Amniotic fluid from healthy term pregnancies does not harbor a detectable microbial community

Abstract Recent studies have conflicting data regarding the presence of intra-amniotic microbiota. Viral communities are increasingly recognized as important although overlooked components of the human microbiota. It is unknown if the developing fetus is exposed to a community of viruses (virome). Given the debate over the existence of an intra-amniotic microbial community and the importance of understanding how the infant gut is populated, we characterized the virome and bacterial microbiota of amniotic fluid from 24 uncomplicated term pregnancies using next-generation sequencing methods. Contrary to expectations, the bacterial microbiota of amniotic fluid was indistinguishable from contamination controls. Viral reads were sparse in the amniotic fluid, and we found no evidence of a core viral community across samples

Discordant transmission of bacteria and viruses from mothers to babies at birth

BACKGROUND: The earliest microbial colonizers of the human gut can have life-long consequences for their hosts. Precisely how the neonatal gut bacterial microbiome and virome are initially populated is not well understood. To better understand how the maternal gut microbiome influences acquisition of the infant gut microbiome, we studied the early life bacterial microbiomes and viromes of 28 infant twin pairs and their mothers. RESULTS: Infant bacterial and viral communities more closely resemble those of their related co-twin than unrelated infants. We found that 63% of an infant\u27s bacterial microbiome can be traced to their mother\u27s gut microbiota. In contrast, only 15% of their viral communities are acquired from their mother. Delivery route did not determine how much of the bacterial microbiome or virome was shared from mother to infant. However, bacteria-bacteriophage interactions were altered by delivery route. CONCLUSIONS: The maternal gut microbiome significantly influences infant gut microbiome acquisition. Vertical transmission of the bacterial microbiome is substantially higher compared to vertical transmission of the virome. However, the degree of similarity between the maternal and infant gut bacterial microbiome and virome did not vary by delivery route. The greater similarity of the bacterial microbiome and virome between twin pairs than unrelated twins may reflect a shared environmental exposure. Thus, differences of the inter-generation transmissibility at birth between the major kingdoms of microbes indicate that the foundation of these microbial communities are shaped by different rules. Video Abstract

Order effects: a randomised study of three major cancer-specific quality of life instruments

BACKGROUND: In methodological studies and outcomes research, questionnaires often comprise several health-related quality of life (HRQoL) measures. Previous psychological studies have suggested that changing the sequential order of measurement scales within a questionnaire could alter the pattern of responses. Yet, information on the presence or absence of order effects on the assessment of HRQoL in cancer patients is limited. METHODS: An incomplete block design was used in this study of 1277 cancer patients. Each patient filled out a questionnaire package that contained two of the three major cancer-specific HRQoL instruments, namely the Functional Assessment of Cancer Therapy – General, the European Organization for the Research and Treatment of Cancer Core Quality of Life Questionnaire and the Functional Living Index – Cancer. Within a questionnaire package the sequential order of the instruments contained were randomised. Measurement properties of the instruments, including the number of missing values, mean HRQoL scores, known-groups validity and internal consistency were compared between samples of different presentation orders. RESULTS: No effect of presentation order on the four properties aforementioned was found. CONCLUSION: Presentation order is unlikely to alter the responses to these HRQoL instruments administered in cancer patients when any two of them are used together

Relationship between family meals away from home and nutritional status of adolescents

Introduction: Despite the many benefits of family meals, data on association between family meals away from home (FMAFH) and nutritional status of adolescents is limited. This study determined the association between FMAFH with dietary intake and body mass index of adolescents (N=408). Methods: Data were obtained through interviewer-administered questionnaire and anthropometric measurements of adolescents. Results: Respondents comprised 53.7% females, 67.6% Chinese with the mean age of sample being 13.7 ± 0.6 years old. Generally, male adolescents had higher intakes of energy, macronutrients and micronutrients. All nutrients except calcium (51.3%), iron (females - 54.7%) and vitamin A (females - 86.1%) met the recommended intakes. A higher proportion of male (25.4%) than female (13.6%) adolescents were overweight and obese. About 44% of respondents had family meals ≥ 7 times in the previous week with 48.9% reported having family meals at home ≥ 7 times weekly. The majority (91.2%) of adolescents had FMAFH at least once a week either at restaurants (53%), fast food outlets (41.6%), food courts in shopping complexes (40%) or food stalls (30.2%). As the frequency of FMAFH increased, there was an increasing trend in energy and energy-adjusted nutrient intakes. However, only energy-adjusted fat intake was significantly high (p 7 times weekly. No significant association was observed for frequency of FMAFH and body mass index. Conclusion: With increasing dependence on foods outside the home, FMAFH can be a source of healthy diet for families provided they have the knowledge, skills and motivation to make healthy food choices

Dentin Sialophosphoprotein: A Regulatory Protein for Dental Pulp Stem Cell Identity and Fate

