Body weight, body image and primary postpartum haemorrhage: a review of the literature.

The prevalence of obesity during pregnancy is rising. Elevated BMI is a significant risk factor for adverse maternal and fetal outcomes, including primary postpartum haemorrhage (PPH). Addressing the issues surrounding obesity in pregnancy presents many biological, social and psychological challenges. BMI is an easily measured and modifiable anthropometrical risk factor and should be recorded in all pregnancies. BMI should be proactively managed prior to and during pregnancy. All women should be educated as to the risks of an elevated BMI during pregnancy and those at risk should have access to specialist medical and surgical support if required. Our aim was to investigate the associations between elevated BMI and adverse maternal and fetal outcomes including PPH, and to explore the psychological challenges of having an elevated BMI during pregnancy.

National audit of the use of fibrinogen concentrate to correct hypofibrinogenaemia.

BACKGROUND: Massive haemorrhage occurs in a variety of clinical settings resulting in consumptive and dilutional coagulopathies leading to hypofibrinogenaemia. METHODS/MATERIALS: A prospective observational national cohort study was performed between November 2008 and June 2010 to collect safety data on the off-label use of a fibrinogen concentrate to treat acquired hypofibrinogenaemia. RESULTS: A prospective cohort of 63 patients with varying causes of hypofibrinogenaemia resulted from this data collection. A single infusion of fibrinogen concentrate was given in 49 (77%) of patients studied and 12 received more than one infusion. The median inter-quartile range (IQR) dose of fibrinogen infused was 49 (26-61) mg kg(-1). The median (IQR) fibrinogen level before and after infusion was 0.9 (0.6-1.3) and 1.8 (1.4-4.3) g L(-1), respectively (P < 0.001). In 31 patients (67%), bleeding stopped within 4 h and fibrinogen was reported to have contributed to this outcome by the treating clinicians. In 84% of cases the treating clinician reported that the use of fibrinogen concentrate reduced the rate of bleeding. Fibrinogen was associated with a statistically significant reduction in red blood cell transfusion (median 4 units before and 0 units after, P < 0.001) and fresh frozen plasma infusion (median 4 units before and 0 units after, P < 0.001). Three venous and one arterial non-fatal thrombotic events were recorded in the patients treated with fibrinogen. CONCLUSION: Fibrinogen concentrate can be used to correct hypofibrinogenaemia and may reduce blood product usage.

Antibacterial properties of whole body extracts and haemolymph of Lucilia sericata maggots.

OBJECTIVE: To partially characterise maggot-secreted antibacterial substances and determine their range of activity against different bacteria. METHOD: Sterile and non-sterile maggots maintained in the laboratory and taken from chronic wounds of treated patients were used. Whole body extracts and haemolymph were fractionated and their range of activity against bacteria was tested using the zone of inhibition assay. The mode of action of bacterial destruction was examined by viable counts, influx of K+ and changes in the membrane potential by scanning electron microscope (SEM). RESULTS: Extracts of sterile and non-sterile maggots showed an activity of 200 arbitrary units (AU)/ml and 400AU/ml respectively. Maggots removed from chronic wounds had an activity of 1200AU/ml. Injuring sterile maggots with a sterile needle doubled the antibacterial activity within 24 hours, while the antibacterial activity of haemolymph increased fourfold after injury with a sterile needle and sixteenfold with an infected needle. The fractions with a molecular weight of < 1kDa and 3-10kDa showed antibacterial activity against Gram-positive and Gram-negative bacteria including Pseudomonas aeruginosa, Klebsiella pneumoniae and methicillin-resistant Staphylococcus aureus (MRSA) isolated from wounds. The fraction with a molecular weight of < 1kDa lysed over 90% of the bacteria within 15 minutes by causing an influx of K+ and changing the membrane potential of bacteria. CONCLUSION: The nature of the antibacterial materials extracted from maggots not only indicates their ability to ingest the necrotic tissue on the wound, but also their potential significance in wound healing,

Impact of cardiovascular risk factors and disease on length of stay and mortality in patients with acute coronary syndromes.

