Evaluation of myosin VI, E-cadherin and beta-catenin immunostaining in renal cell carcinoma

<p>Abstract</p> <p>Background</p> <p>Renal cell carcinoma (RCC) is a cancer of increasing incidence and mortality. Currently, there are no immunohistochemical prognostic markers for RCCs in routine use. The aim of this study was to examine for the first time the immunostaining of myosin VI in RCCs as well as its association with E-cadherin and beta-catenin immunostaining and the prognostic significance of these markers in RCCs.</p> <p>Methods</p> <p>Our study population consisted of 152 patients who underwent surgery for RCCs between 1990 and 1999. The tumours were examined with three immunohistochemical markers: myosin VI, E-cadherin and beta-catenin.</p> <p>Results</p> <p>The immunostaining for cytoplasmic myosin VI was common (72%). One-third of the tumours were immunopositive for nuclear myosin VI. Cytoplasmic myosin VI immunopositivity and nuclear beta-catenin immunostaining were associated with lower Fuhrman grades (<it>p </it>= 0.04 and <it>p </it>= 0.005, respectively), but not stages. There was no significant association between myosin VI immunostaining and the histological subtype of RCC. Nuclear myosin VI was associated with the nuclear expression of beta-catenin. A direct association could also be proven between membranous E-cadherin and cytoplasmic beta-catenin. Cytoplasmic myosin VI immunostaining was a marker of poorer prognosis in multivariate Cox regression model adjusted with stage and Fuhrman grade with hazard ratio 2.4 (95% confidence interval 1.1 to 5.0 with <it>p </it>= 0.024).</p> <p>Conclusions</p> <p>Cytoplasmic myosin VI immunopositivity and nuclear beta-catenin immunostaining were associated with lower Fuhrman grades, and there was a strong positive relationship between E-cadherin immunostaining and beta-catenin immunostaining in RCCs. Cytoplasmic myosin VI immunostaining was associated with poorer prognosis in RCCs.</p

Oral Health in Women with a History of High Gestational Diabetes Risk

We studied oral health in 115 women with and without a history of gestational diabetes (GDM), expecting poorer oral health in the GDM group. Full-mouth examinations were performed 5 years postpartum and the number of teeth, total dental index (TDI) and decayed, missing, filled teeth (DMFT) index were calculated. Bleeding on probing (BOP), probing depth (PD), visible plaque index (VPI), and clinical attachment level (CAL) were recorded. The periodontal inflammatory burden index (PIBI) was calculated. Panoramic radiographs were taken and signs of infections recorded. Oral health habits, symptoms and participants’ own opinion of oral health were recorded with questionnaires. At the time of examination, 45% of the women had a history of GDM in the index pregnancy. Mild periodontitis (62%) and bleeding on probing (46%) were common. VPI (13% and 17%, p = 0.009) and PIBI (13.1 and 17.5, p = 0.041) were lower among women with a history of GDM compared with those with no history of GDM. There was no difference between groups in DMFT scores. All women reported good subjective oral health. Thus, contrary to our hypothesis, women with a history of GDM showed better oral health parameters than women without a history of GDM

Physical activity and health-related quality of life among high-risk women for type 2 diabetes in the early years after pregnancy

Background Previous studies have shown that physical activity (PA) correlates positively with health-related quality of life (HRQoL) in the general population. Few studies have investigated associations between device-measured PA and HRQoL among premenopausal women at risk for type 2 diabetes (T2D). In addition to physical well-being, general well-being improved by PA has been suggested to strengthen PA's benefits in reducing metabolic diseases. The aim of this study was to examine the associations between PA and HRQoL (general and dimensions) among high-risk women in the early post-pregnancy years when T2D risk is highest and to estimate whether current obesity or prior gestational diabetes (GDM) modified these associations. Methods This cross-sectional study of high-risk women [body mass index (BMI) >= 30 kg/m(2) and/or prior GDM)]4-6 years after delivery measured sleep, sedentary time, daily steps, and light (LPA), moderate-to-vigorous (MVPA), and vigorous PA (VPA) with the SenseWear ArmbandTM accelerometer for seven days and HRQoL with the 15D instrument. Results The analyses included 204 women with a median (IQR) age of 39 (6.0) years and a median BMI of 31.1 kg/m(2) (10.9). 54% were currently obese (BMI >= 30 kg/m(2)), and 70% had prior gestational diabetes (GDM+). Women with obesity had lower PA levels than women with normal weight or overweight (p = 30 kg/m(2)), the associations remained significant only in women without obesity. Among them, sleep, total steps, MVPA, and VPA were positively associated with 15D. Conclusions Higher PA levels are associated with better HRQoL among high-risk women with normal weight and overweight but no differences were found among women affected by obesity in the early years after pregnancy. Trial registration Ethics committees of Helsinki University Hospital (Dnro 300/e9/06) and South Karelian Central Hospital (Dnro 06/08).Peer reviewe

Absent Toll-like receptor-9 expression predicts poor prognosis in renal cell carcinoma

