Implications of High-Frequency Trading for Security Markets

High frequency trading (HFT) has grown substantially in recent years, due to fast-paced technological developments and their rapid uptake, particularly in equity markets. This paper investigates how HFT could evolve and, by developing a robust understanding of its effects, to identify potential risks and opportunities that it could present in terms of financial stability and other market outcomes such as volatility, liquidity, price efficiency and price discovery. Despite commonly held negative perceptions, the available evidence indicates that HFT and algorithmic trading (AT) may have several beneficial effects on markets. However, they may cause instabilities in financial markets in specific circumstances. Carefully chosen regulatory measures are needed to address concerns in the shorter term. However, further work is needed to inform policies in the longer term, particularly in view of likely uncertainties and lack of data. This will be vital to support evidence-based regulation in this controversial and rapidly evolving field

The role of 17β-estradiol and estrogen receptors in regulation of Ca(2+) channels and mitochondrial function in cardiomyocytes

Numerous epidemiological, clinical, and animal studies showed that cardiac function and manifestation of cardiovascular diseases (CVDs) are different between males and females. The underlying reasons for these sex differences are definitely multifactorial, but major evidence points to a causal role of the sex steroid hormone 17β-estradiol (E2) and its receptors (ER) in the physiology and pathophysiology of the heart. Interestingly, it has been shown that cardiac calcium (Ca(2+)) ion channels and mitochondrial function are regulated in a sex-specific manner. Accurate mitochondrial function and Ca(2+) signaling are of utmost importance for adequate heart function and crucial to maintaining the cardiovascular health. Due to the highly sensitive nature of these processes in the heart, this review article highlights the current knowledge regarding sex dimorphisms in the heart implicating the importance of E2 and ERs in the regulation of cardiac mitochondrial function and Ca(2+) ion channels, thus the contractility. In particular, we provide an overview of in-vitro and in-vivo studies using either E2 deficiency; ER deficiency or selective ER activation, which suggest that E2 and ERs are strongly involved in these processes. In this context, this review also discusses the divergent E2-responses resulting from the activation of different ER subtypes in these processes. Detailed understanding of the E2 and ER-mediated molecular and cellular mechanisms in the heart under physiological and pathological conditions may help to design more specifically targeted drugs for the management of CVDs in men and women

Epidemiology of female reproductive cancers in Iran: Results of the gholestan population-based cancer registry

Background: Malignancies of the female reproductive tract are estimated to be the third most common group of cancers in women. Objectives: We here aimed to present their epidemiological features in Golestan provincelocated in Northeast of Iran. Materials and Methods: Data on primary female reproductive cancers diagnosed between 2004-2010 were obtained from Golestan Population-based Cancer Registry (GPCR). CanReg-4 and SPSS software were used for data entry and analysis. Age standardized incidence rates (ASR) (per 100,000 person-years) were calculated using the world standard population. Poisson regression analysis was used to compare incidence rates. P-values of less than 0.05 were considered as significant. Results: A total of 6,064 cancer cases were registered in Golestan females in the GPCR during 2004-2010, of which 652 cases (11%) were female reproductive cancers. Cancers of the ovary (ASR=6.03) and cervix (ASR=4.97) were the most common. We found significant higher rates in females living in cities than in villages. Our results showed a rapid increase in age specific incidence rates of female reproductive cancers at the age of 30 years. Conclusions: We found significant higher rates of female reproductive cancers among residents of cities than villages. Differences in the prevalence of risk factors including reproductive behavior between the two populations may partly explain such diversity. Our results also showed a rapid increase in incidence rates of these cancers in young age females. Further studies are warranted to determine risk factors of female reproductive cancers in our population

Treatment of Steroid and Cyclosporine-Resistant Idiopathic Nephrotic Syndrome in Children

