Elucidating the factors that impinge on the stability of bacterial communities in the vagina may help in predicting the risk of diseases that affect women's health. Here, we describe the temporal ...dynamics of the composition of vaginal bacterial communities in 32 reproductive-age women over a 16-week period. The analysis revealed the dynamics of five major classes of bacterial communities and showed that some communities change markedly over short time periods, whereas others are relatively stable. Modeling community stability using new quantitative measures indicates that deviation from stability correlates with time in the menstrual cycle, bacterial community composition, and sexual activity. The women studied are healthy; thus, it appears that neither variation in community composition per se nor higher levels of observed diversity (co-dominance) are necessarily indicative of dysbiosis.
Human stem cell-derived hepatocyte-like cells (HLCs) offer an attractive platform to study liver biology. Despite their numerous advantages, HLCs lack critical in vivo characteristics, including cell ...polarity. Here, we report a stem cell differentiation protocol that uses transwell filters to generate columnar polarized HLCs with clearly defined basolateral and apical membranes separated by tight junctions. We show that polarized HLCs secrete cargo directionally: Albumin, urea, and lipoproteins are secreted basolaterally, whereas bile acids are secreted apically. Further, we show that enterically transmitted hepatitis E virus (HEV) progeny particles are secreted basolaterally as quasi-enveloped particles and apically as naked virions, recapitulating essential steps of the natural infectious cycle in vivo. We also provide proof-of-concept that polarized HLCs can be used for pharmacokinetic and drug-drug interaction studies. This novel system provides a powerful tool to study hepatocyte biology, disease mechanisms, genetic variation, and drug metabolism in a more physiologically relevant setting.
Unintended pregnancy is common in the US and is associated with adverse maternal and infant health outcomes; however, estimates of these associations specific to current US populations are lacking.
...To evaluate associations of unintended pregnancy with maternal and infant health outcomes during pregnancy and post partum with studies relevant to current clinical practice and public health in the US.
Cochrane Central Register of Controlled Trials and Database of Systematic Reviews, PsycINFO, SocINDEX, and MEDLINE databases (January 1, 2000, to June 15, 2022) and manual review of reference lists.
Epidemiologic studies relevant to US populations that compared key maternal and infant health outcomes for unintended vs intended pregnancies and met prespecified eligibility criteria were included after investigators' independent dual review of abstracts and full-text articles.
Investigators abstracted data from publications on study methods, participant characteristics, settings, pregnancy intention, comparators, confounders, and outcomes; data were validated by a second investigator. Risk of bias was independently dual rated by investigators using criteria developed by the US Preventive Services Task Force. Results of studies controlling for confounders were combined by using a profile likelihood random-effects model.
Prenatal depression, postpartum depression, maternal experience of interpersonal violence, preterm birth, and infant low birth weight.
Thirty-six studies (N = 524 522 participants) were included (14 cohort studies rated good or fair quality; 22 cross-sectional studies); 12 studies used large population-based data sources. Compared with intended pregnancy, unintended pregnancy was significantly associated with higher odds of depression during pregnancy (23.3% vs 13.9%; adjusted odds ratio aOR, 1.59 95% CI, 1.35-1.92; I2 = 85.0%; 15 studies n = 41 054) and post partum (15.7% vs 9.6%; aOR, 1.51 95% CI, 1.40-1.70; I2 = 7.1%; 10 studies n = 82 673), interpersonal violence (14.6% vs 5.5%; aOR, 2.22 95% CI, 1.41-2.91; I2 = 64.1%; 5 studies n = 42 306), preterm birth (9.4% vs 7.7%; aOR, 1.21 95% CI, 1.12-1.31; I2 = 1.7%; 10 studies n = 94 351), and infant low birth weight (7.3% vs 5.2%; aOR, 1.09 95% CI, 1.02-1.21; I2 = 0.0%; 8 studies n = 87 547). Results were similar in sensitivity analyses based on controlling for history of depression for prenatal and postpartum depression and on study design and definition of unintended pregnancy for relevant outcomes. Studies provided limited sociodemographic data and measurement of confounders and outcomes varied.
