Max dD/Dt: A Novel Parameter to Assess Fetal Cardiac Contractility and a Substitute for Max dP/Dt

Publication date: Available online 2 April 2018
Source:Ultrasound in Medicine & Biology
Author(s): Yasuyuki Fujita, Ryo Kiyokoba, Yasuo Yumoto, Kiyoko Kato
Aortic pulse waveforms are composed of a forward wave from the heart and a reflection wave from the periphery. We focused on this forward wave and suggested a new parameter, the maximum slope of aortic pulse waveforms (max dD/dt), for fetal cardiac contractility. Max dD/dt was calculated from fetal aortic pulse waveforms recorded with an echo-tracking system. A normal range of max dD/dt was constructed in 105 healthy fetuses using linear regression analysis. Twenty-two fetuses with suspected fetal cardiac dysfunction were divided into normal and decreased max dD/dt groups, and their clinical parameters were compared. Max dD/dt of aortic pulse waveforms increased linearly with advancing gestational age (r = 0.93). The decreased max dD/dt was associated with abnormal cardiotocography findings and short- and long-term prognosis. In conclusion, max dD/dt calculated from the aortic pulse waveforms in fetuses can substitute for max dP/dt, an index of cardiac contractility in adults.



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Hepatic Steatosis Assessment with Ultrasound Small-Window Entropy Imaging

Publication date: Available online 2 April 2018
Source:Ultrasound in Medicine & Biology
Author(s): Zhuhuang Zhou, Dar-In Tai, Yung-Liang Wan, Jeng-Hwei Tseng, Yi-Ru Lin, Shuicai Wu, Kuen-Cheh Yang, Yin-Yin Liao, Chih-Kuang Yeh, Po-Hsiang Tsui
Nonalcoholic fatty liver disease is a type of hepatic steatosis that is not only associated with critical metabolic risk factors but can also result in advanced liver diseases. Ultrasound parametric imaging, which is based on statistical models, assesses fatty liver changes, using quantitative visualization of hepatic-steatosis–caused variations in the statistical properties of backscattered signals. One constraint with using statistical models in ultrasound imaging is that ultrasound data must conform to the distribution employed. Small-window entropy imaging was recently proposed as a non–model-based parametric imaging technique with physical meanings of backscattered statistics. In this study, we explored the feasibility of using small-window entropy imaging in the assessment of fatty liver disease and evaluated its performance through comparisons with parametric imaging based on the Nakagami distribution model (currently the most frequently used statistical model). Liver donors (n = 53) and patients (n = 142) were recruited to evaluate hepatic fat fractions (HFFs), using magnetic resonance spectroscopy and to evaluate the stages of fatty liver disease (normal, mild, moderate and severe), using liver biopsy with histopathology. Livers were scanned using a 3-MHz ultrasound to construct B-mode, small-window entropy and Nakagami images to correlate with HFF analyses and fatty liver stages. The diagnostic values of the imaging methods were evaluated using receiver operating characteristic curves. The results demonstrated that the entropy value obtained using small-window entropy imaging correlated well with log10(HFF), with a correlation coefficient r = 0.74, which was higher than those obtained for the B-scan and Nakagami images. Moreover, small-window entropy imaging also resulted in the highest area under the receiver operating characteristic curve (0.80 for stages equal to or more severe than mild; 0.90 for equal to or more severe than moderate; 0.89 for severe), which indicated that non–model-based entropy imaging—using the small-window technique—performs more favorably than other techniques in fatty liver assessment.



