Murine norovirus infection does not cause major disruptions in the murine intestinal microbiota

BACKGROUND: Murine norovirus (MNV) is the most common gastrointestinal pathogen of research mice and can alter research outcomes in biomedical mouse models of inflammatory bowel disease (IBD). Despite indications that an altered microbiota is a risk factor for IBD, the response of the murine intestinal microbiota to MNV infection has not been examined. Microbiota disruption caused by MNV infection could introduce the confounding effects observed in research experiments. Therefore, this study investigated the effects of MNV infection on the intestinal microbiota of wild-type mice. RESULTS: The composition of the intestinal microbiota was assessed over time in both outbred Swiss Webster and inbred C57BL/6 mice following MNV infection. Mice were infected with both persistent and non-persistent MNV strains and tissue-associated or fecal-associated microbiota was analyzed by 16S rRNA-encoding gene pyrosequencing. Analysis of intestinal bacterial communities in infected mice at the phylum and family level showed no major differences to uninfected controls, both in tissue-associated samples and feces, and also over time following infection, demonstrating that the intestinal microbiota of wild-type mice is highly resistant to disruption following MNV infection. CONCLUSIONS: This is the first study to describe the intestinal microbiota following MNV infection and demonstrates that acute or persistent MNV infection is not associated with major disruptions of microbial communities in Swiss Webster and C57BL/6 mice

Murine norovirus infection does not cause major disruptions in the murine intestinal microbiota

Abstract Background Murine norovirus (MNV) is the most common gastrointestinal pathogen of research mice and can alter research outcomes in biomedical mouse models of inflammatory bowel disease (IBD). Despite indications that an altered microbiota is a risk factor for IBD, the response of the murine intestinal microbiota to MNV infection has not been examined. Microbiota disruption caused by MNV infection could introduce the confounding effects observed in research experiments. Therefore, this study investigated the effects of MNV infection on the intestinal microbiota of wild-type mice. Results The composition of the intestinal microbiota was assessed over time in both outbred Swiss Webster and inbred C57BL/6 mice following MNV infection. Mice were infected with both persistent and non-persistent MNV strains and tissue-associated or fecal-associated microbiota was analyzed by 16S rRNA-encoding gene pyrosequencing. Analysis of intestinal bacterial communities in infected mice at the phylum and family level showed no major differences to uninfected controls, both in tissue-associated samples and feces, and also over time following infection, demonstrating that the intestinal microbiota of wild-type mice is highly resistant to disruption following MNV infection. Conclusions This is the first study to describe the intestinal microbiota following MNV infection and demonstrates that acute or persistent MNV infection is not associated with major disruptions of microbial communities in Swiss Webster and C57BL/6 mice.http://deepblue.lib.umich.edu/bitstream/2027.42/112329/1/40168_2012_Article_7.pd

Guideline for the management of clostridium difficile infection in children and adolescents with cancer and pediatric hematopoietic stem-cell transplantation recipients

Purpose The aim of this work was to develop a clinical practice guideline for the prevention and treatment of Clostridium difficile infection (CDI) in children and adolescents with cancer and pediatric hematopoietic stem-cell transplantation (HSCT) patients. Methods An international multidisciplinary panel of experts in pediatric oncology and infectious diseases with patient advocate representation was convened. We performed systematic reviews of randomized controlled trials for the prevention or treatment of CDI in any population and considered the directness of the evidence to children with cancer and pediatric HSCT patients. We used the Grading of Recommendations Assessment, Development, and Evaluation approach to generate recommendations. Results The panel made strong recommendations to administer either oral metronidazole or oral vancomycin for the initial treatment of nonsevere CDI and oral vancomycin for the initial treatment of severe CDI. Fidaxomicin may be considered in the setting of recurrent CDI. The panel suggested that probiotics not be routinely used for the prevention of CDI, and that monoclonal antibodies and probiotics not be routinely used for the treatment of CDI. A strong recommendation to not use fecal microbiota transplantation was made in this population. We identified key knowledge gaps and suggested directions for future research. Conclusion We present a guideline for the prevention and treatment of CDI in children and adolescents with cancer and pediatric HSCT patients. Future research should include randomized controlled trials that involve children with cancer and pediatric HSCT patients to improve the management of CDI in this population

Mutations in thyroid hormone receptor α1 cause premature neurogenesis and progenitor cell depletion in human cortical development.

