SV-IV Peptide1–16 reduces coagulant power in normal Factor V and Factor V Leiden

Native Factor V is an anticoagulant, but when activated by thrombin, Factor X or platelet proteases, it becomes a procoagulant. Due to these double properties, Factor V plays a crucial role in the regulation of coagulation/anticoagulation balance

Hydatid disease of the liver: thirty years of surgical experience.

Hydatid disease of the liver is a relatively frequent disease. Although the natural history is almost completely known, several complications may occur. The aim of this study was to show that radical surgical resection of the hepatic hydatid cyst is a safe and very effective technique, based on our results after 30-year experience. A review of most significant studies was carried out. We retrospectively evaluated our surgical cases. From January 1973 to December 2003 we treated 216 patients, 98 males and 118 females. Survival was compared with the Kaplan-Meier test, using log-rank analysis to compare data. Differences with a p value less than 0.05 were considered significant. A total of 279 cysts were excised. We performed pericystectomy in 122 cases, 73 of which closed. We also performed 19 atypical resections, 10 segmentectomies, 20 lobectomies and 2 percutaneous treatments. In more than 90% of cases, preoperative data collection was completed by preoperative ultrasound. The cumulative morbidity was 13%. The recurrence rate amounted to 4.3% at 5 years and 7% at 10 years: of these, 6 occurred after non-radical surgery and 2 after total pericystectomy or liver resection (p < 0.001). Technical advances and accumulated experience permit safe treatment of hepatic hydatid cysts by radical resection, with an almost zero recurrence rate, making it the treatment of choice over partial resection. The utility of percutaneous treatment remains confined to limited indications, such as laparoscopy

Tuning Local Hydration Enables a Deeper Understanding of Protein-Ligand Binding: The PP1-Src Kinase Case

Water plays a key role in biomolecular recognition and binding. Despite the development of several computational and experimental approaches, it is still challenging to comprehensively characterize water-mediated effects on the binding process. Here, we investigate how water affects the binding of Src kinase to one of its inhibitors, PP1. Src kinase is a target for treating several diseases, including cancer. We use biased molecular dynamics simulations, where the hydration of predetermined regions is tuned at will. This computational technique efficiently accelerates the SRC-PP1 binding simulation and allows us to identify several key and yet unexplored aspects of the solvent's role. This study provides a further perspective on the binding phenomenon, which may advance the current drug design approaches for the development of new kinase inhibitors

Measurement of neutron detection efficiency between 22 and 174 MeV using two different kinds of Pb-scintillating fiber sampling calorimeters

We exposed a prototype of the lead-scintillating fiber KLOE calorimeter to neutron beam of 21, 46 and 174 MeV at The Svedberg Laboratory, Uppsala, to study its neutron detection efficiency. This has been found larger than what expected considering the scintillator thickness of the prototype. %To check our method, we measured also the neutron %detection efficiency of a 5 cm thick NE110 scintillator. We show preliminary measurement carried out with a different prototype with a larger lead/fiber ratio, which proves the relevance of passive material to neutron detection efficiency in this kind of calorimeters

Measurement of the neutron detection efficiency of a 80% absorber - 20% scintillating fibers calorimeter

The neutron detection efficiency of a sampling calorimeter made of 1 mm diameter scintillating fibers embedded in a lead/bismuth structure has been measured at the neutron beam of the The Svedberg Laboratory at Uppsala. A significant enhancement of the detection efficiency with respect to a bulk organic scintillator detector with the same thickness is observed.Comment: 10 pages, 7 figure

Direct interation of garcinol and related polyisoprenylated benzophenones of Garcinia cambogia fruits with the transcription factor STAT-1 as a likely mechanism of their inhibitory effect on cytokine signaling pathways.

Garcinol (1), a polyisoprenylated benzophenone occurring in Garcinia species, has been reported to exert anti-inflammatory activity in LPS-stimulated macrophages, through inhibition of NF-κB and/or JAK/STAT-1 activation. In order to provide deeper insight into its effects on the cytokine signaling pathway and to clarify the underlying molecular mechanisms, 1 was isolated from the fruits of Garcinia cambogia along with two other polyisoprenylated benzophenones, guttiferones K (2) and guttiferone M (3), differing from each other in their isoprenyl moieties and their positions on the benzophenone core. The affinities of 1-3 for the STAT-1 protein have been evaluated by surface plasmon resonance and molecular docking studies and resulted in KD values in the micromolar range. Consistent with the observed high affinity toward the STAT-1 protein, garcinol and guttiferones K and M were able to modulate cytokine signaling in different cultured cell lines, mainly by inhibiting STAT-1 nuclear transfer and DNA binding, as assessed by an electrophorectic mobility shift assay

Cardiovascular comorbidities and pharmacological treatments of covid-19 patients not requiring hospitalization