BACKGROUND: Traditional risk factors for cardiovascular disease (CVD) have been thoroughly investigated. We aimed to investigate the impact of comorbid cardiovascular risk factors and diseases on length of stay (LOS) and mortality in patients presenting with acute coronary syndromes (ACS). METHODS: We examined prevalence of CVD, LOS and mortality from 25,287 consecutive admissions for ACS from seven hospitals across North West England between 2000 and 2013 using the ACALM (Algorithm for Comorbidities, Associations, Length of stay and Mortality) protocol using ICD-10 and OPCS-4 coding systems. RESULTS: Mean LOS was 7.0days and there were 9653 (38.2%) deaths in the ACS cohort over the 13-year period. Hypertension and hyperlipidaemia were associated with decreased LOS (6.95 and 4.8days respectively, P<0.001) and mortality (36.8% and 19.4% respectively, P<0.001), as was angina pectoris (5.4days and 33.5%, P<0.001). Type 2 diabetes was associated with increased LOS and mortality (7.8days, P<0.05; 44.4%, P<0.001), whereas type 1 diabetes was associated with increased mortality only (7.0days, P=0.42; 41.3%, P<0.001). Other concomitant CVD was associated with an increased LOS and mortality: peripheral vascular disease (8.6days, P<0.05; 53%, P<0.001), atrial fibrillation (10.9days, P<0.001; 63.5%, P<0.001), cerebrovascular disease (15.9days, P<0.001; 76%, P<0.001), heart failure (11days, P<0.001; 69.9%, P<0.001), and ischaemic heart disease (6.7days, P<0.001; 38.7%, P<0.05). CONCLUSION: CVD risk factors have a significant and varied impact on LOS and mortality in patients with ACS and it may be inappropriate to group them when assessing in-hospital risk. These factors should be used to identify patients at an increased risk of prolonged admissions and death post-ACS, and services should be directed accordingly.

Inhibition of acetohydroxy acid synthase by leucine.

The enzymatic reaction of acetohydroxy acid synthase in crude extracts of Escherichia coli K-12 is inhibited by leucine. Inhibition is most pronounced at low pH values and is low at pH values higher than 8.0. Both isoenzymes of acetohydroxy acid synthase present in E. coli K-12 (isoenzyme I and isoenzyme III) are inhibited by leucine. Isoenzyme I, which is responsible for the majority of acetohydroxy acid synthase activity in E. coli K-12 at physiological pH, is inhibited almost completely by 30 mM leucine at pH 6.25-7.0 and is not affected at all at pH values higher than 8.4. Inhibition of isoenzyme I by leucine is a mixed noncompetitive process. Leucine inhibition of isoenzyme III is pH-independent and reaches only 40% at 30 mM leucine. The inhibition of acetohydroxy acid synthase by leucine at physiological pH, observed in vitro in this study, correlates with the idea that acetohydroxy acid synthase is a target for the toxicity of the abnormally high concentrations of leucine in E. coli K-12.

Metabolism of the Flavonoid Epicatechin by Laccase of Colletotrichum gloeosporioides and Its Effect on Pathogenicity on Avocado Fruits.

ABSTRACT During avocado fruit ripening, decreasing levels of the flavonoid epicatechin have been reported to modulate the metabolism of preformed antifungal compounds and the activation of quiescent Colletotrichum gloeosporioides infections. Epicatechin levels decreased as well when C. gloeosporioides was grown in the presence of epicatechin in culture. Extracts of laccase enzyme obtained from decayed tissue and culture media fully metabolized the epicatechin substrate within 4 and 20 h, respectively. Purified laccase protein from C. gloeosporioides showed an apparent MW of 60,000, an isoelectric point at pH 3.9, and maximal epicatechin degradation at pH 5.6. Inhibitors of fungal laccase such as EDTA and thioglycolic acid reduced C. gloeosporioides symptom development when applied to ripening susceptible fruits. Isolates of C. gloeosporioides with reduced laccase activity and no capability to metabolize epicatechin showed reduced pathogenicity on ripening fruits. On the contrary, Mexican isolates with increasing capabilities to metabolize epicatechin showed early symptoms of disease in unripe fruits. Transcript levels of cglac1, encoding C. gloeosporioides laccase, were enhanced during fungal development in the presence of epicatechin at pH 6.0, where avocado fruits are susceptible to fungal attack. But transcript increase was not detected at pH 5.0, where the fruit is resistant to fungal attack. The present results suggest that biotransformation of epicatechin by C. gloeosporioides in ripening fruits is followed by the decline of the preformed antifungal diene compound, resulting in the activation of quiescent infections.