Mutations in the thyroid hormone receptor α 1 gene (THRA) have recently been identified as a cause of intellectual deficit in humans. Patients present with structural abnormalities including microencephaly, reduced cerebellar volume and decreased axonal density. Here, we show that directed differentiation of THRA mutant patient-derived induced pluripotent stem cells to forebrain neural progenitors is markedly reduced, but mutant progenitor cells can generate deep and upper cortical layer neurons and form functional neuronal networks. Quantitative lineage tracing shows that THRA mutation-containing progenitor cells exit the cell cycle prematurely, resulting in reduced clonal output. Using a micropatterned chip assay, we find that spatial self-organization of mutation-containing progenitor cells in vitro is impaired, consistent with down-regulated expression of cell-cell adhesion genes. These results reveal that thyroid hormone receptor α1 is required for normal neural progenitor cell proliferation in human cerebral cortical development. They also exemplify quantitative approaches for studying neurodevelopmental disorders using patient-derived cells in vitro.NIHR Cambridge Biomedical Centr

The daily association between affect and alcohol use: a meta-analysis of individual participant data

Influential psychological theories hypothesize that people consume alcohol in response to the experience of both negative and positive emotions. Despite two decades of daily diary and ecological momentary assessment research, it remains unclear whether people consume more alcohol on days they experience higher negative and positive affect in everyday life. In this preregistered meta-analysis, we synthesized the evidence for these daily associations between affect and alcohol use. We included individual participant data from 69 studies (N = 12,394), which used daily and momentary surveys to assess affect and the number of alcoholic drinks consumed. Results indicate that people are not more likely to drink on days they experience high negative affect, but are more likely to drink and drink heavily on days high in positive affect. People self-reporting a motivational tendency to drink-to-cope and drink-to-enhance consumed more alcohol, but not on days they experienced higher negative and positive affect. Results were robust across different operationalizations of affect, study designs, study populations, and individual characteristics. These findings challenge the long-held belief that people drink more alcohol following increases in negative affect. Integrating these findings under different theoretical models and limitations of this field of research, we collectively propose an agenda for future research to explore open questions surrounding affect and alcohol use.The present study was funded by the Canadian Institutes of Health Research Grant MOP-115104 (Roisin M. O’Connor), Canadian Institutes of Health Research Grant MSH-122803 (Roisin M. O’Connor), John A. Hartford Foundation Grant (Paul Sacco), Loyola University Chicago Research Support Grant (Tracy De Hart), National Institute for Occupational Safety and Health Grant T03OH008435 (Cynthia Mohr), National Institutes of Health (NIH) Grant F31AA023447 (Ryan W. Carpenter), NIH Grant R01AA025936 (Kasey G. Creswell), NIH Grant R01AA025969 (Catharine E. Fairbairn), NIH Grant R21AA024156 (Anne M. Fairlie), NIH Grant F31AA024372 (Fallon Goodman), NIH Grant R01DA047247 (Kevin M. King), NIH Grant K01AA026854 (Ashley N. Linden-Carmichael), NIH Grant K01AA022938 (Jennifer E. Merrill), NIH Grant K23AA024808 (Hayley Treloar Padovano), NIH Grant P60AA11998 (Timothy Trull), NIH Grant MH69472 (Timothy Trull), NIH Grant K01DA035153 (Nisha Gottfredson), NIH Grant P50DA039838 (Ashley N. Linden-Carmichael), NIH Grant K01DA047417 (David M. Lydon-Staley), NIH Grant T32DA037183 (M. Kushner), NIH Grant R21DA038163 (A. Moore), NIH Grant K12DA000167 (M. Potenza, Stephanie S. O’Malley), NIH Grant R01AA025451 (Bruce Bartholow, Thomas M. Piasecki), NIH Grant P50AA03510 (V. Hesselbrock), NIH Grant K01AA13938 (Kristina M. Jackson), NIH Grant K02AA028832 (Kevin M. King), NIH Grant T32AA007455 (M. Larimer), NIH Grant R01AA025037 (Christine M. Lee, M. Patrick), NIH Grant R01AA025611 (Melissa Lewis), NIH Grant R01AA007850 (Robert Miranda), NIH Grant R21AA017273 (Robert Miranda), NIH Grant R03AA014598 (Cynthia Mohr), NIH Grant R29AA09917 (Cynthia Mohr), NIH Grant T32AA07290 (Cynthia Mohr), NIH Grant P01AA019072 (P. Monti), NIH Grant R01AA015553 (J. Morgenstern), NIH Grant R01AA020077 (J. Morgenstern), NIH Grant R21AA017135 (J. Morgenstern), NIH Grant R01AA016621 (Stephanie S. O’Malley), NIH Grant K99AA029459 (Marilyn Piccirillo), NIH Grant F31AA022227 (Nichole Scaglione), NIH Grant R21AA018336 (Katie Witkiewitz), Portuguese State Budget Foundation for Science and Technology Grant UIDB/PSI/01662/2020 (Teresa Freire), University of Washington Population Health COVID-19 Rapid Response Grant (J. Kanter, Adam M. Kuczynski), U.S. Department of Defense Grant W81XWH-13-2-0020 (Cynthia Mohr), SANPSY Laboratory Core Support Grant CNRS USR 3413 (Marc Auriacombe), Social Sciences and Humanities Research Council of Canada Grant (N. Galambos), and Social Sciences and Humanities Research Council of Canada Grant (Andrea L. Howard)

