During cultivation under storage conditions with BG11 medium containing acetate as a carbon source, Synechocystis sp. PCC6803 accumulated poly(3-hydroxybutyrate) up to 10% (w/w) of the cell dry weight. Our analysis of the complete Synechocystis sp. PCC6803 genome sequence, which had recently become available, revealed that not only the open reading frame slr1830 (which was designated as phaC) but also the open reading frame slr1829, which is located colinear and upstream of phaC, most probably represent a polyhydroxyalkanoic acid (PHA) synthase gene. The open reading frame slr1829 was therefore designated as phaE. The phaE and phaC gene products exhibited striking sequence similarities to the corresponding PHA synthase subunits PhaE and PhaC of Thiocystis violacea, Chromatium vinosum, and Thiocapsa pfennigii. The Synechocystis sp. PCC6803 genes were cloned using PCR and were heterologously expressed in Escherichia coli and in Alcaligenes eutrophus. Only coexpression of phaE and phaC partially restored the ability to accumulate poly(3-hydroxybutyrate) in the PHA-negative mutant A. eutrophus PHB-4. These results confirmed our hypothesis that coexpression of the two genes is necessary for the synthesis of a functionally active Synechocystis sp. PCC6803 PHA synthase. PHA granules were detected by electron microscopy in these cells, and the PHA-granule-associated proteins were studied. Western blot analysis of Synechocystis sp. PCC6803 crude cellular extracts and of granule-associated proteins employing antibodies raised against the PHA synthases of A. eutrophus (PhaC) and of C. vinosum (PhaE and PhaC) revealed no immunoreaction.

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BackgroundPatients who develop herpes zoster or herpes zoster ophthalmicus may be at risk for cerebrovascular and cardiac complications. We systematically reviewed the published literature to determine the association between herpes zoster and its subtypes with the occurrence of cerebrovascular and cardiac events.Methods/ResultsSystematic searches of PubMed (MEDLINE), SCOPUS (Embase) and Google Scholar were performed in December 2016. Eligible studies were cohort, case-control, and self-controlled case-series examining the association between herpes zoster or subtypes of herpes zoster with the occurrence of cerebrovascular and cardiac events including stroke, transient ischemic attack, coronary heart disease, and myocardial infarction. Data on the occurrence of the examined events were abstracted. Odds ratios and their accompanying confidence intervals were estimated using random and fixed effects models with statistical heterogeneity estimated with the I2 statistic. Twelve studies examining 7.9 million patients up to 28 years after the onset of herpes zoster met our pre-defined eligibility criteria. Random and fixed effects meta-analyses showed that herpes zoster, type unspecified, and herpes zoster ophthalmicus were associated with a significantly increased risk of cerebrovascular events, without any evidence of statistical heterogeneity. Our meta-analysis also found a significantly increased risk of cardiac events associated with herpes zoster, type unspecified.ConclusionsOur results are consistent with the accumulating body of evidence that herpes zoster and herpes zoster ophthalmicus are significantly associated with cerebrovascular and cardiovascular events.

BackgroundDirect oral anticoagulants (DOACs) have emerged as promising alternatives to vitamin K antagonists (VKAs) for patients with non-valvular atrial fibrillation (NVAF) or venous thromboembolism (VTE). Few meta-analyses have included all DOACs that have received FDA approval for these cardiovascular indications, and their overall comparisons against VKAs have shortcomings in data and methods. We provide an updated overall assessment of the efficacy and safety of those DOACs at dosages currently approved for NVAF or VTE, in comparison with VKAs.MethodsWe used data from Phase 3 randomized trials that compared an FDA-approved DOAC with VKA for primary prevention of stroke in patients with NVAF or for treatment of acute VTE.ResultsAmong trial participants with NVAF, DOAC recipients had a lower risk of stroke or systemic embolism [Pooled Odds Ratio (OR) 0.76, 95% Confidence Interval (CI) (0.68–0.84)], any stroke (0.80, 0.73–0.88), systemic embolism (0.56, 0.34–0.93), and total mortality (0.89, 0.84–0.95). Safety outcomes also showed a lower risk of fatal, major, and intracranial bleeding but higher risk for gastrointestinal bleeding (GIB). Patients with acute VTE randomized to DOACs had comparable risk of recurrent VTE and death (OR 0.88, 95% CI 0.75–1.03), recurrent DVT (0.83, 0.66–1.05), recurrent non-fatal PE (0.97, 0.75–1.25), and total mortality (0.94, 0.79–1.12). Safety outcomes for DOACs showed a lower risk of major, fatal, and intracranial bleeding, but similar risk of GIB.ConclusionsPatients receiving DOACs for NVAF had predominantly superior efficacy and safety. Patients who were treated with DOACs for acute VTE had non-inferior efficacy, but an overall superior safety profile.

