Progesterone-mediated reversal of mifepristone-induced pregnancy termination in a rat model: an exploratory investigation.

Globally, a substantial proportion of pregnancies end in induced (particularly medication) abortion. However, data also indicates a percentage of women who seek assistance in potentially reversing the medication abortion process. While previous literature has suggested the potential for progesterone-mediated reversal of mifepristone-induced abortion, this process has not been effectively investigated pre-clinically. Our study explored the potential reversal of mifepristone-induced pregnancy termination using progesterone in a rat model, following a clear initiation of pregnancy termination. Female Long-Evans rats were divided into three groups (n = 10-16/group): Pregnant control (M-P-), mifepristone-only/pregnancy termination (M+P-) and mifepristone + progesterone (M+P+). Drug/vehicle administration occurred on day 12 of gestation (first-trimester human equivalent). Rat weight was measured throughout gestation. Uterine blood, collected post-drug/vehicle administration, was analyzed spectrophotometrically to measure blood loss. Additionally, at the end of gestation (day 21), ultrasound was utilized to confirm pregnancy and measure fetal heart rate. Number of gestational sacs, uterine weights and diameters were obtained following tissue collection. Our results indicate that progesterone administration following initiation of mifepristone-induced pregnancy termination (indicated by weight loss and uterine bleeding) reversed the process in 81% of rats in the M+P+ group. Following the initial weight loss, these rats proceeded to gain weight at a similar rate to the M-P- group, in contrast to the continued decrease displayed by the M+P- group (and unsuccessful reversals). Moreover, while uterine blood loss was similar to that of the M+P- group (confirming pregnancy termination initiation), number of gestational sacs, uterine weights, diameters, approximate fetal weights and fetal heart rates were similar to the M-P- group. Thus, our results indicate a clear progesterone-mediated reversal of an initiated mifepristone-induced pregnancy termination in a rat model at first-trimester human equivalent, with resultant fully developed living fetuses at the end of gestation, clearly indicating the necessity for further pre-clinical investigation to assist in better informing the scientific/medical communities of the potential implications in humans.

The Impact of COVID-19 and Associated Interventions on Mental Health: A Cross-Sectional Study in a Sample of University Students.

BACKGROUND: Mental health issues have continued to rise globally, including among university students. The COVID-19 pandemic has exacerbated the previously existing and concerning problem. Given that coping mechanisms have been proposed to mediate the relationship between stressors and mental health, the aim of our cross-sectional study was to investigate the mediation of coping mechanisms on the relationship between the impact of the COVID-19 pandemic and mental health. METHODS: University students (≥18 years old; N = 676; 31% male, 69% female) were administered an anonymous survey addressing current demographics, COVID-19 pandemic-related demographics, personal experiences, sources of stress and perceived effect on mental health, politics, sources of news/information, and various pre-validated scales addressing mental health (DASS-21), the impact of the COVID-19 pandemic (IES-R) and coping strategies utilized (Brief COPE). RESULTS: Our results indicate a substantial proportion of our sample reporting scores in the severe and extremely severe DASS-21 categories, in addition to ~50% reporting a perceived deterioration in mental health relative to pre-COVID-19 pandemic. Moreover, a substantial proportion of students reported IES-R scores at levels where PTSD is of clinical concern. Alarmingly, a significant proportion of females (~15%) reported scores reflecting potential long-term PTSD-related implications. Females tended to be more severely impacted in all mental health measures. Mediation analysis indicated that while dysfunctional coping mediated the relationship between the impact of the event (COVID-19 pandemic) and all three mental health outcomes, overall, this was not the case with the positive coping strategies. CONCLUSION: Our study appears to indicate a reduced buffering influence on negative mental health outcomes by the positive coping mechanisms investigated in relation to the COVID-19 pandemic and secondary interventions implemented. While the findings of this study pertain specifically to university students, they corroborate the existing extensive body of research (from physiological to behavioral, preclinical to clinical) pertaining to the response associated with major stressful events at every level of society. In this regard, the findings imply the necessity for health and other authorities, tasked with safeguarding public well-being, to avoid reactive interventions that do not appropriately balance the risks and benefits, potentially exacerbating pre-existing psychopathologies and compromising social order.

Pregnancy-induced long-term uterine vascular remodeling in the rat.

Despite the available research investigating uterine physiology during and immediately following pregnancy, including at the vascular and muscular levels, knowledge of the potential long-term timeline of such changes is limited. Thus, our study sought to investigate the potential long-term changes in uterine vasculature and horn length in the postpartum rat, following delivery and weaning. Female Long-Evans rats (n = 9-11 rats/group/timepoint) were divided into two groups: a pregnant group and an age-matched virgin control group. Rat weight, food consumption and vaginal impedance measurements were recorded throughout the experiment. Rats in the pregnant group were bred and pregnancy was confirmed using ultrasound imaging. The uterus and its vasculature were collected at various timepoints following weaning: 3 (week of weaning), 8-9 and 13 weeks postpartum, and at age-equivalent timepoints in the virgin group, and the diameters of the main uterine artery and vein, and lengths of the mesometrial segmental vessels (MSV) and uterine horns were recorded. The results indicated a significant difference between the previously-pregnant and virgin rats in both internal and external arterial diameters (but not arterial wall thickness), as well as the uterine horn length, 3 weeks postpartum, but not 8-9 and 13 weeks postpartum. Significant differences were observed in both venous diameter and MSV length at all timepoints measured. Placental scars were also observed in previously-pregnant rats at all timepoints measured. Our study highlights the long-term impact of pregnancy on the uterine vasculature and the necessity for consideration of such changes on subsequent pregnancies, as well as pregnancy-related vascular pathologies.

