Shikonin and Alkannin inhibit ATP synthase and impede the cell growth in Escherichia coli.

Naturally occurring naphthoquinones, shikonin and alkannin, are important ingredients of traditional Chinese medicine Zicao. These constituents are reported to have many therapeutic uses, such as wound healing; scar treatment; and anti-inflammation, anti-acne, anti-ulcer, anti-HIV, anticancer, and antibacterial properties. The primary objective of this investigation was to explore the effect of shikonin and alkannin on Escherichia coli ATP synthase and its cell growth. Shikonin caused complete (100 %) inhibition, and alkannin caused partial (79 %) inhibition of wild-type E. coli ATP synthase. Both caused partial (4 %-27 %) inhibition of ATP synthase with genetically modified phytochemical binding site. The growth inhibition of strains expressing normal, deficient, and mutant ATP synthase by shikonin and alkannin, corroborated the inhibition observed in isolated normal wild-type and mutant ATP synthase. Trivial inhibition of mutant enzymes indicated αR283D, αE284R, ßV265Q, and γT273A are essential for formation of the phytochemical binding site where shikonin and alkannin bind. Further, shikonin was a potent inhibitor of ATP synthase than alkannin. The antimicrobial properties of shikonin and alkannin were tied to the binding at phytochemical site of microbial ATP synthase. Selective targeting of bacterial ATP synthase by shikonin and alkannin may be an advantageous alternative to address the antibiotic resistance issue.

Motivators and Barriers to Accessing Sexual Health Care Services for Transgender/Genderqueer Individuals Assigned Female Sex at Birth.

Purpose: Individuals who were assigned female sex at birth (AFAB) but do not conform to the gender binary (i.e., transgender/genderqueer) often do not seek out necessary sexual health care, including Papanicolaou (Pap) tests, placing them at heightened risk of cervical cancer. Despite growing awareness, scant research has focused on the sexual health care experiences of this population in Midwestern and rural states. Methods: We used two approaches to develop a more detailed understanding of factors that determine sexual health care use. Seventeen transgender/genderqueer AFAB individuals completed a quantitative knowledge survey then participated in a semistructured qualitative interview to further elaborate their experiences with sexual health care services as well as the motivators and barriers related to accessing the health care system. We produced descriptive summaries of quantitative data and conducted a thematic analysis of interview transcripts. Results: The sample was mostly young adults, of whom nearly all were white and 65% self-identified as transgender men. Participants displayed good knowledge about human papillomavirus (HPV) and Pap tests; however, 41% rated themselves as "unaware" and 59% rated themselves as "aware but not well informed" about HPV. Fifty-nine percent had ever obtained a Pap test. We identified one facilitating factor (health care provider's role and relationship) and three inhibiting factors (availability of competent care; distress about seeking sexual health care; health care setting characteristics) related to obtaining Pap tests. Conclusion: As this study was conducted in the U.S. Midwest, findings extend the geographic scope of existing knowledge and may inform future risk reduction interventions and clinical practice.

Predictors of common femoral artery access site complications in patients on oral anticoagulants and undergoing a coronary procedure.

BACKGROUND: It is unclear whether patients on oral anticoagulants (OAC) undergoing a procedure using common femoral artery access have higher adverse events when compared to patients who are not anticoagulated at the time of the procedure. METHODS: We retrospectively reviewed data from consecutive patients who underwent a cardiac procedure at a tertiary medical center. Patients were considered (group A) fully or partially anticoagulated if they had an international normalized ratio (INR) ≥1.6 on the day of the procedure or were on warfarin or new OAC within 48 h and 24 h of the procedure, respectively. The nonanticoagulated group (group B) had an INR <1.6 or had stopped their warfarin and new OAC >48 h and >24 h preprocedure, respectively. The index primary end point of the study was defined as the composite end point of major bleeding, vascular complications, or cardiovascular-related death during index hospitalization. The 30-day primary end point was defined as the occurrence of the index primary end point and up to 30 days postprocedure. RESULTS: A total of 779 patients were included in this study. Of these patients, 27 (3.5%) patients were in group A. The index primary end point was met in 11/779 (1.4%) patients. The 30-day primary composite end point was met in 18/779 (2.3%) patients. There was no difference in the primary end point at index between group A (1/27 [3.7%]) and group B (10/752 [1.3%]; P=0.3155) and no difference in the 30-day primary composite end point between group A (2/27 [7.4%]) and group B (16/752 [2.1%]; P=0.1313). Multivariable analysis showed that a low creatinine clearance (odds ratio [OR] =0.56; P=0.0200) and underweight patients (<60 kg; OR =3.94; P=0.0300) were independent predictors of the 30-day primary composite end point but not oral anticoagulation (P=0.1500). CONCLUSION: Patients on OAC did not have higher 30-day major adverse events than those who were not anticoagulated at index procedure.

