Localization of Catecholaminergic Neurofibers in Pregnant Cervix as a Possible Myometrial Pacemaker.

In eutocic labor, the autonomic nervous system is dominated by the parasympathetic system, which ensures optimal blood flow to the uterus and placenta. This study is focused on the detection of the quantitative presence of catecholamine (C) neurofibers in the internal uterine orifice (IUO) and in the lower uterine segment (LUS) of the pregnant uterus, which could play a role in labor and delivery. A total of 102 women were enrolled before their submission to a scheduled cesarean section (CS); patients showed a singleton fetus in a cephalic presentation outside labor. During CS, surgeons sampled two serial consecutive full-thickness sections 5 mm in depth (including the myometrial layer) on the LUS and two randomly selected samples of 5 mm depth from the IUO of the cervix. All histological samples were studied to quantify the distribution of A nerve fibers. The authors demonstrated a significant and notably higher concentration of A fibers in the IUO (46 ± 4.8) than in the LUS (21 ± 2.6), showing that the pregnant cervix has a greater concentration of A neurofibers than the at-term LUS. Pregnant women's mechanosensitive pacemakers can operate normally when the body is in a physiological state, which permits normal uterine contractions and eutocic delivery. The increased frequency of C neurofibers in the cervix may influence the smooth muscle cell bundles' activation, which could cause an aberrant mechano-sensitive pacemaker activation-deactivation cycle. Stressful circumstances (anxiety, tension, fetal head position) cause the sympathetic nervous system to become more active, working through these nerve fibers in the gravid cervix. They might interfere with the mechano-sensitive pacemakers, slowing down the uterine contractions and cervix ripening, which could result in dystocic labor.

The Vermian-Crest Angle: A New Method to Assess Fetal Vermis Position within the Posterior Fossa Using 3-Dimensional Multiplanar Sonography.

BACKGROUND: Normal morphometry of the vermis and its relation to the posterior fossa (PF) rule out most major anomalies of the cerebellum. However, accurate categorization of the position and size of the fetal vermis remains a challenge. OBJECTIVE: Our aim was to test a new method to assess the position and size of fetal vermis on 3-dimensional ultrasound (3D-US). METHODS: We measured the vermian-crest angle (VCA) in normal fetuses using multiplanar 3D-US. We also assessed the diameters (superoinferior, anteroposterior, and horizontal) and volume of the vermis. The Spearman rank test and linear and polynomial regression analyses were used for statistical purposes. RESULTS: We included 126 fetuses. Mean ± SD gestational age (GA) was 26.3 ± 4.6 (range 17-35.5) weeks. Mean ± SD superoinferior, anteroposterior, and horizontal diameters were 16.2 ± 4.9, 11.2 ± 3.6, and 5.6 ± 1.6 mm, respectively. Median (range) vermian volume was 0.50 (0.05-2.9) cm3. The VCA was 64.49° ± 11.45. We found no correlation between GA and VCA (r = 0.15; p = 0.13), a linear correlation between GA and vermian diameters, and a quadratic correlation between GA and vermian volume. CONCLUSIONS: We provide a new method to assess vermian position and size within the PF using 3D-US. The combined information may be of value for screening purposes, particularly to differentiate between the various pathological situations encountered within the PF.

Prevalence of human papillomavirus infection in a clinic sample of transsexuals in Italy.

OBJECTIVES: Detectable human papillomavirus (HPV) DNA is the most common sexually transmitted infection. Reports on the prevalence of detectable HPV DNA among transsexuals (not sex workers) are scarce. The objective of the study was to determine the prevalence of detectable HPV DNA in a clinic sample of transsexuals and to assess the relationship between detectable HPV DNA and cytological outcomes. METHODS: Clinical samples (oral, anal, vaginal, cervicovaginal and penile scraped cells) from 35 transsexuals (surgically treated and surgically untreated) who attended the outpatient Clinic of Gender Identity Dysphoria of the Department of Obstetrics and Gynecology of Policlinico Hospital (Bari, Italy) were collected for cytological analysis and HPV DNA detection and typing. All enrolled subjects answered an anonymous structured questionnaire about their sexual habits. Serological status for other sexually transmitted diseases (hepatitis B virus (HBV), hepatitis C virus (HCV), HIV and syphilis) was also evaluated. RESULTS: HPV DNA was detected in 14 of 35 patients (40.0%). The prevalence of detectable HPV DNA was 38.2% (13/34) in tested anal samples, 9.1% (2/22) in vaginal samples and 8.3% (1/12) in penile samples. Oncogenic HPV genotypes have been detected in 93% of HPV-positive transsexuals. More than one-third (35.7%) of HPV-positive transsexuals were infected with at least one of the four vaccine-preventable genotypes, 6, 11, 16 and 18. CONCLUSIONS: The high rate of detectable HPV DNA by oncogenic types suggests that periodic cytological screening and clinical evaluation may be necessary since transsexuals are at high risk of anogenital cancer. Also promoting HPV vaccination in younger subjects may be advisable.

