Mifepristone for preoperative treatment of uterine leiomyoma

AIM: To explore the clinical impact and its molecular regulation on uterine leiomyomas in preoperative treatment with mifepristone, a progesterone receptor modulator (PRM). BACKGROUND: Uterine leiomyomas are highly prevalent in fertile women, increasing with age up to 35-50 % in a population approaching the age of 50. These most often benign tumors, frequently cause menorrhagia, and may interfere with fertility and the outcome of pregnancy. Progesterone and estrogen have a role in leiomyoma growth regulation, as well as in endometrial and breast cell proliferation and the development of endometrial and breast cancer. The objective of the current project was to study the effect of mifepristone on leiomyoma growth, as well as on cell proliferation in human endometrial and breast tissue in premenopausal women. METHODS: Thirty premenopausal women scheduled for surgical treatment due to uterine leiomyoma were randomized to either 50 mg mifepristone or non active treatment every other day, for 12 weeks before surgical intervention. Uterine and leiomyoma blood flow and leiomyoma volume were measured once a month until surgery. Endometrial biopsies were obtained and analyzed before and at end of treatment. Breast biopsies were assessed at baseline and at the end of the study for the expression of Ki-67 by immunocytochemical analysis in order to evaluate mammary epithelial cell proliferation. On surgery biopsies were collected from the periphery of the dominant leiomyoma. In order to investigate the gene expression leading to volume change in myoma, microarray analysis followed by Real time PCR analysis was performed. The degree of apoptosis was studied by TUNEL. Functional studies using primary cell cultures from fresh and untreated leiomyoma biopsies were performed to investigate the antiglucocorticoid response of mifepristone in the Integrin pathway. RESULTS: There was a significant difference in percentual volume regression of the dominant leiomyoma between the treatment groups (p=0.014). The controls (N=15) had a percentual n.s. increase in volume of mean (± 95% Confidence interval), +8% (-10%, +26%) over time. The mifepristone group (N=12) had a significant volume regression of -27% (-47%, -8%), p=0.028 within the mifepristone group and between the treatment groups at the end of study (p=0.014). Mifepristone treatment significantly reduced the number of bleeding days (p<0.001) and increased blood haemoglobin values (p=0.046). The breast Ki-67-index was significantly reduced by mifepristone treatment (p=0.012). Breast symptoms, like soreness (p=0.035), swelling (p=0.028) and the score for sense of increased volume (p=0.043), were reduced within the mifepristone treated group. The incidence of hot flushes was more frequent in the mifepristone treated group (p=0.012). Endometrial morphology showed no hyperplasia or atypia. Microarray displayed 17 pathways significantly changed by mifepristone exposure, among which Integrin, EGF, NRF-2 mediated Oxidative Stress response and Ephrine pathways were the top 4 most significant. In a subgroup analysis of good (N=4) versus poor (N=4) responders, with regard to the effect of mifepristone in induction of volume regression, the Glutathione pathway was the second most significant. Among good responders GSTM1 was expressed, while it was not detectable by Real time PCR in non responders. In primary cell cultures, the genes PIK3R1 and PAK3 proved to respond to the antiglucocorticoid effect of mifepristone. CONCLUSION: Mifepristone may offer an effective, well tolerated preoperative treatment option for women with uterine leiomyoma and the associated uterovaginal bleeding. Our results also show an antiproliferative effect of mifepristone in normal premenopausal breast epithelium, implicating a possible protective effect. It is suggested that GSTM1 may be of importance for the response in leiomyoma volume regression as induced by mifepristone, and could have a role as a biomarker for tailoring of the medical treatment of uterine leiomyomas

Design and Validation of a Wearable, Continuous, and Non-Invasive Hydration Monitor that uses Ultrasonic Pulses to Detect Changes in Tissue Hydration Status

