Interleukin-17D and Nrf2 mediate initial innate immune cell recruitment and restrict MCMV infection.

Innate immune cells quickly infiltrate the site of pathogen entry and not only stave off infection but also initiate antigen presentation and promote adaptive immunity. The recruitment of innate leukocytes has been well studied in the context of extracellular bacterial and fungal infection but less during viral infections. We have recently shown that the understudied cytokine Interleukin (IL)-17D can mediate neutrophil, natural killer (NK) cell and monocyte infiltration in sterile inflammation and cancer. Herein, we show that early immune cell accumulation at the peritoneal site of infection by mouse cytomegalovirus (MCMV) is mediated by IL-17D. Mice deficient in IL-17D or the transcription factor Nuclear factor (erythroid-derived 2)-like 2 (Nrf2), an inducer of IL-17D, featured an early decreased number of innate immune cells at the point of viral entry and were more susceptible to MCMV infection. Interestingly, we were able to artificially induce innate leukocyte infiltration by applying the Nrf2 activator tert-butylhydroquinone (tBHQ), which rendered mice less susceptible to MCMV infection. Our results implicate the Nrf2/IL-17D axis as a sensor of viral infection and suggest therapeutic benefit in boosting this pathway to promote innate antiviral responses

A Multicenter, Long-Term Study on Arrhythmias in Children with Ebstein Anomaly

To assess the prevalence, history, and treatment of arrhythmias, in particular preexcitation and Wolff–Parkinson–White (WPW) syndrome, in patients with Ebstein anomaly (EA) during childhood and adolescence, we performed a multicenter retrospective study of all consecutive live-born patients with EA, diagnosed, and followed by pediatric cardiologists between 1980 and 2005 in The Netherlands. During a follow-up after EA diagnosis of 13 years 3 months (range: 6 days to 28 years 2 months), 16 (17%) of the 93 pediatric EA patients exhibited rhythm disturbances. Nine patients showed arrhythmic events starting as of the neonatal period. Supraventricular tachycardia was noted in 11 patients. One patient died in the neonatal period due to intractable supraventricular tachycardia resulting in heart failure and one patient died at 5 weeks of age most probably due to an arrhythmic event. The 14 surviving patients all show preexcitation, albeit 4 of them intermittently, and all have a right-sided accessory pathway location. Nine patients underwent catheter ablation of an accessory pathway. Only four patients are currently on antiarrhythmic drugs. The 17% prevalence of rhythm disturbances in pediatric EA patients, most commonly supraventricular arrhythmias, is significantly lower than in adult EA patients. Life-threatening rhythm disturbances are not frequent early in life. Symptomatic patients are well treated with radiofrequency catheter ablation

Genome-wide association study identifies three novel genetic markers associated with elite endurance performance

To investigate the association between multiple single-nucleotide polymorphisms (SNPs), aerobic performance and elite endurance athlete status in Russians. By using GWAS approach, we examined the association between 1,140,419 SNPs and relative maximal oxygen consumption rate (VO2max) in 80 international-level Russian endurance athletes (46 males and 34 females). To validate obtained results, we further performed case-control studies by comparing the frequencies of the most significant SNPs (with P<10-5-10-8) between 218 endurance athletes and opposite cohorts (192 Russian controls, 1367 European controls, and 230 Russian power athletes). Initially, six 'endurance alleles' were identified showing discrete associations with •VO2maxboth in males and females. Next, case-control studies resulted in remaining three SNPs (NFIA-AS2 rs1572312, TSHR rs7144481, RBFOX1 rs7191721) associated with endurance athlete status. The C allele of the most significant SNP, rs1572312, was associated with high values of •VO2max(males: P=0.0051; females: P=0.0005). Furthermore, the frequency of the rs1572312 C allele was significantly higher in elite endurance athletes (95.5%) in comparison with non-elite endurance athletes (89.8%, P=0.0257), Russian (88.8%, P=0.007) and European (90.6%, P=0.0197) controls and power athletes (86.2%, P=0.0005). The rs1572312 SNP is located on the nuclear factor I A antisense RNA 2 (NFIA-AS2) gene which is supposed to regulate the expression of the NFIA gene (encodes transcription factor involved in activation of erythropoiesis and repression of the granulopoiesis). Our data show that the NFIA-AS2 rs1572312, TSHR rs7144481 and RBFOX1 rs7191721 polymorphisms are associated with aerobic performance and elite endurance athlete status

