Functional estrogen receptor signal transduction pathway activity and antihormonal therapy response in low-grade ovarian carcinoma

Background

Advanced low-grade ovarian carcinoma (LGOC) is difficult to treat. In several studies, high estrogen receptor (ER) protein expression was observed in patients with LGOC, which suggests that antihormonal therapy (AHT) is a treatment option. However, only a subgroup of patients respond to AHT, and this response cannot be adequately predicted by currently used immunohistochemistry (IHC). A possible explanation is that IHC only takes the ligand, but not the activity, of the whole signal transduction pathway (STP) into account. Therefore, in this study, the authors assessed whether functional STP activity can be an alternative tool to predict response to AHT in LGOC.

Methods

Tumor tissue samples were obtained from patients with primary or recurrent LGOC who subsequently received AHT. Histoscores of ER and progesterone receptor (PR) were determined. In addition, STP activity of the ER STP and of six other STPs known to play a role in ovarian cancer was assessed and compared with the STP activity of healthy postmenopausal fallopian tube epithelium.

Results

Patients who had normal ER STP activity had a progression-free survival (PFS) of 16.1 months. This was significantly shorter in patients who had low and very high ER STP activity, with a median PFS of 6.0 and 2.1 months, respectively (p < .001). Unlike ER histoscores, PR histoscores were strongly correlated to the ER STP activity and thus to PFS.

Conclusions

Aberrant low and very high functional ER STP activity and low PR histoscores in patients with LGOC indicate decreased response to AHT. ER IHC is not representative of functional ER STP activity and is not related to PFS.     

The effect of immediate postpartum levonorgestrel contraceptive implant use on breastfeeding and infant growth: a randomized controlled trial

Objective

This study assessed whether immediate postpartum insertion of levonorgestrel contraceptive implants is associated with a difference in infant growth from birth to 6 months, onset of lactogenesis, or breastfeeding continuation at 3 and 6 months postpartum compared to delayed insertion at 6 to 8 weeks postpartum.

Development of a patient-reported measure of the interpersonal quality of family planning care

Objective

The objective was to describe the development and assess evidence of the validity of a patient-reported scale measuring the interpersonal quality of contraceptive counseling.

Improving program targeting to combat early-life mortality by identifying high-risk births: an application to India

Background

It is widely recognized that there are multiple risk factors for early-life mortality. In practice most interventions to curb early-life mortality target births based on a single risk factor, such as poverty. However, most premature deaths are not from the targeted group. Thus interventions target many births that are at not at high risk and miss many births at high risk.

Methods

Using data from the second wave of Demographic and Health Surveys from India and a hierarchical Bayesian model, we estimate infant mortality risk for 73.320 infants in India as a function of 4 risk factors. We show how this information can be used to improve program targeting. We compare our novel approach against common programs that target groups based on a single risk factor.

Results

A conventional approach that targets mothers in the lowest quintile of income correctly identifies only 30% of infant deaths. By contrast, using four risk factors simultaneously we identify a group of births of the same size that includes 57% of all deaths. Using the 2012 census to translate these percentages into numbers, there were 25.642.200 births in 2012 and 4.4% died before the age of one. Our approach correctly identifies 643.106 of 1.128.257 infant deaths while poverty only identifies 338.477 infant deaths.

Conclusion

Our approach considerably improves program targeting by identifying more infant deaths than the usual approach that targets births based on a single risk factor. This leads to more efficient program targeting. This is particularly useful in developing countries, where resources are lacking and needs are high.

     

Enterococcus spp. in endodontically treated teeth with and without periradicular lesions

The purpose of this study was to determine if Enterococcus spp. are more prevalent in endodontically treated teeth with periradicular lesions compared with teeth that require retreatment but have no periradicular rarefaction. Fifty-eight teeth that had received root canal therapy more than 1 yr previously and required retreatment were included. Designation of lesion versus no lesion was determined by two experienced endodontists. DNA extraction and PCR amplification were performed using ubiquitous 16S rDNA bacterial primers, as well as Enterococcus spp.-specific primers. The results showed that the overall prevalence of bacteria was 90% and Enterococcus spp. was 12%. chi analysis revealed a statistically significant relationship between the presence of a lesion and the presence of bacteria, as detected by the universal primers (p = 0.032). Using logistic regression, a statistically significant relationship was found between teeth with normal periapex and the presence of Enterococcus spp. (p = 0.023). This study revealed that bacteria are significantly associated with endodontic treatment failure but enterococci are not associated with disease.     

The effect of antibiotics and endodontic antimicrobials on the polymerase chain reaction

The effectiveness of endodontic antimicrobial treatment could be determined using sensitive molecular methods. The purpose of this study was to determine if antibiotics or endodontic reagents interfere with the ability of PCR to detect Enterococcus faecalis in vitro. Amoxicillin (25 mg/ml), clindamycin (15 mg/ml), tetracycline (25 mg/ml), doxycycline (10 mg/ml), calcium hydroxide, 1% buffered sodium hypochlorite (NaOCl1), 3% and 6% unbuffered NaOCl (NaOCl3 and NaOCl6), 2% chlorhexidine (CHX), 5% tincture iodine (TI), 2% iodine potassium iodide (IKI), chloroform (CF), 70% ethyl alcohol, 5% sodium thiosulphate, 5% citric acid or saline were added to 10 or 10 cells/ml E. faecalis ATCC 19433 for 1 h (1 wk for Ca(OH)2). Using PCR, all specimens were positive except for NaOCl3 and NaOCl6. PCR with Ca(OH)2 was positive with 10 cells/ml but negative with 10 cells/ml. The following reagents yielded negative culturing results: all antibiotics, Ca(OH)2, CHX, IKI, TI, NaOCl3, NaOCl6, and CF. BacLight nuclear staining revealed the presence of viable cells in all PCR positive, culture negative combinations, except for those with CF. Therefore, in the presence of threshold values of bacterial concentrations, all reagents tested except for NaOCl3 and NaOCl6 do not interfere with the detection of E. faecalis using PCR.     

Comparison of detrending methods for optimal fMRI preprocessing

Because of the inherently low signal to noise ratio (SNR) of fMRI data, removal of low frequency signal intensity drift is an important preprocessing step, particularly in those brain regions that weakly activate. Two known sources of drift are noise from the MR scanner and aliasing of physiological pulsations. However, the amount and direction of drift is difficult to predict, even between neighboring voxels. Further, there is no concensus on an optimal baseline drift removal algorithm. In this paper, five voxel-based detrending techniques were compared to each other and an auto-detrending algorithm, which automatically selected the optimal method for a given voxel time-series. For a significance level of P < 10(-6), linear and quadratic detrending moderately increased the percentage of activated voxels. Cubic detrending decreased activation, while a wavelet approach increased or decreased activation, depending on the dataset. Spline detrending was the best single algorithm. However, auto-detrending (selecting the best algorithm or none, if detrending is not useful) appears to be the most judicious choice, particularly for analyzing fMRI data with weak activations in the presence of baseline drift.