Chronic dehydration is an endemic problem for many population groups. Current methods of monitoring hydration status are invasive, time consuming, cannot be performed while exercising, and require lab resources. A proposed solution is a wearable, continuous, and non-invasive device that uses harm-free ultrasonic pulses to detect changes in tissue hydration status over time. Customer and engineering requirements were defined and used to guide the design process. Literature reviews were performed to identify essential information on dehydration, assess current methods, discover state of the art devices, and describe ultrasonic theory. Market research was performed to identify athletes as the target population group. An adjustable elastic nylon bicep band prototype was manufactured and the integration of more advanced components was proposed. The theoretical signal processing method used to detect hydration status was validated through initial tests with a prototype electrical system composed of a Teensy 3.1 board, two 18 kHz piezoceramic disc elements, and an Arduino/LabVIEW interface. Tests with aluminum, rubber, and sponge materials were performed to compare the signal response to propagation through materials with different acoustic properties and water contents. Finally, tests performed with dehydrated bovine muscle tissue revealed a statistically significant difference between hydrated and dehydrated tissue, a promising indication for future device refinement

And Then There Were Two: Why is the United States One of Only Two Countries in the World That Has Not Ratified the Convention on the Rights of the Child?

Twenty-five years ago, the United Nations General Assembly (‘U.N. General Assembly’) unanimously adopted the Convention on the Rights of the Child (hereinafter the “CRC”), which became the most widely accepted human rights treaty in history. Today, every nation in the world is a party to the CRC – except for two: Somalia, and the United States. This article will analyze the politics behind America’s failure to ratify this treaty. That may seem a little out of place in a law journal, but in reality the United States’ (‘U.S.’) acceptance or rejection of international law is as much a matter of politics as it is of policy

Lateralization in a partial migrating roach population

Lateralization is the functional specialization to use one brain hemisphere to carry out certain cognitive tasks. Lateralization is widespread across numerous taxa and gives the organism the possibility to increase neural capacity without increasing brain size. The degree and direction of lateralization varies within populations, suggesting that there also are disadvantages to being lateralized. Here I examined correlates between behavioral lateralization and alternative migratory strategies in a partially migratory population of Roach (Rutilus rutilus). I assessed behavioral lateralization in migratory and resident phenotypes and also measured the repeatability of behavioral lateralization in this species. My results show no signs of lateralization in either migrant or resident fish, which suggests that there is a disadvantage, like lower ability to evaluate the environment equally with both eyes, connected to being lateralized

