Erratum: Momentum-Resolved Observation of Thermal and Quantum Depletion in a Bose Gas [Phys. Rev. Lett. 117, 235303 (2016)].

This corrects the article DOI: 10.1103/PhysRevLett.117.235303.

[Reproducibility evaluation of air-charged catheter for rest urethral pressure profilometry].

We retrospectively included 53 (9 males, 44 females) patients who underwent rest urethral pressure profilometry (RUPP) due to lower urinary tract symptoms (LUTS) in Beijing Chaoyang Hospital from May 2021 to March 2022. The age of patients was (55±16) (25-76) years old. The clinical diagnoses of the included patients with lower urinary tract symptoms were classified as: benign prostatic hyperplasia in 9 cases, interstitial cystitis in 1 case, stress urinary incontinence in 11 cases and non-obstructive dysuria in 32 cases. The full set of urodynamic examination was composed of bladder pressure measurement during the filling period, pressure flow study (PFS) and RUPP. All the urodynamic examination was performed by air-charged catheter (ACC) and corresponding equipment. All patients underwent RUPP measurements twice. The vesical pressure (Pves) values were (35.30±6.15), (35.81±5.91) cmH2O (1 cmH2O=0.098 kPa); the Pura@max were (141.91±36.53), (145.02±38.85) cmH2O; functional urethral length were (41.70±16.34), (42.55±16.40) mm; the maximum urethral closure pressure for the two RUPP measurements were (106.57±36.44), (109.41±39.27) cmH2O. There was no statistical difference between the two RUPP measurements (P>0.05). The reproducibility of the RUPP measurements obtained by ACC is good and deserves further study.

[Safety and feasibility of robotic-assisted thoracoscopic day surgery for pulmonary nodules: a retrospective analysis based on propensity score matching].

Objective: To evaluate the safety and feasibility of robotic-assisted thoracoscopic day surgery for pulmonary nodules. Methods: Clinical data of 523 patients with pulmonary nodule underwent robotic-assisted thoracoscopic surgery in the Department of Thoracic Surgery, Xiangya Hospital, Central South University from January 2021 to June 2022 were retrospectively analyzed, which including 223 males and 300 females, aged from 19 to 72 (54.0±11.7) years. Those patients were divided into the day surgery group (DSG) and inpatient surgery group (ISG) according to perioperative management methods. Propensity score matching (PSM) (1∶2) was performed according to the general baseline information, T stage of the tumor, surgery approach, and tumor position, and a total of 178 patients were finally included. Clinical outcomes of DSG were observed. The differences in incidence of postoperative complications, treatment-related costs and resource consumption between DSG and ISG were compared. Subgroup analysis was performed according to surgery method to evaluate the difference between DSG and ISG in lobectomy and sublobectomy. Results: In 81 cases DSG, eight patients were transferred to thoracic surgery ward, and the day surgery discharge rate was 90% (73/81). There was no statistically significant difference in incidence of postoperative complications between DSG and ISG (P=0.612). The length of stay after surgery, period of chest draining, average hospital cost, and drug cost of DSG were statistically significant lower than ISG, ((2.19±0.84) vs (4.74±1.81) days, (1.70±0.65) vs (3.45±1.85) days, (6.64±0.74) vs (8.29±0.97)×104 CNY, (0.35±0.07) vs (0.69±0.18)×104 CNY), respectively(all P<0.05). The drainage volume and VAS score at discharge in DSG and ISG group were(220.47±120.02) ml and(242.21±129.96) ml, 1.68±0.79 and 1.64±0.91, respectively, with no statistically significant difference (P>0.05). In subgroup analysis, there was no statistically significant difference in incidence of postoperative complications, drainage volume after surgery and VAS score at discharge between DSG and ISG both for lobectomy and sublobectomy patients. And the results of the length of stay after surgery, period of chest draining, and drug cost in DSG were also significantly lower than ISG (P<0.05). Conclusions: Robotic-assisted thoracoscopic day surgery for pulmonary nodule is safe and feasible, with the advantage of short length of stay after surgery, short period of chest draining, less average hospital cost and drug cost. There is no difference in incidence of postoperative complications between DSG and ISG.

First-line treatment and overall survival in EGFR mutation-positive advanced non-small cell lung cancer: a national cohort study.

