Quadricuspid aortic valve by using intraoperative transesophageal echocardiography

Quadricuspid aortic valve is a rare congenital malformation of the aortic valve. Its diagnosis is often missed even with the use of transthoracic echocardiogram. Many of these patients progress to aortic incompetence later in life, hence requiring surgical intervention

Quadricuspid aortic valve not discovered by transthoracic echocardiography

BACKGROUND: Quadricuspid aortic valve is a rare congenital heart defect. Several different anatomical variations of a quadricuspid aortic valve has been described and aortic regurgitation is the predominant valvular dysfunction associated with quadricuspid aortic valve. CASE PRESENTATION: A 68-year-old woman presented with almost a years history of increasing dyspnoea on exertion. The patient have had two previous transthoracic echocardiographic exams in the last six years and they had only documented moderate aortic regurgitation. Transoesophageal echocardiography displayed a rare case of quadricuspid aortic valve with three cusps of equal size and one larger cusp. The malformation was associated with severe aortic regurgitation. CONCLUSION: Liberal use of transoesophageal echocardiography is often warranted if optimal display of valvular morphology is desired

Type F congenital quadricuspid aortic valve: A very rare case diagnosed by 3-dimenional transoesophageal echocardiography

Congenital quadricuspid aortic valve (QAV) is a rare cardiac anomaly. Several different anatomical variations of a quadricuspid aortic valve have been described. Aortic regurgitation is the predominant valvular dysfunction associated with QAV and patients tend to present in their 5(th) or 6(th) decade of life. This anomaly is rarely picked up by transthoracic echocardiogram (TTE). A comprehensive transoesophageal echocardiography (TOE) study is more likely to diagnose it. We describe a very rare type of QAV - Type F in a 52-year-old lady who presented with symptoms of shortness of breath and pre-syncope. We include TOE images and intra-operative valve images

Nuclear and membrane expression of the angiogenesis regulator delta-like ligand 4 (DLL4) in normal and malignant human tissues.

AIMS: Delta-like ligand 4 (DLL4) is one of five known Notch ligands in mammals and interacts predominantly with Notch 1. DLL4 is induced by vascular endothelial growth factor (VEGF) and acts downstream of VEGF as a 'brake' on VEGF-induced vessel growth, forming an autoregulatory negative feedback loop inactivating VEGF. This action was believed to occur only in vascular development, raising hopes that DLL4 could be a specific drug target for controlling vessel growth in tumours and other pathological conditions. Our aim was to pursue this by raising a monoclonal antibody to the internal domain of DLL4 and assess its distribution in normal and malignant tissues in comparison with antibodies against the external domain of DLL4. METHODS AND RESULTS: The anti-DLL4 monoclonal antibody was raised using conventional mouse hybridoma techniques. The antibody has been fully characterized by Western blotting and transfectant immunostaining. It has also been comprehensively compared with other antibodies against both the internal and external domains of DLL4. The antigen is widely expressed on human tissues not only on endothelium but also on epithelium and stromal cells. Indeed, in our comprehensive survey only pulmonary alveoli failed to express DLL4. Of a wide range of malignancies, most also expressed DLL4 on tumour cells with a predominantly cytoplasmic pattern, although a number also displayed nuclear positivity. CONCLUSIONS: Contrary to previous beliefs, DLL4 is widely distributed in tissues other than vessels including many malignancies. Furthermore, the molecule is internalized on binding its receptor and often transported to the nucleus. These findings raise many interesting possibilities for further study of DLL4 and its potential as a therapeutic target

A novel series solution to the renormalization group equation in QCD

Recently, the QCD renormalization group (RG) equation at higher orders in MS-like renormalization schemes has been solved for the running coupling as a series expansion in powers of the exact 2-loop order coupling. In this work, we prove that the power series converges to all orders in perturbation theory. Solving the RG equation at higher orders, we determine the running coupling as an implicit function of the 2-loop order running coupling. Then we analyze the singularity structure of the higher order coupling in the complex 2-loop coupling plane. This enables us to calculate the radii of convergence of the series solutions at the 3- and 4-loop orders as a function of the number of quark flavours $n_{\rm f}$. In parallel, we discuss in some detail the singularity structure of the ${\bar{\rm MS}}$ coupling at the 3- and 4-loops in the complex momentum squared plane for $0\leq n_{\rm f} \leq 16$. The correspondence between the singularity structure of the running coupling in the complex momentum squared plane and the convergence radius of the series solution is established. For sufficiently large $n_{\rm f}$ values, we find that the series converges for all values of the momentum squared variable $Q^2=-q^2>0$. For lower values of $n_{\rm f}$, in the ${\bar{\rm MS}}$ scheme, we determine the minimal value of the momentum squared $Q_{\rm min}^2$ above which the series converges. We study properties of the non-power series corresponding to the presented power series solution in the QCD Analytic Perturbation Theory approach of Shirkov and Solovtsov. The Euclidean and Minkowskian versions of the non-power series are found to be uniformly convergent over whole ranges of the corresponding momentum squared variables.Comment: 29 pages,LateX file, uses IOP LateX class file, 2 figures, 13 Tables. Formulas (4)-(7) and Table 1 were relegated to Appendix 1, some notations changed, 2 footnotes added. Clarifying discussion added at the end of Sect. 3, more references and acknowledgments added. Accepted for publication in Few-Body System

