Fecal indicator organisms in northern oligotrophic rivers: An explorative study on Escherichia coli prevalence in a mountain region with intense tourism and reindeer herding.

Increasing pollution levels in waters from remote mountain areas in northern Sweden have been observed. To support a sustainable water quality management, it is necessary to know which environmental and antrophogenic factors influence the water quality. The purpose of this study was to map the Escherichia coli prevalence in the catchment area of the upper part of a large northern Scandinavian river and investigate the controlling factors of microbial contamination. A total of 112 water samples were collected from various locations in the research area between July 2020 and December 2020. These samples were analyzed for microbial and chemical characteristics, and information about tourism and reindeer herding was compiled. Additionally, microbial and physicochemical water characteristics collected by Indalsälven Water Conservation Association (IWCA, 1993-2020) and Swedish Meteorological and Hydrological Institute (SMHI, 2004-2020) were analyzed. The results showed that E. coli enumerations ranged between 0 and 500 CFU/100 ml. There was generally no obvious relation between suspected point sources, e.g., sewage treatment plants at mountain stations, and E. coli levels at downstream sampling points. Principal component analysis showed that E. coli was correlated to coliforms, total heterotrophic count, river discharge, CODMn and river color. Since microbial analyses are time-consuming, expensive and difficult to perform in remote areas, it is important to find more easily extracted water parameters that can serve as a proxy for E. coli. In particular, river color and discharge are promising parameters that may serve as an early indication of bacterial outbreak and fecal contamination in mountain waters.

A decade of catheter ablation of cardiac arrhythmias in Sweden: ablation practices and outcomes.

AIMS: Catheter ablation is considered the treatment of choice for many tachyarrhythmias, but convincing 'real-world' data on efficacy and safety are lacking. Using Swedish national registry data, the ablation spectrum, procedural characteristics, as well as ablation efficacy and reported adverse events are reported. METHODS AND RESULTS: Consecutive patients (≥18 years of age) undergoing catheter ablation in Sweden between 01 January 2006 and 31 December 2015 were included in the study. Follow-up (repeat ablation and vital status) was collected through 31 December 2016. A total of 26 642 patients (57 ± 15 years, 62% men), undergoing a total of 34 428 ablation procedures were included in the study. In total, 4034 accessory pathway/Wolff-Parkinson-White syndrome (12%), 7358 AV-nodal re-entrant tachycardia (21%), 1813 atrial tachycardia (5.2%), 5481 typical atrial flutter (16%), 11 916 atrial fibrillation (AF, 35%), 2415 AV-nodal (7.0%), 581 premature ventricular contraction (PVC, 1.7%), and 964 ventricular tachycardia (VT) ablations (2.8%) were performed. Median follow-up time was 4.7 years (interquartile range 2.7-7.0). The spectrum of treated arrhythmias changed over time, with a gradual increase in AF, VT, and PVC ablation (P < 0.001). Decreasing procedural times and utilization of fluoroscopy with time, were seen for all arrhythmia types. The rates of repeat ablation differed between ablation types, with the highest repeat ablation seen in AF (41% within 3 years). The rate of reported adverse events was low (n = 595, 1.7%). Death in the immediate period following ablation was rare (n = 116, 0.34%). CONCLUSION: Catheter ablations have shifted towards more complex procedures over the past decade. Fluoroscopy time has markedly decreased and the efficacy of catheter ablation seems to improve for AF.

Losartan has no additive effect on the response to heavy-resistance exercise in human elderly skeletal muscle.

