Melanoma risk alleles are associated with downregulation of the MTAP gene and hypermethylation of a CpG island upstream of the gene in dermal fibroblasts

Several association studies and GWAS on melanoma skin cancer risk have reported statistically significant signals on 9p21.3 region, where MTAP gene maps. None of the associated SNPs identified in these studies lie in the coding region of the gene and the causative relation of risk alleles with melanoma predisposition has not been elucidated. MTAP has a tumor suppressor activity and epigenetic silencing has been described in melanoma cell lines. In the present study, we show that melanoma risk alleles correlate with a MTAP allele‐specific hyper‐methylation and down‐regulation of gene expression.     

Transarterial chemoembolization as adjuvant treatment after surgery: The cure of huge hepatocellular carcinoma?

正Hepatocellular carcinoma(HCC) represents the sixth common cancer and the second leading cause of cancer-related death. Its incidence is higher in Eastern countries. HCC is frequently detected at advanced stage of disease, and therefore, the mortality is high [1].     

In Vitro Direct and Indirect Cytotoxicity Comparative Analysis of One Pre-Hydrated versus One Dried Acellular Porcine Dermal Matrix

Aim: The aim of the present study was to compare the direct and indirect cytotoxicity of a porcine dried acellular dermal matrix (PDADM) versus a porcine hydrated acellular dermal matrix (PHADM) in vitro. Both are used for periodontal and peri-implant soft tissue regeneration. Materials and methods: Two standard direct cytotoxicity tests—namely, the Trypan exclusion method (TEM) and the reagent WST-1 test (4-3-[4-iodophenyl]-2-[4-nitrophenyl]-2H-[5-tetrazolio]-1,3-benzol-desulphonated)—were performed using human primary mesenchymal stem cells (HPMSCs) seeded directly onto a PDADM and PHADM after seven days. Two standard indirect cytotoxicity tests—namely, lactate dehydrogenase (LTT) and MTT (3-[4,5-dimethyl-2-thiazolyl]-2,5-diphenyl-2H-tetrazoliumbromide)—were performed using HPMSCs cultivated in eluates from the matrices incubated for 0.16 h (10 min), 1 h, and 24 h in a serum-free cell culture medium. Results: The WST and the TEM tests revealed significantly lower direct cytotoxicity values of HPMSCs on the PHADM compared with the PDADM. The indirect cytotoxicity levels were low for both the PHADM and PDADM, peaking in short-term eluates and decreasing with longer incubation times. However, they were lower for the PHADM with a statistically significant difference (p < 0.005). Conclusions: The results of the current study demonstrated a different biologic behavior between the PHADM and the PDADM, with the hydrated form showing a lower direct and indirect cytotoxicity.     

Challenges to the improvement of Colombian medical brigades aimed at the diagnosis of congenital heart disease: A qualitative approach

Qualitative research of brigades and the family experience of congenital heart disease is of current interest and has been previously neglected. This study aimed to explore the social factors conditioning outcomes of paediatric cardiology care in the setting of Colombian medical brigades and to identify feasible strategies to improve the experience of the beneficiary populations. Participants were selected using purposeful sampling. Semi-structured interviews were conducted with members of logistic and health care teams, caregivers and custodians of beneficiary children of the Programme. The data collected provided an understanding of the health culture, social background, household and intrafamily dynamics. The outcomes of the Programme are influenced by sociocultural dynamics such as communication gaps and the socioeconomic status of the beneficiary populations. Findings may be specific to brigades, but also cross-relevant to any family experience of a new diagnosis of Congenital Heart Disease (CHD) communicating with healthcare professionals. It is important to foresee the role and further development of the Programme. Recommendations are provided suggesting innovative work by means of telemedicine and other sociocultural measures to reduce healthcare inequity and strengthen comprehensive healthcare programmes.     

Normal motor learning during pharmacological prevention of Purkinje cell long-term depression

Systemic delivery of (1R-1-benzo thiophen-5-yl-2[2-diethylamino)-ethoxy] ethanol hydrochloride (T-588) prevented long-term depression (LTD) of the parallel fiber (PF)-Purkinje cell (PC) synapse induced by conjunctive climbing fiber and PF stimulation in vivo. However, similar concentrations of T-588 in the brains of behaving mice and rats affected neither motor learning in the rotorod test nor the learning of motor timing during classical conditioning of the eyeblink reflex. Rats given doses of T-588 that prevented PF-PC LTD were as proficient as controls in learning to adapt the timing of their conditioned eyeblink response to a 150- or 350-ms change in the timing of the paradigm. The experiment indicates that PF-PC LTD under control of the climbing fibers is not required for general motor adaptation or the learning of response timing in two common models of motor learning for which the cerebellum has been implicated. Alternative mechanisms for motor timing and possible functions for LTD in protection from excitotoxicity are discussed.