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Background: Hyaluronan, a tumor promoting extracellular matrix polysaccharide, is elevated in malignant epithelial ovarian tumors, and associates with an unfavorable prognosis. To explore possible contributors to the accumulation of hyaluronan, we examined the expression of hyaluronan synthases (HAS1, HAS2 and HAS3) and hyaluronidases (HYAL1 and HYAL2), correlated with hyaluronidase enzyme activity hyaluronan content and HAS1-3 immunoreactivity.Methods: Normal ovaries (n = 5) and 34 serous epithelial ovarian tumors, divided into 4 groups: malignant grades 1+2 (n = 10); malignant grade 3 (n = 10); borderline (n = 4) and benign epithelial tumors (n = 10), were analyzed for mRNA by real-time RT-PCR and compared to hyaluronidase activity, hyaluronan staining, and HAS1-3 immunoreactivity in tissue sections of the same specimens.Results: The levels of HAS2 and HAS3 mRNA (HAS1 was low or absent), were not consistently increased in the carcinomas, and were not significantly correlated with HAS protein or hyaluronan accumulation in individual samples. Instead, the median of HYAL1 mRNA level was 69% lower in grade 3 serous ovarian cancers compared to normal ovaries (P = 0.01). The expression of HYAL1, but not HYAL2, significantly correlated with the enzymatic activity of tissue hyaluronidases (r = 0.5; P = 0.006). An inverse correlation was noted between HYAL1 mRNA and the intensity of hyaluronan staining of the corresponding tissue sections (r = -0.4; P = 0.025).Conclusion: The results indicate that in serous epithelial ovarian malignancies HAS expression is not consistently elevated but HYAL1 expression is significantly reduced and correlates with the accumulation of hyaluronan. (233 words). [ABSTRACT FROM AUTHOR]

This investigation examined how people perceive field afforestation in two valuable landscape areas in northeastern Finland. Altogether 190 respondents assessed the scenic beauty of the views shown on 11 slides of five different afforestation options. The alternatives were created from two basic scenes using computer-assisted photographic simulation. Afforestation was considered disturbing even though the afforested area was small. Afforestation especially disturbed local residents, who had learned to appreciate their everyday landscape highly. The location of the afforested area was the most important factor affecting afforestation preferences. Our results suggest that afforestation should be located at the forest edge, whereas afforestation located in the middle of a field was the least preferred option. Afforestation site shapes reflecting the forms of the surrounding landscape were appreciated. The tree species used in afforestation had no bearingon preferences. Apparently, afforestation was more disturbing, and the details of afforestation more important, in appealing and valuablelandscapes than in less attractive environments. (C) 1998 Elsevier Science B.V. [ABSTRACT FROM AUTHOR]

Background: As n-3 long-chain polyunsaturated fatty acids and probiotics possess immunomodulatory properties, theoretically they could lower the risk of allergic diseases. But their effects remain controversial. We aimed to study the effects of fish oil and probiotics separately or in combination from early pregnancy onwards to lower the risk of allergic diseases in the infants., Methods: In this double-blind trial, women (n = 439) in early pregnancies were randomized into four intervention groups: fish oil + placebo, probiotics + placebo, fish oil + probiotics, and placebo + placebo. Fish oil (1.9 g docosahexaenoic acid and 0.22 g eicosapentaenoic acid) and probiotic (Lacticaseibacillus rhamnosus HN001 and Bifidobacterium animalis ssp. lactis 420, 10 10 colony-forming units each) supplements were provided for daily consumption from randomization up to 6 months postpartum. All analyses were adjusted with pet ownership., Results: No difference between the infants in the four intervention groups were found regarding physician-diagnosed food allergy, atopic eczema, or atopy at the age of 12 or 24 months (all p > .05). The probiotic intervention was associated with lower odds of recurrent wheezing at 24 months (OR 0.39, 95% CI 0.18-0.84, p = .017), but not at 12 months., Conclusions: The use of fish oil and/or probiotics from early pregnancy onwards did not lower the odds of childhood allergic diseases or atopy, with the exception of the probiotic intervention which decreased the risk of recurrent wheezing when the infants were two years old. This suggests that the incidence of asthma could also decrease later in childhood and thus these outcomes need to be clarified in further investigations., (© 2023 The Authors. Pediatric Allergy and Immunology published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Rhinovirus (RV) and respiratory syncytial virus (RSV) are common causes of bronchiolitis. Unlike an RSV etiology, an RV etiology is associated with a markedly increased risk of asthma. We investigated the cytokine profiles of RV- and RSV-induced first wheezing episode and their correlation with prognosis. We recruited 52 sole RV- and 11 sole RSV-affected children with a severe first wheezing episode. Peripheral blood mononuclear cells (PBMCs) were isolated during acute illness and 2 weeks later and stimulated in vitro with anti-CD3/anti-CD28. Culture medium samples were analyzed for 56 different cytokines by multiplex ELISA. Recurrences were prospectively followed for 4 years. In adjusted analyses, the cytokine response from PBMCs in the RV group was characterized by decreased expression of interleukin 1 receptor antagonist (IL-1RA), interleukin 1 beta (IL-1β), and monocyte chemoattractant protein-1 (MCP-1) and increased expression of eosinophil chemotactic protein 2 (eotaxin-2), thymus- and activation-regulated chemokine (TARC), and epithelial-derived neutrophil-activating peptide 78 (ENA-78) in the acute phase and increased expression of fractalkine in the convalescent phase compared to those in the RSV group. An analysis of the change in cytokine expression between study points revealed an increased expression of fractalkine and IL-1β and decreased expression of I-309 (CCL1) and TARC in the RV group compared to those in the RSV group.. Considering hospitalization time, a significant non-adjusted group × cytokine interaction was observed in the levels of interferon gamma (IFN-γ), macrophage-derived chemokine (MDC), IL-1RA, and vascular endothelial growth factor (VEGF), indicating that a higher expression of cytokine was associated with shorter hospitalization time in the RSV group but not in the RV group. A significant interaction was also found in interleukin 6 (IL-6), but the cytokine response was not associated with hospitalization time in the RSV or RV group. In the RV group, increased expression of I-309 (CCL1) and TARC was associated with fewer relapses within 2 months, and decreased expression of interleukin 13 (IL-13) and increased expression of I-309 (CCL1) were associated with less relapses within 12 months. Differences in cytokine response from PBMCs were observed between RV- and RSV-induced first severe wheezing episode. Our findings also reveal new biomarkers for short- and medium-term prognosis in first-time wheezing children infected with RV or RSV., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Hurme, Komulainen, Tulkki, Leino, Rückert, Turunen, Vuorinen, Akdis, Akdis and Jartti.)