Ultrasonographic approach to diagnosis of fetal inflammatory response syndrome: a tool for at-risk fetuses?

Preterm parturition is a syndrome that may result from many underlying mechanisms. Infection and inflammation are the prominent ones. Intrauterine infection and inflammation have an effect akin to sepsis, and that is similar to systemic inflammatory response in adults. Indeed, there is evidence to support the association of a fetal inflammatory response syndrome (FIRS) to systemic infection and inflammation. The utilization of invasive procedures for the prenatal diagnosis of FIRS is associated with a risk for complications resulting from the invasive method. The progress in the imaging quality of obstetrical ultrasound and the development of novel methods for functional anatomical assessment of the fetal organs may help to identify, noninvasively, fetuses at risk for FIRS in patients presenting with preterm labor. We review the studies describing advanced sonographic modalities and the imaging findings in the heart, thymus, kidney, adrenal glands, and spleen of these fetuses.

Doppler Ultrasound Flow Evaluation of the Uterine Arteries Significantly Correlates with Tumor Size in Cervical Cancer Patients.

PURPOSE: The aim of this present study was to evaluate the sonographic correlation between Doppler flow characteristics of the uterine arteries and tumor size in patients with cervical cancer, in order to establish a new potential marker to monitor treatment response. METHODS: This was a retrospective cohort study of 25 patients who underwent a sonographic evaluation of Doppler flow characteristics of the uterine arteries before surgery or radiochemotherapy for early and locally advanced/advanced cervical cancer, respectively, was analyzed. The primary outcome was the correlation between Doppler flow characteristics of the uterine arteries and tumor size in patients with cervical cancer. RESULTS: Median age was 49 (range 26-85) years, and mean tumor size was 40.8 ± 17 mm. A significant positive correlation was found between tumor diameter and the uterine artery end-diastolic velocity (r = 0.47, p < 0.05) as well as the peak systolic velocity (r = 0.41, p < 0.05). No correlation was found between tumor size and the pulsatility index or resistance index. CONCLUSIONS: In cervical cancer, uterine artery velocity parameters are associated with tumor size. This finding could become particularly useful in the follow-up of locally advanced cervical cancer patients undergoing radiochemotherapy or in corroborating the selection of women with more possibility of a high response rate during neoadjuvant chemotherapy before surgery.

Impact of school-based educational programs on sexual behaviors among adolescents in northern Italy.

This article aimed to determine sexual behaviors among female and male adolescents in northern Italy. An anonymous self-administered questionnaire evaluating sexual attitudes was distributed in middle and high schools in northern Italy. Adolescents between 13 and 19 years of age were asked to participate at the survey. The study group included 664 participants. Overall, 164 (25%) adolescents had had at least one sexual intercourse. Among adolescents who have had sexual intercourse, 90 (55%) use condoms, 25 (15%) use hormonal contraception, and 49 (30%) do not use any contraception method. A total of 559 adolescents (84%) participated in school-based sexual education programs. This group had better knowledge on sexually transmitted diseases and contraception methods in comparison with adolescents who have never participated in such educational programs (p <.05), and no difference in high-risk sexual behaviors was observed (p = 1.0). School-based sexual education programs improve knowledge of sexual transmitted diseases and contraception methods. However, this knowledge does not correlate to high-risk sexual behaviors reduction.

Chemotherapy reduces para-aortic node recurrences in endometrial cancer with positive pelvic and unknown para-aortic nodes.