Characterizing the Dynamics of Loneliness, Depression, and the Role of Social Interactions: An Experience Sampling Study

Thesis (Ph.D.)--University of Washington, 2023Loneliness is becoming increasingly recognized as a problem of clinical and public health significance (Badcock et al., 2023). Although this increase is concerning on its own, given the importance of social relationships and relational well-being to the human experience (Baumeister & Leary, 1995; Bugental, 2000), loneliness is also associated with numerous mental and physical health problems (Courtin & Knapp, 2017; Luanaigh & Lawlor, 2008; Ong et al., 2016; Park et al., 2020), including depression. Despite decades of observational research showing that loneliness is a risk factor for increased depression symptom severity and caseness (Erzen & Ã ikrikci, 2018; Kuczynski, in prep), however, how loneliness may increase risk for depression is poorly understood. Cacioppo and colleagues’ (2006; 2018) evolutionary theory of loneliness suggests that the answer may lie in one’s response to feelings of loneliness. Do individuals engage in social interaction and reestablish connection with others or instead withdraw from others in an attempt to avoid social rejection? This study aimed to examine this very idea. Using ecological momentary assessment with a sample of 102 depressed adults, we explored whether acute (i.e., state) feelings of loneliness were associated with changes in depressed mood throughout the course of the day and whether the quantity and quality of one’s social interactions moderated this association. Guided by Kanter and colleagues’ (2020) contextual-behavioral formulation of the interpersonal process model (Reis & Shaver, 1988), we hypothesized that the association between loneliness and depressed mood would be weaker when individuals engaged in social interaction characterized by greater self- and other-disclosure and perceived responsiveness following feelings of loneliness and stronger for individuals who experience chronic feelings of loneliness. Results demonstrated that feelings of loneliness throughout the day were associated with changes in depressed mood not only at the same time point, but also 3 and 6 hours later. Individuals varied considerably in the degree to which loneliness was associated with subsequent depressed mood. Contrary to our hypotheses, neither social interaction quantity nor quality moderated this association. Methodological factors such as the timing of momentary assessments, sample demographics, and measurement strategy are considered, and implications for theory and clinical practice are discussed

Preliminary Development and Psychometric Evaluation of the ACL Scale: Factor Structure, Measurement Invariance, Reliability, and Validity

Thesis (Master's)--University of Washington, 2016-08Humans have evolved such that social connectedness (i.e., interpersonal closeness, belongingness) plays an integral role in the health, happiness, and survival of our species. Intimacy has been the target of much research over the past few decades in the effort to gain a more nuanced, behavioral understanding of social connectedness and, in particular, points amenable to intervention. Despite the importance of this pursuit, however, few self-report measures exist that capture theoretically and empirically grounded aspects of intimacy, and those that do exist have important shortcomings that limit their utility in research. The purpose of this study was to create a self report measure of intimacy that has a strong theoretical and empirical foundation, is applicable to a broad population of individuals across a broad range of contexts, is useful in a clinical setting, and is situated in the behavioral psychological tradition. The authors report on the development and preliminary psychometric evaluation of the ACL Scale, a 20-item, 4-factor self-report measure of intimacy based on Reis and Shaver’s (1988) model. Factor structure, measurement invariance, internal and test-retest reliability, and validity of the measure are discussed