Site directed mutagenesis as a tool to understand the catalytic mechanism of human cytidine deaminase.

Cytidine deaminase (CDA), is one of the enzymes involved in the pyrimidine salvage pathways, which catalyzes the formation of uridine and deoxyuridine by the hydrolytic deamination of cytidine and deoxycytidine, respectively. Human CDA is a tetrameric enzyme of identical 15 kDa subunits, each containing an essential zinc atom in the active site. The substrate binds to each active site independently and the cooperativity between subunits has not been reported. CDA is able to recognize as substrates some antitumor and antiviral cytidine analogs rendering them pharmacologically inactive. In light of the role played by this enzyme, a deep knowledge of CDA active site and mechanism of catalysis is required. Site-directed mutagenesis, associated with molecular modeling studies, may be an important tool to discover the active site structure of an enzyme and consequently its mechanism of action. In this review are summarized the site-directed mutagenesis experiments performed on human CDA: through these studies it was possible to understand the role exerted by specific amino acid residues in CDA active site and in the contacts between subunits. The obtained results may open a way for designing new cytidine based drugs or more potent CDA inhibitors

Pengaruh Komposisi Media Terhadap Pertumbuhan Kalus Dan Kadar Tannin Dari Daun Jati Belanda (Guazuma Ulmifolia Lamk) Secara in Vitro

West Indian Elm ( Guazuma ulmifolia Lamk.) is one of potentialplant producing tannin which is useful for controlling obesity. Tannin canbe produced through in vitro and this compound could be increased bycalli culture. The medium composition for calli induction was necessary toproduce the optimal calli. The aim of this research was to obtain themedium composition for calli induction through in vitro. Young leaves ofWest Indian Elm from glass house were used as explants. Murashige andSkoog (MS) medium enriched with B vitamin group was used as basicmedium. The experiments were arranged in completely randomized designin factorial pattern with ten replications. For calli induction, variousconcentration of 2,4-D (0.1; 0.3; and 0.5 mg/l) and its combination withBenzyl Adenin of 0.1 and 0.3 mg/l were used as treatments. Parametersobserved were calli diameter, structure, colour, fresh weight andperformance during culture. Analysis of tannin was conducted by usingdried samples both (in vitro and leaves from glass house) and thenextracted. The result showed that there was interaction between 2,4-D 0.3mg/l and Benzyl Adenin 0.1 mg/l on calli diameter (28.7 mm), the biggestcalli diameter after sub culture (31.9 mm), and fresh calli weight (5.02 g)eight weeks after treatments. Tannin content obtained from all of the invitro treatments (3.72 – 4.27%) was higher than tannin from leaves(2.24%)

Global food security and food riots – an agent-based modelling approach

Due to negative consequences of climate change for agriculture and food production shocks affecting different areas of the world, the past two decades saw the conditions of global food security increasingly worsen. This has resulted in negative consequences for the world economy, partly causing international food price spikes and social upheavals. In this paper we present statistical findings along with a preliminary version of an original agent-based model called the Dawe Global Security Model that simulates the global food market and the political fragility of countries. The model simulates the effects of food insecurity on international food prices and how these, coupled with national political fragility and international food trade can, in turn, increase the probability of food riots in countries. The agents in the model are the 213 countries of the world whose characteristics reflect empirical data and the international trade of food is also simulated based on real trade partnerships and data. The model has been informed, calibrated and validated using real data and the results of these procedures are presented in the paper. To further test the model we also present the model’s forecasts for the near future in terms of food prices and incidence of food riots. The Dawe Global Security Model can be used to test scenarios on the evolution of shocks to global food production and analyse consequences for food riots. Further developments of the model can include national responses to food crises to investigate how countries can influence the spread of global food crises

