Promising Directions: A Systematic Review of Psychosocial and Behavioral Interventions with Cultural Incorporation for Advanced and Metastatic Cancer.

BACKGROUND: Improving quality of life (QOL) in advanced and metastatic cancer is a priority with increasing survivorship. This systematic review synthesizes psychosocial and behavioral interventions incorporating culture with the goal of examining their benefit for understudied and medically underserved populations with advanced and metastatic cancer. METHOD: Reports were systematically screened for (1) a focus on advanced and metastatic cancer survivors, (2) psychosocial or behavioral intervention intended to improve QOL, (3) evidence of incorporating the culture(s) of understudied/underserved populations, and (4) availability in English. Bias was evaluated using the JBI Critical Appraisal Checklist and the Methodological index for non-randomized studies. Qualitative synthesis and quantitative meta-analyses were completed. RESULTS: Eighty-six reports containing 5981 participants' data were examined. Qualitative synthesis of 23 studies identified four overarching themes relevant for incorporating culture in interventions. Meta-analysis of 19 RCTs and 4 quasi-experimental studies containing considerable heterogeneity indicated greater improvements in QOL (g = 0.84), eudaimonic well-being (g = 0.53), distress (g = -0.49), and anxiety (g = -0.37) for main intervention conditions compared to controls. Meta-analysis of 10 single-arm trials containing minimal to moderate heterogeneity found benefit for anxiety (g = -0.54), physical symptoms (g = -0.39), and depression (g = -0.38). CONCLUSION: Psychosocial and behavioral interventions with cultural incorporation appear beneficial for improving QOL-related outcomes in advanced and metastatic cancer. Studies incorporating culture in psychosocial or behavioral interventions offer noteworthy insight and suggestions for future efforts such as attending to deep cultural structure.

Translating mentoring interventions research into practice: Evaluation of an evidence-based workshop for research mentors on developing trainees' scientific communication skills.

A key part of keeping doctoral and postdoctoral trainees in STEM research careers is mentoring. Our previous research indicates that mentoring trainees in scientific communication (SC) skill development increases research career intention through two social-cognitive constructs, self-efficacy in and outcome expectations for acquiring SC skills, as well as science identity. While many mentor training interventions exist, no programs focus on developing SC skills specifically. The "Scientific Communication Advances Research Excellence" (SCOARE) program trains mentors to address trainee scientific communication (SC) skill development as an innovative approach to increase trainee research career persistence. The SCOARE training is a half-day workshop for faculty mentors of research trainees at five sites nationally. Informed by previous research, workshop content focuses on practical, effective mentoring strategies to develop trainee speaking and writing skills. Anonymous evaluation data collected after each workshop indicates participant satisfaction and reported positive increases in skills and knowledge in applying new and various techniques when mentoring trainees (skills) and how linguistic bias influences our perception of others (knowledge). This article outlines the research-based development of the SCOARE program, the first two years' of workshop evaluations showing positive increases in skills and knowledge, and lessons learned to increase participant satisfaction with the program.

A Conserved PP2A Regulatory Subunit Enforces Proportional Relationships Between Cell Size and Growth Rate.

Cell size is proportional to growth rate. Thus, cells growing rapidly in rich nutrients can be nearly twice the size of cells growing slowly in poor nutrients. This proportional relationship appears to hold across all orders of life, yet the underlying mechanisms are unknown. In budding yeast, most growth occurs during mitosis, and the proportional relationship between cell size and growth rate is therefore enforced primarily by modulating growth in mitosis. When growth is slow, the duration of mitosis is increased to allow more time for growth, yet the amount of growth required to complete mitosis is reduced, which leads to the birth of small daughter cells. Previous studies have found that Rts1, a member of the conserved B56 family of protein phosphatase 2A regulatory subunits, works in a TORC2 signaling network that influences cell size and growth rate. However, it was unclear whether Rts1 influences cell growth and size in mitosis. Here, we show that Rts1 is required for the proportional relationship between cell size and growth rate during mitosis. Moreover, nutrients and Rts1 influence the duration and extent of growth in mitosis via Wee1 and Pds1/securin, two conserved regulators of mitotic progression. Together, the data are consistent with a model in which global signals that set growth rate also set the critical amount of growth required for cell cycle progression, which would provide a simple mechanistic explanation for the proportional relationship between cell size and growth rate.

H-reflex modulation preceding changes in soleus EMG activity during balance perturbation.

