The "PepSAVI-MS" Pipeline for Natural Product Bioactive Peptide Discovery.

The recent increase in extensively drug-resistant bacterial pathogens and the associated increase of morbidity and mortality demonstrate the immediate need for new antibiotic backbones with novel mechanisms of action. Here, we report the development of the PepSAVI-MS pipeline for bioactive peptide discovery. This highly versatile platform employs mass spectrometry and statistics to identify bioactive peptide targets from complex biological samples. We validate the use of this platform through the successful identification of known bioactive peptides from a botanical species, Viola odorata. Using this pipeline, we have widened the known antimicrobial spectrum for V. odorata cyclotides, including antibacterial activity of cycloviolacin O2 against A. baumannii. We further demonstrate the broad applicability of the platform through the identification of novel anticancer activities for cycloviolacins by their cytotoxicity against ovarian, breast, and prostate cancer cell lines.

Prospective evaluation of luteal phase length and natural fertility.

OBJECTIVE: To evaluate the impact of a short luteal phase on fecundity. DESIGN: Prospective time-to-pregnancy cohort study. SETTING: Not applicable. PATIENT(S): Women trying to conceive, ages 30-44 years, without known infertility. INTERVENTION(S): Daily diaries, ovulation prediction testing, standardized pregnancy testing. MAIN OUTCOME MEASURE(S): Subsequent cycle fecundity. RESULT(S): Included in the analysis were 1,635 cycles from 284 women. A short luteal phase (≤11 days including the day of ovulation) occurred in 18% of observed cycles. Mean luteal phase length was 14 days. Significantly more women with a short luteal phase were smokers. After adjustment for age, women with a short luteal phase had 0.82 times the odds of pregnancy in the subsequent cycle immediately following the short luteal phase compared with women without a short luteal phase. Women with a short luteal length in the first observed cycle had significantly lower fertility after the first 6 months of pregnancy attempt, but at 12 months there was no significant difference in cumulative probability of pregnancy. CONCLUSION(S): Although an isolated cycle with a short luteal phase may negatively affect short-term fertility, incidence of infertility at 12 months was not significantly higher among these women. CLINICAL TRIAL REGISTRATION NUMBER: NCT01028365.

Effects of perfluorinated chemicals on thyroid function, markers of ovarian reserve, and natural fertility.

Perfluorinated chemicals (PFCs) can act as endocrine-disrupting chemicals, but there has been limited study of their effects on ovarian reserve or fecundability. 99 women, 30-44 years old, without infertility were followed until pregnancy. Initially, serum was evaluated for Antimullerian hormone (AMH), thyroid hormones: thyroid stimulating hormone (TSH), thyroxine (T4), free thyroxine (fT4), and triiodothyronine (T3), and PFCs: perfluorooctanoate (PFOA), perfluorooctane sulfonate (PFOS), perfluorononanoic acid (PFNA), and perfluorohexanesulfonic acid (PFHxS). Bivariate analyses assessed the relationship between thyroid hormones, AMH, and PFCs. Fecundability ratios (FR) were determined for each PFC using a discrete time-varying Cox model and a day-specific probability model. PFC levels were positively correlated with each other (r 0.24-0.90), but there was no correlation with TSH (r 0.02-0.15) or AMH (r -0.01 to -0.15). FR point estimates for each PFC were neither strong nor statistically significant. Although increased exposure to PFCs correlates with thyroid hormone levels, there is no significant association with fecundability or ovarian reserve.

Prospective evaluation of the impact of intermenstrual bleeding on natural fertility.

