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Herein we report clinical and virological data in a patient with COVID-19 infection and a prior history of kidney transplantation who had a good clinical recovery despite systemic infection.Reverse transcriptase quantitative PCR analysis for the RdRp, N and E target genes detected viral RNA in different types of biological specimens. Whole viral genome sequences were obtained and analyzed from respiratory tract, feces and blood.Viral sequences showed high (~99.9%) homology with the Wuhan seafood market pneumonia virus. Phylogenetic analysis assigned of the SARS-CoV-2 strains to clade G. A rare variant in the orf1ab gene was present in both sequences, while a missense variant was detected only in viral RNA from stool.The evolution of the COVID-19 systemic infection in the patient presented here was favorable to the hypothesis that immunosuppressive therapy in organ transplant recipients might be involved in viral dissemination. A missense mutation was present in only one specimen from the same patient implying the occurrence of a mutational event in viral RNA, which is suggestive for the presence of an active virus, even though viral isolation is necessary to demonstrate infectivity.

(17) O NMR is not routinely used for structure characterization, and kinetic studies of fluxional organic compounds are seldom undertaken because poor sensitivity and fast quadrupole relaxation are frequently regarded as intractable issues. This work shows how, nowadays, quantitative (17) O dynamic NMR studies on small organic molecules are feasible without enrichment being needed. It reports on acetoxysilanes, a class of fluxional compounds whose structure and dynamics were to be clarified. Natural abundance (17) O NMR spectra were recorded over a wide range of temperatures using standard instrumentation. The analysis relies on simple linewidth measurements and directly provides the activation parameters. The activation enthalpy is found to decrease with increasing number of acetoxy groups bound to silicon. Density functional theory calculations properly predict this trend and show that a single oxygen atom of the acetoxy group is bound to silicon, excluding chelation as binding mode, and that the dynamic process involves the shift of the silicon atom between the two oxygen atoms of the acetoxy group. Copyright © 2012 John Wiley & Sons, Ltd.

Acquired hemophilia due to autoantibody to Factor VIII coagulant (Factor VIIIc) is a rare event which may be observed in patients with different autoimmune diseases. To our knowledge, this association has been reported only once in patients with autoimmune thyroid disease. Here we describe a patient presenting with a severe hemorrhagic disorder due to Factor VIIIc antibody in whom biochemical screening for thyroid diseases led to a diagnosis of hyperthyroid Graves' disease not associated to overt clinical features. This case underlines the importance of carrying out a complete screening for autoimmunity, including thyroid autoimmune disease, in all patients with apparently isolated serum Factor VIIIc inhibitors.

The principal aim of this study was to evaluate, on biochemical grounds, whether injection of a low-osmolar nonionic contrast medium (iohexol) can induce a prothrombotic state and/ or a change in fibrinolysis. Fifteen patients were submitted to urographic examination and the assays listed below were performed: before the injection (To), 1 h after (Ti), and 24 h after (T24) the injection of the contrast medium. The following assays were performed: fibrinopeptide A (FPA), prothrombin fragment 1+2 (F1+2), thrombin-antithrombin complex (TAT), and D dimer (D-D). The assays were carried out on 6 of the patients to whom a saline infusion was administered. Only a mild statistically significant increase was found in FPA levels at 1 h after injection of the contrast medium (mean and CI 95%: T0 4.4, 3.7-5.5; T, 6.0, 4.9-9.1; p = 0.003). F1+2, TAT and D-D did not show any significant change after the injection. These findings show that after injection of iohexol, only a mild, though statistically significant, increase in FPA levels was observed as an expression of increased thrombin activity. In the absence of any significant increases in TAT, F1+2 and D-D, we have no evidence of a prethrombotic state.

