Objective
Characterise the vaginal metabolome of cervical HPV‐infected and uninfected women.
Design
Cross‐sectional.
Setting
The Center for Health Behavior Research at the University of Maryland ...School of Public Health.
Sample
Thirty‐nine participants, 13 categorised as HPV‐negative and 26 as HPV‐positive (any genotype; HPV+), 14 of whom were positive with at least one high‐risk HPV strain (hrHPV).
Method
Self‐collected mid‐vaginal swabs were profiled for bacterial composition by 16S rRNA gene amplicon sequencing, metabolites by both gas and liquid chromatography mass spectrometry, and 37 types of HPV DNA.
Main outcome measures
Metabolite abundances.
Results
Vaginal microbiota clustered into Community State Type (CST) I (Lactobacillus crispatus‐dominated), CST III (Lactobacillus iners‐dominated), and CST IV (low‐Lactobacillus, ‘molecular‐BV’). HPV+ women had higher biogenic amine and phospholipid concentrations compared with HPV– women after adjustment for CST and cigarette smoking. Metabolomic profiles of HPV+ and HPV− women differed in strata of CST. In CST III, there were higher concentrations of biogenic amines and glycogen‐related metabolites in HPV+ women than in HPV– women. In CST IV, there were lower concentrations of glutathione, glycogen, and phospholipid‐related metabolites in HPV+ participants than in HPV– participants. Across all CSTs, women with hrHPV strains had lower concentrations of amino acids, lipids, and peptides compared with women who had only low‐risk HPV (lrHPV).
Conclusions
The vaginal metabolome of HPV+ women differed from HPV− women in terms of several metabolites, including biogenic amines, glutathione, and lipid‐related metabolites. If the temporal relation between increased levels of reduced glutathione and oxidised glutathione and HPV incidence/persistence is confirmed in future studies, anti‐oxidant therapies may be considered as a non‐surgical HPV control intervention.
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Metabolomics study: Vaginal microenvironment of HPV+ women may be informative for non‐surgical interventions.
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Metabolomics study: Vaginal microenvironment of HPV+ women may be informative for non‐surgical interventions.
The personality dimension of schizotypy is well established, and schizotypal traits can be taken to represent a proneness toward developing psychosis. Yet, there are competing theories about the ...latent structure of schizotypy. More specifically, there is controversy over the extent to which this propensity toward psychosis is present only in a small proportion of the population, or whether it is spread dimensionally throughout the general community. On the basis of accumulating research findings the present article argues for a fully dimensional model of schizotypy. It describes recent neurobiological, neuropsychological, social and environmental evidence supporting the idea that schizotypy in healthy populations, and disorders on the schizophrenia spectrum are fundamentally linked. Directions for further research are also considered.
Campylobacter species cause 1.4 million infections each year in the United States. Fluoroquinolones (e.g., ciprofloxacin) are commonly used in adults with Campylobacter infection and other ...infections. Fluoroquinolones (e.g., enrofloxacin) are also used in veterinary medicine. Human infections with fluoroquinolone-resistant Campylobacter species have become increasingly common and are associated with consumption of poultry. These findings, along with other data, prompted the US Food and Drug Administration to propose the withdrawal of fluoroquinolone use in poultry in 2000. A lengthy legal hearing concluded with an order to withdraw enrofloxacin from use in poultry (effective in September 2005). Clinicians are likely to continue to encounter patients with fluoroquinolone-resistant Campylobacter infection and other enteric infection because of the continued circulation of fluoroquinolone-resistant Campylobacter species in poultry flocks and in persons returning from foreign travel who have acquired a fluoroquinolone-resistant enteric infection while abroad. Judicious use of fluoroquinolones and other antimicrobial agents in human and veterinary medicine is essential to preserve the efficacy of these important chemotherapeutic agents.
This study assessed survival and neurodevelopmental outcomes among infants born at 22 to 24 weeks of gestation, as measured at 18 to 22 months of corrected age, and showed that the rate of survival ...without neurodevelopmental impairment increased between 2000 and 2011.
