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Dental caries is a costly and prevalent disease characterized by the demineralization of the tooth's enamel. Disease outcome is influenced by host factors, dietary intake, cariogenic bacteria, and other microbes. The cariogenic bacterial species Streptococcus mutans metabolizes sucrose to initiate biofilm formation on the tooth surface and consequently produces lactic acid to degrade the tooth's enamel. Persistence of S. mutans biofilms in the oral cavity can lead to tooth decay. To date, no anticaries therapies that specifically target S. mutans biofilms but do not disturb the overall oral microbiome are available. We screened a library of 2-aminoimidazole antibiofilm compounds with a biofilm dispersion assay and identified a small molecule that specifically targets S. mutans biofilms. At 5 µM, the small molecule annotated 3F1 dispersed 50% of the established S. mutans biofilm but did not disperse biofilms formed by the commensal species Streptococcus sanguinis or Streptococcus gordonii. 3F1 dispersed S. mutans biofilms independently of biofilm-related factors such as antigen I/II and glucosyltransferases. 3F1 treatment effectively prevented dental caries by controlling S. mutans in a rat caries model without perturbing the oral microbiota. Our study demonstrates that selective targeting of S. mutans biofilms by 3F1 was able to effectively reduce dental caries in vivo without affecting the overall oral microbiota shaped by the intake of dietary sugars, suggesting that the pathogenic biofilm-specific treatment is a viable strategy for disease prevention. [ABSTRACT FROM AUTHOR]

The current study was designed to alter experimentally mothers' style when discussing sexuality and AIDS with their adolescent children. Mothers of 11- to 15-year-olds (N = 50) were assigned to an intervention or control group, resulting in 20 dyads in each group. All dyads were assessed twice, on self-reported and observed communication, AIDS knowledge, and perceived vulnerability to AIDS. Intervention group mothers received two training sessions. Observational data revealed that intervention group mothers reduced their amount of speaking, asked more open-ended questions, acted less judgmental, and discussed dating and sexuality more than did control group mothers. Intervention group adolescents reported increased discussions of birth control and increased daily comfort talking to their mothers. There was some evidence that intervention group girls increased in AIDS knowledge. There was no change in AIDS-related beliefs. [ABSTRACT FROM AUTHOR]

Objective: To examine the relationship between sudden infant death syndrome (SIDS) and smoking during pregnancy; postnatal tobacco smoke exposure from the mother, father, live-in-adults, and day care providers; and postnatal smoke exposure from breast-feeding.Design: Case-control study.Setting: Five counties in Southern California.Participants: A total of 200 white, African-American, Hispanic, and Asian parents of infants who died of SIDS between 1989 and 1992 were compared with 200 control parents who delivered healthy infants. Case infants were matched to control infants on the basis of birth hospital, birth date, gender, and race. All information was obtained from a detailed telephone interview and validated with medical records.Main Outcome Measures: Risk of SIDS associated with passive smoking by the mother, father, live-in adults, and day care providers; smoking in the same room as the infant; total number of cigarettes smoked by all adults; and maternal smoking during the time period of breast-feeding.Results: Conditional logistic regression resulted in overall adjusted odds ratios (ORs) for SIDS associated with passive smoke from the mother of 2.28, the father of 3.46, other live-in adults of 2.18, and all sources of 3.50 (95% confidence interval, 1.81 to 6.75), while simultaneously adjusting for birth weight, sleep position, prenatal care, medical conditions at birth, breast-feeding, and maternal smoking during pregnancy. A dose-response effect was noted for SIDS associated with increasing numbers of cigarettes, as well as total number of smokers. Breast-feeding was protective for SIDS among nonsmokers (OR = 0.37) but not smokers (OR = 1.38), when adjusting for potential confounders.Conclusions: Passive smoking in the same room as the infant increases the risk for SIDS. Physicians should educate new and prospective parents about the risk of tobacco smoke exposure during pregnancy and the first year of the infant's life. [ABSTRACT FROM AUTHOR]