Oral anticoagulants are widely used for preventing thromboembolic events in many pathological conditions, such as mechanical or biological heart valve prosthesis, atrial fibrillation, deep vein thrombosis and post-myocardial infarction (1). Particularly, the intensity of anticoagulation to be induced in patients with mechanical heart prosthesis is not well established. In fact, the Dutch Thrombosis Policy recommends deep anticoagulation (3.6-4.8 INR) irrespective of whether the prosthesis is aortal or mitral (2). In contrast the Consensus Committee for antithrombotic therapy in patients with mechanical prosthetic valves, with North American thromboplastins, suggests a therapeutic range between 2.2 and 3.3 INR for both ball and tilt disk prosthesis (3). Again, the guidelines on oral anticoagulation published on behalf of the British Society for Hematology recommend a target of between 3 and 4.5 for mechanical heart valves (1). But is deeper anticoagulation more effective in the biochemical inhibition of the coagulation cascade ? Is there any difference between aortal and mitral prosthesis considering that a higher thromboembolic risk may be present in the latter due to hypercoagulability secondary to atrial fibrillation and blood stagnation ? For this purpose we chose to measure prothrombin F 1+2 peptide that is cleaved by factor Xa from the prothrombin molecule, since it has recently been shown that F 1+2 is reduced during oral anticoagulants (4).

(RDI) and partial rootzone drying (PRD) with two restoration volumes: 80% and 40% of the crop evapotranspiration (ETc). The irrigation strategy and the restoration volume significantly affected xilematic potential trends, but treatments did not show values over a moderate stress level. Water use efficiency was influenced by the irrigation strategy only in 2009, whereas it was affected by the restoration volume and was higher in 40% ETc treatment in all three years. PRD-80% ETc showed the highest J. lybica density, whereas the RDI-40% ETc was the least infested. Z. rhamni was very abundant only in 2009, but showed no differences among treatments. The 3-years trial demonstrates that the lower restoration volume (40% ETc) allow a better water use efficiency and lower J. lybica infestations.

The aim of this study was to evaluate the balance between thrombin and plasmin activity in a group of 79 diabetic patients (IDDM and NIDDM). For this purpose we determined fibrinopeptide A (FPA) and B beta 15-42, specific products of thrombin and plasmin activity. Moreover we investigated the behaviour of antithrombin III and alpha 2 antiplasmin, important inhibitors of blood coagulation and fibrinolysis. Results show an increase both in FPA and B beta 15-42 in IDDM and NIDDM patients when compared to healthy controls. However the ratio between B beta 15-42 and FPA was lower than in controls indicating an imbalance between thrombin and plasmin activity. Antithrombin III levels were not different from the controls and no correlation was found with Hb A1c. alpha 2 antiplasmin was found to be higher in IDDM when compared both with NIDDM and controls. A non linear correlation was found between Hb A1c and alpha 2 AP in both diabetic groups. We conclude that the imbalance between thrombin and plasmin activity may have a role in determining fibrin deposition. These subclinical abnormalities, unrelated to vascular complications and duration of the disease, may progressively contribute to the development of the vascular complications in diabetes.

We investigated the behavior of prothrombin fragment F1+2 and thrombin-antithrombin complexes in 70 patients treated with chronic anticoagulant therapy. Moreover, in a longitudinal study 37 patients were evaluated twice and 16 patients three times. Twenty-eight age-and sex-matched healthy subjects were also studied as a control group. Prothrombin fragment F1+2 and thrombinantithrombin complexes were significantly higher in controls than in patients on anticoagulants. There were no differences in prothrombin fragment F1+2 or thrombinantithrombin values among patients with different International Normalized Ratios, nor in the same patients studied two or three times. Our results confirm that oral anticoagulant treatment can effectively reduce thrombin activity. However, strong anticoagulation does not induce a further significant decrease in fragment F1+2 values. Therefore, we feel measurement of fragment F1+2 might be less useful than thought in optimizing oral anticoagulant therapy.

