Metformin therapy in a hyperandrogenic anovulatory mutant murine model with polycystic ovarian syndrome characteristics improves oocyte maturity during superovulation

<p>Abstract</p> <p>Background</p> <p>Metformin, an oral biguanide traditionally used for the treatment of type 2 diabetes, is widely used for the management of polycystic ovary syndrome (PCOS)-related anovulation. Because of the significant prevalence of insulin resistance and glucose intolerance in PCOS patients, and their putative role in ovulatory dysfunction, the use of metformin was touted as a means to improve ovulatory function and reproductive outcomes in PCOS patients. To date, there has been inconsistent evidence to demonstrate a favorable effect of metformin on oocyte quality and competence in women with PCOS. Given the heterogeneous nature of this disorder, we hypothesized that metformin may be beneficial in mice with aberrant metabolic characteristics similar to a significant number of PCOS patients. The aim of this study was to gain insight into the <it>in vitro </it>and <it>in vivo </it>effects of metformin on oocyte development and ovulatory function.</p> <p>Methods</p> <p>We utilized metformin treatment in the transgenic <it>ob/ob </it>and <it>db/db </it>mutant murine models which demonstrate metabolic and reproductive characteristics similar to women with PCOS. Results: Metformin did not improve <it>in vitro </it>oocyte maturation nor did it have an appreciable effect on <it>in vitro </it>granulosa cell luteinization <it>(</it>progesterone production) in any genotype studied. Although both mutant strains have evidence of hyperandrogenemia, anovulation, and hyperinsulinemia, only <it>db/db </it>mice treated with metformin had a greater number of mature oocytes and total overall oocytes compared to control. There was no observed impact on body mass, or serum glucose and androgens in any genotype.</p> <p>Conclusions</p> <p>Our data provide evidence to suggest that metformin may optimize ovulatory performance in mice with a specific reproductive and metabolic phenotype shared by women with PCOS. The only obvious difference between the mutant murine models is that the <it>db/db </it>mice have elevated leptin levels raising the questions of whether their response to metformin is related to elevated leptin levels and/or if a subset of PCOS women with hyperleptinemia may be responsive to metformin therapy. Further study is needed to better define a subset of women with PCOS that may be responsive to metformin.</p

Functional Massage of the Teres Major Muscle in Patients with Subacromial Impingement Syndrome. A Randomized Controlled Case Series Study.

Objective: the purpose of the present study was to analyze the concurrent validity and reliability of a force platform clinical COBS Feedback® for the estimation of the height of vertical jumps. Design: a cross-sectional correlational and comparative study. Setting: University Human Movement and Physiotherapy Laboratory. Participants: healthy university students (14 female and 13 male) aged between 18 and 25 years old (mean = 20.074 ±1.542). Main Outcome Measures: vertical jump heights, technical error and grade of agreement between methods of measurement. Results: after the 27 subjects performed a total of 135 vertical jumps on COBS Feedback®platform while simultaneously being recorded with a high-speed camera-based method, the intraclass correlation coefficient showed an almost perfect concordance between the two methods (ICC = 0.916, CI95%= 0.882 to 0.940, p<0.001). The technical error of the COBS Feedback® against HSC-Kinovea video analysis was at 0.310±0.223m, being higher in males than in females (t= -2.822, CI95%: -0.376 to -0.574, p=0.001). Conclusions: the COBS Feedback® method provided a valid measurement of the flight times for estimate the vertical jump height as a number of well-known tests and devices.Aims: Subacromial impingement syndrome is the most common shoulder condition. Myofascial trigger points in teres major muscle can be associated with this syndrome. Our objective is to determine whether adding manual therapy specifically for teres major trigger points can produce better results in these patients. Study Design: Randomized controlled case series. Place and Duration of Study: Public Primary Care Center in the Spanish National Health System (Cornellà de Llobregat - Barcelona) and the FREMAP Mutual Society for Work-related Injuries and Occupational Illness (Arnedo - La Rioja), between January and March 2014. Methodology: Fifty-eight people were recruited but 8 subjects were lost during the follow-up period. The sample consisted of 50 patients (17 male and 33 female, age range 23-80 years) randomly assigned to one of two groups: the intervention group or the control group. Both groups received a protocolized physical therapy treatment, while the intervention group also received manual therapy for teres major trigger points. Results: Pain intensity (p=.01) and function (p=.01) showed significant improvement in the control group, whereas pain intensity (p=.01), function (p=.01) and active range of motion (p=.01) showed significant improvement in the intervention group. Between-group differences were statistically significant for abduction (p=.01), extension (p=.02) and lateral rotation (p=.02), and clinically significant (Cohen’s d) for function, flexion, extension, lateral rotation and abduction. Conclusion: Although our findings must be considered as preliminary, they suggest that adding manual therapy to treat teres major trigger points achieves better results in the glenohumeral range of motion