Our purpose here was to investigate the potential of blocking the angiotensin II type I receptor (AT1R) on the hypertrophy response of elderly human skeletal muscle to 4 mo of heavy-resistance exercise training. Fifty-eight healthy elderly men (+65 yr) were randomized into three groups, consuming either AT1R blocker (losartan, 100 mg/day) or placebo for 4 mo. Two groups performed resistance training (RT) and were treated with either losartan or placebo, and one group did not train but was treated with losartan. Quadriceps muscle biopsies, MR scans, and strength tests were performed at baseline and after 8 and 16 wk. Biopsies were sectioned for immunohistochemistry to determine the number of satellite cells, capillaries, fiber type distribution, and fiber area. Gene expression levels of myostatin, connective tissue, and myogenic signaling pathways were determined by real-time RT-PCR. Four months of heavy-resistance training led in both training groups to expected improvements in quadriceps (∼3-4%) and vastus lateralis (∼5-6%), cross-sectional area, and type II fiber area (∼10-18%), as well as dynamic (∼13%) and isometric (∼19%) quadriceps peak force, but with absolutely no effect of losartan on these outcomes. Furthermore, no changes were seen in satellite cell number with training, and most gene targets failed to show any changes induced by training or losartan treatment. We conclude that there does not appear to be any effect of AT1R blocking in elderly men during 4 mo of resistance training. Therefore, we do not find any support for using AT1R blockers for promoting muscle adaptation to training in humans. NEW & NOTEWORTHY Animal studies have suggested that blocking angiotensin II type I receptor (AT1R) enhances muscle regeneration and prevents disuse atrophy, but studies in humans are limited. Focusing on hypertrophy, satellite cells, and gene expression, we found that AT1R blocking did not result in any greater responses with 4 mo of resistance training. These results do not support previous findings and question the value of blocking AT1R in the context of preserving aging human muscle.

The state of the residential fire fatality problem in Sweden: Epidemiology, risk factors, and event typologies.

INTRODUCTION: Residential fires represent the largest category of fatal fires in Sweden. The purpose of this study was to describe the epidemiology of fatal residential fires in Sweden and to identify clusters of events. METHOD: Data was collected from a database that combines information on fatal fires with data from forensic examinations and the Swedish Cause of Death-register. Mortality rates were calculated for different strata using population statistics and rescue service turnout reports. Cluster analysis was performed using multiple correspondence analysis with agglomerative hierarchical clustering. RESULTS: Male sex, old age, smoking, and alcohol were identified as risk factors, and the most common primary injury diagnosis was exposure to toxic gases. Compared to non-fatal fires, fatal residential fires more often originated in the bedroom, were more often caused by smoking, and were more likely to occur at night. Six clusters were identified. The first two clusters were both smoking-related, but were separated into (1) fatalities that often involved elderly people, usually female, whose clothes were ignited (17% of the sample), (2) middle-aged (45-64years old), (often) intoxicated men, where the fire usually originated in furniture (30%). Other clusters that were identified in the analysis were related to (3) fires caused by technical fault, started in electrical installations in single houses (13%), (4) cooking appliances left on (8%), (5) events with unknown cause, room and object of origin (25%), and (6) deliberately set fires (7%). CONCLUSIONS: Fatal residential fires were unevenly distributed in the Swedish population. To further reduce the incidence of fire mortality, specialized prevention efforts that focus on the different needs of each cluster are required. PRACTICAL APPLICATIONS: Cooperation between various societal functions, e.g. rescue services, elderly care, psychiatric clinics and other social services, with an application of both human and technological interventions, should reduce residential fire mortality in Sweden.

Catheter ablation of ventricular tachycardia in a patient with a left endoventricular patch: a case report.

Surgical resection of a left ventricular aneurysm in the setting of ventricular tachycardia (VT) was first described by Couch in 1959. The technique was further developed by Dor et al. with performance of endocardiectomy and complete myocardial revascularization. Despite an attempt to remove the arrhythmogenic substrate, however, recurrences of VT remain an issue. Furthermore, the surgical technique used entails limited access to the potential area of interest with regard to a percutaneous catheter ablation procedure. We present a case report of a 65-year-old man who was referred for catheter ablation due to recurrent episodes of VT. He had undergone a coronary artery bypass surgery 8 years previously. During surgery, resection of an apical thrombus and reconstruction of an apical aneurysm with a Fontan stitch and an endoventricular patch were performed. The mapping and ablation procedure was aided by intracardiac echocardiography. During mapping, the ablation catheter was noticed to enter the apical pouch from the inferoseptal border of the endoventricular patch. During the ablation procedure, one of the VTs was successfully ablated in the inferior aspect of the apical pouch. This report confirms that the arrhythmogenic substrate underneath an endoventricular patch may be accessed in some instances and that these complex catheter ablation procedures may benefit from the use of intracardiac echocardiography.

Using Shoulder Straps Decreases Heart Rate Variability and Salivary Cortisol Concentration in Swedish Ambulance Personnel.

