Wnt/β-catenin signaling plays a key role in maintaining homeostasis, which is disturbed in hypertension. Taking into account the lack of literature describing changes in the Wnt/β-catenin pathway in the adrenal glands under conditions of elevated arterial pressure, here we compare the expression of WNT4, WNT10A, β-catenin, and GSK-3β in the adrenal glands of hypertensive rats of various etiologies. The studies were carried out on the adrenal glands of rats with spontaneous hypertension (SHR), renalvascular (2K1C), and deoxycorticosterone acetate (DOCA)-salt. Immunohistochemical and PCR methods were used to identify the molecular components of the canonical signaling pathway and to evaluate gene expression. Immunoreactivity and expression of WNT4, WNT10A, β-catenin, and GSK-3β in adrenals of SHR was decreased, compared to control rats. In adrenals of 2K1C rats, intensity of immunohistochemical reaction and expression of WNT4 and β-catenin was lower, while immunoreactivity and expression of WNT10A and GSK-3β were higher, compared to normotensive animals. Significantly stronger immunoreaction and expression of WNT4, β-catenin and GSK-3β but weaker immunoreactivity and expression of WNT10A were noted in adrenals in DOCA-salt rats, compared to control rats. In conclusion, our data provide new molecular information indicating that the canonical WNT pathway is disrupted in the adrenal glands of hypertensive rats. They show that the dysregulation of the WNT pathway depends on the etiology of hypertension.
Irena Kasacka, Żaneta Piotrowska, Natalia Domian, and Alicja Lewandowska
Huda M Elsharkasi, Suet C Chen, Lewis Steell, Shuko Joseph, Naiemh Abdalrahaman, Christie McComb, Blair Johnston, John Foster, Sze Choong Wong, and S Faisal Ahmed
The aim of this study is to investigate the role of 3T-MRI in assessing musculoskeletal health in children and young people.
Bone, muscle and bone marrow imaging was performed in 161 healthy participants with a median age of 15.0 years (range, 8.0, 30.0).
Detailed assessment of bone microarchitecture (constructive interference in the steady state (CISS) sequence, voxel size 0.2 × 0.2 × 0.4 mm3), bone geometry (T1-weighted turbo spin echo (TSE) sequence, voxel size 0.4 × 0.4 × 2 mm3) and bone marrow (1H-MRS, point resolved spectroscopy sequence (PRESS) (single voxel size 20 × 20 × 20 mm3) size and muscle adiposity (Dixon, voxel size 1.1 × 1.1 × 2 mm3).
There was an inverse association of apparent bone volume/total volume (appBV/TV) with age (r = −0.5, P < 0.0005). Cortical area, endosteal and periosteal circumferences and muscle cross-sectional area showed a positive association to age (r > 0.49, P < 0.0001). In those over 17 years of age, these parameters were also higher in males than females (P < 0.05). This sex difference was also evident for appBV/TV and bone marrow adiposity (BMA) in the older participants (P < 0.05). AppBV/TV showed a negative correlation with BMA (r = −0.22, P = 0.01) which also showed an association with muscle adiposity (r = 0.24, P = 0.04). Cortical geometric parameters were highly correlated with muscle area (r > 0.57, P < 0.01).
In addition to providing deep insight into the normal relationships between bone, fat and muscle in young people, these novel data emphasize the role of MRI as a non-invasive method for performing a comprehensive and integrated assessment of musculoskeletal health in the growing skeleton.
Ling Sun, Wenwu Zhu, Yuan Ji, Ailin Zou, Lipeng Mao, Boyu Chi, Jianguang Jiang, Xuejun Zhou, Qingjie Wang, and Fengxiang Zhang
Post-treatment contrast-induced acute kidney injury (CI-AKI) is associated with poor outcomes in patients with acute myocardial infarction (AMI). A lower free triiodothyronine (FT3) level predicts a poor prognosis of AMI patients. This study evaluated the effect of plasma FT3 level in predicting CI-AKI and short-term survival among AMI patients.
Coronary arteriography or percutaneous coronary intervention was performed in patients with AMI. A 1:3 propensity score (PS) was used to match patients in the CI-AKI group and the non-CI-AKI group.
Of 1480 patients enrolled in the study, 224 (15.1%) patients developed CI-AKI. The FT3 level was lower in CI-AKI patients than in non-CI-AKI patients (3.72 ± 0.88 pmol/L vs 4.01 ± 0.80 pmol/L, P < 0.001). Compared with those at the lowest quartile of FT3, the patients at quartiles 2–4 had a higher risk of CI-AKI respectively (P for trend = 0.005). The risk of CI-AKI increased by 17.7% as FT3 level decreased by one unit after PS-matching analysis (odds ratio: 0.823; 95% CI: 0.685–0.988, P = 0.036). After a median of 31 days of follow-up (interquartile range: 30–35 days), 78 patients died, including 72 cardiogenic deaths and 6 non-cardiogenic deaths, with more deaths in the CI-AKI group than in the non-CI-AKI group (53 vs 25, P < 0.001). Kaplan–Meier survival analysis showed that patients at a lower FT3 quartile achieved a worse survival before and after matching.
