Correlation of carotid artery reactivity with cardiovascular risk factors and coronary artery vasodilator responses in asymptomatic, healthy volunteers.

OBJECTIVES: Carotid artery reactivity (CAR%), involving carotid artery diameter responses to a cold pressor test (CPT), is a noninvasive measure of conduit artery function in humans. This study examined the impact of age and cardiovascular risk factors on the CAR% and the relationship between CAR% and coronary artery vasodilator responses to the CPT. METHODS: Ultrasound was used to measure resting and peak carotid artery diameters during the CPT, with CAR% being calculated as the relative change from baseline (%). We compared CAR% between young (n = 50, 24 ± 3 years) and older participants (n = 44, 61 ± 8 years), and subsequently assessed relationships between CAR% and traditional cardiovascular risk factors in 50 participants (44 ± 21 years). Subsequently, we compared left anterior descending (LAD) artery velocity (using transthoracic Doppler) with carotid artery diameter (i.e. CAR%) during the CPT (n = 33, 37 ± 17 years). RESULTS: A significantly larger CAR% was found in young versus older healthy participants (4.1 ± 3.7 versus 1.8 ± 2.6, P < 0.001). Participants without cardiovascular risk factors demonstrated a higher CAR% than those with at least two risk factors (2.9 ± 2.9 versus 0.5 ± 2.9, P = 0.019). Carotid artery diameter and LAD velocity increased during CPT (P < 0.001). Carotid diameter and change in velocity correlated with LAD velocity (r = 0.486 and 0.402, P < 0.004 and 0.02, respectively). CONCLUSION: Older age and cardiovascular risk factors are related to lower CAR%, while CAR% shows good correlation with coronary artery responses to the CPT. Therefore, CAR% may represent a valuable technique to assess cardiovascular risk, while CAR% seems to reflect coronary artery vasodilator function

Non-small cell lung carcinoma in an adolescent manifested by acute paraplegia due to spinal metastases: a case report

<p>Abstract</p> <p>Introduction</p> <p>Bronchial carcinomas in childhood and adolescence are extremely rare; only individual cases have been reported previously.</p> <p>Case presentation</p> <p>We report on a 16-year-old Caucasian German boy with non-small cell lung carcinoma (squamous cell non-small cell lung carcinoma) stage IV, T4N2M1, without epidermal growth factor receptor overexpression and/or mutation or k-ras mutation. He presented with paraplegia due to spinal metastases of the bronchial carcinoma. No familial predisposition or toxin exposure was identified. Treatment following adult protocols consisted of surgical intervention for spinal metastases, first-line cisplatinum and gemcitabine, irradiation and second-line docetaxel. After a transient response our patient experienced disease progression and died about 10 months later.</p> <p>Conclusion</p> <p>Response and survival in our 16-year-old patient were similar to adult patients with stage IV non-small cell lung carcinoma.</p

High energy emission from microquasars

The microquasar phenomenon is associated with the production of jets by X-ray binaries and, as such, may be associated with the majority of such systems. In this chapter we briefly outline the associations, definite, probable, possible, and speculative, between such jets and X-ray, gamma-ray and particle emission.Comment: Contributing chapter to the book Cosmic Gamma-Ray Sources, K.S. Cheng and G.E. Romero (eds.), to be published by Kluwer Academic Publishers, Dordrecht, 2004. (19 pages

Catalytic Roles of Flexible Regions at the Active Site of Ribulose-Bisphosphate Carboxylase/Oxygenase (Rubisco)

Chemical and mutagenesis studies of Rubisco have identified Lys329 and Glu48 as active-site residues that are located in distinct, interacting domains from adjacent subunits. Crystallographic analyses have shown that Lys329 is the apical residue in a 12-residue flexible loop (loop 6) of the {Beta},{alpha}-barrel domain of the active site and that Glu48 resides at the end of helix B of the N-terminal domain of the active site. When phosphorylated ligands are bound by the enzyme, loop 6 adopts a closed conformation and, in concert with repositioning of helix B, thereby occludes the active site from the external environment. In this closed conformation, the {gamma}-carboxylate of Glu48 and the {epsilon}-amino group of Lys329 engage in intersubunit electrostatic interaction. By use of appropriate site-directed mutants of Rhodospirillum rubrum Rubisco, we are addressing several issues: the catalytic roles of Lys329 and Glu48, the functional significance of the intersubunit salt bridge comprised of these two residues, and the roles of loop 6 and helix B in stabilizing labile reaction intermediates. Characterization of novel products derived from misprocessing of D-ribulose-1,5-bisphosphate (RuBP) by the mutant proteins have illuminated the structure of the key intermediate in the normal oxygenase pathway