The Escherichia coli adenylyl cyclase complex: stimulation by GTP and other nucleotides.

Escherichia coli cells permeabilized by treatment with low concentrations of toluene contain an adenylyl cyclase activity that can be stimulated 3.6-7.6-fold by GTP. The stimulatory effect of GTP is maximal at concentrations of the nucleotide in the physiological range (above 0.7 mM). Studies of the dependence of velocity on substrate (ATP) concentration indicate that the velocity vs. substrate plots are sigmoid in the absence of GTP but hyperbolic in the presence of GTP, suggesting an allosteric regulatory site that can be occupied by either ATP or GTP. Replacement of ATP by AMPPNP as substrate results in velocity vs. substrate plots that are hyperbolic in the absence or presence of GTP, although GTP increases the Vmax by a factor of 2.2; these findings indicate that AMPPNP specifically occupies the substrate site and GTP exclusively occupies the regulatory site. A test of the capacity of other guanine nucleotides to stimulate adenylyl cyclase activity showed that 2'-deoxy-GTP was almost as effective as GTP, but that GDP, GMP, ppGpp, and 3',5'-cGMP were not stimulatory effectors; GTP-gamma-S and GMPPNP stimulated adenylyl cyclase activity but to a lesser degree than did GTP. In addition to the previous indication that ATP can occupy the regulatory site on adenylyl cyclase, it was found that CTP and UTP were potent stimulators. Thus, all the naturally occurring RNA precursor nucleoside triphosphates are capable of stimulating adenylyl cyclase activity. In contrast, PPPi inhibits adenylyl cyclase activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Localization of the membrane binding sites of Era in Escherichia coli.

Era is a GTP-binding protein that is essential for normal cell growth and division in Escherichia coli. In view of the fact that eukaryotic proteins similar to Era are membrane-associated and important in membrane signalling pathways, experiments were carried out to establish the intracellular location of Era. Immunoelectron microscopy was employed to demonstrate that Era resides at or very near the internal surface of the cytoplasmic membrane, which is a location expected for a membrane signalling protein. In addition, Era occurs in patches that may correspond to areas that are potential sites of septation.

How does subintimal angioplasty compare to transluminal angioplasty for the treatment of femoral occlusive disease?

A best evidence topic in surgery was written according to a structured protocol. The question addressed how subintimal angioplasty (SIA) compares to transluminal angioplasty (TA) for the treatment of femoral occlusive disease. One hundred and thirty two papers were found using the reported search; the 5 which represented the best evidence to answer the question are discussed. The evidence on this subject is limited; there are no randomised controlled trials (RCTs) comparing SIA to TA for pathologically equivalent lesions. However SIA remains a safe and effective alternative to surgical bypass grafting when TA cannot be performed.

Should infected laparotomy wounds be treated with negative pressure wound therapy?

A best evidence topic in surgery was written according to a structured protocol. The question addressed whether there is any benefit in treating infected laparotomy wounds with negative pressure wound therapy (NPWT). Forty-five papers were found using the reported search; of which 4 represented the best evidence to answer the question. The evidence on this subject is limited; there is a single non-randomised controlled trial, 2 prospective cohort studies, and 1 retrospective cohort study discussed in this paper. From the available literature, the use of NPWT in infected laparotomy wounds does reduce the length of hospital stay, the number of dressing changes required and promote faster wound healing.

Is open surgery or endovascular therapy best to treat acute mesenteric occlusive disease?