Steroid-resistant nephrotic syndrome (SRNS) in children carries a significant risk of progression to end-stage renal failure (ESRF). We report a two-step protocol adapted in children with SRNS. Thirty-seven SRNS were treated with cyclosporine A (CyA) in association with prednisolone (alternate day) for 6 months (first-step treatment). Twelve patients (32.4%) went into complete remission, and 2 (5.4%) got partial remission. The other 23 cases who were steroid and CyA resistant entered a second-step treatment with withdrawing steroids, with CyA (5 mg/kg/day) in association with mycophenolate mofetil (MMF) 30 mg/kg/day for 6 months. Complete remission was observed in 11 cases (47.82%) and partial remission in 2 cases (8.7%). After two steps of treatment, 27/37 children went into total remission. In steroid and CyA-resistant INS, the association of MMF with CyA was able to induce remission in about half cases without relevant side effects

Editorial: Sexual dimorphism in biomedical research and its therapeutic implications

Metabolic health: pathophysiological trajectories and therap

Cardiomyocyte-specific estrogen receptor alpha increases angiogenesis, lymphangiogenesis and reduces fibrosis in the female mouse heart post-myocardial infarction

Experimental studies showed that 17{beta}-estradiol (E2) and activated Estrogen Receptors (ER) protect the heart from ischemic injury. However, the underlying molecular mechanisms are not well understood. To investigate the role of ER{alpha} in cardiomyocytes in the setting of myocardial ischemia, we generated transgenic mice with cardiomyocyte-specific overexpression of ER-{alpha} (ER{alpha}-OE) and subjected them to Myocardial Infarction (MI). At the basal level, female and male ER{alpha}-OE mice showed increased Left Ventricular (LV) mass, LV volume and cardiomyocyte length. Two weeks after MI, LV volume was significantly increased and LV wall thickness decreased in female and male WT-mice and male ER{alpha}-OE, but not in female ER{alpha}-OE mice. ER{alpha}-OE enhanced expression of angiogenesis and lymphangiogenesis markers (Vegf, Lyve-1), and neovascularization in the peri-infarct area in both sexes. However, attenuated level of fibrosis and higher phosphorylation of JNK signaling pathway could be detected only in female ER{alpha}-OE after MI. In conclusion, our study indicates that ER{alpha} protects female mouse cardiomyocytes from the sequelae of ischemia through induction of neovascularization in a paracrine fashion and impaired fibrosis, which together may contribute to the attenuation of cardiac remodelling

Treatment of Complicated Henoch-Schönlein Purpura with Mycophenolate Mofetil: A Retrospective Case Series Report

Background. Henoch-Schönlein purpura (HSP) is the most common childhood vasculitis with an incidence of approximately 10 per 100 000 children. There is some evidence to support steroid therapy in the treatment of severe abdominal pain, severe nephritis, and central nervous system involvement. However, the routine use of corticosteroids is controversial. Frequent relapses, lack of response to steroid, steroid dependency, and steroid side effects may occur in some patients. Mycophenolate mofetil (MMF) gains increasing popularity in the treatment of autoimmune disorders, but hitherto, the available evidence to support the use of MMF in HSP is limited to some case study reports. Case Presentation. We report six children with HSP who failed to respond to systemic steroid therapy, whereas MMF successfully treated the manifestations of the disease. Conclusion. The manifestations of HSP disappeared mainly during the first week of treatment with MMF and all the patients were in a complete remission at the end and after discontinuation of the therapy. In our experience, MMF appeared to be safe and effective for the maintenance of remission in the HSP patients

Alteration Pattern of Taste Perception After Bariatric Surgery: a Systematic Review of Four Taste Domains