Heterocyclic scaffolds as promising anticancer agents against tumours of the central nervous system: Exploring the scope of indole and carbazole derivatives

Tumours of the central nervous system are intrinsically more dangerous than tumours at other sites, and in particular, brain tumours are responsible for 3% of cancer deaths in the UK. Despite this, research into new therapies only receives 1% of national cancer research spend. The most common chemotherapies are temozolomide, procarbazine, carmustine, lomustine and vincristine, but because of the rapid development of chemoresistance, these drugs alone simply aren’t sufficient for long-term treatment. Such poor prognosis of brain tumour patients prompted us to research new treatments for malignant glioma, and in doing so, it became apparent that aromatic heterocycles play an important part, especially the indole, carbazole and indolocarbazole scaffolds. This review highlights compounds in development for the treatment of tumours of the central nervous system which are structurally based on the indole, carbazole and indolocarbazole scaffolds, under the expectation that it will highlight new avenues for research for the development of new compounds to treat these devastating neoplasms

Rabbit Knee Joint Biomechanics: Motion Analysis and Modeling of Forces during Hopping

Although the rabbit hindlimb has been commonly used as an experimental animal model for studies of osteoarthritis, bone growth and fracture healing, the in vivo biomechanics of the rabbit knee joint have not been quantified. The purpose of this study was to investigate the kinematic and kinetic patterns during hopping of the adult rabbit, and to develop a model to estimate the joint contact force distribution between the tibial plateaus. Force platform data and three-dimensional motion analysis using infrared markers mounted on intracortical bone pins were combined to calculate the knee and ankle joint intersegmental forces and moments. A statically determinate model was developed to predict muscle, ligament and tibiofemoral joint contact forces during the stance phase of hopping. Variations in hindlimb kinematics permitted the identification of two landing patterns, that could be distinguished by variations in the magnitude of the external knee abduction moment. During hopping, the prevalence of an external abduction moment led to the prediction of higher joint contact forces passing through the lateral compartment as compared to the medial compartment of the knee joint. These results represent critical data on the in vivo biomechanics of the rabbit knee joint, which allow for comparisons to both other experimental animal models and the human knee, and may provide further insight into the relationships between mechanical loading, osteoarthritis, bone growth, and fracture healing

Is comorbidity in adolescence a predictor for adult low back pain? A prospective study of a young population

BACKGROUND: It has previously been shown that low back pain (LBP) often presents already in the teenage years and that previous LBP predicts future LBP. It is also well documented that there is a large degree of comorbidity associated with LBP, both in adolescents and adults. The objective of this study is to gain a deeper insight into the etiology of low back pain and to possibly develop a tool for early identification of high-risk groups. This is done by investigating whether different types of morbidity in adolescence are associated with LBP in adulthood. METHODS: Almost 10,000 Danish twins born between 1972 and 1982 were surveyed by means of postal questionnaires in 1994 and again in 2002. The questionnaires dealt with various aspects of general health, including the prevalence of LBP, classified according to number of days affected during the previous year (0, 1–7, 8–30, >30). The predictor variables used in this study were LBP, headache, asthma and atopic disease at baseline; the outcome variable was persistent LBP (>30 days during the past year) at follow-up. Associations between morbidity in 1994 and LBP in 2002 were investigated. RESULTS: LBP, headache and asthma in adolescence were positively associated with future LBP. There was no association between atopic disease and future LBP. Individuals with persistent LBP at baseline had an odds ratio of 3.5 (2.8–4.5) for future LBP, while the odds ratio for those with persistent LBP, persistent headache and asthma was 4.5 (2.5–8.1). There was a large degree of clustering of these disorders, but atopic disease was not part of this pattern. CONCLUSION: Young people from 12 to 22 years of age with persistent LBP during the previous year have an odds ratio of 3.5 persistent LBP eight years later. Both headache and asthma are also positively associated with future LBP and there is a large clustering of LBP, headache and asthma in adolescence

Elimination of visceral leishmaniasis in the Indian subcontinent: a comparison of predictions from three transmission models.

We present three transmission models of visceral leishmaniasis (VL) in the Indian subcontinent (ISC) with structural differences regarding the disease stage that provides the main contribution to transmission, including models with a prominent role of asymptomatic infection, and fit them to recent case data from 8 endemic districts in Bihar, India. Following a geographical cross-validation of the models, we compare their predictions for achieving the WHO VL elimination targets with ongoing treatment and vector control strategies. All the transmission models suggest that the WHO elimination target (<1 new VL case per 10,000 capita per year at sub-district level) is likely to be met in Bihar, India, before or close to 2020 in sub-districts with a pre-control incidence of 10 VL cases per 10,000 people per year or less, when current intervention levels (60% coverage of indoor residual spraying (IRS) of insecticide and a delay of 40days from onset of symptoms to treatment (OT)) are maintained, given the accuracy and generalizability of the existing data regarding incidence and IRS coverage. In settings with a pre-control endemicity level of 5/10,000, increasing the effective IRS coverage from 60 to 80% is predicted to lead to elimination of VL 1-3 years earlier (depending on the particular model), and decreasing OT from 40 to 20days to bring elimination forward by approximately 1year. However, in all instances the models suggest that L. donovani transmission will continue after 2020 and thus that surveillance and control measures need to remain in place until the longer-term aim of breaking transmission is achieved