Human immunodeficiency virus type 1 (HIV-1) Tat is a potent transcriptional activator of the HIV-1 promoter and also has the ability to modulate a number of cellular regulatory circuits including apoptosis. Tat exerts its effects through interaction with viral as well as cellular proteins. Here, we studied the influence of p73, a protein that is implicated in apoptosis and cell cycle control, on Tat functions in the central nervous system. Protein interaction studies using immunoprecipitation followed by Western blot and glutathione S-transferase pull-down assays demonstrated the association of Tat with p73. Tat bound to the N-terminal region of p73 spanning amino acids 1 to 120, and this interaction required the cysteine-rich domain (amino acids 30 to 40) of Tat. Association of p73 with Tat prevented the acetylation of Tat on lysine 28 by PCAF. Functional studies including RNA interference showed that p73 inhibited Tat stimulation of the HIV-1 promoter. Furthermore, p73 prevented the interaction of Tat with cyclin T1 in vitro but not in vivo. These findings suggest possible new therapeutic approaches, using p73, for Tat-mediated AIDS pathogenesis.

We studied blood coagulation and fibrinolysis activities in hyperthyroidism before and after methimazole or 131I. Fibrinopeptide A and B beta 15-42, in vivo indicators of thrombin and plasmin activity, were measured by RIA, while fibrinogen by the Clauss method. We studied 50 patients, affected by toxic diffuse goiter. We evaluated 21 of them before and after treatment. Fibrinogen, fibrinopeptide A, and B beta 15-42 were higher in patients than in controls (p less than 0.0001). There was no difference in fibrinopeptide A nor in B beta 15-42 before or after treatment. In euthyroidism fibrinogen returned to normal values. Inflammation of the thyroid gland secondary to autoimmunity may activate blood coagulation by release of tissue factor. High fibrinogen before treatment may be explained as an aspecific response. Since it persists in euthyroidism, autoimmunity could account for high fibrinopeptide A and B beta 15-42 aftertreatment.

The distributions of some genetic markers in 106 Sardinian individuals with insulin-dependent diabetes mellitus (IDDM) and in a control sample of 186 nondiabetic Sardinians were studied. A strong association of IDDM with some phenotypes of ACP, PGM1, C3 and GC genetic markers was found. In the IDDM patients there is a significant increase of ACP B, ACP B-C, PGM1 1S-1F and GC 1S-2 phenotypes. Particularly the individuals with the ACP B, PGM1 1S-1F and GC 1S-2 phenotypes show the highest values of the relative risk (RR) and the attributable risk (AR) and seem to be more susceptible to IDDM disease.

A hypercoagulable state is associated with an increased incidence of cardiovascular disease, the most important cause of permanent grounding of flying personnel.The aim of our study was to investigate whether a hypercoagulable state is present in jet pilots, and whether it can be due to flight activity.To this purpose we studied Fibrinopeptide A (FPA), Thrombin-Antithrombin complexes (TAT) and D-Dimer (DD), sensitive biochemical markers of blood coagulation and fibrinolysis activation, in 10 jet pilots after a standardized training flight mission, and in a control group. Also evaluated before flight were 6 jet pilots.We were able to show increased thrombin and plasmin activity both in jet pilots compared to the control group, and after flight in the 6 pilots who were evaluated twice.We conclude that a hypercoagulable state due to flight activity is present in jet pilots after flight. Possible mechanisms involve an effect of psycho-physical stress mediated by a neuroendocrine response to flight activity, or an effect of chronic +Gz exposure on cardiovascular structure and function.

The diagnostic iter of a case of Streptococcus mitis endocarditis is reported. Bacterial endocarditis was diagnosed in a 32-year-old patient following ultrasound cardiography and microbiological tests. The paper stresses the importance of ultrasound cardiography in the diagnosis of bacterial endocarditis.

