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.
Aspergillus fumigatus is the most common agent of invasive aspergillosis (IA). In recent years, resistance to triazoles, the mainstay of IA therapy, has emerged in different countries worldwide. IA ...caused by azole-resistant A. fumigatus (ARAF) shows an exceedingly high mortality. In this study, IA due to ARAF isolates in HSCT recipients in Germany was investigated.
The epidemiology of azole resistance in IA was analysed in two German haematology departments. Between 2012 and 2013, 762 patients received HSCT in Essen (n = 388) and Cologne (n = 374). Susceptibility testing of A. fumigatus isolates was performed by Etest, followed by EUCAST broth microdilution testing if elevated MICs were recorded. In all ARAF isolates the cyp51A gene was sequenced and the genotype was determined by microsatellite typing using nine short tandem repeats.
In total, A. fumigatus was recovered from 27 HSCT recipients. Eight patients had azole-resistant IA after HSCT, and seven of the cases were fatal (88%). All except one patient received antifungal prophylaxis (in five cases triazoles). TR34/L98H was the most common mutation (n = 5), followed by TR46/Y121F/T289A (n = 2). In one resistant isolate no cyp51A mutation was detected. Genotyping revealed genetic diversity within the German ARAF isolates and no clustering with resistant isolates from the Netherlands, India and France.
This report highlights the emergence of azole-resistant IA with TR34/L98H and TR46/Y121F/T289A mutations in HSCT patients in Germany and underscores the need for systematic antifungal susceptibility testing of A. fumigatus.
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.
Although tissue-resident memory T cells (T
cells) have been shown to regulate host protection in infectious disorders, their function in inflammatory bowel disease (IBD) remains to be investigated. ...Here we characterized T
cells in human IBD and in experimental models of intestinal inflammation. Pro-inflammatory T
cells accumulated in the mucosa of patients with IBD, and the presence of CD4
CD69
CD103
T
cells was predictive of the development of flares. In vivo, functional impairment of T
cells in mice with double knockout of the T
-cell-associated transcription factors Hobit and Blimp-1 attenuated disease in several models of colitis, due to impaired cross-talk between the adaptive and innate immune system. Finally, depletion of T
cells led to a suppression of colitis activity. Together, our data demonstrate a central role for T
cells in the pathogenesis of chronic intestinal inflammation and suggest that these cells could be targets for future therapeutic approaches in IBD.
Spectral conversion of sunlight is a promising route to reduce spectral mismatch losses that are responsible for the major part of the efficiency losses in solar cells. Both upconversion and ...downconversion materials are presently explored. In an upconversion process, photons with an energy lower than the band gap of the solar cell are converted to higher energy photons. These higher photons are directed back to the solar cell and absorbed, thus increasing the efficiency. Different types of upconverter materials are investigated, based on luminescent ions or organic molecules. Proof of principle experiments with lanthanide ion based upconverters have indicated that the benefit of an upconversion layer is limited by the high light intensities needed to reach high upconversion quantum efficiencies. To address this limitation, upconverter materials may be combined with quantum dots or plasmonic particles to enhance the upconversion efficiency and improve the feasibility of applying upconverters in commercial solar cells.
Photon upconversion of sunlight for solar cells is reviewed and the possibilities to increase the efficiencies of the upconverter materials are discussed.
Biodiversity conservation is a worldwide concern and proper management of threatened species or communities depends on reliable and accurate data collection. Despite the broad utility of ...environmental DNA (eDNA) for conservation management and the necessity for appropriate biodiversity management in the tropics, eDNA‐based research conducted in tropical regions so far comprises only a small proportion of the cumulative eDNA literature. To address the growing demand for rapid and reliable species and community level ecological data in tropical regions, we provide an aquatic eDNA‐focused review of (1) challenges and considerations for sampling design and inference of eDNA data in the tropics, and (2) eDNA applications relevant to ecological research and biodiversity management in the tropics. We propose that the collaborative incorporation of eDNA sampling with conventional field surveys harbours the potential to revolutionize the effectiveness of biodiversity conservation management in tropical regions.
All organisms naturally release their DNA into the environment through epidermal shedding, waste excretion, gamete release or decomposition. This environmental DNA (eDNA) can be isolated and analyzed through quantitative PCR for species‐specific detection or next‐generation sequencing to assess whole communities. The eDNA approach is less costly and labor intensive than traditional conservation management and biodiversity survey methods. However, to date, the majority of eDNA research and development has been conducted in temperate regions. A review of the literature indicated that of the 1,402 research articles containing the term ‘environmental DNA’ only 362 included the terms ‘tropic’ or ‘tropical’. Of those, 54 original articles addressed conservation‐related questions across a range of countries and ecosystems. This review highlights the value of eDNA research in the tropics and discusses some of the unique challenges and considerations for conducting eDNA in tropical environments.
