Oral anticoagulant management of patients with mechanical heart valves at the Salam Centre of Khartoum:Observations on quality of anticoagulation and thrombotic risk

IntroductionRheumatic heart disease with mechanical heart valve (MHV) replacement is common in Africa. However, MHV requires long-life anticoagulation and managing this can be challenging.Methods and resultsWe report data of a prospective observational study conducted between August 2018 and September 2019 in MHV patients in the Salam Centre for Cardiac Surgery built in Khartoum, by Emergency, an Italian Non-Governmental Organization, to evaluate the quality of anticoagulation control and the risk of thrombotic complications.ResultsWe studied 3647 patients (median age 25.1 years; 53.9 % female). Median Time in Therapeutic Range (TTR) was 53 % (interquartile range 37 % to 67 %) and 70 thrombotic events (rate 1.8 × 100 pt-years [95 % CI 1.38-2.23]) were recorded. Among patients in the first quartile of TTR (≤37 %), we recorded 34/70 (48.6 %) of all thrombotic events (rate 3.7 × 100 pt-years [95 % CI 2.5-5.1]), with a high mortality rate (2.2 × 100 pt-years [95 % CI 1.3-3.3]). In patients with guideline-recommended TTR (≥65 %) the event rate was 0.8 × 100 pt-years for thrombotic events [95 % CI 0.3-1.5] and 0.4 × 100 pt-years for mortality [95 % CI 0.1-0.9]. Multivariable analysis showed that having a TTR in the lowest quartile (≤37 %) and being noncompliant are significantly associated with increased thrombotic risk. Aspirin use or different valve type did not influence the thrombotic risk. Almost 40 % of all thromboembolic complications could have been potentially prevented by further improving VKA management to obtain a TTR > 37 %.ConclusionThe thrombotic risk of MHV patients on VKAs living in a low-income country like Sudan is associated with low quality of anticoagulation control. Efforts should be made to decrease the number of non-compliant patients and to reach a guideline-recommended TTR of ≥65 %

A Systems Biology Approach to Characterize the Regulatory Networks Leading to Trabectedin Resistance in an In Vitro Model of Myxoid Liposarcoma

Trabectedin, a new antitumor compound originally derived from a marine tunicate, is clinically effective in soft tissue sarcoma. The drug has shown a high selectivity for myxoid liposarcoma, characterized by the translocation t(12;16)(q13; p11) leading to the expression of FUS-CHOP fusion gene. Trabectedin appears to act interfering with mechanisms of transcription regulation. In particular, the transactivating activity of FUS-CHOP was found to be impaired by trabectedin treatment. Even after prolonged response resistance occurs and thus it is important to elucidate the mechanisms of resistance to trabectedin. To this end we developed and characterized a myxoid liposarcoma cell line resistant to trabectedin (402-91/ET), obtained by exposing the parental 402-91 cell line to stepwise increases in drug concentration. The aim of this study was to compare mRNAs, miRNAs and proteins profiles of 402-91 and 402-91/ET cells through a systems biology approach. We identified 3,083 genes, 47 miRNAs and 336 proteins differentially expressed between 402-91 and 402-91/ET cell lines. Interestingly three miRNAs among those differentially expressed, miR-130a, miR-21 and miR-7, harbored CHOP binding sites in their promoter region. We used computational approaches to integrate the three regulatory layers and to generate a molecular map describing the altered circuits in sensitive and resistant cell lines. By combining transcriptomic and proteomic data, we reconstructed two different networks, i.e. apoptosis and cell cycle regulation, that could play a key role in modulating trabectedin resistance. This approach highlights the central role of genes such as CCDN1, RB1, E2F4, TNF, CDKN1C and ABL1 in both pre- and post-transcriptional regulatory network. The validation of these results in in vivo models might be clinically relevant to stratify myxoid liposarcoma patients with different sensitivity to trabectedin treatment

Acute Delta Hepatitis in Italy spanning three decades (1991–2019): Evidence for the effectiveness of the hepatitis B vaccination campaign

Updated incidence data of acute Delta virus hepatitis (HDV) are lacking worldwide. Our aim was to evaluate incidence of and risk factors for acute HDV in Italy after the introduction of the compulsory vaccination against hepatitis B virus (HBV) in 1991. Data were obtained from the National Surveillance System of acute viral hepatitis (SEIEVA). Independent predictors of HDV were assessed by logistic-regression analysis. The incidence of acute HDV per 1-million population declined from 3.2 cases in 1987 to 0.04 in 2019, parallel to that of acute HBV per 100,000 from 10.0 to 0.39 cases during the same period. The median age of cases increased from 27 years in the decade 1991-1999 to 44 years in the decade 2010-2019 (p < .001). Over the same period, the male/female ratio decreased from 3.8 to 2.1, the proportion of coinfections increased from 55% to 75% (p = .003) and that of HBsAg positive acute hepatitis tested for by IgM anti-HDV linearly decreased from 50.1% to 34.1% (p < .001). People born abroad accounted for 24.6% of cases in 2004-2010 and 32.1% in 2011-2019. In the period 2010-2019, risky sexual behaviour (O.R. 4.2; 95%CI: 1.4-12.8) was the sole independent predictor of acute HDV; conversely intravenous drug use was no longer associated (O.R. 1.25; 95%CI: 0.15-10.22) with this. In conclusion, HBV vaccination was an effective measure to control acute HDV. Intravenous drug use is no longer an efficient mode of HDV spread. Testing for IgM-anti HDV is a grey area requiring alert. Acute HDV in foreigners should be monitored in the years to come

