bluuebunny/crossref_metadata_2025_split huggingface dataset:
Systemic Inflammation among Pregnant African American Women Is Related to Depressive Symptoms and Intimate Partner Violence
Authors: Saadat Nadia , Zhang Liying , Padmanabhan Vasantha , Engeland Christopher G , Misra Dawn P , Giurgescu Carmen 
Published: May 2021

Abstract
Systemic inflammation (e.g., higher levels of pro-inflammatory cytokine interleukin [IL]-6 and C-reactive protein [CRP]) during pregnancy increases risk for both the mother and the infant. For the mother, systemic inflammation is associated with an increased risk of pregnancy complications (e.g., preeclampsia). For the infant, cytokine dysregulation may lead to long term immune dysregulation and susceptibility to metabolic diseases. Pregnant African American women are more likely to have greater systemic inflammation compared with pregnant non-Hispanic White women. They also experience a higher prevalence of chronic conditions (e.g., asthma), have higher levels of depressive symptoms, and report more incidents of intimate partner violence (IPV). We hypothesize that maternal systemic inflammation is related to chronic disease, depressive symptoms, and IPV among pregnant African American women. Pregnant African American women (n=180) were recruited at prenatal clinics in the Midwest. Women completed a questionnaire and had blood drawn at a prenatal visit. Plasma cytokine levels (interferon [IFN]-γ, tumor necrosis factor [TNF]-α, IL-6, IL8 and IL10) were measured by multiplex array and CRP was measured by ELISA. Data were log (x+1) transformed and analyzed using descriptive statistics and correlational analysis (Pearson and point-biserial correlations). Women had a mean age of 27±5.5 years (range 18-41) and a mean gestational age at data collection of 16±5.8 weeks (range 8-29). Fifty-five percent of women were employed, 42% had annual household income &lt; $10,000, and 16% smoked cigarettes during pregnancy. Twenty-five percent of women reported asthma, 8% hypertension, 6% diabetes, and 4% thyroid disease. Twenty-seven percent of women had Center for Epidemiological Studies-Depression (CES-D) scores ≥ 23, which have been correlated with depression diagnosis. IPV during the year before pregnancy was more frequent (8%) than IPV during pregnancy (5.1%). Women who reported hypertension had higher levels of TNF-α (r= 0.151, p&lt; 0.05); and women with asthma had higher levels of CRP (r= 0.20, p&lt; 0.01). Women who reported higher CES-D scores (r= 0.19, p&lt; 0.05) had higher CRP levels. Women who reported IPV during pregnancy had higher IL-8 levels (r= 0.17, p&lt; 0.05). Women who were employed had lower levels of IL-6 compared to women who were not employed (r= -0.180, p&lt; 0.05). These results indicate that systemic inflammation is related to chronic health conditions (hypertension, asthma), depressive symptoms, IPV and employment status in pregnant African American women. The relationships between systemic inflammation, depressive symptoms and IPV, with a focus on metabolic and molecular pathways should be investigated to better understand the mechanisms by which maternal and fetal health are affected.
The Circadian Clock Gene Bmal1 Modulates Myometrium Contractile Function in Pregnant Mice
Authors: Van Quynh Duong Thu , Yaw Alexandra , Nguyen Duong , Hoffmann Hanne Mette 
Published: May 2021

Abstract
Caesarian section should be avoided unless medically required. Caesarian section is often a result of failed labor enhancement. While most natural births occur at night, labor enhancement is often scheduled during the day. We propose that the disparity between the commonly used timing of labor enhancement in the clinic, from the timing of natural birth, could contribute to the high rate of labor induction failure. Oxytocin receptor agonists are the most used labor enhancing agents. In pregnant non-human primates, oxytocin enhances uterine contractions more efficiently at night than during the day, suggesting a daily change in uterine sensitivity to oxytocin in pregnancy. To identify the molecular mechanisms generating daily changes in uterine function, we here explore the role of the molecular clock gene, Bmal1 (Brain and muscle ARNTL1-like), in the pregnant mouse myometrium. BMAL1 is a transcription factor required to generated circadian rhythms at the cellular level. We hypothesize that Bmal1 in uterine myometrial cells generates circadian rhythms and establishes the daily change in uterine contractile response to oxytocin. To evaluate circadian rhythms ex vivo, we collected myometrium samples from the validated circadian Per2:luciferase reporter mice at gestation day 17-18. We found that the pregnant mouse myometrium possesses circadian rhythms, which are generated by the molecular clock, as triple transgenic Per2:luciferase mice with Bmal1 conditionally deleted in the myometrium (cKO) do not have rhythmic expression of the Per2:luciferase reporter. To determine if BMAL1 is required to establish uterine contractions, we used a myograph to measure ex vivo uterine contractions at gestation day 17-18. In controls, uterine contraction force was significantly higher at ZT15 (3h after lights OFF) versus ZT3 (3h after lights ON). Interestingly, our preliminary data show increased basal contractile force at ZT15 in cKO as compared to controls. In addition, the cKO uterus contracted stronger to oxytocin than controls. Our findings identify Bmal1 as a clock gene modulating basal contractions in the mouse uterus and indicate Bmal1 might be a regulator of uterine sensitivity to oxytocin. Future work will focus on identifying the molecular mechanisms driven by BMAL1 to regulate uterine function in pregnancy. This work has the potential to provide insights into how we can improve labor enhancing treatment strategies in the clinic in the future.