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Effect of Fluid Intake on Hydration Status and Skin Barrier Characteristics in Geriatric Patients: An Explorative Study

Background/Aim: Inadequate fluid intake is assumed to be a trigger of water-loss dehydration, which is a major health risk in aged and geriatric populations. Thus, there is a need to search for easy to use diagnostic tests to identify dehydration. Our overall aim was to investigate whether skin barrier parameters could be used for predicting fluid intake and/or hydration status in geriatric patients. Methods: An explorative observational comparative study was conducted in a geriatric hospital including patients aged 65 years and older. We measured 3-day fluid intake, skin barrier parameters, Overall Dry Skin Score, serum osmolality, cognitive and functional health, and medications. Results: Forty patients were included (mean age 78.45 years and 65% women) with a mean fluid intake of 1,747 mL/day. 20% of the patients were dehydrated and 22.5% had an impending dehydration according to serum osmolality. Multivariate analysis suggested that skin surface pH and epidermal hydration at the face were associated with fluid intake. Serum osmolality was associated with epidermal hydration at the leg and skin surface pH at the face. Fluid intake was not correlated with serum osmolality. Diuretics were associated with high serum osmolality. Conclusions: Approximately half of the patients were diagnosed as being dehydrated according to osmolality, which is the current reference standard. However, there was no association with fluid intake, questioning the clinical relevance of this measure. Results indicate that single skin barrier parameters are poor markers for fluid intake or osmolality. Epidermal hydration might play a role but most probably in combination with other tests.
Skin Pharmacol Physiol 2018;31:155–162

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Variation laws and release characteristics of phosphorus on surface sediment of Dongting Lake

Abstract

The variation trend and growth rate of P were analyzed by the concentration of the phosphorus fraction on surface sediment of Dongting Lake from 2012 to 2016, to reveal the cumulative effect of P in the actual environment. Meanwhile, the adsorption kinetics and adsorption isotherm were employed to examine the P-release possibility of sediment, which predicts the yearly released sediment phosphorus in Dongting Lake. The actual growth rate of TP (Total Phosphorus) is 53 mg·(kg·year)⁻¹ in East Dongting Lake, 39 mg·(kg·year)⁻¹ in South Dongting Lake, and 29 mg·(kg·year)⁻¹ in West Dongting Lake, while the sum of the phosphorus fraction growth rates has little difference from the rate of TP in sediments of the three areas of Dongting Lake. Furthermore, the Elovich model and the Langmuir crossover-type equations are established to present the adsorption characteristic of sediment in Dongting Lake; the result shows that the sediments play a source role for phosphorus in East and South Dongting Lake from zero equilibrium phosphorus concentration (EPC₀) in the present situation, but an adsorption effect on TP is shown in West Dongting Lake. When the conditions of environment change are ignored, the maximum P-sorption level in sediments of East Dongting Lake will reach in 2040 according to the actual growth rate of sediments, while that in West Dongting Lake and South Dongting Lake will be in 2046 and 2061, respectively.

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Cost-Effectiveness Evaluation of Heparin Coated Versus Standard Graft for Bypass Surgery in Peripheral Artery Disease Alongside a Randomised Controlled Trial

Publication date: Available online 2 April 2018
Source:European Journal of Vascular and Endovascular Surgery
Author(s): Marie K. Villemoes, Jes S. Lindholt, Kim C. Houlind, Bo Gottschalksen, Christian N. Petersen, Martin Rasmussen, Charlotte Wedel, Morten B. Bramsen, Rikke Søgaard
Objective/BackgroundHeparin coating has recently been shown to reduce the risk of graft failure in arterial revascularisation, at least transiently. The aim of this study was to assess the cost-effectiveness of heparin coated versus standard polytetrafluoroethylene grafts for bypass surgery in peripheral artery disease from a long-term healthcare system perspective.MethodsCost-effectiveness evaluation was conducted alongside the Danish part of the Scandinavian Propaten trial in which 431 patients planned for femoro-femoral or femoro-popliteal bypass surgery were randomised to either type of graft and followed for 5 years. Based on the intention to treat principle, the differences in healthcare costs (general practice, prescription medication, hospital admission, rehabilitation, and long-term care in 2015 Euros), life years (LYs), and quality adjusted life years (QALYs) were analysed as arithmetic means with bootstrapped 95% confidence intervals. Cost-effectiveness acceptability curves were used to illustrate the probability of cost-effectiveness for a range of threshold values of willingness to pay (WTP).ResultsNo statistically significant differences between the randomisation groups were observed for costs or gains of LYs or QALYs. The average cost per QALY was estimated at €10,792. For a WTP threshold of €40,000 per QALY, the overall probability of cost-effectiveness was estimated at 62%, but owing to cost savings in patients with critical ischaemia (cost per QALY <€0), it increased to 89% for this subgroup.ConclusionUntil further evidence, heparin coated grafts appear overall, to be cost-effective over standard grafts, but important heterogeneity between claudication and critical ischaemia should be noted. While the optimal choice for claudication remains uncertain, heparin coated grafts should be used for critical ischaemia.