OBJECTIVE: The objective of this study was to evaluate how the administration of different adjuvant therapies influences the risk for developing recurrences in the para-aortic area in endometrial cancer (EC) with positive pelvic and unknown para-aortic nodes. METHODS: We retrospectively evaluated the data of 58 patients with EC affected by stage IIIC1 who had undergone pelvic but not para-aortic lymphadenectomy from January 1, 1990 to December 31, 2011. Survival outcomes within the first 5 years after surgery were assessed using the Kaplan-Meier model. RESULTS: Chemotherapy plus radiotherapy, chemotherapy only, and external radiotherapy only were administered in 12 (23%), 18 (34%), and 23 (43%) patients, respectively. Five (9%) patients, who were selected to forego adjuvant therapy due to poor performance status, were excluded from the analysis. Disease-free and overall survivals assessed at 5 years were 54%, and 61%, respectively. All para-aortic recurrences were observed among the patients with endometrioid EC, whereas no cases of para-aortic recurrences were found in patients with nonendometrioid histology (5/36 (14%) vs 0/17 (0%); P = 0.16); the latter were more likely to develop distant (hematogenous, peritoneal, and distant lymphatic) recurrences (P = 0.09). Type of adjuvant therapy was the only factor influencing para-aortic failure: chemotherapy (± radiotherapy) reduced the rate of para-aortic node recurrence in comparison with pelvic radiotherapy as a sole modality (P = 0.01). However, adjuvant therapy did not influence the 5-year survival outcomes (P > 0.05). CONCLUSIONS: In the absence of local treatment (ie, para-aortic lymphadenectomy and radiotherapy), the administration of chemotherapy seems effective in reducing recurrences in the para-aortic area among patients with stage IIIC1 endometrioid EC.

Improving standard of care through introduction of laparoscopy for the surgical management of gynecological malignancies.

OBJECTIVE: This study aimed to evaluate the impact on perioperative and medium-term oncologic outcomes of the implementation of laparoscopy into a preexisting oncologic setting. METHODS: Data from consecutive 736 patients undergoing surgery for apparent early stage gynecological malignancies (endometrial, cervical, and adnexal cancers) between 2000 and 2011 were reviewed. Complications were graded per the Accordion classification. Survival outcomes within the first 5 years were analyzed using Kaplan-Meier method. RESULTS: Overall, 493 (67%), 162 (22%), and 81 (11%) had surgery for apparent early stage endometrial, cervical, and adnexal cancer. We assisted at an increase of the number of patients undergoing surgery via laparoscopy through the years (from 10% in the years 2000-2003 to 82% in years 2008-2011; P < 0.001 for trend); while the need to perform open surgery decreased dramatically (from 83% to 10%; P < 0.001). Vaginal approach was nearly stable over the years (from 7% to 8%; P = 0.76). A marked reduction in estimated blood loss, length of hospital stay, blood transfusions as well as grade greater than or equal to 3 postoperative complications over the years was observed (P < 0.001). Surgical radicality assessed lymph nodes count was not influenced by the introduction of laparoscopic approach (P > 0.05). The introduction of laparoscopy did not adversely affect medium-term (within 5 years) survival outcomes of patients undergoing surgery for apparent early stage cancers of the endometrium, uterine cervix, and adnexa (P > 0.05 log-rank test). CONCLUSIONS: The introduction of laparoscopy into a preexisting oncologic service allows an improvement of standard of care due to a gain in perioperative results, without detriments of medium-term oncologic outcomes.

Nerve-sparing approach reduces sexual dysfunction in patients undergoing laparoscopic radical hysterectomy.

INTRODUCTION: Although growing evidence suggests the beneficial effects of a nerve-sparing (NS) approach to surgery in cervical cancer patients, only limited data on NS laparoscopic radical hysterectomy (LRH) are available, and no studies have investigated the effects of NS-LRH on sexual function. AIM: This study aims to determine whether the implementation of NS-LRH impacts on sexual function in cervical cancer patients. METHODS: Sexually active cervical cancer patients undergoing type C (class III) LRH between 2004 and 2013 were enrolled in this prospective study. MAIN OUTCOME MEASURES: Preoperative and postoperative sexual function were assessed using a validated questionnaire, the Female Sexual Function Index (FSFI). The FSFI evaluates desire, arousal, lubrication, orgasm, satisfaction, and pain. RESULTS: Forty patients undergoing radical hysterectomy (20 conventional LRH vs. 20 NS-LRH) represented the study group. Baseline characteristics were similar between groups (P > 0.05). No differences in preoperative FSFI scores were recorded (P > 0.05). We observed that both LRH and NS-LRH worsened postoperative FSFI scores (P < 0.001). However, patients undergoing NS-LRH had higher postoperative FSFI scores than patients undergoing LRH (21.3 ± 9.4 vs. 14.2 ± 12.5; P = 0.04). Considering postoperative domain scores, we observed that desire, arousal, orgasm, and pain scores were similar between groups (P > 0.05), while patients undergoing NS-LRH experienced higher lubrication (3.4 ± 2.3 vs. 1.7 ± 2.2; P = 0.02) and satisfaction (4.6 ± 3.9 vs. 2.8 ± 2.2; P = 0.004) scores in comparison with patients undergoing conventional LRH. No between-group differences in survival outcomes were found. CONCLUSIONS: Both conventional LRH and NS-LRH impact negatively on patients' sexual function. However, the NS approach impairs sexual function less, minimizing the effects of radical surgery.

