An optimal growth pattern during pregnancy and early childhood associates with better fertility in men

Peer reviewe

Women with polycystic ovary syndrome present with altered endometrial expression of stanniocalcin-1

Stanniocalcin-1 (STC-1) is a pro-survival factor that protects tissues against stressors, such as hypoxia and inflammation. STC-1 is co-expressed with the endometrial receptivity markers, and recently endometrial STC-1 was reported to be dysregulated in endometriosis, a condition linked with endometrial progesterone resistance and inflammation. These features are also common in the endometrium in women with polycystic ovary syndrome (PCOS), the most common endocrine disorder in women. Given that women with PCOS present with subfertility, pregnancy complications, and increased risk for endometrial cancer, we investigated endometrial STC-1 expression in affected women. Endometrial biopsy samples were obtained from women with PCOS and controls, including samples from overweight/obese women with PCOS before and after a 3-month lifestyle intervention. A total of 98 PCOS and 85 control samples were used in immunohistochemistry, reverse-transcription polymerase chain reaction, or in vitro cell culture. STC-1 expression was analyzed at different cycle phases and in endometrial stromal cells (eSCs) after steroid hormone exposure. The eSCs were also challenged with 8-bromo-cAMP and hypoxia for STC-1 expression. The findings indicate that STC-1 expression is not steroid hormone mediated although secretory-phase STC-1 expression was blunted in PCOS. Lower expression seems to be related to attenuated STC-1 response to stressors in PCOS eSCs, shown as downregulation of protein kinase A activity. The 3-month lifestyle intervention did not restore STC-1 expression in PCOS endometrium. More studies are warranted to further elucidate the mechanisms behind the altered endometrial STC-1 expression and rescue mechanism in the PCOS endometrium. Summary sentence Endometrial expression of STC-1 in the secretory phase is blunted in women with PCOS, suggesting impaired protection against stress.Peer reviewe

Association of growth from birth until middle age with sex hormone parameters and reproductive function in the Northern Finland Birth cohort 1966

