Study protocol: A comparison of mobile and clinic-based spirometry for capturing the treatment effect in moderate asthma.

Several inefficiencies in drug development trial implementation may be improved by moving data collection from the clinic to mobile, allowing for more frequent measurements and therefore increased statistical power while aligning to a patient-centric approach to trial design. Sensor-based digital health technologies such as mobile spirometry (mSpirometry) are comparable to clinic spirometry for capturing outcomes, such as forced expiratory volume in 1 s (FEV1); however, the impact of remote spirometry measurements on the detection of treatment effect has not been investigated. A protocol for a multicenter, single-arm, open-label interventional trial of long-acting beta agonist (LABA) therapy among 60 participants with uncontrolled moderate asthma is described. Participants will complete twice-daily mSpirometry at home and clinic spirometry during weekly visits, alongside continuous use of a wrist-worn wearable and regular completion of several diaries capturing asthma symptoms as well as participant- and site-reported satisfaction and ease of use of mSpirometry. The co-primary objectives of this study are (A) to quantify the treatment effect of LABA therapy among participants with moderate asthma, using both clinical spirometry (FEV1c ) and mSpirometry (FEV1m ); and (B) to investigate whether FEV1m is as accurate as FEV1c in detecting the treatment effect using a mixed-effect model for repeated measures. Study results will help inform whether the deployment of mSpirometry and a wrist-worn wearable for remote data collection are feasible in a multicenter setting among participants with moderate asthma, which may then be generalizable to other populations with respiratory disease.

Androgen Receptor-Mediated Nuclear Transport of NRDP1 in Prostate Cancer Cells Is Associated with Worse Patient Outcomes.

To our knowledge, our group is the first to demonstrate that NRDP1 is located in the nucleus as well as the cytoplasm of CaP cells. Subcellular fractionation, immunohistochemistry, and immunofluorescence analysis combined with confocal microscopy were used to validate this finding. Subcellular fractionation followed by western blot analysis revealed a strong association between AR and NRDP1 localization when AR expression and/or cellular localization was manipulated via treatment with R1881, AR-specific siRNA, or enzalutamide. Transfection of LNCaP with various NRDP1 and AR constructs followed by immunoprecipitation confirmed binding of NRDP1 to AR is possible and determined that binding requires the hinge region of AR. Co-transfection with NRDP1 constructs and HA-ubiquitin followed by subcellular fractionation confirmed that nuclear NRDP1 retains its ubiquitin ligase activity. We also show that increased nuclear NRDP1 is associated with PSA recurrence in CaP patients (n = 162, odds ratio; 1.238, p = 0.007) and that higher levels of nuclear NRDP1 are found in castration resistant cell lines (CWR22Rv1 and PC3) compared to androgen sensitive cell lines (LNCaP and MDA-PCa-3B). The combined data indicate that NRDP1 plays a role in mediating CaP progression and supports further investigation of both the mechanism by which nuclear transport occurs and the identification of specific nuclear targets.

Neuroblastoma in a Neonate: A Case Report.

Neuroblastoma represents approximately 6 to 10 percent of childhood cancers, yet is one of the most common solid tumors observed in neonates; approximately 700 cases are reported in the United States each year. Neuroblastoma occurs secondary to oncogene mutations that cause abnormal proliferation of neural crest cells and tumor formation anywhere along the spinal cord. Visible manifestations include a blueberry rash and subcutaneous skin nodules. Common histologic findings include multifocal, small, round, blue cell tumors. Cytogenetics testing differentiates aggressive versus nonaggressive forms of neuroblastoma. Treatment ranges from supportive care to surgery and chemotherapy; targeted molecular therapies and immunotherapy offer opportunity to individualize treatment. Morbidity and mortality are contingent upon age at diagnosis and genetic abnormalities. Neonatal clinicians must establish and maintain active knowledge of the current science pertaining to this neoplasm to assist in early identification and timely initiation of medical management. This article presents a case report and comprehensive discussion of the state of the science on metastatic familial (congenital) neuroblastoma.