Meta-analysis of the effect of an essential oil–containing mouthrinse on gingivitis and plaque

AbstractBackgroundStandard recommendations for oral hygiene practices have focused on mechanical methods (toothbrushing and interdental cleaning). Published evidence indicates antimicrobial mouthrinses provide oral health benefits beyond mechanical methods alone. The purpose of this meta-analysis was to evaluate the combined effectiveness of mechanical methods with essential oil–containing mouthrinses (MMEO) versus mechanical methods (MM) alone in achieving site-specific, healthy gingival tissue and reducing plaque and gingivitis.Types of Studies ReviewedAll industry-sponsored clinical trials investigating the antigingivitis and antiplaque effects of essential oil (EO)–containing mouthrinses conducted from 1980 to 2012 were reviewed; 29 of 32 studies met the inclusion criteria of 6 months or longer duration, randomized, observer-masked, placebo-controlled, and with individual-level site-specific data. By-study treatment effects were estimated through generalized linear models for binary data and analysis of covariance for continuous data, and then combined using standard meta-analysis techniques; heterogeneity was also assessed.ResultsSummary odds ratios for a healthy gingival site and for a plaque-free site were, respectively, 5.0 (95% confidence interval [CI], 3.3-7.5) and 7.8 (95% CI, 5.4-11.2) for MMEO participants versus MM participants at 6 months. The summary percentage reductions in whole-mouth mean gingivitis and plaque at 6 months were 16.0 (95% CI, 11.3-20.7) and 27.7 (95% CI, 22.4-32.9), respectively. Responder analyses using aggregate individual-level data showed 44.8% of MMEO participants and 14.4% of MM participants achieved at least 50% healthy sites in their mouths at 6 months. Similarly, 36.9% of MMEO participants and 5.5% of MM participants achieved at least 50% plaque-free sites in their mouths at 6 months.Conclusions and Practical ImplicationsThis is the first meta-analysis to demonstrate the clinically significant, site-specific benefit of adjunctive EO treatment in people within a 6-month period (that is, between dental visits)

Characterization of systematic error in Advanced LIGO calibration

The raw outputs of the detectors within the Advanced Laser Interferometer Gravitational-Wave Observatory need to be calibrated in order to produce the estimate of the dimensionless strain used for astrophysical analyses. The two detectors have been upgraded since the second observing run and finished the year-long third observing run. Understanding, accounting, and/or compensating for the complex-valued response of each part of the upgraded detectors improves the overall accuracy of the estimated detector response to gravitational waves. We describe improved understanding and methods used to quantify the response of each detector, with a dedicated effort to define all places where systematic error plays a role. We use the detectors as they stand in the first half (six months) of the third observing run to demonstrate how each identified systematic error impacts the estimated strain and constrain the statistical uncertainty therein. For this time period, we estimate the upper limit on systematic error and associated uncertainty to be $< 7\%$ in magnitude and $< 4$ deg in phase ($68\%$ confidence interval) in the most sensitive frequency band 20-2000 Hz. The systematic error alone is estimated at levels of $< 2\%$ in magnitude and $< 2$ deg in phase

Combining Asian and European genome-wide association studies of colorectal cancer improves risk prediction across racial and ethnic populations

Polygenic risk scores (PRS) have great potential to guide precision colorectal cancer (CRC) prevention by identifying those at higher risk to undertake targeted screening. However, current PRS using European ancestry data have sub-optimal performance in non-European ancestry populations, limiting their utility among these populations. Towards addressing this deficiency, we expand PRS development for CRC by incorporating Asian ancestry data (21,731 cases; 47,444 controls) into European ancestry training datasets (78,473 cases; 107,143 controls). The AUC estimates (95% CI) of PRS are 0.63(0.62-0.64), 0.59(0.57-0.61), 0.62(0.60-0.63), and 0.65(0.63-0.66) in independent datasets including 1681-3651 cases and 8696-115,105 controls of Asian, Black/African American, Latinx/Hispanic, and non-Hispanic White, respectively. They are significantly better than the European-centric PRS in all four major US racial and ethnic groups (p-values < 0.05). Further inclusion of non-European ancestry populations, especially Black/African American and Latinx/Hispanic, is needed to improve the risk prediction and enhance equity in applying PRS in clinical practice

Cumulative Burden of Colorectal Cancer-Associated Genetic Variants Is More Strongly Associated With Early-Onset vs Late-Onset Cancer.

BACKGROUND & AIMS: Early-onset colorectal cancer (CRC, in persons younger than 50 years old) is increasing in incidence; yet, in the absence of a family history of CRC, this population lacks harmonized recommendations for prevention. We aimed to determine whether a polygenic risk score (PRS) developed from 95 CRC-associated common genetic risk variants was associated with risk for early-onset CRC. METHODS: We studied risk for CRC associated with a weighted PRS in 12,197 participants younger than 50 years old vs 95,865 participants 50 years or older. PRS was calculated based on single nucleotide polymorphisms associated with CRC in a large-scale genome-wide association study as of January 2019. Participants were pooled from 3 large consortia that provided clinical and genotyping data: the Colon Cancer Family Registry, the Colorectal Transdisciplinary Study, and the Genetics and Epidemiology of Colorectal Cancer Consortium and were all of genetically defined European descent. Findings were replicated in an independent cohort of 72,573 participants. RESULTS: Overall associations with CRC per standard deviation of PRS were significant for early-onset cancer, and were stronger compared with late-onset cancer (P for interaction = .01); when we compared the highest PRS quartile with the lowest, risk increased 3.7-fold for early-onset CRC (95% CI 3.28-4.24) vs 2.9-fold for late-onset CRC (95% CI 2.80-3.04). This association was strongest for participants without a first-degree family history of CRC (P for interaction = 5.61 × 10-5). When we compared the highest with the lowest quartiles in this group, risk increased 4.3-fold for early-onset CRC (95% CI 3.61-5.01) vs 2.9-fold for late-onset CRC (95% CI 2.70-3.00). Sensitivity analyses were consistent with these findings. CONCLUSIONS: In an analysis of associations with CRC per standard deviation of PRS, we found the cumulative burden of CRC-associated common genetic variants to associate with early-onset cancer, and to be more strongly associated with early-onset than late-onset cancer, particularly in the absence of CRC family history. Analyses of PRS, along with environmental and lifestyle risk factors, might identify younger individuals who would benefit from preventive measures