Abstract Obesity predisposes people to numerous morbidities and less well-known reproductive problems. In women, obesity increases the risk of infertility and polycystic ovary syndrome (PCOS). In men, obesity impairs reproductive health and is associated with testosterone (T) deficiency. Since the above-mentioned problems affect a significant proportion of the population, this study focuses on the association between early risk factors and reproductive problems, providing a great opportunity to identify the sensitive time periods for preventive actions. The aim of this study was to assess the impact of prenatal factors, birth weight (BW), and BMI, from birth until middle age, on sex hormone levels and reproductive function in both women and men. The study populations (women and men with impaired reproductive function, women with PCOS and men with low T at age 31) were derived from the Northern Finland Birth Cohort 1966 with additional data from the Finnish Medical Birth Register. Multiple confounding factors, such as socioeconomic and lifestyle factors, marital status, attempts to have children, and adult obesity, could be considered. The results revealed that in girls, obesity in mid-childhood and especially in puberty — and in boys, low BMI in early childhood — predicted impaired reproductive function, as well as an increased risk of childlessness regardless of confounding factors. In boys, overweight and obesity in early childhood was associated with a decreased risk of infertility, but BMI from mid-childhood onwards did not affect their subsequent reproductive function. Both women with PCOS and men with low T at age 31 already had higher weight gain from childhood onwards; their weight gain began earlier, and their BMIs remained higher until age 46. In boys, maternal obesity was associated significantly with later T deficiency, suggesting that metabolic factors during pregnancy affect boys’ endocrine function later in life. Lower BW and prematurity in girls were associated with PCOS later in life. Given the well-known health risks related to obesity and the steadily rising prevalence of maternal obesity, the study results emphasize the importance of preventing obesity, maintaining an optimal growth during childhood, and preventing maternal obesity, as all these factors affect reproductive health later in life.Tiivistelmä Lihavuus aiheuttaa monien sairauksien lisäksi myös merkittäviä lisääntymisterveyden ongelmia ja lisää riskiä lapsettomuudelle. Lihavuus lisää naisilla munasarjojen monirakkulaoireyhtymän (PCOS) ja miehillä mieshormonivajeen riskiä. Nämä ongelmat koskettavat merkittävää osaa väestöstä. Tämä tutkimus antaa mahdollisuuden tunnistaa varhaisten riskitekijöiden yhteyksiä lisääntymisterveyden ongelmiin ja siten löytää keinoja oikea-aikaisiin ennaltaehkäiseviin toimiin. Tässä tutkimuksessa arvioitiin raskauden aikaisten tekijöiden, syntymäpainon ja painoindeksin (BMI) kehityksen vaikutusta hormonaalisiin muuttujiin ja lisääntymisterveyteen sekä naisilla että miehillä keski-ikään saakka. Tutkimuspopulaatiot (lapsettomuudesta kärsivät naiset ja miehet, PCOS-naiset sekä miehet, joilla todettiin mieshormonivaje 31-vuotiaana) koostuivat Pohjois-Suomen syntymäkohortista 1966, johon yhdistettiin Terveyden ja hyvinvoinninlaitoksen syntymärekisterin tietoja. Tutkimusaineisto mahdollisti useiden sekoittavien tekijöiden, kuten sosioekonomisen aseman, elintapojen, siviilisäädyn, lapsitoiveen ja aikuisiän lihavuuden, huomioimisen analyyseissa. Tutkimuksessa havaittiin, että keskilapsuuden ja murrosiän lihavuus tytöillä ja varhaislapsuuden matala BMI pojilla olivat yhteydessä lapsettomuusongelmiin ja riskiin jäädä myöhemmin lapsettomaksi siviilisäädystä riippumatta. Toisaalta poikien ylipaino ja lihavuus varhaislapsuudessa, mutta ei enää sen jälkeen, vähensivät lapsettomuusongelmien riskiä. Sekä PCOS-naisilla että 31-vuotiaana mieshormonivajeesta kärsivillä miehillä todettiin suurempi painon kertyminen jo varhaislapsuudessa, ja BMI pysyi korkeampana kuin kontrolleilla aina keski-ikään saakka. Pojilla äidin lihavuus liittyi merkittävästi itsenäisenä riskitekijänä myöhempään mieshormonivajeeseen viitaten siihen, että raskauden aikaiset aineenvaihdunnalliset tekijät vaikuttavat merkittävästi myöhempään hormonaalisen toimintaan. Tytöillä matalampi syntymäpaino ja ennenaikaisuus lisäsivät riskiä PCOS:lle. Tämän tutkimuksen tulokset korostavat synnyttäjien ylipainon ja lapsuusiän lihavuuden ehkäisemisen sekä optimaalisen kasvun tukemisen tärkeyttä, varsinkin kun otetaan huomioon lihavuuteen liittyvät muut terveysriskit ja synnyttäjien ylipainon jatkuva lisääntyminen, koska nämä kaikki vaikuttavat myöhempään lisääntymisterveyteen