What is known about the patient's experience of medical tourism? A scoping review

<p>Abstract</p> <p>Background</p> <p>Medical tourism is understood as travel abroad with the intention of obtaining non-emergency medical services. This practice is the subject of increasing interest, but little is known about its scope.</p> <p>Methods</p> <p>A comprehensive scoping review of published academic articles, media sources, and grey literature reports was performed to answer the question: what is known about the patient's experience of medical tourism? The review was accomplished in three steps: (1) identifying the question and relevant literature; (2) selecting the literature; (3) charting, collating, and summarizing the information. Overall themes were identified from this process.</p> <p>Results</p> <p>291 sources were identified for review from the databases searched, the majority of which were media pieces (<it>n </it>= 176). A further 57 sources were included for review after hand searching reference lists. Of the 348 sources that were gathered, 216 were ultimately included in this scoping review. Only a small minority of sources reported on empirical studies that involved the collection of primary data (<it>n </it>= 5). The four themes identified via the review were: (1) decision-making (e.g., push and pull factors that operate to shape patients' decisions); (2) motivations (e.g., procedure-, cost-, and travel-based factors motivating patients to seek care abroad); (3) risks (e.g., health and travel risks); and (4) first-hand accounts (e.g., patients' experiential accounts of having gone abroad for medical care). These themes represent the most discussed issues about the patient's experience of medical tourism in the English-language academic, media, and grey literatures.</p> <p>Conclusions</p> <p>This review demonstrates the need for additional research on numerous issues, including: (1) understanding how multiple information sources are consulted and evaluated by patients before deciding upon medical tourism; (2) examining how patients understand the risks of care abroad; (3) gathering patients' prospective and retrospective accounts; and (4) the push and pull factors, as well as the motives of patients to participate in medical tourism. The findings from this scoping review and the knowledge gaps it uncovered also demonstrate that there is great potential for new contributions to our understanding of the patient's experience of medical tourism.</p

Surgical repair of transposition of the great arteries in neonates with persistent pulmonary hypertension.

ackground. Pulmonary hypertension due to persistent fetal circulation is rarely associated with transposition of the great arteries and intact ventricular septum. Previous attempts at management of affected neonates using prostaglandin El and balloon atrial septotomy followed by surgical repair have been largely unsuccessful. Methods. Between September 1992 and April 1995, 45 neonates underwent repair of transposition of the great arteries with the arterial switch operation. Two patients (4%) with transposition of the great arteries and intact ventricular septum presented with profound reversed differential desaturation and right-to-left shunting at the level of the ductus arteriosus after balloon atrial septotomy. A diagnosis of persistent pulmonary hypertension was established and both neonates entered an experimental management protocol using inhaled nitric oxide and rapid arterial switch operation. Results. Preoperative hemodynamic stabilization was achieved in 1 patient using 40 parts per million of inhaled nitric oxide, whereas the other required in addition extracorporeal membrane oxygenation for severe biventricular dysfunction. Both underwent successful surgical repair 4 to 5 days after admission, but received postoperatively 1 week of inhaled nitric oxide therapy for persistent pulmonary hypertension. Follow-up echocardiography at 3 months showed good biventricular function and normal geometry of the ventricular septum, suggesting low pulmonary artery pressure, in both. Conclusions. A management protocol using inhaled nitric oxide and extracorporeal membrane oxygenation followed by the arterial switch operation was successfully used in neonates with transposition of the great arteries, intact ventricular septum, and persistent pulmonary hypertension. Wider use of preoperative and postoperative inhaled nitric oxide may improve the surgical outcome of this difficult subset of patients. inhaled nitric oxide, whereas the other required in addition extracorporeal membrane oxygenation for severe biventricular dysfunction. Both underwent successful surgical repair 4 to 5 days after admission, but received postoperatively 1 week of inhaled nitric oxide therapy for persistent pulmonary hypertension. Follow-up echocardiography at 3 months showed good biventricular function and normal geometry of the ventricular septum, suggesting low pulmonary artery pressure, in both. Conclusions. A management protocol using inhaled nitric oxide and extracorporeal membrane oxygenation followed by the arterial switch operation was successfully used in neonates with transposition of the great arteries, intact ventricular septum, and persistent pulmonary hypertension. Wider use of preoperative and postoperative inhaled nitric oxide may improve the surgical outcome of this difficult subset of patients