Estimating the number of children exposed to parental psychiatric disorders through a national health survey

<p>Abstract</p> <p>Objective</p> <p>Children whose parents have psychiatric disorders experience an increased risk of developing psychiatric disorders, and have higher rates of developmental problems and mortality. Assessing the size of this population is important for planning of preventive strategies which target these children.</p> <p>Methods</p> <p>National survey data (CCHS 1.2) was used to estimate the number of children exposed to parental psychiatric disorders. Disorders were diagnosed using the World Psychiatric Health Composite International Diagnostic Interview (WMH-CIDI) (12 month prevalence). Data on the number of children below 12 years of age in the home, and the relationship of the respondents with the children, was used to estimate exposure. Parent-child relations were identified, as was single parenthood. Using a design-based analysis, the number of children exposed to parental psychiatric disorders was calculated.</p> <p>Results</p> <p>Almost 570,000 children under 12 live in households where the survey respondent met criteria for one or more mood, anxiety or substance use disorders in the previous 12 months, corresponding to 12.1% of Canadian children under the age of 12. Almost 3/4 of these children have parents that report receiving no mental health care in the 12 months preceding the survey. For 17% of all Canadian children under age 12, the individual experiencing a psychiatric disorder is the only parent in the household.</p> <p>Conclusion</p> <p>The high number of children exposed causes major concern and has important implications. Although these children will not necessarily experience adversities, they possess an elevated risk of accidents, mortality, and of developing psychiatric disorders. We expect these estimates will promote further research and stimulate discussion at both health policy and planning tables.</p

Vaccine Platforms Combining Circumsporozoite Protein and Potent Immune Modulators, rEA or EAT-2, Paradoxically Result in Opposing Immune Responses

Malaria greatly impacts the health and wellbeing of over half of the world's population. Promising malaria vaccine candidates have attempted to induce adaptive immune responses to Circumsporozoite (CS) protein. Despite the inclusion of potent adjuvants, these vaccines have limited protective efficacy. Conventional recombinant adenovirus (rAd) based vaccines expressing CS protein can induce CS protein specific immune responses, but these are essentially equivalent to those generated after use of the CS protein subunit based vaccines. In this study we combined the use of rAds expressing CS protein along with rAds expressing novel innate immune response modulating proteins in an attempt to significantly improve the induction of CS protein specific cell mediated immune (CMI) responses.BALB/cJ mice were co-vaccinated with a rAd vectors expressing CS protein simultaneous with a rAd expressing either TLR agonist (rEA) or SLAM receptors adaptor protein (EAT-2). Paradoxically, expression of the TLR agonist uncovered a potent immunosuppressive activity inherent to the combined expression of the CS protein and rEA. Fortunately, use of the rAd vaccine expressing EAT-2 circumvented CS protein's suppressive activity, and generated a fivefold increase in the number of CS protein responsive, IFNγ secreting splenocytes, as well as increased the breadth of T cells responsive to peptides present in the CS protein. These improvements were positively correlated with the induction of a fourfold improvement in CS protein specific CTL functional activity in vivo.Our results emphasize the need for caution when incorporating CS protein into malaria vaccine platforms expressing or containing other immunostimulatory compounds, as the immunological outcomes may be unanticipated and/or counter-productive. However, expressing the SLAM receptors derived signaling adaptor EAT-2 at the same time of vaccination with CS protein can overcome these concerns, as well as significantly improve the induction of malaria antigen specific adaptive immune responses in vivo

Mitoxantrone pleurodesis to palliate malignant pleural effusion secondary to ovarian cancer

