Non-pharmacological management of infant and young child procedural pain.

BACKGROUND: Despite evidence of the long-term implications of unrelieved pain during infancy, it is evident that infant pain is still under-managed and unmanaged. Inadequately managed pain in infancy, a period of exponential development, can have implications across the lifespan. Therefore, a comprehensive and systematic review of pain management strategies is integral to appropriate infant pain management. This is an update of a previously published review update in the Cochrane Database of Systematic Reviews (2015, Issue 12) of the same title. OBJECTIVES: To assess the efficacy and adverse events of non-pharmacological interventions for infant and child (aged up to three years) acute pain, excluding kangaroo care, sucrose, breastfeeding/breast milk, and music. SEARCH METHODS: For this update, we searched CENTRAL, MEDLINE-Ovid platform, EMBASE-OVID platform, PsycINFO-OVID platform, CINAHL-EBSCO platform and trial registration websites (ClinicalTrials.gov; International Clinical Trials Registry Platform) (March 2015 to October 2020). An update search was completed in July 2022, but studies identified at this point were added to 'Awaiting classification' for a future update.  We also searched reference lists and contacted researchers via electronic list-serves.  We incorporated 76 new studies into the review.  SELECTION CRITERIA: Participants included infants from birth to three years in randomised controlled trials (RCTs) or cross-over RCTs that had a no-treatment control comparison. Studies were eligible for inclusion in the analysis if they compared a non-pharmacological pain management strategy to a no-treatment control group (15 different strategies). In addition, we also analysed studies when the unique effect of adding a non-pharmacological pain management strategy onto another pain management strategy could be assessed (i.e. additive effects on a sweet solution, non-nutritive sucking, or swaddling) (three strategies). The eligible control groups for these additive studies were sweet solution only, non-nutritive sucking only, or swaddling only, respectively. Finally, we qualitatively described six interventions that met the eligibility criteria for inclusion in the review, but not in the analysis.  DATA COLLECTION AND ANALYSIS: The outcomes assessed in the review were pain response (reactivity and regulation) and adverse events. The level of certainty in the evidence and risk of bias were based on the Cochrane risk of bias tool and the GRADE approach. We analysed the standardised mean difference (SMD) using the generic inverse variance method to determine effect sizes.  MAIN RESULTS: We included total of 138 studies (11,058 participants), which includes an additional 76 new studies for this update. Of these 138 studies, we analysed 115 (9048 participants) and described 23 (2010 participants) qualitatively. We described qualitatively studies that could not be meta-analysed due to being the only studies in their category or statistical reporting issues. We report the results of the 138 included studies here. An SMD effect size of 0.2 represents a small effect, 0.5 a moderate effect, and 0.8 a large effect. The thresholds for the I2 interpretation were established as follows: not important (0% to 40%); moderate heterogeneity (30% to 60%); substantial heterogeneity (50% to 90%); considerable heterogeneity (75% to 100%). The most commonly studied acute procedures were heel sticks (63 studies) and needlestick procedures for the purposes of vaccines/vitamins (35 studies). We judged most studies to have high risk of bias (103 out of 138), with the most common methodological concerns relating to blinding of personnel and outcome assessors. Pain responses were examined during two separate pain phases: pain reactivity (within the first 30 seconds after the acutely painful stimulus) and immediate pain regulation (after the first 30 seconds following the acutely painful stimulus). We report below the strategies with the strongest evidence base for each age group. In preterm born neonates, non-nutritive sucking may reduce pain reactivity (SMD -0.57, 95% confidence interval (CI) -1.03 to -0.11, moderate effect; I2 = 93%, considerable heterogeneity) and improve immediate pain regulation (SMD -0.61, 95% CI -0.95 to -0.27, moderate effect; I2 = 81%, considerable heterogeneity), based on very low-certainty evidence. Facilitated tucking may also reduce pain reactivity (SMD -1.01, 95% CI -1.44 to -0.58, large effect; I2 = 93%, considerable heterogeneity) and improve immediate pain regulation (SMD -0.59, 95% CI -0.92 to -0.26, moderate effect; I2 = 87%, considerable heterogeneity); however, this is also based on very low-certainty evidence. While swaddling likely does not reduce pain reactivity in preterm neonates (SMD -0.60, 95% CI -1.23 to 0.04, no effect; I2 = 91%, considerable heterogeneity), it has been shown to possibly improve immediate pain regulation (SMD -1.21, 95% CI -2.05 to -0.38, large effect; I2 = 89%, considerable heterogeneity), based on very low-certainty evidence. In full-term born neonates, non-nutritive sucking may reduce pain reactivity (SMD -1.13, 95% CI -1.57 to -0.68, large effect; I2 = 82%, considerable heterogeneity) and improve immediate pain regulation (SMD -1.49, 95% CI -2.20 to -0.78, large effect; I2 = 92%, considerable heterogeneity), based on very low-certainty evidence.  In full-term born older infants, structured parent involvement was the intervention most studied. Results showed that this intervention has little to no effect in reducing pain reactivity (SMD -0.18, 95% CI -0.40 to 0.03, no effect; I2 = 46%, moderate heterogeneity) or improving immediate pain regulation (SMD -0.09, 95% CI -0.40 to 0.21, no effect; I2 = 74%, substantial heterogeneity), based on low- to moderate-certainty evidence. Of these five interventions most studied, only two studies observed adverse events, specifically vomiting (one preterm neonate) and desaturation (one full-term neonate hospitalised in the NICU) following the non-nutritive sucking intervention. The presence of considerable heterogeneity limited our confidence in the findings for certain analyses, as did the preponderance of evidence of very low to low certainty based on GRADE judgements. AUTHORS' CONCLUSIONS: Overall, non-nutritive sucking, facilitated tucking, and swaddling may reduce pain behaviours in preterm born neonates. Non-nutritive sucking may also reduce pain behaviours in full-term neonates. No interventions based on a substantial body of evidence showed promise in reducing pain behaviours in older infants. Most analyses were based on very low- or low-certainty grades of evidence and none were based on high-certainty evidence. Therefore, the lack of confidence in the evidence would require further research before we could draw a definitive conclusion.