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Endovascular Versus Open Surgical Intervention in Patients with Takayasu's Arteritis: A Meta-analysis

Publication date: Available online 3 April 2018
Source:European Journal of Vascular and Endovascular Surgery
Author(s): Jae Hyun Jung, Young Ho Lee, Gwan Gyu Song, Han Saem Jeong, Jae-Hoon Kim, Sung Jae Choi
Objective/BackgroundAlthough medical treatment has advanced, surgical treatment is needed to control symptoms of Takayasu's arteritis (TA), such as angina, stroke, hypertension, or claudication. Endovascular or open surgical intervention is performed; however, there are few comparative studies on these methods. This meta-analysis and systematic review aimed to examine the outcome of surgical treatment of TA.MethodsA meta-analysis comparing outcomes of endovascular and open surgical intervention was performed using MEDLINE and Embase. This meta-analysis included only observational studies, and the evidence level was low to moderate. Data were pooled and analysed using a fixed or random effects model with the I² statistic.ResultsThe included studies involved a total of 770 patients and 1363 lesions, with 389 patients treated endovascularly and 420 treated by surgical revascularization. Restenosis was more common with endovascular than open surgical intervention (odds ratio [OR] 5.18, 95% confidence interval [CI] 2.78–9.62; p < .001). In subgroup analysis according to the involved lesions, endovascular intervention patients showed more restenosis than open surgical intervention patients in the coronary artery, supra-aortic branches, and renal artery. In both the active and inactive stages, restenosis was more common in those treated endovascularly than in those treated by open surgery. However, stroke occurred less often with endovascular intervention than with open surgical intervention (OR 0.33, 95% CI 0.12–0.90; p = .003). Mortality and complications other than stroke and mortality did not differ between endovascular and open surgical intervention.ConclusionThis meta-analysis has shown a lower risk of restenosis with open surgical intervention than with endovascular intervention. Stroke was generally more common with open surgical intervention than with endovascular intervention. However, there were differences according to the location of the lesion, and the risk of stroke in open surgery is higher when the supra-aortic branches are involved rather than the renal arteries.



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Integrated Care for Older People: Guidelines on Community-Level Interventions to Manage Declines in Intrinsic Capacity.

The provision of integrated care is key for older people. The WHO Guidelines on Integrated Care for Older People (ICOPE) propose evidence-based recommendations for health care professionals to prevent, slow or reverse declines in the physical and mental capacities of older people. These recommendations require countries to place the needs and preferences of older adults at the centre and to coordinate care. The ICOPE Guidelines will allow countries to improve the health and well-being of their older populations, and to move closer to the achievement of universal health coverage for all at all ages.

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The health impacts of energy performance investments in low-income areas: a mixed-methods approach.

The study found improvements in subjective well-being and a number of psychosocial outcomes, but there was no evidence of changes in physical health

https://ift.tt/2JeV2LD

Positive behaviour support training for staff for treating challenging behaviour in people with intellectual disabilities: a cluster RCT.