BACKGROUND: Previous research has shown that paramedics are exposed to risks in the form of injuries to the musculoskeletal system. In addition, there are studies showing that they are also at increased risk of cardiovascular disease, cancer, and psychiatric diseases, which can partly be explained by their constant exposure to stress. The aim of this study is to evaluate whether the use of shoulder straps decreases physical effort in the form of decreased heart rate and cortisol concentration. METHODS: A stretcher with a dummy was carried by 20 participants for 400 m on two occasions, one with and one without the shoulder straps. Heart rate was monitored continuously and cortisol samples were taken at intervals of 0 minutes, 15 minutes, 30 minutes, 45 minutes, and 60 minutes. Each participant was her or his own control. RESULTS: A significant decrease in heart rate and cortisol concentration was seen when shoulder straps were used. The median values for men (with shoulder straps) at 0 minutes was 78 bpm/21.1 nmol/L (heart rate/cortisol concentration), at 15 minutes was 85 bpm/16.9 nmol/L, and at 60 minutes was 76 bpm/15.7 nmol/L; for men without shoulder straps, these values were 78 bpm/21.9 nmol/L, 93 bpm/21.9 nmol/L, and 73 bpm/20.5 nmol/L. For women, the values were 85 bpm/23.3 nmol/L, 92 bpm/20.8 nmol/L, and 70 bpm/18.4 nmol/L and 84 bpm/32.4 nmol/L, 100 bpm/32.5 nmol/L, and 75 bpm/25.2 nmol/L, respectively. CONCLUSION: The use of shoulder straps decreases measurable physical stress and should therefore be implemented when heavy equipment or a stretcher needs to be carried. An easy way to ensure that staff use these or similar lifting aids is to provide them with personalized, well-adapted shoulder straps. Another better option would be to routinely sewn these straps into the staff's personal alarm jackets so they are always in place and ready to be used.

Investigating the effect of banning non-reduced ignition propensity cigarettes on fatal residential fires in Sweden.

BACKGROUND: Annually, 100 people die as a result of residential fires in Sweden and almost a third of the fatal fires are known to be caused by smoking. In an attempt to reduce the occurrence of these events, reduced ignition propensity (RIP) cigarettes have been developed. They are designed to reduce the risk of fire by preventing the cigarette from burning through the full length when left unattended. In November 2011, a ban was introduced, forbidding the production and sale of all non-RIP cigarettes in all member states of the European Union, including Sweden. METHODS: Monthly data on all recorded residential fires and associated fatalities in Sweden from January 2000 to December 2013 were analyzed using an interrupted time series design. The effect of the intervention [in relative risk (RR)] was quantified using generalised additive models for location, shape and scale. RESULTS: There were no statistically significant intervention effects on residential fires (RR 0.95 [95% CI: 0.89-1.01]), fatal residential fires (RR 0.99 [95% CI: 0.80-1.23]), residential fires where smoking was a known cause (RR 1.10 [95% CI: 0.95-1.28]) or fatal residential fires where smoking was a known cause (RR 0.92 [95% CI: 0.63-1.35]). CONCLUSION: No evidence of an effect of the ban on all non-RIP cigarettes on the risk of residential fires in Sweden was found. The results may not be generalisable to other countries.

Transcatheter mitral valve implantation via transapical approach: an early experience.

OBJECTIVES: As many as 50% of patients with severe symptomatic mitral valve regurgitation are denied surgical valve replacement or repair due to high operative risk. We describe an early series of cases of transcatheter implantation with a CardiAQ™ mitral valve via a transapical approach. METHODS: Three consecutive patients with an Society of Thoracic Surgeons (STS) mortality score of >22% were selected for transcatheter mitral valve implantation (TMVI) on compassionate grounds. All patients were elderly, had severe mitral regurgitation (MR), were in Class IV heart failure and deemed unsuitable for the MitraClip. Two of the patients had functional MR in the setting of ischaemic cardiomyopathy with left ventricular ejection fraction (LVEF) <40%, deemed while the remaining patient had chordal rupture with extensive anterior leaflet flail (preserved LVEF). Comorbidities included previous coronary artery bypass surgery (n = 2), severe pulmonary hypertension (n = 1) and moderate to severe chronic renal failure (n = 3). A CardiAQ mitral valve was implanted using fluoroscopy and transoesophageal (TEE) guidance via a standard transapical approach. RESULTS: Accurate prosthesis positioning and deployment with immediate elimination of the MR was achieved in all 3 cases. Two patients made full clinical recovery and were discharged home. Post-procedural TEE performed on Days 1, 30 and 60 days showed good valve function, stable valve position and minimal LVOT gradient. One patient expired on the postoperative day 9 due to pneumonia. CONCLUSIONS: TMVI using the CardiAQ™ device via a transapical approach is feasible and effective.

