Case Report: A Case Report of Stereotactic Ventricular Arrhythmia Radioablation (STAR) on Large Cardiac Target Volume by Highly Personalized Inter- and Intra-fractional Image Guidance.

Introduction: Although catheter ablation is the current gold standard treatment for refractory ventricular arrhythmias, sometimes its efficacy is not optimal and it's associated with high risks of procedural complication and death. Stereotactic arrhythmia radioablation (STAR) is increasingly being adopted for such clinical presentation, considering its efficacy and safety. Case Presentation: We do report our experience managing a case of high volume of left ventricle for refractory ventricular tachycardia in advanced heart failure patient, by delivering a single fraction of STAR through an highly personalization of dose delivery applying repeated inter- and continuous intra-fraction image guidance. Conclusion: According to the literature reports, we recommend considering increasing as much as possible the personalization features and safety technical procedure as long as that is not significantly affecting the STAR duration. Moreover, the duration in itself shouldn't be the main parameter, but balanced into the frame of possibly obtainable outcome improvement. At best of our knowledge, this is the first report applying such specific technology onto this clinical setting. Future studies will clarify these issues.

Dietary Conjugated Linoleic Acid-Enriched Cheeses Influence the Levels of Circulating n-3 Highly Unsaturated Fatty Acids in Humans.

n-3 highly unsaturated fatty acids (n-3 HUFA) directly and indirectly regulate lipid metabolism, energy balance and the inflammatory response. We investigated changes to the n-3 HUFA score of healthy adults, induced by different types and amounts of conjugated linoleic acid (CLA)-enriched (ENCH) cheeses consumed for different periods of time, compared to dietary fish oil (FO) pills (500 mg, each containing 100 mg of eicosapentaenoic and docosahexaenoic acids­EPA+DHA) or α-linolenic acid (ALA)-rich linseed oil (4 g, containing 2 g of ALA). A significant increase in the n-3 HUFA score was observed, in a dose-dependent manner, after administration of the FO supplement. In terms of the impact on the n-3 HUFA score, the intake of ENCH cheese (90 g/day) for two or four weeks was equivalent to the administration of one or two FO pills, respectively. Conversely, the linseed oil intake did not significantly impact the n-3 HUFA score. Feeding ENCH cheeses from different sources (bovine, ovine and caprine) for two months improved the n-3 HUFA score by increasing plasma DHA, and the effect was proportional to the CLA content in the cheese. We suggest that the improved n-3 HUFA score resulting from ENCH cheese intake may be attributed to increased peroxisome proliferator-activated receptor alpha (PPAR-α) activity. This study demonstrates that natural ENCH cheese is an alternative nutritional source of n-3 HUFA in humans.

Metabolism of c9,t11-conjugated linoleic acid (CLA) in humans.

The c9,t11 isomer of conjugated linoleic acid (CLA) is the most abundant CLA form present in the human diet, and is particularly prevalent in milk and dairy products, and is known to exert several health benefits in experimental animal models. A possible mechanism of action of c9,t11CLA relies on its metabolism via desaturases and elongases and partial beta oxidation in peroxisomes. In this study, we aimed to establish plasma incorporation of c9,t11CLA and its downstream metabolites in healthy volunteers after daily dietary intakes of 0.8g, 1.6g or 3.2g of c9,t11CLA in capsule form for two months. Following supplementation, the plasma concentrations of c9,t11CLA and its metabolites conjugated dienes (CD) 18:3 and the beta oxidation product CD 16:2 were incorporated in a linear fashion, while on the other hand CD 20:3 reached a plateau following intakes of 1.6g/d of dietary intake, and was not further increased following higher CLA intakes. We may conclude that supplementation of c9,t11 CLA levels result in linear responses of CLA and its main metabolites in plasma. In addition, only the highest concentration of CLA intake tested (3.2g/d) yielded plasma concentrations of CLA and metabolites close to the range found sufficient to exert nutritional effects in experimental animal models.

Feasibilty of in utero DNA vaccination following naked gene transfer into pig fetal muscle: transgene expression, immunity and safety.

The high toll of death among first-week infants is due to infections occurring at the end of pregnancy, during birth or by breastfeeding. This problem significantly concerns industrialized countries also. To prevent the typical "first-week infections", a vaccine would be protective as early as at the birth. In utero DNA immunization has demonstrated the effectiveness in inducing specific immunity in newborns. We have already published results of a 2-year follow-up showing long-term safety, protective antibody titers at birth and long-term immune memory, following intramuscular in utero anti-HBV DNA immunization in 90-days pig fetuses. We have now analyzed further parameters of short-term safety. Two different reporter genes were injected in the thigh muscles of 90-days fetuses. At 8 days following DNA injection, we found high-level of transgenes expression in all injected fetuses. A step gradient of expression from the area of injection was observed with both reporter genes. CMV promoter/enhancer produced higher levels of expression compared to SV40 promoter/enhancer. Moreover, no evidence of local or systemic flogistic alterations or fetal malformations, mortality or haemorrhage following intramuscular injection were observed. A single anti-HBV s-antigen DNA immunization in 90-days fetuses supported protective antibody levels in all immunized newborns, lasting at least up to 4 months after birth. Our report further sustains safety and efficacy of intramuscular in utero naked gene transfer and immunization. This approach may support therapeutic or prophylactic procedure in many early life-threatening pathologic conditions.