Pasta from Red Lentils (Lens culinaris): The Effect of Pasta-Making Process on Starch and Protein Features, and Cooking Behavior

The effect of pasta-making processes on starch and protein features, as well as cooking behavior, and nutritional properties (i.e., resistant starch and starch in vitro digestibility) were assessed. Pasta from raw red lentils (R) was prepared by conventional extrusion (C_R) and extrusion-cooking (EC_R), whereas heat-treated red lentils (HT) were processed into pasta by conventional extrusion (C_HT). A “high protein” and “high fiber” pasta was prepared. Using HT was effective in increasing the luminosity (that was about 88, 91, and 96 for EC_R, C_R, and C_HT, respectively), and decreasing the presence of defects on the pasta surface (heterogeneity was 5%, 36%, and 45% for C_HT, EC_R, and C_R, respectively). Heat treatment on grains or flour significantly increased starch susceptibility to α-amylase (6.6, 7.4, and 8.6% for C_R, C_HT, and EC_R, respectively) and decreased the final viscosity (from 335 BU in C_R to 287 and 291 BU in EC_R and C_HT), resulting in a significant increase in starch digestibility (slowly digestible starch was about 41, 27, and 26% in C_R, C_HT, and EC_R, respectively). As regards proteins, the main effect on their structure was observed in C_HT, where the cooking behavior was much improved and cooking losses were lowest (5.7%). On the other hand, protein and starch organization in EC_R might have accounted for pasta resistance in overcooking

Validation of a General and Sports Nutrition Knowledge Questionnaire in Italian Early Adolescents

To the best of our knowledge, no specific questionnaires on sports nutrition knowledge (NK) have been validated so far in Italian early adolescents. The aim of the present study was to validate a short (26-item) general and sports NK questionnaire in a group of Italian early adolescents. To this aim, the questionnaire was administered to 264 subjects for analysis of internal consistency, and in a subgroup (n = 39) for evaluating the reliability over time. The questionnaire revealed good overall internal consistency and reliability (Cronbach’s α = 0.684) and a highly significant correlation over time (r = 0.977, p < 0.001). Comparison with other validated questionnaires is tricky, because the previous questionnaires were validated in different populations, such as middle or late adolescents or adults, with a higher number of items compared to our questionnaire. Furthermore, data on adolescent NK in Italy are very limited. This study provides a brief, feasible, and validated questionnaire that can be used for investigating sports NK in young subjects. It could be used for evaluating the efficacy of education on general and sports nutrition in both the general population and athletes, and for investigating the relationship between NK and different sports in early adolescence

Nutritive Evaluation of the Bambara Groundnut Ci12 Landrace [Vigna subterranea (L.) Verdc. (Fabaceae)] Produced in Côte d’Ivoire

The nutritional evaluation of the Bambara groundnut Ci12 landrace (Vigna subterranea (L.) Verdc.) seeds produced in Côte d’Ivoire shows a 19% content of protein, containing all the essential amino acids with tryptophan as the limiting amino acid, a total dietary fiber level of 10%, with a low soluble fraction content, and a fat content of 1.4%, with a high proportion of total unsaturated fatty acids (61%) of which 36% were n-6 fatty acids. This legume contains phosphorus, as the major mineral, followed by magnesium and calcium, and trace elements (iron, copper and zinc). It is characterized by the same amount of α-tocopherol and antioxidant capacity as common legumes. The high concentration of essential amino acids, n-6 fatty acids and minerals, mainly Fe, in the Ci12 landrace of Bambara groundnut indicates that this local legume has the potentiality to improve the nutritional status in Côte d’Ivoire and it could be regarded as a nutrient dense food

Effects of Red Rice or Buckwheat Addition on Nutritional, Technological, and Sensory Quality of Potato-Based Pasta

This work investigates the effects of red rice (R) or buckwheat (B) flour addition on nutritional, technological, and sensory quality of potato-based pasta (gnocchi). Three gluten-free (GF) and three conventional (C) samples were produced in an industrial line without any addition or with 20% R or B. R and B addition significantly (p < 0.05) reduced starch content and increased fat amount and ready digestible starch fraction (potential higher glycemic impact). R addition significantly (p < 0.05) worsened GF pasta structure, increasing solid loss in cooking water (5.4 ± 1.2 vs. 4.1 ± 0.5 g/100 g pasta) and reducing product firmness (408 ± 13 vs. 108 ± 2 N). B addition resulted in intermediate consistency (243 ± 8 N), despite the highest total fiber content and weight increase during cooking. Similar trends were found in C samples, indicating a better texturizing capacity of B in comparison to R. Samples without any addition were the most liked (C = 67.4 and GF = 60.6). Texture was the major contributor to liking: uniform structure and firm texture were positive predictors of liking, whereas a granular and coarse matrix contributed negatively. The outcomes of this research can be useful in developing GF potato-based pasta for consumers focused on healthier foods and for industries willing to better valorize their products

Radiosynthesis of 68Ga-labelled DOTA-biocytin (68Ga-r-BHD) and assessment of its pharmaceutical quality for clinical use

Biocytin analogues labelled with indium-111, yttrium-90 and lutetium-177 have shown their effectiveness in the imaging of infections/inflammation in patients with osteomyelitis and function as efficient tools in pretargeted antibody-guided radioimmunotherapy. In this study, the labelling of a biocytin analogue coupled with DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid), namely, r-BHD, with gallium-68 (68Ga) was optimized, and the quality and stability of the preparations were assessed for clinical use