MLST of housekeeping genes captures geographic population structure and suggests a European origin of Borrelia burgdorferi

Lyme borreliosis, caused by the tick-borne bacterium Borrelia burgdorferi, has become the most common vector-borne disease in North America over the last three decades. To understand the dynamics of the epizootic spread and to predict the evolutionary trajectories of B. burgdorferi, accurate information on the population structure and the evolutionary relationships of the pathogen is crucial. We, therefore, developed a multilocus sequence typing (MLST) scheme for B. burgdorferi based on eight chromosomal housekeeping genes. We validated the MLST scheme on B. burgdorferi specimens from North America and Europe, comprising both cultured isolates and infected ticks. These data were compared with sequences for the commonly used genetic markers rrs-rrlA intergenic spacer (IGS) and the gene encoding the outer surface protein C (ospC). The study demonstrates that the concatenated sequences of the housekeeping genes of B. burgdorferi provide highly resolved phylogenetic signals and that the housekeeping genes evolve differently compared with the IGS locus and ospC. Using sequence data, the study reveals that North American and European populations of B. burgdorferi correspond to genetically distinct populations. Importantly, the MLST data suggest that B. burgdorferi originated in Europe rather than in North America as proposed previously.     

Resolution of migraine by transcatheter patent foramen ovale closure with Premere Occlusion System in a preliminary series of patients with previous cerebral ischemia.

BACKGROUND: Transcatheter closure of PFO with nitinol devices may be problematic in young patients with migraine due the risk of late erosions. Alternative devices with less amount of metal as the last generation devices may be preferable in such cases. We present the results of transcatheter closure of PFO with the last generation Premere Occlusion System device in a preliminary series of young adults with migraine and previous cerebral ischemia. METHODS: During a 12-month period (January 31, 2006 to December 31, 2006) 26 patients (18 female and 8 male, mean age 40 +/- 3.7 years) with previous stroke and severe disabling migraine were referred to our center for transcatheter closure of PFO. Migraine disability assessment score (MIDAS) was used to assess MHA incidence and severity. Patients were selected for Premere occlusion system (absence of atrial septal aneurysm and length >15 mm) on the basis of presence/absence of right and left bulging atrial septal aneurysm and length of PFO channel (<15 mm or >15 mm) on transesophageal echocardiography. Transesophageal echocardiography and transcranial Doppler were performed at 1 month, transthoracic echocardiography and cerebral magnetic resonance imaging at 6 and 12 months. Cardiologic and neurological visit was scheduled at 1, 6, and 12 months with MIDAS questionnaire administration. RESULTS: Ten patients (2 males, mean age 32 +/- 7.6 years, mean MIDAS score 38.9 +/- 5.8) underwent transcatheter PFO closure with the Premere occlusion system. Mean fossa ovalis diameters by ICE measurement was 20.6 +/- 3.1 mm. Thus, two 20-mm and eight 25-mm Premere devices were implanted. The procedure was successful in all of the patients with no perioperative and in-hospital complications. After a mean follow-up of 10.9 +/- 5.8 months, all patients were free from migraine symptoms (mean MIDAS score 2.9 +/- 1.9) with PFO complete closure in all patients on transesophageal and transcranial Doppler ultrasound. CONCLUSION: While waiting for larger studies evaluating the impact of new generation devices in curing PFO-related migraine, this preliminary anecdotal series suggests that the Premere occlusion system may be an effective and safe device for young patients with previous cerebral ischemia and migraine at least in the midterm period.     

Genome-wide copy number profiling reveals molecular evolution from diagnosis to relapse in childhood acute lymphoblastic leukemia

The underlying pathways that lead to relapse in childhood acute lymphoblastic leukemia (ALL) are unknown. To comprehensively characterize the molecular evolution of relapsed childhood B-precursor ALL, we used human 500K single-nucleotide polymorphism arrays to identify somatic copy number alterations (CNAs) in 20 diagnosis/relapse pairs relative to germ line. We identified 758 CNAs, 66.4% of which were less than 1 Mb, and deletions outnumbered amplifications by approximately 2.5:1. Although CNAs persisting from diagnosis to relapse were observed in all 20 cases, 17 patients exhibited differential CNA patterns from diagnosis to relapse. Of the 396 CNAs observed in 20 relapse samples, only 69 (17.4%) were novel (absent in the matched diagnosis samples). EBF1 and IKZF1 deletions were particularly frequent in this relapsed ALL cohort (25.0% and 35.0%, respectively), suggesting their role in disease recurrence. In addition, we noted concordance in global gene expression and DNA copy number changes (P = 2.2 x 10(-16)). Finally, relapse-specific focal deletion of MSH6 and, consequently, reduced gene expression were found in 2 of 20 cases. In an independent cohort of children with ALL, reduced expression of MSH6 was associated with resistance to mercaptopurine and prednisone, thereby providing a plausible mechanism by which this acquired deletion contributes to drug resistance at relapse.     