Predictors of postoperative morbidity after laparoscopic versus open radical hysterectomy plus external beam radiotherapy: a propensity-matched comparison.

BACKGROUND: Identification of peri-operative variables predicting postoperative morbidity may improve postoperative patients' care. We aimed to identify patients' characteristics and operative factors predictive of early (≤ 30-day) and late (≤ 6-month) morbidity in cervical cancer patients undergoing surgery plus external beam radiotherapy (EBRT). METHODS: We studied 45 propensity-matched patient pairs (90 patients) undergoing laparoscopic radical hysterectomy (LRH) plus EBRT vs. abdominal radical hysterectomy (RAH) plus EBRT. Basic descriptive, multivariable and artificial neuronal network analyses (ANN) were used to design predicting models influencing outcomes. RESULTS: Baseline characteristics of the study populations were similar. Patients undergoing LRH experienced lower blood loss (200 (range, 10-700) vs. 400 (range, 100-2000) ml; P < 0.001), shorter length of hospital stay (4 (range, 1-10) vs. 8 (range, 5-52) days; P < 0.001) and similar operative time (235 (± 67.3) vs. 258 (± 70.2) min; P = 0.14) than patients undergoing RAH. We observed that, at multivariate analysis, open approach correlated with overall (OR: 1.2; 95%CI: 1.03-1.46), early (OR: 1.14; 95%CI:0.99-1.3) and late (OR: 1.13; 95%CI: 1.001-1.28) postoperative complications. CONCLUSIONS: Open approach is the main predictor for developing morbidity among cervical cancer patients undergoing radical hysterectomy followed by adjuvant radiotherapy. Laparoscopic surgery enhances peri-operative surgical results and minimizes the occurrence of late complications.

Laparoscopic and open abdominal staging for early-stage ovarian cancer: our experience, systematic review, and meta-analysis of comparative studies.

OBJECTIVES: The aim of this study was to analyze perioperative and long-term survival outcomes after either laparoscopic or open abdominal staging for apparent early-stage ovarian cancer. METHODS: Data of consecutive women with early-stage ovarian cancer undergoing comprehensive laparoscopic staging between 2003 and 2010 were matched with a historical cohort of patients undergoing open surgery. Five-year survival outcomes were analyzed using the Kaplan-Meier method. In addition, a systematic review of the literature and meta-analysis of comparative studies was performed RESULTS: A total of 35 women undergoing staging via laparoscopy were compared with a cohort of 32 patients undergoing open surgery. Baseline characteristics were similar between groups. Spillage occurred in 6 and 4 patients in laparoscopic and open group, respectively (P = 0.59). Patients undergoing laparoscopy experienced longer operative time (P < 0.001), shorter hospital stay (P = 0.03), and lower postoperative complication rate (3% vs 28%; P = 0.005) than patients undergoing staging via open surgery. The median (range) follow-up period was 64 (37-106) and 100 (61-278) months for case and control, respectively (P < 0.001). Five-year disease-free survival (P = 0.12, log-rank test) and overall survival (P = 0.26, log-rank test) were not influenced by surgical approach. Pooled analyses of the literature results corroborate our results suggesting an improvement of perioperative results in the laparoscopic group in comparison with the open abdominal one. In comparison with open surgery, laparoscopy did not influenced spillage (odds ratio [OR], 0.78; 95% confidence interval [CI], 0.35-1.73) and upstaging rate (OR, 0.7; 95% CI, 0.38-1.27). No between-group differences in survival were observed (OR, 0.5; 95% CI, 0.21-1.21). CONCLUSIONS: Laparoscopy upholds open surgery in long-term oncologic control, reducing morbidity.

Fetal megacystis: experience of a single tertiary center in Switzerland over 20 years.

