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Over the past four decades, the question of the relationship between divine omniscience and human freedom has led analytic philosophy of religion to analyze medieval thought on foreknowledge. To avoid fatalism, many of them have been inspired by Luis de Molina’s doctrine of middle knowledge. Created to provide a libertarian account of how God knows future contingents, the Molinist solution has divided contemporary interpreters into two camps: those who argue that Molinism implies determinism and those who have developed new analytical strategies to support Molina’s thesis. This study provides a map for moving through the debate.

Background: The potential role of digestive endoscopy as a mode for transmission of hepatitis C virus (HCV) is controversial. Objective: To evaluate the role of digestive endoscopy in transmiring HCV by comparing the incidence of HCV infection in a cohort of patients undergoing endoscopy and in a cohort of blood donors. Design: Prospective cohort study. Setting: 3 endoscopic units and 2 blood banks in northwestern Italy. Patients: The potentially exposed cohort consisted of 9188 outpatients consecutively recruited from 3 endoscopic units. Of 9008 patients negative for antibody to HCV (anti-HCV), 8260 (92%) were retested for anti-HCV 6 months after endoscopy. The unexposed cohort consisted of 51 230 healthy, anti-HCV-negative persons who donated blood at 2 blood banks in the same area and during the same time period; 38 280 of them (75%) were tested again for anti-HCV 6 to 48 months after the first blood donation (95 317 person-years of observation). Measurements: Differences in the anti-HCV seroconversion rate between the exposed cohort (patients undergoing endoscopy) and the unexposed cohort (blood donors). Seroconversion was evaluated by a third-generation enzyme immunoassay for anti-HCV; persons positive for anti-HCV were tested for HCV RNA by polymerase chain reaction. Results: All 8260 persons undergoing endoscopy remained negative for anti-HCV 6 months after the procedure (risk per 1000 persons, 0 [95% CI, 0 to 0.465]); in particular, none of the 912 patients who underwent endoscopy with the same instrument previously used on HCV carriers showed anti-HCV seroconversion (risk per 1000 persons, 0 [CI, 0 to 4.195]). Four blood donors became positive for anti-HCV and HCV RNA (mean follow-up, 2.49 years; 0.042 case per 1000 person-years [CI, 0.011 to 0.107 case per 1000 person-years]); each had undergone minor surgery before the second test. Limitations: In the endoscopy cohort, 8.3% of patients were lost to follow-up. Conclusions: These findings support the hypothesis that properly performed digestive endoscopy is not a major risk factor for the transmission of HCV.

In the relatively new field of cardiac tissue engineering, different biomaterials, methods and techniques have been tested for cardiac repair, but we are still far from the achievement of a valid model that can be tested for therapeutic goals. In this study, the authors examined the efficacy of newly preformed membranes based on collagen type I for the transplantation of cardiac cells. The membrane prototype, cross-linked with 1,4-butanediol diglycidyl ether (BDDGE) and fibronectin-enriched, gave rise to spontaneously beating heart cell constructs, 5–9 days after seeding with neonatal rat cardiac cells. This membrane was grafted, with and without beating cardiac cells, onto the infarcted area of rat models of heart failure. Seriate echocardiography, performed on rats before transplantation and at 4 and 8 weeks after transplantation, demonstrated that rats treated with collagen membranes previously seeded with beating cells showed an improvement in cardiac function after 8 weeks. These results suggest that this new type of collagen membrane can be used as vector for the transplantation of beating heart cells for the regeneration of the injured myocardium and hence represents an important potential tool for cardiac tissue repair technologies.In the relatively young field of cardiac tissue engineering, different biomaterials, methods and techniques have been tested for cardiac repair, but we are still far from the achievement of a valid model that can be tested for therapeutic goals. In this study we examined the efficacy of new preformed membranes based on collagen type I for the transplantation of cardiac cells. The membrane prototype, cross-linked with 1,4-butanediol diglycidyl ether (BDDGE) and fibronectin-enriched, gave rise to spontaneously beating heart cell constructs 5–9 days after seeding with neonatal rat cardiac cells. This membrane was grafted, with and without beating cardiac cells, onto the infarcted area of rat models of heart failure. Seriate echocardiography, performed on rats before transplantation and at 4 and 8 weeks after transplantation, demonstrated that rats treated with collagen membranes previously seeded with beating cells showed an improvement in cardiac function after 8 weeks. These results suggest that this new type of collagen membrane can be used as vector for the transplantation of beating heart cells for the regeneration of the injured myocardium and hence represents an important potential tool for cardiac tissue repair technologies.

Large-animal models for Duchenne muscular dystrophy (DMD) are crucial for the evaluation of diagnostic procedures and treatment strategies. Pigs cloned from male cells lacking DMD exon 52 (DMDΔ52) exhibit molecular, clinical and pathological hallmarks of DMD, but die before sexual maturity and cannot be propagated by breeding. Therefore, we generated female DMD+/− carriers. A single founder animal had 11 litters with 29 DMDY/−, 34 DMD+/− as well as 36 male and 29 female wild-type offspring. Breeding with F1 and F2 DMD+/− carriers resulted in an additional 114 DMDY/− piglets. With intensive neonatal management, the majority survived for 3-4 months, providing statistically relevant cohorts for experimental studies. Pathological investigations and proteome studies of skeletal muscles and myocardium confirmed the resemblance to human disease mechanisms. Importantly, DMDY/− pigs displayed progressive myocardial fibrosis and increased expression of connexin-43, associated with significantly reduced left ventricular ejection fraction, at 3 months. Furthermore, behavioral tests provided evidence for impaired cognitive ability. Our breeding cohort of DMDΔ52 pigs and standardized tissue repositories provide important resources for studying DMD disease mechanisms and for testing novel treatment strategies.

The cost of a recurrently bleeding duodenal ulcer (DU) is very high, both from a human and an economic point-of-view. Helicobacter pyloriinfection plays an important role in the pathogenesis of DU disease and its complications, such as bleeding. Cure of H. pyloriinfection is recommended in patients with DU and its complications, although in the latter case, the most efficient management is not yet a defined issue. In particular, acid secretion inhibitors may not contribute to long-term cure. Our aims were to ascertain whether the recurrence of bleeding because of DU could be prevented by H. pylorieradication and whether long-term inhibition of gastric acid output is needed to prevent recurrence. Eighty-four patients (65 men; mean age, 55.1 years), who had bled because of recurrent DU, were followed after the cure of H. pyloriinfection. None of the patients were on therapy with nonsteroidal antiinflammatory drugs. Successful cure of H. pyloriwas determined by gastroscopy, histology, and serology performed at 3, 6, 12, 24, and 48 months after the eradication treatment. A 13C urea breath test was performed when the results of serology were unclear and also at recurrence of DU or bleeding. After the antibiotic treatment, 46 patients stopped all medications, whereas 38 continued long-term therapy with histamine type 2 receptor antagonists. During a mean follow-up period of 47.2 months (range, 37–65 months), recurrence of DU at endoscopy was observed in three patients in each group (p0.56), but none bled again. We conclude that H. pylorieradication prevents DU recurrence and rebleeding, that reinfection rate by H. pyloriafter cure was nil at 4 years, and that long-term inhibition of acid secretion may not improve outcome after cure of H. pylori, even in patients whose DU was complicated by hemorrhage.