Background: In general, ovarian cancer incidence and mortality is higher in northern than southern latitudes. This ecologic study tests the hypothesis that vitamin D produced in the skin from sunlight exposure may be associated with a protective action in ovarian cancer mortality.Methods: The association between average annual sunlight energy and age-specific ovarian cancer mortality rates in counties containing the 100 largest US cities was evaluated for 1979-1988. Simple linear regression was performed by decade using sunlight and ozone as independent variables and ovarian cancer rates as the dependent variable. Multiple regression was used to adjust for ozone and sulphur dioxide, since these atmospheric components may absorb ultraviolet light.Results: Fatal ovarian cancer in these areas was inversely proportional to mean annual intensity of local sunlight in a univariate analysis (P = 0.0001), and in a regression adjusted for air pollution (P = 0.04). The association was also seen when restricted to 27 major urban areas of the US; however, probably due to a small sample size, this statistic did not reach significance.Conclusions: This ecologic study supports the hypothesis that sunlight may be a protective factor for ovarian cancer mortality. [ABSTRACT FROM AUTHOR]

In a longitudinal study, following a community sample (N = 386) from age 5, early risk factors for depressive symptomatology at age 18 were examined separately for females and males. For females, predictors included low birthweight and death of a parent; for males, they included emotional dependency and internalizing behavior problems. Depressive symptomatology at age 15 emerged as an important risk factor for both genders. Clinical implications are discussed, and areas for further research are proposed. [ABSTRACT FROM AUTHOR]

It is common practice in speech research to only sample participants who self-report being "native English speakers." Although there is research on differences in language processing between native and nonnative listeners (see Lecumberri et al., 2010, for a review), the majority of speech research that aims to establish general findings (e.g., testing models of spoken word recognition) only includes native speakers in their sample. Not only is the "native English speaker" criterion poorly defined, but it also excludes historically underrepresented groups from speech perception research, often without attention to whether this exclusion is likely to affect study outcomes. The purpose of this study is to empirically test whether and how using different inclusion criteria ("native English speakers" vs. "nonnative English speakers") affects several well-known phenomena in speech perception research. Five hundred participants completed word ( N = 200) and sentence (N = 300) identification tasks in quiet and in moderate levels of background noise. Results indicate that multiple classic findings in speech perception research-including the effects of noise level, lexical density, and semantic context on speech intelligibility-persist regardless of "native English" speaking status. However, the magnitude of some of these effects differed across participant groups. Taken together, these results suggest that researchers should carefully consider whether native speaker status is likely to affect outcomes and make decisions about inclusion criteria on a study-by-study basis. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Accumulating evidence has revealed that alterations in the gut microbiome following spinal cord injury (SCI) exhibit similarities to those observed in metabolic syndrome. Considering the causal role of gut dysbiosis in metabolic syndrome development, SCI-induced gut dysbiosis may be a previously unidentified contributor to the increased risk of cardiometabolic diseases, which has garnered attention. With a cross-sectional design, we evaluated the correlation between gut microbiome composition and functional potential with indicators of metabolic health among 46 individuals with chronic SCI. Gut microbiome communities were profiled using next-generation sequencing techniques. Indices of metabolic health, including fasting lipid profile, glucose tolerance, insulin resistance, and inflammatory markers, were assessed through fasting blood tests and an oral glucose tolerance test. We used multivariate statistical techniques (i.e., regularized canonical correlation analysis) to identify correlations between gut bacterial communities, functional pathways, and metabolic health indicators. Our findings spotlight bacterial species and functional pathways associated with complex carbohydrate degradation and maintenance of gut barrier integrity as potential contributors to improved metabolic health. Conversely, those correlated with detrimental microbial metabolites and gut inflammatory pathways demonstrated associations with poorer metabolic health outcomes. This cross-sectional investigation represents a pivotal initial step toward comprehending the intricate interplay between the gut microbiome and metabolic health in SCI. Furthermore, our results identified potential targets for future research endeavors to elucidate the role of the gut microbiome in metabolic syndrome in this population. NEW & NOTEWORTHY Spinal cord injury (SCI) is accompanied by gut dysbiosis and the impact of this on the development of metabolic syndrome in this population remains to be investigated. Our study used next-generation sequencing and multivariate statistical analyses to explore the correlations between gut microbiome composition, function, and metabolic health indices in individuals with chronic SCI. Our results point to potential gut microbial species and functional pathways that may be implicated in the development of metabolic syndrome.