Lower FT3 may increase the risk of CI-AKI and 1-month mortality in AMI patients.
Matteo Scopel, Eugenio De Carlo, Francesca Bergamo, Sabina Murgioni, Riccardo Carandina, Anna Rita Cervino, Marta Burei, Federica Vianello, Vittorina Zagonel, Matteo Fassan, and Roberto Vettor
We considered 351 patients affected by neuroendocrine tumors (NETs), followed at the University Hospital of Padua and at the Veneto Oncological Institute. Of these, 72 (20.5%) suffered from bone metastases. The sample was divided according to the timing of presentation of bone metastases into synchronous (within 6 months of diagnosis of primary tumor) and metachronous (after 6 months). We collected data on the type and grading of the primary tumor and on the features of bone metastases. Our analysis shows that the group of synchronous metastases generally presents primary tumors with a higher degree of malignancy rather than the ones of the metachronous group. This is supported by the finding of a Ki-67 level in GEP-NETs, at the diagnosis of bone metastases, significantly higher in the synchronous group. Moreover, in low-grade NETs, chromogranin A values are higher in the patients with synchronous metastases, indicating a more burden of disease. The parameters of phospho-calcium metabolism are within the normal range, and we do not find significant differences between the groups. Serious bone complications are not frequent and are not correlated with the site of origin of the primary tumor. From the analysis of the survival curves of the total sample, a cumulative survival rate of 33% at 10 years emerges. The average survival is 80 months, higher than what is reported in the literature, while the median is 84 months. In our observation period, synchronous patients tend to have a worse prognosis than metachronous ones with 52-months survival rates of 58 and 86%.
Judith Gebauer, Roderick Skinner, Riccardo Haupt, Leontien Kremer, Helen van der Pal, Gisela Michel, Greg Armstrong, Melissa M Hudson, Lars Hjorth, Hendrik Lehnert, and Thorsten Langer
Many long-term childhood cancer survivors suffer from treatment-related late effects, which may occur in any organ and include a wide spectrum of conditions. Long-term follow up (LTFU) is recommended to facilitate early diagnosis and to ensure better health outcomes. Due to the heterogeneity of these sequelae, different specialists work together in diagnosis and treatment of these conditions. Experts from both pediatric and internal medicine are involved in age-appropriate care by providing a transition process. Hence, LTFU of childhood cancer survivors is a prototypic example for multidisciplinary care of patients with complex needs treated in a specialized setting. International collaborations of health care professionals and scientists involved in LTFU of childhood cancer survivors, such as the International Guideline Harmonization Group, compile surveillance recommendations that can be clinically adopted all over the world. These global networks of clinicians and researchers make a joint effort to address gaps in knowledge, increase visibility and awareness of cancer survivorship and provide an excellent example of how progress in clinical care and scientific research may be achieved by international and multidisciplinary collaboration.
Ziting Liang, Mengge Yang, Changjuan Xu, Rong Zeng, and Liang Dong
Aim: This study aimed to investigate the effects and safety of metformin in patients with concurrent diabetes mellitus (DM) and chronic obstructive pulmonary disease (COPD).
Methods: PubMed, Embase, Web of Science, the China National Knowledge, and Cochrane Database were searched to find studies that examined the effects and safety of metformin in patients with concurrent DM and COPD. We conducted a meta-analysis with a risk ratio (RR) and assessed the quality of included studies and pooled evidence.
Results: Eight articles were involved. Metformin decreased the risk of COPD-related hospitalizations (RR 0.72, 95% CI 0.53-0.98; I2=89%) and all-cause mortality (RR 0.60, 95% CI 0.36–1.01, I2=69%) in patients with concurrent DM and COPD, but didn’t increase the risk of hyperlactatemia (RR 1.14, 95%CI 0.92-1.41, I2 =8%).
Conclusions: Metformin use in patients with concurrent DM and COPD might lower COPD-related hospitalizations and the risk of all-cause mortality without increasing the risk of hyperlactatemia. Considerations should be given to conduct more high-quality randomized trials involving larger samples.
Selina Mäkinen, Neeta Datta, Yen H Nguyen, Petro Kyrylenko, Markku Laakso, and Heikki A Koistinen
Olli Helminen, Tytti Pokka, Susanna Aspholm, Jorma Ilonen, Olli G. Simell, Mikael Knip, and Riitta Veijola
Objective: Subtypes in type 1 diabetes pathogenesis have been implicated based on the first appearing autoantibody (primary autoantibody). We set out to describe the glucose metabolism in preclinical diabetes in relation to the primary autoantibody in children with HLA-conferred disease susceptibility.
