Recurrent CDH1 mutations in families with hereditary diffuse gastric cancer are due to both independent mutational events and common ancestry. The presence of a founder mutation from Newfoundland is strongly supported.

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TAC, MMF and MP are used in pediatric kidney tx. The cytochrome P450 (CYP)3A5 enzyme appears to play a role in TAC metabolism. The aims of this study were to investigate CYP3A5 polymorphism's effect on TAC dosing and the age dependency of TAC dosing by testing blood concentrations, and the interaction between steroids and TAC during the first year after tx. Genomic DNA was extracted and amplified with specific primers. CYP3A5 alleles were confirmed by direct sequencing of PCR products on an automated AB13100 capillary sequencer. We studied 48 renal transplant patients (age at tx 12±0.5yr, 22 boys) receiving TAC, MMF, MP. Of these, 79% were CYP3A5*3/*3 (non-expressers homozygotes) and 21% were CYP3A5*1/*3 (expressers). TAC trough levels were 7.1±0.4ng/mL in CYP3A5*3/*3 patients and 6.5±0.7ng/mL in CYP3A5*1/*3 group (p=0.03). CYP3A5*1/*3 patients had lower levels of dose-adjusted TAC (36.7±5.8ng/mL/mg/kg/day) to achieve target blood concentration and required higher daily dose per weight (0.21±0.03mg/kg/day) than CYP3A5*3/*3 patients, 72.4±8.0ng/mL/mg/kg/day and 0.13±0.01mg/kg/day (p<0.001). Prepubertal patients with different CYP3A5 polymorphisms required significant higher TAC doses and achieved lower dose-normalized concentration compared with pubertal patients. Both TAC dose and adjusted-dose correlated with daily MP dose in CYP3A5*1*3 (r: 0.4, p<0.03 and r: 0.4, p<0.03) and in CYP3A5*3*3 (r: 0.6, p<0.01 and r: 0.47, p<0.001) patients. CYP3A5 polymorphism performed before tx could contribute to a better individualization of TAC therapy. The higher TAC dose in prepubertal patients and the pharmacological interactions between MP and TAC may not be fully explained by different CYP3A5 polymorphisms.

Dust storm is a common phenomenonand, a severe environmental hazard in western Saudi Arabia. In this study, simultaneous measurement of PM 10 , PM 2.5 and PM 1.0 and elemental compositions analysis of PM 2.5 in Jeddah city during springtime (March 2012) dust storm (DS) and non-dust storm (non-DS) periods were carried out to investigate the impact of DS on the levels, characterization and elemental compositions of atmospheric particles. Results indicate that PM fractions concentrations were higher in DS environment compared to non-DS. The diurnal variation of PM fractions concentrations was uni-modal in non-DS environment and bimodal in DS. PM 1.0 /PM 10 , PM 2.5 /PM 10 and PM 2.5 /PM 2.5-10 ratios were relatively lower in DS, indicating that sand-dust events in spring carry much more coarse than fine particles to Jeddah. PM 10 , PM 2.5 and PM 1.0 in DS and PM 10 and PM 2.5 in non-DS might originate from similar sources. PM 10 , PM 2.5 , PM 1.0 in DS and PM 10 in non-DS were correlated negatively with relative humidity and positively with wind speed. PM 2.5 and PM 1.0 in non-DS were correlated positively with relative humidity and negatively with wind speed. The crustal elements accounted for 44.62 and 67.53% of the total concentrations of elements in non-DS and DS, respectively. The elements concentrations increased in DS, with highest DS/non-DS ratios for Ca, Si, Al and Fe. This indicates that the soil originating species contributed mainly in DS particles.The enrichment factors values and non-crustal fractions in both non-DS and DS indicate that the main sources of Na, Mg, Si, K, Ca, Ti, Cr, Mn, Fe, Rb and Sr are of a crustal type, whereas S, Cl, Co, Cu, Zn, Ga, As, Pb and Cd are anthropogenic. V and Ni in DS only are emitted from anthropogenic sources. The enrichment factors of these anthropogenic elements were lower in DS. They might originate mainly from local sources in Jeddah.

Pharmacogenetics and Pharmacogenomics areas are currently emerging fields focused to manage pharmacotherapy that may prevent undertreatment while avoiding associated drug toxicity in patients. Large international differences in the awareness and in the use of pharmacogenomic testing are presumed, but not well assessed to date. In the present study we review the awareness of Latin American scientific community about pharmacogenomic testing and the perceived barriers for their clinical application. In order to that, we have compiled information from 9 countries of the region using a structured survey which is compared with surveys previously performed in USA and Spain. The most relevant group of barriers was related to the need for clear guidelines for the use of pharmacogenomics in clinical practice, followed by insufficient awareness about pharmacogenomics among clinicians and the absence of regulatory institutions that facilitate the use of pharmacogenetic tests. The higher ranked pairs were TPMT/thioguanine, TPMT/azathioprine, CYP2C9/warfarin, UGT1A1/irinotecan, CYP2D6/amitriptiline, CYP2C19/citalopram and CYP2D6/clozapine. The lower ranked pairs were SLCO1B1/simvastatin, CYP2D6/metoprolol and GP6D/chloroquine. Compared with USA and Spanish surveys, 25 pairs were of lower importance for Latin American respondents. Only CYP2C19/esomeprazole, CYP2C19/omeprazole, CYP2C19/celecoxib and G6PD/dapsone were ranked higher or similarly to the USA and Spanish surveys. Integration of pharmacogenomics in clinical practice needs training of healthcare professionals and citizens, but in addition legal and regulatory guidelines and safeguards will be needed. We propose that the approach offered by pharmacogenomics should be incorporated into the decision-making plans in Latin America.