TRIAGERESULTAT OG PASIENTTILFREDSHET PÅ LEGEVAKTEN

Sammendrag Bakgrunn: Når kvalitet av akuttmedisinske tjenester skal evalueres, er brukererfaringer og tilfredshet hos pasienter viktig kunnskap. En faktor som kan påvirke pasienttilfredshet er triageresultatet, som er en kategorisering av hastegrad. Hvis det brukes to triagesystemer, ett ved telefonkontakt og senere ett ved oppmøte, kan det bli endringer i vurdering av hastegrad som ytterligere kan påvirke pasienttilfredshet. Det er behov for oppdaterte studier på hva som påvirker pasienttilfredshet ved norske legevakter og det er ikke funnet studier som har undersøkt om endringer i hastegrad mellom telefon- og oppmøtetriage påvirker pasient-tilfredshet med legevakten. Mål: Bidra med kunnskap om hvordan pasientens triageresultatet og andre faktorer er assosiert med pasienttilfredshet på en kommunal legevakt som bruker to ulike triagesystemer. Ett for telefonhenvendelser og ett for fysisk oppmøte. Metode: Det ble gjennomført en observasjonsstudie med en elektronisk spørreskjemaundersøkelse av pasienttilfredshet og innhenting av registreringsinformasjon om legevaktbesøket og triageresultater. Det ble brukt deskriptive analyser for å beskrive pasienttilfredshet og triageresultat, og bivariable- og regresjonsanalyser for å undersøke assosiasjonen mellom pasienttilfredshet (avhengig variabel), triageresultat og andre uavhengige variabler. Resultat: Pasientene (N=715) skåret generelt høyt på totaltilfredshet med opplevelsen av legevakten (75,6 på en skala fra 0 til 100). De skåret noe lavere på tilfredshet med organisering, enn på tilfredshet med telefon-, lege- og sykepleierkontakt. Totalt var det 59% (420 av 715 personer) som fikk samme hastegrad i både telefon- og oppmøtetriage, mens 17% (121) ble nedtriagert (lavere triage ved oppmøte enn ved telefon) og 24 % (174) ble opptriagert. Regresjonsanalysene viste at hverken nedtriagering (lavere triage ved oppmøte enn ved telefon) eller opptriagering (høyere triage ved oppmøte enn ved telefon) påvirket pasienttilfredsheten generelt. Det å få tilstrekkelig informasjon om tilstanden var den eneste variabelen som hadde en sammenheng med alle målene for tilfredshet. Totaltilfredshet økte mest hvis hjelpen fra legevakten var som forventet eller bedre, mens over 3 timers ventetid var det som reduserte den mest. Konklusjon: Pasienter er generelt tilfreds med legevakten, men minst tilfreds med organiseringen. Seks av ti personer får samme hastegrad i både telefon og oppmøtetriage. Funnene i denne studien tyder på at endring i triage ikke påvirker pasienttilfredshet, og at forventninger og ventetid er det som henger sterkest sammen med totaltilfredshet. Nøkkelord: Pasienttilfredshet, legevakt, triage, Manchester Triage system, Norsk Indeks for Medisinsk Nødhjel

Design of films for oral dosage formulations

Pharmaceutical dosage forms, more specifically tablets, are typically coated in order to taste mask and protect the core from e.g. light. Conventionally tablets are film-coated where an aqueous/organic solution is sprayed onto the tablet. This may cause stability and safety issues, for example, if the tablet core is moisture-sensitive while on the other hand, the use of organic solvents may increase the cost and introduce safety issues Also there may be a need for alternative and possibly more effective coating method in pharmaceutical industry therefore a novel method for tablet coating was studied where a thin polymer film was cast (pre-formed film), dried and applied as a coating hence eliminating the need for using any solvent during the actual coating process.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

In vivo effects of AZD4547, a novel fibroblast growth factor receptor inhibitor, in a mouse model of endometriosis

Abstract Endometriosis is a chronic disease, characterized by the growth of endometrial‐like cells outside the uterine cavity. Due to its complex pathophysiology, a totally resolving cure is yet to be found. The aim of this study was to compare the therapeutic efficacy of AZD4547, a novel fibroblast growth factor receptor inhibitor (FGFRI), with a well‐characterized progestin, etonogestrel (ENG) using a validated in vivo mouse model of endometriosis. Endometriosis was induced by transplanting uterine fragments from donor mice in proestrus into the peritoneal cavity of recipient mice, which then developed into cyst‐like lesions. AZD4547 and ENG were administered systemically either from the day of endometriosis induction or 2‐weeks post‐surgery. After 20 days of treatment, the lesions were harvested; their size and weight were measured and analyzed histologically or by qRT‐PCR. Stage of estrous cycle was monitored throughout. Compared to vehicle, AZD4547 (25 mg/kg) was most effective in counteracting lesion growth when treating from day of surgery and 2 weeks after; ENG (0.8 mg/kg) was similarly effective in reducing lesion growth but only when administered from day of surgery. Each downregulated FGFR gene expression (p < 0.05). AZD4547 at all doses and ENG (0.008 mg/kg) caused no disturbance to the estrous cycle. ENG at 0.08 and 0.8 mg/kg was associated with partial or complete estrous cycle disruption and hyperemia of the uteri. AZD4547 and ENG both attenuated endometriotic lesion size, but only AZD4547 did not disrupt the estrous cycle, suggesting that targeting of FGFR is worthy of further investigation as a novel treatment for endometriosis