Franchisors' disclosure duty: market transparency and franchisee protection

The franchisee is usually the most vulnerable part of the franchise relationship, and should therefore receive greater protection from the legal framework. In this regard, the franchisor's pre-contractual disclosure duty has evolved in its legal status. Whereas its original purpose was to ensure transparency in the market, it now serves to protect the franchisee. In this paper, we compare the franchisor's obligations established by the legal framework in Spain with those set out in the Model Law drawn up by The International Institute for the Unification of Private Law.Lapiedra-Alcami, R.; Reig Fabado, I.; Rueda Armengot, C. (2014). Franchisors' disclosure duty: market transparency and franchisee protection. Service Industries Journal. 34(9-10):788-795. doi:10.1080/02642069.2014.905917S788795349-10Chaudey, M., & Fadairo, M. (2010). Contractual design and networks performance: empirical evidence from franchising. Applied Economics, 42(4), 529-533. doi:10.1080/00036840701704428Collins, H. (2008). Principles, Definitions and Model Rules of European Private Law: Draft Common Frame of Reference (DCFR) Interim Outline Edition, prepared by the Study Group on a European Civil Code and the Research group on EC Private Law (Acquis group) by Christian von Bar, Eric Clive, Hans Schulte-Nöcke (eds). Modern Law Review, 71(5), 840-844. doi:10.1111/j.1468-2230.2008.00718.xPeris-Ortiz, M., Peris Bonet, F. J., & Rueda-Armengot, C. (2011). Vertical integration in production and services: development in transaction cost economics. Service Business, 5(1), 87-97. doi:10.1007/s11628-011-0103-0Perryman, A. A., & Combs, J. G. (2011). Who should own it? An agency-based explanation for multi-outlet ownership and co-location in plural form franchising. Strategic Management Journal, 33(4), 368-386. doi:10.1002/smj.1947Rondan-Cataluña, F. J., Navarro-Garcia, A., Diez-De Castro, E. C., & Rodriguez-Rad, C. J. (2012). Reasons for the expansion in franchising: is it all said? The Service Industries Journal, 32(6), 861-882. doi:10.1080/02642069.2010.550041Shane, S. (2001). Organizational Incentives and Organizational Mortality. Organization Science, 12(2), 136-160. doi:10.1287/orsc.12.2.136.10108Vázquez, L. (2008). Complementarities between franchise contract duration and multi-unit propensity in franchise systems. The Service Industries Journal, 28(8), 1093-1105. doi:10.1080/0264206080218794

Aneuploidy prediction and tumor classification with heterogeneous hidden conditional random fields

Motivation: The heterogeneity of cancer cannot always be recognized by tumor morphology, but may be reflected by the underlying genetic aberrations. Array comparative genome hybridization (array-CGH) methods provide high-throughput data on genetic copy numbers, but determining the clinically relevant copy number changes remains a challenge. Conventional classification methods for linking recurrent alterations to clinical outcome ignore sequential correlations in selecting relevant features. Conversely, existing sequence classification methods can only model overall copy number instability, without regard to any particular position in the genome

Production and economic potentials of cattle in pasture-based systems of the Western Amazon region of Brazil.

Our objectives were to evaluate strategies to improve productivity and economic returns from beef and dual-purpose cattle systems based on data collected on one dual-purpose (Bos taurus × Bos indicus) and two beef (Nellore) cattle farms in the western Amazon region of Brazil. Forage chemical composition and digestion rates of carbohydrate fractions of grazed Brachiaria decumbens and Brachiaria brizantha cv. Marandu grasses and Pueraria phaseoloides (tropical kudzu) legume were measured monthly during a 9-mo period from the end of one dry season to the end of the subsequent rainy season. Measurements of milk and growth responses to grazing these forages were used to predict animal productivity responses to dietary nutrient availability throughout an annual cycle. The ME available for gain in our simulations was always more limiting than metabolizable protein. The predicted ME available for gain was 0.50 kg/d for steers grazing B. brizantha and 0.40 kg/d for finishing steers grazing B. decumbens. Grasses contained more NDF and neutral detergent insoluble protein and less ME (P < 0.05) in the rainiest months than in the less rainy season, which resulted in 20% less predicted weight gain by growing steers (P < 0.05). Supplementation with sorghum grain was required to increase milk production and growth by 25 or 50% per animal, respectively, but this strategy was less profitable than current forage-only diets. Greater productivity of land and labor from higher stocking indicated greater net margins for beef production, but not for milk. This study suggested that more intensive beef production by judicious fertilization of grass-legume pastures and greater stocking density is the preferable strategy for owners of these cattle systems to improve economic returns under current conditions. It also might help decrease the motivation for additional forest clearing