We have performed the BT test in 55 patients undergoing oral anticoagulant therapy monitored by means of Thrombotest (TT). Patients in steady state of anticoagulation showed longer BT than normal controls; patients in overdose phase had longer BT values than either controls or patients in steady state. After recovery the overdose phase patients showed BT values not different from those of the controls. Moreover we were able to find in our patients a significant linear correlation between BT and TT. Impairment in primary haemostasis could be due either to a scarce fibrin deposition in the haemostatic plug or to deficiency of a possible vitamin K dependent vascular "bleeding factor".

We have read with interest the reports published in this journal by Ford at al. (3), van Doormaal et al. (1) and Haubenstock et al. (2) on the abnormalities of platelet count (PC) and mean platelet volume (MPV) in patients with hyperthyroidism and hypothyroidism. We believe that the results of these authors are rather inconclusive and here report our results on PC and MPV measurements in a large group of patients with various thyroid diseases

Plasma Bβ 15–42 and fibrinopeptide A (FPA) concentrations, which are respectively indicators of plasmin and thrombinin vivo activity, were measured in 46 patients with ischemic arterial disease without signs of acute thrombosis. In the group as a whole, an increase in both Bβ 15–42 and FPA was found. When the patients were divided in two groups on the basis of their reversible (transitory ischemic attacks and unstable angina) or irreversible (stroke and myocardial infarction) ischemic episodes, the levels of Bβ 15–42 were significantly elevated only in the former group when compared to controls (p

In order to detect even minimal fibrinolysis activation in liver cirrhosis, we measured fibrinopeptide Bβ 15–42 (Bβ 15–42), an indicator of plasmin activity in vivo and α2-antiplasmin (α2-AP) in a group of cirrhotic patients. The second goal of this study was to investigate whether an increased fibrinolytic activity is related to a chronic disseminated intravascular coagulation. For this purpose we concomitantly measured fibrinopeptide A (FPA), marker of thrombin activity in vivo. Results show significantly higher levels of Bβ 15–42 in cirrhotic patients than in control (p < 0.01). In patients with high FPA levels we found significantly higher values than in patients with normal FPA (p < 0.01). α2-AP was lower in patients with high FPA levels than in patients with normal FPA (p < 0.05). A significant negative correlation was found between FPA and α2-AP only in patients with high FPA (p < 0.05). There was no relationship between Bβ 15–42 and FPA nor between Bβ 15–42 and α2-AP when all patients were considered. These findings confirm that in liver cirrhosis fibrinolysis activation may occur. The primary pathogenetic role of DIC may be important in this respect. However the lack of correlation between FPA and Bβ 15–42 suggests that other pathogenetic factors may be involved in determining fibrinolysis activation.

In vivo study of blood coagulation and fibrinolysis activities in non insulin dependent diabetes mellitus. The aim of the study was to investigate in vivo blood coagulation and fibrinolysis activities in a group of diabetic patients NIDDM with and without vascular complications. For this purpose we determined two sensitive indicators in vivo of blood coagulation and fibrinolytic activities such as fibrinopeptide A and B beta 15-42 respectively. Moreover, we computed the ratio between B beta 15-42 and fibrinopeptide A in order to investigate a possible imbalance in vivo between blood coagulation and fibrinolysis. Control groups were 15 healthy subjects and 28 non diabetic patients affected by atherosclerotic disease. Fibrinopeptide A and B beta values were significantly higher in the diabetic patients than controls but there was no difference between the former group and the atherosclerotic patients. Also, no correlation was found for FPA, B beta, B beta/FPAr and HbAlc, fructosamine and blood glucose levels. There was no difference in B beta, FPA and B beta/FPAr values for patients treated with insulin and for those treated with either hypoglycemic agents or diet. Our data indicate that in diabetic patients fibrinolysis activity is increased, but it cannot counterbalance thrombin activity which appears much more enhanced. Finally, the lack of correlation for FPA, B beta, B beta/FPAr and HbAlc, fructosamine and blood glucose suggests that blood coagulation and fibronolysis abnormalities are not related to the degree of blood glucose control.