OBJECTIVES: Megacystis (MC) is rare and often associated with other structural and chromosomal anomalies. In euploid cases with early oligohydramnios, prognosis is poor mainly due to pulmonary hypoplasia and renal damage. We report our experience of the past 20 years. METHODS: A retrospective review of cases with prenatally diagnosed MC was performed. Complete prenatal as well as postnatal medical records from 1989 to 2009 were reviewed focusing on diagnostic precision, fetal interventions [vesicocentesis (VC), vesicoamniotic shunt (VAS)], short- and long-term outcome, and potential prognostic factors. RESULTS: 68 cases were included. Follow-up was available in 54 cases (9 girls and 45 boys including 3 cases with aneuploidy). We found 39 isolated MC at sonography (5 girls and 34 boys). 24 fetuses with isolated MC underwent VC and VAS at 19.6 ± 6.3 and 20 ± 4.9 weeks of gestation, respectively. Survival rate was higher in male than in female fetuses (51 vs. 33%). Renal problems occurred in 4/14 prenatally treated fetuses and in 1/10 when cases with prune belly syndrome (PBS) were excluded from the analysis. CONCLUSIONS: Our study shows that a careful selection of cases with MC excluding fetuses with PBS and early treatment has still the potential to improve outcome.

"Lights and Shades" of Fertility Preservation in Transgender Men Patients: A Clinical and Pathological Review.

Fertility preservation (FP) is becoming a critical issue in transgender men who desire biological offspring in the future. The prevalence of transgender individuals in the United States is increasing, and as a result, the demand for gender-affirming surgeries (GAS) and associated FP techniques is rising. Despite the growing demand, there is currently no personalized approach to FP for transgender men, and the available techniques have limitations that require further investigation. In the present review we carefully examine the existing literature on this topic to highlight the shortcomings of current methods and areas where additional research is needed to advance the field. Hormonal therapy (HT), which is an integral part of gender transition in transgender men, can have a significant impact on fertility and may increase the risk of various diseases. Moreover, GAS usually leads to permanent sterility in these patients. Therefore, it is essential to provide patients with accurate information about the benefits and potential risks of different FP techniques, taking into account the patient's reproductive goals. This review underscores the complex and multifaceted nature of FP in transgender men and emphasizes the need for further research to develop more effective and personalized approaches to FP for this population.

Intrapartum ultrasound and mother acceptance: A study with informed consent and questionnaire.

Introduction: Intrapartum ultrasound (IU) is used in the delivery ward; even if IU monitors the labouring women, it could be perceived as a discomfort and even as an" obstetric violence", because it is a young technique, not often well "accepted". A group of clinicians aimed at obtain an informed consent from patients, prior to perform a translabial ultrasound (TU). The aim of this study was to evaluate the acceptance of both translabial and transabdominal IU. Methods: In this study, performed at the University Hospital of Bari (Unit of Obstetrics and Gynecology), were enrolled 103 patients in the first or second stage of labor in singleton cephalic presentation. A statistical frequency and an association analysis were performed. As a significant result, we consider the peace of mind/satisfaction and the" obstetric violence". IU was performed both transabdominal and translabial to determine the presentation, head positions, angle of progression and head perineum distance. During the first and second stage of labor, the ASIUG questionnaires (Apulia study intrapartum ultrasonography group) were administered. Results: 74 (71, 84%) patients underwent IU and 29 had a vaginal examination (28, 15%). Significant less "violence" has been experienced with a IU (73 out 74/98, 65%) and only one person (1 /1, 35%) recorded that. On the contrary, 10 patients (10/29) perceived that "violence" (34, 48%) while 19 (65, 52%) did not respond on a similar way, after a vaginal examination (VE). More patients felt satisfaction (71 out 74/95, 95%) with the use of IU and only 3 (3/4, 05%) felt unease. A different picture was evident in the vaginal examination group. Only 17 patients (17 out 29/58, 62%) felt comfort while 12 (41, 38%) felt unease. Conclusions: In our study, IU use is well accepted by most of patients, because it could reassure women about their fetal condition. Moreover, they can see the fetus on the screen, while the obstetrician is performing the US and this is important for a visual feedback, in comparison with the classical VE.

Cornual Pregnancy.

