The Trans-Pacific Partnership Agreement: Looking Ahead to the Next Steps

Pressure has been building for the conclusion of the 12-country Trans-Pacific Partnership (TPP) negotiations. Getting the deal done is important, but the TPP is not just another free trade agreement (FTA). It represents the chance to set a trade agenda for the future across a wide range of topics for countries throughout the Asia-Pacific region. This means that the agreement should not be settled in haste. More importantly, it also means that key decisions need to be reached about broader issues related to the institutional structure of the TPP. These decisions must be made now, before the deal is closed, on issues such as how to create the TPP as a living agreement, the formation of a TPP Secretariat, and the clarification of entry conditions for future members such as the People’s Republic of China (PRC). These choices must be made deliberately and carefully even while officials are struggling with reaching closure on the most highly sensitive issues still remaining in the agreement. It will not be easy, but wise decisions are necessary now to ensure the long-term success of the TPP

The outcome of kidney transplants with multiple renal arteries

BACKGROUND: The use of grafts with multiple renal arteries has been considered a relative contraindication because of the increased incidence of vascular and urologic complications The aim of this study is to determine whether the kidney grafts with multiple arteries have any adverse effect upon post-transplant graft and patient survival. METHODS: We reviewed the records of 225 adult kidney transplants done consecutively at our institution. Twenty-nine patients (12.8%) had grafts with multiple renal arteries. We analyzed the incidence of post-transplant hypertension and vascular complications, mean creatinine levels, patient and graft survival. In 17 cases reconstruction was done as conjoined anastomosis between two arteries of equal size, and in 6 cases as end-to-side anastomosis of smaller arteries to larger arteries. Multiple anastomoses were performed in 6 cases. RESULTS: In one patient postoperative bleeding occurred. Mean systolic blood pressures, creatinine levels at first year and last follow-up and complication rates were all in acceptable ranges. There was no significant difference in graft and patient survival between multiple and single renal artery allografts. CONCLUSION: Although the kidney grafts with multiple renal arteries have been considered a relative contraindication because of the increased risk of complications, in our study allografts with multiple arteries were used successfully in kidney transplantation

Comparison of 5-year progression of retinitis pigmentosa involving the posterior pole among siblings by means of SD-OCT: a retrospective study

The blockchain technology promises to transform finance, money and evengovernments. However, analyses of blockchain applicability and robustness typicallyfocus on isolated systems whose actors contribute mainly by running the consensusalgorithm. Here, we highlight the importance of considering trustless platformswithin the broader ecosystem that includes social and communication networks. Asan example, we analyse the flash-crash observed on 21st June 2017 in the Ethereumplatform and show that a major phenomenon of social coordination led to acatastrophic cascade of events across several interconnected systems. We proposethe concept of “emergent centralisation” to describe situations where a single systembecomes critically important for the functioning of the whole ecosystem, and arguethat such situations are likely to become more and more frequent in interconnectedsocio-technical systems. We anticipate that the systemic approach we propose willhave implications for future assessments of trustless systems and call for the attentionof policy-makers on the fragility of our interconnected and rapidly changing world

Bilateral cystoid macular edema following docetaxel chemotherapy in a patient with retinitis pigmentosa: a case report.

BACKGROUND: Docetaxel is a chemotherapeutic agent of the taxane class of drugs for the treatment of breast cancer. We present a female patient who noted decreased vision after docetaxel treatment. CASE PRESENTATION: A 45-year-old female patient received docetaxel treatment after resection of a breast carcinoma. Funduscopy and optical coherence tomography (OCT) showed cystoid macular edema on both eyes. Dilated funduscopy also showed bone spicule-like pigmented deposits, typical for retinitis pigmentosa. Besides the fundus appearance restricted peripheral vision and scotopic electroretinogram confirmed the diagnosis of retinitis pigmentosa. Chemotherapy was discontinued following a consulation with the oncologist of the patient. After five weeks, visual acuity improved significantly along with decrease of retinal thickness measured by OCT. CONCLUSION: Docetaxel may cause ocular adverse effects such as cystoid macular edema. Ophthalmological examination is warranted for patients with visual complaints during docetaxel chemotherapy

