Seminal plasma and prostaglandin E2 up-regulate fibroblast growth factor 2 expression in endometrial adenocarcinoma cells via E-series prostanoid-2 receptor-mediated transactivation of the epidermal growth factor receptor and extracellular signal-regulated kinase pathway

BACKGROUND: Prostaglandin E(2) (PGE(2)) has been shown to modulate angiogenesis and tumour progression via the E-series prostanoid-2 (EP2) receptor. Endometrial adenocarcinomas may be exposed to endogenous PGE(2) and exogenous PGE(2), present at high concentration in seminal plasma. METHODS: This study investigated fibroblast growth factor 2 (FGF2) mRNA expression and cell signalling in response to seminal plasma or PGE(2), using an endometrial adenocarcinoma (Ishikawa) cell line stably expressing the EP2 receptor (EP2 sense cells) and endometrial adenocarcinoma explants. RESULTS: Seminal plasma and PGE(2) induced a significant up-regulation of FGF2 expression in EP2 sense but not parental untransfected Ishikawa (wild-type) cells (P < 0.05). These effects were inhibited by co-treatment with EP2 receptor antagonist or inhibitors of protein kinase A, c-Src, epidermal growth factor receptor (EGFR) kinase or extracellular signal-regulated kinase (ERK) signalling. The treatment of EP2 sense cells with seminal plasma induced cAMP accumulation and phosphorylation of c-Src, EGFR kinase and ERK via the EP2 receptor. Finally, seminal plasma and PGE(2) significantly increased FGF2 mRNA expression in endometrial adenocarcinoma tissue explants via the EP2 receptor (P < 0.05). CONCLUSIONS: Seminal plasma and PGE(2) can similarly activate FGF2 expression and EP2 receptor signalling in endometrial adenocarcinoma cells. These data highlight the potential for seminal plasma exposure to facilitate tumorigenesis–angiogenesis in endometrial adenocarcinomas in vivo

Environment, human reproduction, menopause, and andropause.

As the hypothalamic gonadotropin-releasing hormone (GnRH) pulse generator is an integrator of hormonal, metabolic, and neural signals, it is not surprising that the function of the hypothalamogonadal axis is subject to the influence of a large array of environmental factors. Before puberty, the central nervous system (CNS) restrains the GnRH pulse generator. Undernutrition, low socioeconomic status, stress, and emotional deprivation, all delay puberty. During reproductive life, among peripheral factors that effect the reproductive system, stress plays an important role. Stress, via the release of corticotropin-releasing factor (CRF), eventually triggered by interleukin 1, inhibits GnRH release, resulting in hypogonadism. Effects of CRF are probably mediated by the opioid system. Food restriction and underweight (anorexia nervosa), obesity, smoking, and alcohol all have negative effects on the GnRH pulse generator and gonadal function. Age and diet are important determinants of fertility in both men and women. The age-associated decrease in fertility in women has as a major determinant chromosomal abnormalities of the oocyte, with uterine factors playing a subsidiary role. Age at menopause, determined by ovarian oocyte depletion, is influenced by occupation, age at menarche, parity, age at last pregnancy, altitude, smoking, and use of oral contraceptives. Smoking, however, appears to be the major determinant. Premature menopause is most frequently attributable to mosaicism for Turner Syndrome, mumps ovaritis, and, above all, total hysterectomy, which has a prevalence of about 12-15% in women 50 years old. Premature ovarian failure with presence of immature follicles is most frequently caused by autoimmune diseases or is the consequence of irradiation or chemotherapy with alkylating cytostatics. Plasma estrogens have a physiological role in the prevention of osteoporosis. Obese women have osteoporosis less frequently than women who are not overweight. Early menopause, suppression of adrenal function (corticoids), and thyroid hormone treatment all increase the frequency of osteoporosis. Aging in men is accompanied by decreased Leydig cell and Sertoli cell function, which has a predominantly primary testicular origin, although changes also occur at the hypothalamopituitary level. Plasma testosterone levels, sperm production, and sperm quality decrease, but fertility, although declining, is preserved until senescence. Stress and disease states accelerate the decline on Leydig cell function. Many occupational noxious agents have a negative effect on fertility.(ABSTRACT TRUNCATED AT 400 WORDS

Demographic, clinical and antibody characteristics of patients with digital ulcers in systemic sclerosis: data from the DUO Registry