Staff training in positive behaviour support did not reduce challenging behaviour in people with intellectual disability, although both service users and carers reported some benefits from the training.

https://ift.tt/2q0YDEr

Scholar : These new articles for Critical Discourse Studies are available online

The online platform for Taylor & Francis Online content New for Critical Discourse Studies and online now on Taylor & Francis Online: Original Articles Some thoughts on CDS and its Marxist political economy bases David Block Pages: 1-12 | DOI: 10.1080/17405904.2018.1456943 To update which email alerts you receive, manage your alerts within the My Account area. Unsubscribe from new content alerts for this journal (both new issue and latest article notifications) with one click. If you need any further help, please contact us at support@tandfonline.com Please do not reply to this email. To ensure that you receive your alerts and information from Taylor & Francis Online, please add "alerts@tandfonline.com" and "info@tandfonline.com" to your safe senders list. Taylor & Francis, an Informa business. Taylor & Francis is a trading name of Informa UK Limited, registered in England under no. 1072954. Registered office: 5 Howick Place, London, SW1P 1WG.

A Comparative Study of Two Types of Organ-Sparing Surgeries for Early Stage Penile Cancer: Wide Local Excision vs Partial Penectomy

Publication date: Available online 3 April 2018
Source:European Journal of Surgical Oncology
Author(s): Xiang Wan, Dachao Zheng, Chong Liu, Huan Xu, Minkai Xie, Juan Zhou, Hai-Jun Yao, Zhong Wang
IntroductionTill date, there have been few reports of comparative studies on the outcomes of these different treatment modalities. In this study, we have aimed to comparatively evaluate the quality-of-life parameters, including sexual function, urinary function, and health-related quality of life (HRQOL), in patients with early stage penile cancers who underwent two different organ-sparing surgeries.Material and MethodsFrom March 2012 to March 2015, we enrolled 15 patients with early stage penile cancers who underwent either wide local excision or partial penectomy as organ-sparing surgical treatments. We assessed their sexual and urinary functions and their HRQOL, using the International Index of Erectile Function (IIEF-15), Self-Esteem and Relationship (SEAR), and Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) questionnaires and urodynamic determinations, and comparatively analyzed the outcomes of these patients who underwent either type of surgery.ResultsAll patients who underwent these two types of surgeries experienced satisfactory outcomes. The patients who underwent wide local excision performed relatively better, in terms of their sexual functions, urinary functions, and HRQOL, but no statistically significant differences were observed in the data collected via the IIEF-15, SEAR, EDITS, and EORTC-QLQ-C30 questionnaires and urodynamic determinations (p>0.05), except in the data corresponding to the orgasmic function (p=0.033).ConclusionBoth types of organ-sparing surgeries assessed in this study achieved good outcomes, in terms of the aesthetics, sexual functions, urinary functions, and HRQOL in patients, without compromising the therapeutic effects of these surgeries. However, the observed decreases in orgasmic function will need to be addressed further.



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Discovery and Evaluation of nNav1.5 Sodium Channel Blockers with Potent Cell Invasion Inhibitory Activity in Breast Cancer Cells

Publication date: Available online 3 April 2018
Source:Bioorganic & Medicinal Chemistry
Author(s): Shilpa Dutta, Osbaldo Lopez Charcas, Samuel Tanner, Frédéric Gradek, Virginie Driffort, Sébastien Roger, Katri Selander, Sadanandan E. Velu, Wayne Brouillette
Voltage-gated sodium channels (VGSC) are a well-established drug target for anti-epileptic, anti-arrhythmic and pain medications due to their presence and important roles that they play in excitable cells. Recently, their presence has been recognized in non-excitable cells such as cancer cells and their overexpression has been shown to be associated with metastatic behavior in a variety of human cancers. The neonatal isoform of the VGSC subtype, Nav1.5 (nNav1.5) is overexpressed in the highly aggressive human breast cancer cell line, MDA-MB-231. The activity of nNav1.5 is known to promote the breast cancer cell invasion in vitro and metastasis in vivo, and its expression in primary mammary tumors has been associated with metastasis and patient death. Metastasis development is responsible for the high mortality of breast cancer and currently there is no treatment available to specifically prevent or inhibit breast cancer metastasis. In the present study, a 3D-QSAR model is used to assist the development of low micromolar small molecule VGSC blockers. Using this model we have designed, synthesized and evaluated five small molecule compounds as blockers of nNav1.5-dependent inward currents in whole-cell patch-clamp experiments in MDA-MB-231 cells. The most active compound identified from these studies blocked sodium currents by 34.9 ± 6.6% at 1 μM. This compound also inhibited the invasion of MDA-MB-231 cells by 30.3 ± 4.5% at 1 μM concentration without affecting the cell viability. The potent small molecule compounds presented here have the potential to be developed as drugs for breast cancer metastasis treatment.