Atrial arrhythmogenicity in aged Scn5a+/∆KPQ mice modeling long QT type 3 syndrome and its relationship to Na+ channel expression and cardiac conduction

Recent studies have reported that human mutations in Nav1.5 predispose to early age onset atrial arrhythmia. The present experiments accordingly assess atrial arrhythmogenicity in aging Scn5a+/∆KPQ mice modeling long QT3 syndrome in relationship to cardiac Na+ channel, Nav1.5, expression. Atrial electrophysiological properties in isolated Langendorff-perfused hearts from 3- and 12-month-old wild type (WT), and Scn5a+/∆KPQ mice were assessed using programmed electrical stimulation and their Nav1.5 expression assessed by Western blot. Cardiac conduction properties were assessed electrocardiographically in intact anesthetized animals. Monophasic action potential recordings demonstrated increased atrial arrhythmogenicity specifically in aged Scn5a+/ΔKPQ hearts. These showed greater action potential duration/refractory period ratios but lower atrial Nav1.5 expression levels than aged WT mice. Atrial Nav1.5 levels were higher in young Scn5a+/ΔKPQ than young WT. These levels increased with age in WT but not Scn5a+/ΔKPQ. Both young and aged Scn5a+/ΔKPQ mice showed lower heart rates and longer PR intervals than their WT counterparts. Young Scn5a+/ΔKPQ mice showed longer QT and QTc intervals than young WT. Aged Scn5a+/ΔKPQ showed longer QRS durations than aged WT. PR intervals were prolonged and QT intervals were shortened in young relative to aged WT. In contrast, ECG parameters were similar between young and aged Scn5a+/ΔKPQ. Aged murine Scn5a+/ΔKPQ hearts thus exhibit an increased atrial arrhythmogenicity. The differing Nav1.5 expression and electrocardiographic indicators of slowed cardiac conduction between Scn5a+/ΔKPQ and WT, which show further variations associated with aging, may contribute toward atrial arrhythmia in aged Scn5a+/ΔKPQ hearts

Bactericidal activity of human eosinophilic granulocytes against Escherichia coli

Eosinophils participate in allergic inflammation and may have roles in the bodys defense against helminthic infestation. Even under noninflammatory conditions, eosinophils are present in the mucosa of the large intestine, where large numbers of gram-negative bacteria reside. Therefore, roles for eosinophils in host defenses against bacterial invasion are possible. In a system for bacterial viable counts, the bactericidal activity of eosinophils and the contribution of different cellular antibacterial systems against Escherichia coli were investigated. Eosinophils showed a rapid and efficient killing of E. coli under aerobic conditions, whereas under anaerobic conditions bacterial killing decreased dramatically. In addition, diphenylene iodonium chloride (DPI), an inhibitor of the NADPH oxidase and thereby of superoxide production, also significantly inhibited bacterial killing. The inhibitor of nitric oxide (NO) production L-N5-(1-iminoethyl)-ornithine dihydrochloride did not affect the killing efficiency, suggesting that NO or derivatives thereof are of minor importance under the experimental conditions used. To investigate the involvement of superoxide and eosinophil peroxidase (EPO) in bacterial killing, EPO was blocked by azide. The rate of E. coli killing decreased significantly in the presence of azide, whereas addition of DPI did not further decrease the killing, suggesting that superoxide acts in conjunction with EPO. Bactericidal activity was seen in eosinophil extracts containing granule proteins, indicating that oxygen-independent killing may be of importance as well. The findings suggest that eosinophils can participate in host defense against gram-negative bacterial invasion and that oxygen-dependent killing, i.e., superoxide acting in conjunction with EPO, may be the most important bactericidal effector function of these cells