Cornual pregnancy (CP) is a subtype of ectopic pregnancy that is implanted in the interstitial segment of the fallopian tube which is defined as the tubal section crossing uterine muscular tissue. Widely recognized risk factors for CP are endometriosis, uterine leiomyomata, or pelvic inflammatory disease; all these diseases can cause tubal anatomic changes and consequently alter embryo physiological implant process. Many treatment options are available for this condition each one must be tailored according to patient and operating scenario. The incidence of uterine ruptures in the scarred uterus appears to be low, but the fear of it remains and therefore medical treatment might be favored over cornual wedge resection. The actual risk of uterine rupture after medical treatment is unknown. Multiple testing strategies exist to diagnose CP, but caution needs to be used to avoid a false diagnosis.

The Effect of Menopause Hypoestrogenism on Osteogenic Differentiation of Periodontal Ligament Cells (PDLC) and Stem Cells (PDLCs): A Systematic Review.

(1) Background: Menopause is a physiological condition typified by drastic hormonal changes, and the effects of this transition have long-term significant clinical implications on the general health, including symptoms or physical changes. In menopausal women, the periodontium can be affected directly or through neural mechanism by oestrogen (E2) deficiency. The majority of the biological effects of E2 are modulated via both oestrogen receptor-α (ERα) and oestrogen receptor- ß (ERß). There is evidence that hypoestrogenism has a substantial impact on the aetiology, manifestation and severity of periodontitis, via the regulation of the expression of osteoprogesterin and RANKL in human periodontal ligament cells through ERß. However, the mechanistic understanding of oestrogen in periodontal status has been partially clarified. The aim of this paper was to synopsize the recent scientific evidence concerning the link between the menopause and periodontitis, through the investigation of physio-pathological impact of the oestrogen deficiency on osteogenic differentiation of PDLSCs and PDLSC, as well as the dynamic change of ERα and ERß. (2) Methods: Search was conducted for significant studies by exploring electronic PubMed and EMBASE databases, and it was independently performed by two researchers. All studies on the impact of oestrogen level on alveolar bone resorption were searched from 2005 to July 2020. Data selection was in concordance with PRISMA guidelines. (3) Results: Eight studies met the criteria and were included in this systematic review. All studies reported that oestrogen deficiency impairs the osteogenic and osteoblastic differentiation of PDL cells and oestrogen affects the bone formation capacity of cells. Seven studies were conducted on animal samples, divided into two groups: the OVX animals and animals who received the sham operation. (4) Conclusions: There is a multitude of data available showing the influence of menopause on periodontal status. However, the evidence of this line to investigation needs more research and could help explain the physiological linkage between menopause state and periodontal disease.

Hormone therapy in female-to-male transgender patients: searching for a lifelong balance.

BACKGROUND: Reassignment of a female-to-male (FtM) person requires gender-affirming, androgenic hormonal treatment that is planned to induce appropriate structural changes. This therapy must be prolonged long term, even after the sex reassignment surgery (SRS). The purpose of this study is to evaluate the effects of hormone therapy with testosterone in FtM subjects during a 24-month follow-up in order to highlight the occasional need for early decompensation and to make adequate hormone therapy modulations. METHODS: Fifteen out of 23 FtM persons had been previously treated with SRS, while eight were still awaiting surgery. During hormone therapy, both groups were followed for 24 months, with evaluation of desired changes, adverse effects, and functional or metabolic indicators. RESULTS: In the group of operated FtM subjects (15/23), a significant increase of total testosterone (total T) and free testosterone (free T) was found after 24 months. Luteinizing hormone (LH) maintained a low level, decreasing after ovariectomy, while FSH increased. Voice deepening, facial and body hair variation, male-pattern balding, and body mass index (BMI) increase are all physical changes due to androgenization. In both groups of patients who have been closely monitored, the side effects and thromboembolic, metabolic, and cardiovascular risks of androgen therapy, even in the long term, appear to be irrelevant. CONCLUSION: Total T, free T, and LH dosages are shown to be reliable markers of correct androgenization. Strict monitoring of lipid profile, evaluation of BMI and hematocrit, avoidance of self-initiated therapeutic modifications, adherence to a healthy lifestyle, and avoidance of excessive daily calorie intake can limit risks linked to long-term testosterone administration. TRIAL REGISTRATION: Retrospectively registered.

Pregnancy Complications, Correlation With Placental Pathology and Neonatal Outcomes.

