Prognostic genome and transcriptome signatures in colorectal cancers.

Colorectal cancer is caused by a sequence of somatic genomic alterations affecting driver genes in core cancer pathways1. Here, to understand the functional and prognostic impact of cancer-causing somatic mutations, we analysed the whole genomes and transcriptomes of 1,063 primary colorectal cancers in a population-based cohort with long-term follow-up. From the 96 mutated driver genes, 9 were not previously implicated in colorectal cancer and 24 had not been linked to any cancer. Two distinct patterns of pathway co-mutations were observed, timing analyses identified nine early and three late driver gene mutations, and several signatures of colorectal-cancer-specific mutational processes were identified. Mutations in WNT, EGFR and TGFß pathway genes, the mitochondrial CYB gene and 3 regulatory elements along with 21 copy-number variations and the COSMIC SBS44 signature correlated with survival. Gene expression classification yielded five prognostic subtypes with distinct molecular features, in part explained by underlying genomic alterations. Microsatellite-instable tumours divided into two classes with different levels of hypoxia and infiltration of immune and stromal cells. To our knowledge, this study constitutes the largest integrated genome and transcriptome analysis of colorectal cancer, and interlinks mutations, gene expression and patient outcomes. The identification of prognostic mutations and expression subtypes can guide future efforts to individualize colorectal cancer therapy.

Antibiotic or gastric acid inhibitor use during pregnancy and postpartum depression: Population-based cohort study.

INTRODUCTION: Postpartum depression is one of the most common non-obstetric postnatal complications. As the microbiome (and gut-brain axis) as well as inflammation may be involved in the mechanism, we aimed to assess if antibiotic or gastric acid inhibition use during pregnancy affects the risk of postpartum depression (clinical diagnosis and/or antidepressant use up to 1 year after childbirth). MATERIAL AND METHODS: This population-based cohort study used first singleton pregnancy resulting in a live birth in Sweden from 2006 to 2016. Women with history of depression were excluded. Multivariable logistic regression models were used to assess the impact of antibiotics and gastric acid inhibitors and other risk factors, presented as odds ratios (ORs) with 95% confidence intervals (CI). RESULTS: Overall, 29% of all 10 666 women with postpartum depression were exposed to antibiotics and 6.2% to gastric acid inhibitors, compared to, respectively, 21% and 3.2% of 613 205 women without postpartum depression. Antibiotic use during pregnancy was associated with postpartum depression (OR 1.43, 95% CI 1.37-1.49), particularly for quinolones and other antibacterials (including nitroimidazole derivatives). Gastric acid inhibition was associated with an even higher risk than antibiotics (OR 2.04, 95% CI 1.88-2.21). Both antibiotics and gastric acid inhibitors suggested higher risk with increased dose in a dose-response analysis. CONCLUSIONS: The use of antibiotics and gastric acid inhibition drugs during pregnancy appeared to be associated with a higher risk of postpartum depression. However, it is important to consider that other predisposing factors could contribute to this increased risk, even after excluding individuals with a history of depression.

Global prevalence of antibiotic consumption during pregnancy: A systematic review and meta-analysis.