Measuring venous oxygenation using the photoplethysmograph waveform

OBJECTIVE: We investigate the hypothesis that the photoplethysmograph (PPG) waveform can be analyzed to infer regional venous oxygen saturation. METHODS: Fundamental to the successful isolation of the venous saturation is the identification of PPG characteristics that are unique to the peripheral venous system. Two such characteristics have been identified. First, the peripheral venous waveform tends to reflect atrial contraction. Second, ventilation tends to move venous blood preferentially due to the low pressure and high compliance of the venous system. Red (660 nm) and IR (940 nm) PPG waveforms were collected from 10 cardiac surgery patients using an esophageal PPG probe. These waveforms were analyzed using algorithms written in Mathematica. Four time-domain saturation algorithms (ArtSat, VenSat, ArtInstSat, VenInstSat) and four frequency-domain saturation algorithms (RespDC, RespAC, Cardiac, and Harmonic) were applied to the data set. RESULTS: Three of the algorithms for calculating venous saturation (VenSat, VenInstSat, and RespDC) demonstrate significant difference from ArtSat (the conventional time-domain algorithm for measuring arterial saturation) using the Wilcoxon signed-rank test with Bonferroni correction (p < 0.0071). CONCLUSIONS: This work introduces new algorithms for PPG analysis. Three algorithms (VenSat, VenInstSat, and RespDC) succeed in detecting lower saturation blood. The next step is to confirm the accuracy of the measurement by comparing them to a gold standard (i.e., venous blood gas)

Design of a modular Autonomous Underwater Vehicle for archaeological investigations

MARTA (MARine Tool for Archaeology) is a modular AUV (Autonomous Underwater Vehicle) designed and developed by the University of Florence in the framework of the ARROWS (ARchaeological RObot systems for the World's Seas) FP7 European project. The ARROWS project challenge is to provide the underwater archaeologists with technological tools for cost affordable campaigns: i.e. ARROWS adapts and develops low cost AUV technologies to significantly reduce the cost of archaeological operations, covering the full extent of an archaeological campaign (underwater mapping, diagnosis and cleaning tasks). The tools and methodologies developed within ARROWS comply with the "Annex" of the 2001 UNESCO Convention for the protection of Underwater Cultural Heritage (UCH). The system effectiveness and MARTA performance will be demonstrated in two scenarios, different as regards the environment and the historical context, the Mediterranean Sea (Egadi Islands) and the Baltic Sea

Prediction of arterial pressure increase after fluid challenge

<p>Abstract</p> <p>Background</p> <p>Mean arterial pressure above 65 mmHg is recommended for critically ill hypotensive patients whereas they do not benefit from supranormal cardiac output values. In this study we investigated if the increase of mean arterial pressure after volume expansion could be predicted by cardiovascular and renal variables. This is a relevant topic because unnecessary positive fluid balance increases mortality, organ dysfunction and Intensive Care Unit length of stay.</p> <p>Methods</p> <p>Thirty-six hypotensive patients (mean arterial pressure < 65 mmH) received a fluid challenge with hydroxyethyl starch. Patients were excluded if they had active bleeding and/or required changes in vasoactive agents infusion rate in the previous 30 minutes. Responders were defined by the increase of mean arterial pressure value to over 65 mmHg or by more than 20% with respect to the value recorded before fluid challenge. Measurements were performed before and at one hour after the end of fluid challenge.</p> <p>Results</p> <p>Twenty-two patients (61%) increased arterial pressure after volume expansion. Baseline heart rate, arterial pressure, central venous pressure, central venous saturation, central venous to arterial PCO₂difference, lactate, urinary output, fractional excretion of sodium and urinary sodium/potassium ratio were similar between responder and non-responder. Only 7 out of 36 patients had valuable dynamic indices and then we excluded them from analysis. When the variables were tested as predictors of responders, they showed values of areas under the ROC curve ranging between 0.502 and 0.604. Logistic regression did not reveal any association between variables and responder definition.</p> <p>Conclusions</p> <p>Fluid challenge did not improve arterial pressure in about one third of hypotensive critically ill patients. Cardiovascular and renal variables did not enable us to predict the individual response to volume administration.</p> <p>Trial registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00721604">NCT00721604</a>.</p

