Aims
The aim of this study was to investigate the effects of lactobacilli strains in preventing the recurrences of vaginal candidiasis (VC) in 78 pregnant women with VC (lactobacilli, n = 39; ...placebo, n = 39) and the potential benefits on quality of life.
Methods and Results
The lactobacilli putative probiotic (SynForU‐HerCare; two capsules/day of 9·5 log CFU per capsule) or placebo was administered for 8‐weeks in a randomized, double‐blind, placebo‐controlled study. Subjects were assessed for vaginal and gut health conditions at baseline, week‐4 and week‐8 via questionnaires. The vulvovaginal symptom questionnaire not only covered aspects pertaining to vulvovaginal symptoms but also the quality of life impacts such as emotional, social and sexual. The administration of lactobacilli reduced symptoms of irritation (P = 0·023) and discharge (P = 0·011) starting week‐4 and continued after week‐8 (P < 0·05), accompanied by reduced symptoms for burning after week‐8 (P = 0·046) as compared to the placebo. Patients consuming lactobacilli also showed reduced concern about symptoms after week‐4 (P = 0·010) and continued after week‐8 (P = 0·001), accompanied by reduced impairment of daily activities attributed to vulvovaginal symptoms (P = 0·012) and continued after week‐8 (P = 0·026). Insignificant differences were observed for sexual impacts between treatment groups. The administration of lactobacilli also reduced recurrences of both emotional and social stress as compared to the placebo at both week‐4 and week‐8 (P < 0·05). Patients consuming lactobacilli showed higher defecation times per week at week‐4 (P = 0·010) and week‐8 (P = 0·001) as compared to the placebo group, indicating the potential to reduce risks of pregnancy‐induced constipation.
Conclusions
Lactobacilli probiotics are beneficial towards pregnant women, especially in reducing vulvovaginal symptoms and recurrences of VC, accompanied by improved emotional and social distress attributed to VC.
Significance and Impact of the Study
The study demonstrated the preventive and modulatory roles of lactobacilli strains against VC in pregnant women. Taken altogether, our present data illustrated that lactobacilli probiotics are beneficial towards pregnant women, especially in reducing vulvovaginal symptoms and recurrences of VC, accompanied by improved emotional and social distress attributed to VC, thus could be a potential strategy for the maintenance of vaginal health during pregnancy.
Enterotoxigenic Bacteroides fragilis (ETBF), a human commensal and candidate pathogen in colorectal cancer (CRC), is a potent initiator of interleukin-17 (IL-17)-dependent colon tumorigenesis in Min
...mice. We examined the role of IL-17 and ETBF on the differentiation of myeloid cells into myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages, which are known to promote tumorigenesis. The myeloid compartment associated with ETBF-induced colon tumorigenesis in Min mice was defined using flow cytometry and gene expression profiling. Cell-sorted immature myeloid cells were functionally assayed for inhibition of T-cell proliferation and inducible nitric oxide synthase expression to delineate MDSC populations. A comparison of ETBF infection with that of other oncogenic bacteria (Fusobacterium nucleatum or pks
Escherichia coli) revealed a specific, ETBF-associated colonic immune infiltrate. ETBF-triggered colon tumorigenesis is associated with an IL-17-driven myeloid signature characterized by subversion of steady-state myelopoiesis in favor of the generation of protumoral monocytic-MDSCs (MO-MDSCs). Combined action of the B. fragilis enterotoxin BFT and IL-17 on colonic epithelial cells promoted the differentiation of MO-MDSCs, which selectively upregulated Arg1 and Nos2, produced NO, and suppressed T-cell proliferation. Evidence of a pathogenic inflammatory signature in humans colonized with ETBF may allow for the identification of populations at risk for developing colon cancer.
Despite the current screening approach for Cushing syndrome (CS), delayed diagnosis is common due to broad spectrum of presentation, poor discriminant symptoms featured in diabetes and obesity, and ...low clinical index of suspicion. Even if initial tests are recommended to screen CS, divergent results are not infrequent. As global prevalence of type 2 diabetes and obesity increases, CS may not be frequent enough to back routine screening to avoid false-positive results. This represents a greater challenge in countries with limited health resources. The development of indexes incorporates clinical features and biochemical data that are largely used to provide a tool to predict the presence of disease. In clinical endocrinology, indexes have been used in Graves' ophthalmology, hirsutism, and hypothyroidism. The use of clinical risk scoring system may assist clinicians in discriminating CS in the context of at-risk populations and, thus, may provide a potential intervention to decrease time to diagnosis. Development and validation of clinical model to estimate pre-test probability of CS in different geographic source population may help to establish regional prediction model for CS. Here, we review on the latest progress in clinical risk scoring system for CS and attempt to raise awareness for the use, validation, and/or development of clinical risk scores in CS.
Background and Objective
Recently it was reported that deferoxamine (DFO), an iron chelator, stimulates bone formation from MG63 and mesenchymal stem cells, but inhibits differentiation in rat ...calvarial cells; however, the effect of DFO on osteoblastic differentiation in human periodontal ligament cells (hPDLCs) has not been reported. The aim of this study was to investigate the effects and the possible underlying mechanism of DFO on osteoblastic differentiation of hPDLCs.
Material and Methods
The effect of DFO on osteoblast differentiation was determined by the staining intensity of calcium deposits with Alizarin red and by RT‐PCR analysis of the expression of osteoblastic markers. Signal transduction pathways were analyzed by western blotting.