Children's shyness and frontal electroencephalogram delta-beta correlation in the pediatric surgical setting.

The prospect of surgery is a unique psychologically threatening context for children, often leading to experiences of preoperative anxiety. Recent research suggests that individual differences in children's temperament may influence responses to the surgical setting. In the present study, we examined whether individual differences in shyness were related to differences in frontal electroencephalogram (EEG) delta-beta correlation, a proposed neural correlate of emotion regulation and dysregulation, among children anticipating surgery. Seventy-one children (36 boys, Mage  = 10.3 years, SDage  = 1.7 years) undergoing elective surgery self-reported on their own shyness, and their parents also reported on their child's shyness. Using a mobile, dry sensor EEG headband, frontal EEG measures were collected and self- and observer-reported measures of state anxiety were obtained at the children's preoperative visit (Time 1) and on the day of surgery (Time 2). A latent cluster analysis derived classes of low shy (n = 37) and high shy (n = 34) children using the child- and parent-reported shyness measures. We then compared the two classes on frontal EEG delta-beta correlation using between- and within-subjects analyses. Although children classified as high versus low in shyness had higher self- and observer-reported state anxiety across both time periods, frontal EEG delta-beta correlation increased from T1 to T2 only among low shy children using a between-subjects delta-beta correlation measure. We discuss the interpretation of a relatively higher delta-beta correlation as a correlate of emotion regulatory versus dysregulatory strategies for some children in a "real-world," surgical context.

Systematic Review: Audiovisual Interventions for Reducing Preoperative Anxiety in Children Undergoing Elective Surgery.

OBJECTIVE: To examine the effectiveness of Audiovisual (AV) interventions at reducing preoperative anxiety and its associated outcomes in children undergoing elective surgery. METHODS: A systematic review of randomized controlled trials (RCTs) and nonrandomized studies where the primary outcome was children's preoperative anxiety was conducted. Secondary outcomes included postoperative pain, behavioral changes, recovery, induction compliance, satisfaction, and cost-effectiveness. The risk of bias of each study was assessed. RESULTS: In all, 18 studies were identified. A meta-analytic approach and narrative synthesis of findings were used to summarize the results of the studies. CONCLUSIONS: This systematic review suggests that AV interventions can be effective in reducing children's preoperative anxiety. Videos, multi-faceted programs, and interactive games appear to be most effective, whereas music therapy and Internet programs are less effective. While AV interventions appear potentially useful, adequately powered RCTs are required to conclusively pinpoint the components and mechanisms of the most effective AV interventions and guide practice.

Global declines in oceanic nitrification rates as a consequence of ocean acidification.