Abstract
Melatonin is synthesized in the pineal gland during nighttime in response to nocturnal increase in the activity of the enzyme aralkylamine
N
‐acetyltransferase (AANAT), the transcription of ...which is modulated by several homeodomain transcription factors. Recent work suggests that the homeodomain transcription factor ISL LIM homeobox 2 (ISL2) is expressed in the pineal gland, but its role is currently unknown. With the purpose of identifying the mechanisms that control pineal expression of
Isl2
and the possible function of
Isl2
in circadian pineal biology, we report that
Isl2
is specifically expressed in the pinealocytes of the rat pineal gland. Its expression exhibits a 24 h rhythm with high transcript and protein levels during the day and a trough in the second half of the night. This rhythm persists in darkness, and lesion studies reveal that it requires intact function of the suprachiasmatic nuclei, suggesting intrinsic circadian regulation. In vivo and in vitro experiments show that pineal
Isl2
expression is repressed by adrenergic signaling acting via cyclic AMP; further,
Isl2
is negatively regulated by the nocturnal transcription factor cone‐rod homeobox. During development, pineal
Isl2
expression is detectable from embryonic day 19, preceding
Aanat
by several days. In vitro knockdown of
Isl2
is accompanied by an increase in
Aanat
transcript levels suggesting that ISL2 represses its daytime expression. Thus, rhythmic expression of ISL2 in pinealocytes is under the control of the suprachiasmatic nucleus acting via adrenergic signaling in the gland to repress nocturnal expression, while ISL2 itself negatively regulates daytime pineal expression of
Aanat
and thereby suggestively enhances the circadian rhythm in melatonin synthesis.
Abstract Objective The objective of this study was to evaluate peri-operative and survival outcomes of ovarian cancer patients undergoing percutaneous upper gastrointestinal decompression for ...malignant bowel obstruction (MBO). Methods Retrospective chart review was used to identify patients with ovarian, peritoneal, or fallopian tube cancer who underwent palliative decompressive treatment for MBO from 1/2002 to 12/2010. Kaplan–Meier methods were used to estimate the median survival (MS) and multivariate analysis used to determine if any variables were associated with the hazard of death. Results Fifty-three patients met inclusion criteria. Median length of diagnosis prior to intervention was 21 months. Fifteen (28.3%) patients experienced complications and 9 required revision. Forty-nine (92.5%) experienced relief of symptoms after placement, and 91% tolerated some form of oral intake. Following placement, 19 (36%) patients received additional chemotherapy and 21(41%) patients received total parental nutrition (TPN). Thirty-five patients were discharged home/outpatient facility, 16 to hospice care, and 2 died prior to discharge. MS for all patients was 46 days. Patients who received chemotherapy had a MS of 169 days compared to 33 days (p < 0.001). We failed to find an association between survival and TPN or performance status. Conclusions Malignant bowel obstruction is a common complication of ovarian cancer. Management is palliative; risks and benefits of any therapy must be considered. Percutaneous decompressive therapy provides relief from associated symptoms, and allows patients to be discharged home. Median survival in this group is limited, and decisions regarding aggressive therapy should be individualized.
By May 2021, South Africa (SA) had experienced two 'waves' of COVID-19 infections, with an initial peak of infections reached in July 2020, followed by a larger peak of infections in January 2021. ...Public health decisions rely on accurate and timely disease surveillance and epidemiological analyses, and accessibility of data at all levels of government is critical to inform stakeholders to respond effectively. In this paper, we describe the adaptation, development and operation of epidemiological surveillance and modelling systems in SA in response to the COVID-19 epidemic, including data systems for monitoring laboratory-confirmed COVID-19 cases, hospitalisations, mortality and recoveries at a national and provincial level, and how these systems were used to inform modelling projections and public health decisions. Detailed descriptions on the characteristics and completeness of individual datasets are not provided in this paper. Rapid development of robust data systems was necessary to support the response to the SA COVID-19 epidemic. These systems produced data streams that were used in decision-making at all levels of government. While much progress was made in producing epidemiological data, challenges remain to be overcome to address gaps to better prepare for future waves of COVID-19 and other health emergencies.
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