Safety Considerations and Proposed Workflow for Laboratory-Scale Chemical Synthesis by Ball Milling

Chemical reactions that take place in a ball mill and in the absence of a bulk reaction solvent present different safety profiles to stirred solution reactions. Herein, we present and describe steps that a researcher may take to better ensure that they have considered some of the hazards and measures that emerge and minimize the risk to themselves and their colleagues

Inquérito sorológico para a detecção de anticorpos contra o vírus da Imunodeficiência Humana (VIH) em crianças internadas em enfermaria geral

São apresentados os resultados de um inquérito sorológico para a detecção de anticorpos contra o Vírus da Imunodeficiência Humana (VIH), em grupo não selecionado de crianças, internadas numa enfermaria geral de pediatria. Foram testados 441 pacientes pelo método ELISA, com uma positividade de 1,1 %, cujos resultados foram confirmados pelos testes de Western-Blot e/ou ImunoBlot. Nenhum dos cinco pacientes com teste positivo apresentou história de transfusão anterior, enquanto que 4,3% dos pacientes estudados apresentaram história transfusional. Todas as mães apresentaram também testes ELISA positivos. Em quatro casos, pelo menos um dos genitores referiu uso de drogas por via endovenosa. Em todas as crianças, o modo de transmissão foi vertical. A partir desses achados sugere-se a necessidade de a equipe de saúde tomar precauções quando da manipulação de sangue ou secreções. Recomenda-se a realização de inquéritos anônimos em enfermarias de hospitais gerais para auxiliar na determinação da real prevalência das infecções pelo VIH.The results of a serum inquiry for detection of antibodies against the Human Immunodeficiency Virus in a non selected group of children, patients of a general pediatric ward, are reported. Of the 441 cases, the ELISA test gave a positive result for 1.1% of them. This result was confirmed by the Western-Blot or ImmunoBlot test. None of the five children who tested positive had a previous history of blood transfusion. These children's mothers showed positive results to the ELISA test. Of four cases, at least one of the parents was IV drug addicted. In every case the transmission was vertical. On the basis of these findings, it is suggested that hospital staff should take the necessary precautions when manipulating blood and secretions and it is recommended that serum inquiries be made on the wards of general hospitals in the attempt to establish reliable data on the prevalence of HIV

The management of acute venous thromboembolism in clinical practice. Results from the European PREFER in VTE Registry

Venous thromboembolism (VTE) is a significant cause of morbidity and mortality in Europe. Data from real-world registries are necessary, as clinical trials do not represent the full spectrum of VTE patients seen in clinical practice. We aimed to document the epidemiology, management and outcomes of VTE using data from a large, observational database. PREFER in VTE was an international, non-interventional disease registry conducted between January 2013 and July 2015 in primary and secondary care across seven European countries. Consecutive patients with acute VTE were documented and followed up over 12 months. PREFER in VTE included 3,455 patients with a mean age of 60.8 ± 17.0 years. Overall, 53.0 % were male. The majority of patients were assessed in the hospital setting as inpatients or outpatients (78.5 %). The diagnosis was deep-vein thrombosis (DVT) in 59.5 % and pulmonary embolism (PE) in 40.5 %. The most common comorbidities were the various types of cardiovascular disease (excluding hypertension; 45.5 %), hypertension (42.3 %) and dyslipidaemia (21.1 %). Following the index VTE, a large proportion of patients received initial therapy with heparin (73.2 %), almost half received a vitamin K antagonist (48.7 %) and nearly a quarter received a DOAC (24.5 %). Almost a quarter of all presentations were for recurrent VTE, with >80 % of previous episodes having occurred more than 12 months prior to baseline. In conclusion, PREFER in VTE has provided contemporary insights into VTE patients and their real-world management, including their baseline characteristics, risk factors, disease history, symptoms and signs, initial therapy and outcomes

Anthocyanidins and anthocyanins: colored pigments as food, pharmaceutical ingredients, and the potential health benefits