Ocean acidification produced by dissolution of anthropogenic carbon dioxide (CO(2)) emissions in seawater has profound consequences for marine ecology and biogeochemistry. The oceans have absorbed one-third of CO(2) emissions over the past two centuries, altering ocean chemistry, reducing seawater pH, and affecting marine animals and phytoplankton in multiple ways. Microbially mediated ocean biogeochemical processes will be pivotal in determining how the earth system responds to global environmental change; however, how they may be altered by ocean acidification is largely unknown. We show here that microbial nitrification rates decreased in every instance when pH was experimentally reduced (by 0.05-0.14) at multiple locations in the Atlantic and Pacific Oceans. Nitrification is a central process in the nitrogen cycle that produces both the greenhouse gas nitrous oxide and oxidized forms of nitrogen used by phytoplankton and other microorganisms in the sea; at the Bermuda Atlantic Time Series and Hawaii Ocean Time-series sites, experimental acidification decreased ammonia oxidation rates by 38% and 36%. Ammonia oxidation rates were also strongly and inversely correlated with pH along a gradient produced in the oligotrophic Sargasso Sea (r(2) = 0.87, P < 0.05). Across all experiments, rates declined by 8-38% in low pH treatments, and the greatest absolute decrease occurred where rates were highest off the California coast. Collectively our results suggest that ocean acidification could reduce nitrification rates by 3-44% within the next few decades, affecting oceanic nitrous oxide production, reducing supplies of oxidized nitrogen in the upper layers of the ocean, and fundamentally altering nitrogen cycling in the sea.

Health Care Professionals' and Parents' Perspectives on the Use of AI for Pain Monitoring in the Neonatal Intensive Care Unit: Multisite Qualitative Study.

BACKGROUND: The use of artificial intelligence (AI) for pain assessment has the potential to address historical challenges in infant pain assessment. There is a dearth of information on the perceived benefits and barriers to the implementation of AI for neonatal pain monitoring in the neonatal intensive care unit (NICU) from the perspective of health care professionals (HCPs) and parents. This qualitative analysis provides novel data obtained from 2 large tertiary care hospitals in Canada and the United Kingdom. OBJECTIVE: The aim of the study is to explore the perspectives of HCPs and parents regarding the use of AI for pain assessment in the NICU. METHODS: In total, 20 HCPs and 20 parents of preterm infants were recruited and consented to participate from February 2020 to October 2022 in interviews asking about AI use for pain assessment in the NICU, potential benefits of the technology, and potential barriers to use. RESULTS: The 40 participants included 20 HCPs (17 women and 3 men) with an average of 19.4 (SD 10.69) years of experience in the NICU and 20 parents (mean age 34.4, SD 5.42 years) of preterm infants who were on average 43 (SD 30.34) days old. Six themes from the perspective of HCPs were identified: regular use of technology in the NICU, concerns with regard to AI integration, the potential to improve patient care, requirements for implementation, AI as a tool for pain assessment, and ethical considerations. Seven parent themes included the potential for improved care, increased parental distress, support for parents regarding AI, the impact on parent engagement, the importance of human care, requirements for integration, and the desire for choice in its use. A consistent theme was the importance of AI as a tool to inform clinical decision-making and not replace it. CONCLUSIONS: HCPs and parents expressed generally positive sentiments about the potential use of AI for pain assessment in the NICU, with HCPs highlighting important ethical considerations. This study identifies critical methodological and ethical perspectives from key stakeholders that should be noted by any team considering the creation and implementation of AI for pain monitoring in the NICU.

Risk and protective factors in predicting pediatric acute postsurgical pain: A systematic review and meta-analysis.

OBJECTIVE: Acute postsurgical pain (APSP), defined as pain within 3 months after surgery, is reported in most surgical pediatric patients, and a significant number of patients experience pain interfering with their daily life activities. We aimed to identify perioperative and psychosocial factors associated with APSP severity in pediatric patients undergoing surgery. METHOD: MEDLINE, EMBASE, CINAHL, PsycINFO, Web of Science, and CENTRAL were searched from database inception to October 2021. Studies that reported an association between risk or protective factors and acute pain in children were included. The primary outcome was the magnitude of association between identified factors and APSP, as measured by standardized effect sizes. RESULTS: Thirty-eight studies (7,936 participants aged 1-18 years) were included. Meta-analysis of 12 studies (1,192 participants) revealed child preoperative pain, pain immediately after surgery, anticipated pain, temperament, pain catastrophizing, age, preoperative anxiety, parent pain catastrophizing, and parent preoperative anxiety were positively associated with APSP. Child pain coping efficacy was protective against APSP. We identified several modifiable child and parent psychosocial factors as predictors of APSP severity. CONCLUSION: Given the small degree of association between identified factors and postsurgical pain, there is value in pursuing other factors that may better explain the variability in pain. Recognizing patients at risk for moderate to severe APSP enables early implementation of interventions to minimize pain burden. Interventions to enhance coping, an adaptive characteristic, may also help to reduce APSP. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

StrainSelect: A novel microbiome reference database that disambiguates all bacterial strains, genome assemblies and extant cultures worldwide.