Transapical valve-in-valve-in-ring for stenotic mitral valve repair.

A 53-year-old woman, previously treated with irradiation and chemotherapy for Hodgkin lymphoma, was referred for redo valve surgery. She had had a pacemaker implantation and undergone coronary bypass surgery, mitral valve repair with a Carpentier-Edwards 28-mm Physio-annuloplasty ring, as well as a mechanical tricuspid valve replacement and a transfemoral CoreValve 26-mm implantation. She had cardiac cachexia, pleura effusion, and a failed mitral valve repair with stenosis. She was judged inoperable for open surgery but suitable for a transapical valve-in-valve implantation on partial femorofemoral bypass. A 26-mm Edwards SAPIEN XT aortic valve inversely mounted on the Ascendra + delivery catheter was balloon expanded into the Physio ring. During expansion, the introducer sheath remained too deep into the left ventricle and rotated the SAPIEN valve upward to the left atrium, creating the onset of a new mitral regurgitation and retaining the stenosis. Another Edwards SAPIEN XT 26-mm valve was then positioned into the first valve in a "valve-in-valve-in-ring" tandem configuration. Both valves were supported by the Physio ring. The stenosis and the regurgitation were thereafter eliminated.

Sources of information influencing decision-making in orthopaedic surgery - an international online survey of 1147 orthopaedic surgeons.

BACKGROUND: Manufacturers of implants and materials in the field of orthopaedics use significant amounts of funding to produce informational material to influence the decision-making process of orthopaedic surgeons with regards to choice between novel implants and techniques. It remains unclear how far orthopaedic surgeons are really influenced by the materials supplied by companies or whether other, evidence-based publications have a higher impact on their decision-making. The objective was to evaluate the subjective usefulness and usage of different sources of information upon which orthopaedic surgeons base their decisions when acquiring new implants or techniques. METHODS: We undertook an online survey of 1174 orthopaedic surgeons worldwide (of whom n = 305 were head of their department). The questionnaire included 34 items. Sequences were randomized to reduce possible bias. Questions were closed or semi-open with single or multiple answers. The usage and relevance of different sources of information when learning about and selecting orthopaedic treatments were evaluated. Orthopaedic surgeons and trainees were targeted, and were only allowed to respond once over a period of two weeks. Baseline information included country of workplace, level of experience and orthopaedic subspecialisation. The results were statistically evaluated. RESULTS: Independent scientific proof had the highest influence on decisions for treatment while OEM (Original Equipment Manufacturer) driven activities like newsletters, white papers or workshops had the least impact. Comparison of answers from the three best-represented countries in this study (Germany, UK and USA) showed some significant differences: Scientific literature and congresses are significantly more important in the US than in the UK or Germany, although they are very important in all countries. CONCLUSIONS: Independent and peer-reviewed sources of information are preferred by surgeons when choosing between methods and implants. Manufacturers of medical devices in orthopaedics employ a considerable workforce to inform or influence hospital managers and leading doctors with marketing activities. Our results indicate that it might be far more effective to channel at least some of these funds into peer-reviewed research projects, thereby assuring significantly higher acceptance of the related products.

Decision support system in prehospital care: a randomized controlled simulation study.

INTRODUCTION: Prehospital emergency medicine is a challenging discipline characterized by a high level of acuity, a lack of clinical information and a wide range of clinical conditions. These factors contribute to the fact that prehospital emergency medicine is a high-risk discipline in terms of medical errors. Prehospital use of Computerized Decision Support System (CDSS) may be a way to increase patient safety but very few studies evaluate the effect in prehospital care. The aim of the present study is to evaluate a CDSS. METHODS: In this non-blind block randomized, controlled trial, 60 ambulance nurses participated, randomized into 2 groups. To compensate for an expected learning effect the groups was further divided in two groups, one started with case A and the other group started with case B. The intervention group had access to and treated the two simulated patient cases with the aid of a CDSS. The control group treated the same cases with the aid of a regional guideline in paper format. The performance that was measured was compliance with regional prehospital guidelines and On Scene Time (OST). RESULTS: There was no significant difference in the two group's characteristics. The intervention group had a higher compliance in the both cases, 80% vs. 60% (p<0.001) but the control group was complete the cases in the half of the time compare to the intervention group (p<0.001). CONCLUSION: The results indicate that this CDSS increases the ambulance nurses' compliance with regional prehospital guidelines but at the expense of an increase in OST.

