Oxidative cyclization of prodigiosin by an alkylglycerol monooxygenase-like enzyme

Prodiginines, which are tripyrrole alkaloids displaying a wide array of bioactivities, occur as linear and cyclic congeners. Identification of an unclustered biosynthetic gene led to the discovery of the enzyme responsible for catalyzing the regiospecific C-H activation and cyclization of prodigiosin to cycloprodigiosin in Pseudoalteromonas rubra. This enzyme is related to alkylglycerol monooxygenase and unrelated to RedG, the Rieske oxygenase that produces cyclized prodiginines in Streptomyces, implying convergent evolution

New algorithm for the prediction of cardiovascular risk in symptomatic adults with stable chest pain

To review the landmark studies in predicting obstructive coronary artery disease (CAD) in symptomatic patients with stable chest pain and identify better prediction tools and propose a simplified algorithm to guide the health care providers in identifying low risk patients to defer further testing.There are a few risk prediction models described for stable chest pain patients including Diamond-Forrester (DF), Duke Clinical Score (DCS), CAD Consortium Basic, Clinical, and Extended models. The CAD Consortium models demonstrated that DF and DCS models overestimate the probability of CAD. All CAD Consortium models performed well in the contemporary population. PROMISE trial secondary data results showed that a clinical tool using readily available ten very low-risk pre-test variables could discriminate low-risk patients to defer further testing safely. In the contemporary population, CAD Consortium Basic or Clinical model could be used with more confidence. Our proposed simple algorithm would guide the physicians in selecting low risk patients who can be managed conservatively with deferred testing strategy. Future research is needed to validate our proposed algorithm to identify the low-risk patients with stable chest pain for whom further testing may not be warranted

Seven-membered ring azasugars as glycosidase inhibitors and anticancer agents

1311-1321<span style="font-size:14.5pt;mso-bidi-font-size:6.5pt;font-family:Fd5747-Identity-H; mso-bidi-font-family:Fd5747-Identity-H;color:#101010">Synthesis of various C2 symmetrical tetrahydroxyazepanes has been reported by the reaction of bisepoxides with various primary amines. The tetrahydroxyazepanes inhibit β-glucosidases in micromolar range and also exhibit anticancer activity in various cancer cell lines with GI50 values in the range of 2 to 9×10-5 <span style="font-size:15.0pt;mso-bidi-font-size: 7.0pt;font-family:Fd5776-Identity-H;mso-bidi-font-family:Fd5776-Identity-H; color:#101010">M<span style="font-size:15.0pt;mso-bidi-font-size: 7.0pt;font-family:Fd5776-Identity-H;mso-bidi-font-family:Fd5776-Identity-H; color:#101010">. <span style="font-size:14.5pt;mso-bidi-font-size:6.5pt;font-family:Fd5747-Identity-H; mso-fareast-font-family:" times="" new="" roman";mso-bidi-font-family:fd5747-identity-h;="" color:#101010;mso-ansi-language:en-us;mso-fareast-language:en-us;mso-bidi-language:="" ar-sa"="">The azepanes are poor inhibitors of HIV protease and their IC50 values are in the range 2×10-4 <i style="mso-bidi-font-style: normal"><span style="font-size:15.0pt;mso-bidi-font-size:7.0pt;font-family: Fd5776-Identity-H;mso-fareast-font-family:" times="" new="" roman";mso-bidi-font-family:="" fd5776-identity-h;color:#101010;mso-ansi-language:en-us;mso-fareast-language:="" en-us;mso-bidi-language:ar-sa"="">M<span style="font-size:15.0pt; mso-bidi-font-size:7.0pt;font-family:Fd5776-Identity-H;mso-fareast-font-family: " times="" new="" roman";mso-bidi-font-family:fd5776-identity-h;color:#101010;="" mso-ansi-language:en-us;mso-fareast-language:en-us;mso-bidi-language:ar-sa"="">.</span

Safety and Efficacy of Radial Versus Femoral Access for Rotational Atherectomy: A Systematic Review and Meta-Analysis