Cardiac sodium channelopathies

Cardiac sodium channel are protein complexes that are expressed in the sarcolemma of cardiomyocytes to carry a large inward depolarizing current (INa) during phase 0 of the cardiac action potential. The importance of INa for normal cardiac electrical activity is reflected by the high incidence of arrhythmias in cardiac sodium channelopathies, i.e., arrhythmogenic diseases in patients with mutations in SCN5A, the gene responsible for the pore-forming ion-conducting α-subunit, or in genes that encode the ancillary β-subunits or regulatory proteins of the cardiac sodium channel. While clinical and genetic studies have laid the foundation for our understanding of cardiac sodium channelopathies by establishing links between arrhythmogenic diseases and mutations in genes that encode various subunits of the cardiac sodium channel, biophysical studies (particularly in heterologous expression systems and transgenic mouse models) have provided insights into the mechanisms by which INa dysfunction causes disease in such channelopathies. It is now recognized that mutations that increase INa delay cardiac repolarization, prolong action potential duration, and cause long QT syndrome, while mutations that reduce INa decrease cardiac excitability, reduce electrical conduction velocity, and induce Brugada syndrome, progressive cardiac conduction disease, sick sinus syndrome, or combinations thereof. Recently, mutation-induced INa dysfunction was also linked to dilated cardiomyopathy, atrial fibrillation, and sudden infant death syndrome. This review describes the structure and function of the cardiac sodium channel and its various subunits, summarizes major cardiac sodium channelopathies and the current knowledge concerning their genetic background and underlying molecular mechanisms, and discusses recent advances in the discovery of mutation-specific therapies in the management of these channelopathies

Long-Term Follow-Up of a Pediatric Cohort With Short QT Syndrome

ObjectivesThe purpose of this study was to define the clinical characteristics and long-term follow-up of pediatric patients with short QT syndrome (SQTS).BackgroundSQTS is associated with sudden cardiac death. The clinical characteristics and long-term prognosis in young patients have not been reported.MethodsThis was an international case series involving 15 centers. Patients were analyzed for electrocardiography characteristics, genotype, clinical events, Gollob score, and efficacy of medical or defibrillator (implantable cardioverter-defibrillator [ICD]) therapy. To assess the possible prognostic value of the Gollob score, we devised a modified Gollob score that excluded clinical events from the original score.ResultsTwenty-five patients 21 years of age or younger (84% males, median age: 15 years, interquartile range: 9 to 18 years) were followed up for 5.9 years (interquartile range: 4 to 7.1 years). Median corrected QT interval for heart rate was 312 ms (range: 194 to 355 ms). Symptoms occurred in 14 (56%) of 25 patients and included aborted sudden cardiac death in 6 patients (24%) and syncope in 4 patients (16%). Arrhythmias were common and included atrial fibrillation (n = 4), ventricular fibrillation (n = 6), supraventricular tachycardia (n = 1), and polymorphic ventricular tachycardia (n = 1). Sixteen patients (84%) had a familial or personal history of cardiac arrest. A gene mutation associated with SQTS was identified in 5 (24%) of 21 probands. Symptomatic patients had a higher median modified Gollob score (excluding points for clinical events) compared with asymptomatic patients (5 vs. 4, p = 0.044). Ten patients received medical treatment, mainly with quinidine. Eleven of 25 index cases underwent ICD implantation. Two patients had appropriate ICD shocks. Inappropriate ICD shocks were observed in 64% of patients.ConclusionsSQTS is associated with aborted sudden cardiac death among the pediatric population. Asymptomatic patients with a Gollob score of <5 remained event free, except for an isolated episode of supraventricular tachycardia, over an average 6-year follow-up. A higher modified Gollob score of 5 or more was associated with the likelihood of clinical events. Young SQTS patients have a high rate of inappropriate ICD shocks