Introduction: The Coronavirus disease 2019 (COVID-19) outbreak is a whole Earth health emergency related to a highly pathogenic human coronavirus responsible for severe acute respiratory syndrome (SARS-CoV-2). Despite the fact that the majority of infected patients were managed in outpatient settings, little is known about the clinical characteristics of COVID-19 patients not requiring hospitalization. The aim of our study was to describe the clinical comorbidity and the pharmacological therapies of COVID-19 patients managed in outpatient settings. Materials and Methods: We performed an observational, retrospective analysis of laboratory-confirmed COVID-19 patients managed in outpatient settings in Naples, Italy between March 9 and May 1, 2020. Data were sourced from the prospectively maintained Health Search (HS)/Thales database, shared by 128 primary care physicians (PCPs) in Naples, Italy. The clinical features and pharmacological therapies of COVID-19 patients not requiring hospitalization and managed in outpatient settings have been described. Results: A total of 351 laboratory-confirmed COVID-19 patients (mean age 54 ± 17 years; 193 males) with outpatient management were evaluated. Hypertension was the most prevalent comorbidity (35%). The distribution of cardiovascular comorbidities showed no gender-related differences. A total of 201 patients (57.3%) were treated with at least one experimental drug for COVID-19. Azithromycin, alone (42.78%) or in combination (27.44%), was the most widely used experimental anti-COVID drug in outpatient settings. Low Molecular Weight Heparin and Cortisone were prescribed in 24.87% and 19.4% of the study population, respectively. At multivariate regression model, diabetes (risk ratio (RR): 3.74; 95% CI 1.05 to 13.34; p = 0.04) and hypertension (RR: 1.69; 95% CI 1.05 to 2.7; p = 0.03) were significantly associated with the experimental anti-COVID drug administration. Moreover, only diabetes (RR: 2.43; 95% CI 1.01 to 5.8; p = 0.03) was significantly associated with heparin administration. Conclusions: Our data show a high prevalence of hypertension, more likely treated with renin– angiotensin–aldosterone system (RASS) inhibitors, among COVID-19 patients not requiring hospitalization. Experimental COVID-19 therapies have been prescribed to COVID-19 patients considered at risk for increased venous thromboembolism based on concomitant comorbidities, in particular diabetes and hypertension

A global fit to determine the pseudoscalar mixing angle and the gluonium content of the eta' meson

We update the values of the eta-eta' mixing angle and of the eta' gluonium content by fitting our measurement R_phi = BR(phi to eta' gamma)/ BR(phi to eta gamma) together with several vector meson radiative decays to pseudoscalars (V to P gamma), pseudoscalar mesons radiative decays to vectors (P to V gamma) and the eta' to gamma gamma, pi^0 to gamma gamma widths. From the fit we extract a gluonium fraction of Z^2_G = 0.12 +- 0.04, the pseudoscalar mixing angle psi_P = (40.4 +- 0.6) degree and the phi-omega mixing angle psi_V = (3.32 +- 0.09) degree. Z^2_G and psi_P are fairly consistent with those previously published. We also evaluate the impact on the eta' gluonium content determination of future experimental improvements of the eta' branching ratios and decay width.Comment: 13 pages, 7 figures to submit to JHE

Thromboelastographic profiles as a tool for thrombotic risk in digestive tract cancer