Introduction: Over the recent years, there has been increased interest in the use of transradial (TR) access for percutaneous coronary intervention (PCI), including rotational atherectomy (RA). However, a large proportion of operators seem to be reluctant to use TR access for complex PCI including rotational atherectomy for heavily calcified coronary lesions. Methods: We searched MEDLINE, ClinicalTrials.gov and the Cochrane Library for studies comparing radial versus femoral access in patients undergoing RA. Studies were included if they reported at least one of the following outcomes in each group separately: major adverse cardiac events (MACE), major bleeding, stent thrombosis, myocardial infarction (MI), hospital length of stay, radiation exposure, procedure time, procedure success and all-cause mortality. Odds ratio (OR) or mean difference (MD) with 95% confidence interval (CI) were calculated and a p-value of \u3c0.05 was considered as a level of significance. Results: This meta-analysis included 5 retrospective studies with 3315 patients undergoing RA via radial access and 5838 patients via femoral access. Radial access was associated with lower major access site bleeding (OR: 0.45, 95% CI: 0.31–0.67, p \u3c 0.001), and radiation exposure (MD: −16.1, 95%CI: −25.4–−6.7 Gy cm 2 , p = 0.0007). There were no significant differences observed in all-cause in-hospital mortality (OR: 0.92, 95% CI: 0.69–1.23, p = 0.58); MACE (OR: 0.80, CI: 0.63, 1.02, p = 0.08), stent thrombosis (OR: 0.28, 95%CI: 0.06–1.33 p = 0.11); and MI (OR: 0.43, 95%CI: 0.15–1.24, p = 0.12). There were no significant differences in hospital stay, procedure time or procedure success between the two groups (p \u3e 0.05). Conclusion: This meta-analysis of 9153 patients from observational studies demonstrates similar all-cause mortality, MACE, procedural success and procedural time during RA performed using TR access and TF access. However, TR access was associated with decreased access site bleeding and radiation exposure. Given the observational nature of these findings, a randomized controlled trial is warranted for further evidence

Safety and efficacy of radial versus femoral access for rotational Atherectomy: A systematic review and meta-analysis

Over the recent years, there has been increased interest in the use of transradial (TR) access for percutaneous coronary intervention (PCI), including rotational atherectomy (RA). However, a large proportion of operators seem to be reluctant to use TR access for complex PCI including rotational atherectomy for heavily calcified coronary lesions. We searched MEDLINE, ClinicalTrials.gov and the Cochrane Library for studies comparing radial versus femoral access in patients undergoing RA. Studies were included if they reported at least one of the following outcomes in each group separately: major adverse cardiac events (MACE), major bleeding, stent thrombosis, myocardial infarction (MI), hospital length of stay, radiation exposure, procedure time, procedure success and all-cause mortality. Odds ratio (OR) or mean difference (MD) with 95% confidence interval (CI) were calculated and a p-value of <0.05 was considered as a level of significance. This meta-analysis included 5 retrospective studies with 3315 patients undergoing RA via radial access and 5838 patients via femoral access. Radial access was associated with lower major access site bleeding (OR: 0.45, 95% CI: 0.31–0.67, p  0.05). This meta-analysis of 9153 patients from observational studies demonstrates similar all-cause mortality, MACE, procedural success and procedural time during RA performed using TR access and TF access. However, TR access was associated with decreased access site bleeding and radiation exposure. Given the observational nature of these findings, a randomized controlled trial is warranted for further evidence. •This article compares Radial versus Femoral access for Rotational Atherectomy.•Similar all-cause mortality, MACE rates between both groups•Similar procedural success and procedural time between both groups•Transradial approach associated with decreased bleeding and radiation exposur

Synthesis, Structure–Activity Relationships, and Biological Studies of Chromenochalcones as Potential Antileishmanial Agents

Antileishmanial activities of a library of synthetic chalcone analogues have been examined. Among them, five compounds (<b>11</b>, <b>14</b>, <b>16</b>, <b>17</b>, <b>22</b>, and <b>24</b>) exhibited better activity than the marketed drug miltefosine in in vitro studies against the intracellular amastigotes form of Leishmania donovani. Three promising compounds, <b>16</b>, <b>17</b>, and <b>22</b>, were tested in a L. donovani/hamster model. Oral administration of chalcone <b>16</b>, at a concentration of 100 mg/kg of body weight per day for 5 consecutive days, resulted in >84% parasite inhibition at day 7 post-treatment and it retained the activity until day 28. The molecular and immunological studies revealed that compound <b>16</b> has a dual nature to act as a direct parasite killing agent and as a host immunostimulant. Pharmacokinetics and serum albumin binding studies also suggest that compound <b>16</b> has the potential to be a candidate for the treatment of the nonhealing form of leishmaniasis