Graphical abstract

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Design and discovery of thioether and nicotinamide containing sorafenib analogs as multikinase inhibitors targeting B-Raf, B-RafV600E and VEGFR-2

Publication date: Available online 3 April 2018
Source:Bioorganic & Medicinal Chemistry
Author(s): Shaofeng Sun, Zuopeng He, Mindong Huang, Ningning Wang, Zongzhong He, Xiangkai Kong, Jianwen Yao
New sorafenib derivatives containing thioether and nicotinamide moiety were designed and synthesized as B-Raf, B-Raf^V600E and VEGFR-2 multikinase inhibitors. Their in vitro enzymatic inhibitory activities against B-Raf, B-Raf^V600E and VEGFR-2 and their antiproliferative activities against HCT-116 and B16BL6 cell lines were evaluated and described. Most of the compounds showed potent activities against both cell lines and specific kinases. Compounds a1, b1 and c4, which exhibited the most potent inhibitory activities against B-Raf with IC50 of 21 nM, 27 nM and 17 nM, B-Raf^V600E with IC50 of 29 nM, 28 nM and 16 nM, VEGFR-2 with IC50 of 84 nM, 46 nM and 63 nM, respectively, and good antiproliferative activities, also demonstrated competitive antiangiogenic activities to sorafenib in in vitro HUVEC tube formation assay.

Graphical abstract

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Design, synthesis and biological evaluation of novel tetrahydroisoquinoline derivatives as P-glycoprotein-mediated multidrug resistance inhibitors

Publication date: Available online 3 April 2018
Source:Bioorganic & Medicinal Chemistry
Author(s): Yang Gao, Wei Shi, Jian Cui, Chunxia Liu, Xinzhou Bi, Zhuo Li, Wenlong Huang, Guangji Wang, Hai Qian
Multidrug resistance (MDR) is one of the main obstacles of clinical chemotherapy. A great deal of research shows that the occurrence of drug resistance in various malignant tumors is closely related to the expression of P-glycoprotein (P-gp) on the surface of the cell membrane. In this paper, based on the structure-activity relationship of phenylethyl tetrahydroisoquinoline, we choose tariquidar as the lead compound for the design and synthesis of 17 novel tetrahydroisoquinoline P-gp inhibitors. Additionally, in vitro and in vivo cytotoxicity assays and reversed MDR activity assays were evaluated. Among them, compound 3 had a good reversal of MDR activity and the reversal mechanism study of it was carried out. All of these results demonstrated that compound 3 was considered to be a promising P-gp-mediated MDR reversal candidate.

Graphical abstract

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Pseudoesterase activity of albumin: A probable determinant of cholesterol biosynthesis

Publication date: June 2018
Source:Medical Hypotheses, Volume 115
Author(s): Deepak Kumar, Sakshi Behal, Rajasri Bhattacharyya, Dibyajyoti Banerjee
The association between hypoalbuminemia and coronary artery disease is known from some time. However, the reason as to how such phenomenon is correlated remains unknown. We have observed from published scientific literature that HSA has the potential to control cholesterol biosynthesis due to its pseudoesterase activity. In-silico observations have supported our view since acetyl coA, the precursor molecule of cholesterol biosynthesis is shown to bind with Tyr 411 of HSA. Incidentally, Tyr411 is a critical moiety for pseudoesterase activity of albumin. With this frame of reference in mind we hypothesize that pseudoesterase activity of HSA is an important determinant of lipid metabolism including cholesterol biosynthesis. Therefore, albumin has the potential to influence the atherosclerotic state important for pathogenesis of coronary artery diseases.



