Melatonin modulates dysregulated circadian clocks in mice with diethylnitrosamine‐induced hepatocellular carcinoma

Disruption of circadian rhythms, which are regulated by the circadian clock machinery, plays an important role in different long‐term diseases including hepatocellular carcinoma (HCC ). Melatonin has been reported to alleviate promotion and progression of HCC , but the potential contribution of circadian clock modulation is unknown. We investigated the effects of melatonin in mice which received diethylnitrosamine (DEN ) (35 mg/kg body weight ip) once a week for 8 weeks. Melatonin was given at 5 or 10 mg kg^?1d^?1 ip beginning 4 weeks after the onset of DEN administration and ending at the sacrifice time (10, 20, 30, or 40 weeks). Liver expression of Bmal1, Clock, Npas2, Rorα, and Sirt1 increased, whereas Cry1, Per1, Per2, Per3, CK 1ε, Rev‐erbα, and Rev‐erbβ decreased following DEN administration. Melatonin treatment prevented changes in the expression of clock genes, and this effect was accompanied by an upregulation of the MT 1 receptor and reduced levels of the hypoxia‐inducible factors Hif‐1α and Hif‐2α. An increased expression of p21, p53, and PARP 1/2, a higher Bax/Bcl‐2 ratio, and a lower expression of Cyclin D1, CDK 6, HSP 70, HSP 90, and GRP 78 proteins were also observed in melatonin‐treated mice. Melatonin significantly potentiated the suppression of proliferation and cell cycle arrest induced by the synthetic REV ‐ERB agonist SR 9009 in human Hep3B cells, and BMAL 1 knocking down attenuated the pro‐apoptotic and antiproliferative effect of melatonin. Results support a contribution of changes in the circadian clock components to the beneficial effects of melatonin in HCC and highlight the usefulness of strategies modulating the circadian machinery in hepatocarcinogenesis.     

Relationship between European Mitochondrial Haplogroups and Chronic Renal Allograft Rejection in Patients with Kidney Transplant

Mitochondrial DNA variants may contribute to differences in mitochondrial function, leading to an altered immune system. The aim of this study was to analyze the relationship between mtDNA haplogroups and the development of chronic allograft dysfunction in patients with kidney transplant. A retrospective observational study was carried out on 261 patients who received kidney transplant (114 had stable transplant and 147 patients developed chronic allograft dysfunction). DNA samples were genotyped for 14 mtDNA polymorphisms by using Sequenom''s MassARRAY platform (San Diego, CA, USA). Only European white patients within the N macro-cluster were included. Patients with haplogroups V (odds ratio (OR)=0.32; p=0.037) and J (OR=0.36; p=0.038) showed lower odds for developing CRAD than patients with haplogroup H. After adjusting for the most significant variables, haplogroups V and J tended to statistical significance (p=0.091 and p=0.067 respectively). This is a preliminary study in which mtDNA haplogroups seem to be implicated in susceptibility or protection for developing chronic allograft dysfunction.     

Variabilidad en el consumo de recursos en pacientes con espondiloartritis en España. Datos descriptivos preliminares del estudio emAR II

ObjectiveOur objective was to describe the variability in the management of spondyloarthritis (SA) in Spain in terms of healthcare resources and their use.MethodsA review of 1168 medical files of patients seen in randomly selected Spanish hospital rheumatology departments. We analyzed demographic variables and variables related to the consumption of health resources.ResultsThe total number of visits to rheumatology were 5,908 with a rate of 254 visits/100 patient-years. The total number of visits to rheumatology specialty nurses was 775, with a rate of 39 visits/100 patient-years, and there were 446 hospitalizations, representing a rate of 22 per 100 patient-years. The number of admissions due to SA was 89, with a rate of 18 admissions/100 patient-years. Total visits to other specialists was 4,307 with a rate of 200/100 patient-years. The total number of orthopedic surgeries was 41, which leads to a rate of 1.8 surgeries/100 patient-years.ConclusionsThe data regarding visits to the rheumatologist and prosthetic surgery of patients with in Spain is similar to most studies published in our environment, however, other aspects concerning the use of health resources are different compared to other countries. This data may help to understand and improve organizational aspects of management of SA in Spanish hospitals.     

Metatarsalgia

Metatarsalgia is a clinical syndrome characterized by pain in the forefoot. To understand the physiopathogenesis and treatment of this condition, an understanding of the anatomy and biomechanics of the foot is essential. There are a large number of causes of metatarsalgia and some, such as rheumatoid arthritis, may be highly complex. The use of ortheses should be individualized and adjusted to the diagnosis. To prevent this condition, the use of appropriate footwear is essential.     

Preschoolers’ mathematical play and colour preferences: a new window into the development of gendered beliefs about math

In play, children often explore mathematical ideas that are vital for future learning. Children’s play also reveals gender differences in both colour and toy preferences. The authors examined how gender-related colour preferences of 5-year-olds are related to preferences for math-specific games/toys and gendered beliefs about math. Spanish preschoolers (N?=?143) completed a self-report measure of gendered beliefs about math. Children then indicated their favourite colour and were given five math-specific games/toys in that colour. Play times for each game/toy were recorded. Three findings emerged. First, girls preferred games/toys of particular colours (pink/purple) that differed from boys’ preferences (blue/red). Second, play time with math games/toys did not differ between girls and boys. Third, 5-year-olds of both genders thought that girls liked math more than boys did. This is the youngest age at which these gendered beliefs about math have been shown, and suggests new theorizing about stereotypes, gender, and math.