Design and Methods: Dysglycemic markers were defined as 10% increase in HbA1c in a 3-12 months interval or HbA1c ≥5.9% (41mmol/mol) in two consecutive samples, impaired fasting glucose or impaired glucose tolerance, or a random plasma glucose value ≥7.8mmol/l. A primary autoantibody could be detected in 295 children who later developed at least one additional biochemical autoantibody. These children were divided into groups: IAA multiple (n=143), GADA multiple (n=126) and IA-2A multiple (n=26). Another 229 children seroconverted to positivity only for a single biochemical autoantibody and were grouped: IAA only (n=87), GADA only (n=114) and IA-2A only (n=28).
Results: No consistent differences were observed in selected autoantibody groups during the preclinical period. At diagnosis, children with IAA only showed the highest HbA1c (P<0.001 between groups) and the highest random plasma glucose (P=0.005 between groups). Children with IA-2A only progressed to type 1 diabetes as frequently as those with IA-2A multiple (46% vs 54%, P=0.297) whereas those with IAA only or GADA only progressed less often than children with IAA multiple or GADA multiple (22% vs 62% (P<0.001) and 7% vs 43% (P<0.001)), respectively.
Conclusions: The phenotype of preclinical diabetes defined by the primary autoantibody is not associated with any discernible differences in glucose metabolism before the clinical disease manifestation.
Carmen Sydlik, Ilja Dubinski, Susanne Bechtold, and Heinrich Schmidt
Thyroid-stimulating hormone is generally regarded as a standard parameter for the evaluation of thyroid function. However, relying on this hormone alone can be misleading. Therefore, thyroxine/free-thyroxine levels are used in patients with levothyroxine substitution for the adjustment of therapy. Even with normal values for free thyroxine, decreased values for the free-triiodothyronine/free-thyroxine ratio have already been described in adults. In this study, the free-triiodothyronine/free-thyroxine ratio of 25 children with congenital hypothyroidism was compared with 470 healthy children seen for other reasons and then for thyroid dysfunction. Mean free thyroxine in congenital hypothyroidism was just below the upper limit of normal and significantly higher than in control group. Mean values for free triiodothyronine showed no significant difference between the two groups. The mean value for the free triiodothyronine/free-thyroxine ratio in control group was 3.23. Significantly lower ratios were found in the congenital hypothyroidism group with a mean value of 2.5, due to higher values for free thyroxine compared to free triiodothyronine. Furthermore, an increased free triiodothyronine/free-thyroxine ratio was found at higher thyroid-stimulating hormone values due to lower values for free thyroxine. In this study, we demonstrate that the free triiodothyronine/free-thyroxine ratio was significantly lower in children with congenital hypothyroidism compared to the control group. This is most likely due to the higher values for free thyroxine in this group compared to similar values for free triiodothyronine in both groups. Further studies with differentiated thyroid hormone therapy are needed in order to understand the role of peripheral euthyroidism.
Amar Osmancevic, Kristin Ottarsdottir, Margareta Hellgren, Ulf Lindblad, and Bledar Daka
Obesity seems to decrease levels of testosterone. It is still unknown what role inflammation plays in the secretion of testosterone in men.
The objective is to study the association between levels of C-reactive protein and testosterone and its role in predicting biochemical hypogonadism in men.
This was a longitudinal observational study between 2002 and 2014 in Sweden.
Patients or other participants
At the first visit, a random population sample of 1400 men was included, and 645 men fulfilled a similar protocol at a 10-year follow-up visit. After exclusion, 625 men remained to be included in the final analyses.
Main outcome measure(s)
Serum concentrations of testosterone and C-reactive protein (CRP) were measured at both visits. Bioavailable testosterone was calculated. Biochemical hypogonadism was defined as total testosterone levels <8 nmol/L.
At the first visit and in the longitudinal analyses, a strong association was found between high levels of CRP and low levels of calculated bioavailable testosterone even after adjustments for age, waist–hip ratio, hypertension, smoking, type 2 diabetes, and leisuretime physical activity (B = −0.31, 95% CI −0.49 to −0.13, P = 0.001, B = −0.26, 95% CI −0.41 to −0.11, P = 0.001). Similarly, increase with one s. d. in CRP was associated with increased risk of having hypogonadism after adjustment in the final model (odds ratio (OR) 1.76, 95% CI 1.12–2.78, P = 0.015, OR 1.80, 95% CI 1.16–2.78, P =0.008).
In this representative cohort of men in southwestern Sweden, high levels of CRP were longitudinally associated with low concentrations of calculated bioavailable testosterone and increased risk of biochemical hypogonadism.