Background: Older patients with ovarian cancer represent a heterogeneous population. The French National Group of Investigators for the Study of Ovarian and Breast Cancer developed the geriatric vulnerability score (GVS) to identify geriatric parameters predictive of poor outcomes. A prospective validation of the GVS was needed., Methods: The EWOC-1 study (NCT02001272) was an international, open-label, phase 2, three-arm trial designed according to a two-step process. Patients aged 70 years or older with newly diagnosed stage III or IV ovarian cancer were identified and the GVS determined. Those with a GVS of 3 or greater were randomly assigned to the EWOC-1 trial, stratified by country and surgical outcome, to receive three different carboplatin with or without paclitaxel regimens; those not included in the EWOC-1 trial were followed up in the EWOC-1 registry. External validation of the GVS was a secondary endpoint of the trial. Three validation cohorts were identified: the total population (validation cohort 1 [V1], n=447), the registry-only population (validation cohort 2 [V2], n=327), and the carboplatin-paclitaxel-treated population (validation cohort 3 [V3], n=320)., Findings: From Dec 11, 2013, to Nov 16, 2018, 447 patients were included in 48 academic centres in six countries; 120 in the EWOC-1 trial and 327 in the EWOC-1 registry. Median follow-up was 19·7 (95% CI 8·5-29·7) months for the total cohort; missing values were low (<2%). According to the maximum likelihood analysis, the hazard ratio (HR) of death in V1 was 1·8 (95% CI 1·1-3·1, p=0·029) for those with a GVS of 1; 2·4 (1·4-4·0, p=0·0009) with a GVS of 2; 4·1 (2·5-7·0, p<0·0001) for a GVS of 3; 5·5 (3·3-9·3, p<0·0001) for a GVS of 4; and 9·1 (4·7-17·5, p<0·0001) for a GVS of 5 compared with a score of 0. Whatever the validation cohort, GVS of 3 or more significantly segregated two groups with different overall survival: V1 (median 13·2 [95% CI: 10·8-18·7] vs 40·8 [32·0-45·6] months; HR 2·8 [95% CI 2·2-3·7]; p<0·0001); V2 (11·9 [95% CI 8·8-18·1] vs 40·8 [32·0-45·6] months, HR 3·5 [2·5-4·9]; p<0·0001); and V3 (18·1 [95% CI 15·8-31·8] vs 43·0 [40·6-49·7] months, HR 2·6 [1·9 to 3·7]; p<0·0001)., Interpretation: The GVS has high prognostic performance for overall survival in patients with advanced ovarian cancer, independently of geographic and historic effect (V1), as well as treatment patterns (V3), validated in an international population. Even though the GVS is time consuming it will allow the stratification of populations for clinical research and might permit the orientation of the geriatric intervention to specific domains., Funding: French National Cancer Institute., Translation: For the French translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests CF reports a grant from the French National Cancer Institute during the conduct of the study; personal fees from Leo Pharma, Pfizer, MSD Oncology, Teva, AstraZeneca, Baxter, Eisai, Janssen Oncology, Novartis, Chugai Pharma, and Astellas Pharma, outside the submitted work; grants from Chugai Pharma, Pfizer, Pierre Fabre, and Astellas Pharma, outside the submitted work; and non-financial support from Janssen Oncology, Pierre Fabre, AstraZeneca, and Leo Pharma, outside the submitted work. FT reports grants from French National Institute (via Hospices Civils de Lyon), during the conduct of the study. DL reports grants from PharmaMar, Merck Serono, Novartis, AstraZeneca, Clovis Oncology, Tesaro, GSK, Roche, Genmab, and Immunogen, during the conduct of the study. AF reports personal fees from MSD, AstraZeneca, GSK, and Clovis Oncology, outside the submitted work. FR reports participation in a specialist advisory board for Bristol Myers Squibb. OT reports grants and personal fees from Roche and MSD, grants from BMS, and personal fees from Novartis-Sandoz, Pfizer, Lilly, AstraZeneca, Daiichi Sankyo, Eisai, Pierre Fabre, and Seagen, outside the submitted work. EP-L reports personal fees and non-financial support from AstraZeneca, Tesaro, and Roche; personal fees from Clovis, Incyte, and Pfizer; and other from Association de Recherche sur les CAncers dont GYnécologiques (ARCAGY) Research, outside the submitted work. All other authors declare no competing interests., (Copyright © 2022 The Authors. Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Ovarian cancer is the most lethal gynaecological cancer. It appears that seemingly ovarian or primary peritoneal carcinomas, in fact, originate from fimbriae. BRCA1/2 mutation carriers are recommended for the removal of ovaries and fimbriae, to reduce the risk of cancer. Treatment of epithelial ovarian cancer is based on the combination of surgery and chemotherapy. The residual tumour volume at the primary operation is the most important predictive factor of survival. The best response at the primary treatment is observed with combination chemotherapy with taxane and platinum. Adding bevacitzumab to first line chemotherapy may improve survival.