Motivation: Microbial metagenomic profiling software and databases are advancing rapidly for development of novel disease biomarkers and therapeutics yet three problems impede analyses: 1) the conflation of "genome assembly" and "strain" in reference databases; 2) difficulty connecting DNA biomarkers to a procurable strain for laboratory experimentation; and 3) absence of a comprehensive and unified strain-resolved reference database for integrating both shotgun metagenomics and 16S rRNA gene data. Results: We demarcated 681,087 strains, the largest collection of its kind, by filtering public data into a knowledge graph of vertices representing contiguous DNA sequences, genome assemblies, strain monikers and bio-resource center (BRC) catalog numbers then adding inter-vertex edges only for synonyms or direct derivatives. Surprisingly, for 10,043 important strains, we found replicate RefSeq genome assemblies obstructing interpretation of database searches. We organized each strain into eight taxonomic ranks with bootstrap confidence inversely correlated with genome assembly contamination. The StrainSelect database is suited for applications where a taxonomic, functional or procurement reference is needed for shotgun or amplicon metagenomics since 636,568 strains have at least one 16S rRNA gene, 245,005 have at least one annotated genome assembly, and 36,671 are procurable from at least one BRC. The database overcomes all three aforementioned problems since it disambiguates strains from assemblies, locates strains at BRCs, and unifies a taxonomic reference for both 16S rRNA and shotgun metagenomics. Availability: The StrainSelect database is available in igraph and tabular vertex-edge formats compatible with Neo4J. Dereplicated MinHash and fasta databases are distributed for sourmash and usearch pipelines at http://strainselect.secondgenome.com. Contact:todd.desantis@gmail.com. Supplementary information: Supplementary data are available online.

Children's Shyness, Frontal Brain Activity, and Anxiety in the Perioperative Context.

Although preoperative anxiety affects up to 75% of children undergoing surgery each year and is associated with many adverse outcomes, we know relatively little about individual differences in how children respond to impending surgery. We examined whether patterns of anterior brain electrical activity (i.e., a neural correlate of anxious arousal) moderated the relation between children's shyness and preoperative anxiety on the day of surgery in 70 children (36 girls, Mage = 10.4 years, SDage = 1.7, years, range 8 to 13 years) undergoing elective surgery. Shyness was assessed using self-report approximately 1 week prior to surgery during a preoperative visit (Time 1), preoperative anxiety was assessed using self-report, and regional EEG (left and right frontal and temporal sites) was assessed using a dry sensory EEG headband on the day of surgery (Time 2). We found that overall frontal EEG alpha power moderated the relation between shyness and self-reported preoperative anxiety. Shyness was related to higher levels of self-reported anxiety on the day of surgery for children with lower average overall frontal alpha EEG power (i.e., higher cortical activity) but not for children with higher average overall frontal alpha EEG power (i.e., lower cortical activity). These results suggest that the pattern of frontal brain activity might amplify some shy children's affective responses to impending surgery. Findings also extend prior results linking children's shyness, frontal brain activity, and anxiety observed in the laboratory to a real-world, ecologically salient environment.

Parents' physiological reactivity to child distress and associations with parenting behaviour: A systematic review.

This systematic review and narrative synthesis characterized parents' physiological stress responses to child distress and how parents' physiological and behavioural responses relate. The review was pre-registered with PROSPERO (#CRD42021252852). In total, 3607 unique records were identified through Medline, Embase, PsycINFO, and CINAHL. Fifty-five studies reported on parents' physiological stress responses during their young child's (0-3 years) distress and were included in the review. Results were synthesized based on the biological outcome and distress context used and risk of bias was evaluated. Most studies examined cortisol or heart rate variability (HRV). Small to moderate decreases in parents' cortisol levels from baseline to post-stressor were reported across studies. Studies of salivary alpha amylase, electrodermal activity, HRV, and other cardiac outcomes reflected weak or inconsistent physiological responses or a paucity of relevant studies. Among the studies that examined associations between parents' physiological and behavioural responses, stronger associations emerged for insensitive parenting behaviours and during dyadic frustration tasks. Risk of bias was a significant limitation across studies and recommendations for future research are discussed.

Seasonality and monthly dynamics of marine myovirus communities.