OBJECTIVE: Non-squamous non-small cell lung cancer (NSCLC) is the first leading cause of cancer-related deaths in Taiwan. This study aimed at evaluating the effectiveness of first-line targeted therapy for advanced epidermal growth factor receptor (EGFR) mutation-positive non-squamous NSCLC in Taiwan. PATIENTS AND METHODS: This was a real-world, retrospective, observational study of patients diagnosed with advanced non-squamous NSCLC (N=63,248). Between 2011 and 2019, 19,458 patients received targeted therapy and 22,994 patients received chemotherapy alone; between 2002 and 2010, 20,796 patients received chemotherapy alone. Overall survival (OS) was determined. RESULTS: The median OS for patients treated with first-line targeted therapy (22.9 months) was longer than that of patients receiving chemotherapy alone (11.7 months). HR: 0.521, log-rank test, p<0.001. CONCLUSIONS: These data represent the potential survival outcomes of Taiwanese patients with advanced EGFR mutation-positive non-squamous NSCLC in clinical practice.

Ovarian response to follicle-stimulating hormone in women with polycystic ovary syndrome is diminished compared to ovulatory controls.

OBJECTIVE: The mechanisms underlying ovarian dysfunction in polycystic ovary syndrome (PCOS) have not been definitively established. Our objective was to perform a detailed examination of ovarian responses to recombinant follicle-stimulating hormone (rFSH) in women with PCOS and controls. DESIGN: This prospective, crossover, dose-response study included three rFSH stimulation periods. Each stimulation period involved three consecutive, daily, subcutaneous injections of rFSH administered at a single dose. Low, medium and high rFSH doses were weight-adjusted, corresponding to 0.5, 1.1 and 2.2 IU/kg/d, respectively. Stimulation periods occurred in randomized order and were separated by 8-week washouts. PATIENTS: Thirty participants (8 PCOS and 22 controls) were studied. PCOS was defined by oligomenorrhea and clinical or biochemical androgen excess, excluding other aetiologies of ovulatory dysfunction. MEASUREMENTS: Blood samples were obtained for hormone measurements before and 24 h after each rFSH injection. RESULTS: Participants with PCOS had significantly greater body mass index, antral follicle count and circulating testosterone, anti-mullerian hormone (AMH) and luteinizing hormone concentrations compared with controls participants. Baseline estradiol (E2) concentrations were similar in both groups. At the lowest dose of rFSH, PCOS participants did not demonstrate E2 increments, whereas a significant increase occurred in controls. rFSH-induced E2 production per follicle was significantly reduced in PCOS participants compared with controls at all rFSH doses. Increasing T and decreasing AMH concentrations were associated with augmented E2 production per follicle. COONCLUSIONS: Women with PCOS exhibited diminished initial E2 responses to rFSH compared with controls. These findings suggest that the mechanism of anovulation in PCOS may involve altered ovarian response to gonadotropins.

Effect of the spatial-temporal specific theca cell Cyp17 overexpression on the reproductive phenotype of the novel TC17 mouse.

BACKGROUND: In the ovarian follicle, the Theca Cells (TCs) have two main functions: preserving morphological integrity and, importantly, secreting steroid androgen hormones. TCs express the essential enzyme 17α-hydroxylase/17,20-desmolase (CYP17), which permits the conversion of pregnenolone and progesterone into androgens. Dysregulation of CYP17 enzyme activity due to an intrinsic ovarian defect is hypothesized to be a cause of hyperandrogenism in women. Androgen excess is observed in women with polycystic ovary syndrome (PCOS) resulting from excess endogenous androgen production, and in transgender males undergoing exogenous testosterone therapy after female sex assignment at birth. However, the molecular and morphological effects of Cyp17 overexpression and androgen excess on folliculogenesis is unknown. METHODS: In this work, seeking a comprehensive profiling of the local outcomes of the androgen excess in the ovary, we generated a transgenic mouse model (TC17) with doxycycline (Dox)-induced Cyp17 overexpression in a local and temporal manner. TC17 mice were obtained by a combination of the Tet-dependent expression system and the Cre/LoxP gene control system. RESULTS: Ovaries of Dox-treated TC17 mice overexpressed Cyp17 specifically in TCs, inducing high testosterone levels. Surprisingly, TC17 ovarian morphology resembled the human ovarian features of testosterone-treated transgender men (partially impaired folliculogenesis, hypertrophic or luteinized stromal cells, atretic follicles, and collapsed clusters). We additionally assessed TC17 fertility denoting a perturbation of the normal reproductive functions (e.g., low pregnancy rate and numbers of pups per litter). Finally, RNAseq analysis permitted us to identify dysregulated genes (Lhcgr, Fshr, Runx1) and pathways (Extra Cellular Matrix and Steroid Synthesis). CONCLUSIONS: Our novel mouse model is a versatile tool to provide innovative insights into study the effects of Cyp17 overexpression and hyperandrogenism in the ovary.