Tacrolimus ointment in nickel sulphate-induced steroid-resistant allergic contact dermatitis.

Tacrolimus ointment is a topical immunomodulator. Currently, there is available evidence regarding the potential use of topical tacrolimus in a range of dermatological disorders. The aim of this study was to evaluate the efficacy and safety of tacrolimus ointment 0.1% for the nickel sulfate-induced steroid-resistant allergic contact dermatitis (ACD). A randomized, double-blind, placebo-controlled, parallel-group study design was performed in a total of 28 patients affected by nickel sulfate-induced steroid-resistant ACD after a 14-day run-in period. Then, the enrolled patients were randomized into two subgroups. Group A was treated with tacrolimus for 14 days and finally observed for a 7-day follow-up period. Group B, instead, was treated with placebo (vehicle). Four major symptoms (erythema, oozing, scaling, and itching) were considered as outcomes during the different phases of the study. In group A, during the treatment period with tacrolimus, a significant improvement was observed in all four considered symptoms. On the other hand, no improvement in symptoms was observed in the placebo-treated group B. Local adverse events in the tacrolimus-treated group, such as burning/itching at the application site, were transient and well tolerated. No patients withdrew because of burning/itching. In our study, tacrolimus ointment 0.1% appeared to be both effective and safe in the treatment of nickel sulfate-induced steroid-resistant ACD.     

Effects of the progestagen-only contraceptive implant Implanon on cardiovascular risk factors

Objective Epidemiological studies on the cardiovascular risk of progestagen‐only contraceptives are rare. With the present study we aimed to investigate the effect of the low‐dose etonogestrel‐releasing contraceptive implant Implanon^® on cardiovascular risk factors, including markers of inflammation. Design Longitudinal study. Setting Family planning centre of a University Hospital. Subjects Thirty‐six healthy, nonsmoking women with regular cycles (n = 18 controls without hormonal contraception; n = 18 cases requesting the insertion of Implanon^®). Measurements Blood samples for the determination of C‐reactive protein (CRP), nitric oxide (NO), sex hormones and plasma lipids were taken in the early follicular phase of the cycle in both groups. A second sample was taken 12 weeks after Implanon insertion or in the controls during the early follicular phase of cycle 4. Results Implanon treatment caused a 36% decrease in CRP (P < 0·06) and a significant decrease in high density lipoprotein (HDL) (P < 0·007), low density lipoprotein (LDL) (P < 0·001), cholesterol (P < 0·001), testosterone (P < 0·05) and SHBG (P < 0·002). Levels of NO, oestradiol and progesterone were not affected in either group. The cholesterol/HDL ratio did not change in Implanon carriers. There was a significant correlation between the cardiovascular risk factors CRP, cholesterol/HDL ratio and NO. Conclusion The progestagen‐only implant Implanon does not exert a negative effect on the cardiovascular risk factors CRP, cholesterol/HDL ratio and NO. These results suggest that the use of a progestagen‐only contraception does not increase cardiovascular risk factors in healthy young women.     

Catecholamines and vasopressin during critical illness.

This article summarizes the effects of catecholamines and vasopressin on the cardiovascular system, focusing on their metabolic and immunologic properties. Particular attention is dedicated to the septic shock condition.     

Children's perceptions of smile esthetics and their influence on social judgment

Objective:To define a threshold of acceptance of smile esthetics for children and adolescents.Materials and Methods:A systematic search in the medical literature (PubMed, PubMed Central, National Library of Medicine''s Medline, Embase, Cochrane Central Register of Controlled Clinical Trials, Web of Knowledge, Scopus, Google Scholar, and LILACs) was performed to identify all peer-reviewed papers reporting data regarding the evaluation of children''s and adolescents'' perceptions of dental esthetic factors. The search was conducted using a research strategy based on keywords such as “children,” “adolescents,” “smile aesthetics perception,” “smile aesthetics evaluation.” Studies analyzing smile esthetics involving at least 10 observers younger than 18 years of age were selected.Results:Among the 1667 analyzed articles, five studies were selected for the final review process. No study included in the review analyzed perception of smile anomalies in a quantitative or qualitative way, thus no threshold was identified for smile features. Among the analyzed samples, unaltered smiles were always significantly associated with better evaluation scores when compared with altered smiles.Conclusions:Smile esthetics influence social perception during childhood and adolescence. However, thresholds of smile esthetic acceptance in children and adolescents are still not available.     