The dentin sialophosphoprotein (dspp) transcript is expressed during tooth development as a DSPP precursor protein, which then undergoes cleavage to form mature dentin sialoprotein (DSP) and phosphophoryn (PP) proteins. Previous studies using DSPP-knockout (KO) mice have reported that these animals have hypomineralized teeth, thin dentin, and a large dental pulp chamber, similar to those from patients with dentinogenesis imperfecta III. However, there is no information about factors that regulate dental pulp stem cell lineage fate, a critical early event in the odontoblast-dentin mineralization scheme. To reveal the role of DSPP in odontoblast lineage differentiation during tooth development, we systematically examined teeth from wild-type (wt) and DSPP-KO C57BL/6 mice between the ages of postnatal day 1 and 3 months. We found developmental abnormalities not previously reported, such as circular dentin formation within dental pulp cells and altered odontoblast differentiation in DSPP-KO mice, even as early as 1 day after birth. Surprisingly, we also identified chondrocyte-like cells in the dental pulp from KO-mice teeth. Thus, these studies that compare wt and DSPP-KO mice suggest that the expression of DSPP precursor protein is required for normal odontoblast lineage differentiation and that the absence of DSPP allows dental pulp cells to differentiate into chondrocyte-like cells, which could negatively impact pulpal wound healing and tissue regeneration.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140203/1/scd.2014.0066.pd

Predicting Risk of End-Stage Liver Disease in Antiretroviral-Treated HIV/Hepatitis C Virus-Coinfected Patients

Background. End-stage liver disease (ESLD) is an important cause of morbidity among HIV/hepatitis C virus (HCV)-coinfected patients. Quantifying the risk of this outcome over time could help determine which coinfected patients should be targeted for risk factor modification and HCV treatment. We evaluated demographic, clinical, and laboratory variables to predict risk of ESLD in HIV/HCV-coinfected patients receiving antiretroviral therapy (ART). Methods. We conducted a retrospective cohort study among 6,016 HIV/HCV-coinfected patients who received ART within the Veterans Health Administration between 1997 and 2010. The main outcome was incident ESLD, defined by hepatic decompensation, hepatocellular carcinoma, or liver-related death. Cox regression was used to develop prognostic models based on baseline demographic, clinical, and laboratory variables, including FIB-4 and aspartate aminotransferase-to-platelet ratio index, previously validated markers of hepatic fibrosis. Model performance was assessed by discrimination and decision curve analysis. Results. Among 6,016 HIV/HCV patients, 532 (8.8%) developed ESLD over a median of 6.6 years. A model comprising FIB-4 and race had modest discrimination for ESLD (c-statistic, 0.73) and higher net benefit than alternative strategies of treating no or all coinfected patients at relevant risk thresholds. For FIB-4 \u3e3.25, ESLD risk ranged from 7.9% at 1 year to 26.0% at 5 years among non-blacks and from 2.4% at 1 year to 14.0% at 5 years among blacks. Conclusions. Race and FIB-4 provided important predictive information on ESLD risk among HIV/HCV patients. Estimating risk of ESLD using these variables could help direct HCV treatment decisions among HIV/HCV-coinfected patients

Veterans health administration hepatitis B testing and treatment with anti-CD20 antibody administration

AIM: To evaluate pretreatment hepatitis B virus (HBV) testing, vaccination, and antiviral treatment rates in Veterans Affairs patients receiving anti-CD20 Ab for quality improvement. METHODS: We performed a retrospective cohort study using a national repository of Veterans Health Administration (VHA) electronic health record data. We identified all patients receiving anti-CD20 Ab treatment (2002-2014). We ascertained patient demographics, laboratory results, HBV vaccination status (from vaccination records), pharmacy data, and vital status. The high risk period for HBV reactivation is during anti-CD20 Ab treatment and 12 mo follow up. Therefore, we analyzed those who were followed to death or for at least 12 mo after completing anti-CD20 Ab. Pretreatment serologic tests were used to categorize chronic HBV (hepatitis B surface antigen positive or HBsAg+), past HBV (HBsAg-, hepatitis B core antibody positive or HBcAb+), resolved HBV (HBsAg-, HBcAb+, hepatitis B surface antibody positive or HBsAb+), likely prior vaccination (isolated HBsAb+), HBV negative (HBsAg-, HBcAb-), or unknown. Acute hepatitis B was defined by the appearance of HBsAg+ in the high risk period in patients who were pretreatment HBV negative. We assessed HBV antiviral treatment and the incidence of hepatitis, liver failure, and death during the high risk period. Cumulative hepatitis, liver failure, and death after anti-CD20 Ab initiation were compared by HBV disease categories and differences compared using the χ2 test. Mean time to hepatitis peak alanine aminotransferase, liver failure, and death relative to anti-CD20 Ab administration and follow-up were also compared by HBV disease group. RESULTS: Among 19304 VHA patients who received anti-CD20 Ab, 10224 (53%) had pretreatment HBsAg testing during the study period, with 49% and 43% tested for HBsAg and HBcAb, respectively within 6 mo pretreatment in 2014. Of those tested, 2% (167/10224) had chronic HBV, 4% (326/7903) past HBV, 5% (427/8110) resolved HBV, 8% (628/8110) likely prior HBV vaccination, and 76% (6022/7903) were HBV negative. In those with chronic HBV infection, ≤ 37% received HBV antiviral treatment during the high risk period while 21% to 23% of those with past or resolved HBV, respectively, received HBV antiviral treatment. During and 12 mo after anti-CD20 Ab, the rate of hepatitis was significantly greater in those HBV positive vs negative (P = 0.001). The mortality rate was 35%-40% in chronic or past hepatitis B and 26%-31% in hepatitis B negative. In those pretreatment HBV negative, 16 (0.3%) developed acute hepatitis B of 4947 tested during anti-CD20Ab treatment and follow-up. CONCLUSION: While HBV testing of Veterans has increased prior to anti-CD20 Ab, few HBV+ patients received HBV antivirals, suggesting electronic health record algorithms may enhance health outcomes