Impact of Testosterone Therapy on Hematocrit and Polycythemia: Evaluation of Data From Two Ongoing Open-Label Randomized Single-Center Clinical Trials
Authors: Gonzalez Daniel , Kresch Eliyahu , Ory Jesse , Nackeeran Sirpi , Blachman-Braun Ruben , Molina Manuel , Ramasamy Ranjith 
Published: May 2021

Abstract
Introduction & Objective: Testosterone (T) replacement therapy (TRT) is the mainstay treatment for male hypogonadism. The most commonly reported adverse event among men using TRT is polycythemia. What is unknown is whether the short-acting vs. long-acting testosterone preparations have different effects on hematocrit. We hypothesized that short-acting testosterone therapy will be physiologic and have lesser effect on hematocrit compared to long-acting TRT. We evaluated data from two simultaneous ongoing open-label, randomized, two-arm clinical trials to evaluate the impact of TRT on Hematocrit and compared prevalence rates of polycythemia among subcutaneous T pellets (long-acting) and Intranasal Testosterone (Natesto) or Intramuscular Testosterone cypionate (TC) (short-acting).
Subject and Methods: Hypogonadal men (2 AM serum T &lt; 300 ng/dL assayed by LC-MS/MS) aged 18-65 years were randomized into open-label randomized clinical trials. Eligible subjects received: Trial 1: 800mg subcutaneous Testopel T pellets; Trial 2: 11mg TID Intranasal testosterone (Natesto) or 200mg x 2 weeks TC for 2 months. Serum T, Hematocrit (HCT), and prevalence of polycythemia (as defined as HCT &gt;50%) were collected at baseline and after 2 months of therapy. Data are presented as a post-hoc analysis of the two randomized clinical trials and reported as median and interquartile range [25th-75th], paired sample analysis (baseline versus follow-up) was performed with the Wilcoxon rank test to determine change during time within the different TRT modalities, with p&lt;0.05 considered significant.
Results: Median change for serum T between baseline and 2mo follow-up to subcutaneous T pellets was 542 [454-757] ng/dL, Intranasal Testosterone 706 [517-1010] ng/dL, and TC 525 [280-712]ng/dL. T pellets showed a statistically significant increase in HCT from 44.6 [42.0-46.6] to 46.7 [42.6-48.9] (p&lt;0.001), with a prevalence of 7/47 (14%) men developing polycythemia. A safety trigger for HCT greater than 54% occurred in 2/47 (4%). The treatment effect was independent of baseline serum testosterone. TRT with Natesto decreased HCT, from 43.4 [41.6-46.1] to 43.4 [40.6-46.5], however not statistically significant (p=0.262). TC statistically increased HCT from 41.6 [40.3-43.1] to 43.8 [43.5-47.4] (p=0.018), with 0% of men developing polycythemia in both groups.
Conclusions: Long acting TRT appears to increase hematocrit compared to short-acting testosterone therapies. Treatment of hypogonadal men with Intranasal T Natesto and testosterone cypionate successfully achieved target serum T level and maintained HCT levels. Longer-term durability and safety effects of the intervention remain to be further investigated.