Care of periviable infants remains a great challenge in neonatal and perinatal medicine.
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Infants born between 22 and 24 weeks of gestation often die or survive with long-term neurodevelopmental impairment.
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The approach to resuscitation and management at these early gestational ages varies substantially.
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Data reported during the past 5 years indicate that mortality has declined among extremely premature infants.
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Investigators at the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Neonatal Research Network (NRN) reported a decrease in mortality over the past two decades, with the greatest gains in survival seen among infants . . .
Pegylated interferon‐α (PEG‐IFN‐α or PEG‐IFN 2a and 2b)– and ribavirin (RBV)‐based regimens are the mainstay for treatment of hepatitis C virus (HCV) genotype 1. IFNL3 (IL28B) genotype is the ...strongest baseline predictor of response to PEG‐IFN‐α and RBV therapy in previously untreated patients and can be used by patients and clinicians as part of the shared decision‐making process for initiating treatment for HCV infection. We provide information regarding the clinical use of PEG‐IFN‐α‐ and RBV‐containing regimens based on IFNL3 genotype.
Clinical Pharmacology & Therapeutics (2014); 95 2, 141–146. doi:10.1038/clpt.2013.203
Acoustically excited microstructures have demonstrated significant potential for small-scale biomedical applications by overcoming major microfluidic limitations. Recently, the application of ...oscillating microbubbles has demonstrated their superiority over acoustically excited solid structures due to their enhanced acoustic streaming at low input power. However, their limited temporal stability hinders their direct applicability for industrial or clinical purposes. Here, we introduce the embedded microbubble, a novel acoustofluidic design based on the combination of solid structures (poly(dimethylsiloxane)) and microbubbles (air-filled cavity) to combine the benefits of both approaches while minimizing their drawbacks. We investigate the influence of various design parameters and geometrical features through numerical simulations and experimentally evaluate their manipulation capabilities. Finally, we demonstrate the capabilities of our design for microfluidic applications by investigating its mixing performance as well as through the controlled rotational manipulation of individual HeLa cells.
Cigarette smoking has been associated with both the diagnosis of bacterial vaginosis (BV) and a vaginal microbiota lacking protective Lactobacillus spp. As the mechanism linking smoking with vaginal ...microbiota and BV is unclear, we sought to compare the vaginal metabolomes of smokers and non-smokers (17 smokers/19 non-smokers). Metabolomic profiles were determined by gas and liquid chromatography mass spectrometry in a cross-sectional study. Analysis of the 16S rRNA gene populations revealed samples clustered into three community state types (CSTs) --- CST-I (L. crispatus-dominated), CST-III (L. iners-dominated) or CST-IV (low-Lactobacillus). We identified 607 metabolites, including 12 that differed significantly (q-value < 0.05) between smokers and non-smokers. Nicotine, and the breakdown metabolites cotinine and hydroxycotinine were substantially higher in smokers, as expected. Among women categorized to CST-IV, biogenic amines, including agmatine, cadaverine, putrescine, tryptamine and tyramine were substantially higher in smokers, while dipeptides were lower in smokers. These biogenic amines are known to affect the virulence of infective pathogens and contribute to vaginal malodor. Our data suggest that cigarette smoking is associated with differences in important vaginal metabolites, and women who smoke, and particularly women who are also depauperate for Lactobacillus spp., may have increased susceptibilities to urogenital infections and increased malodor.
