Influence of beta-blocker therapy on aortic blood flow in patients with bicuspid aortic valve

In patients with bicuspid aortic valve (BAV), beta-blockers (BB) are assumed to slow ascending aorta (AAo) dilation by reducing wall shear stress (WSS) on the aneurysmal segment. The aim of this study was to assess differences in AAo peak velocity and WSS in BAV patients with and without BB therapy. BAV patients receiving BB (BB+, n = 30, age: 47 ± 11 years) or not on BB (BB?, n = 30, age: 46 ± 13 years) and healthy controls (n = 15, age: 43 ± 11 years) underwent 4D flow MRI for the assessment of in vivo aortic 3D blood flow. Peak systolic velocities and 3D WSS were calculated at the anterior and posterior walls of the AAo. Both patient groups had higher maximum and mean WSS relative to the control group (p = 0.001 to p = 0.04). WSS was not reduced in the BB+ group compared to BB? patients in the anterior AAo (maximum: 1.49 ± 0.47 vs. 1.38 ± 0.49 N/m², p = 0.99, mean: 0.76 ± 0.2 vs. 0.74 ± 0.18 N/m², p = 1.00) or posterior AAo (maximum: 1.45 ± 0.42 vs. 1.39 ± 0.58 N/m², p = 1.00; mean: 0.65 ± 0.16 vs. 0.63 ± 0.16 N/m², p = 1.00). AAo peak velocity was elevated in patients compared to controls (p < 0.01) but similar for BB+ and BB? groups (p = 0.42). Linear models identified significant relationships between aortic stenosis severity and increased maximum WSS (β = 0.186, p = 0.007) and between diameter at the sinus of Valsalva and reduced mean WSS (β = ?0.151, p = 0.045). Peak velocity and systolic WSS were similar for BAV patients irrespective of BB therapy. Further prospective studies are needed to investigate the impact of dosage and duration of BB therapy on aortic hemodynamics and development of aortopathy.     

Pattern of distribution of 35 red cell antigens in regular voluntary blood donors of South Gujarat,India

Background

Extended phenotyping is one of the important method of reducing red cell alloimmunisation. Extended phenotyping of red cells from voluntary donors have many uses in addition to its application in population genetics. As there was very little data extended phenotyping on a cohort of Indian Voluntary blood donors this project was undertaken.

Gender‐specific Research on Mental Illness in the Emergency Department: Current Knowledge and Future Directions

Mental illness is a growing, and largely unaddressed, problem for the population and for emergency department (ED) patients in particular. Extensive literature outlines sex and gender differences in mental illness' epidemiology and risk and protective factors. Few studies, however, examined sex and gender differences in screening, diagnosis, and management of mental illness in the ED setting. Our consensus group used the nominal group technique to outline major gaps in knowledge and research priorities for these areas, including the influence of violence and other risk factors on the course of mental illness for ED patients. Our consensus group urges the pursuit of this research in general and conscious use of a gender lens when conducting, analyzing, and authoring future ED‐based investigations of mental illness.     

Direct structural insight into the substrate-shuttling mechanism of yeast fatty acid synthase by electron cryomicroscopy

Yeast fatty acid synthase (FAS) is a 2.6-MDa barrel-shaped multienzyme complex, which carries out cyclic synthesis of fatty acids. By electron cryomicroscopy of single particles we obtained a three-dimensional map of yeast FAS at 5.9-Å resolution. Compared to the crystal structures of fungal FAS, the EM map reveals major differences and new features that indicate a considerably different arrangement of the complex in solution compared to the crystal structures, as well as a high degree of variance inside the barrel. Distinct density regions in the reaction chambers next to each of the catalytic domains fitted the substrate-binding acyl carrier protein (ACP) domain. In each case, this resulted in the expected distance of ∼18 Å from the ACP substrate-binding site to the active site of the catalytic domains. The multiple, partially occupied positions of the ACP within the reaction chamber provide direct structural insight into the substrate-shuttling mechanism of fatty acid synthesis in this large cellular machine.     

Ophthalmoplegia With Migraine in Adults: Is It Ophthalmoplegic Migraine?

Objective.— Ophthalmoplegic migraine (OM) is a rare disorder characterized by recurrent oculomotor nerve palsy in children, following migraine headaches. We report 62 adults, seen consecutively, who developed acute ophthalmoplegia with severe attacks of migraine over a 10-year (1996-2005) period. An overwhelming majority of these patients had an antecedent worsening in severity of migraine headaches, before the ophthalmoplegic attack.
Methods.— Sixty-two patients, aged 15-68 years, with an acute attack of OM underwent detailed clinical, biochemical, and neuroradiological evaluation.
Results.— There were 62 patients with 86 attacks of OM. Whereas 48 patients had a single attack, 14 had 2 or more attacks, fulfilling the International Headache Society criteria for probable and definite OM, respectively. At presentation, isolated abducens, oculomotor, and trochlear nerve involvements were seen in 35 (56.5%), 21 (33.9%), and 5 (8.1%) patients, respectively. One patient had simultaneous involvement of 3rd and 6th nerves. Fifty-one (82.3%) patients exhibited an antecedent worsening in severity of migraine, before developing ophthalmoplegia during (59/95.2%) or within 24 hours (3/4.8%) of a severe migraine attack, respectively. Detailed biochemistry and cranial neuroimaging were normal. No case had any nerve enhancement. Use of steroids hastened recovery ( P  < .05).
Conclusion.— We conclude: (1) OM in adults is characterized by single attacks of ophthalmoplegia in a great majority of patients; and (2) 6th nerve involvement occurs commonly. Our results indicate that moving OM to the chapter on cranial neuralgias in the second edition of the International Headache Classification may be premature, since nerve palsy occurred during a severe migraine attack in all patients.     