Anthocyanins are colored water-soluble pigments belonging to the phenolic group. The pigments are in glycosylated forms. Anthocyanins responsible for the colors, red, purple, and blue, are in fruits and vegetables. Berries, currants, grapes, and some tropical fruits have high anthocyanins content. Red to purplish blue-colored leafy vegetables, grains, roots, and tubers are the edible vegetables that contain a high level of anthocyanins. Among the anthocyanin pigments, cyanidin-3-glucoside is the major anthocyanin found in most of the plants. The colored anthocyanin pigments have been traditionally used as a natural food colorant. The color and stability of these pigments are influenced by pH, light, temperature, and structure. In acidic condition, anthocyanins appear as red but turn blue when the pH increases. Chromatography has been largely applied in extraction, separation, and quantification of anthocyanins. Besides the use of anthocyanidins and anthocyanins as natural dyes, these colored pigments are potential pharmaceutical ingredients that give various beneficial health effects. Scientific studies, such as cell culture studies, animal models, and human clinical trials, show that anthocyanidins and anthocyanins possess antioxidative and antimicrobial activities, improve visual and neurological health, and protect against various non-communicable diseases. These studies confer the health effects of anthocyanidins and anthocyanins, which are due to their potent antioxidant properties. Different mechanisms and pathways are involved in the protective effects, including free-radical scavenging pathway, cyclooxygenase pathway, mitogen-activated protein kinase pathway, and inflammatory cytokines signaling. Therefore, this review focuses on the role of anthocyanidins and anthocyanins as natural food colorants and their nutraceutical properties for health. Abbreviations: CVD: Cardiovascular disease VEGF: Vascular endothelial growth factor

Extended Non-Vitamin K Antagonist Oral Anticoagulation Therapy for Prevention of Recurrent Venous Thromboembolism. a Review of Phase III and Phase IV Studies

Abstract Duration of anticoagulation can be categorised into initial treatment, lasting 3, 6 or 12 months, and long-term treatment beyond 12 months. There is a strong rationale for anticoagulation treatment beyond the acute phase in many patients with venous thromboembolism (VTE), being the risk of recurrent VTE after stopping anticoagulation high, particularly for unprovoked deep vein thrombosis (DVT). Several non-vitamin K antagonist oral anticoagulants (NOACs) have been approved in the acute setting; accumulating evidence suggests continuing treatment with these agents beyond 12 months offers additional benefits to patients with VTE. Apixaban, dabigatran and rivaroxaban have been studied in this setting in a series of phase III extension studies (AMPLIFY-EXT, RE-MEDY and RE-SONATE, and EINSTEIN EXT, respectively). AMPLIFY-EXT evaluated patients who had completed 6-12 months of anticoagulation treatment with apixaban. Patients received either a further 12 months of apixaban at a dose of 2.5 mg or 5 mg twice daily, or placebo. Recurrent VTE or mortality from any cause were 3.8%, 4.2% and 11.6%, respectively (relative risk [95% confidence interval (CI)] vs placebo: 0.33 [0.22-0.48] and 0.66 [0.25-0.53], respectively); for major bleeding, rates were 0.2%, 0.1% and 0.5%, respectively (relative risk [95% CI] vs placebo: 0.49 [0.09-2.64] and 0.25 [0.03-2.24], respectively). In RE-MEDY, patients received either dabigatran (150 mg twice daily) or warfarin for 6-36 months after at least 3 months of prior anticoagulation treatment. Recurrent or fatal VTE occurred in 1.8% of patients treated with dabigatran versus 1.3% of warfarin-treated patients (P=0.01 for non-inferiority); major bleeding rates were lower with dabigatran (0.9% vs 1.8%) but this difference was not statistically significant. In the RE-SONATE study, dabigatran (150 mg twice daily) or placebo was administered for up to 12 months. Recurrent or fatal VTE was significantly lower with dabigatran (0.4% vs 5.6%; P&lt;0.001). Rates of major bleeding were low in both groups (0.3% with dabigatran; no major bleeding episodes occurred in the placebo group); however, for the composite of major or non-major clinically relevant bleeding, the rate was significantly greater with dabigatran (5.3% vs 1.8%; P=0.001). In EINSTEIN EXT, patients who had completed 6-12 months of rivaroxaban or VKA anticoagulation treatment were randomised to receive either rivaroxaban or placebo for 6 or 12 months. Extended rivaroxaban treatment was associated with a significantly lower rate of recurrent VTE (1.3% vs 7.1%, respectively; P&lt;0.001), and there was a moderate, non-significant, increase in the rate of major bleeding complications (0.7% of patients in the rivaroxaban group vs none in the placebo group; P=0.11). The phase III extension studies demonstrate the benefits of extended NOAC use versus treatment cessation, with reduced recurrence rates versus placebo, although associated with a potential moderate increase in bleeding risk; in addition, based on outcomes in patients given placebo, it is clear that not prescribing anticoagulation treatment is not a viable approach. VTE is associated with substantial costs, and recurrent episodes increase costs further. The costs are attributable to hospitalisation, treatment facility and staff and outpatient management. The lack of routine coagulation monitoring needed with use of NOACs may simplify patient management, thereby further reducing the burden on healthcare providers and patients. US and European guidelines advise long-term therapy in certain instances. They support NOAC use where they have been selected as the initial therapy choice and therapy needs to be extended beyond 3 months. In addition to clinical trials of extended anticoagulation, assessment of this therapy in routine clinical practice is essential, in order to confirm whether the results of clinical trials apply to a broad range of patients beyond the highly controlled setting of a clinical study. Phase IV data are now emerging (Dresden Noacs Registry, Xalia Study, Einstein Choice Study, Start Register) and are supportive of the findings from phase III studies. Future studies involving all NOACs will be valuable in determining the safety and effectiveness of long-term NOAC use in a wider patient population. Disclosures Piovella: GlaxoSmithKline: Speakers Bureau; Portola: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; PFIZER/BMS: Speakers Bureau; Bayer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. </jats:sec