Surgical site infection after caesarean section. Space for post-discharge surveillance improvements and reliable comparisons

Surgical site infections (SSI) after caesarean section (CS) represent a substantial health system concern. Surveying SSI has been associated with a reduction in SSI incidence. We report the findings of three (2008, 2011 and 2013) regional active SSI surveillances after CS in community hospital of the Latium region determining the incidence of SSI. Each CS was surveyed for SSI occurrence by trained staff up to 30 post-operative days, and association of SSI with relevant characteristics was assessed using binomial logistic regression. A total of 3,685 CS were included in the study. A complete 30 day post-operation follow-up was achieved in over 94% of procedures. Overall 145 SSI were observed (3.9% cumulative incidence) of which 131 (90.3%) were superficial and 14 (9.7%) complex (deep or organ/space) SSI; overall 129 SSI (of which 89.9% superficial) were diagnosed post-discharge. Only higher NNIS score was significantly associated with SSI occurrence in the regression analysis. Our work provides the first regional data on CS-associated SSI incidence, highlighting the need for a post-discharge surveillance which should assure 30 days post-operation to not miss data on complex SSI, as well as being less labour intensive

Safety profile of enhanced thromboprophylaxis strategies for critically ill COVID-19 patients during the first wave of the pandemic: observational report from 28 European intensive care units

Introduction: Critical illness from SARS-CoV-2 infection (COVID-19) is associated with a high burden of pulmonary embolism (PE) and thromboembolic events despite standard thromboprophylaxis. Available guidance is discordant, ranging from standard care to the use of therapeutic anticoagulation for enhanced thromboprophylaxis (ET). Local ET protocols have been empirically determined and are generally intermediate between standard prophylaxis and full anticoagulation. Concerns have been raised in regard to the potential risk of haemorrhage associated with therapeutic anticoagulation. This report describes the prevalence and safety of ET strategies in European Intensive Care Unit (ICUs) and their association with outcomes during the first wave of the COVID pandemic, with particular focus on haemorrhagic complications and ICU mortality. Methods: Retrospective, observational, multi-centre study including adult critically ill COVID-19 patients. Anonymised data included demographics, clinical characteristics, thromboprophylaxis and/or anticoagulation treatment. Critical haemorrhage was defined as intracranial haemorrhage or bleeding requiring red blood cells transfusion. Survival was collected at ICU discharge. A multivariable mixed effects generalised linear model analysis matched for the propensity for receiving ET was constructed for both ICU mortality and critical haemorrhage. Results: A total of 852 (79% male, age 66 [37\u201385] years) patients were included from 28 ICUs. Median body mass index and ICU length of stay were 27.7 (25.1\u201330.7) Kg/m2 and 13&nbsp;(7\u201322) days, respectively. Thromboembolic events were reported in 146 patients (17.1%), of those 78 (9.2%) were PE. ICU mortality occurred in 335/852 (39.3%) patients. ET was used in 274 (32.1%) patients, and it was independently associated with significant reduction in ICU mortality (log odds = 0.64 [95% CIs 0.18\u20131.1; p = 0.0069]) but not an increased risk of critical haemorrhage (log odds = 0.187 [95%CI 12 0.591 to 12 0.964; p = 0.64]). Conclusions: In a cohort of critically ill patients with a high prevalence of thromboembolic events, ET was associated with reduced ICU mortality without an increased burden of haemorrhagic complications. This study suggests ET strategies are safe and associated with favourable outcomes. Whilst full anticoagulation has been questioned for prophylaxis in these patients, our results suggest that there may nevertheless be a role for enhanced / intermediate levels of prophylaxis. Clinical trials investigating causal relationship between intermediate thromboprophylaxis and clinical outcomes are urgently needed