Stromal cell-derived factor 1/CXCR4 signaling is critical for early human T-cell development.

The present study investigated the potential role of stromal cell-derived factor 1 (SDF-1) in human intrathymic T-cell differentiation. Results show that SDF-1 is produced by human thymic epithelial cells from the subcapsular and medullary areas, and its receptor, CXCR4, is up-regulated on CD34(+) precursor cells committed to the T-cell lineage. Chimeric human-mouse fetal thymus organ culture (FTOC) seeded with purified CD34(+) thymic progenitors and treated with neutralizing antibodies against SDF-1 or CXCR4 showed a significant reduction of the number of human thymocytes and an arrested thymocyte differentiation in the transition between CD34(+) precursor cells and CD4(+) immature thymocytes. SDF-1-treated FTOC showed an increase of human thymocyte numbers, mainly affecting the most immature subpopulations. Moreover, these results suggest that CXCR4/SDF-1 signaling is not critical for the CD34(+) cell precursor recruitment to the thymus. On the other hand, SDF-1 significantly increased the viability of CD34(+) T-cell precursors modulating the expression of BCL-2 and BAX genes, and stimulated the proliferation of CD34(+) thymic precursor cells, particularly in synergy with interleukin 7 (IL-7), but not with other cytokines, such as stem cell factor or flt3-ligand. Accordingly, only IL-7 was able to up-regulate CXCR4 expression on CD34(+) thymic progenitors. In addition, deprivation of SDF-1 partially inhibited human thymocyte expansion induced by IL-7 in human-mouse FTOC. This study indicates that SDF-1/CXCR4 signaling is required for the survival, expansion, and subsequent differentiation of human early thymocytes and identifies a new mechanism by which IL-7 mediates its effects on human thymopoiesis.     

Risk factors for development of dehydration in young children with acute watery diarrhoea: a case-control study

In a case-control study to understand the risk factors for development of life-threatening dehydration, a total of 379 children comprising 243 cases (moderate or severe dehydration) and 136 controls (non or mild dehydration) up to 2 years of age suffering from acute watery diarrhoea were studied. By univariate analysis, the presence of vibrios in stool, withdrawal of breast feeding during diarrhoea, not giving fluids, including oral rehydration solution (ORS), during diarrhoea, frequent purging (> 8/ day), vomiting (> 2/day) and undernutrition were identified as risk factors. However, by multivariate analysis after controlling for confounders, withdrawal of breast feeding during diarrhoea (odds ratio (OR) = 6.8, p < 0.00001) and not giving ORS during diarrhoea (OR = 2.1, p < 0.006) were identified as significant risk factors. The confounding variables which also contributed significantly to increasing the risk were age (≤ 12 months; OR = 2.7, p = 0.001), frequent purging (> 8/day; OR = 4.1, p < 0.00001), vomiting (> 2/day; OR = 2.4, p = 0.001) and severe undernutrition (%median <60 weight-for-age of Indian Academy of Paediatrics classification; OR = 3.1, p = 0.001). We feel that these findings will be useful for Global and National Diarrhoeal Diseases Control Programmes for formulating intervention strategies for preventing death due to diarrhoeal dehydration.     

HIV seroprevalence in street youth, St. Petersburg, Russia

BACKGROUND: Reliable data on HIV infection among Russian street youth are unavailable. The purpose of this study was to assess HIV seroprevalence among street youth in St Petersburg and to describe social, sexual, and behavioral characteristics associated with HIV infection. METHODS: A cross-sectional assessment conducted during January-May 2006 included city-wide mapping of 41 street youth locations, random selection of 22 sites, rapid HIV testing for all consenting 15-19-year-old male and female street youth at these sites, and an interviewer-administered survey. Adjusted odds ratios (AOR) were calculated using logistic regression, accounting for intracluster homogeneity. RESULTS: Of 313 participants, 117 (37.4%, 95% confidence interval 26.1-50.2%) were HIV infected. Subgroups with the highest seroprevalences included double orphans (64.3%), those with no place to live (68.1%), those previously diagnosed with a sexually transmitted infection (STI; 70.5%), those currently sharing needles (86.4%), and those currently using inhalants (60.5%) or injection drugs (78.6%), including Stadol (82.3%) or heroin (78.1%). Characteristics independently associated with HIV infection included injecting drugs (AOR 23.0), sharing needles (AOR 13.3), being a double or single orphan (AOR 3.3 and 1.8), having no place to live (AOR 2.4), and being diagnosed with a STI (AOR 2.1). Most HIV-infected street youth were sexually active (96.6%), had multiple partners (65.0%), and used condoms inconsistently (80.3%). DISCUSSION: Street youth aged 15-19 years in St Petersburg, Russia, have an extraordinarily high HIV seroprevalence. In street youth who are injection drug users, HIV seroprevalence is the highest ever reported for eastern Europe and is among the highest in the world.     

Immunosensory signalling by carotid body chemoreceptors

Injections of lipopolysaccharide (LPS) have been used to produce the signs of sepsis and study their underlying mechanisms. Intravenous (IV) injections of LPS in anesthetized cats induce tachypnea, tachycardia and hypotension, but ventilatory changes are suppressed after sectioning carotid and aortic nerves. Otherwise, LPS increases the basal frequency of carotid chemosensory discharges, but reduces ventilatory and chemosensory responses to hypoxia and nicotine injections. Increases in cytokines (IL-1β, IL-6 and TNF-α) are observed in plasma and tissues after injecting LPS. In carotid bodies perfused in vitro, TNF-α reduces chemosensory discharges induced by hypoxia. The rat carotid body and its sensory ganglion constitutively express LPS canonical receptor, TLR4, as well as TNF-α and its receptors (TNF-R1 and TNF-R2). Increases of TNF-α and TNF-R2 expression occur after LPS administration. The activation of peripheral and central autonomic pathways induced by LPS or IL's is partly dependent on intact vagus nerves. Thus, the carotid and vagus nerves provide routes between the immune system and CNS structures involved in systemic inflammatory responses.     

Pseudomembranes in reflux esophagitis

Three cases are presented in which double-contrast esophagograms revealed one or more plaquelike lesions in the distal esophagus, representing pseudomembrane formation in patients with severe reflux esophagitis. Although to our knowledge this finding has not been reported previously in the radiologic literature, pseudomembranes have been documented endoscopically in patients with reflux esophagitis and biopsy-proved Barrett esophagus. Radiologists should be aware of this finding, since these pseudomembranes may be indistinguishable radiographically from plaquelike carcinomas arising in Barrett esophagus.     

Sensitivity Analysis and Model Assessment: Mathematical Models for Arterial Blood Flow and Blood Pressure

The complexity of mathematical models describing the cardiovascular system has grown in recent years to more accurately account for physiological dynamics. To aid in model validation and design, classical deterministic sensitivity analysis is performed on the cardiovascular model first presented by Olufsen, Tran, Ottesen, Ellwein, Lipsitz and Novak (J Appl Physiol 99(4):1523–1537, 2005). This model uses 11 differential state equations with 52 parameters to predict arterial blood flow and blood pressure. The relative sensitivity solutions of the model state equations with respect to each of the parameters is calculated and a sensitivity ranking is created for each parameter. Parameters are separated into two groups: sensitive and insensitive parameters. Small changes in sensitive parameters have a large effect on the model solution while changes in insensitive parameters have a negligible effect. This analysis was successfully used to reduce the effective parameter space by more than half and the computation time by two thirds. Additionally, a simpler model was designed that retained the necessary features of the original model but with two-thirds of the state equations and half of the model parameters.