OBJECTIVES: The Digital Ulcers Outcome (DUO) Registry was designed to describe the clinical and antibody characteristics, disease course and outcomes of patients with digital ulcers associated with systemic sclerosis (SSc). METHODS: The DUO Registry is a European, prospective, multicentre, observational, registry of SSc patients with ongoing digital ulcer disease, irrespective of treatment regimen. Data collected included demographics, SSc duration, SSc subset, internal organ manifestations, autoantibodies, previous and ongoing interventions and complications related to digital ulcers. RESULTS: Up to 19 November 2010 a total of 2439 patients had enrolled into the registry. Most were classified as either limited cutaneous SSc (lcSSc; 52.2%) or diffuse cutaneous SSc (dcSSc; 36.9%). Digital ulcers developed earlier in patients with dcSSc compared with lcSSc. Almost all patients (95.7%) tested positive for antinuclear antibodies, 45.2% for anti-scleroderma-70 and 43.6% for anticentromere antibodies (ACA). The first digital ulcer in the anti-scleroderma-70-positive patient cohort occurred approximately 5 years earlier than the ACA-positive patient group. CONCLUSIONS: This study provides data from a large cohort of SSc patients with a history of digital ulcers. The early occurrence and high frequency of digital ulcer complications are especially seen in patients with dcSSc and/or anti-scleroderma-70 antibodies

Elevmedvirkning i kroppsøving - En kvalitativ studie av noen lærere- og elevers beskrivelser av elevmedvirkning i kroppsøving på ungdomsskolen.

Denne masteroppgaven er en kvalitativ studie som har til hensikt å belyse hvordan noen elever i ungdomsskolen opplever elevmedvirkning og hvordan noen lærere i ungdomsskolen praktiserer elevmedvirkning. Dette gjøres gjennom problemstillingen: Hva kjennetegner noen læreres og elevers beskrivelser rundt begrepet elevmedvirkning i kroppsøving? Med to underliggende forskningsspørsmål. a) Hvordan beskriver lærere i denne studien at de legger til rette for elevmedvirkning i kroppsøving? b) Hvordan beskriver elevene i denne studien sine opplevelser med elevmedvirkning i kroppsøving? Undersøkelsen baserer seg på semistrukturerte dybdeintervjuer med tre ulike ungomdsskolelærere og tre gruppeintervjuer med elever fra 8. 9. og 10. trinn ved en ungdomsskole. Oppgavens bakgrunn er knyttet til resultater fra elevundersøkelsen og tidligere forskning rundt elevmedvirkning i kroppsøving. Innholdet i begrepet elevmedvirkning forankres og forklares ved en gjennomgang av hvordan elevmedvirkning står beskrevet i læreplanen. Elevmedvirkning knyttes til å involvere tilpasset opplæring og vurdering for læring. Studiens funn diskuteres i lys av læreplanen, tidligere forskning og et teoretisk rammeverk i form av læringsteorien The Spectrum of Teaching Styles av Mosston og Ashworth (2008). Denne læringsteorien forklarer fenomenet undervisning som en prosess som er definert av hvem som tar beslutninger i interaksjonen mellom lærer og elev. Funnene viser at beskrivelser av elevmedvirkning ikke er så forskjellige fra det tidligere forskning viser, det er rom for å praktisere mer elevmedvirkning enn det gjøres i dag (Aarskog et al., 2021; Engebretsen et al., 2020; Utdanningsdirektoratet, 2021; Moen et al. 2018; Leirhaug, 2016; Standal et al., 2020; Wendelborg et al., 2018). Elevene beskriver tilpasset opplæring, og inkludering i planlegging og vurdering, som viktige aspekter ved elevmedvirkning. Det å være inkludert på en slik måte at kroppsøvingsundervisningen føles relevant, pekes på av Beni et al. (2017), som en av de viktigste faktorene for at elevene skal oppleve faget som meningsfullt. Elevene beskriver også at de synes det er utfordrende å bli inkludert i vurderingsarbeid når læreren ikke snakker et språk de forstår. Måten elevene blir inkludert i vurderingsarbeidet er av stor betydning for utbyttet av vurderingen (Aarskog, 2021; Leirhaug & Annerstedt, 2016; Leirhaug et al., 2016)

Nomogram predicting macroscopic finding with limited or no clinical implication in 19175 patients referred to esophagogastroduodenoscopy

Objective: The diagnostic yield of esophagogastroduodenoscopy (EGD) depends on appropriate patient selection. The aim of the current study was to create a nomogram predicting findings with limited or no clinical implication in patients referred to EGD. Patients and methods: Indications and findings were registered prospectively in patients who underwent first-time EGD from 1994 to 2013. All findings were classified as “finding with limited or no clinical implication” or “finding with or possibly with clinical implication,” and used to create a predicting nomogram. Results: A total of 19175 patients were included (female: 59.0% [n = 11,312], male: 41.0% [n = 7,863]) with 30821 combinations of indications and findings, of which 20,512 (66.6%) constituted findings with limited or no clinical implication. The median age was 61 (58.9 ± 20.6 [mean ± standard deviation]) years and age was the strongest factor associated with normal EGD. Risk relationships were determined for age and indications by sex and used to create a nomogram. Receiver operating characteristics analysis was used to validate the nomogram-calculated probability of a finding with limited or no clinical implication (area under curve: 0.721; p < 0.001). Conclusion: The present nomogram may clarify the EGD yield challenges to referring physicians and patients. Early use of the nomogram may prevent unnecessary EDGs and assist to increase the diagnostic yield of the procedure