Identifiering av lämpliga platser för stadsodling

Städerna i Sverige växer allt mer vilket ofta innebär förtätning av den befintliga stadsmiljön. Till följd av detta minskar städernas gröna miljöer. Gröna ytor kan innebära olika typer av miljöer och ett exempel är stadsodlingar som bidrar med många positiva egenskaper till både staden och dess invånare. Stressreducering, fysisk aktivitet och sociala mötesplatser är bara några av de många fördelar som urbana odlingar ger. I Uppsala finns det 34 befintliga eller planerade odlingsområden men i Uppsalas innerstad återfinns endast tre av dessa. Eftersom intresset för stadsodling är stort ger det ett högt tryck på de befintliga stadsodlingarna i Uppsala, speciellt då majoriteten av odlingsområdena återfinns i Uppsalas utkanter. Med tanke på stadsodlingarnas fördelar och det låga antalet befintliga stadsodlingar inom Uppsalas innerstad kommer arbetet undersöka möjligheterna att införa mer urban odling i Uppsala. Vidare kommer arbetet lyfta kunskap om hur landskapsarkitekter kan utreda lämpliga platser för stadsodling och hur dessa kan integreras i den befintliga stadsmiljön. Arbetet har därför utgått ifrån två frågeställningar. 1. Vilka rekommendationer kan guida val av plats för stadsodling i Uppsalas innerstad då odlingsplatsen ska integreras i närområdet? 2. Vilka platser kan identifieras som lämpliga för stadsodling i Uppsalas innerstad enligt de framtagna rekommendationerna? För att svara på den första frågan gjordes en litteraturundersökning. Under litteraturundersökningen inhämtades information kring stadsodling, dess effekter samt integreringen av urban odling i stadsmiljö. Informationen kunde sedan omformuleras till rekommendationer för val av lämpliga platser för urban odling. Som ett resultat av den första frågan kunde totalt elva rekommendationer identifieras. Dessa delades upp i Rekommendationer för platsen och Rekommendationer för omgivningen. Uppdelningen underlättade den efterföljande identifieringen av nya platser för stadsodling. För att svara på arbetets andra fråga applicerades rekommendationerna på Uppsalas innerstad. Via kartundersökningar kunde sju platser identifieras i fyra av Uppsalas stadsdelar; Boländerna, Fjärdingen, Fålhagen och Luthagen. De rekommendationer och tillvägagångssätt som använts under arbetets gång är utformade för att kunna användas av andra svenska städer och kommuner.Swedish cities are growing, which often means densification of the existing urban environment. As a result, there is a decrease in the city’s green spaces. Urban gardens contribute with many positive qualities to both the city and its inhabitants. Stress reduction, physical activity and places for social meetings are just some of the many benefits that urban agriculture provides. In Uppsala, there are 34 existing or planned sites for urban gardening, but in Uppsala’s inner city there are only three. Since there is a large interest in urban gardening, it puts a lot of pressure on the existing urban gardening sites in Uppsala. Especially since most of the areas are located on the outskirts of Uppsala. Given the benefits of urban gardening and the low number of existing urban gardening sites within Uppsala’s inner city, this thesis will investigate the possibilities of introducing more sites for urban gardening in Uppsala. Furthermore, it will emphasise how landscape architects can investigate suitable places for urban agriculture and how these can be integrated into the existing urban environment. The work has therefore explored two research questions. 1. What recommendations can guide the choice of sites for urban gardening in Uppsala’s inner city when the site is to be integrated in the immediate area? 2. Which sites can be identified as suitable for urban gardening in Uppsala’s inner city according to the recommendations? To answer the first question, a literature review was made. During the literature review, information regarding urban gardening, its effects and the integration of urban gardening in an urban environment, was gathered. The information could then be reformulated as recommendations for the selection of suitable sites for urban gardening. As a result of the first research question a total of eleven recommendations could be identified. These were divided into Recommendations for the site and Recommendations for the surrounding. The division facilitated the following identification of new sites for urban gardening. To answer the second research question the recommendations were applied to the inner city of Uppsala. Via map surveys, seven sites were identified in four of Uppsala’s districts; Boländerna, Fjärdingen, Fålhagen and Luthagen. The recommendations and approaches used during the work are designed to be used by other Swedish cities and municipalities

Educational Concerns of Implementing Biosand Water Filters in Rural Uganda

The world is facing a shortage of clean drinking water. Current predictions, due to growing population, urbanization, and climate change estimate access to clean water to be further challenged in the coming years. Research has indicated that point of use (POU) technologies are likely to be the most efficient at delivering clean water (water cleaned of diarrhea causing microbes and bacteria) to rural populations. POU technologies, and specifically the biosand filter (BSF) are shown to be affordable, effective, and sustainable in rural areas. Many studies point to the need of proper education and follow-up with BSF users. BSF technology has been used for the last 4 years in Nkokonjeru, Uganda by a partnership between Engineers Without Borders, Davis Branch and a local nongovernmental development agency, Rural Agency for Sustainable Development (RASD). Both quantitative and qualitative data were gathered at 10 sites with 23 water filters to identify the bacteria count before and after BSF use. Users at sites answered questions from a structured interview and demonstrated their BSF procedure. The survey indicated many BSFs were not being used or were not yielding clean water, due most likely to insufficient education and follow up. Implications of research led to the development of a training and implementation approach to improve the BSF program in Nkokonjeru, to modify RASD’s ongoing program of BSF distribution

Intrinsic Spectral Geometry of the Kerr-Newman Event Horizon

We uniquely and explicitly reconstruct the instantaneous intrinsic metric of the Kerr-Newman Event Horizon from the spectrum of its Laplacian. In the process we find that the angular momentum parameter, radius, area; and in the uncharged case, mass, can be written in terms of these eigenvalues. In the uncharged case this immediately leads to the unique and explicit determination of the Kerr metric in terms of the spectrum of the event horizon. Robinson's ``no hair" theorem now yields the corollary: One can ``hear the shape" of noncharged stationary axially symmetric black hole space-times by listening to the vibrational frequencies of its event horizon only.Comment: Final version with improved abstract, updated references, corrected typos, and additional discussio