Compulsive Internet Pornography Use and Mental Health: A Cross-Sectional Study in a Sample of University Students in the United States.

BACKGROUND: The sustained rise in negative mental health reports among university students is a source of continued global concern, and investigation continues into potential contributors to this rise. This includes the increased prevalence of risky sexual behaviors. Related is the increased prevalence of pornography use. Our study sought to explore the potential relationship between compulsive use of pornography and mental health in university students. METHODS: Our sample consisted of university students (N = 1031; 34% male, 66% female) from Franciscan University of Steubenville, Steubenville, Ohio. An anonymous survey was sent to all students at the university over the age of 18. The survey was comprised of the following: (1) demographic questions, (2) questions on pornography use and perception, (3) a modified version of the Compulsive Internet Use Scale (mCIUS) assessing various factors associated with compulsive internet pornography use, (4) questions assessing emotional and sexual states relative to pornography use (EmSS), and (5) the 21-question version of the Depression, Anxiety and Stress Scale (DASS-21). RESULTS: Our results indicate that 56.6% of those surveyed reported lifetime pornography use, with a significantly higher proportion of males than females reporting such use. The majority of students reported accessing pornography through internet-related technologies. Additionally, 17.0, 20.4, and 13.5% of students reported severe or extremely severe levels of depression, anxiety and stress, respectively, with compulsive pornography use significantly affecting all three mental health parameters in both sexes. Exploratory Factor Analysis identified three factors suggesting emotional coping, dependence and preoccupation for the mCIUS items and three factors reflecting interoceptive, impotent, and extrinsic characteristics for the EmSS items. Regression analysis indicated that various demographics, items pertaining to reduced control and social impairment, and other variables pertaining to pornography use predicted mental health outcomes. Faith, morals and personal motivation were the primary variables reported to help reduce pornography use. CONCLUSION: Our analyses indicate a significant relationship between mental health and pornography use, including behaviors reflecting behavioral addictions, highlighting the necessity for a better understanding and consideration of the potential contribution of internet pornography to negative mental health among university students.

Biological, Behavioral and Physiological Consequences of Drug-Induced Pregnancy Termination at First-Trimester Human Equivalent in an Animal Model.

Given the significant physiological changes that take place during and resulting from pregnancy, as well as the relative absence of such information in relation to pregnancy termination, this study investigated the potential for developing a valid animal model to objectively assess the biological, physiological and behavioral consequences of drug-induced pregnancy termination. Female Long-Evans rats were divided into four groups (n = 19-21/group), controlling for drug [mifepristone (50 mg/kg/3 ml, i.g.)/misoprostol (0.3 mg/kg/ml, i.g.) or vehicle (1% Carboxymethylcellulose Sodium/0.2% Tween® 80 suspension, i.g.)] and pregnancy. Drug administration took place on days 12-14 of gestation (days 28-40 human gestational equivalent). Vehicle was administered to the controls on the same days. Parameters measured included rat body weight, food intake, vaginal impedance, sucrose consumption/preference, locomotor activity, forced swim test, and home-cage activity. At the termination of the study, rats were deeply anesthetized using urethane, and blood, brain, and liver were collected for biochemical analysis. Following drug/vehicle administration, only the pregnancy termination group (pregnant, drug) displayed a significant decrease in body weight, food intake, locomotor activity-related behaviors and home-cage activity relative to the control group (non-pregnant, vehicle). Additionally, the pregnancy termination group was the only group that displayed a significant reduction in sucrose consumption/preference during Treatment Week relative to Pre-Treatment Week. Vaginal impedance did not significantly decrease over time in parous rats in contrast to all other groups, including the rats in the pregnancy termination group. Biochemical analysis indicated putative drug- and pregnancy-specific influences on oxidative balance. Regression analysis indicated that pregnancy termination was a predictor variable for body weight, food intake and all locomotor activity parameters measured. Moreover, pertaining to body weight and food intake, the pregnancy termination group displayed significant changes, which were not present in a group of naturally miscarrying rats following pregnancy loss. Overall, our results appear to suggest negative biological and behavioral effects following pregnancy termination, that appear to also be distinct from natural miscarriage, and potential benefits of parity pertaining to fecundity. Thus, our findings indicate the importance for further objective investigation of the physiological and behavioral consequences of medical abortion, in order to provide further insight into the potential implications in humans.