Endometriosis-derived miRNAs regulate macrophage cytokine production that contributes to inflammation associated with this condition.
Background Endometriosis is an estrogen dependent, inflammatory disorder occurring in 5–10% of reproductive-aged women. Women with endometriosis have a lower body mass index (BMI) and decreased body fat compared to those without the disease, yet few studies have focused on the metabolic abnormalities in adipose tissue in women with endometriosis. Previously, we identified microRNAs that are differentially expressed in endometriosis and altered in the serum of women with the disease. Here we explore the effect of endometriosis on fat tissue and identified a role for endometriosis-related microRNAs in fat metabolism and a reduction in adipocyte stem cell number. Methods Primary adipocyte cells cultured from 20 patients with and without endometriosis were transfected with mimics and inhibitors of microRNAs 342-3p or Let 7b-5p to model the status of these microRNAs in endometriosis. RNA was extracted for gene expression analysis by qRT-PCR. PCNA expression was used as a marker of adipocyte proliferation. Endometriosis was induced experimentally in 9-week old female C57BL/6 mice and after 10 months fat tissue was harvested from both the subcutaneous (inguinal) and visceral (mesenteric) tissue. Adipose-derived mesenchymal stem cells in fat tissue were characterized in both endometriosis and non-endometriosis mice by FACS analysis. Results Gene expression analysis showed that endometriosis altered the expression of Cebpa , Cebpb , Ppar-γ , leptin , adiponectin , IL-6 , and HSL , which are involved in driving brown adipocyte differentiation, appetite, insulin sensitivity and fat metabolism. Each gene was regulated by an alteration in microRNA expression known to occur in endometriosis. Analysis of the stem cell content of adipose tissue in a mouse model of endometriosis demonstrated a reduced number of adipocyte stem cells. Conclusions We demonstrate that microRNAs Let-7b and miR-342-3p affected metabolic gene expression significantly in adipocytes of women with endometriosis. Similarly, there is a reduction in the adipose stem cell population in a mouse model of endometriosis. Taken together these data suggest that endometriosis alters BMI in part through an effect on adipocytes and fat metabolism.
BACKGROUND: Intravenous acetaminophen reaches a higher mean peak plasma concentration than oral acetaminophen in a shorter period of time. The favorable pharmacokinetics of intravenous acetaminophen may be beneficial for treating intrapartum maternal fever. OBJECTIVE: The primary objective was to compare intravenous and oral acetaminophen in time to defervescence (temperature <38 C). The secondary objective was to compare intravenous and oral acetaminophen in the percentage of participants being afebrile and percent reduction in maternal temperature 30 minutes after administration of first dose. Other outcomes evaluated were histopathological placental findings; neonatal outcomes; oxidative stress; and levels of RANTES, interferon-d, interleukin 1b, interleukin 2, interleukin 4, interleukin 6, interleukin 8, interleukin 10, interleukin 13, and tumor necrosis factor-a in maternal and neonatal blood. STUDY DESIGN: This was a randomized, comparator-controlled, double-dummy, double-blind clinical trial. At the onset of intrapartum fever !38 C, patients !36 weeks' gestation were either randomized to the control or experimental study arm. Patients in the control arm received 1000 mg of oral acetaminophen capsules and an intravenous placebo resembling intravenous acetaminophen. Patients randomized to the experimental arm received 1000 mg of intravenous acetaminophen and oral placebo capsules resembling acetaminophen. Maternal temperatures and fetal heart rates were recorded at consecutive intervals following administration of the first dose of acetaminophen. Maternal blood, collected at the onset of fever and after delivery, and neonatal cord blood collected at delivery were evaluated for oxidative stress (glutathione levels), levels of RANTES and cytokines (interferon-d, interleukin 1b, interleukin 2, interleukin 4, interleukin 6, interleukin 8, interleukin 10, interleukin 13, and tumor necrosis factor-a). Placentas were collected for pathologic review. A P value of <.05 was considered statically significant. RESULTS: A total of 121 patients (55 in the intravenous and 66 in the oral group) were recruited from December 1, 2016, to February 28, 2018. Patient demographics and intrapartum factors were similar between both arms. The intravenous group showed a mean time of 54.86 minutes (95% confidence interval, 20.57e39.43) to defervescence vs 52.58 minutes (95% confidence interval, 16.58e43.42) in the oral group (P¼.71). In addition, intravenous and oral acetaminophen showed similar results in percentage of patients being afebrile and percent reduction in maternal temperature 30 minutes after administration of the first dose. Histopathological findings, neonatal outcomes, oxidative stress markers, and RANTES and cytokine levels were not statistically significant between intravenous and oral acetaminophen groups. CONCLUSION: Intravenous acetaminophen did not demonstrate a higher efficacy than oral acetaminophen in treating intrapartum maternal fever. Select patients may benefit from intravenous acetaminophen for treatment o...
Objective. To investigate patient knowledge and attitudes toward surgical approaches in gynecology. Design. An anonymous Institutional Review Board (IRB) approved questionnaire survey. Patients/Setting. A total of 219 women seeking obstetrical and gynecological care in two offices affiliated with an academic medical center. Results. Thirty-four percent of the participants did not understand the difference between open and laparoscopic surgeries. 56% of the participants knew that laparoscopy is a better surgical approach for patients than open abdominal surgeries, while 37% thought that laparoscopy requires the surgeon to have a higher technical skill. 46% of the participants do not understand the difference between laparoscopic and robotic procedures. 67.5% of the participants did not know that the surgeon moves the robot's arms to perform the surgery. Higher educational level and/or history of previous abdominal surgeries were associated with the highest rates of answering all the questions correctly (p < 0.05), after controlling for age and race. Conclusions. A substantial percentage of patients do not understand the difference between various surgical approaches. Health care providers should not assume that their patients have an adequate understanding of their surgical options and accordingly should educate them about those options so they can make truly informed decisions.
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