Results
DFO increased osteogenic differentiation in a concentration‐dependent manner by expression of the mRNA for differentiation markers and calcium nodule formation. Exposure of hPDLCs to DFO resulted in increases in the production of reactive oxygen species and in the levels of nuclear factor erythroid 2‐related factor (Nrf2) protein in nuclear extractions, as well as a dose‐dependent increase in the expression of Nrf2 target genes, including glutathione (GSH), glutathione S‐transferase, γ‐glutamylcysteine lygase, glutathione reductase and glutathione peroxidase. Pretreatment with Nrf2 small interfering RNA, GSH depletion by buthionine sulfoximine and diethyl maleate, and with antioxidants by N‐acetylcysteine and vitamin E, blocked DFO‐stimulated osteoblastic differentiation. Furthermore, pretreatment with GSH depletion and antioxidants blocked DFO‐induced p38 MAPK, ERK, JNK and nuclear factor‐kappaB pathways.
Conclusion
These data indicate, for the first time, that nontoxic DFO promotes osteoblastic differentiation of hPDLCs via modulation of the Nrf2‐mediated antioxidant pathway.
Peritoneum is the most common site for ovarian cancer metastasis. Here we investigate how cancer epigenetics regulates reciprocal tumor-stromal interactions in peritoneal metastasis of ovarian ...cancer. Firstly, we find that omental stromal fibroblasts enhance colony formation of metastatic ovarian cancer cells, and de novo expression of transforming growth factor-alpha (TGF-α) is induced in stromal fibroblasts co-cultured with ovarian cancer cells. We also observed an over-expression of tumor necrosis factor-alpha (TNF-α) in ovarian cancer cells, which is regulated by promoter DNA hypomethylation as well as chromatin remodeling. Interestingly, this ovarian cancer-derived TNF-α induces TGF-α transcription in stromal fibroblasts through nuclear factor-κB (NF-κB). We further show that TGF-α secreted by stromal fibroblasts in turn promotes peritoneal metastasis of ovarian cancer through epidermal growth factor receptor (EGFR) signaling. Finally, we identify a TNFα-TGFα-EGFR interacting loop between tumor and stromal compartments of human omental metastases. Our results therefore demonstrate cancer epigenetics induces a loop of cancer-stroma-cancer interaction in omental microenvironment that promotes peritoneal metastasis of ovarian cancer cells via TNFα-TGFα-EGFR.
There have been inconsistencies on the prognosis and controversies as to the proper management of acute basilar artery dissection. The aim of this study was to evaluate acute basilar artery ...dissection and its outcome after management.
A total of 21 patients (mean age, 53 years; range, 24-78 years) with acute basilar artery dissection were identified between January 2001 and October 2007. Clinical presentation, management, and outcomes were retrospectively evaluated.
The patients presented with subarachnoid hemorrhage (n = 10), brain stem ischemia (n = 10), or stem compression sign (n = 1). Ruptured basilar artery dissections were treated by stent placement with coiling (n = 4), single stent placement (n = 3), or conservatively (n = 3). Of the patients treated with endovascular technique, 6 had favorable outcome (modified Rankin scale mRS, 0-2) and the remaining patient, who was treated by single stent placement, died from rebleeding. All 3 conservatively managed patients experienced rebleeding, of whom 2 died and the other was moderately disabled. Unruptured basilar artery dissections were treated conservatively (n = 7) or by stent placement (n = 4). Of the patients with unruptured basilar artery dissection, 9 had favorable outcome and the remaining 2 patients, both of whom were conservatively managed, had poor outcome because of infarct progression. The group with the ruptured basilar artery dissection revealed a higher mortality rate than the group with the unruptured dissection (30% vs 0%). The group treated with endovascular means revealed more favorable outcome than the group that was treated with conservative measures (90.9% vs 50%).
The ruptured basilar artery dissections were at high risk for rebleeding, resulting in a grave outcome. Stent placement with or without coiling may be considered to prevent rebleeding in ruptured basilar dissections and judiciously considered in unruptured dissections with signs of progressive brain stem ischemia.
The genetic basis for developing asthma has been extensively studied. However, association studies to date have mostly focused on mild to moderate disease and genetic risk factors for severe asthma ...remain unclear.
To identify common genetic variants affecting susceptibility to severe asthma.
A genome-wide association study was undertaken in 933 European ancestry individuals with severe asthma based on Global Initiative for Asthma (GINA) criteria 3 or above and 3346 clean controls. After standard quality control measures, the association of 480 889 genotyped single nucleotide polymorphisms (SNPs) was tested. To improve the resolution of the association signals identified, non-genotyped SNPs were imputed in these regions using a dense reference panel of SNP genotypes from the 1000 Genomes Project. Then replication of SNPs of interest was undertaken in a further 231 cases and 1345 controls and a meta-analysis was performed to combine the results across studies.
An association was confirmed in subjects with severe asthma of loci previously identified for association with mild to moderate asthma. The strongest evidence was seen for the ORMDL3/GSDMB locus on chromosome 17q12-21 (rs4794820, p=1.03×10((-8)) following meta-analysis) meeting genome-wide significance. Strong evidence was also found for the IL1RL1/IL18R1 locus on 2q12 (rs9807989, p=5.59×10((-8)) following meta-analysis) just below this threshold. No novel loci for susceptibility to severe asthma met strict criteria for genome-wide significance.
The largest genome-wide association study of severe asthma to date was carried out and strong evidence found for the association of two previously identified asthma susceptibility loci in patients with severe disease. A number of novel regions with suggestive evidence were also identified warranting further study.
A test circuit for modular multilevel converter (MMC)-based voltage-sourced converter valves in high-voltage direct current (HVDC) system is dealt with. The proposed scheme has an ability to provide ...a submodule current having DC component as well as AC component to represent real operating condition of HVDC transmission system. There is no need of extra power supply to provide the DC current component because the scheme has inherent circulating DC current between rectifier and inverter valves. Therefore, only one small power rated DC power supply is necessary. Experiments are carried out to show the validity of the proposed test circuit.
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