Clonal hematopoiesis detection in patients with cancer using cell-free DNA sequencing.

In the context of cancer, clonal hematopoiesis of indeterminate potential (CHIP) is associated with the development of therapy-related myeloid neoplasms and shorter overall survival. Cell-free DNA (cfDNA) sequencing is becoming widely adopted for genomic screening of patients with cancer but has not been used extensively to determine CHIP status because of a requirement for matched blood and tumor sequencing. We present an accurate classification approach to determine the CH status from cfDNA sequencing alone, applying our model to 4324 oncology clinical cfDNA samples. Using this method, we determined that 30.3% of patients in this cohort have evidence of CH, and the incidence of CH varies by tumor type. Matched RNA sequencing data show evidence of increased inflammation, especially neutrophil activation, within the tumors and tumor microenvironments of patients with CH. In addition, patients with CH had evidence of neutrophil activation systemically, pointing to a potential mechanism of action for the worse outcomes associated with CH status. Neutrophil activation may be one of many mechanisms, however, because patients with estrogen receptor-positive breast cancer harboring TET2 frameshift mutations had worse outcomes but similar neutrophil frequencies to patients without CH. Together, these data show the feasibility of detecting CH through cfDNA sequencing alone and an application of this method, demonstrating increased inflammation in patients with CH both systemically and in the tumor microenvironment.

Integrative Therapies for Women with a High Risk Pregnancy During Antepartum Hospitalization.

BACKGROUND: High-risk pregnancies that require lengthy hospitalization can cause anxiety and stress for pregnant women. Integrative medicine therapies may be beneficial for this population, but have not been widely studied. PURPOSE: The purpose of this study was to evaluate potential effects of acupuncture, guided imagery, Healing Touch, massage therapy, and reflexology on pain and anxiety of hospitalized pregnant women. METHODS: A retrospective analysis of the effects of integrative medicine therapies was conducted; N = 554 individual therapies were provided to hospitalized women with high-risk pregnancies. They included acupuncture (n = 83), guided imagery (n = 71), Healing Touch (n = 119), massage therapy (n = 196), and reflexology (n = 85) over an 18-month period. Pain and anxiety were measured pre- and posttherapy using a scale of 0 to 10, where 0 means no pain or no anxiety and 10 means high pain or high anxiety. RESULTS: Analysis of mean scores of pre- and posttherapies for pain and anxiety found a decrease of pain and anxiety after all of the therapies, ranging from an 84.5% to 61.4% decrease for pain (p < .0001) and a 91% to 70. 9% decrease for anxiety (p < .0001). Overall, patients rated their anxiety higher than pain prior to each therapy. CLINICAL IMPLICATIONS: Hospitalized pregnant women responded favorably to the therapies. There were no adverse reactions reported. Results suggest potential benefits of integrative medicine therapies for this group of inpatients. Anxiety was more prevalent than pain among hospitalized pregnant women who received integrative medicine therapy.

The walnut (Juglans regia) genome sequence reveals diversity in genes coding for the biosynthesis of non-structural polyphenols.

The Persian walnut (Juglans regia L.), a diploid species native to the mountainous regions of Central Asia, is the major walnut species cultivated for nut production and is one of the most widespread tree nut species in the world. The high nutritional value of J. regia nuts is associated with a rich array of polyphenolic compounds, whose complete biosynthetic pathways are still unknown. A J. regia genome sequence was obtained from the cultivar 'Chandler' to discover target genes and additional unknown genes. The 667-Mbp genome was assembled using two different methods (SOAPdenovo2 and MaSuRCA), with an N50 scaffold size of 464 955 bp (based on a genome size of 606 Mbp), 221 640 contigs and a GC content of 37%. Annotation with MAKER-P and other genomic resources yielded 32 498 gene models. Previous studies in walnut relying on tissue-specific methods have only identified a single polyphenol oxidase (PPO) gene (JrPPO1). Enabled by the J. regia genome sequence, a second homolog of PPO (JrPPO2) was discovered. In addition, about 130 genes in the large gallate 1-ß-glucosyltransferase (GGT) superfamily were detected. Specifically, two genes, JrGGT1 and JrGGT2, were significantly homologous to the GGT from Quercus robur (QrGGT), which is involved in the synthesis of 1-O-galloyl-ß-d-glucose, a precursor for the synthesis of hydrolysable tannins. The reference genome for J. regia provides meaningful insight into the complex pathways required for the synthesis of polyphenols. The walnut genome sequence provides important tools and methods to accelerate breeding and to facilitate the genetic dissection of complex traits.