BackgroundThe goal of this study was to characterize viral loads and factors affecting viral clearance in persons with severe influenza MethodsThis was a 1-year prospective, observational study ...involving consecutive adults hospitalized with influenza. Nasal and throat swabs were collected at presentation, then daily until 1 week after symptom onset. Real-time reverse-transcriptase polymerase chain reaction to determine viral RNA concentration and virus isolation were performed. Viral RNA concentration was analyzed using multiple linear or logistic regressions or mixed-effect models ResultsOne hundred forty-seven inpatients with influenza A (H3N2) infection were studied (mean age ± standard deviation, 72±16 years). Viral RNA concentration at presentation positively correlated with symptom scores and was significantly higher than that among time-matched outpatients (control subjects). Patients with major comorbidities had high viral RNA concentration even when presenting >2 days after symptom onset (mean ± standard deviation, 5.06±1.85 vs 3.62±2.13 log10 copies/mL; P=.005; β, +0.86 95% confidence interval, +0.03 to +1.68). Viral RNA concentration demonstrated a nonlinear decrease with time; 26% of oseltamivir-treated and 57% of untreated patients had RNA detected at 1 week after symptom onset. Oseltamivir started on or before symptom day 4 was independently associated with an accelerated decrease in viral RNA concentration (mean β standard error, −1.19 0.43 and −0.68 0.33 log10 copies/mL for patients treated on day 1 and days 2–3, respectively; P<.05) and viral RNA clearance at 1 week (odds ratio, 0.10 95% confidence interval, 0.03–0.35 and 0.30 0.10–0.90 for patients treated on day 1–2 and day 3–4, respectively). Conversely, major comorbidities and systemic corticosteroid use for asthma or chronic obstructive pulmonary disease exacerbations were associated with slower viral clearance. Viral RNA clearance was associated with a shorter hospital stay (7.0 vs 13.5 days; P=.001) ConclusionPatients hospitalized with severe influenza have more active and prolonged viral replication. Weakened host defenses slow viral clearance, whereas antivirals started within the first 4 days of illness enhance viral clearance
Noise due to scattered light has been a frequent disturbance in the advanced LIGO gravitational wave detectors, hindering the detection of gravitational waves. The non stationary scatter noise caused ...by low frequency motion can be recognized as arches in the time-frequency plane of the gravitational wave channel. In this paper, we characterize the scattering noise for LIGO and Virgo's third observing run O3 from April, 2019 to March, 2020. We find at least two different populations of scattering noise and we investigate the multiple origins of one of them as well as its mitigation. We find that relative motion between two specific surfaces is strongly correlated with the presence of scattered light and we implement a technique to reduce this motion. We also present an algorithm using a witness channel to identify the times this noise can be present in the detector.
Previous studies that have examined genetic influences on suicidal behaviour were confounded by genetic vulnerability for psychiatric risk factors. The present study examines genetic influences on ...suicidality (i.e. suicidal ideation and/or suicide attempt) after controlling for the inheritance of psychiatric disorders.
Sociodemographics, combat exposure, lifetime DSM-III-R major depression, bipolar disorder, childhood conduct disorder, adult antisocial personality disorder, panic disorder, post-traumatic stress disorder, drug dependence, alcohol dependence and lifetime suicidal ideation and attempt were assessed in 3372 twin pairs from the Vietnam Era Twin Registry who were assessed in 1987 and 1992. Genetic risk factors for suicidality were examined in a multinomial logistic regression model. Additive genetic, shared environmental and non-shared environmental effects on suicidality were estimated using structural equation modelling, controlling for other risk factors.
The prevalence of suicidal ideation and suicide attempt were 16.1% and 2.4% respectively. In a multinomial regression model, co-twin's suicidality, being white, unemployment, being other than married, medium combat exposure and psychiatric disorders were significant predictors for suicidal ideation. Co-twin's suicidality, unemployment, marital disruption, low education attainment and psychiatric disorders (except childhood conduct disorder) were significant predictors for suicide attempt. Model-fitting suggested that suicidal ideation was influenced by additive genetic (36%) and non-shared environmental (64%) effects, while suicide attempt was affected by additive genetic (17%), shared environmental (19%) and non-shared environmental (64%) effects.
There may be a genetic susceptibility specific to both suicidal ideation and suicide attempt in men, which is not explained by the inheritance of common psychiatric disorders.
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