Safety and Efficacy of Clomiphene Citrate in the Treatment of Secondary Hypogonadism. A Retrospective Study
Authors: Garcia-Touza Mariana 
Published: May 2021

Abstract
“Introduction: Clomiphene (Clomid) has an off-label indication to treat hypogonadism in select populations. “Based on clinical practice, this medication in certain types of hypogonadism is equally effective as testosterone in treating hypogonadism. It will lead to less side effects, lower treatment cost, and will decrease rates of infertility in the male veteran population.” Secondary hypogonadism can be most often caused by opioid use, obesity, sleep apnea, and diabetes.” “Aim of Study: To evaluate the safety and efficacy of Clomiphene Citrate in Treatment of Secondary Hypogonadism in comparison with testosterone. “Study Population: Data was obtained from the Veterans Administration Data Warehouse through the Veterans Administration Informatics and Computing Infrastructure. Data was extracted using SQL. There were 405,824 male patients with a diagnosis of hypogonadism (87.1%)and infertility (12.9%). nationally at the VA. Of these, 9566 patients have been treated with clomiphene citrate and 232,123 with various testosterone therapy. “ The two groups were then matched by propensity method to controls at a ratio of about 1:1 for Age, race, BMI and time for follow-up as potential confounding factors hat could have affected inclusion in the study controls. Patients without either Clomiphene or testosterone treatment were excluded. Statistical Analysis: SAS was used for propensity matching (PSM, greedy near) Categorical variables were evaluated as frequency counts with percentage within group, as well as ODDS ratio (OR) and differences were evaluated by a chi-square method. Comparisons of continuous variables were done were done by simple and paired t-test. Kaplan Meier plots and Cox Hazard ratio calculations were used to examine time dependent risk between treatments. Actual p-values are shown and p-values lower than 0.0001 are shown as such. All comparisons used a two-sided assumption. Measurements: Testosterone laboratory measures were recorded for start and end of trial. Survival was taken as the difference in days between start date and date of death. New diagnosis of Osteoporosis and Polycythemia was that which occurred after initiation of therapy. “Results: Clomid treatment normalized testosterone levels in 53.2% versus 46.8% in the testosterone group (OR 1.32 P&lt;0.005). All-cause mortality was in the clomid group 0.16% and 1.62%in the testosterone group (OR 0.16 P&lt;0.001). The incidence of new Osteoporosis for clomid was 3.9 % versus 5.9% for testosterone (OR 0.65 P&lt;0.001)” Conclusion: This is a retrospective study comparing the efficacy and side effects of clomiphene versus testosterone for treatment of hypogonadism. The study showed that clomiphene is more effective than testosterone to treat secondary hypogonadism. We also found decreased overall mortality and incidence of polycythemia and osteoporosis.
Assessment of Chronic Supraphysiological Glucocorticoid Dosing Needs of Patients With Adrenal Insufficiency
Authors: Mun Jeff , McGlotten Raven , Nieman Lynnette K 
Published: May 2021

Abstract
Background: Patients who require higher than replacement glucocorticoid doses to avoid symptoms of adrenal insufficiency (AI) may have inadequate adherence or abnormal drug absorption or metabolism. The goal of this study was to identify why excessive glucocorticoid doses were needed in patients with ongoing AI symptoms. Methods: We performed pharmacokinetic (PK) analysis of glucocorticoid plasma concentrations (prednisone, prednisolone and dexamethasone measured by tandem mass spectrometry, Mayo Laboratories, and cortisol by immunoassay, Clinical Center) in 8 AI patients after weight-based oral hydrocortisone (HC) dose (1), IV HC 20 mg and /or prednisone 5 mg PO. The time (Tmax) to maximal plasma concentrations (Cmax), time to a 50% decrease in concentration (T1/2), elimination rate (ER) and area under the concentration curve (AUC) were determined using MATLAB and SimBiology, and compared to literature reference ranges (RR) (1,2). Results: Patients included one man; six had secondary AI due to previous supraphysiologic hydrocortisone or prednisone treatment and two had primary autoimmune AI. One of the latter was appropriately replaced with thyroid hormone. No patient was taking any medication known to be a strong inhibitor or inducer of CYP3A4 and none were taking oral estrogens. To study the potential contribution of intestinal absorption to abnormal pharmacokinetics, serum cortisol values were compared to expected values at 3.5 or 4 hours after a weight-based oral dose of HC in eight patients (1); 7 patients had values at the 50 - 80th centile of expected values. The eighth patient’s cortisol level at 4 hours after 5 mg HC was 30.3 nmol/L, below the 10th centile. She then underwent the same sampling with a 15 mg dose, with values also at the 10th centile. To