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chanism(s), and provide comparison data necessary for future phase II trials in chronic disease(s). The design and robustness of the planned safety and mechanistic evaluations planned provide a model for drug discovery pursuits from natural products.
ClinicalTrials.gov NCT03735420 . Registered on November 8, 2018.
ClinicalTrials.gov NCT03735420 . Registered on November 8, 2018.
The vaginal microbiota has been reported to be associated with HPV infection and cervical cancer. This study was performed to compare the vaginal microbiota at two timepoints in women performing self-sampling and had a persistent or transient HPV16 infection. The women were tested for 12 high-risk HPV (hrHPV) types but only women with single type (HPV16) were included to reduce confounding variables.
In total 96 women were included in this study. Of these, 26 were single positive for HPV16 in the baseline test and HPV negative in the follow-up test and 38 were single positive for HPV16 in both tests and diagnosed with CIN2+ in histology. In addition, 32 women that were negative for all 12 HPV tested were included. The samples of vaginal fluid were analyzed with the Ion 16S™ Metagenomics Kit and Ion 16S™ metagenomics module within the Ion Reporter™ software.
K-means clustering resulted in two Lactobacillus-dominated groups, one with Lactobacillus sp. and the other specifically with Lactobacillus iners. The two remaining clusters were dominated by a mixed non-Lactobacillus microbiota. HPV negative women had lower prevalence (28%) of the non-Lactobacill dominant cluster in the baseline test, as compared to women with HPV16 infection (42%) (p value = 0.0173). Transition between clusters were more frequent in women with persistent HPV16 infection (34%) as compared in women who cleared the HPV16 infection (19%) (p value = 0.036).
The vaginal microbiota showed a higher rate of transitioning between bacterial profiles in women with persistent HPV16 infection as compared to women with transient infection. This indicate an instability in the microenvironment in women with persistent HPV infection and development of CIN2+.
The vaginal microbiota showed a higher rate of transitioning between bacterial profiles in women with persistent HPV16 infection as compared to women with transient infection. This indicate an instability in the microenvironment in women with persistent HPV infection and development of CIN2+.
Emerging evidence indicates that an elevated C-reactive protein-to-albumin ratio (CAR) may be associated with a poor prognosis in pancreatic ductal adenocarcinoma (PDAC). Further evidence showing that this ratio has significant prognostic value could contribute to current prediction models and clinical decision-making.
Data were analysed of consecutive patients who underwent curative pancreatic resection between 2013 and 2018 and were histologically diagnosed with PDAC. We investigated the relation between the ultimate preoperative CAR and overall survival.
A total of 163 patients were analysed. Median overall survival was 18months (IQR 9-36). Multivariate analysis demonstrated that a higher CAR (HR 1.745, P = 0.004), a higher age (HR 1.062, P < 0.001), male sex (HR 1.977, P = 0.001), poor differentiation grade (HR 2.812, P < 0.001), and positive para-aortic lymph node(s) (HR 4.489, P < 0.001) were associated with a lower overall survival. Furthermore, a CAR ≥ 0.2 was associated with decreased overall survival (16vs. 26months, P = 0.003).
We demonstrated that an ultimate preoperative elevated CAR is an independent indicator of decreased overall survival after resection for PDAC. The preoperative CAR may be of additional value to the current prediction models.
We demonstrated that an ultimate preoperative elevated CAR is an independent indicator of decreased overall survival after resection for PDAC. The preoperative CAR may be of additional value to the current prediction models.
Cardiovascular disease (CVD) is the leading cause of death in women, responsible for approximately a third of all female deaths. Pregnancy complications are known to be associated with a greater risk of incident CVD in mothers. However, the relationships between pregnancy loss due to miscarriage, stillbirth, or therapeutic abortion, and future maternal cardiovascular health are under-researched. This study seeks to provide an up-to-date systematic review and meta-analysis of the relationship between these three forms of pregnancy loss and the subsequent development of CVD.
This systematic review will follow the Preferred Reporting Items for Systematic Review and Meta-Analysis checklist (PRISMA) and the Meta-analyses Of Observational Studies in Epidemiology (MOOSE) Checklist. A systematic search will be undertaken using publications identified in MEDLINE (PubMed), Scopus, Web of Knowledge, the CINAHL Nursing Database, and the Cochrane Library. The eligibility of each publication will be determined by predefined selection criteria. The quality of the included studies will be rated using the Newcastle-Ottawa Scale. Pooled measures of association will be computed using random-effects model meta-analyses. Between-study heterogeneity will be assessed using the I
statistic and the Cochrane χ
statistic. Small study effects will be evaluated for meta-analyses with sufficient studies through the use of funnel plots and Egger’s test.
The results of this systematic review will discuss the long-term risks of multiple types of cardiovascular disease in women who have experienced miscarriage, stillbirth, and/or therapeutic abortion. It will contribute to the growing field of cardio-obstetrics as the first to consider the full breadth of literature regarding the association between all forms of pregnancy loss and future maternal cardiovascular disease.
PROSPERO registration number .
PROSPERO registration number .
Even though new therapies are available against melanoma, novel approaches are needed to overcome resistance and high-toxicity issues. SP600125negativecontrol In the present study the anti-melanoma activity of Nicotinamide (NAM), the amide form of Niacin, was assessed in vitro and in vivo.
Human (A375, SK-MEL-28) and mouse (B16-F10) melanoma cell lines were used for in vitro investigations. Viability, cell-death, cell-cycle distribution, apoptosis, Nicotinamide Adenine Dinucleotide
(NAD
), Adenosine Triphosphate (ATP), and Reactive Oxygen Species (ROS) levels were measured after NAM treatment. NAM anti-SIRT2 activity was tested in vitro; SIRT2 expression level was investigated by in silico transcriptomic analyses. Melanoma growth in vivo was measured in thirty-five C57BL/6 mice injected subcutaneously with B16-F10 melanoma cells and treated intraperitoneally with NAM. Interferon (IFN)-γ-secreting murine cells were counted with ELISPOT assay. Cytokine/chemokine plasmatic levels were measured by xMAP technology. Niacin receptors expression in human melanoma samples was also investigated by in silico transcriptomic analyses.