Mechanism-centric regulatory network identifies NME2 and MYC programs as markers of Enzalutamide resistance in CRPC.

Heterogeneous response to Enzalutamide, a second-generation androgen receptor signaling inhibitor, is a central problem in castration-resistant prostate cancer (CRPC) management. Genome-wide systems investigation of mechanisms that govern Enzalutamide resistance promise to elucidate markers of heterogeneous treatment response and salvage therapies for CRPC patients. Focusing on the de novo role of MYC as a marker of Enzalutamide resistance, here we reconstruct a CRPC-specific mechanism-centric regulatory network, connecting molecular pathways with their upstream transcriptional regulatory programs. Mining this network with signatures of Enzalutamide response identifies NME2 as an upstream regulatory partner of MYC in CRPC and demonstrates that NME2-MYC increased activities can predict patients at risk of resistance to Enzalutamide, independent of co-variates. Furthermore, our experimental investigations demonstrate that targeting MYC and its partner NME2 is beneficial in Enzalutamide-resistant conditions and could provide an effective strategy for patients at risk of Enzalutamide resistance and/or for patients who failed Enzalutamide treatment.

Functional Status and Engagement in Physical Activity Among Maintenance Dialysis Patients: A Mixed Methods Study.

Rationale & Objective: People receiving maintenance hemodialysis (HD) experience significant activity barriers but desire the ability to do more and remain independent. To learn about how to help people who require dialysis stay active, a mixed methods study was designed to assess functional status and explore participants' lived activity experiences. Study Design: A concurrent mixed methods design was chosen to increase understanding of the real-life activity experiences of people who require dialysis through in-depth interviews paired with functional status measures. The qualitative findings were fully integrated with the quantitative results to link characteristics associated with different physical activity levels. Setting & Participants: A purposive sample of 15 adult patients receiving maintenance HD for at least 3 months was recruited from 7 dialysis centers in Newark, New Jersey. Analytical Approach: Thematic analysis using principles of interpretive phenomenology. Fully integrated quantitative and qualitative data with joint displays and conversion mixed methods. Results: Participants had a median age of 58 years and were predominantly African American (83%) and men (67%). Three descriptive categories were generated about the participants. They described physical activity as a routine daily activity rather than structured exercise. All participants experienced substantial hardship in addition to chronic kidney disease and expressed that family, friends, and faith were essential to their ability to be active. An overarching theme was generated for participants' mindsets about physical activity. Within the mindset theme, we discerned 3 subthemes comprising characteristics of participants' mindsets by levels of engagement in physical activity. Limitations: While code saturation and trends in functional status measures were achieved with 15 participants, a larger sample size would allow for deeper meaning saturation and statistical inference. Conclusions: Patients receiving maintenance HD with an engaged mindset exhibited more adaptive coping skills, moved more, wanted to help others, and had a normal body weight habitus. These participants employed adaptive coping skills to carry out daily life activities of importance, highlighting the value of adaptive coping to help overcome the challenges of being physically active.

The relation between neck strength and psychological distress: preliminary evidence from collegiate soccer athletes.

AIM: To examine whether neck strength and symmetry are associated with psychological function in athletes with exposure to repetitive head impacts. METHODS: Collegiate soccer (n = 29) and limited/noncontact (n = 63) athletes without a history of concussion completed the Brief Symptom Inventory 18 and assessments of isometric neck strength. Neck strength symmetry was calculated as the difference in strength between opposing muscle groups. RESULTS: The results demonstrated that lower neck strength was associated with more symptoms of anxiety, whereas asymmetry in neck strength was associated with more symptoms of somatization and depression in soccer athletes only. CONCLUSION: These preliminary results suggest that greater neck strength/symmetry is related to better psychological function in athletes who have higher exposure to repetitive head impacts.

Examining the Phenomenon of the Administrative Burden in Health Care, Allied Health, and Respiratory Care.

Documentation expectations for allied health professional appears to have changed dramatically in the past decade. The purpose of this essay is to discuss the literature related to clinician perceptions of these documentation expectations and changes in the workload attributable to such administrative duties, review the results of a recent pilot project surveying respiratory therapists' perception of documentation, and reflect upon the potential ramifications of excessive documentation. This commentary also discusses some recommendations for the future in terms of the design of documentation systems and the need for additional research to further explore this area.