Marine myoviruses (i.e. bacteriophages with a contractile tail sheath) are numerically abundant and genetically diverse. We developed a terminal restriction fragment length polymorphism assay (TRFLP) for g23, the conserved gene encoding the major capsid protein, to investigate T4-like myovirus communities at USC's Microbial Observatory at the San Pedro Ocean Time-series (SPOT), where we previously reported bacterial seasonality. Between 71 and 154 operational taxonomic units (OTUs) were observed monthly over 3 years. Roughly 25% of OTUs were detected in 31 or more months. T4-like myoviral community structure varied seasonally with some OTUs peaking repeatedly in spring-summer and others in fall-winter, while moderately abundant OTUs persisted year-round. Recurring community structure was demonstrated using discriminant function analysis (DFA, selecting taxa that best predict months) and average Bray-Curtis similarity. DFA showed communities from adjacent months or 12 months apart were positively auto-correlated, while communities 3-7 months apart were negatively auto-correlated. Bray-Curtis similarity was highest between adjacent months - with a local maximum at 12-month and local minima at 6- and 18- to 20-month lags. The T4-like virus community at SPOT exhibited seasonality, yet the somewhat unexpected persistence of moderately abundant OTUs and predictability of the community add new twists to existing conceptual models of marine viruses.

Strain level and comprehensive microbiome analysis in inflammatory bowel disease via multi-technology meta-analysis identifies key bacterial influencers of disease.

Objective: Inflammatory bowel disease (IBD) is a heterogenous disease in which the microbiome has been shown to play an important role. However, the precise homeostatic or pathological functions played by bacteria remain unclear. Most published studies report taxa-disease associations based on single-technology analysis of a single cohort, potentially biasing results to one clinical protocol, cohort, and molecular analysis technology. To begin to address this key question, precise identification of the bacteria implicated in IBD across cohorts is necessary. Methods: We sought to take advantage of the numerous and diverse studies characterizing the microbiome in IBD to develop a multi-technology meta-analysis (MTMA) as a platform for aggregation of independently generated datasets, irrespective of DNA-profiling technique, in order to uncover the consistent microbial modulators of disease. We report the largest strain-level survey of IBD, integrating microbiome profiles from 3,407 samples from 21 datasets spanning 15 cohorts, three of which are presented for the first time in the current study, characterized using three DNA-profiling technologies, mapping all nucleotide data against known, culturable strain reference data. Results: We identify several novel IBD associations with culturable strains that have so far remained elusive, including two genome-sequenced but uncharacterized Lachnospiraceae strains consistently decreased in both the gut luminal and mucosal contents of patients with IBD, and demonstrate that these strains are correlated with inflammation-related pathways that are known mechanisms targeted for treatment. Furthermore, comparative MTMA at the species versus strain level reveals that not all significant strain associations resulted in a corresponding species-level significance and conversely significant species associations are not always re-captured at the strain level. Conclusion: We propose MTMA for uncovering experimentally testable strain-disease associations that, as demonstrated here, are beneficial in discovering mechanisms underpinning microbiome impact on disease or novel targets for therapeutic interventions.

The role of anxiety and related states in pediatric postsurgical pain.

Background: Nearly 20% of children and adolescents have pain with disability 1 year after surgery, and they experience poor sleep, school absence, and decreased activities. Negative clinical, psychological, and developmental effects include greater pain medication use, longer recovery, and fear of future medical care. Research has found psychological and family influences (i.e., child and parental anxiety) on pediatric chronic postsurgical pain (CPSP), but a better understanding of the role of perioperative anxiety and its related states in predicting pediatric postsurgical pain is needed. The poor understanding of the causes of child CPSP can lead to misdiagnosis and inadequate treatment, with significant short- and long-term effects. Objectives: The aim of this review was to summarize the literature on children's perioperative anxiety and parental anxiety in relation to acute postsurgical pain, CPSP, and pain trajectories. We also examined other related psychological factors (i.e., anxiety sensitivity, catastrophizing, pain anxiety, and fear of pain) in relation to pediatric acute and chronic postsurgical pain. Lastly, we discuss the interventions that may be effective in reducing children's and parents' preoperative anxiety. Conclusions: Our findings may improve the understanding of the causes of CPSP and highlight the gaps in research and need for further study.