Microwave Ablation in Mitral Valve Surgery for Atrial Fibrillation (MAMA).

Objective: Microwave ablation in conjunction with open heart surgery is effective in restoring sinus rhythm (SR) in patients with atrial fibrillation (AF). In patients assigned for isolated mitral valve surgery no prospective randomized trial has reported its efficacy. Methods: 70 patients with longlasting AF where included from 5 different centres. They were randomly assigned to mitral valve surgery and atrial microwave ablation or mitral valve surgery alone. Results: Out of 70 randomized, 66 and 64 patients were available for evaluation at 6 and 12 months. At 12 months SR was restored and preserved in 71.0 % in the ablation group vs 36.4 % in the control group (P=0.006), corresponding figures at 6 months was 62.5 % vs 26.5 % (P=0.003). The 30-day mortality rate was 1.4 %, with one death in the ablation group vs zero deaths in the control group. At 12 months the mortality rate was 7,1 % (Ablation n=3 vs Control n=2). No significant differences existed between the groups with regard to the overall rate of serious adverse events (SAE) during the perioperative period or at the end of the study. 16 % of patients randomized to ablation were on antiarrhytmic drugs compared to 6 % in the control group after 1 year (p=0.22). Conclusion: Microwave ablation of left and right atrium in conjunction with mitral valve surgery is safe and effectively restores sinus rhythm in patients with longlasting AF as compared to mitral valve surgery alone.

In vivo tissue response to ultrasound assisted application of biodegradable pins into cortical and cancellous bone structures: a histological and densitometric analysis in rabbits.

In orthopaedic traumatology biodegradable pins are increasingly used for fixation of small bone fragments. In the present study, the ultrasound-assisted anchoring technique (SonicFusion technique), a osteosynthesis method being recently introduced in cranial applications, in which ultrasonic energy is used to insert and anchor polymer pins in bone, was compared with the conventional pin application procedure. The aim of the present study was to assess the short and long term thermal impact of two different ultrasonic energy levels on different bone structures in the distal medial femur of rabbits. The treatment groups consisted of customized polylactide pins applied at a low and a high energy level, the Reference Control and a Negative Control. The thermal effect on bone tissues was evaluated by means of qualitative and semi-quantitative histology and micro-computerized tomography. Five days following surgery, all implant sites showed no tissue damage but normal signs of early ongoing tissue repair. Enhancing the energy level by about 30% had no significant impact on the tissue response. At 4 weeks after surgery test sites covered by ultrasound-aided implantation showed a significantly enhanced bone/implant contact as compared to pins applied by conventional application. In conclusion, the ultrasound assisted anchoring technique not only did not impair bone regeneration, but even improved implant integration.

High frequency of p16(INK4A) promoter methylation in NRAS-mutated cutaneous melanoma.

The p16(INK4A) tumor suppressor is often deleted, or otherwise inactivated, in malignant melanoma. To investigate the loss of p16(INK4A) in greater detail, we analyzed 77 cutaneous melanoma metastases. Of these 56 retained at least one p16(INK4A) allele, and 21 had biallelic deletions. Using methylation-specific PCR, direct sequencing, and immunohistochemical methods, we analyzed p16(INK4A) promoter methylation, mutations, and protein expression, respectively. In addition, 14 corresponding primary tumors were analyzed for protein expression. Results were compared to clinicopathological parameters and previously obtained data regarding mutations in proto-oncogenes NRAS and BRAF. Results revealed that p16(INK4A) promoter methylation was present in 15 of 59 (25%) metastases; nonsynonymous mutations in 9 of 56 (16%) metastases; and protein expression in 12 of 67 (18%) metastases. Protein expression was lost during progression from primary to metastatic tumors, 71% (10 of 14) and 43% (6 of 14) being positive, respectively. However, the genetic and epigenetic alterations of p16(INK4A) observed could not explain the lack of p16(INK4A) protein in 27 metastases, indicating the presence of additional inactivating mechanisms for p16(INK4A). Interestingly, p16(INK4A) promoter methylation was significantly overrepresented in NRAS-mutated samples compared to NRAS wild-type samples (P=0.0004), indicating an association between these two events.