Discovery of common and rare genetic risk variants for colorectal cancer.

To further dissect the genetic architecture of colorectal cancer (CRC), we performed whole-genome sequencing of 1,439 cases and 720 controls, imputed discovered sequence variants and Haplotype Reference Consortium panel variants into genome-wide association study data, and tested for association in 34,869 cases and 29,051 controls. Findings were followed up in an additional 23,262 cases and 38,296 controls. We discovered a strongly protective 0.3% frequency variant signal at CHD1. In a combined meta-analysis of 125,478 individuals, we identified 40 new independent signals at P < 5 × 10-8, bringing the number of known independent signals for CRC to ~100. New signals implicate lower-frequency variants, Krüppel-like factors, Hedgehog signaling, Hippo-YAP signaling, long noncoding RNAs and somatic drivers, and support a role for immune function. Heritability analyses suggest that CRC risk is highly polygenic, and larger, more comprehensive studies enabling rare variant analysis will improve understanding of biology underlying this risk and influence personalized screening strategies and drug development.Goncalo R Abecasis has received compensation from 23andMe and Helix. He is currently an employee of Regeneron Pharmaceuticals. Heather Hampel performs collaborative research with Ambry Genetics, InVitae Genetics, and Myriad Genetic Laboratories, Inc., is on the scientific advisory board for InVitae Genetics and Genome Medical, and has stock in Genome Medical. Rachel Pearlman has participated in collaborative funded research with Myriad Genetics Laboratories and Invitae Genetics but has no financial competitive interest

A global experiment on motivating social distancing during the COVID-19 pandemic

Finding communication strategies that effectively motivate social distancing continues to be a global public health priority during the COVID-19 pandemic. This cross-country, preregistered experiment (n = 25,718 from 89 countries) tested hypotheses concerning generalizable positive and negative outcomes of social distancing messages that promoted personal agency and reflective choices (i.e., an autonomy-supportive message) or were restrictive and shaming (i.e., a controlling message) compared with no message at all. Results partially supported experimental hypotheses in that the controlling message increased controlled motivation (a poorly internalized form of motivation relying on shame, guilt, and fear of social consequences) relative to no message. On the other hand, the autonomy-supportive message lowered feelings of defiance compared with the controlling message, but the controlling message did not differ from receiving no message at all. Unexpectedly, messages did not influence autonomous motivation (a highly internalized form of motivation relying on one’s core values) or behavioral intentions. Results supported hypothesized associations between people’s existing autonomous and controlled motivations and self-reported behavioral intentions to engage in social distancing. Controlled motivation was associated with more defiance and less long-term behavioral intention to engage in social distancing, whereas autonomous motivation was associated with less defiance and more short- and long-term intentions to social distance. Overall, this work highlights the potential harm of using shaming and pressuring language in public health communication, with implications for the current and future global health challenges

Linking psychological need experiences to daily and recurring dreams

The satisfaction of individuals’ psychological needs for autonomy, competence, and relatedness, as conceived from a self-determination theory perspective, is said to be conducive to personal growth and well-being. What has been unexamined is whether psychological need-based experiences, either their satisfaction or frustration, manifests in people’s self-reported dream themes as well as their emotional interpretation of their dreams. A cross-sectional study (N = 200; M age = 21.09) focusing on individuals’ recurrent dreams and a three-day diary study (N = 110; M age = 25.09) focusing on daily dreams indicated that individuals experiencing psychological need frustration, either more enduringly or on a day-to-day basis, reported more negative dream themes and interpreted their dreams more negatively. The contribution of psychological need satisfaction was more modest, although it related to more positive interpretation of dreams. The discussion focuses on the role of dreams in the processing and integration of psychological need-frustrating experiences

Comprehensive Molecular Portraits of Invasive Lobular Breast Cancer

Invasive lobular carcinoma (ILC) is the second most prevalent histologic subtype of invasive breast cancer. Here, we comprehensively profiled 817 breast tumors, including 127 ILC, 490 ductal (IDC), and 88 mixed IDC/ILC. Besides E-cadherin loss, the best known ILC genetic hallmark, we identified mutations targeting PTEN, TBX3 and FOXA1 as ILC enriched features. PTEN loss associated with increased AKT phosphorylation, which was highest in ILC among all breast cancer subtypes. Spatially clustered FOXA1 mutations correlated with increased FOXA1 expression and activity. Conversely, GATA3 mutations and high expression characterized Luminal A IDC, suggesting differential modulation of ER activity in ILC and IDC. Proliferation and immune-related signatures determined three ILC transcriptional subtypes associated with survival differences. Mixed IDC/ILC cases were molecularly classified as ILC-like and IDC-like revealing no true hybrid features. This multidimensional molecular atlas sheds new light on the genetic bases of ILC and provides potential clinical options