<p>Abstract</p> <p>Background</p> <p>Toll-like receptor 9 (TLR9) is a cellular DNA-receptor whose activation with cognate ligands triggers an immune reaction, with increased production of inflammatory cytokines. The aim of this study was to examine the expression of TLR9 in renal cell carcinoma (RCC), which is generally renowned of its immunogenic nature. We also evaluated the prognostic value of TLR9 in RCC.</p> <p>Methods</p> <p>TLR9 expression in RCC was characterized with immunohistochemistry in a retrospective study population of 152 RCC patients who underwent renal surgery. The TLR9 staining intensity was compared with clinical parameters.</p> <p>Results</p> <p>Of the studied tumours, 112 (81%) exhibited cytoplasmic TLR9 immunostaining. No association was detected between cytoplasmic TLR9 immunoexpression intensity and stage, nuclear grade, histological subtype or tumour necrosis. Cytoplasmic TLR9 immunoexpression was, however, a marker of favourable RCC specific survival both in univariate analysis and in multivariate regression model.</p> <p>Conclusions</p> <p>We conclude that TLR9 expression is an independent prognostic marker of RCC and the absence of TLR9 expression is related to poorer prognosis in RCC.</p

Ascending Growth is Associated with Offspring Adiposity in Pregnancies Complicated with Obesity or Gestational Diabetes

Context: Early growth is associated with childhood adiposity, but the influence of lifestyle remains unknown. Objective: This work aimed to investigate the association of growth profiles from high-risk pregnancies with adiposity at age 5 years, taking into account lifestyle and several antenatal/postnatal exposures. Methods: This prospective cohort study included 609 children born during the Finnish Gestational Diabetes Prevention Study (RADIEL), recruiting women with body mass index (BMI) greater than or equal to 30 and/or prior gestational diabetes mellitus (GDM) (2008-2013). Altogether 332 children attended the 5-year follow-up (2014-2017). Main outcome measures included growth profiles based on ponderal index (PI = weight/height(3)), investigated using latent class mixed models. Adiposity was assessed with anthropometrics and body composition (InBody720). Results: We identified 3 growth profiles: ascending (n = 82), intermediate (n = 351), and descending (n = 149). Children with ascending growth had a higher body fat percentage, ISO-BMI, and waist circumference (P Conclusion: Accelerated early growth was associated with higher adiposity in 5-year-old children from high-risk pregnancies, even when adjusted for lifestyle. Reducing cesarean deliveries and promoting breastfeeding may be beneficial for postnatal growth.Peer reviewe

Genetic risk of type 2 diabetes modifies the effects of a lifestyle intervention aimed at the prevention of gestational and postpartum diabetes

Aims/hypothesis The aim of this study was to assess the interaction between genetic risk and lifestyle intervention on the occurrence of gestational diabetes mellitus (GDM) and postpartum diabetes. Methods The RADIEL study is an RCT aimed at prevention of GDM and postpartum diabetes through lifestyle intervention. Participants with a BMI >= 30 kg/m(2) and/or prior GDM were allocated to intervention and control groups before pregnancy or in early pregnancy. The study visits took place every 3 months before pregnancy, once in each trimester, and at 6 weeks and 6 and 12 months postpartum. We calculated a polygenic risk score (PRS) based on 50 risk variants for type 2 diabetes. Results Altogether, 516 participants provided genetic and GDM data. The PRS was associated with higher glycaemic levels (fasting glucose and/or HbA(1c)) and a lower insulin secretion index in the second and third trimesters and at 12 months postpartum, as well as with a higher occurrence of GDM and glycaemic abnormalities at 12 months postpartum (n = 356). There was an interaction between the PRS and lifestyle intervention (p=0.016 during pregnancy and p=0.024 postpartum) when analysing participants who did not have GDM at the first study visit during pregnancy (n = 386). When analysing women in tertiles according to the PRS, the intervention was effective in reducing the age-adjusted occurrence of GDM only among those with the highest genetic risk (OR 0.37; 95% CI 0.17, 0.82). The risk of glycaemic abnormalities at 12 months postpartum was reduced in the same group after adjusting additionally for BMI, parity, smoking and education (OR 0.35; 95% CI 0.13, 0.97). Conclusions/interpretation Genetic predisposition to diabetes modifies the response to a lifestyle intervention aimed at prevention of GDM and postpartum diabetes. This suggests that lifestyle intervention may benefit from being tailored according to genetic risk.Peer reviewe

Long-term effects of a preconception lifestyle intervention on cardiometabolic health of overweight and obese women