Contexte: Près de 20 % des enfants et adolescents ont des douleurs avec incapacité un après la chirurgie, et ils ont un mauvais sommeil, des absences scolaires et une diminution de leurs activités. Les effets cliniques, psychologiques et développementaux négatifs comprennent une utilisation accrue des analgésiques, une récupération plus longue et la peur des soins médicaux futurs. La recherche a révélé des influences psychologiques et familiales (c.-à-d. de l'anxiété chez les enfants et les parents) sur la douleur chronique postchirurgicale pédiatrique, mais une meilleure compréhension du rôle de l'anxiété périopératoire et ses états associés pour prédire la douleur postchirurgicale pédiatrique est nécessaire. Une mauvaise compréhension des causes de la douleur chronique postchirurgicale pédiatrique peut entraîner un diagnostic erroné et un traitement inadéquat, avec des effets importants à court et à long terme.Objectifs: Le but de cette revue était de résumer la littérature sur l'anxiété périopératoire des enfants et l'anxiété parentale en lien avec la douleur postchirurgicale aiguë, la douleur chronique postchirurgicale et les trajectoires de la douleur. Nous avons aussi examiné d'autres facteurs psychologiques connexes (ex. : sensibilité à l'anxiété, catastrophisme, anxiété de la douleur, et peur de la douleur) en lien avec la douleur chronique postchirurgicale pédiatrique aigue. Enfin, nous discutons des interventions qui peuvent être efficaces pour réduire l'anxiété préopératoire des enfants et des parents.Conclusions: Nos résultats peuvent améliorer la compréhension des causes de la douleur chronique postchirurgicale et mettre en évidence les lacunes dans la recherche, ainsi que la nécessité d'études plus poussées.

Some Gammaproteobacteria are enriched within CD14+ macrophages from intestinal lamina propria of Crohn's disease patients versus mucus.

Crohn's disease causes chronic inflammation in the gastrointestinal tract and its pathogenesis remains unclear. In the intestine of Crohn's disease patients, CD14+CD11+CD163low macrophages contribute to inflammation through the induction of Th17 cells and production of inflammatory cytokines; the CD14+CD11c+163high fraction is anti-inflammatory through the production of IL-10 in normal cases. In this report, the 16S rRNA gene amplicon sequencing method was used to identify bacteria that are specifically present in intestinal CD14+CD11c+ macrophages of Crohn's disease patients. Bacteria present in intestinal CD14+CD11c+ macrophages and mucus of Crohn's disease patients were separated into different clusters in principal coordinates analysis. There was a statistically significant increase in the relative composition of CD14+CD11c+ macrophages from mucus in two phyla (Proteobacteria [p = 0.01] and Actinobacteria [p = 0.02]) and two families (Moraxellaceae [p < 0.001] and Pseudomonadaceae [p = 0.01]). In addition, OTU-1: Acinetobacter and OTU-8: Pseudomonadaceae tended to concentrate in the CD14+CD11c+CD163low subset, whereas OTU-10: Proteus, OTU-15: Collinsella tended to concentrate more in the CD14+CD11c+CD163high subset than the other subset and mucus.

Impact of a probiotic product on bowel habits and microbial profile in participants with functional constipation: A randomized controlled trial.

OBJECTIVE: To investigate the clinical efficacy of a multi-strain probiotic product on bowel habits and microbial profile in participants with functional constipation. METHODS: This was a randomized, double-blind, placebo-controlled and parallel-arm study. Altogether 94 otherwise healthy adults aged 18 to 65 years with symptoms of functional constipation were randomized as part of the intention-to-treat population. The participants received a placebo or the probiotic product (1.5 × 1010 CFU/day), consisting of Lactobacillus acidophilus DDS-1, Bifidobacterium animalis subsp. lactis UABla-12, Bifidobacterium longum UABl-14 and Bifidobacterium bifidum UABb-10 over 4 weeks. Outcomes included the patient assessment of constipation-symptom (PAC-SYM) questionnaire, stool frequency and consistency, and microbial profile. RESULTS: There were no significant between-group differences in the PAC-SYM score, despite significant within-group differences (P < 0.001) over the study period. The probiotic group showed a faster normalization of stool frequency and consistency, with most participants achieving a normalized profile after 1 week. Fecal samples of the probiotic group exhibited higher relative abundance of Ruminococcaceae (P = 0.0047), including the Ruminococcus genus, and lower relative abundance of Erysipelotrichaceae (P = 0.0172) at end-point compared with baseline. Placebo group samples showed similar abundance profiles over the study, with the exception of Clostridiaceae, which was lower at the study end-point (P = 0.0033). Among treated participants, all four probiotic strains were significantly more abundant after the intervention. CONCLUSIONS: No significant differences were observed in symptomology, with both groups showing a more than 20% improvement. However, the probiotic helped modulate bowel function earlier than the placebo, with a corresponding shift to a more fibrolytic microbiota.