MitraClip catheter-based mitral valve repair system.

The ongoing evolution of transcatheter valve technology is impressive. Mitral valve regurgitation is the most common type of heart valve insufficiency and mitral valve surgery is, next to aortic valve surgery, the second leading valvular surgical procedure in the western world. However, there is a large patient population suffering from mitral valve regurgitation that is currently not treated with heart surgery because of significant morbidity and mortality risks. This large underserved patient population could benefit from a less invasive treatment. The MitraClip system (Abbott Vascular, Menlo Park, CA, USA) is the first commercially available medical technology providing a catheter-based nonsurgical repair alternative for patients suffering from mitral valve regurgitation and has the greatest clinical experience compared with other alternative devices. The device is currently in late-stage clinical trials in the USA and has received the CE mark.

Barley as a green factory for the production of functional Flt3 ligand.

Biologically active recombinant human Flt3 ligand was expressed and isolated from transgenic barley seeds. Its expression is controlled by a tissue specific promoter that confines accumulation of the recombinant protein to the endosperm tissue of the seed. The recombinant Flt3 ligand variant expressed in the seeds contains an HQ-tag for affinity purification on immobilized metal ion affinity chromatography (IMAC) resin. The tagged protein was purified from seed extracts to near homogeneity using sequential chromatography on IMAC affinity resin and cation exchange resin. We also show that the recombinant Flt3 ligand protein undergoes posttranslational modifications: it is a glycoprotein containing alpha-1,3-fucose and alpha-1,2-xylose. The HQ-tagged Flt3 ligand variant exhibits comparable biological activity to commercial Flt3 ligand. This is the first report showing expression and accumulation of recombinant human growth factor in barley seeds with a yield of active protein similar to a bacterial expression system. The present results demonstrate that plant molecular farming is a viable approach for the bioproduction of human-derived growth factors.

Long-term follow-up of persistent atrial fibrillation ablation using termination as a procedural endpoint.

AIMS: Catheter ablation of long-lasting persistent atrial fibrillation (AF) has been performed with varying results using a combination of different techniques. Whether arrhythmia termination during ablation is associated with an improved clinical outcome is controversial. METHODS AND RESULTS: In this prospective study, 153 consecutive patients (56 +/- 10 years) underwent catheter ablation of persistent AF (25 +/- 33 months) using a stepwise approach with the desired procedural endpoint being AF termination. Repeat ablation was performed for patients with recurrent AF or atrial tachycardia (AT) after a 1 month blanking period. A minimum follow-up of 12 months with repeated Holter monitoring was performed. Atrial fibrillation was terminated in 130 patients (85%). There was a lower incidence of AF in those patients in whom AF was terminated during the index procedure compared with those who had not (5 vs. 39% P < 0.0001, mean follow-up 32 +/- 11 months). Seventy-nine patients underwent repeat procedures: 64/130 in the termination group (6 AF, 58 AT) and 15 in the non-termination group (9 AF, 7 AT). After repeat ablation, sinus rhythm was maintained in 95% in whom AF was terminated compared with 52% in those in whom AF could not be terminated. CONCLUSION: Procedural termination of long-lasting AF by catheter ablation alone is associated with an improved outcome.

Interaction of the signal transduction protein GlnJ with the cellular targets AmtB1, GlnE and GlnD in Rhodospirillum rubrum: dependence on manganese, 2-oxoglutarate and the ADP/ATP ratio.

