Effective non-pharmacological interventions for cancer related cognitive impairment in adults (excluding central nervous system or head and neck cancer): systematic review and meta-analysis.

INTRODUCTION: Cancer-related cognitive impairment (CRCI) is prevalent in cancer survivors, and impairments affect daily living tasks and overall wellbeing. This review aimed to identify and evaluate published randomized controlled trials (RCTs) of interventions to manage CRCI in adult populations, to analyze their effectiveness and to investigate the quality of the studies. EVIDENCE ACQUISITION: Seven databases were searched (Medline, Scopus, CINAHL, AMED, PsychINFO, OTseeker, and the Cochrane Database of Systematic Reviews), including years 2005-2020, for randomized controlled trials (RCTs) investigating interventions to address cognition for adults with cancer. The final search was conducted in February 2021. The quality of studies was assessed using the Joanna Briggs Institute (JBI) Critical Appraisal Checklist for RCTs. Meta-analysis used comprehensive meta-analysis software. The study protocol was registered with PROSPERO (registration N. CRD42017076868). EVIDENCE SYNTHESIS: A total of 45 studies involving 4727 participants examined interventions for CRCI and met selection criteria. Categories of interventions included cognitive training-based intervention (N.=15), cognitive behavior therapy (CBT) (N.=4), physical activity (N.=16) and other supportive therapies (N.=10). Meta-analysis indicated beneficial overall effects for all categories of interventions: cognitive training (standardized mean difference [SMD]=0.41, 95% CI: 0.28-0.53, I2=88.87%); CBT (SMD=0.30, 95% CI: 0.14-0.46, I2=44.86%); physical activity (SMD=0.27, 95% CI: 0.20-0.35, I2=37.67%); and supportive therapies (SMD=0.27, 95% CI: 0.16-0.39, I2=64.94%). Studies used self-report cognitive outcome measures and neurocognitive testing, or a mixture. CONCLUSIONS: Findings suggest that effective intervention for CRCI exist, and cognitive training is consistently supported as an effective intervention; however, a high level of heterogeneity was found. CRCI research is currently dominated by breast cancer survivors, and quality research is also needed to address the broader population of cancer survivors who experience CRCI.

Generality in multispecies responses to ocean acidification revealed through multiple hypothesis testing.

Decades of research have demonstrated that many calcifying species are negatively affected by ocean acidification, a major anthropogenic threat in marine ecosystems. However, even closely related species may exhibit different responses to ocean acidification and less is known about the drivers that shape such variation in different species. Here, we examine the drivers of physiological performance under ocean acidification in a group of five species of turf-forming coralline algae. Specifically, quantitating the relative weight of evidence for each of ten hypotheses, we show that variation in coralline calcification and photosynthesis was best explained by allometric traits. Across ocean acidification conditions, larger individuals (measured as noncalcified mass) had higher net calcification and photosynthesis rates. Importantly, our approach was able to not only identify the aspect of size that drove the performance of coralline algae, but also determined that responses to ocean acidification were not dependent on species identity, evolutionary relatedness, habitat, shape, or structural composition. In fact, we found that failure to test multiple, alternative hypotheses would underestimate the generality of physiological performances, leading to the conclusion that each species had different baseline performance under ocean acidification. Testing among alternative hypotheses is an essential step toward determining the generalizability of experiments across taxa and identifying common drivers of species responses to global change.

A conserved maternal-specific repressive domain in Zelda revealed by Cas9-mediated mutagenesis in Drosophila melanogaster.