When balance is compromised, postural strategies are induced to quickly recover from the perturbation. However, neuronal mechanisms underlying these strategies are not fully understood. Here, we assessed the amplitude of the soleus (SOL) H-reflex during forward and backward tilts of the support surface during standing (n = 15 healthy participants). Electrical stimulation of the tibial nerve was applied randomly before platform tilt (control) and 0, 25, 50, 75, 100 or 200 ms after tilt onset. During backward tilt, a significant decrease in H-reflex amplitude was observed at 75, 100 and 200 ms. The onset of the decreased H-reflex amplitude significantly preceded the onset of the SOL EMG decrease (latency: 144 ± 16 ms). During forward tilt, the amplitude of the H-reflex increased at 100 and 200 ms after tilt onset. The onset of H-reflex increase did not occur significantly earlier than the onset of the SOL EMG increase (127 ± 5 ms). An important inter-subject variability was observed for the onset of H-reflex modulation with respect to EMG response for each direction of tilt, but this variability could not be explained by the subject's height. Taken together, the results establish the time course of change in SOL H-reflex excitability and its relation to the increase and decrease in SOL EMG activity during forward and backward tilts. The data presented here also suggest that balance mechanisms may differ between forward and backward tilts.

Wdr68 Mediates Dorsal and Ventral Patterning Events for Craniofacial Development.

Birth defects are among the leading causes of infant mortality and contribute substantially to illness and long-term disability. Defects in Bone Morphogenetic Protein (BMP) signaling are associated with cleft lip/palate. Many craniofacial syndromes are caused by defects in signaling pathways that pattern the cranial neural crest cells (CNCCs) along the dorsal-ventral axis. For example, auriculocondylar syndrome is caused by impaired Endothelin-1 (Edn1) signaling, and Alagille syndrome is caused by defects in Jagged-Notch signaling. The BMP, Edn1, and Jag1b pathways intersect because BMP signaling is required for ventral edn1 expression that, in turn, restricts jag1b to dorsal CNCC territory. In zebrafish, the scaffolding protein Wdr68 is required for edn1 expression and subsequent formation of the ventral Meckel's cartilage as well as the dorsal Palatoquadrate. Here we report that wdr68 activity is required between the 17-somites and prim-5 stages, that edn1 functions downstream of wdr68, and that wdr68 activity restricts jag1b, hey1, and grem2 expression from ventral CNCC territory. Expression of dlx1a and dlx2a was also severely reduced in anterior dorsal and ventral 1st arch CNCC territory in wdr68 mutants. We also found that the BMP agonist isoliquiritigenin (ISL) can partially rescue lower jaw formation and edn1 expression in wdr68 mutants. However, we found no significant defects in BMP reporter induction or pSmad1/5 accumulation in wdr68 mutant cells or zebrafish. The Transforming Growth Factor Beta (TGF-ß) signaling pathway is also known to be important for craniofacial development and can interfere with BMP signaling. Here we further report that TGF-ß interference with BMP signaling was greater in wdr68 mutant cells relative to control cells. To determine whether interference might also act in vivo, we treated wdr68 mutant zebrafish embryos with the TGF-ß signaling inhibitor SB431542 and found partial rescue of edn1 expression and craniofacial development. While ISL treatment failed, SB431542 partially rescued dlx2a expression in wdr68 mutants. Together these findings reveal an indirect role for Wdr68 in the BMP-Edn1-Jag1b signaling hierarchy and dorso-anterior expression of dlx1a/2a.

Bioanalysis of urine samples after manipulation by oxidizing chemicals: technical considerations.

Drug testing programs are established to help achieve a drug-free work environment, promote fair competition in sport, facilitate harm minimization and rehabilitation programs, better manage patient care by clinicians and service law enforcement authorities. Urine remains the most popular and appropriate testing matrix for such purposes. However, urine is prone to adulteration, where chemicals, especially oxidizing chemicals, are purposely added to the collected urine specimens to produce a false-negative test result. This article will describe the effect of various popular oxidizing adulterants on urine drug test results, the countermeasures taken by laboratories in dealing with adulterated urine samples and the prospect of developing more robust and economical methods to combat urine adulteration in the future.

Synthesis, characterization, and biological evaluation of poly(L-γ-glutamyl-glutamine)- paclitaxel nanoconjugate.

The purpose of this study was to develop a novel, highly water-soluble poly(L-γ-glutamyl-glutamine)-paclitaxel nanoconjugate (PGG-PTX) that would improve the therapeutic index of paclitaxel (PTX). PGG-PTX is a modification of poly(L-glutamic acid)- paclitaxel conjugate (PGA-PTX) in which an additional glutamic acid has been added to each glutamic side chain in the polymer. PGG-PTX has higher water-solubility and faster dissolution than PGA-PTX. Unlike PGA-PTX, PGG-PTX self-assembles into nanoparticles, whose size remains in the range of 12-15 nm over the concentration range from 25 to 2,000 µg/mL in saline. Its critical micellar concentration in saline was found to be ~25 µg/mL. The potency of PGG-PTX when tested in vitro against the human lung cancer H460 cell line was comparable to other known polymer-PTX conjugates. However, PGG-PTX possesses lower toxicity compared with PGA-PTX in mice. The maximum tolerated dose of PGG-PTX was found to be 350 mg PTX/kg, which is 2.2-fold higher than the maximum tolerated dose of 160 mg PTX/kg reported for the PGA-PTX. This result indicates that PGG-PTX was substantially less toxic in vivo than PGA-PTX.