Genetic variants associated with addictive behavior in Colombian addicted and non-addicted to heroin or cocaine

Objective:

Determine the prevalence and compare some genetic markers involved in addictive behavior in a group of addicts to derivative of coca (cocaine/crack) or heroin and a control group of non-addicted people matched for gender, age and ethnicity.

Methods:

A 120 addicts and 120 non-addicts Colombian male were surveyed and genotyped for 18 polymorphism of the OPRM1, DRD2, DRD4, SLC6A3, SLC6A4, ABCB1, DβH and CYP2B6 genes. For the identification of alleles markers were used mini-sequencing and fragment multiplex PCR techniques; ethnicity of cases and controls was analyzed with 61 AIMs.

Results:

The age of onset use of heroin or coca derivatives (cocaine/crack) was 16.5±6 years and 99.2% of them consume several illicit drugs. It showed that controls and addicts belong to the same ethnic group. Significant differences between addicts and controls in relation to schooling, marital status, social security family history of substance abuse (p <0.001), Int8-VNTR SLC6A3 gene (p= 0.015) and SNP 3435C>T ABCB1 gene (p= 0.001) were found.

Conclusion:

The present results indicate that the VNTR- 6R polymorphism of the gene SLC6A3 and the genotype 3435CC in the ABCB1 gene, are both associated with addictive behavior to heroin or cocaine.     

Novel light-curable materials containing experimental bioactive micro-fillers remineralise mineral-depleted bonded-dentine interfaces

This study aimed at evaluating the therapeutic remineralising effects of innovative light-curable materials (LCMs) containing two experimental calcium silicate-based micro-fillers (TCS) modified with β-TCP only or β-TCP, zinc oxide (ZnO)/polyacrylic acid (PAA) on mineral-depleted bonded-dentine interfaces in simulated body fluids (SBFS). Three experimental LCMs were formulated: (1) resin A, containing a β-TCP-modified TCS (βTCS) micro-filler; (2) resin B, containing a polycarboxylated β-TCP/ZnO-modified TCS (βZn-TCS) micro-filler; and 3) resin C, containing no filler (control). Acid-etched (35% H₃PO₄) dentine specimens were bonded using the three LCMs and submitted to atomic force microscope (AFM)/nano-indentation analysis to evaluate the modulus of elasticity (Ei) and hardness (Hi) across the interface after SBFS storage (24?h/1?m/3?m). The ultramorphology and micropermeability of the resin–dentine interface were evaluated using confocal laser microscopy. Resin–dentine sticks were created and submitted to microtensile bond strength (μTBS) test (SBFS: 24?h/3?m). Scanning electron microscopy (SEM) was performed after de-bonding. The LCMs containing the experimental bioactive micro-fillers reduced the micropermeability and induced a significant increase of the Ei and Hi along the bonding interface. The specimens created using the resin B (βZn-TCS) attained the highest μTBS values both after 24?h and 3?m of SBFS storage. In conclusion, the innovative bioactive light-curable materials tested in this study are able to induce a therapeutic remineralising effect on the nano-mechanical properties and on the sealing ability of mineral-depleted resin–dentine interfaces. The contemporary idea of minimally invasive operative treatment, where therapeutic restorations are performed to combat the carious process and remineralise the dental hard tissues, may be satisfied by using such resin-base systems, containing βTCS or βZn-TCS bioactive micro-fillers.     

Headache Gauge: a real-life calendar-based tool for headache monitoring

Neurological Sciences - This study aimed to validate a semi-quantitative composite score tool, “Headache Gauge” (HG), to monitor the treatment effect in primary headaches in everyday...     