BACKGROUND: Antibiotic use during pregnancy is widespread with notable variations across regions. METHODS: This systematic review and meta-analysis (Prospero protocol CRD42023418979) examines the prevalence and variability of antibiotic use in pregnancy globally and regionally, considering different methodologies and maternal characteristics. We searched Embase, PubMed, and Web of Science for observational studies published in English from the year 2000 and onwards. Random-effect meta-analyses were used to pool the prevalence of antibiotic consumption during pregnancy, presented as percentages with 95% confidence intervals (CI). Joanna Briggs Institute Critical appraisal checklist for prevalence studies was used for bias assessment. FINDINGS: Overall, 116 studies (14 from Africa, 24 from the Americas, six from Eastern Mediterranean, 57 from Europe, four from South-East Asia and 11 from Western Pacific) were included (33,821,194 pregnancies). The majority of studies (84.5%) were appraised with a low risk of bias. The prevalence of antibiotic consumption during pregnancy ranged between 0.04 to 90%, with a pooled estimate of 23.6% (95% CI: 20.1-27.5, I2 =100%). Low-income countries had the highest pooled prevalence (45.3%, 95% CI: 15.4-79.1, I2 =99.6%). Regionally, the Western Pacific had the highest pooled prevalence (34.4%, 95% CI: 13.4-64.1, I2 =100%). The prevalence of antibiotic consumption during pregnancy increased over time in the Americas and Western Pacific. The studies exhibited considerable heterogeneity (I2 >95%), and the trim-and-fill method estimated a potential 10% underestimation of the overall pooled prevalence, suggesting publication bias. INTERPRETATION: This meta-analysis suggests that about 1/4 of women worldwide use antibiotics during pregnancy. This study suggests a high prevalence of antibiotic consumption during pregnancy with disparities according to region and level of country income, ethnicity and whether antibiotics were prescribed or self-medicated. There was a variability in reported findings across age categories, potential bias from small sample sizes, and language bias from including only studies published in English.

Pre-pregnancy complications - associated factors and wellbeing in early pregnancy: a Swedish cohort study.

BACKGROUND: Many couples experience difficulties to become pregnant or carry a pregnancy to term due to unknown causes. Here we define pre-pregnancy complications as having prior recurrent pregnancy loss, prior late miscarriages, time to pregnancy more than one year, or the use of artificial reproductive technologies. We aim to identify factors associated with pre-pregnancy complications and poor well-being in early pregnancy. METHODS: Online questionnaire data from 5330 unique pregnancies in Sweden were collected from November 2017 - February 2021. Multivariable logistic regression modelling was used to investigate potential risk factors for pre-pregnancy complications and differences in early pregnancy symptoms. RESULTS: Pre-pregnancy complications were identified in 1142 participants (21%). Risk factors included diagnosed endometriosis, thyroid medication, opioids and other strong pain medication, body mass index > 25 kg/m2 and age over 35 years. Different subgroups of pre-pregnancy complications had unique risk factors. The groups also experienced different pregnancy symptoms in early pregnancy, where women that had experienced recurrent pregnancy loss were at higher risk of depression in their current pregnancy. CONCLUSION: We report one of the largest pregnancy cohorts with high frequency of pre-pregnancy complications compared to the Swedish population. Prescribed drug use and body weight were the top potentially modifiable risk factors in all groups. Participants that experienced pre-pregnancy complications also had higher risk of depression and pregnancy problems in early pregnancy.

The salivary microbiota is altered in cervical dysplasia patients and influenced by conization.

This study supports the correlation between the salivary microbiota and cervical dysplasia and suggests that smoking influences the salivary microbiota.

Cohort profile: the Swedish Maternal Microbiome project (SweMaMi) - assessing the dynamic associations between the microbiome and maternal and neonatal adverse events.

PURPOSE: The Swedish Maternal Microbiome (SweMaMi) project was initiated to better understand the dynamics of the microbiome in pregnancy, with longitudinal microbiome sampling, shotgun metagenomics, extensive questionnaires and health registry linkage. PARTICIPANTS: Pregnant women were recruited before the 20th gestational week during 2017-2021 in Sweden. In total, 5439 pregnancies (5193 unique women) were included. For 3973 pregnancies (73%), samples were provided at baseline, and for 3141 (58%) at all three timepoints (second and third trimester and postpartum). In total, 38 591 maternal microbiome samples (vaginal, faecal and saliva) and 3109 infant faecal samples were collected. Questionnaires were used to collect information on general, reproductive and mental health, diet and lifestyle, complemented by linkage to the nationwide health registries, also used to follow up the health of the offspring (up to age 10). FINDINGS TO DATE: The cohort is fairly representative for the total Swedish pregnant population (data from 2019), with 41% first-time mothers. Women with university level education, born in Sweden, with normal body mass index, not using tobacco-products and aged 30-34 years were slightly over-represented. FUTURE PLANS: The sample and data collection were finalised in November 2021. The next steps are the characterisation of the microbial DNA and linkage to the health and demographic information from the questionnaires and registries. The role of the microbiome on maternal and neonatal outcomes and early-childhood diseases will be explored (including preterm birth, miscarriage) and the role and interaction of other risk factors and confounders (including endometriosis, polycystic ovarian syndrome, diet, drug use). This is currently among the largest pregnancy cohorts in the world with longitudinal design and detailed and standardised microbiome sampling enabling follow-up of both mothers and children. The findings are expected to contribute greatly to the field of reproductive health focusing on pregnancy and neonatal outcomes.