uncover any discrepancy between PK oral and IV HC administration, four patients, including the patient with a low 4 hour value (LowHC4h) underwent sampling after 20 mg hydrocortisone, IV (2). Tmax and Cmax were within the RR in all four patients, while one patient had a faster T1/2 but an AUC similar to others. The LowHC4h patient had a dexamethasone level 8 hours after a 1 mg dose that was also within the RR and was maintained on dexamethasone. All others were eventually able to be weaned to a conventional glucocorticoid replacement dose. Conclusions: Evaluation of oral and IV HC PK may be useful in patients suspected of having abnormal absorption of oral glucocorticoids. Ref: 1. Mah PM et al. Clin Endo 61:367,20042. Thomson AH et al. Clin Endo 66:789,2007
Dietary Coconut Oil Mitigates Hyperandrogenemia in Obese Female Pigs Due to Suppression of Androgen Steroidogenesis in the Adrenal Cortex and Theca Externa
Authors: Shah Payal , Kothmann Kadden Heinrich , Skenandore Cassandra Suzanne , Browning Luke , Goblet Camille , Chau Laura , Grizzaffi Matthew , Newell-Fugate Anne Elizabeth 
Published: May 2021

Abstract
Western-style diets (WSD) cause cardiometabolic disease and hyperandrogenemia in reproductive-age women. A promising alternative for improved fertility in obese women may derive from the nutraceutical, coconut oil. We hypothesized that dietary coconut oil included in a high fat diet would mitigate hyperandrogenemia due to obesity through depression of androgen steroidogenesis in theca externa and adrenal cortex. Seventeen sexually mature female Ossabaw pigs were divided into 3 diet groups: control (n=6; C; 2200 kcal/pig/day), WSD (n=5; WSD; 5000 kcal/pig/day), or high fat coconut oil diet (n=6; COC; 5000 kcal/pig/day). Ingredients in WSD and COC diets were the same except 9% of calories in WSD were from lard and 9% of calories in COC were from coconut oil. Pigs were fed for 9 cycles (~ 8 mos) and fasting blood was collected at cycle 0 (baseline), 7, and 9. After cycle 7, ovarian steroidogenesis was suppressed by oral progestogen for 18 days. On day 18 while ovarian steroidogenesis was still suppressed, an ACTH stimulation was performed. On day 19, progestogen was withdrawn and 7.5 µg/kg IM dexamethasone was given every 12 hours to suppress adrenal steroidogenesis. On day 20, 3000 IU/m2 human chorionic gonadotropin (hCG) was given IV. Pigs underwent a washout cycle post-stimulations and were euthanized when they had dominant ovarian follicles in cycle 9 for collection of follicular fluid (FF), theca externa, and adrenal cortex. FF was assessed for steroid hormones by LC-MS/MS. Adrenal cortex and theca cells were cultured as follows for 48 hours after which cells and media were collected: 1) theca: control, insulin (I; 100 ng/ml), LH (10 ng/ml), or LH+I (10 ng/ml + 100 ng/ml); 2) adrenal: control or 1 µM ACTH. WSD pigs had a protracted estrous cycle length and increased FF testosterone, dehydroepiandrosterone sulfate, androstenedione (A4), androstenediol, and allo-pregnanolone (Allo-Preg) compared to C pigs. Both serum and cell culture media A4 concentrations were higher in response to ACTH in WSD pigs. By 72 hours post-hCG, COC pigs had higher serum A4 than C or WSD pigs, but in vitro LH yielded decreased cell culture media A4 in both WSD and COC pigs. COC pigs had increased FF dihydrotestosterone and Allo-Preg compared to C pigs. These results suggest that dietary coconut oil administration in obese females may depress excessive androgen steroidogenesis by adrenal cortex but may only partially mitigate excessive androgen production by theca externa.
Audit on Steroid Replacement in Confirmed or Suspected COVID-19 Patients With Adrenal Insufficiency or Adrenal Suppression in a District General Hospital
Authors: Haddad Aiman 
Published: May 2021

Abstract
Aim: In response to new updated guidance from Society For Endocrinology April 2020, this Audit was conduct to assess the adequacy of steroid replacement in confirmed or suspected COVID-19 patients with adrenal insufficiency or adrenal suppression admitted to Bedford District General Hospital. In steroid dependent patients (Addison’s disease, adrenal insufficiency, pituitary steroid insufficiency, use of long term steroids for other conditions - 5mg or more of prednisolone (or equivalent doses) daily for longer than 4 weeks) admitted to hospital very unwell with confirmed or suspected COVID recommendations is to start on Hydrocortisone 100 mg per IV injection followed by continuous IV infusion of 200 mg hydrocortisone/24h (alternatively 50 mg every 6 h per intravenous or IM bolus injection). Method: Retrospect data collection on Patients admitted in May 2020 to Bedford Hospital with suspected or confirmed COVID 19 disease with adrenal insufficiency or on long term steroid use. Those patients should be started on Hydrocortisone 100 mg per IV injection followed by continuous IV infusion of 200 mg hydrocortisone/24h (alternatively 50 mg every 6 h per intravenous or IM bolus injection).