Background: Efforts continue to understand the underlying mechanism of weight loss after bariatric surgery. Taste perception has shown to be a contributing factor. However, the alteration pattern in different taste domains and among bariatric procedures has not been sufficiently investigated. Objectives: To study the alteration pattern in the perception of four taste domains after different bariatric procedures. Settings: Private Research Institute, USA. Methods: A systematic review was conducted to pool available data in the literature on post-operative changes in the perception of sensitivity to four taste domains after Roux-en-Y gastric bypass (RYGB), laparoscopic sleeve gastrectomy (LSG), and adjustable gastric banding (AGB). Results: Our study showed that bariatric surgery is associated with significant change in sensitivity to all four taste domains especially salt taste, sweetness, and sourness. LSG patients showed an increased sensitivity to all four taste domains. However, RYGB patients had a variable alteration pattern of taste perception but more commonly a decreased sensitivity to sweetness and an increased sensitivity to salt taste and sourness. Additionally, AGB patients had a decreased sensitivity to sweetness, salt taste, and sourness. Conclusion: Bariatric surgery is associated with taste change in a way which results in less preference for high-calorie food and possibly reduced calorie intake. This may explain one of the mechanisms by which bariatric surgery produces weight loss. However, data are heterogeneous, the potential effect dilutes over time, and the alteration varies significantly between different procedures. © 2019, Springer Science+Business Media, LLC, part of Springer Nature

Remote controlling of CAR-T cells and toxicity management: Molecular switches and next generation CARs

Cell-based immunotherapies have been selected for the front-line cancer treatment approaches. Among them, CAR-T cells have shown extraordinary effects in hematologic diseases including chemotherapy-resistant acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL), and non-Hodgkin lymphoma (NHL). In this approach, autologous T cells isolated from the patient's body genetically engineered to express a tumor specific synthetic receptor against a tumor antigen, then these cells expanded ex vivo and re-infusion back to the patient body. Recently, significant clinical response and high rates of complete remission of CAR T cell therapy in B-cell malignancies led to the approval of Kymriah and Yescarta (CD19-directed CAR-T cells) were by FDA for treatment of acute lymphoblastic leukemia and diffuse large B-cell lymphoma. Despite promising therapeutic outcomes, CAR T cells also can elicit the immune-pathologic effects, such as Cytokine Release Syndrome (CRS), Tumor Lysis Syndrome (TLS), and on-target off-tumor toxicity, that hampered its application. Ineffective control of these highly potent synthetic cells causes discussed potentially life-threatening toxicities, so researchers have developed several mechanisms to remote control CAR T cells. In this paper, we briefly review the introduced toxicities of CAR-T cells, then describe currently existing control approaches and review their procedure, pros, and cons. © 2021 The Author

Molecular mechanism regulating myosin and cardiac functions by ELC

The essential myosin light chain (ELC) is involved in modulation of force generation of myosin motors and cardiac contraction, while its mechanism of action remains elusive. We hypothesized that ELC could modulate myosin stiffness which subsequently determines its force production and cardiac contraction. We therefore generated heterologous transgenic mouse (TgM) strains with cardiomyocyte-specific expression of ELC with human ventricular ELC (hVLC-1; TgM(hVLC-1)) or E56G-mutated hVLC-1 (hVLC-1(E56G); TgM(E56G)). hVLC-1 or hVLC-1(E56G) expression in TgM was around 39% and 41%, respectively of total VLC-1. Laser trap and in vitro motility assays showed that stiffness and actin sliding velocity of myosin with hVLC-1 prepared from TgM(hVLC-1) (1.67pN/nm and 2.3{my}m/s, respectively) were significantly higher than myosin with hVLC-1(E56G) prepared from TgM(E56G) (1.25pN/nm and 1.7{my}m/s, respectively) or myosin with mouse VLC-1 (mVLC-1) prepared from C57/BL6 (1.41 pN/nm and 1.5+-0.03 {my}m/s, respectively). Maximal left ventricular pressure development of isolated perfused hearts in vitro prepared from TgM(hVLC-1) (80.0mmHg) were significantly higher than hearts from TgM(E56G) (66.2mmHg) or C57/BL6 (59.3+-3.9 mmHg). These findings show that ELCs decreased myosin stiffness, in vitro motility, and thereby cardiac functions in the order hVLC-1 > hVLC-1(E56G) ≈ mVLC-1. They also suggest a molecular pathomechanism of cardiomyopathies caused by hVLC-1 mutations