Rate of change in adiposity and its relationship to concomitant changes in cardiovascular risk variables among biracial (black-white) children and young adults: The Bogalusa Heart Study

To assess the annual rate of change in adiposity and its relationship to concomitant changes in cardiovascular risk variables during childhood and young adulthood, serial data on black and white children (n = 3,459; initial and follow-up mean age, 8.1 and 14.4 years) and young adults (n = 1,263; initial and follow-up mean age, 22.5 and 30.9 years) enrolled in the Bogalusa Heart Study were examined. Body mass index (BMI) and sum of subscapular and triceps skinfolds were used as indicators of adiposity. In addition, measurements were made of systolic and diastolic blood pressure and fasting levels of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides, insulin, and glucose. Annualized rate of change for each variable was estimated. The rate of increase in adiposity was significantly more pronounced during childhood versus adulthood. Race difference (blacks > whites) in the rate of increase in adiposity was seen only among females. Females, black females in particular, displayed greater rate of increase in adiposity than males. In a multivariate analysis, the rate of increase in adiposity was related independently of baseline age and baseline adiposity to adverse changes in measured cardiovascular risk variables, except glucose. Many of these associations were modulated significantly by race, sex, and age group. The impact was relatively greater for blood pressure and LDL cholesterol in adults and for triglycerides in children. The changes in blood pressure, LDL cholesterol, and HDL cholesterol were greater in whites, while the rate of increase in insulin was greater in blacks. Females displayed greater changes in blood pressure, HDL cholesterol, and insulin. On the other hand, the rate of increase in triglycerides was greater in males. These results indicate that increases in adiposity regardless of initial status of body fatness alter cardiovascular risk variables towards increased risk beginning in childhood, and that this deleterious trend underscores the importance of weight control early in life.     

Aberrant retropharyngeal (submucosal) internal carotid artery: an under-recognized, clinically significant variant

We present a case of a 71-year-old woman who was incidentally found to have aberrant retropharyngeal internal carotid artery, lying very close to the pharyngeal mucosa, on imaging. Radiologists, otolaryngologists and anaesthetists should be aware of this clinically significant variant which can result in life-threatening bleeding during procedures in the oral cavity or oropharynx.     

Clinical profile of acute kidney injury in a pediatric intensive care unit from Southern India: A prospective observational study

Background:

Although the term acute renal failure was replaced by acute kidney injury (AKI) recently, there is a paucity of data on the incidence and profile of AKI in critically ill children from the developing world.

Objectives:

The objective of this study is to determine the incidence, etiology, short term outcome and predictors of fatality in critically ill children admitted to the pediatric intensive care unit (PICU) with AKI, aged 1 month to 13 years.

Materials and Methods:

In this prospective observational study, from June 2010 to March 2011, 215 children admitted to the PICU were screened for AKI, defined according to the AKI Network criteria. The patients with AKI were followed-up until discharge/death. Their clinical and biochemical data were recorded.

Results:

The incidence of AKI among 215 patients screened was 54 (25.1%). The common etiologies were infections, [34 (62.9%)], acute glomerulonephritis (7.6%), snake envenomation (5.7%), hemolytic uremic syndrome (3.8%) and congestive cardiac failures (3.8%). Among infections, pneumonia and septicemia constituted 26.5% each, meningoencephalitis accounted for 23.5%, and dengue, scrub typhus, tuberculosis and malaria constituted 9.3% of children with AKI. 27.8% of patients required dialysis. Overall mortality was 46.3%. On logistic regression analysis, requirement of mechanical ventilation was an independent predictor of fatality in AKI.

Conclusions:

Besides the high incidence of AKI in critically ill-children admitted to the PICU (25.1%), the condition was associated with adverse outcomes, including high mortality (46.3%) and need for dialysis (27.8%). Infections dominated the etiological profile. Requirement of mechanical ventilation predicted an adverse outcome in our patient population.     

