Intra- and Intermolecular Cooperativity in the Catalytic Activity of Phosphodiester Cleavage by Self-Assembled Systems Based on Guanidinylated Calix[4]arenes.

The calix[4]arene scaffold, blocked in the cone conformation through alkylation with long alkyl chains, and decorated at the upper rim with four guanidine or arginine units, effectively catalyzes the cleavage of the phosphodiester bond of DNA and RNA model compounds in water. An exhaustive kinetic investigation unequivocally points to the existence of spontaneous aggregation phenomena, driven by hydrophobic effect, occurring at different critical concentrations that depend on the identity of the compound. A pronounced superiority of the assembled structures compared with the monomers in solution was observed. Moreover, the catalytically active units, clustered on the macrocyclic tetrafunctional scaffold, were proved to efficiently cooperate in the catalytic mechanism and result in improved reaction rates compared to those of the monofunctional model compounds. The kinetic analysis is also integrated and corroborated with further experiments based on fluorescence spectroscopy and light scattering. The advantage of the supramolecular assemblies based on tetrafunctional calixarenes leads to believe that the active units can cooperate not only intramolecularly but also intermolecularly. The molecules in the aggregates can probably mold, flex and rearrange but, at the same time, keep an ordered structure that favors phosphodiester bond cleavage. This dynamic preorganization can allow the catalytic units to reach a better fitting with the substrates and perform a superior catalytic activity.

Impact of COVID-19 Pandemic on Colorectal Cancer Screening Program.

INTRODUCTION: One of the main clusters of coronavirus disease-2019 (COVID-19) has been identified in Italy. Following European and local guidelines, Italian endoscopy units modulated their activity. We aimed at analyzing the need and safety to continue selective colorectal cancer screening (CRCS) colonoscopies during the COVID-19 pandemic. PATIENTS AND METHODS: We carried out a retrospective controlled cohort study in our "COVID-free" hospital to compare data of the CRCS colonoscopies of the lockdown period (March 9 to May 4, 2020) with those of the same period of 2019 (control group). A pre/post endoscopic sanitary surveillance for COVID-19 infection was organized for patients and sanitary staff. RESULTS: In the lockdown group, 60 of 137 invited patients underwent endoscopy, whereas in the control group, 238 CRCS colonoscopies (3.9-fold) were performed. In the lower number of examinations during the lockdown, we found more colorectal cancers (5 cases; 8% vs. 3 cases; 1%; P = .002). The "high-risk" adenomas detection rate was also significantly higher in the "lockdown group" than in controls (47% vs. 25%; P = .001). A multiple regression analysis selected relevant symptoms (hazard ratio [HR], 3.1), familiarity (HR, 1.99), and lockdown period (HR, 2.2) as independent predictors of high-risk lesions (high-risk adenomas and colorectal cancer). No COVID-19 infections were reported among staff and patients. CONCLUSIONS: The overall adherence to CRCS decreased during the pandemic, but the continuation of CRCS colonoscopies was efficacious and safe.

The planimetric Grothoff's criteria by cardiac magnetic resonance can improve the specificity of left ventricular non-compaction diagnosis in thalassemia intermedia.