Elevation of markers of endotoxemia in women with polycystic ovary syndrome.

STUDY QUESTION: Is polycystic ovary syndrome (PCOS) associated with an elevation of markers of endotoxemia? SUMMARY ANSWER: In women with PCOS serum levels of lipopolysaccharides (LPS), the LPS to high-density lipoprotein (HDL) ratio and LPS-binding protein (LBP) are significantly greater than those of normal control subjects. WHAT IS KNOWN ALREADY: Mononuclear cells from women with PCOS respond excessively to LPS by releasing pro-inflammatory cytokines. In rat ovarian theca-interstitial cell cultures LPS stimulates androgen production. STUDY DESIGN, SIZE, DURATION: Cross-sectional study comparing markers of endotoxemia in women with PCOS (n = 62), healthy ovulatory women with polycystic ovary morphology (PCOM, n = 39) and a control group of healthy ovulatory women without PCOM [normal (NL), n = 43]. PARTICIPANTS/MATERIALS, SETTING, METHODS: LPS was measured using a chromogenic assay. LBP was measured by ELISA. Total cholesterol and lipids were measured using a homogeneous enzyme colorimetric method. Androgens, gonadotrophins, prolactin, insulin, high-sensitivity C-reactive protein (hs-CRP) and sex hormone-binding globulin were determined by electrochemiluminescence assays. Glucose was measured using an enzymatic reference method with hexokinase. MAIN RESULTS AND THE ROLE OF CHANCE: Women with PCOS, when compared with NL subjects, had a significantly higher mean LPS (P = 0.045), LPS/HDL ratio (P = 0.007) and LBP (P = 0.01). Women with PCOM had intermediate levels of markers of endotoxemia. Comparison among all groups revealed that markers of endotoxemia correlated positively with testosterone level, ovarian volume, number of antral follicles and hirsutism score, but negatively with the number of spontaneous menses per year. In multiple regression analysis, all measures of endotoxemia correlated independently and positively with hs-CRP and with ovarian volume. LIMITATIONS, REASONS FOR CAUTION: This cross-sectional study reveals that markers of endotoxemia are associated with several clinical features observed in women with PCOS. However, responsible mechanisms and causation remain unknown. Steroid quantification was carried out by electrochemiluminescence assays and not by the current gold standard: liquid chromatography-mass spectrometry. Hence, the relationship of endotoxemia with features of PCOS and the extent to which endotoxemia contributes to reproductive and metabolic dysfunction warrants further investigation. WIDER IMPLICATIONS OF THE FINDINGS: This study reveals the novel observation that markers of endotoxemia are elevated in young and otherwise healthy women with PCOS without significant metabolic dysfunction. Moreover, the association of clinical and endocrine markers of PCOS with those of endotoxemia may represent a pathophysiologic link to reproductive dysfunction as well as metabolic and long-term cardiovascular risks associated with this disorder. STUDY FUNDING/COMPETING INTEREST(S): Intramural funding from Poznan University of Medical Sciences. The authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

Androgens Modulate Rat Granulosa Cell Steroidogenesis.