The aim of this work was to investigate whether the thrombin activity is related to the degree of anticoagulation induced by oral anticoagulants. Moreover, we tried to detect an optimal anticoagulation range at which the lowest possible thrombin activity can be reached. We investigated 28 patients (19 women and 9 men, mean age 54 ± 9 years). Anticoagulation had been induced by acenocoumarol for at least 1 year before the beginning of this study. The degree of anticoagulation was monitored by the thrombotest coagulation method. The therapeutic range was 5–13%. The thrombin activity was measured by means of the fibrinopeptide A radioimmunological assay. In 15, 7, and 6 of the patients, thrombotest and fibrinopeptide A were carried out twice, once, and three times, respectively. Our results show first of all a significant positive relationship between thrombotest and fibrinopeptide A (p < 0.001). Once this result was obtained, we tried to improve our identification of the behaviour of the thrombin activity in relation to the degree of anticoagulation assessed by thrombotest. For this purpose we employed a third-degree polynomial regression analysis which showed a better fit of the data. Since the curve became steeper from about 10% thrombotest levels, we divided the FPA values on the basis of thrombotest ranges. FPA values for the 14- to 25% thrombotest range were significantly different from those in the thrombotest range of 4–10 %. Moreover, FPA levels in the 11 to 13 % thrombotest range were significantly different from those in the thrombotest range of 4–10%. Our results suggest that a significant decrease in thrombin activity may be achieved only with a deep anticoagulation.

The present study is a preliminary approach to detect both blood coagulation and fibrinolysis activation by employing RIA for fibrinopeptide A (FPA) (Mallinckrodt) and BB 15-42 (IMCO and SORIN Biomedica) in 30 patients with atherosclerotic disease.The patients (20 men and 10 women, mean age 57.4 ± 11.9 years) were affected by myocardial infarction (n=12), stroke (n=5), transitory ischemic attacks (n=7) and unstable angina (n=8).Because of the non normal distribution of FPA as well as of BB 15-42, results are expressed as median and range.Mann-Whitney test has been used for statistical analysis.FPA levels in patients (3.5, 1.1-9.5 ng/ml) were significantly higher than those of the controls (2.6, 0.5-4.9 ng/ml) (p

In order to investigate whether high fibrinogen levels were associated with elevated thrombin activity, we measured fibrinogen and fibrinopeptide A in 37 elderly healthy subjects ranging from 60 to 93 years. Fibrinogen levels (519.1 ± 127.0 mg/dl) and fibrinopeptide A (5.9, 0.9–18.1 ng/ml) were significantly higher than in younger controls. A highly significant negative linear correlation was found between fibrinogen and fibrinopeptide A in the elderly subjects (p < 0.01). However, a polynomial regression showed that this negative relationship was present at the fibrinogen levels ranging between 420 and 700 mg/dl. Our results suggest that high fibrinogen levels in elderly subjects do not necessarily mean that their thrombin activity is concomitantly increased.

Plasma B beta 15-42 and fibrinopeptide A (FPA) concentrations, which are respectively indicators of plasmin and thrombin in vivo activity, were measured in 46 patients with ischemic arterial disease without signs of acute thrombosis. In the group as a whole, an increase in both B beta 15-42 and FPA was found. When the patients were divided in two groups on the basis of their reversible (transitory ischemic attacks and unstable angina) or irreversible (stroke and myocardial infarction) ischemic episodes, the levels of B beta 15-42 were significantly elevated only in the former group when compared to controls (p less than 0.01). In the latter group we found significantly increased levels of FPA with respect to both controls (p less than 0.01) and patients with reversible and transient ischemic episodes (p less than 0.05). Moreover, the B beta 15-42/FPA ratio was significantly lower in patients with irreversible ischemic episodes than in controls (p less than 0.01) and patients with transient ischemic episodes (p less than 0.01), while no difference was found between the latter group and controls, although FPA and B beta 15-42 were significantly higher. These results suggest that in patients with transient and reversible ischemic episodes fibrinolytic activity is able to counterbalance an increased thrombin activity, while this does not appear to occur in patients with irreversible ischemic episodes.