Results: In May 2020, 295 patients admitted under the medical team in Bedford Hospital with confirmed or suspected COVID-19. Only 12 patients met the inclusion criteria, one patient with a diagnosis of Addison disease and the remaining 11 patients on long term steroids. None of these patients were managed as per updated guidelines. 6 patients had less than the adequate dose, they were started on prednisolone 30-40mg. 4 patients dose of oral steroids was only doubled, 1 patient received the same dose of oral steroid and the only confirmed Addison had higher dose of hydrocortisone. Moreover, In June 2020, The RECOVERY Outcome trial results showed that Dexamethasone 6mg for 10 days reduces the death by one third in hospitalised patient with severe respiratory complications of COVID-19. Dexamethasone 6mg is 12 times the physiological required steroid dose, this is equivalent to 240mg hydrocortisone, which is adequate for steroid replacement in patients with adrenal insufficiency or suppression.
Conclusion: In view of these results and the outcome of the RECOVERY Trial, Local trust guidelines updated, indicated that any patient with Adrenal insufficiency or suppression including those on long term steroids very unwell admitted to the hospital should receive Dexamethasone if requiring oxygen or Hydrocortisone if not requiring oxygen. Recommendation of changes included teaching sessions delivered to doctors, posters on updated guidelines distributed in major areas in hospital and trust guidelines updated on the intranet.
Hepatic Dysregulation of Bile Acid Homeostasis in Hyperandrogenemic Female Mouse Model of Polycystic Ovary Syndrome
Authors: Huffman Alexandra M , Rezq Samar , Basnet Jelina , Cardozo Licy L Yanes , Romero Damian G 
Published: May 2021

Abstract
Introduction and Purpose: Polycystic Ovary Syndrome (PCOS) is recognized as the most common endocrine disorder in women of reproductive age. Notably, PCOS women with hyperandrogenism have a pronounced increased risk for cardio-metabolic comorbidities compared with healthy individuals. Bile acids are endocrine signaling molecules that modulate hepatic lipid, glucose, and energy metabolism by aiding in absorption of lipids. Alteration of bile acid homeostasis affects overall metabolic homeostasis and contributes to pathogenesis of an array of metabolic diseases, although the molecular mechanisms of this have not been studied in PCOS. Methods: Four-week old C57BL/6N female mice were implanted subcutaneously with dihydrotestosterone (DHT, 8.0 mg) or vehicle silastic tubes (n=8/grp). Weekly body weight, food intake, and body composition was assessed. Fasting serum was obtained and the oral glucose tolerance test (OGTT) was performed in the last week of treatment. Animals were euthanized on treatment day 90 and livers were harvested. Expression levels of mRNA were assessed using RT-qPCR. Results: DHT treated females had significantly higher liver mass (1,387 ± 51 vs 1,197 ± 29 g, p&lt;0.05), increased lean mass (21.25 ± 0.27 vs 19.58 ± 0.23 g, p&lt;0.05) and increased fat mass (4.83 ± 0.47 vs 3.59 ± 0.36 g, p&lt;0.05) compared to the vehicle counterparts. These hyperandrogenemic females additionally showed altered glucose homeostasis, having increased fasting glucose (201.10 ± 11.11 vs 152.80 ± 9.23 mg/dL, p&lt;0.05) and an increased area under the curve (209.2± 11.0 vs 160.8± 3.5 mg.min/dL, p&lt;0.05) following OGTT. Hepatic expression of both classic (Cyp8b1, 1.4 ± 0.1-fold, p&lt;0.05) and alternative (Cyp7b1, 2.0 ± 0.3-fold, p&lt;0.05) bile acid synthesis cytochrome P450 enzyme genes were significantly upregulated in DHT treated animals. Additionally, expression of sulfotransferase Sult2a2 was completely abolished in DHT treated animals compared with vehicle animals, indicating the possibility of androgen regulation of the sulfonation of bile acids marked for elimination. Liver expression of both the bile acid receptor G-protein coupled bile acid receptor 1 and the androgen receptor were both significantly downregulated (Gpbar1: 0.68 ± 0.08-fold, AR: 0.46 ± 0.04-fold, p&lt;0.05) in DHT treated animals. Conclusions: Bile acid synthesis, transport, and elimination are tightly controlled processes in the liver to maintain a constant bile acid pool and limit reabsorption. Together, our results highlight the potential role of androgens in DHT-treated female mice in the dysregulation of bile acid homeostasis and its potential contribution to influence metabolic dysfunction. (Supported by NIH grants NIGMS P20GM-121334 to LLYC and DGR, and NIH NIDDK R21DK-113500 to DGR and the Mississippi Center of Excellence in Perinatal Research.)