Efficacy and safety of atorvastatin compared to pravastatin in patients with hypercholesterolemia

Plasma cholesterol and other lipoproteins play a significant role in the development of atherosclerosis and subsequent coronary heart disease (CHD). This 1 year study was designed to confirm the efficacy and safety of atorvastatin (Lipitor) compared to pravastatin, a marketed agent for low density lipoprotein cholesterol (LDL-C) reduction in hypercholesterolemic patients. Patients were recruited at 26 centers in six European countries. After a 6 week placebo baseline phase, patients were randomized to receive atorvastatin 10 mg or pravastatin 20 mg daily. The dose could be doubled at week 16, if LDL-C levels remained ≥3.4 mmol/l (135 mg/dl). Atorvastatin significantly lowered LDL-C from baseline by 35% compared with 23% for pravastatin (P<0.05). A total of 72% of atorvastatin patients attained the LDL-C target level of <3.4 mmol/l, compared to 26% of pravastatin patients. Atorvastatin also significantly reduced TC, TG and apo B (P<0.05). Safety was assessed by recording adverse events and measuring clinical laboratory parameters. The adverse event profile was similar for both treatment groups and neither treatment caused clinically relevant laboratory abnormalities. Atorvastatin 10 and 20 mg once daily is superior to pravastatin 20 and 40 mg once daily in treating patients with hypercholesterolemia.     

Clinical utility of intrathoracic impedance monitoring to alert patients with an implanted device of deteriorating chronic heart failure.

AIMS: To evaluate the utility of intrathoracic impedance monitoring for detecting heart failure (HF) deterioration in patients with an implanted cardiac resynchronization/defibrillation device. METHODS AND RESULTS: Patients enrolled in the European InSync Sentry Observational Study were audibly alerted by a device algorithm if a decrease in intrathoracic impedance suggested fluid accumulation. Clinical HF status and device data were assessed at enrolment, during regular follow-up, and if patients presented with an alert or HF deterioration. Data from 373 subjects were analysed. Fifty-three alert events and a total of 53 clinical events (HF deterioration defined by worsening of HF signs and symptoms) were reported during a median of 4.2 months. Adjusted for multiple events per patient, the alert detected clinical HF deterioration with 60% sensitivity (95% CI 46-73) and with a positive predictive value of 60% (95% CI 46-73). Higher NYHA class at baseline was predictive for adequate alert events during follow-up (P < 0.05). In 11 of 20 HF deteriorations without preceding alert, an upstroke of the fluid index occurred without reaching the programmed alert threshold. CONCLUSION: A device-based algorithm that alerts patients in case of decreasing intrathoracic impedance facilitates the detection of HF deterioration. Future randomized, controlled trials are needed to test whether the tailored use of intrathoracic impedance monitoring can improve the ambulatory management of patients with chronic HF and an implanted device.     

Effect of potassium canrenoate, an anti-aldosterone agent, on incidence of ascites and variceal progression in cirrhosis.

BACKGROUND & AIMS: Because aldosterone-dependent sodium and water retention contribute to portal hypertension, the safety and effect of an antialdosteronic drug (Kcanrenoate) have been evaluated on the occurrence of de novo appearance of ascites and the development of esophageal varices or the progression of small varices. METHODS: Inclusion criteria were as follows: Child-Pugh A viral pre-ascitic cirrhosis, with either F1 esophageal varices or no varices, but endoscopic and/or ultrasound evidence of portal hypertension. Thirteen Italian Liver Units prospectively enrolled 120 patients randomized to receive double-blind either Kcanrenoate (100 mg/day; 66 patients) or placebo (54 patients). Endoscopy and sonography were performed at entry and at 52 weeks unless the patient developed ascites earlier, whereas laboratory examinations were performed at entry and every 3 months thereafter. An intention-to-treat analysis was performed, with each end point assessed by the Fisher exact test; the cumulative risk for the appearance of any end point was analyzed by the adjusted log-rank test (Tarone-Ware), with censoring for drop-outs. RESULTS: The progression of variceal status or appearance of ascites, analyzed independently, was not significantly more frequent on placebo (24.1% and 9.2%, respectively) than on Kcanrenoate (12.1% and 1.5%, respectively), whereas the cumulative occurrence of end points was decreased on Kcanrenoate (17.6% vs 38.3% with placebo; P < .05, Tarone-Ware test). The incidence of adverse events was negligible and did not differ between groups. CONCLUSIONS: This preliminary study shows that 100 mg/day of Kcanrenoate is well tolerated and does not reduce the individual incidence of ascites and/or the appearance or progression of esophageal varices in preascitc cirrhosis, but may decrease their 1-year cumulative occurrence.