Association of Temperament With Preoperative Anxiety in Pediatric Patients Undergoing Surgery: A Systematic Review and Meta-analysis.

Importance: Preoperative anxiety is associated with poor behavioral adherence during anesthetic induction and adverse postoperative outcomes. Research suggests that temperament can affect preoperative anxiety and influence its short- and long-term effects, but these associations have not been systematically examined. Objective: To examine the associations of temperament with preoperative anxiety in young patients undergoing surgery. Data Sources: Studies from MEDLINE, Embase, CINAHL, PsycINFO, Web of Science, and the Cochrane Central Register of Controlled Trials databases were searched from database inception to June 2018. Study Selection: All prospective studies reporting associations of temperament with preoperative anxiety were included. Overall, 43 of 5451 identified studies met selection criteria. Data Extraction and Synthesis: Using the PRISMA guidelines, reviewers independently read 43 full-text articles, extracted data on eligible studies, and assessed the quality of each study. Data were pooled using the Lipsey and Wilson random-effects model. Main Outcomes and Measures: Primary outcome was the association of temperament with preoperative anxiety in patients undergoing surgery. Results: A total of 23 studies, with 4527 participants aged 1 to 18 years, were included in this review. Meta-analysis of 12 studies including 1064 participants revealed that emotionality (r = 0.11; 95% CI, 0.04 to 0.19), intensity of reaction (r = 0.29; 95% CI, 0.11 to 0.46), and withdrawal (r = 0.40; 95% CI, 0.23 to 0.55) were positively associated with preoperative anxiety, whereas activity level (r = -0.23; 95% CI, -0.31 to -0.16) was negatively correlated with preoperative anxiety. Impulsivity was not significantly associated with preoperative anxiety. Conclusions and Relevance: This systematic review and meta-analysis provided evidence suggesting that temperament may help identify pediatric patients at risk of preoperative anxiety and guide the design of prevention and intervention strategies. Future studies should continue to explore temperament and other factors influencing preoperative anxiety and their transactional effects to guide the development of precision treatment approaches and to optimize perioperative care.

Cervical Microbiome and Response to a Human Papillomavirus Therapeutic Vaccine for Treating High-Grade Cervical Squamous Intraepithelial Lesion.

Human papillomavirus (HPV) infection is associated with the vast majority of cervical cancer cases as well as with other anogenital cancers. PepCan is an investigational HPV therapeutic vaccine for treating cervical high-grade squamous intraepithelial lesions. The present study was performed to test whether the cervical microbiome influences vaccine responses and to explore host factors as determinants of the cervical microbiome composition in women with biopsy-proven high-grade squamous intraepithelial lesions. In a recently completed Phase I clinical trial of PepCan, histological response rate of 45% (14 of 31 patients), a significant increase in circulating T-helper type 1 cells, and a significant decrease in HPV 16 viral load were reported. DNA, extracted from liquid cytology specimens collected before and after vaccinations, were amplified and then hybridized to a G4 PhyloChip assay to characterize the microbiome. We describe trends that certain bacterial taxa in the cervix may be enriched in non-responders in comparison to responders (Padj = .052 for phylum Caldithrix and Padj = .059 for phylum Nitrospirae). There was no difference in bacterial diversity between the 2 groups. A permutational analysis of variance performed for various demographic and immune parameters showed significant clustering with microbiome beta diversity for race, HPV 16 status, peripheral T-helper type 1 cells, and HLA-B40 (P = .001, .014, .037, and .024, respectively). Further analyses showed significant differences at the empirical Operational Taxonomic Unit level for race and HPV 16 status. As these results are from a small Phase I study, further studies are needed to examine the role of cervical microbiome in response to HPV therapeutic vaccines.

The kinetoplastid-infecting Bodo saltans virus (BsV), a window into the most abundant giant viruses in the sea.

Giant viruses are ecologically important players in aquatic ecosystems that have challenged concepts of what constitutes a virus. Herein, we present the giant Bodo saltans virus (BsV), the first characterized representative of the most abundant group of giant viruses in ocean metagenomes, and the first isolate of a klosneuvirus, a subgroup of the Mimiviridae proposed from metagenomic data. BsV infects an ecologically important microzooplankton, the kinetoplastid Bodo saltans. Its 1.39 Mb genome encodes 1227 predicted ORFs, including a complex replication machinery. Yet, much of its translational apparatus has been lost, including all tRNAs. Essential genes are invaded by homing endonuclease-encoding self-splicing introns that may defend against competing viruses. Putative anti-host factors show extensive gene duplication via a genomic accordion indicating an ongoing evolutionary arms race and highlighting the rapid evolution and genomic plasticity that has led to genome gigantism and the enigma that is giant viruses.