Background: Quantification of the magnitude of thrombotic risk associated with malignancy and with anti-cancer therapy is indispensable to use anticoagulant drugs which selectively interfere with haemostatic mechanisms protecting patients from venous thromboembolism (VTE) and probably from tumor progression. However, none of activation coagulation markers has any predictive value for the occurrence of the thrombotic events in one individual patient. Current clotting methods can’t reveal the overall dynamic clot formation; in contrast thromboelastographic methods specifically assess overall coagulation kinetics and its strength in whole blood. Aim: Objective of study was to evaluate if the activation of coagulation as eventually revealed by ROTEM® thromboelastometry could assess an hypercoagulable state in surgical neoplastic patients. Patients and Methods: Fifty consecutive patients with carcinoma of the digestive tract in preoperative period (23 M, 27 F aging 61.5 (45–79 years) and 147 healthy subjects (71 M, 76 F) were studied. A recent thromboelastometric method based on thrombelastography after Hartert was employed. Measurements were performed on ROTEM Coagulation Analyzer. The continuous coagulation data from 50 min course were transformed into dynamic velocity profiles of WB clot formation. Results: Standard parameters (CT, CFT, MCF) of cancer patients were similar to controls. CT (in cancer patients): females 50 s (38.3–58.7), males 50 s (42–71.2) vs 51 s (42–59), p = 0.1210 / 53 s (42–74.8), p = 0.1975 (in controls). CFT (in cancer patients): females 72 s (32- 92.4), males 80 s (50.2- 128.7) vs 78 s (62–100), p = 0.0128 / 80 s (59–124.4), p = 0.9384 (in controls). MCF (in cancer patients): females 70 mm (59.9–82.5), males 63 mm (56–73.7) vs 69 mm (59–95.8), p = 0.9911 / 69 mm (53.6–90), p = 0.0135 (in controls). Females showed a higher MaxVel when compared to males. The MaxVel was increased in cancer patients: females 19 mm /100 s (14.3–49.5) males 18 mm / 100 s (11–27) vs 15 mm 100 s (11.8–22), p < 0.001 / 13 mm / 100 s (10–21.8), p < 0.001 in controls .The t-MaxVel was shortened in cancer patients: females 65 s (48.6–112.8), males 81 s (50.1–135.9) vs 115 s (56.8–166), p <0.001 / 115 s (59.8–180.8), p = 0.0002 in controls. The AUC was increased in cancer patients: females 6451 mm 100 (5511–8148), males 5984 mm 100 (5119-6899) vs 5778 mm 100 (4998–6655), p < 0.001 / 5662 mm 100 (4704–6385), p = 0.0105. Conclusion: Unlike other assays measuring variations in a single component during coagulation, the thrombelastographic method records a profile of real-time continuous WB clot formation, and may provide extensive informations on haemostasis in neoplastic patients before surgery.Предпосылки исследования количественная оценка риска тромбоза, связанного со злокачественными заболеваниями и противоопухолевой терапией, обязательно включает в себя применение средств-антикоагулянтов, защищающих больного от развития венозной тромбоэмболии (VTE)и возможно п рогрессии заболевания . Тем не менее ни один из маркеров ак- тивации коагуляции не имеет прогностической ценности с точки зрения возможности возникновения тромбоза у каждого отдельно взятого пациента. Современные мето ды оценки свертывания крови не отража ют образование тромба винамике ; наоборот, метод тромбо эластографии дает возможность специфически оценить кинетику свертывания крови целом . Цель: определить, в какой мере активность коагуляции, определяемой методом тромбоэ ластометрии, отражает состояние гиперсвертываемости крови у больных онкологического профиля после хирургического вмешательства. Пациенты и м ды: обследованы 50 больных раком пищ еваритель ного тракта в дооп ерационный п ериод (27 женщин, 23 му жчины, средний возраст 61,5 года (45–79 лет) и 147 здоровых доноров (71 мужчина, 76 женщин). Применяли метод тромбоэластометрии , основанный на тромбоэластографии Гартерта, с использованием анализатора коагуляциифирмыROTEM. Текущие д анные о свертывании за 50 мин измерений представили в виде динамичных профилей вязкости при образовании сгустка крови. Результаты: стандартные параметры (перио д коагуляции (CT), перио д образования сгу стка (CFT), максимал ь ная п лот- ность сгустка (MCF)) больных онкологического п рофиля близки к контроль ным . CT у больных онкологического п рофиля составлял: у женщин — 50 с (38,3–58,7), у му жчин 50 (42–71,2) vs 51 (42–59), p = 0,1210/53 ( 42–74,8 ), p = 0,1975 в контрольной группе . CFT у таких пациентов составлял : у женщин — 72 ( 32–92,4 м жчин – 80 с (50,2–128,7) vs 78 (62–100), p = 0,0128 80 (59–124,4), p = 0,9384 в контрол ьной группе . MCF у больных онкологического п составлял: у женщин — 70 мм (59,9–82,5), у мужчин — 63 мм (56–73,7) vs 69 мм (59–95,8), p = 0,9911 / 69 мм (53,6–90), p = 0,0135 в контрол ьной группе. У женщинпоказатели вязкости крови MaxVel были выше, чем у му жчин . Показатели MaxVel повышены у таких пациентов : у женщин — 19 мм/100 с (14,3–49,5) у му жчин — 18 мм/100 (11–27 ) vs 15 мм / 100 (11,8–22), p < 0,001 / 13 мм / 100 с (10–21,8), p <0,001 в контрол ьной группе. ь t-MaxVel понижен у больных онкологического профиля: у женщин – 65 с (48,6–112,8) , у мужчин – 81 с (50,1–135,9) vs 115 с (56,8–166), p < 0,001 / 115 с (59,8–180,8), p = 0,0002 в контрольной группе. Показатель AUC у повышен у женщин — 6451 мм 100 (5511–8148), у мужчин — 5984 мм 100 (5119–6899) vs 5778 мм 100 (4998–6655), p < 0,001 / 5662 мм 100 (4704–6385), p = 0.0105. Выводы в отличие от других мето дов, измеря ющих вариации отдельных комп онентов системы крови, метод тромбо эластографии отражает текущийп рофиль образования сгу сткав режиме реаль ного времени является информативным споссобом оценки состояния гемостаза у онкологических больных

Boost operators in Coulomb-gauge QCD: the pion form factor and Fock expansions in phi radiative decays

In this article we rederive the Boost operators in Coulomb-Gauge Yang-Mills theory employing the path-integral formalism and write down the complete operators for QCD. We immediately apply them to note that what are usually called the pion square, quartic... charge radii, defined from derivatives of the pion form factor at zero squared momentum transfer, are completely blurred out by relativistic and interaction corrections, so that it is not clear at all how to interpret these quantities in terms of the pion charge distribution. The form factor therefore measures matrix elements of powers of the QCD boost and Moeller operators, weighted by the charge density in the target's rest frame. In addition we remark that the decomposition of the eta' wavefunction in quarkonium, gluonium, ... components attempted by the KLOE collaboration combining data from phi radiative decays, requires corrections due to the velocity of the final state meson recoiling against a photon. This will be especially important if such decompositions are to be attempted with data from J/psi decays.Comment: 14 pages, 4 figure