In nearly all metazoans, the earliest stages of development are controlled by maternally deposited mRNAs and proteins. The zygotic genome becomes transcriptionally active hours after fertilization. Transcriptional activation during this maternal-to-zygotic transition (MZT) is tightly coordinated with the degradation of maternally provided mRNAs. In Drosophila melanogaster, the transcription factor Zelda plays an essential role in widespread activation of the zygotic genome. While Zelda expression is required both maternally and zygotically, the mechanisms by which it functions to remodel the embryonic genome and prepare the embryo for development remain unclear. Using Cas9-mediated genome editing to generate targeted mutations in the endogenous zelda locus, we determined the functional relevance of protein domains conserved amongst Zelda orthologs. We showed that neither a conserved N-terminal zinc finger nor an acidic patch were required for activity. Similarly, a previously identified splice isoform of zelda is dispensable for viability. By contrast, we identified a highly conserved zinc-finger domain that is essential for the maternal, but not zygotic functions of Zelda. Animals homozygous for mutations in this domain survived to adulthood, but embryos inheriting these loss-of-function alleles from their mothers died late in embryogenesis. These mutations did not interfere with the capacity of Zelda to activate transcription in cell culture. Unexpectedly, these mutations generated a hyperactive form of the protein and enhanced Zelda-dependent gene expression. These data have defined a protein domain critical for controlling Zelda activity during the MZT, but dispensable for its roles later in development, for the first time separating the maternal and zygotic requirements for Zelda. This demonstrates that highly regulated levels of Zelda activity are required for establishing the developmental program during the MZT. We propose that tightly regulated gene expression is essential to navigate the MZT and that failure to precisely execute this developmental program leads to embryonic lethality.

Effects of Flexibility and Balance on Driving Distance and Club Head Speed in Collegiate Golfers.

Good balance, flexibility, and strength are all required to maintain a steady stance during the kinematic chain to produce successful golf shots. When the body can produce more power, more club head speed is generated. This formation of power translates into greater distance and accuracy. Athletes today are seeking exercise programs to enhance these qualities of their golf swing. The purpose of this study is to investigate the correlations between flexibility and balance with club head speed and driving distance in the golf swing of male and female collegiate golfers. Five male and five female collegiate golfers participated in the study. They completed multiple range of motion tests, the Balance Error System Test, and multiple flexibility tests. Subjects then participated in a short hitting session. Ten shots were hit with the subject's own driver. The Optishot simulator measured distance and club head speed generated. There was a significant negative correlation between the BESS test score and average distance for male subjects (r=-0.850, p=0.034). There were also a few trends between the balance, flexibility, and club head speed findings of both male and female subjects. This data shows there is a significant relationship between better balance and driving the ball farther. Other trends show better balance and flexibility will result in greater driving distance and club head speed. Balance and flexibility exercises should be incorporated into a golfer's practice or workout regiment.

Hyaluronan Binding Identifies a Functionally Distinct Alveolar Macrophage-like Population in Bone Marrow-Derived Dendritic Cell Cultures.

Although classical dendritic cells (DCs) arise from distinct progenitors in the bone marrow, the origin of inflammatory DCs and the distinction between monocyte-derived DCs and macrophages is less clear. In vitro culture of mouse bone marrow cells with GM-CSF is a well-established method to generate DCs, but GM-CSF has also been used to generate bone marrow-derived macrophages. In this article, we identify a distinct subpopulation of cells within the GM-CSF bone marrow-derived DC culture based on their ability to bind hyaluronan (HA), a major component of the extracellular matrix and ligand for CD44. HA identified a morphologically distinct subpopulation of cells within the immature DC population (CD11c(+) MHC II(mid/low)) that were CCR5(+)/CCR7(-) and proliferated in response to GM-CSF, but, unlike immature DCs, did not develop into mature DCs expressing CCR7 and high levels of MHC II, even after stimulation with LPS. The majority of these cells produced TNF-α in response to LPS but were unable to activate naive T cells, whereas the majority of mature DCs produced IL-12 and activated naive T cells. This HA binding population shared many characteristics with alveolar macrophages and was retained in the alveolar space after lung instillation even after LPS stimulation, whereas the MHC II(high) mature DCs were found in the draining lymph node. Thus, HA binding in combination with MHC II expression can be used to identify alveolar-like macrophages from GM-CSF-treated bone marrow cultures, which provides a useful in vitro model to study alveolar macrophages.