The learning curve in treating coronary chronic total occlusion early in the experience of an operator at a tertiary medical center: The role of the hybrid approach.

BACKGROUND: Treatment of chronic total occlusion (CTO) is complex and has a low adoption rate by interventional cardiologists. The introduction of the hybrid approach has provided a systematic step-by-step approach to treat complex CTO lesions with a high success rate. We describe the overall experience with the use of the hybrid approach of a non-CTO operator and analyze differences in the procedural and long term outcomes before and after the initial 30 cases performed. METHODS: A total of 67 unselected, consecutive patients (68 lesions) underwent PCI of a CTO between January 2012 and June 2013 by a non-CTO operator. Patients were followed up for 1year using office and hospital medical records and death certificates. Cases were divided into the first consecutive 30 patients and compared to the subsequent 37 patients. The primary endpoint was acute procedural success defined as residual narrowing of ≤30% with no major adverse events. Secondary endpoints included the independent outcomes of death, major bleeding, perforations with cardiac tamponade, acute stent thrombosis (ST), target lesion revascularization (TLR) and target vessel revascularization (TVR). Descriptive analysis was performed on all variables. Univariate analysis was used to compare both groups. RESULTS: Baseline characteristics were as follows: mean age 63.9±10.6years, males 80.6%, diabetes 41.8%, de novo lesions 100%, ejection fraction 49.9±13.8%, CTO length 76.9±45.7mm, number of drug eluting stents per CTO 2.8±1.6 (median 3), contrast use 397±161.3ml, fluoroscopy time 51±32min and procedure time 134.3±74.7min. Lesions were crossed using an antegrade approach in 70.6% and a combined retrograde/antegrade approach in 29.4%. Crossing was intraluminal in 83.8% and subintimal in 16.2%. Acute procedural success was 95.5%. MAE included pericardial effusion with tamponade in 4.5%. On follow-up, TLR occurred in 6.6% of patients and TVR in 13.1%. There were no definite ST, one (1.6%) probable ST and one (1.6%) possible ST. Cardiac death occurred in 4.8% and non-cardiac death 1.6%. When comparing early experience (first 30 cases) with subsequent one, there were no differences in CTO length (60±47.6mm vs 83.2±43.7mm, p=0.206) or coronary distribution of the CTO. The number of drug eluting stents used per CTO (2.6±1.7 vs 3.0±1.5, p=0.289), contrast use (401±141.2ml vs 393.7±177.8ml, p=0.856), fluoroscopy time (48.9±25.6min vs 52.9±36.5min, p=0.617), or procedure time (116.8±48.6min vs 148.5±88.7min, p=0.068) were statistically similar between the 2 groups. Less crossing catheters were used (1.1±1 vs 0.6±0.7, p=0.024) and more lesions were crossed via antegrade approach after the initial experience (antegrade crossing: 53.3% vs 84.2% respectively, p=0.008). There was numerically more procedural success after the initial experience (90 vs 100%, p=0.085). MAE, TLR and TVR were similar on 1year follow-up. CONCLUSION: A high success rate was seen using the hybrid approach to treat CTO by a non-CTO operator. Although less crossing catheters were used and more lesions were treated via the antegrade approach after the initial experience, procedural and long term outcomes were otherwise similar between the early versus the late experience.