In this systematic review and meta-analysis of epidemiologic observational studies relevant to US populations, unintended pregnancy, compared with intended pregnancy, was significantly associated with adverse maternal and infant outcomes.
PROSPERO Identifier: CRD42020192981.
In recent years, immersive technology tools have burgeoned. After the release of the affordable Oculus Go headset and the Merge Cube, there has been increasing use of virtual, augmented, and extended ...reality (VR, AR, XR) in classrooms. Of significance to chemistry educators are the virtual lab simulations developed by Labster and HoloLab Champions and the VR app Nanome, which can be used to virtually manipulate chemicals and proteins. So far, however, there are no commercially developed products that address the transfer of chemicals and contaminants during experiments or procedures that require gloves. Herein, we discuss how VR can be used as an active learning approach to lab safety about correct glove hygiene. The work is the result of a collaboration among chemistry, computer science, and library faculty on a VR instructional module on glove hygiene. This experience is useful to bring a realistic and interactive laboratory experience to students who may have limited experience in a laboratory setting. Additionally, the project explores how to optimally use the academic library space to deploy the VR module to a large number of student users. Despite shortcomings we encountered in the first phase of development, we believe that, with technological improvements, there is significant potential for a virtual reality instructional environment that teaches glove hygiene when there may be limited access to physical laboratories.
Phagocytes destroy ingested microbes by producing hypochlorous acid (HOCl) from chloride ions (Cl
) and hydrogen peroxide within phagolysosomes, using the enzyme myeloperoxidase. HOCl, the active ...ingredient in bleach, has antibacterial/antiviral properties. As myeloperoxidase is needed for HOCl production, non-myeloid cells are considered incapable of producing HOCl. Here, we show that epithelial, fibroblast and hepatic cells have enhanced antiviral activity in the presence of increasing concentrations of sodium chloride (NaCl). Replication of enveloped/non-enveloped, DNA (herpes simplex virus-1, murine gammaherpesvirus 68) and RNA (respiratory syncytial virus, influenza A virus, human coronavirus 229E, coxsackievirus B3) viruses are inhibited in a dose-dependent manner. Whilst treatment with sodium channel inhibitors did not prevent NaCl-mediated virus inhibition, a chloride channel inhibitor reversed inhibition by NaCl, suggesting intracellular chloride is required for antiviral activity. Inhibition is also reversed in the presence of 4-aminobenzoic hydrazide, a myeloperoxidase inhibitor, suggesting epithelial cells have a peroxidase to convert Cl
to HOCl. A significant increase in intracellular HOCl production is seen early in infection. These data suggest that non-myeloid cells possess an innate antiviral mechanism dependent on the availability of Cl
to produce HOCl. Antiviral activity against a broad range of viral infections can be augmented by increasing availability of NaCl.
Bacterial vaginosis (BV) is a common gynecologic diagnosis characterized by dysbiosis of the vaginal microbiota. It is often accompanied by vaginal symptoms such as odor and discharge, but can be ...asymptomatic. Despite over 50 years of research, the etiology of BV is not well understood, which is a major impediment to treatment and prevention of BV.
Here we report on the temporal dynamics of 25 vaginal communities over a 10 week period using samples collected daily from women who were diagnosed with symptomatic BV (15 women), asymptomatic BV (6 women), and women who did not have BV (4 women).
This unique resource of samples and data will contribute to a better understanding of the role that the vaginal microbes have in the natural history of BV and lead to improved diagnosis and treatment.
Being the most common cause of acute viral hepatitis with >20 million cases per year and 70,000 deaths annually, HEV presents a long-neglected and underinvestigated health burden. Although the entry ...process of viral particles is an attractive target for pharmacological intervention, druggable host factors to restrict HEV entry have not been identified so far.
Here we identify the EGF receptor (EGFR) as a novel host factor for HEV and reveal the significance of EGFR for the HEV entry process. By utilizing RNAi, chemical modulation with Food and Drug Administration-approved drugs, and ectopic expression of EGFR, we revealed that EGFR is critical for HEV infection without affecting HEV RNA replication or assembly of progeny virus. We further unveiled that EGFR itself and its ligand-binding domain, rather than its signaling function, is responsible for the proviral effect. Modulation of EGF expression in HepaRG cells and primary human hepatocytes affected HEV infection.