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Scholar : These new articles for Critical Inquiry in Language Studies are available online

The online platform for Taylor & Francis Online content New for Critical Inquiry in Language Studies and online now on Taylor & Francis Online: Book Review BOOK REVIEW Carl Ruest Pages: 1-3 | DOI: 10.1080/15427587.2018.1452332 To update which email alerts you receive, manage your alerts within the My Account area. Unsubscribe from new content alerts for this journal (both new issue and latest article notifications) with one click. If you need any further help, please contact us at support@tandfonline.com Please do not reply to this email. To ensure that you receive your alerts and information from Taylor & Francis Online, please add "alerts@tandfonline.com" and "info@tandfonline.com" to your safe senders list. Taylor & Francis, an Informa business. Taylor & Francis is a trading name of Informa UK Limited, registered in England under no. 1072954. Registered office: 5 Howick Place, London, SW1P 1WG.

Commentary on the “Evidence- and Consensus-Based (S3) Guidelines for the Treatment of Actinic Keratosis” Published by the International League of Dermatological Societies in Cooperation with the European Dermatology Forum

In 2015, the International League of Dermatological Societies and the European Dermatology Forum published a guideline for the treatment of actinic keratosis, which is classified as an evidence- and consensus-based S3 guideline. From the point of view of the GD Task Force "Licht.Hautkrebs.Prävention," an interdisciplinary expert panel of the Society for Dermopharmacy for the prevention and treatment of skin cancer, this guideline reveals strengths and weaknesses but, in summary, does not meet the claim for an evidence- and consensus-based S3 guideline.
Skin Pharmacol Physiol 2018;31:144–146

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Optimizing Cancer Treatment for Older Adults

Publication date: Available online 2 April 2018
Source:Clinical Therapeutics
Author(s): William W. Hung




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Scholar : Acta Agriculturae Scandinavica, Section B — Soil & Plant Science, Volume 68, Issue 6, September 2018 is now available online on Taylor & Francis Online