The vaginal microbiome and the risk of preterm birth: a systematic review and network meta-analysis.

Preterm birth is a major cause of neonatal morbidity and mortality worldwide. Increasing evidence links the vaginal microbiome to the risk of spontaneous preterm labour that leads to preterm birth. The aim of this systematic review and network meta-analysis was to investigate the association between the vaginal microbiome, defined as community state types (CSTs, i.e. dominance of specific lactobacilli spp, or not (low-lactobacilli)), and the risk of preterm birth. Systematic review using PubMed, Web of Science, Embase and Cochrane library was performed. Longitudinal studies using culture-independent methods categorizing the vaginal microbiome in at least three different CSTs to assess the risk of preterm birth were included. A (network) meta-analysis was conducted, presenting pooled odds ratios (OR) and 95% confidence intervals (CI); and weighted proportions and 95% CI. All 17 studies were published between 2014 and 2021 and included 38-539 pregnancies and 8-107 preterm births. Women presenting with "low-lactobacilli" vaginal microbiome were at increased risk (OR 1.69, 95% CI 1.15-2.49) for delivering preterm compared to Lactobacillus crispatus dominant women. Our network meta-analysis supports the microbiome being predictive of preterm birth, where low abundance of lactobacilli is associated with the highest risk, and L. crispatus dominance the lowest.

Vaginal microbiota and human papillomavirus infection among young Swedish women.

Human papillomavirus (HPV) infection is one of the most common sexually transmitted diseases. To define the HPV-associated microbial community among a high vaccination coverage population, we carried out a cross-sectional study with 345 young Swedish women. The microbial composition and its association with HPV infection, including 27 HPV types, were analyzed. Microbial alpha-diversity was found significantly higher in the HPV-infected group (especially with oncogenic HPV types and multiple HPV types), compared with the HPV negative group. The vaginal microbiota among HPV-infected women was characterized by a larger number of bacterial vaginosis-associated bacteria (BVAB), Sneathia, Prevotella, and Megasphaera. In addition, the correlation analysis demonstrated that twice as many women with non-Lactobacillus-dominant vaginal microbiota were infected with oncogenic HPV types, compared with L. crispatus-dominated vaginal microbiota. The data suggest that HPV infection, especially oncogenic HPV types, is strongly associated with a non-Lactobacillus-dominant vaginal microbiota, regardless of age and vaccination status.

The relationship between occupational physical activity and self-reported vs measured total physical activity.