Background: Colorectal cancer (CRC), the third leading cause of cancer-related deaths in the US, has been associated with an overrepresentation or paucity of several microbial taxa in the gut microbiota, but causality has not been established. Black men and women have among the highest CRC incidence and mortality rates of any racial/ethnic group. This study will examine the impact of the Dietary Approaches to Stop Hypertension (DASH) diet on gut microbiota and fecal metabolites associated with CRC risk., Methods: A generally healthy sample of non-Hispanic Black and white adults (n = 112) is being recruited to participate in a parallel-arm randomized controlled feeding study. Participants are randomized to receive the DASH diet or a standard American diet for a 28-day period. Fecal samples are collected weekly throughout the study to analyze changes in the gut microbiota using 16 s rRNA and selected metagenomics. Differences in bacterial alpha and beta diversity and taxa that have been associated with CRC (Bacteroides, Fusobacterium, Clostridium, Lactobacillus, Bifidobacterium, Ruminococcus, Porphyromonas, Succinivibrio) are being evaluated. Covariate measures include body mass index, comorbidities, medication history, physical activity, stress, and demographic characteristics., Conclusion: Our findings will provide preliminary evidence for the DASH diet as an approach for cultivating a healthier gut microbiota across non-Hispanic Black and non-Hispanic White adults. These results can impact clinical, translational, and population-level approaches for modification of the gut microbiota to reduce risk of chronic diseases including CRC., Trial Registration: This study was registered on ClinicalTrials.gov, identifier NCT04538482, on September 4, 2020 (https://clinicaltrials.gov/ct2/show/NCT04538482)., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction: The presence of masking noise can impair speech intelligibility and increase the attentional and cognitive resources necessary to understand speech. The first study to demonstrate the negative cognitive effects of noisy speech found that participants had poorer recall for aurally-presented digits early in a list when later digits were presented in noise relative to quiet (Rabbitt, 1968). However, despite being cited nearly 500 times and providing the foundation for a wealth of subsequent research on the topic, the original study has never been directly replicated., Methods: This study replicated Rabbitt (1968) with a large online sample and tested its robustness to a variety of analytical and scoring techniques., Results: We replicated Rabbitt's key finding that listening to speech in noise impairs recall for items that came earlier in the list. The results were consistent when we used the original analytical technique (an ANOVA) and a more powerful analytical technique (generalized linear mixed effects models) that was not available when the original paper was published., Discussion: These findings support the claim that effortful listening can interfere with encoding or rehearsal of previously presented information., Competing Interests: The authors report no conflicts of interest.

Next generation sequencing (NGS) is becoming increasingly integrated into oncological practice and clinical research. NGS methods have also provided evidence for clonal evolution of cancers during disease progression and treatment. The number of variants associated with response to specific therapeutic agents keeps increasing. However, the identification of novel driver mutations as opposed to passenger (phenotypically silent or clinically irrelevant) mutations remains a major challenge. We conducted targeted exome sequencing of advanced solid tumors from 44 pre-treated patients with solid tumors including breast, colorectal and lung carcinomas, neuroendocrine tumors, sarcomas and others. We catalogued established driver mutations and putative new drivers as predicted by two distinct algorithms. The established drivers we detected were consistent with published observations. However, we also detected a significant number of mutations with driver potential never described before in each tumor type we studied. These putative drivers belong to key cell fate regulatory networks, including potentially druggable pathways. Should our observations be confirmed, they would support the hypothesis that new driver mutations are selected by treatment in clinically aggressive tumors, and indicate a need for longitudinal genomic testing of solid tumors to inform second line cancer treatment.