We differentiated the left ventricle non-compaction (LVNC) from hypertrabeculated myocardium due to a negative remodeling in thalassemia intermedia (TI) patients applying linear and planimetric criteria and comparing the cardiovascular magnetic resonance (CMR) findings. CMR images were analyzed in 181 TI patients enrolled in the Myocardial Iron Overload in Thalassemia Network and 27 patients with proved LVNC diagnosis. The CMR diagnostic criteria applied in TI patients were: a modified linear CMR Petersen's criterion based on a more restrictive ratio of diastolic NC/C > 2.5 at segmental level and the combination of planimetric Grothoff's criteria (percentage of trabeculated LV myocardial mass LV-MM ≥ 25% of global LV mass and total LV-MMI NC ≥ 15 g/m2). Seventeen TI patients showed at least one positive NC/C segment. Compared to LVNC patients, these patients showed a lower frequency of segments with non-compaction areas (2.41 ± 1.33 vs 5.48 ± 2.26; P < 0.0001), significantly lower LV-MM NC percentage (10.99 ± 4.09 vs 28.20 ± 4.27%; P < 0.0001), LV-MMI (7.58 ± 4.86 vs 19.88 ± 5.02 g/m2; P < 0.0001) and extension of macroscopic fibrosis (0.44 ± 0.18 vs 4.65 ± 2.89; P = 0.004), and significantly higher LV ejection fraction (61.29 ± 5.17 vs 48.50 ± 17.55%; P = 0.016) and cardiac index (4.80 ± 1.49 vs 3.46 ± 1.11 l/min/m2; P = 0.002). No TI patient fulfilled the Grothoff's criteria. All TI patients with an NC/C ratio > 2.5 showed morphological and functional CMR parameters significantly different from the patients with a proved diagnosis of LVNC. Differentiation of LVNC from hypertrabeculated LV in ß-TI patients due to a negative heart remodeling depends on the selected CMR criterion. We suggest using planimetric Grothoff's criteria to improve the specificity of LVNC diagnosis.

Participation in colorectal cancer screening with FOBT and colonoscopy: an Italian, multicentre, randomized population study.

BACKGROUND: Data on the adherence rate to screening colonoscopy (OC) in the average-risk general population are limited and variable. Aim of this study was to compare the uptake of OC screening with that of fecal occult blood (FOBT). METHODS: A nationwide, population-based, multicentre, randomized trial comparing attendance to OC with that to FOBT was performed. Sixty-four general practitioners (GPs), overall including in their lists 9889 average-risk subjects aged 55-64 years, were randomized between OC and FOBT screening programs. Eligible subjects were mailed a personal invitation letter co-signed by their GP and the coordinator of the area-reference GI centre. Attendance rate and detection rate for advanced neoplasia (colorectal cancer, adenoma >10mm or with villous histology or high-grade dysplasia) for each arm of the study were assessed. RESULTS: The overall attendance rate was 18.7% (1563/8378 eligible subjects). It was markedly lower in the OC than in the FOBT strategy (10% vs. 27.1%; OR 0.28, 95% CI: 0.25-0.32; P<0.0001). In particular, participation in OC screening arm was extremely low in South Italy (2.8%), whilst it was higher in North-Central Italy (12.4%; P<0.0001). Compliance to colonoscopy in those with a positive FOBT was only 58%. Advanced neoplasia was detected in 28 (6.8%) patients in the OC arm and in 6 (18%) in those with a positive FOBT submitted to OC. CONCLUSIONS: The results of our study underline the difficulties and barriers to implement a OC population screening in Italy, at least through primary care. Although attendance to FOBT was higher, it was disappointingly less than 30%. Significant actions to improve awareness amongst GPs and the population are a high priority.

Explaining gastric cancer survival differences among European countries.

Wide geographic variability in incidence and mortality rates for gastric cancer exists throughout the world despite persistent decreases over several decades. Variability in survival from gastric cancer is also evident and countries with higher incidence rates of gastric cancer show better survival rates than countries with lower incidence. The aim of this study was to identify reasons for the association between incidence and survival and to obtain survival estimates and differences corrected for this variation, thus facilitating further interpretation by clinical factors such as stage and treatment. Relative survival rates for gastric cancer derived from the EUROCARE-2 database for 47 cancer registries in 17 European countries were analyzed with regression methods to adjust differences by age, sex, period of diagnosis, subsite of the stomach, histologic type and stage at diagnosis. Overall, nearly 60% of the variability in gastric cancer relative survival was explained by differences in these variables. Factors are related to treatment and general management of patients is expected to explain the residual variability in gastric cancer survival between European countries. There is a need to improve completeness and standardization of detailed information collected on gastric cancer patients to allow detailed comparative analyses and interpretation.