Activation of the NF-kB pathway downregulates TFF-1 in gastric carcinogenesis

Trefoil factor 1 (TFF1) is expressed in the normal superficial epithelium of the stomach and is implicated in the maintenance of gastric epithelial structure and function. During gastric carcinogenesis, in which pro-inflammatory cytokines play a crucial role, its expression level decreases suggesting a role as tumor suppressor factor. We have compared expression of TFF1 in gastric mucosa from cancer patients, in which several degrees of inflammatory infiltrate are present, with that in normal mucosa from non-cancer patients without infiltrating inflammatory cells. TFF1 is less expressed in the superficial gastric epithelium from cancer patients than in that from normal individuals in which the nuclear factor (NF)-κB pathway is not activated. We analyzed TFF1 expression in ex vivo samples of gastric mucosa from cancer patients, and in MKN45 gastric cancer cell line after exposure to proinflammatory cytokines interleukin (IL)-1β or tumor necrosis factor (TNF)-α, that activate the NF-κB pathway. We found that IL-1β and TNF-α activate the NF-κB pathway, as reflected in the nuclear expression of p65 and the activation of p-IκBα, and downregulate TFF1 expression after 1 or 2 h of exposure. Moreover, cells in the superficial gastric epithelium in ex vivo samples co-expressed TFF1/p65 at cellular level, whereas tumor cells did not. In summary, downregulation of TFF1 expression during gastric neoplastic transformation is associated with activation of the NF-κB pathway through IL-1β or TNF-α, but other regulatory mechanisms might also be involved.     

Perceptions of safety and subjective well‐being of Brazilian children

Safety is considered an important aspect of life and well‐being. However, few studies have examined the relationship between safety and well‐being among children, especially in Latin American. This study aims at analyzing the relationship between perceptions of safety and children's subjective well‐being, considering children's school, city context, and sex. Participants were 2,200 Brazilian children (10–13 years old) who answered the single item on Overall Life Satisfaction, the Satisfaction With Life Student Scale, and four items regarding safety perceptions. Through analysis of variance and structural equation modeling (SEM), results indicate that children who live in inner cities and study in private schools have significantly higher averages of safety perception. Also, boys present higher averages about how safe they feel. SEM presents a positive and significant relationship between safety perception and children's subjective well‐being and multigroup SEM indicates invariance of the model across groups. Safety is presented as an important component of well‐being. Interventions aimed at promoting safety and community ties can enhance children's well‐being.     

Heterozygous mutations in the PALB2 hereditary breast cancer predisposition gene impact on the three‐dimensional nuclear organization of patient‐derived cell lines

PALB2/FANCN is a BRCA1‐ and BRCA2‐interacting Fanconi Anemia (FA) protein crucial for key BRCA2 genome caretaker functions. Heterozygous germline mutations in PALB2 predispose to breast cancer and biallelic mutations cause FA. FA proteins play a critical role in the telomere maintenance pathway, with telomeric shortening observed in FA cells. Less is known about telomere maintenance in the heterozygous state. Here, we investigate the roles of PALB2 heterozygous mutations in genomic instability, an important carcinogenesis precursor. Patient‐derived lymphoblastoid (LCL) and fibroblast (FCL) cell lines with monoallelic truncating PALB2 mutations were investigated using a combination of molecular imaging techniques including centromeric FISH, telomeric Q‐FISH and spectral karyotyping (SKY). Mitomycin C and Cisplatin sensitivity was assayed via cellular metabolism of WST‐1. The PALB2 c.229delT FCL showed increases in telomere counts associated with increased mean intensity compared with two wild‐type FCLs generated from first‐degree relatives (P =1.04E‐10 and P =9.68E‐15) and it showed evidence of chromosomal rearrangements. Significant differences in centromere distribution were observed in one of three PALB2 heterozygous FCLs analyzed when compared with PALB2 wild‐type, BRCA1 and BRCA2 heterozygous FCLs. No significant consistently increased sensitivity to Mitomycin C or Cisplatin was observed in LCLs. Our results are suggestive of an altered centromere distribution profile and a telomere instability phenotype. Together, these may indicate critical nuclear organization defects associated with the predisposition to transformation and early stage development of PALB2‐related cancers. © 2013 Wiley Periodicals, Inc.