Subnormal concentrations of alpha 2 Antiplasmin (alpha 2 AP) in liver cirrhosis may be due to an impaired hepatic synthesis and/or to a fibrinolysis activation in disseminated intravascular coagulation (DIC). In order to clarify this problem, in 26 cirrhotic patients (15 compensated and 11 decompensated) alpha 2 AP plasma activity and plasma Fibrinopeptide A (FPA) were measured. Serum albumin, p-Cholinesterase (p-CHE), Fibrinogen and Fibrinogen Degradation Products (FDP) were also carried out. Our data show that alpha 2 AP and FPA were equally abnormal in compensated and decompensated cirrhosis. The significant negative correlation obtained between alpha 2 AP and FPA as well as the lack of correlation between alpha 2 AP and albumin, alpha 2 AP and p-CHE in both groups suggests that, in our patients, alpha 2 AP decrease may be due to a fibrinolysis activation induced by a DIC which appears chronic since Fibrinogen and FDP were normal. These findings are in agreement with the results obtained in the four subgroups a posteriori selected on the basis of FPA levels: alpha 2 AP in subgroups with high FPA was significantly different from controls while it did not differ in subgroups with normal FPA.

The aim of our study was to investigate the effect of a diet with a known vitamin K content on the monitor test for oral anticoagulant therapy. We studied 10 poorly controlled patients (7 women and 3 men, mean age 48+15 years) in therapy with acenocoumarol for at least 1 year. Another group of 10 poorly controlled patients was considered as a control group. After a baseline period, during which a free diet was allowed, patients were administered a diet with a controlled vitamin K content; in the same period, control subjects were not subjected to any dietary restriction. Thrombotest (Nyegaard, Oslo) was employed for monitoring oral anticoagulant therapy, with a therapeutic range between 2.3 and 4.8 INR. We found a significant difference by thrombotest between the percentages within the therapeutic range obtained before and during dietary treatment (p = 0.0001). The difference in percentages was -0.31 and the 95% CI, of the difference ranged from -0.45 to -0.17. No significant difference was shown in the control group in the same periods. Our data suggest that a diet with a controlled vitamin K content is effective in increasing the percentage of tests within the therapeutic range in patients with poorly controlled anticoagulation.

Nello studio dell’efficacia scolastica i modelli teorici di riferimento suggeriscono l’importanza di utilizzare approcci multifattoriali. In questo studio sono stati considerati fattori riconducibili ai processi organizzativi e didattici, con l’obiettivo di indagare differenze tra istituti con effetto-scuola (elaborato da Invalsi) positivo e negativo. Sono stati coinvolti 1774 insegnanti provenienti da 73 scuole di tre regioni italiane, i quali hanno compilato un questionario on-line. I risultati di confronto tra istituti con livelli positivi versus negativi di effetto-scuola hanno evidenziato alcune differenze. In particolare, le scuole con risultati di apprendimento migliori mostrano livelli significativamente più alti di leadership di supporto del dirigente scolastico e di decision-making partecipativo. I risultati e le proposte di intervento vengono discussi utilizzando un approccio multifattoriale e interdisciplinare Theoretical models suggest multifactorial approaches for the investigation of school effectiveness. Therefo-re, in this study factors related to organizational and educational processes have been considered, with the aim of investigating differences between institutions with positive versus negative added value (developed by Invalsi). The study involved 1174 teachers, employed in 73 schools in three different Italian regions, who filled in an on-line questionnaire. The comparison between schools with a positive versus negative added value showed some differences. Particularly, schools with more positive learning outcomes showed significantly higher levels of supportive leadership and a participative decision-making style. Results and intervention pro-posals are discussed using a multifactorial and interdisciplinary approach.