In this work we have demonstrated a powerful disinfectant ability of colloidal silver nanoparticles (NPs) for the prevention of gastrointestinal bacterial infections. The silver NPs colloid was synthesized by a UV-enhanced chemical precipitation. Two gastrointestinal bacterial strains of Escherichia coli (ATCC 43888-O157:k-:H7) and Vibrio cholerae (O1) were used to verify the antibacterial activity of the as-prepared silver NPs colloid by means of surface disinfection assay in agar plates and turbidity assay in liquid media. Transmission electron microscopy was also employed to analyze the ultrastructural changes of bacterial cells caused by silver NPs. Noticeably, our silver NPs colloid displayed a highly effective bactericidal effect against two tested gastrointestinal bacterial strains at a silver concentration as low as ∼3 mg l −1. More importantly, the silver NPs colloid showed an enhancement of antibacterial activity and long-lasting disinfectant effect as compared to conventional chloramin B (5%) disinfection agent. These advantages of the as-prepared colloidal silver NPs make them very promising for environmental treatments contaminated with gastrointestinal bacteria and other infectious pathogens. Moreover, the powerful disinfectant activity of silver-containing materials can also help in controlling and preventing further outbreak of diseases.

BackgroundLittle is known about the association of hyperglycemia with the development of ventricular tachycardia (VT) in patients hospitalized with acute myocardial infarction (AMI) which we examined in the present study. The objectives of this community-wide observational study were to examine the relation between elevated serum glucose levels at the time of hospital admission for AMI and occurrence of VT, and time of occurrence of VT, during the patient’s acute hospitalization.MethodsWe used data from a population-based study of patients hospitalized with AMI at all central Massachusetts medical centers between 2001 and 2011. Hyperglycemia was defined as a serum glucose level ≥ 140 mg/dl at the time of hospital admission. The development of VT was identified from physicians notes and electrocardiographic findings by our trained team of data abstractors.ResultsThe average age of the study population was 70 years, 58.0% were men, and 92.7% were non-Hispanic whites. The mean and median serum glucose levels at the time of hospital admission were 171.4 mg/dl and 143.0, respectively. Hyperglycemia was present in 51.9% of patients at the time of hospital admission; VT occurred in 652 patients (15.8%), and two-thirds of these episodes occurred during the first 48 h after hospital admission (early VT). After multivariable adjustment, patients with hyperglycemia were at increased risk for developing VT (adjusted OR = 1.48, 95% CI = 1.23–1.78). The presence of hyperglycemia was significantly associated with early (multivariable adjusted OR = 1.39, 95% CI = 1.11–1.73) but not with late VT. Similar associations were observed in patients with and without diabetes and in patients with and without ST-segment elevation AMI.ConclusionsEfforts should be made to closely monitor and treat patients who develop hyperglycemia, especially early after hospital admission, to reduce their risk of VT.

It has been previously reported that a neutral DNA equilibrium binding agent based on an N-methylpyrrolecarboxamide dipeptide (lex) and modified with an O-methyl sulfonate ester functionality (MeOSO(2)-lex) selectively affords N3-methyladenine lesions. To study the interaction of the neutral lex dipeptide with calf thymus DNA, we have prepared stable, nonmethylating sulfone analogues of MeOSO(2)-lex that are neutral and cationic. Thermodynamic studies show that both the neutral and monocationic sulfone compounds bind to DNA with K(b)'s of 10(5) in primarily entropy-driven reactions. To determine how the cytotoxic N3-methyladenine adduct generated from MeOSO(2)-lex is repaired in E. coli, MeOSO(2)-lex was tested for toxicity in wild-type E. coli and in mutant strains defective in base excision repair (tag and/or alkA glycosylases or apn endonuclease), nucleotide excision repair (uvrA), and both base and nucleotide excision repair (tag/alkA/uvrA). The results clearly demonstrate the cellular toxicity of the N3-methyladenine lesion, and the protective role of base excision glycosylase proteins. A novel finding is that in the absence of functional base excision glycosylases, nucleotide excision repair can also protect cells from this cytotoxic minor groove lesion. Interaction between base and nucleotide excision repair systems is also seen in the protection of cells treated with cis-diamminedichloroplatinum(II) but not with anti-(+/-)-r-7,t-8-dihydroxy-t-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene.

Non-adherence to self-management guidelines accounted for 50% of hospital readmissions in heart failure patients. Evidence showed that patient activation affects self-management behaviors in populations living with chronic conditions. The purpose of this study was to describe patient activation level and its relationship with knowledge, self-efficacy and self-management behaviors in heart failure patients discharged from rural hospitals. Our study populations were recruited from two hospitals in rural areas of Nebraska. We found that two-thirds of the participants reported low activation levels (e.g., taking no action to manage their heart failure condition). In addition, low patient activation levels were associated with inadequate heart failure knowledge (p=.005), low self-efficacy (p<.001) and low engagement in heart failure self-management behaviors (p<.001) after discharge from hospital.