Paracrine interactions between ovarian theca-interstitial cells (TICs) and granulosa cells (GCs) play an important role in the regulation of follicular steroidogenesis. Androgens serve as substrates for aromatization as well as affect GC function. This study evaluated the effects of co-culture of GC with TICs and the role of testosterone (T) and 5-alpha-dihydrotestosterone (DHT), and estradiol (E2) in modulation of GC expression of genes involved in the production of progesterone: 3ß-hydroxysteroid dehydrogenase/Δ5-4 isomerase (Hsd3b) and cholesterol side-chain cleavage (Cyp11). GCs obtained from immature Sprague-Dawley rats and were cultured in chemically defined media without or with TICs, DHT, or T. Hsd3b and Cyp11 transcripts were analyzed by qt-PCR. Co-culture of GCs with TICs stimulated Hsd3b and CYP11 expression in GCs. DHT and T induced a concentration-dependent upregulation of Hsd3b and CYP11 expression, as well as increased progesterone concentrations in spent media. E2 also increased expression of Hsd3b, and Cyp11. Effects of androgens were abrogated in the presence of an anti-androgen bicalutamide and the antiestrogen ICI 182780 (ICI). In conclusion, present findings demonstrate that androgens upregulate production of progesterone in GCs; these effects are likely due to a combination of direct action on androgen receptors and effects mediated by estrogen receptors.

Inflammatory Stimuli Trigger Increased Androgen Production and Shifts in Gene Expression in Theca-Interstitial Cells.

Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disorder characterized by theca cell hyperplasia and excessive androgen production. An increasing body of evidence has pointed to a close association between PCOS and low-grade chronic systemic inflammation. However, the mechanistic basis for this linkage is unknown. Therefore, we evaluated the effects of the inflammatory agents lipopolysaccharide (LPS) and IL-1ß on rat theca-interstitial cells (TICs). We found that incubation with either LPS or IL-1ß elicited a dose-dependent increase in both TIC viability and androgen production. Using RNA sequencing analysis, we found that both of these inflammatory agents also triggered profound and widespread shifts in gene expression. Using a stringent statistical cutoff, LPS and IL-1ß elicited differential expression of 5201 and 5953 genes, respectively. Among the genes upregulated by both LPS and IL-1ß were key regulatory genes involved in the cholesterol and androgen biosynthesis pathways, including Cyp17a1, Cyp11a1, Hsd3b, and Hmgcr. This provides a molecular explanation for the mechanism of action of inflammatory agents leading to increased androgen production. Gene ontology and pathway analysis revealed that both LPS and IL-1ß regulated genes highly enriched for many common functions, including the immune response and apoptosis. However, a large number of genes (n = 2222) were also uniquely regulated by LPS and IL-1ß, indicating that these inflammatory mediators have substantial differences in their mechanism of action. Together, these findings highlight the potential molecular mechanisms through which chronic low-grade inflammation contributes to the pathogenesis of androgen excess in PCOS.

The National Physicians Cooperative: transforming fertility management in the cancer setting and beyond.

Once unimaginable, fertility management is now a nationally established part of cancer care in institutions, from academic centers to community hospitals to private practices. Over the last two decades, advances in medicine and reproductive science have made it possible for men, women and children to be connected with an oncofertility specialist or offered fertility preservation soon after a cancer diagnosis. The Oncofertility Consortium's National Physicians Cooperative is a large-scale effort to engage physicians across disciplines - oncology, urology, obstetrics and gynecology, reproductive endocrinology, and behavioral health - in clinical and research activities to enable significant progress in providing fertility preservation options to children and adults. Here, we review the structure and function of the National Physicians Cooperative and identify next steps.

Simultaneous Bipedicular Radiofrequency Ablation Combined with Vertebral Augmentation for Local Tumor Control of Spinal Metastases.

BACKGROUND AND PURPOSE: Percutaneous radiofrequency ablation combined with vertebral augmentation has emerged as a minimally invasive treatment for patients with vertebral metastases who do not respond to or have contraindications to radiation therapy. The prevalence of posterior vertebral body metastases presents access and treatment challenges in the unique anatomy of the spine. The purpose of this study was to evaluate the safety and efficacy of simultaneous bipedicular radiofrequency ablation using articulating bipolar electrodes combined with vertebral augmentation for local tumor control of spinal metastases. MATERIALS AND METHODS: Imaging-guided simultaneous bipedicular radiofrequency ablation combined with vertebral augmentation was performed in 27 patients (33 tumors) with vertebral metastases selected following multidisciplinary consultations, to achieve local tumor control in this retrospective study. Tumor characteristics, procedural details, and complications were documented. Pre- and postprocedural cross-sectional imaging was evaluated to assess local tumor control rates. RESULTS: Thirty-three tumors were successfully ablated in 27 patients. Posterior vertebral body or pedicle involvement or both were present in 94% (31/33) of cases. Sixty-seven percent (22/33) of the tumors involved ≥75% of the vertebral body volume. Posttreatment imaging was available for 79% (26/33) of the treated tumors. Local tumor control was achieved in 96% (25/26) of tumors median imaging follow up of 16 weeks. No complications were reported, and no patients had clinical evidence of metastatic spinal cord compression at the treated levels. CONCLUSIONS: Simultaneous bipedicular radiofrequency ablation combined with vertebral augmentation is safe and effective for local tumor control of vertebral metastases. Articulating bipolar electrodes enable the placement and proximity necessary for optimal confluence of the ablation zones. Local tumor control may lead to more durable pain palliation, prevent disease progression, and reduce skeletal-related events of the spine.