Impact of standardized feeding guidelines on enteral nutrition administration, growth outcomes, metabolic bone disease, and cholestasis in the NICU.

OBJECTIVES: The objectives of this study were to determine whether the implementation of standardized feeding guidelines (SFGs) in a neonatal intensive care unit had an impact on the administration of enteral nutrition, growth, and bone and liver health. METHODS: This was a retrospective chart review of infants ≤ 32 weeks' gestation and ≤ 1500 g at birth who received enteral nutrition either via traditional care (TC) or via SFGs. The outcomes of the study were to determine the day of life the first enteral feedings were started, the day of life full, fortified enteral feedings were established, the day of life the infant returned to birth weight, the change in weight z score from birth to day of life 30, and the presence of metabolic bone disease and cholestasis. RESULTS: There were 128 infants in the TC group and 125 infants in the SFG group. Based on the Cox regression, no significant differences were found between the 2 groups in the length of time to the first feed (P=0.110; CI 1.03-1.70), in the length of time to full, fortified enteral feedings (P=0.334; CI 0.87-1.44), in the length of time to return to birth weight (P=0.545; CI 0.77-1.28), incidence of metabolic bone disease (P=0.990), or incidence of cholestasis (P=0.926). CONCLUSIONS: This study provides preliminary evidence that SFGs have an effect on enteral nutrition administration, growth, and morbidity for preterm infants. Although the findings were not statistically significant, they are clinically relevant.

Feeding tube use in patients with head and neck cancer.

BACKGROUND: Use of a prophylactic feeding tube before concurrent chemotherapy and radiotherapy (CRT) for patients with head and neck cancer is often debated. METHODS: A retrospective, exploratory study of 109 veterans with stage III/IV head and neck cancer who completed standard CRT was conducted. Relationships among 3 feeding tube status groups: prophylactic feeding tube (PFT), reactive feeding tube (RFT), and no feeding tube (no-FT) were compared for clinical outcomes. RESULTS: Patients with a PFT had significantly less weight loss during CRT, fewer nutrition-related emergency department visits or hospitalizations, and higher proportions of chemotherapy cycles completed compared to those with an RFT or no-FT. At 12 months post-CRT, there was no relationship between the use of a PFT and 100% feeding tube dependency. CONCLUSION: Use of a PFT in this veteran population with stage III/IV head and neck cancer produced better outcomes when compared to both an RFT or no feeding tube without higher rates of long-term dysphagia.

Symptom burden in head and neck cancer: impact upon oral energy and protein intake.

PURPOSE: This study explored relationships between oral symptom burden (xerostomia, thick secretions, and mucosal sensitivity), energy and protein intake, and weight change over time among head and neck cancer (HNC) patients who have completed concurrent chemoradiation (CCR). METHODS: Symptom burden was assessed utilizing the Vanderbilt Head and Neck Symptom Survey version 2.0. Weight change was measured from diagnosis to treatment completion, and to the early, mid, and late recovery stage. Energy and protein intake were determined utilizing 24-h diet recalls. RESULTS: Forty-three adult patients treated for HNC enrolled in the study. Mean percentage weight loss from diagnosis to treatment completion was 7.91 ± 4.06 %. Within the mid-recovery stage significant inverse relationships were found between oral protein intake and xerostomia and mucosal sensitivity (r = -0.818, p = 0.012; r = -0.726, p = 0.032, respectively). After controlling for weight change, significant inverse relationships were found within the mid-recovery stage between oral energy intake and xerostomia and mucosal sensitivity (r = -0.740, p = 0.046; r = -0.751, p = 0.043, respectively). Significant, inverse relationships were also found between oral protein intake and xerostomia and mucosal sensitivity (r = -0.835, p = 0.019; r = -0.726, p = 0.033, respectively). CONCLUSIONS: Xerostomia and mucosal sensitivity were significantly related to oral energy and protein intake post-CCR in mid-recovery. Weight loss was greatest from diagnosis to treatment completion and continued through the mid-recovery stage. Assessment of oral symptom burden (xerostomia and mucosal sensitivity) and its impact on oral intake and weight post-CCR should be conducted routinely in good patient care.