Taken together, our study provides novel insights into the life cycle of HEV and identified EGFR as a possible target for future antiviral strategies against HEV.
Community-acquired pneumonia is the most common type of pneumonia and remains a leading cause of morbidity and mortality worldwide. Although many different pathogens can contribute to pneumonia,
is ...one of the common bacterial pathogens that underlie community-acquired pneumonia. RIPK3 (receptor-interacting protein kinase 3) is widely recognized as a key modulator of inflammation and cell death. To elucidate a potential role of RIPK3 in pneumonia, we examined plasma from healthy control subjects and patients positive for streptococcal pneumonia. In human studies, RIPK3 protein concentrations were significantly elevated and were identified as a potential plasma marker of pneumococcal pneumonia. To expand these findings, we used an
murine model of pneumococcal pneumonia to demonstrate that RIPK3 deficiency leads to reduced bacterial clearance, severe pathological damage, and high mortality. Our results illustrated that RIPK3 forms a complex with RIPK1, MLKL (mixed-lineage kinase domain-like protein), and MCU (mitochondrial calcium uniporter) to induce mitochondrial calcium uptake and mitochondrial reactive oxygen species(mROS) production during
infection. In macrophages, RIPK3 initiated necroptosis via the mROS-mediated mitochondrial permeability transition pore opening and NLRP3 inflammasome activation via the mROS-AKT pathway to protect against
. In conclusion, our study demonstrated a mechanism by which RIPK3-initiated necroptosis is essential for host defense against
.
Amplification, sequencing, and analysis of the 16S rRNA gene affords characterization of microbial community composition. As this tool has become more popular and amplicon-sequencing applications ...have grown in the total number of samples, growth in sample multiplexing is becoming necessary while maintaining high sequence quality and sequencing depth. Here, modifications to the Illumina HiSeq 2500 platform are described which produce greater multiplexing capabilities and 300-bp paired-end reads of higher quality than those produced by the current Illumina MiSeq platform. To improve the feasibility and flexibility of this method, a 2-step PCR amplification protocol is also described that allows for targeting of different amplicon regions, and enhances amplification success from samples with low bacterial bioburden.
Amplicon sequencing has become a popular and widespread tool for surveying microbial communities. Lower overall costs associated with high-throughput sequencing have made it a widely adopted approach, especially for projects that necessitate sample multiplexing to eliminate batch effect and reduced time to acquire data. The method for amplicon sequencing on the Illumina HiSeq 2500 platform described here provides improved multiplexing capabilities while simultaneously producing greater quality sequence data and lower per-sample cost relative to those of the Illumina MiSeq platform without sacrificing amplicon length. To make this method more flexible for various amplicon-targeted regions as well as improve amplification from low-biomass samples, we also present and validate a 2-step PCR library preparation method.
There are gaps between recommendations on regular screening for diabetic kidney disease (DKD) and clinical practice especially in busy and low resource settings. SUDOSCAN (Impeto Medical, Paris, ...France) is a non-invasive technology for assessing sudomotor function using reverse iontophoresis and chronoamperometry which detects abnormal sweat gland function. Vasculopathy and neuropathy share common risk factors and we hypothesized that SUDOSCAN may be used to detect chronic kidney disease (CKD). Between 2012 and 2013, SUDOSCAN was performed in a consecutive cohort of 2833 Hong Kong Chinese adults with type 2 diabetes. Chronic kidney disease was defined as estimated glomerular filtration rate <60 ml/min/1.73m2. In this cross-sectional cohort (mean age 58.6±9.5 years, 55.7% male, median disease duration 8 interquartile range 3-14 years), 5.8% had CKD. At a cut-off SUDOSCAN-DKD score of 53, the test had sensitivity of 76.7%, specificity of 63.4% and positive likelihood ratio of 2.1 to detect CKD. The area under receiver operating characteristic curve for CKD was 0.75 (95% confidence interval 0.72-0.79). Patients without CKD but low score had worse risk factors and complications than those with high score. We conclude that SUDOSCAN may be used to detect patients at risk of impaired renal function as part of a screening program in Chinese population, especially in outreach or low resource settings.
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