High SLC7A11 expression in normal skin of melanoma patients

Background: Melanoma is one of the highest metastatic cancers and its incidence is rapidly increasing. A great effort has been devoted to determine gene mutations and expression profiles in melanoma cells, but less attention has been given to the possible influence of melanin synthesis in melanocytes on melanomagenesis. SLC7A11 encodes the cystine/glutamate antiporter xCT and its expression increases the antioxidant capacity of cells by providing cysteine that may be used for glutathione (GSH) synthesis. Melanocytes, however, can also use cysteine for pheomelanin synthesis and pigmentation. Therefore, pheomelanin synthesis may lead to chronic oxidative stress. Possible consequences of this for melanomagenesis have never been explored. Methods: We quantified the expression of SLC7A11 and other genes that are involved in the synthesis of pheomelanin but do not regulate the transport of cysteine from the extracellular medium to the cytosol (CTNS, MC1R, ASIP and SLC45A2) in non-tumorous skin of 45 patients of cutaneous melanoma and 50 healthy individuals. We controlled for the effects of Fitzpatrick skin type, age, gender, body mass, frequency of sun exposure and sunburns and number of melanocytic nevi, as well as for the intrinsic antioxidant capacity as given by the expression of the gene NFE2L2. Results: The expression of SLC7A11, but not of the other genes, was significantly higher in melanoma patients than in healthy individuals. This was independent of phenotypic factors and antioxidant capacity, thus supporting an effect of pheomelanin-induced oxidative stress on melanomagenesis. Conclusion: Our findings indicate that SLC7A11 downregulation in normal epidermal melanocytes may represent a preventive treatment against melanoma

Effects of aerobic exercise, cognitive and combined training on cognition in physically inactive healthy late-middle-aged adults: The Projecte Moviment Randomized Controlled Trial

Background: Lifestyle interventions are promising strategies to promote cognitive health in aging. Projecte Moviment examines if aerobic exercise (AE), computerized cognitive training (CCT), and their combination (COMB) improves cognition, psychological health, and physical status compared to a control group. We assessed the moderating role of age and sex and the mediating effects of cardiorespiratory fitness (CRF), physical activity (PA), and psychological health on intervention-related cognitive benefits. Methods: This was a 12-week multi-domain, single-blind, proof-of-concept randomized controlled trial (RCT). 96 healthy adults aged 50–70 years were assigned to AE, CCT, COMB, and a wait-list control group. The per protocol sample, which completed the intervention with a level of adherence > 80%, consisted of 82 participants (62% female; age = 58.38 ± 5.47). We assessed cognition, psychological health, CRF, and energy expenditure in PA at baseline and after the intervention. We regressed change in each outcome on the treatment variables, baseline score, sex, age, and education. We used PROCESS Macro to perform the mediation and moderation analyses. Results: AE benefited Working Memory (SMD = 0.29, p = 0.037) and Attention (SMD = 0.33, p = 0.028) including the Attention-Speed (SMD = 0.31, p = 0.042) domain, compared to Control. COMB improved Attention (SMD = 0.30, p = 0.043), Speed (SMD = 0.30, p = 0.044), and the Attention-Speed (SMD = 0.30, p = 0.041) domain. CTT group did not show any cognitive change compared to Control. Sportive PA (S-PA) and CRF increased in AE and COMB. Age and sex did not moderate intervention-related cognitive benefits. Change in S-PA, but not in CRF, significantly mediated improvements on Attention-Speed in AE. Conclusion: A 12-week AE program improved Executive Function and Attention-Speed in healthy late-middle-aged adults. Combining it with CCT did not provide further benefits. Our results add support to the clinical relevance of even short-term AE as an intervention to enhance cognition and highlight the mediating role of change in S-PA in these benefits

Baseline Description of the Spanish Academy of Dermatology Infantile Haemangioma Nationwide Prospective Cohort. Comparison of Patients Treated with Propranolol in Routine Clinical Practice with Previous Pivotal Clinical Trial Data Descripción basal de la cohorte nacional prospectiva de hemangiomas infantiles de la Academia Española de Dermatología y Venereología. Comparación de los pacientes tratados con propranolol en la práctica clínica rutinaria y los datos del ensayo clínico pivotal previo

Altres ajuts: Fundación Piel Sana AEDV.Background: There are several therapeutic options for infantile haemangiomas (IH). Propranolol is used according to a pivotal trial. We aimed to describe the characteristics of IH in clinical practice, including the therapies used, and to compare the characteristics of patients treated with propranolol with those of the trial to assess its external validity. Methods: Consecutive patients attending 12 Spanish hospitals from June 2016 to October 2019 were included (n = 601). Results: The mean age was 3.9 (SD:1.9) months, with a 2:1 female-to-male ratio. Most IHs were localized (82%, 495), superficial (64%, 383) and located in the face (25%, 157) and trunk (31%, 188). Median size was 17 (IR: 10-30) x 12 (IR: 7-20) mm. Complications were found in 16 (3%) patients. Treatment was initiated for 52% (311). Most patients received timolol (76%, 237); propranolol was reserved for complications or high-risk IHs. Aesthetic impairment was the main reason for starting therapy (64%, 199). Several characteristics of the patients and IHs treated with propranolol are similar to those of the pivotal clinical trial, but 1/3 of IHs did not reach the minimum diameter to meet the inclusion criteria, and important prognostic information was not reported. Conclusions: As most patients receive treatment for aesthetic impairment, there is a need to better understand the aesthetic results of therapies and to increase evidence on the use of timolol, which is currently the most common therapy. Propranolol is being used in a population generally similar to that of the trial; however, this statement cannot be definitely confirmed