Nocturnal Activation of Melatonin Receptor Type 1 Signaling Modulates Diurnal Insulin Sensitivity via Regulation of Pi3k Activity

Recent genetic studies have highlighted the potential involvement of melatonin receptor 1 (MT1) and melatonin receptor 2 (MT2) in the pathogenesis of type 2 diabetes. Here, we report that mice lacking MT1 (MT1 KO) tend to accumulate more fat mass than WT mice and exhibit marked systemic insulin resistance. Additional experiments revealed that the main insulin signaling pathway affected by the loss of MT1 was the activation of phosphatidylinositol-3-kinase (PI3K). Transcripts of both catalytic and regulatory subunits of PI3K were strongly downregulated within MT1 KO mice. Moreover, the suppression of nocturnal melatonin levels within WT mice, by exposing mice to constant light, resulted in impaired PI3K activity and insulin resistance during the day, similar to what was observed in MT1 KO mice. Inversely, administration of melatonin to WT mice exposed to constant light was sufficient and necessary to restore insulin-mediated PI3K activity and insulin sensitivity. Hence, our data demonstrate that the activation of MT1 signaling at night modulates insulin sensitivity during the day via the regulation of the PI3K transcription and activity. Lastly, we provide evidence that decreased expression of MTNR1A (MT1) in the liver of diabetic individuals is associated with poorly controlled diabetes

Influence of real-world characteristics on outcomes for patients with methicillin-resistant Staphylococcal skin and soft tissue infections:a multi-country medical chart review in Europe

BACKGROUND: Patient-related (demographic/disease) and treatment-related (drug/clinician/hospital) characteristics were evaluated as potential predictors of healthcare resource use and opportunities for early switch (ES) from intravenous (IV)-to-oral methicillin-resistant Staphylococcus aureus (MRSA)-active antibiotic therapy and early hospital discharge (ED). METHODS: This retrospective observational medical chart study analyzed patients (across 12 European countries) with microbiologically confirmed MRSA complicated skin and soft tissue infections (cSSTI), ≥3 days of IV anti-MRSA antibiotics during hospitalization (July 1, 2010-June 30, 2011), and discharged alive by July 31, 2011. Logistic/linear regression models evaluated characteristics potentially associated with actual resource use (length of IV therapy, length of hospital stay [LOS], IV-to-oral antibiotic switch), and ES and ED (using literature-based and expert-verified criteria) outcomes. RESULTS: 1542 patients (mean ± SD age 60.8 ± 16.5 years; 61.5% males) were assessed with 81.0% hospitalized for MRSA cSSTI as the primary reason. Several patient demographic, infection, complication, treatment, and hospital characteristics were predictive of length of IV therapy, LOS, IV-to-oral antibiotic switch, or ES and ED opportunities. Outcomes and ES and ED opportunities varied across countries. Length of IV therapy and LOS (r = 0.66, p < 0.0001) and eligibilities for ES and ED (r = 0.44, p < 0.0001) showed relatively strong correlations. IV-to-oral antibiotic switch patients had significantly shorter length of IV therapy (−5.19 days, p < 0.001) and non-significantly shorter LOS (−1.86 days, p > 0.05). Certain patient and treatment characteristics were associated with increased odds of ES (healthcare-associated/ hospital-acquired infection) and ED (patient living arrangements, healthcare-associated/ hospital-acquired infection, initiating MRSA-active treatment 1–2 days post cSSTI index date, existing ED protocol), while other factors decreased the odds of ES (no documented MRSA culture, ≥4 days from admission to cSSTI index date, IV-to-oral switch, IV line infection) and ED (dementia, no documented MRSA culture, initiating MRSA-active treatment ≥3 days post cSSTI index date, existing ES protocol). CONCLUSIONS: Practice patterns and opportunity for further ES and ED were affected by several infection, treatment, hospital, and geographical characteristics, which should be considered in identifying ES and ED opportunities and designing interventions for MRSA cSSTI to reduce IV days and LOS while maintaining the quality of care. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2334-14-476) contains supplementary material, which is available to authorized users