Purpose: We aimed to clarify and contribute to a better comprehension of associations and correlations between placental histological findings, pregnancy evolution, and neonatal outcomes. Study Design: This is a longitudinal and prospective observational study, performed between May 2015 and May 2019, on 506 pregnant women. Clinical data related to pregnancy outcome, neonatal health status, and placental histology were primarily collected. Twin pregnancies or malformed newborns were excluded and therefore the study was conducted on 439 cases. These cases have been then subdivided into the following study groups: (a) 282 placentas from pathological pregnancies; and, (b) a control group of 157 pregnancies over 33 weeks of gestational age, defined as physiological or normal pregnancies due to the absence of maternal, fetal, and early neonatal pathologies, most of which had undergone elective cesarean section for maternal or fetal indication. Results: A normal placenta was present in 57.5% of normal pregnancies and in 42.5% of pathological pregnancies. In contrast, placental pathology was present in 26.2% of normal pregnancies and 73.8% of pathological pregnancies. Comparison of the neonatal health status with the pregnancy outcome showed that, among the 191 newborns classified as normal, 98 (51.3%) were born from a normal pregnancy, while 93 (48.7%) were born from mothers with a pathological pregnancy. Among the 248 pathological infants, 59 (23.8%) were born from a mother with a normal pregnancy, while 189 (76.2%) were born from pregnancies defined as pathological. Conclusion: Placental histology must be better understood in the context of natural history of disease. Retrospective awareness of placental damage is useful in prevention in successive pregnancy, but their early identification in the evolving pregnancy could help in association with biological markers or more sophisticated instruments for early diagnosis.

Myocardial dysfunction in fetuses exposed to intraamniotic infection: new insights from tissue Doppler and strain imaging.

OBJECTIVE: The purpose of this study was to assess myocardial function of fetuses who were exposed to intraamniotic infection compared with fetuses of uncomplicated pregnancies by the application of tissue Doppler and strain rate (SR) imaging. STUDY DESIGN: We evaluated the right ventricular function of fetuses with preterm premature rupture of membranes and proven intraamniotic infection (n = 12 fetuses) and healthy fetuses (n = 27). Tissue Doppler velocities during early diastolic relaxation (E(m)) and atrial contraction (A(m)) and early diastolic SR were measured as indices of diastolic function, whereas the peak systolic strain and SR were used as parameters of systolic function. RESULTS: Fetuses with intraamniotic infection exhibit impairment in both diastolic and systolic performance, which was characterized by increased diastolic compliance (increased E(m)/A(m) ratio, increased early diastolic SR compared with the control fetuses), decreased systolic contractile function (reduced systolic strain and SR), and longitudinal myocardial dyskinesia. CONCLUSION: New echocardiographic tools suggest that fetal heart is a target organ in the context of intraamniotic infection.

p38alpha is required for ovarian cancer cell metabolism and survival.

INTRODUCTION: Ovarian cancer is highly sensitive to chemotherapy but also shows a high rate of recurrence and drug resistance. These negative outcomes mostly depend on altered apoptotic pathways, making the design of new therapeutic strategies based on the induction of other types of cell death highly desirable. Several lines of research are now addressing cancer-specific features to specifically target tumor cells, thus reducing adverse effects. In this light, a great deal of attention has been devoted to the metabolic reprogramming occurring in cancer cells, which display increased levels of glycolysis compared with their normal counterparts. We recently showed that inhibition of p38alpha impairs key metabolic functions of colorectal cancer cells, inducing growth arrest, autophagy, and cell death both in vivo and in vitro. These effects are mediated by a switch from hypoxia-inducible factor 1alpha (HIF1alpha) to forkhead transcription factor O (FoxO)-dependent transcription. METHODS: We first characterized p38 expression in OVCAR-3, A2780, and SKOV-3 ovarian cancer cell lines. Then, we treated these cells with the p38alpha/p38beta-specific inhibitor SB202190 and performed a morphological, proliferation, and survival analyses. Finally, we studied HIF1alpha and FoxO3A expressions and signaling pathways to evaluate their role in SB202190-induced effects. RESULTS: p38alpha blockade induces the formation of intracellular autophagic vacuoles and reduces growth and viability of ovarian cancer cells. As in colorectal cancer, the underlying molecular mechanism seems to rely on a shift from HIF1alpha- to FoxO3A-dependent transcription, which is promoted by the activation of the adenosine monophosphate-activated protein kinase pathway. CONCLUSIONS: These data corroborate the hypothesis that pharmacological modulation of genes involved in cancer-specific homeostasis, such as p38alpha, might be exploited to design new therapeutic approaches to cancer treatment.