, medium and high) of FAS expression. Similarly, the levels of Bcl-2, Bax and Bcl-xL were unchanged in imexon-treated cells. However, Bcl-xL was translocated to the mitochondria. These data suggest that imexon-induced oxidation activates the intrinsic or mitochondrial pathway of apoptosis, involving cytochrome release and activation of caspase-9 and -3.