Associations of Cardiac Structure with Obesity, Blood Pressure, Inflammation, and Insulin Resistance in African-American Adolescents

To determine if obesity, blood pressure (BP), markers of inflammation, and insulin resistance are associated with cardiac structure in African-American adolescents, a cross–sectional study was performed on a cohort oversampled for high BP and obesity. Measurements included the following: anthropometrics, BP, homeostasis model assessment (HOMA) to assess insulin resistance, high-sensitivity C-reactive protein, and plasma adipokines (adiponectin, interleukin-6, plasminogen activator inhibitor-1). Echocardiogram measurements were left-ventricular mass index (LVMI) (g/m^2.7), LV relative wall thickness (LVRWT), left-atrial diameter index [LADI (mm/m)], and LV diastolic time intervals. LADI (r ² = 0.25) was associated with body mass index (BMI) systolic BP (SBP) and female sex. LVMI (r ² = 0.35) variation was associated with BMI SBP, heart rate, age, and male sex. LVRWT (r ² = 0.05) was associated with HOMA. Tissue diastolic intervals were not associated with any risk factor. Inflammatory markers and adipokines were associated with BMI but were not independently associated with any echocardiographic measures. In African-American adolescents, BMI and SBP, but not inflammatory markers or adipokines, are important correlates of LA size and LVM.     

Effects of camber on wheeling efficiency in the experienced and inexperienced wheelchair user

The objective of this study was to determine whether energy costs differed between 0 degrees , 3 degrees , and 6 degrees of camber during steady state overground wheeling. Three subject groups were examined: experienced wheelchair users with disabilities (thoracic lesion level 6 and below), nondisabled individuals with manual wheeling experience, and nondisabled individuals with no manual wheeling experience. Heart rate, rating of perceived exertion, visual analog scale for comfort, and a user preference questionnaire were collected for all subjects. Expired gas analysis data were collected for the group with disabilities. No statistically significant differences emerged in respiratory measures for camber angle or group. A camber of 6 degrees was most preferred in terms of stability on a side slope, hand comfort on the pushrims, maneuverability, and overall preference. Rear-wheel camber angle did not affect the energy expenditure of manual wheelchair propulsion, as measured by cardiopulmonary means. The individual manual wheelchair user's perceived level of comfort should be the determining factor in rear-wheel camber selection.     

Priority actions for the non-communicable disease crisis

The UN High-Level Meeting on Non-Communicable Diseases (NCDs) in September, 2011, is an unprecedented opportunity to create a sustained global movement against premature death and preventable morbidity and disability from NCDs, mainly heart disease, stroke, cancer, diabetes, and chronic respiratory disease. The increasing global crisis in NCDs is a barrier to development goals including poverty reduction, health equity, economic stability, and human security. The Lancet NCD Action Group and the NCD Alliance propose five overarching priority actions for the response to the crisis--leadership, prevention, treatment, international cooperation, and monitoring and accountability--and the delivery of five priority interventions--tobacco control, salt reduction, improved diets and physical activity, reduction in hazardous alcohol intake, and essential drugs and technologies. The priority interventions were chosen for their health effects, cost-effectiveness, low costs of implementation, and political and financial feasibility. The most urgent and immediate priority is tobacco control. We propose as a goal for 2040, a world essentially free from tobacco where less than 5% of people use tobacco. Implementation of the priority interventions, at an estimated global commitment of about US$9 billion per year, will bring enormous benefits to social and economic development and to the health sector. If widely adopted, these interventions will achieve the global goal of reducing NCD death rates by 2% per year, averting tens of millions of premature deaths in this decade.     