A best evidence topic in vascular surgery was written according to a structured protocol. The question addressed whether endovascular treatment improved peri-operative outcomes when compared to an open approach to restore arterial perfusion in acute mesenteric occlusive disease. Four hundred and ninety seven papers were identified using the reported search; of which 4 represented the best evidence to answer the question and are discussed. The evidence on this subject is limited, comprising largely of non-randomised retrospective cohort studies. The evidence suggests that endovascular treatment is associated with reduced mortality and has better short-term peri-operative outcomes, as well as longer-term survival - however many endovascular cases require subsequent open surgery. There is also conflicting evidence to suggest endovascular therapy is associated with longer ICU stays. Aside from procedural complications, factors such as patient status, time delay to diagnosis and treatment may play a greater role in determining mortality rates. In summary, endovascular therapy appears to be a feasible treatment option with post-operative complications and inpatient mortality rates lower than those seen in open surgery.

Antibacterial substances of low molecular weight isolated from the blowfly, Lucilia sericata.

Low molecular weight compounds were isolated by high-performance liquid chromatography from the maggot or haemolymph extracts of Lucilia sericata (Meigen) (Diptera: Calliphoridae). Using gas chromatography-mass spectrometry analysis, three compounds were obtained: p-hydroxybenzoic acid (molecular weight 138 Da), p-hydroxyphenylacetic acid (molecular weight 152 Da) and octahydro-dipyrrolo[1,2-a;1',2'-d] pyrazine-5,10-dione (molecular weight 194 Da), also known as the cyclic dimer of proline (or proline diketopiperazine or cyclo[Pro,Pro]). All three molecules revealed antibacterial activity when tested against Micrococcus luteus and/or Pseudomonas aeruginosa, and the effect was even more pronounced when these molecules were tested in combination and caused lysis of these bacteria.

Cross-stress tolerance and expression of stress-related proteins in osmotically desiccated entomopathogenic Steinernema feltiae IS-6.

Infective juveniles (IJs) of the entomopathogenic nematode (EPN) Steinernema feltiae IS-6 can survive exposure to 24% glycerol solution by entering an osmotically desiccated state. Exposure of osmotically desiccated nematodes to extreme temperature assays (40 degrees C for 10 h and -20 degrees C for 360 h) resulted in gradual reduction in survival, whereas non-desiccated IJs died within a short exposure to the assay conditions. Through SDS-PAGE, a stress-related protein UNC-87 was found in osmotically desiccated IJs exposed to 40 degrees C for 3, 6, and 8 h, whose survival rates were 98.9+/-1.43, 78.5+/-5.87 and 20.9+/-4.93%, respectively. The protein was not found in IJs following exposure of osmotically desiccated individuals to 40 degrees C for 10 h, in which none of the IJs survived. After exposure to -20 degrees C for 360 h, the survival of osmotically desiccated EPNs with a weak band of UNC-87 was 13.0+/-3.32%. To identify other responsive proteins that are required for osmotic stress, we used 2-dimensional electrophoresis to analyse the proteins in osmotically desiccated EPNs. The results revealed that 10 novel protein spots and 10 up-regulated protein spots in osmotically desiccated IJs were detected by digital image analysis. Mass spectrometry analysis of 7 significant spots indicated that osmotic stress in desiccated IJs was associated with the induction of actin, Proteasome regulatory particle (ATPase-like), GroEL chaperonin, GroES co-chaperonin and transposase family member. It seems to show actin, UNC-87 and Proteasome regulatory particle may play distinct roles in specific aspects of organization of macromolecular structures under desiccation stress. GroEL and GroES are members of the Hsp60 family of chaperons.

Antibacterial activity of lactic acid bacteria included in inoculants for silage and in silages treated with these inoculants.