OBJECTIVE: To evaluate the impact of an episode of intermenstrual bleeding on the probability of conception in a menstrual cycle (fecundability). DESIGN: Prospective, time-to-pregnancy cohort study. SETTING: Community-based cohort. PATIENT(S): Women trying to conceive, ages 30 to 44 years, without known infertility. INTERVENTION(S): Not applicable. MAIN OUTCOME MEASURE(S): Current cycle and subsequent cycle fecundability. RESULT(S): A total of 549 women provided 1,552 complete cycles for analysis. Intermenstrual and luteal bleeding were reported in 36% and 34% of cycles, respectively. Ninety-three percent of all intermenstrual bleeding was luteal. Cycles in which women had intermenstrual bleeding or luteal bleeding were statistically significantly less likely to result in conception (fecundability ratio [FR] 0.23; 95% confidence interval [CI], 0.16-0.34; and FR 0.22; 95% CI, 0.14-0.33). Women with an episode of intermenstrual and luteal bleeding had a statistically significant increase in the probability of pregnancy in the subsequent cycle (FR 1.61; 95% CI, 1.15-2.25; and FR 2.01; 95% CI, 1.52-2.87, respectively). CONCLUSION(S): Intermenstrual bleeding statistically significantly decreases the odds of conceiving in that cycle but does not appear to negatively impact a woman's immediate future reproductive potential. CLINICAL TRIAL REGISTRATION NUMBER: NCT01028365.

Peri-implantation intercourse lowers fecundability.

OBJECTIVE: To determine the impact of sexual intercourse around the time of implantation on the probability of achieving a pregnancy. DESIGN: Time-to-pregnancy cohort using day-specific probability of pregnancy modeling to account for intercourse during the fertile window. SETTING: Community cohort. PATIENT(S): Women trying to conceive naturally, ages 30-44, without known infertility. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Positive pregnancy test. RESULT(S): A total of 564 women provided 1,332 complete cycles for analysis. Intercourse frequency during the fertile window and during the peri-implantation window were significantly correlated. Cycles in which couples had 2 or more days with intercourse during the implantation window were significantly less likely to result in a positive pregnancy test compared with cycles in which couples did not have intercourse in this window, after adjusting for age, race, history of regular menstrual cycles, previous pregnancy, and body mass index (fecundability ratio, 0.62; 95% confidence interval, 0.42-0.91). CONCLUSION(S): Intercourse during the peri-implantation window may be detrimental to natural fertility. Methods that allow couples to time intercourse to the fertile window may decrease time to pregnancy by not only increasing the probability of fertilization but also decreasing the probability of failed implantation.

Cervical mucus monitoring prevalence and associated fecundability in women trying to conceive.

OBJECTIVE: To assess the use of cervical mucus monitoring (CMM) in women trying to conceive and determine whether monitoring is associated with increased cycle-specific probability of conception (fecundability). DESIGN: Time-to-pregnancy cohort study. SETTING: Population-based cohort. PATIENT(S): Three hundred thirty-one women trying to conceive, ages 30 to 44 years, without known infertility. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): CMM prevalence and fecundability. RESULT(S): During the first cycle of the study, CMM was performed consistently (checked on >66% of pertinent cycle days) by 20 women (6%), inconsistently (34% to 66% of days) by 60 women (18%), infrequently (≤33% of days) by 73 women (22%), and not performed by 178 women (54%). Cycles in which CMM was consistently performed were statistically significantly more likely to result in conception after adjusting for age, race, previous pregnancy, body mass index, intercourse frequency, and urinary luteinizing hormone (LH) monitoring. Fecundability also increased with increasing consistency of CMM. CONCLUSION(S): Among women trying to conceive, CMM is uncommon, but our study suggests that CMM-a free, self-directed method to determine the fertile window-is associated with increased fecundability independent of intercourse frequency or use of urinary LH monitoring.

An empirical study of self-efficacy and social support in diabetes self-management: implications for home healthcare nurses.

This pilot study was conducted to evaluate relationships among self-efficacy, social support, social problem solving, and diabetes self-management in people living with Type 2 diabetes mellitus. Self-efficacy, social support, and social problem solving were significantly correlated with diabetes self-management. These relationships indicate the importance of including interventions to promote self-efficacy, social support, and social problem solving in diabetes self-management programs.