Effectiveness of school-based violence prevention for children and youth: a research report.

Aggression, bullying and violence in children and youth are prevalent in Canada (18%) and internationally. The authors evaluated the effectiveness of Roots of Empathy (ROE), a school-based mental health promotion and violence prevention program for children that has been widely implemented but rarely evaluated. Eight school divisions were randomly assigned to either a treatment group that received ROE in 2002-2003 (445 students) or a wait-list control group (315 students). These were compared on three child mental health outcomes (physical aggression, indirect aggression and pro-social behaviour), rated by teachers and students (self-rated). The three wait-list school divisions received ROE in 2003-2004 (new cohort of 265 students) and were compared with the control group from 2002-2003 on the three outcomes, for replication purposes. For both comparisons, the authors report multi-level modelling analyses regarding (1) immediate effects after ROE completion at the end of the school year (pretest to post-test) and (2) long-term ROE effects up to three years after post-test. ROE had replicated, beneficial effects on all teacher-rated outcomes, which were generally maintained or further improved across follow-up. However, ROE had almost no statistically significant or replicated effects on student-rated outcomes. This is the first evaluation to suggest that ROE appears effective when implemented on a large scale under real-world delivery conditions.

Prevalence of caries among preschool-aged children in a northern Manitoba community.

BACKGROUND: Early childhood caries (ECC) is a devastating form of dental decay affecting many Canadian children, especially those from northern First Nations communities. ECC is multifactorial in origin, and the notion that the principal etiology is inappropriate feeding modalities is no longer tenable. METHODS: This study was conducted in the community of Garden Hill First Nation, Manitoba, to assess the prevalence of dental decay in young children, to assess risk factors for ECC and to determine the influence of vitamin D supplementation (a modified form of stosstherapy using 100,000 IU vitamin D), both prenatally and at 6 weeks of age, on the oral health of children. The study involved a cross-sectional dental examination of children, an interview with mothers and a maternal chart review. RESULTS: A total of 98 children participated: their mean age was 46.4 +/- 6.3 months. The mean number of decayed, extracted and filled teeth (deft) was 13.7 +/- 3.2. Caries rates were significantly greater among children who had had sugar added to the feeding bottle. Behaviours typically associated with ECC and caries activity, such as poor oral hygiene and late weaning from the bottle, were also exhibited among residents. Although 50% of children had enamel hypoplasia, no statistically significant differences in the amount of enamel hypoplasia and caries were found between those who received modified stosstherapy and those who did not. Not receiving stosstherapy was associated with later eruption time of the first primary tooth (7.2 vs. 5.0 months). Interviews revealed that, during pregnancy, many of the mothers only infrequently consumed foods rich in calcium and vitamin D, elements that are essential to the development of strong bones and teeth. CONCLUSIONS: The mean deft for these First Nations preschoolers was high and 50% had enamel defects. Although daily vitamin D supplementation of 400 IU during pregnancy has been known to reduce primary tooth enamel defects, the supplementation previously administered to participants in this study was not found to result in reduced enamel defects or caries. The high caries burden among children from this community reveals the need for effective prevention methods. It is important for pediatricians, family physicians and other health service providers encountering very young children and expectant mothers to be cognizant of ECC and its ramifications, as their education efforts represent the first line of defence.