INTRODUCTION: Despite the well-established benefits of physical activity (PA), a large portion of U.S. adults are not meeting recommended health-based guidelines. Although PA occurs in several domains, population-based studies tend to focus on leisure-time PA, with few studies examining occupational activity (OA) level as a separate determinant of overall PA. METHODS: Data were obtained from the 2014-2016 Survey of Health of Wisconsin (SHOW). Currently employed SHOW participants (n = 822) were categorized into OA level categories. Bivariate analyses and multinomial logistic regression analyses were used to identify predictors and to test associations between OA and odds of meeting total PA guidelines using both self-reported and accelerometer-based data. RESULTS: Individuals with high OA level jobs tended to be males (p < 0.01), current smokers (p < 0.01), and have low education (p < 0.01). When measured by self-report, a greater proportion of individuals in high OA jobs (89%) met the physical activity guidelines compared to those in medium (78%) and low (76%) OA jobs (p = 0.01). Further, adjusted odds of doing some PA vs meeting PA guidelines were higher for low OA vs. high OA level (OR = 2.40, 95% CI 1.46-3.94, p < 0.01). This trend was not observed when PA was measured via accelerometer (OR = 1.00, 95% CI 0.62-1.60, p = 0.99). CONCLUSIONS: Correlations between low, intermediate, and high OA and levels of overall PA varied by measurement type. Further research is needed to improve PA measurements within subdomains such as OA and to examine the tradeoffs between OA and leisure-time PA and relationships with health.

The relationship between patient functional status and environmental contamination by Clostridium difficile: a pilot study.

INTRODUCTION: Limited data exist on patient factors related to environmental contamination with Clostridium difficile. METHODS: We evaluated the association between the functional status of patients with C. difficile infection (CDI) and environmental contamination with C. difficile. RESULTS: Contamination of patient rooms was frequent and higher functional status was associated with contaminated surfaces remote from the bed. All but one environmental isolates matched the corresponding patient's stool isolate for the seven patients tested. CONCLUSION: Functional status is a factor that influences environmental contamination with C. difficile. Future studies should evaluate strategies to reduce contamination in CDI patient rooms, taking into account the patient's functional status.

The influence of materialism and ideal body internalization on body-dissatisfaction and body-shaping behaviors of young men and women: support for the Consumer Culture Impact Model.

Exposure to media images of the 'body-perfect' ideal has been partly blamed for the pursuit of thinness among women and muscularity among men. Research has largely overlooked the materialistic messages frequently associated with these images. We present findings from two studies with Icelandic students aged 18-21, one focusing on young women (n = 303) and one on young men (n = 226), which test associations of materialistic and body-perfect ideals with body dissatisfaction and excessive body shaping behaviors. In both studies, the internalization of materialistic values is strongly linked to the internalization of body-perfect ideals: the thin-ideal for young women, and the muscular-ideal for young men. A materialist value orientation also predicted body dissatisfaction in both studies, and was linked to body shaping behaviors, albeit differently for young women and men. Thus, the research identifies materialism as a further correlate of both body dissatisfaction and excessive body-shaping behaviors. The findings support Dittmar's (2008) Consumer Culture Impact Model, which proposes that the body-perfect and 'material good life' ideals jointly impact well-being.

Reducing health care-associated infections: patients want to be engaged and learn about infection prevention.

BACKGROUND: Multidrug-resistant organisms (MDROs) are common in health care-associated infection (HAI). The aim of this study was to examine patient's willingness to learn about MDROs and HAIs and their preferred ways of education about MDRO HAIs. METHODS: Interviewer-administered questionnaire at a tertiary care academic medical center. We recruited a sample of 100 adult patients who had HAI and were placed in contact precautions. RESULTS: Ninety-six percent of patients had heard of MDROs. Ninety-eight percent of patients thought that their involvement in learning about MDROs was very important or important. Most of the patients thought that receiving information about MDROs would probably or definitely help them to make choices that would improve their health care. Patients expressed interest in more than 1 form of educational material: 70% chose written material, 57% verbal information, 53% an informational video, and 50% Internet-based material. Patients with a higher level of education were more likely to prefer written material. Patients emphasized simple language and incorporation of actual patient stories. CONCLUSION: Hospitalized patients with MDROs in our study believed that involvement on their part was important. Individuals' level of education affected their preference regarding choice of educational material, but most patients prefered receiving written or verbal information. Patient preferences must be incorporated into education to increase engagement for prevention of MDROs and HAIs.