The most common disease-causing mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene is the out-of-frame deletion of 3 nucleotides (CTT). This mutation leads to the loss of phenylalanine-508 (ΔF508) and a silent codon change (SCC) for isoleucine-507 (I507-ATC→ATT). ΔF508 CFTR is misfolded and degraded by endoplasmic reticulum-associated degradation (ERAD). We have demonstrated that the I507-ATC→ATT SCC alters ΔF508 CFTR mRNA structure and translation dynamics. By comparing the biochemical and functional properties of the I507-ATT and I507-ATC ΔF508 CFTR, we establish that the I507-ATC→ATT SCC contributes to the cotranslational misfolding, ERAD, and to the functional defects associated with ΔF508 CFTR. We demonstrate that the I507-ATC ΔF508 CFTR is less susceptible to the ER quality-control machinery during translation than the I507-ATT, although 27°C correction is necessary for sufficient cell-surface expression. Whole-cell patch-clamp recordings indicate sustained, thermally stable cAMP-activated Cl(-) transport through I507-ATC and unstable function of the I507-ATT ΔF508 CFTR. Single-channel recordings reveal improved gating properties of the I507-ATC compared to I507-ATT ΔF508 CFTR (NPo=0.45±0.037 vs. NPo=0.09±0.002; P<0.001). Our results signify the role of the I507-ATC→ATT SCC in the ΔF508 CFTR defects and support the importance of synonymous codon choices in determining the function of gene products.

Dengue virus currently causes 50-100 million infections annually. Comprehensive knowledge about the evolution of Dengue in response to selection pressure is currently unavailable, but would greatly enhance vaccine design efforts. In the current study, we sequenced 187 new dengue virus serotype 3 (DENV-3) genotype III whole genomes isolated from Asia and the Americas. We analyzed them together with previously-sequenced isolates to gain a more detailed understanding of the evolutionary adaptations existing in this prevalent American serotype. In order to analyze the phylogenetic dynamics of DENV-3 during outbreak periods; we incorporated datasets of 48 and 11 sequences spanning two major outbreaks in Venezuela during 2001 and 2007-2008, respectively. Our phylogenetic analysis of newly sequenced viruses shows that subsets of genomes cluster primarily by geographic location, and secondarily by time of virus isolation. DENV-3 genotype III sequences from Asia are significantly divergent from those from the Americas due to their geographical separation and subsequent speciation. We measured amino acid variation for the E protein by calculating the Shannon entropy at each position between Asian and American genomes. We found a cluster of seven amino acid substitutions having high variability within E protein domain III, which has previously been implicated in serotype-specific neutralization escape mutants. No novel mutations were found in the E protein of sequences isolated during either Venezuelan outbreak. Shannon entropy analysis of the NS5 polymerase mature protein revealed that a G374E mutation, in a region that contributes to interferon resistance in other flaviviruses by interfering with JAK-STAT signaling was present in both the Asian and American sequences from the 2007-2008 Venezuelan outbreak, but was absent in the sequences from the 2001 Venezuelan outbreak. In addition to E, several NS5 amino acid changes were unique to the 2007-2008 epidemic in Venezuela and may give additional insight into the adaptive response of DENV-3 at the population level., (Published by Elsevier B.V.)

The analysis of poxvirus genomes is complex, in part, because of their size (130-360 kb) and the fact that gene content is variable; a common set of 49 genes has been found in all sequenced poxviruses and an additional 41 genes are also present in all sequenced orthopoxviruses. As a group, poxviruses have a very broad range of eukaryotic hosts (including mammals, birds, reptiles and insects) and many poxvirus genes are associated with blocking host anti-viral responses. One consequence of this is that many poxvirus genes are not essential for growth in tissue culture and that extensive passaging in vitro results in the accumulation of mutations, including deletions that result in loss of gene function. Here, we review various comparative analyses of the poxviruses including gene prediction, gene conservation and function, genome organization, and poxvirus taxonomy and evolution.