Background: The global prevalence of obesity in women keeps increasing. The preconception period may be a window of opportunity to improve lifestyle, reduce obesity and improve cardiometabolic health. This study assessed the effect of a preconception lifestyle intervention on long-term cardiometabolic health in two randomized controlled trials (RCTs).Methods: Participants of the LIFEstyle and RADIEL preconception lifestyle intervention studies with a baseline body mass index (BMI) ≥29 kg/m2 were eligible for this follow-up study. Both studies randomized between a lifestyle intervention targeting physical activity, diet and behaviour modification or usual care. We assessed cardiometabolic health 6 years after randomization.Results: In the LIFEstyle study (n = 111) and RADIEL study (n = 39), no statistically significant differences between the intervention and control groups were found for body composition, blood pressure, arterial stiffness, fasting glucose, homeostasis model assessment of insulin resistance, HbA1c, lipids and high sensitive C-reactive protein levels 6 years after randomization. Participants of the LIFEstyle study who successfully lost ≥5% bodyweight or reached a BMI &lt;29 kg/m2 during the intervention (n = 22, [44%]) had lower weight (-8.1 kg; 99% CI [-16.6 to -0.9]), BMI (-3.3 kg/m2; [-6.5 to -0.8]), waist circumference (-8.2 cm; [-15.3 to -1.3]), fasting glucose (-0.5 mmol/L; [-1.1 to -0.0]), HbA1c (-4.1 mmol/mol; [-9.1 to -0.8]), and higher HDL-C (0.3 mmol/L; [0.1-0.5]) compared with controls.Conclusion: We found no evidence of improved cardiometabolic health 6 years after a preconception lifestyle intervention among overweight and obese women in two RCTs. Women who successfully lost weight during the intervention had better cardiometabolic health 6 years later, emphasizing the potential of successful preconception lifestyle improvement.</p

Genetic risk of type 2 diabetes modifies the effects of a lifestyle intervention aimed at the prevention of gestational and postpartum diabetes

Aims/hypothesis The aim of this study was to assess the interaction between genetic risk and lifestyle intervention on the occurrence of gestational diabetes mellitus (GDM) and postpartum diabetes.Methods The RADIEL study is an RCT aimed at prevention of GDM and postpartum diabetes through lifestyle intervention. Participants with a BMI >= 30 kg/m(2) and/or prior GDM were allocated to intervention and control groups before pregnancy or in early pregnancy. The study visits took place every 3 months before pregnancy, once in each trimester, and at 6 weeks and 6 and 12 months postpartum. We calculated a polygenic risk score (PRS) based on 50 risk variants for type 2 diabetes.Results Altogether, 516 participants provided genetic and GDM data. The PRS was associated with higher glycaemic levels (fasting glucose and/or HbA(1c)) and a lower insulin secretion index in the second and third trimesters and at 12 months postpartum, as well as with a higher occurrence of GDM and glycaemic abnormalities at 12 months postpartum (n = 356). There was an interaction between the PRS and lifestyle intervention (p=0.016 during pregnancy and p=0.024 postpartum) when analysing participants who did not have GDM at the first study visit during pregnancy (n = 386). When analysing women in tertiles according to the PRS, the intervention was effective in reducing the age-adjusted occurrence of GDM only among those with the highest genetic risk (OR 0.37; 95% CI 0.17, 0.82). The risk of glycaemic abnormalities at 12 months postpartum was reduced in the same group after adjusting additionally for BMI, parity, smoking and education (OR 0.35; 95% CI 0.13, 0.97).Conclusions/interpretation Genetic predisposition to diabetes modifies the response to a lifestyle intervention aimed at prevention of GDM and postpartum diabetes. This suggests that lifestyle intervention may benefit from being tailored according to genetic risk.</p

Evaluation of neuroendocrine markers in renal cell carcinoma

<p>Abstract</p> <p>Background</p> <p>The purpose of the study was to examine serotonin, CD56, neurone-specific enolase (NSE), chromogranin A and synaptophysin by immunohistochemistry in renal cell carcinomas (RCCs) with special emphasis on patient outcome.</p> <p>Methods</p> <p>We studied 152 patients with primary RCCs who underwent surgery for the removal of kidney tumours between 1990 and 1999. The mean follow-up was 90 months. The expression of neuroendocrine (NE) markers was determined by immunohistochemical staining using commercially available monoclonal antibodies. Results were correlated with patient age, clinical stage, Fuhrman grade and patient outcome.</p> <p>Results</p> <p>Eight percent of tumours were positive for serotonin, 18% for CD56 and 48% for NSE. Chromogranin A immunostaining was negative and only 1% of the tumours were synaptophysin immunopositive. The NSE immunopositivity was more common in clear cell RCCs than in other subtypes (<it>p </it>= 0.01). The other NE markers did not show any association with the histological subtype. Tumours with an immunopositivity for serotonin had a longer RCC-specific survival and tumours with an immunopositivity for CD56 and NSE had a shorter RCC-specific survival but the difference was not significant. There was no relationship between stage or Fuhrman grade and immunoreactivity for serotonin, CD56 and NSE.</p> <p>Conclusions</p> <p>Serotonin, CD56 and NSE but not synaptophysin and chromogranin A are expressed in RCCs. However, the prognostic potential of these markers remains obscure.</p

Impaired Bone Health in Inflammatory Bowel Disease: A Case-Control Study in 80 Pediatric Patients

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