Multiplexing Seven miRNA-Based shRNAs to Suppress HIV Replication

Multiplexed miRNA-based shRNAs (shRNA-miRs) could have wide potential to simultaneously suppress multiple genes. Here, we describe a simple strategy to express a large number of shRNA-miRs using minimal flanking sequences from multiple endogenous miRNAs. We found that a sequence of 30 nucleotides flanking the miRNA duplex was sufficient for efficient processing of shRNA-miRs. We inserted multiple shRNAs in tandem, each containing minimal flanking sequence from a different miRNA. Deep sequencing of transfected cells showed accurate processing of individual shRNA-miRs and that their expression did not decrease with the distance from the promoter. Moreover, each shRNA was as functionally competent as its singly expressed counterpart. We used this system to express one shRNA-miR targeting CCR5 and six shRNA-miRs targeting the HIV-1 genome. The lentiviral construct was pseudotyped with HIV-1 envelope to allow transduction of both resting and activated primary CD4 T cells. Unlike one shRNA-miR, the seven shRNA-miR transduced T cells nearly abrogated HIV-1 infection in vitro. Additionally, when PBMCs from HIV-1 seropositive individuals were transduced and transplanted into NOD/SCID/IL-2R γc^−/− mice (Hu-PBL model) efficient suppression of endogenous HIV-1 replication with restoration of CD4 T cell counts was observed. Thus, our multiplexed shRNA appears to provide a promising gene therapeutic approach for HIV-1 infection.     

Illicit stimulant use in a United States heart failure population presenting to the emergency department (from the Acute Decompensated Heart Failure National Registry Emergency Module)

Illicit stimulant drug use may have a profound clinical impact in acute decompensated heart failure (ADHF). The chronic use of cocaine and methamphetamine may lead to overt cardiomyopathy and ADHF. The Acute Decompensated Heart Failure National Registry Emergency Module (ADHERE-EM) collected data on patients presenting to emergency departments with ADHF at 83 geographically dispersed hospitals in the United States. This registry was queried to determine the rate of self-reported illicit drug use in emergency department patients presenting with ADHF and compare these patients with those without illicit drug use. The registry enrolled 11,258 patients with ADHF with drug use data from January 2004 to March 2006. Of these patients, 594 (5.3%) self-reported current or past stimulant drug use. Compared with nonusers, these patients were more likely to be younger (median age 49.7 vs 76.1 years), to be African American (odds ratio 11.9, 95% confidence interval 9.8 to 14.4), and to have left ventricular ejection fractions <40% (odds ratio 3.4, 95% confidence interval 2.8 to 4.2). Admitted users had no difference in mortality (adjusted odds ratio 0.83, 95% confidence interval 0.25 to 2.72) compared with nonusers. In conclusion, data from ADHERE-EM suggest that a clinically important percentage of patients with ADHF report the use of illicit stimulant drugs. Although these patients are younger with a greater degree of LV dysfunction, they did not have greater risk-adjusted mortality.     

Diagnostic dilemma of antineutrophil cytoplasmic antibody seropositivity in human immunodeficiency virus infection

We present a case of a 48-year-old male who was diagnosed and treated for Wegener's granulomatosis on the basis of history, clinical features, computed tomography (CT) and antineutrophil cytoplasmic antibodies (ANCA) positivity. The patient initially improved and later on during course of the disease he was found to be human immunodeficiency virus (HIV) seropositive. The potential pitfalls of cANCA in a HIV-infected patient are discussed.     

Live/Real Time Three‐Dimensional Transthoracic Echocardiographic Assessment of Inferior Vena Cava and Hepatic Vein Thrombosis in Sickle Cell Disease

We describe the value of live/real time three‐dimensional transthoracic echocardiography (3DTTE) over two‐dimensional transthoracic echocardiography (2DTTE) in the assessment of inferior vena cava (IVC) and hepatic vein (HV) obstruction in a patient with sickle cell disease. 3DTTE provided additional information when compared to 2DTTE by (1) identifying the obstructing lesion as a likely thrombus, (2) by providing assessment of anatomical severity of IVC lumen obstruction since the thrombus could be visualized en face also, and (3) identifying an area of increased mobility of a portion of the thrombus suggesting greater risk of embolization. (Echocardiography 2010;27:594‐596)     

Live/Real Time Three‐Dimensional Transesophageal Echocardiographic Findings in Caseous Mitral Annular Calcification

We describe a 77‐year‐old female with hypertrophic cardiomyopathy in whom live/real time three‐dimensional transesophageal echocardiography (3DTEE) provided incremental value over two‐dimensional transthoracic and transesophageal echocardiography (2DTTE, 2DTEE) and three‐dimensional transthoracic echocardiography (3DTTE) in making a more comprehensive assessment and a more confident diagnosis of caseous mitral annular calcification. 3DTEE revealed a portion of the mass to consist of small, multiple, highly echogenic discrete band‐like and punctate areas within a relatively much less echogenic stroma and surrounded by a well defined highly echogenic border. This appearance correlated with the pathological findings of calcific granules/strands located in a liquefied or semiliquefied interior providing a typical toothpaste like appearance. The highly echogenic outer border represented the residual outer portion or rim of the calcific mass which did not undergo liquefaction. These findings on 3DTEE which correlated with the toothpaste like appearance seen at surgery were not visualized on 2DTTE, 2DTEE, and 3DTTE. (Echocardiography 2010;27:1147‐1150)