THE ROLE OF THE HYDRO-CLIMATIC CONDITIONS IN CAUSING HIGH FLOODS IN THE SUCEVIȚA RIVER CATCHMENT

Located in the north-eastern part of Romania, the Suceviţa catchment has been affected in the last decade, by the most serious known high floods in the modern period of hydrological observations. The significant amounts of rainfall (260 mm in five days in 2008 and 150 mm in four days in 2010) have led to the formation of high floods that have affected large areas of land near the river course. These torrential rainfall led to the recording of maximum flows showing an increased tendency from 214 m3/s in 2007 to 467 m3/s in 2010 (reconstituted value exceeding the probability of occurrence of 0.1%). Even if the afforestation degree, at the level of the catchment and its tributaries, in the mountainous area, is over 80%, the morphometric conditions given by the average high values of the slopes (37-55‰) and also by the circularity ratio (0,60 – 0,73) generate a fast drainage of the precipitation water to the riverbeds. At the same time, the human activity increases the impact of flooding because of the activities carried out near watercourses. Flooding associated with these high floods have highlighted the vulnerability of the communities manifested by weak capacity to absorb the effects of the phenomenon and to recover after such events. Therefore, the high floods of 2008 and 2010 have caused extensive damage to the localities situated in the Sucevița river catchment

THE USE OF HEC-RAS MODELLING IN FLOOD RISK ANALYSIS

The fact that, in the Ozana drainage basin, most of the people have built their homes in the river valley, determines that a study focused on identifying the areas exposed to hydrological risk is vital, mostly in the development decisions for villages and in the creation of management plans for emergency situations. This study analyses the mapping methodology of the flood prone areas in the middle and lower sector of the Pluton river, which is a tributary of Ozana river, in its upper sector. In order to correctly draw the flood risk maps, the HEC-RAS method has been used, together with the HEC-GeoRAS extension, in ArcGIS. The results that have been obtained, correlate with the field situation in a very high proportion: for a 1% occurance flood, almost 123 households have been damaged, and according to the simulation, a number of 147 buildings have been damaged, therefore other probabilities (that overcome the 1% situation) can be used for similar simulations

An Hfq-dependent post-transcriptional mechanism fine tunes RecB expression in Escherichia coli

All living organisms have developed strategies to respond to chromosomal damage and preserve genome integrity. One such response is the repair of DNA double-strand breaks (DSBs), one of the most toxic forms of DNA lesions. In Escherichia coli, DSBs are repaired via RecBCD-dependent homologous recombination. RecBCD is essential for accurate chromosome maintenance, but its over-expression can lead to reduced DNA repair ability. This apparent paradox suggests that RecBCD copy numbers may need to be tightly controlled within an optimal range. Using single-molecule fluorescence mi-croscopy, we have established that RecB is present in very low abundance at mRNA and protein levels. RecB transcription shows high fluctuations, yet cell-to-cell protein variability remains remarkably low. Here, we show that the post-transcriptional regulator Hfq binds to recB mRNA and down-regulates RecB protein translation in vivo. Furthermore, specific disruption of the Hfq-binding site leads to more efficient translation of recB mRNAs. In addition, we observe a less effective reduction of RecB protein fluctuations in the absence of Hfq. This fine-tuning Hfq-mediated mechanism might have the underlying physiological function of maintaining RecB protein levels within an optimal range.Competing Interest StatementThe authors have declared no competing interest