AIMS: To determine antibacterial activity in lactic acid bacteria (LAB) silage inoculants and in wheat and corn silages which were treated with these inoculants. METHODS AND RESULTS: Wheat and two corn silages were prepared in 0.25 l sealed glass jars. Inoculant treatments were prepared for each type of silage with each of 10 LAB silage inoculants at inoculation rate of 10(6) CFU g(-1). Untreated silages served as controls. Antibacterial activity was determined in the inoculants and in their respective silages with Micrococcus luteus and Pseudomonas aeruginosa. Antibacterial activity was detected in nine of the 10 inoculants whereas such activity in the silages varied. Control silages did not have antibacterial activity. CONCLUSIONS: Many LAB silage inoculants have antibacterial activity and in some cases this activity is imparted on inoculated silages. SIGNIFICANCE AND IMPACT OF THE STUDY: This study was conducted as part of a broader research objective, which is to find out how LAB silage inoculants enhance ruminant performance. The results of this study indicate that LAB silage inoculants produce antibacterial activity, and therefore, have a potential to inhibit detrimental micro-organisms in the silage or in the rumen.

Identification of a major autophosphorylation site on postsynaptic density-associated Ca2+/calmodulin-dependent protein kinase.

One of the most abundant proteins in postsynaptic densities is identical or very similar to the alpha-subunit of the Ca2+/calmodulin-dependent protein kinase II. Autophosphorylation of this protein in isolated postsynaptic densities was studied under various conditions, following inhibition of endogenous phosphatase activity with microcystin-LR. Phosphorylation accompanied by a shift in the enzyme's electrophoretic mobility was observed upon incubation with Ca2+ and calmodulin at 37 degrees C. Brief incubation with Ca2+ and calmodulin at 0 degrees C resulted in a low level of phosphorylation and no change in mobility. Following this limited Ca(2+)-dependent phosphorylation, however, a high level of phosphorylation could be achieved in the absence of Ca2+, upon incubation at 37 degrees C. Comparison of reverse-phase HPLC phosphopeptide elution profiles obtained following phosphorylation at 37 degrees C, in the presence and absence of Ca2+, as described above, showed differences, suggesting that certain distinct sites may be phosphorylated under each condition. A major phosphopeptide peak, however, with the amino acid sequence Met-Leu-Thr(P)-Ile-Asn-Pro-Ser-Lys was identified under both conditions. This sequence is identical to the predicted sequence containing Thr-253 of the Ca2+/calmodulin-dependent protein kinase II. The results suggest that phosphorylation at Thr-253 requires an initial Ca(2+)-dependent phosphorylation, which may be at a different site, but does not depend on the continued presence of Ca2+ to proceed. The observed mode of regulation of autophosphorylation at Thr-253 appears to be unique to the postsynaptic density-associated enzyme.

A GTP-binding protein (Era) has an essential role in growth rate and cell cycle control in Escherichia coli.

Era is a membrane-associated GTP-binding protein which is essential for cell growth in Escherichia coli. In order to examine the physiological role of Era, strains in which Era was expressed at 40 degrees C but completely repressed at 27 degrees C were constructed. The growth of these strains was inhibited at the nonpermissive temperature, and cells became elongated. Under such conditions, no constrictions or septum formation could be detected by phase-contrast microscopy, and DNA segregation was apparently normal as revealed by fluorescence staining. These data demonstrate that Era has an essential function in cell growth rate control in liquid media and that depletion of Era blocks cell division either directly or indirectly. Thus, the role of GTP-binding proteins as important regulators of cell growth and division may be ubiquitous in nature.

Acetohydroxy acid synthase is a target for leucine containing peptide toxicity in Escherichia coli.

Acetohydroxy acid synthase from a mutant resistant to leucine-containing peptides was insensitive to leucine inhibition. It is concluded that acetohydroxy acid synthase is a target for the toxicity of the high concentrations of leucine brought into Escherichia coli K-12 by leucine-containing peptides.

A method for simultaneous determination of the two possible products of acetohydroxy acid synthase.

A method for the simultaneous assay of 2-acetolactate and 2-aceto-2-hydroxybutyrate formation catalyzed by acetohydroxy acid synthase in the presence of its substrates pyruvate and 2-ketobutyrate is described. The method, appropriate for the study of the physiologically and mechanistically significant competition between the two reactions, involves oxidative decarboxylation of the acetohydroxy acids to the corresponding 2,3-diketones, transfer of the volatile diketones to methanol, and gas chromatographic analysis with electron-capture detection. Oxidative decarboxylation by air requires catalytic activation, and addition of iron salts is crucial to the success of the method with purified enzymes.