The nonreplicating smallpox candidate vaccines defective vaccinia Lister (dVV-L) and modified vaccinia Ankara (MVA) elicit robust long-term protection

Current smallpox vaccines are live vaccinia viruses that replicate in the vaccinee inducing immunity against the deadly disease smallpox. Replication resulting in virus spread within the host, however, is the major cause of severe postvaccinal adverse events. Therefore, attenuated strains such as modified vaccinia Ankara (MVA) or LC16m8 are candidates as next generation vaccines. These strains are usually grown in primary cells in which mass production is difficult and have an unknown protective potential in humans. Proven vaccine strains of defined origin and modern production techniques are therefore desirable. In this study, defective vaccinia virus (dVV) lacking a gene essential for replication (derived from the Lister vaccine in a complementing cell line) was compared with the Wyeth smallpox vaccine strain and with MVA in mouse animal models using cowpox and ectromelia virus challenge. Similar to MVA, prime-boost immunizations with defective vaccinia induced robust long-term immunity, suggesting it as a promising next generation smallpox vaccine.     

Immunoglobulin mimicry by Hepatitis C Virus envelope protein E2

Hepatitis C virus (HCV) establishes persistent infection in the majority of infected individuals. The currently accepted hypothesis of immune evasion by antigenic variation in hypervariable region 1 (HVR1) of glycoprotein E2 does not however, explain the lack of subsequent immune recognition. Here, we show that the N-terminal region of E2 is antigenically and structurally similar to human immunoglobulin (Ig) variable domains. E2 is recognized by anti-human IgG antibodies and also possesses common amino acid (aa) sequence features of the conserved v-gene framework regions of human Ig light chains in particular but also heavy chains and T cell receptors. Using a position specific scoring system, the degree of similarity of HVR1 to Ig types correlated with immune escape and persistence in humans and experimentally infected chimpanzees. We propose a unique role for threshold levels of Ig molecular mimicry in HCV biology that not only advances our concept of viral immune escape and persistent infection but also provides insight into host-dependent disease patterns.     

Fine-needle aspiration cytology of pseudoangiomatous stromal hyperplasia of the breast

Pseudoangiomatous stromal hyperplasia (PASH) is an uncommon lesion usually found in premenopausal women. Histologically, it is characterized by complex, anatomosing, empty slit-like spaces in a dense collagenous stroma. These pseudoangiomatous spaces are lined by monomorphic spindle cells of myofibroblastic differentiation. Cytological features of PASH are rarely discussed and reported, and may pose diagnostic challenge to surgical pathologists. Two cases of PASH are reported with emphasis on the FNAC features and cytologic differentiation from other benign fibroepithelial lesions.     

Endothelin-1 expression correlates with atypical histological features in mammary phyllodes tumours

BACKGROUND AND AIMS: Endothelin-1 expression is increased in infiltrating duct carcinoma and is associated with larger tumour size, higher histological grade and lymphovascular permeation. This has not been evaluated in phyllodes tumours, which are uncommon fibroepithelial lesions with potential for local recurrences or distant metastasis. While the grading of phyllodes tumours depends on a combination of histological parameters, prediction of their behaviour remains difficult. METHOD: A large series of 461 phyllodes tumours (291 benign, 115 borderline malignant and 55 frankly malignant) were evaluated for endothelin-1 expression in both the epithelial cells and stromal cells by immunohistochemistry; results were correlated with the tumour grade. RESULTS: For benign phyllodes tumours, the epithelial staining of endothelin was negative, weak, moderate and strong in 6%, 26%, 15% and 53% of cases respectively; results were 4%, 18%, 19% and 59% respectively for borderline and 6%, 18%, 6% and 70% respectively for frankly malignant tumours. For the stromal staining, the negative, weak, moderate and strong staining was 32%, 19%, 18% and 31% respectively for benign phyllodes, 24%, 13%, 10% and 53% respectively for borderline and 8%, 16%, 17% and 59% respectively for frankly malignant tumours. There was correlation between epithelial and stromal staining, and the stromal staining correlated with histological features of stromal cellularity, stromal cell nuclear pleomorphism, margin status and stromal overgrowth. CONCLUSION: These observations suggest a close relationship between the epithelial and stromal elements in phyllodes tumours; endothelin may play a significant role in the malignant progression of phyllodes tumours.