[Effect of interleukin-7 on the anti-tumor function of CD8(+) T cells in patients with non-small cell lung cancer].

Objective: To investigate the effect of interleukin (IL)-7 on anti-tumor activity of CD8(+) T cells in non-small cell lung cancer (NSCLC) patients. Methods: Twenty-seven NSCLC patients and ten healthy controls were included from Zhengzhou Central Hospital between January 2017 and July 2017. Plasma, peripheral blood mononuclear cells (PBMCs), and bronchial alveolar lavage fluid (BALF) (both tumor site and non-tumor site) were collect from NSCLC patients, while plasma and PBMCs were also collected from healthy controls. IL-7 level and IL-7 receptor α (CD127) mRNA relative expression was measured. Purified CD8(+) T cells and primary NSCLC cells were stimulated with recombinant IL-7. Cellular proliferation, cytokines secretion, and protein expression in IL-7 signaling pathway were investigated. Direct/indirect contact coculture system of CD8(+) T cells and primary NSCLC cells was also used to assess the cytolytic and noncytolytic activity after IL-7 stimulation. Results: Plasma IL-7 level was significantly reduced in NSCLC patients compared with normal controls[1 731 (1 364, 2 536) vs 2 686 (1 692, 4 786) ng/L, P=0.023). IL-7 level in BALF isolated from tumor site was also remarkably down-regulated compared with non-tumor site in NSCLC patients[1 045 (562, 1 550) vs 1 599 (1 166, 2 107) ng/L, P=0.006 9). There was no statistical difference of CD127 mRNA between the two groups. Recombinant IL-7 stimulation did not affect cellular proliferation and cytokines production in primary NSCLC cells, however, remarkably increased cellular proliferation, interferon (IFN)-γ/tumor necrosis factor (TNF)-α secretion, and signal transducers and activators of transcription 5 (STAT5) phosphorylation and suppressor of cytokine signaling 3 (SOCS3) expression of CD8(+) T cells from NSCLC patients. IL-7 stimulation also significantly enhanced the cytolytic and noncytolytic function of CD8(+) T cells on primary NSCLC cells. Conclusion: IL-7 enhances anti-tumor activity of CD8(+) T cells in NSCLC patients.

Delayed enhancement of the peritumoural cortex in clear cell renal cell carcinoma: correlation with Fuhrman grade.

AIM: To assess the delayed enhancement of the peritumoural cortex (DEC) sign in clear cell renal cell carcinoma (ccRCC), and investigate a possible correlation among DEC and Fuhrman grade. MATERIALS AND METHODS: This retrospective study included 506 patients with 511 histopathologically proven ccRCCs evaluated by computed tomography (CT) angiography. DEC was detected and compared in groups divided by Fuhrman grades (low grade: 1 and 2, high grade: 3 and 4) using univariate and multivariate analyses. RESULTS: DEC was detected in 89 of 511 (17.4%) ccRCCs (grade 1: 5.7%, 2/35; grade 2: 16.2%, 70/433; grade 3: 31.4%, 11/35; grade 4: 75%, 6/8; p<0.001). The incidence was higher in high-grade ccRCCs (39.5%, 17/43) than in low-grade ccRCCs (15.4%, 72/468; p<0.001). In multivariate analysis, tumour size >5.4 cm (p<0.001, odds ratio [OR]=3.57, 95% confidence interval [CI]: 1.76-7.23) and detection of DEC (p=0.021, OR=2.33, 95% CI: 1.13-4.80) were independent predictors of high-grade ccRCC. For all ccRCCs, the area under the receiver operating characteristic (ROC) curve (AUC) of DEC in predicting high-grade ccRCC was 0.62 (95% CI: 0.53-0.72) with 39.5% sensitivity and 84.6% specificity, while for ccRCCs of >5.4 cm diameter, the AUC was 0.66 (95% CI: 0.52-0.80) with 68.4% sensitivity and 62.7% specificity. CONCLUSIONS: The DEC sign may predict aggressive biological behaviour of ccRCC, irrespective of tumour size.