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The online platform for Taylor & Francis Online content Acta Agriculturae Scandinavica, Section B — Soil & Plant Science, Volume 68, Issue 6, September 2018 is now available online on Taylor & Francis Online. This new issue contains the following articles: Reviews Possible benefits and challenges associated with production of chickpea in inland South Africa Tiisetso Mpai & Sipho Thulane Maseko Pages: 479-488 | DOI: 10.1080/09064710.2018.1437926 Original Articles Insecticidal activity of two formulations of essential oils against the cereal leaf beetle Jiří Skuhrovec, Ondřej Douda, Miloslav Zouhar, Marie Maňasová, Pavel Nový, Matěj Božik & Pavel Klouček Pages: 489-495 | DOI: 10.1080/09064710.2018.1432069 Balance and concentration of nitrogen and potassium affect growth and nutrient status in soilless cultivated lisianthus Daniela Alvarado-Camarillo, Ana María Castillo-González, Luis A. Valdez-Aguilar & Juana C. García-Santiago Pages: 496-504 | DOI: 10.1080/09064710.2018.1433873 Effects of long-term application of various organic amendments on soil particulate organic matter storage and chemical stabilisation of vertisol soil Keke Hua, Daozhong Wang & Zhibin Guo Pages: 505-514 | DOI: 10.1080/09064710.2018.1436722 Animal-based organic nutrition induces comparable fruit quality to that of inorganic fertigation in soilless-grown grape tomato Carlos Javier Lozano-Cavazos, Luis Alonso Valdez-Aguilar, Luis Ibarra-Jiménez, Juan Alberto Ascacio-Valdés, Adalberto Benavides-Mendoza, Cristóbal Noé Aguilar-González & Oscar Guajardo-Ríos Pages: 515-523 | DOI: 10.1080/09064710.2018.1437215 Physiological responses of irrigated wheat (Triticum aestivum L.) genotypes to water stress Unathi Liwani, Lembe S. Magwaza, Nkanyiso J. Sithole, Alfred O. Odindo & Toi J. Tsilo Pages: 524-533 | DOI: 10.1080/09064710.2018.1439526 Enhancing of symbiotic efficiency and salinity tolerance of chickpea by phosphorus supply H. Sadji-Ait Kaci, A. Chaker- Haddadj & F. Aid Pages: 534-540 | DOI: 10.1080/09064710.2018.1440001 Variety specific responses of cauliflower varieties (Brassica oleracea var. botrytis) to different N application rates on yield, colour and ascorbic acid content at harvest Madonna N. Mashabela, Martin M. Maboko, Puffy Soundy & Dharini Sivakumar Pages: 541-545 | DOI: 10.1080/09064710.2018.1440002 Distribution of resistance-breaking isolates of beet necrotic yellow vein virus differing in virulence in sugar beet fields in Turkey Nazli Dide Kutluk Yilmaz, Huseyin Uzunbacak, Miray Arli-Sokmen & Riza Kaya Pages: 546-554 | DOI: 10.1080/09064710.2018.1441432 Nitrogen and phosphorus leaching under the potential biennial oilseed plant Lepidium campestre L. in a field trial Barbro Ulén & Helena Aronsson Pages: 555-561 | DOI: 10.1080/09064710.2018.1444786 Tillage and crop straw methods affect energy use efficiency, economics and greenhouse gas emissions in rainfed winter wheat field of Loess Plateau in China Xingli Lu, Xingneng Lu, Yong Cui & Yuncheng Liao Pages: 562-574 | DOI: 10.1080/09064710.2018.1448883 Browse papers on image & data fusion, GIS, LiDAR & more in the International Journal of Image and Data Fusion's exclusive Editor's Choice collection. To update which email alerts you receive, manage your alerts within the My Account area. Unsubscribe from new content alerts for this journal (both new issue and latest article notifications) with one click. If you need any further help, please contact us at support@tandfonline.com Please do not reply to this email. To ensure that you receive your alerts and information from Taylor & Francis Online, please add "alerts@tandfonline.com" and "info@tandfonline.com" to your safe senders list. Taylor & Francis, an Informa business. Taylor & Francis is a trading name of Informa UK Limited, registered in England under no. 1072954. Registered office: 5 Howick Place, London, SW1P 1WG.

Uterine progesterone signaling is a target for metformin therapy in PCOS-like rats

Impaired progesterone (P4) signaling is linked to endometrial dysfunction and infertility in women with polycystic ovary syndrome (PCOS). Here, we report for the first time that elevated expression of progesterone receptor (PGR) isoforms A and B parallels increased estrogen receptor (ER) expression in PCOS-like rat uteri. The aberrant PGR-targeted gene expression in PCOS-like rats before and after implantation overlaps with dysregulated expression of Fkbp52 and Ncoa2, two genes that contribute to the development of uterine P4 resistance. In vivo and in vitro studies of the effects of metformin on the regulation of the uterine P4 signaling pathway under PCOS conditions showed that metformin directly inhibits the expression of PGR and ER along with the regulation of several genes that are targeted dependently or independently of PGR-mediated uterine implantation. Functionally, metformin treatment corrected the abnormal expression of cell-specific PGR and ER and some PGR-target genes in PCOS-like rats with implantation. Additionally, we documented how metformin contributes to the regulation of the PGR-associated MAPK/ERK/p38 signaling pathway in the PCOS-like rat uterus. Our data provide novel insights into how metformin therapy regulates uterine P4 signaling molecules under PCOS conditions.

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