Audiovisual interventions for parental preoperative anxiety: A systematic review and meta-analysis.

OBJECTIVE: To systematically review and meta-analyze studies assessing the effectiveness of audiovisual (AV) interventions aimed at reducing anxiety in parents whose children are undergoing elective surgery. METHODS: A comprehensive search of multiple electronic databases was performed. A narrative synthesis of findings and random-effects meta-analyses were used to summarize the results. Our primary outcome was parental anxiety. Secondary outcomes included children's preoperative anxiety and postoperative outcomes; parental satisfaction, knowledge, and need for anesthesia information. Risk of bias was appraised within and across studies. RESULTS: Our search yielded 723 studies and 11 were included. A Standardized Mean Difference (SMD) of -0.53 (95% CI [-0.91, -0.15], p < .01) was found between parental anxiety scores in AV interventions and control groups. In terms of children's preoperative anxiety, there was a SMD of -0.59 (95% CI [-1.11, -0.07], p < .05) between children's anxiety scores in AV intervention and nonintervention participants. Furthermore, AV interventions were shown to shorten the recovery time for children undergoing surgery (SMD = -0.21; 95% CI [-0.39, -0.02], p = .03) but did not lead to improvements on other postoperative outcomes. CONCLUSIONS: These findings suggest that AV interventions have modest, positive effects on both parental and children's preoperative anxiety. Although a statistically significant medium size effect was detected, the clinical significance of this finding requires further exploration. Further research aimed at developing better AV interventions to help guide future practice is warranted. (PsycINFO Database Record

The urinary microbiome associated with bladder cancer.

Recent findings suggest that human microbiome can influence the development of cancer, but the role of microorganisms in bladder cancer pathogenesis has not been explored yet. The aim of this study was to characterize and compare the urinary microbiome of bladder cancer patients with those of healthy controls. Bacterial communities present in urine specimens collected from 12 male patients diagnosed with bladder cancer, and from 11 healthy, age-matched individuals were analysed using 16S sequencing. Our results show that the most abundant phylum in both groups was Firmicutes, followed by Actinobacteria, Bacteroidetes and Proteobacteria. While microbial diversity and overall microbiome composition were not significantly different between groups, we could identify operational taxonomic units (OTUs) that were more abundant in either group. Among those that were significantly enriched in the bladder cancer group, we identified an OTU belonging to genus Fusobacterium, a possible protumorigenic pathogen. In an independent sample of 42 bladder cancer tissues, 11 had Fusobacterium nucleatum sequences detected by PCR. Three OTUs from genera Veillonella, Streptococcus and Corynebacterium were more abundant in healthy urines. However, due to the limited number of participants additional studies are needed to determine if urinary microbiome is associated with bladder cancer.

Risk factors of new onset anxiety and anxiety exacerbation in the perinatal period: A systematic review and meta-analysis.

BACKGROUND: Even though more than 20% of women meet diagnostic criteria for an anxiety disorder during the perinatal period, very little is known about the predictors of these problems. As a result, we systematically reviewed the literature on risk factors for new onset anxiety and maternal anxiety exacerbation in the perinatal period. METHODS: PubMed, MEDLINE, PsycINFO, CINAHL, Ovid, ProQuest Portal, and Web of Science were searched for studies assessing risk factors for the development of new onset anxiety or anxiety worsening in women during pregnancy and the postpartum period. RESULTS: 11,759 citations were identified, with 11 studies meeting eligibility criteria. New onset anxiety was assessed in 7 studies, anxiety worsening in 3, and 1 assessed both. Lower educational attainment, living with extended family members, multiparity, a family history of psychiatric disorders, hyperemesis gravidarum, comorbid sleep disorders, and prenatal oxytocin exposure were risk factors for new onset perinatal anxiety, while presence of comorbid psychiatric disorders and prenatal oxytocin were risk factors for anxiety worsening. LIMITATIONS: Studies not explicitly stating whether participants had pre-existing anxiety disorders were excluded. As a result, meta-analysis was not possible for several risk factors. CONCLUSIONS: Risk factors for new onset anxiety and anxiety worsening during the perinatal period include psychological, social, and biological exposures. Given the lack of studies differentiating women with and without pre-existing anxiety disorders, additional research is required in order to determine whether these factors differ from the non-puerperal population, as well as from each other.