Evaluation and Treatment of Hirsutism in Premenopausal Women: An Endocrine Society Clinical Practice Guideline.

Objective: To update the "Evaluation and Treatment of Hirsutism in Premenopausal Women: An Endocrine Society Clinical Practice Guideline," published by the Endocrine Society in 2008. Participants: The participants include an Endocrine Society-appointed task force of seven medical experts and a methodologist. Evidence: This evidence-based guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation system to describe the strength of recommendations and the quality of evidence. The task force commissioned two systematic reviews and used the best available evidence from other published systematic reviews and individual studies. Consensus Process: Group meetings, conference calls, and e-mail communications facilitated consensus development. Endocrine Society committees, members, and cosponsoring organizations reviewed and commented on preliminary drafts of the guidelines. Conclusion: We suggest testing for elevated androgen levels in all women with an abnormal hirsutism score. We suggest against testing for elevated androgen levels in eumenorrheic women with unwanted local hair growth (i.e., in the absence of an abnormal hirsutism score). For most women with patient-important hirsutism despite cosmetic measures (shaving, plucking, waxing), we suggest starting with pharmacological therapy and adding direct hair removal methods (electrolysis, photoepilation) for those who desire additional cosmetic benefit. For women with mild hirsutism and no evidence of an endocrine disorder, we suggest either pharmacological therapy or direct hair removal methods. For pharmacological therapy, we suggest oral combined estrogen-progestin contraceptives for the majority of women, adding an antiandrogen after 6 months if the response is suboptimal. We recommend against antiandrogen monotherapy unless adequate contraception is used. We suggest against using insulin-lowering drugs. For most women who choose hair removal therapy, we suggest laser/photoepilation.

Tumor-induced osteomalacia in association with PTEN-negative Cowden syndrome.

Tumor-induced osteomalacia (TIO) is a rare paraneoplastic condition in which phosphaturic mesenchymal tumors (PMTs) secrete high levels of fibroblast growth factor 23 (FGF23) into the circulation. This results in renal phosphate wasting, hypophosphatemia, muscle weakness, bone pain, and pathological fractures. Recent studies suggest that fibronectin-fibroblast growth factor receptor 1 (FN1-FGFR1) translocations may be a driver of tumorigenesis. We present a patient with TIO who also exhibited clinical findings suggestive of Cowden syndrome (CS), a rare autosomal dominant disorder characterized by numerous benign hamartomas, as well as an increased risk for multiple malignancies, such as thyroid cancer. While CS is a clinical diagnosis, most, but not all, harbor a mutation in the tumor suppressor gene PTEN. Genetic testing revealed a somatic FN1-FGFR1 translocation in the FGF23-producing tumor causing TIO; however, a germline PTEN mutation was not identified. To our knowledge, this is the first reported case of concurrent TIO and CS.

An International Consortium Update: Pathophysiology, Diagnosis, and Treatment of Polycystic Ovarian Syndrome in Adolescence.

This paper represents an international collaboration of paediatric endocrine and other societies (listed in the Appendix) under the International Consortium of Paediatric Endocrinology (ICPE) aiming to improve worldwide care of adolescent girls with polycystic ovary syndrome (PCOS)1. The manuscript examines pathophysiology and guidelines for the diagnosis and management of PCOS during adolescence. The complex pathophysiology of PCOS involves the interaction of genetic and epigenetic changes, primary ovarian abnormalities, neuroendocrine alterations, and endocrine and metabolic modifiers such as anti-Müllerian hormone, hyperinsulinemia, insulin resistance, adiposity, and adiponectin levels. Appropriate diagnosis of adolescent PCOS should include adequate and careful evaluation of symptoms, such as hirsutism, severe acne, and menstrual irregularities 2 years beyond menarche, and elevated androgen levels. Polycystic ovarian morphology on ultrasound without hyperandrogenism or menstrual irregularities should not be used to diagnose adolescent PCOS. Hyperinsulinemia, insulin resistance, and obesity may be present in adolescents with PCOS, but are not considered to be diagnostic criteria. Treatment of adolescent PCOS should include lifestyle intervention, local therapies, and medications. Insulin sensitizers like metformin and oral contraceptive pills provide short-term benefits on PCOS symptoms. There are limited data on anti-androgens and combined therapies showing additive/synergistic actions for adolescents. Reproductive aspects and transition should be taken into account when managing adolescents.