The PII family of signal transduction proteins is widespread amongst the three domains of life, and its members have fundamental roles in the general control of nitrogen metabolism. These proteins exert their regulatory role by direct protein-protein interaction with a multitude of cellular targets. The interactions are dependent on the binding of metabolites such as ATP, ADP and 2-oxoglutarate (2-OG), and on whether or not the PII protein is modified. In the photosynthetic nitrogen-fixing bacterium Rhodospirillum rubrum three PII paralogues have been identified and termed GlnB, GlnJ and GlnK. In this report we analysed the interaction of GlnJ with known cellular targets such as the ammonium transporter AmtB1, the adenylyltransferase GlnE and the uridylyltransferase GlnD. Our results show that the interaction of GlnJ with cellular targets is regulated in vitro by the concentrations of manganese and 2-OG and the ADP : ATP ratio. Furthermore, we show here for the first time, to our knowledge, that in the interactions of GlnJ with the three different partners, the energy signal (ADP : ATP ratio) in fact overrides the carbon/nitrogen signal (2-OG). In addition, by generating specific amino acid substitutions in GlnJ we show that the interactions with different cellular targets are differentially affected, and the possible implications of these results are discussed. Our results are important to further the understanding of the regulatory role of PII proteins in R. rubrum, a photosynthetic bacterium in which the nitrogen fixation process and its intricate control mechanisms make the regulation of nitrogen metabolism even more complex than in other studied bacteria.

Grade of left main coronary artery stenosis does not influence long-term mortality after coronary artery bypass surgery.

OBJECTIVE: To assess if grade of left main coronary artery (LMCA) stenosis influences early or long-term mortality after coronary artery bypass grafting (CABG). DESIGN: Among all 1 384 patients with LMCA stenosis at Karolinska Hospital, Stockholm, Sweden during 1990-1999, 131 deaths occurred within 5 years of surgery (cases). Matched controls (n=146) were randomly selected from all surviving LMCA patients taking gender, age and year of surgery into account. Angiographies were classified for grade of LMCA stenosis before the operation. RESULTS: High-grade LMCA stenosis was equally common among cases and controls (50 vs. 45%). The odds ratio (OR) of mortality 5 years after the operation in patients with high-grade versus low-grade LMCA stenosis based on the matched pairs was 1.2 (95% confidence interval (CI) 0.7-2.0) and after multivariable adjustment using information on all subjects the OR was 1.0 (95% CI 0.6-1.7). For early and one year mortality similar odds ratios were observed but with wide confidence intervals. CONCLUSIONS: Grade of LMCA stenosis does not appear to influence early or long-term mortality after CABG performed during 1990-1999.

Source of inflammatory markers in patients with atrial fibrillation.

AIMS: Elevated levels of C-reactive protein and other inflammatory markers have been reported in some patients with atrial fibrillation (AF). Whether this finding is related to AF per se or to other conditions remains unclear. In addition, the source of inflammatory markers is unknown. Therefore, in the present study, we sought to assess the extent and the source of inflammation in patients with AF and no other concomitant heart or inflammatory conditions. METHODS AND RESULTS: The study group consisted of 29 patients referred for radiofrequency catheter ablation: 10 patients with paroxysmal AF, 8 patients with permanent AF, and 10 control patients with Wolf-Parkinson-White (WPW) syndrome and no evidence of AF (mean age 54 +/- 11 vs. 57 +/- 13 vs. 43 +/- 16). No patient had structural heart diseases or inflammatory conditions. High-sensitive C-reactive protein, interleukin-6 (IL-6), and interleukin-8 (IL-8) were assessed in blood samples from the femoral vein, right atrium, coronary sinus, and the left and right upper pulmonary veins. All samples were collected before ablation. Compared with controls and patients with paroxysmal AF, patients with permanent AF had higher plasma levels of IL-8 in the samples from the femoral vein, right atrium, and coronary sinus, but not in the samples from the pulmonary veins (median values in the femoral vein: 2.58 vs. 2.97 vs. 4.66 pg/mL, P = 0.003; right atrium: 2.30 vs. 3.06 vs. 3.93 pg/mL, P = 0.013; coronary sinus: 2.85 vs. 3.15 vs. 4.07, P = 0.016). A high-degree correlation existed between the IL-8 levels in these samples (correlation coefficient between 0.929 and 0.976, P < 0.05). No differences in the C-reactive protein and IL-6 levels were noted between the three groups of patients. CONCLUSION: The normal levels of C-reactive protein and IL-6, along with the elevated levels of IL-8 in patients with permanent AF but not in those with paroxysmal AF, suggest a link between a low-grade inflammatory reaction and long-lasting AF. The elevated IL-8 levels in the peripheral blood, right atrium, and coronary sinus but not in the pulmonary veins suggest a possible source of inflammation in the systemic circulation.