The Diagnostic Dilemma of a Parasympathetic Schwannoma in the Submandibular Gland

Schwannomas are benign soft tissue tumours that arise from nerve sheath cells. They are rare in the salivary glands and are thought to arise from the parasympathetic nerves. We report the case of a 69-year-old man who presented with a painless right submandibular mass that appeared to resemble a pleomorphic adenoma on ultrasonography and, on this basis, proceeded to surgical excision of the gland. We review the relevant literature and highlight the diagnostic pitfalls.     

Mutant G protein alpha subunit activated by Gbeta gamma: a model for receptor activation?

How receptors catalyze exchange of GTP for GDP bound to the Galpha subunit of trimeric G proteins is not known. One proposal is that the receptor uses the G protein's betagamma heterodimer as a lever, tilting it to pull open the guanine nucleotide binding pocket of Galpha. To test this possibility, we designed a mutant Galpha that would bind to betagamma in the tilted conformation. To do so, we excised a helical turn (four residues) from the N-terminal region of alpha(s), the alpha subunit of G(S), the stimulatory regulator of adenylyl cyclase. In the presence, but not in the absence, of transiently expressed beta(1) and gamma(2), this mutant (alpha(s)Delta), markedly stimulated cAMP accumulation. This effect depended on the ability of the coexpressed beta protein to interact normally with the lip of the nucleotide binding pocket of alpha(s)Delta. We substituted alanine for an aspartate in beta(1) that binds to a lysine (K206) in the lip of the alpha subunit's nucleotide binding pocket. Coexpressed with alpha(s)Delta and gamma(2), this mutant, beta(1)-D228A, elevated cAMP much less than did beta(1)-wild type; it did bind to alpha(s)Delta normally, however, as indicated by its unimpaired ability to target alpha(s)Delta to the plasma membrane. We conclude that betagamma can activate alpha(s) and that this effect probably involves both a tilt of betagamma relative to alpha(s) and interaction of beta with the lip of the nucleotide binding pocket. We speculate that receptors use a similar mechanism to activate trimeric G proteins.     

A physical basis for protein secondary structure

A physical theory of protein secondary structure is proposed and tested by performing exceedingly simple Monte Carlo simulations. In essence, secondary structure propensities are predominantly a consequence of two competing local effects, one favoring hydrogen bond formation in helices and turns, the other opposing the attendant reduction in sidechain conformational entropy on helix and turn formation. These sequence specific biases are densely dispersed throughout the unfolded polypeptide chain, where they serve to preorganize the folding process and largely, but imperfectly, anticipate the native secondary structure.     

Involvement of guanine nucleotide binding proteins in neutrophil activation and priming by GM-CSF

Pre-incubation of human neutrophils with pertussis toxin significantly inhibited the neutrophil-directed biologic actions of granulocyte- macrophage colony-stimulating factor (GM-CSF) in three separate assays: the induction of c-fos mRNA, the enhancement of both platelet- activating factor-induced mobilization of intracellular calcium, and stimulation of leukotriene synthesis by the calcium ionophore A23187. Cholera toxin did not have an effect on the latter two assays. Pre- treatment of human neutrophils with pertussis toxin did not affect the binding of GM-CSF to its surface receptor. These results provide the first evidence that a pertussis toxin substrate plays an important mediatory role in the mechanism of action of GM-CSF.     

Calibration and optimization of 3D digital breast tomosynthesis guided near infrared spectral tomography

Calibration of a three-dimensional multimodal digital breast tomosynthesis (DBT) x-ray and non-fiber based near infrared spectral tomography (NIRST) system is challenging but essential for clinical studies. Phantom imaging results yielded linear contrast recovery of total hemoglobin (HbT) concentration for cylindrical inclusions of 15 mm, 10 mm and 7 mm with a 3.5% decrease in the HbT estimate for each 1 cm increase in inclusion depth. A clinical exam of a patient’s breast containing both benign and malignant lesions was successfully imaged, with greater HbT was found in the malignancy relative to the benign abnormality and fibroglandular regions (11 μM vs. 9.5 μM). Tools developed improved imaging system characterization and optimization of signal quality, which will ultimately improve patient selection and subsequent clinical trial results.OCIS codes: (120.3890) Medical optics instrumentation, (170.0110) Imaging systems, (170.3830) Mammography