Activation of Endoplasmic Reticulum Stress in Granulosa Cells from Patients with Polycystic Ovary Syndrome Contributes to Ovarian Fibrosis.

Recent studies report the involvement of intra-ovarian factors, such as inflammation and oxidative stress, in the pathophysiology of polycystic ovary syndrome (PCOS), the most common endocrine disorder of reproductive age women. Endoplasmic reticulum (ER) stress is a local factor that affects various cellular events during a broad spectrum of physiological and pathological conditions. It may also be an important determinant of pro-fibrotic remodeling during tissue fibrosis. In the present study, we showed that ER stress was activated in granulosa cells of PCOS patients as well as in a well-established PCOS mouse model. Pharmacological inducers of ER stress, tunicamycin and thapsigargin, were found to increase the expression of pro-fibrotic growth factors, including transforming growth factor (TGF)-ß1, in human granulosa cells, and their expression also increased in granulosa cells of PCOS patients. By contrast, treatment of PCOS mice with an ER stress inhibitor, tauroursodeoxycholic acid or BGP-15, decreased interstitial fibrosis and collagen deposition in ovaries, accompanied by a reduction in TGF-ß1 expression in granulosa cells. These findings suggest that ER stress in granulosa cells of women with PCOS contributes to the induction of pro-fibrotic growth factors during ovarian fibrosis, and that ER stress may serve as a therapeutic target in PCOS.

The effect of estradiol on granulosa cell responses to FSH in women with polycystic ovary syndrome.

BACKGROUND: The influence of estradiol (E2) on granulosa cell (GC) function has not been tested clinically in women with polycystic ovary syndrome (PCOS). The objective of this study is to determine if E2 influences GC responses to FSH in women with PCOS. METHODS: This is a two phase, single cohort study conducted over a 2-year period at a single academic center. Nine women with PCOS according to NIH criteria. In Phase 1, FSH stimulation of GC responses as measured by E2 and Inhibin B (Inh B) were assessed before and at 5 and 6 weeks after GnRH agonist administration. In Phase 2, the same protocol was employed with the addition of an aromatase inhibitor (letrozole, LET) administered daily beginning at week 4 for 2 weeks. RESULTS: In Phase 1, recovery of FSH, E2 and Inh B from ovarian suppression occurred at 5 and 6 weeks after GnRH agonist injection and preceded resumption of LH and androgen secretion. In Phase 2, hormone recovery after GnRH agonist was characterized by elevated FSH and suppressed E2 levels whereas recovery of LH and androgen levels were unchanged. In Phase 1, FSH stimulated E2 and Inh B responses were unaltered during recovery from ovarian suppression. In Phase 2, E2 and Inh B fold changes after FSH were significantly reduced at weeks 5 (p < 0.04) and 6 (p < 0.01), respectively. CONCLUSION: In anovulatory women with PCOS, chronic, unopposed E2 secretion may contribute, at least in part, to enhanced ovarian responsiveness to FSH. TRIAL REGISTRATION: NCT02389088.

Momentum-Resolved Observation of Thermal and Quantum Depletion in a Bose Gas.

We report on the single-atom-resolved measurement of the distribution of momenta ℏk in a weakly interacting Bose gas after a 330 ms time of flight. We investigate it for various temperatures and clearly separate two contributions to the depletion of the condensate by their k dependence. The first one is the thermal depletion. The second contribution falls off as k^{-4}, and its magnitude increases with the in-trap condensate density as predicted by the Bogoliubov theory at zero temperature. These observations suggest associating it with the quantum depletion. How this contribution can survive the expansion of the released interacting condensate is an intriguing open question.