Objective: To determine the effects of HRT with or without clodronate on bone mineral density (BMD) change and bone turnover markers., Design: Prospective, partly randomized trial., Setting: Kuopio University Hospital, Finland., Population: 167 osteoporotic women (61+/-2.7 years; T-score

Objective: Our recent prospective, nation-wide study indicated better surgical outcome in ovarian cancer patients operated at university hospitals compared to other hospitals. Here we report how this is reflected in 5-year cancer-specific survival (CSS)., Methods: Detailed 5-year follow-up data were obtained on 275 patients by using a special questionnaire, and the data were verified from the Finnish Cancer Registry data. The hospitals were categorized to university and other hospitals and by the number of operations performed in 1999 (<10, 10-20, or >20 operations). Data were analyzed using the Cox's proportional hazards regression analysis., Results: The study population covered 90% of the epithelial ovarian cancer patients operated in 1999, in Finland. Eighty-two percent of the patients received platinum-based chemotherapy. The percentage of patients treated with a platinum-taxane combination was higher in university hospitals (63% vs. 49%, P=0.037). The 5-year CSS was 56% and the median disease-free survival (DFS) was 33 months. In multivariate analysis prognostic factors for CSS were stage (P=0.0027), residual tumor (P=0.0001), and primary chemotherapy (P<0.0001). Hospital operative volume was associated with residual tumor (P=0.027). When hospital operative volume increased with ten patients per year, the odds ratio for no residual disease was 1.203 (95% CI 1.022-1.417)., Conclusion: FIGO stage, residual tumor, and primary chemotherapy are significant prognostic factors for ovarian cancer. Hospital volume is associated with residual tumor. The results favor performance of ovarian cancer surgery in hospitals with higher operative volumes.

Background: Surgical treatment and staging of ovarian borderline tumors have been reported to be often suboptimal and differ considerably. We evaluated the extent of surgical treatment of these tumors in different hospital categories., Material and Methods: A prospective survey performed in 1999 included 65 patients operated on for borderline ovarian tumors and covered 78% of such patients reported to the Finnish Cancer Registry. Detailed information of demographic data and surgical treatment was reported by the responsible physicians using a special questionnaire after confirmation of histopathology., Results: Fifty-eight patients (89%) had stage I tumor, only two patients (3%) had stage II disease and five patients (8%) had stage III disease with peritoneal implants. The majority of the patients underwent bilateral salpingo-oophorectomy (66%) and hysterectomy (58%). Unilateral salpingo-oophorectomy was performed for 21 (32%) and omentectomy for 22 (34%) patients. Ten out of the 16 women under 40 years of age had fertility-sparing surgery. Peritoneal biopsies were taken in 16 (25%) women and lymphadenectomy was performed for 9 (14%) patients with clinical suspicion of invasive ovarian carcinoma. Frozen section was taken in half of the patients and the histology remained the same in 72% of the final pathology reports. No clear differences of the extent of surgical treatment were detected between different hospital categories. Overall cumulative 5-year relative survival rate was 96%., Conclusions: Bilateral salpingo-oophorectomy and hysterectomy was performed for the majority of patients with borderline ovarian tumor. More attention should be paid to adequate staging of borderline tumors in all hospital categories.