BACKGROUND: Advanced ovarian cancer is the leading non-breast gynaecologic cause of malignant pleural effusion. Aim of this study was to assess the efficacy of mitoxantrone sclerotherapy as a palliative treatment of malignant pleural effusions due to ovarian cancer. METHODS: Sixty women with known ovarian cancer and malignant recurrent symptomatic pleural effusion were treated with chest tube drainage followed by intrapleural mitoxantrone sclerotherapy. Survival, complications and response to pleurodesis were recorded. The data are expressed as the mean ± SEM and the median. RESULTS: The mean age of the entire group was 64 ± 11,24 years. The mean interval between diagnosis of ovarian cancer and presentation of the effusion was 10 ± 2,1 months. Eighteen patients (30%) had pleural effusion as the first evidence of recurrence. The mean volume of effusion drained was 1050 ± 105 ml and chest tube was removed within 4 days in 75% of patients. There were no deaths related to the procedure. Side effects of chemical pleurodesis included fever (37–38,5°C) chest pain, nausea and vomiting. At 30 days among 60 treated effusions, there was an 88% overall response rate, including 41 complete responses and 12 partial responses. At 60 days the overall response was 80% (38 complete responses and 10 partial responses). The mean survival of the entire population was 7,5 ± 1,2 months. CONCLUSIONS: Mitoxantrone is effective in the treatment of malignant pleural effusion secondary to ovarian cancer without causing significant local or systemic toxicity

Persistent Cell Motion in the Absence of External Signals: A Search Strategy for Eukaryotic Cells

Eukaryotic cells are large enough to detect signals and then orient to them by differentiating the signal strength across the length and breadth of the cell. Amoebae, fibroblasts, neutrophils and growth cones all behave in this way. Little is known however about cell motion and searching behavior in the absence of a signal. Is individual cell motion best characterized as a random walk? Do individual cells have a search strategy when they are beyond the range of the signal they would otherwise move toward? Here we ask if single, isolated, Dictyostelium and Polysphondylium amoebae bias their motion in the absence of external cues. We placed single well-isolated Dictyostelium and Polysphondylium cells on a nutrient-free agar surface and followed them at 10 sec intervals for ~10 hr, then analyzed their motion with respect to velocity, turning angle, persistence length, and persistence time, comparing the results to the expectation for a variety of different types of random motion. We find that amoeboid behavior is well described by a special kind of random motion: Amoebae show a long persistence time (~10 min) beyond which they start to lose their direction; they move forward in a zig-zag manner; and they make turns every 1-2 min on average. They bias their motion by remembering the last turn and turning away from it. Interpreting the motion as consisting of runs and turns, the duration of a run and the amplitude of a turn are both found to be exponentially distributed. We show that this behavior greatly improves their chances of finding a target relative to performing a random walk. We believe that other eukaryotic cells may employ a strategy similar to Dictyostelium when seeking conditions or signal sources not yet within range of their detection system.Comment: 15 pages, 11 figures, accepted for publication in PLOS On

Population-Specific Responses to Interspecific Competition in the Gut Microbiota of Two Atlantic Salmon (Salmo salar) Populations

The gut microbial community in vertebrates plays a role in nutrient digestion and absorption, development of intestine and immune systems, resistance to infection, regulation of bone mass and even host behavior and can thus impact host fitness. Atlantic salmon (Salmo salar) reintroduction efforts into Lake Ontario, Canada, have been unsuccessful, likely due to competition with non-native salmonids. In this study, we explored interspecific competition effects on the gut microbiota of two Atlantic salmon populations (LaHave and Sebago) resulting from four non-native salmonids. After 10 months of rearing in semi-natural stream tanks under six interspecific competition treatments, we characterized the gut microbiota of 178 Atlantic salmon by parallel sequencing the 16S rRNA gene. We found 3978 bacterial OTUs across all samples. Microbiota alpha diversity and abundance of 27 OTUs significantly differed between the two populations. Interspecific competition reduced relative abundance of potential beneficial bacteria (six genera of lactic acid bacteria) as well as 13 OTUs, but only in the LaHave population, indicating population-specific competition effects. The pattern of gut microbiota response to interspecific competition may reflect local adaptation of the host-microbiota interactions and can be used to select candidate populations for improved species reintroduction success