Endovascular management of visceral artery aneurysms: When to watch,when to intervene?

Visceral artery aneurysms (VAA) include splanchnic and renal artery aneurysms. They represent a rare clinical entity, although their detection is rising due to an increased use of cross-sectional imaging. Rupture is the most devastating complication, and is associated with a high morbidity and mortality. In addition, increased percutaneous endovascular interventions have raised the incidence of iatrogenic visceral artery pseudoaneurysms (VAPAs). For this reason, elective repair is preferable in the appropriately chosen patient. Controversy still exists regarding their treatment. Over the past decade, there has been steady increase in the utilization of minimally invasive, non-operative interventions, for vascular aneurysmal disease. All VAAs and VAPAs can technically be fixed by endovascular techniques but that does not mean they should. These catheter-based techniques constitute an excellent approach in the elective setting. However, in the emergent setting it may carry a higher morbidity and mortality. The decision for intervention has to take into account the size and the natural history of the lesion, the risk of rupture, which is high during pregnancy, and the relative risk of surgical or radiological intervention. For splanchnic artery aneurysms, we should recognize that we are not, in reality, well informed about their natural history. For most asymptomatic aneurysms, expectant treatment is acceptable. For large, symptomatic or aneurysms with a high risk of rupture, endovascular treatment has become the first-line therapy. Treatment of VAPAs is always mandatory because of the high risk of rupture. We present our point of view on interventional radiology in the splanchnic arteries, focusing on what has been achieved and the remaining challenges.     

Impact of home oxygen therapy on hospital stay for infants with acute bronchiolitis

Acute bronchiolitis has been associated with an increasing hospitalization rate over the past decades. The aim of this paper was to estimate the impact of home oxygen therapy (HOT) on hospital stay for infants with acute bronchiolitis. A retrospective cohort study was done including all children aged ??12?months discharged from a pediatric tertiary-care center with a diagnosis of bronchiolitis, between November 2007 and March 2008. Oxygen was administered according to a standardized protocol. We assumed children with the following criteria could have been sent home with O₂, instead of being kept in hospital: age ??2?months, distance between home and hospital <50?km, in-hospital observation ??24?h, O₂ requirement ??1.0?L/min, stable clinical condition, no enteral tube feeding, and intravenous fluids <50?mL/kg/day. Children with significant underlying disease were excluded. A total of 177 children were included. Median age was 2.0?months (range 0?C11), and median length of stay was 3.0?days (range 0?C18). Forty-eight percent of patients (85/177) received oxygen during their hospital stay. Criteria for discharge with HOT were met in 7.1?% of patients, a mean of 1.8?days (SD 1.8) prior to real discharge. The number of patient-days of hospitalization which would have been saved had HOT been available was 21, representing 3.0?% of total patient-days of hospitalization for bronchiolitis over the study period (21/701). Conclusions: In this study setting, few children were eligible for an early discharge with HOT. Home oxygen therapy would not significantly decrease the overall burden of hospitalization for bronchiolitis.     

Identification of suitable qPCR reference genes in leaves of Brassica oleracea under abiotic stresses

Real-time quantitative PCR is nowadays a standard method to study gene expression variations in various samples and experimental conditions. However, to interpret results accurately, data normalization with appropriate reference genes appears to be crucial. The present study describes the identification and the validation of suitable reference genes in Brassica oleracea leaves. Expression stability of eight candidates was tested following drought and cold abiotic stresses by using three different softwares (BestKeeper, NormFinder and geNorm). Four genes (BolC.TUB6, BolC.SAND1, BolC.UBQ2 and BolC.TBP1) emerged as the most stable across the tested conditions. Further gene expression analysis of a drought- and a cold-responsive gene (BolC.DREB2A and BolC.ELIP, respectively), confirmed the stability and the reliability of the identified reference genes when used for normalization in the leaves of B. oleracea. These four genes were finally tested upon a benzene exposure and all appeared to be useful reference genes along this toxicological condition. These results provide a good starting point for future studies involving gene expression measurement on leaves of B. oleracea exposed to environmental modifications.     

Nitric oxide signaling in the brain: A new target for inhaled nitric oxide?

Nitric oxide (NO) is a powerful vasodilator, involved in both physiological functions and pathophysiological alterations of various regulatory processes, for example, the maintenance of vascular tone and inflammation. The recently demonstrated impact of exogenous NO on the central nervous system extends its role under normal and pathological conditions. At times neuroprotective, at times neurotoxic, NO is capable of different effects depending upon the extent of cerebral damage, the cellular redox state, and the spatiotemporal coordinates and concentration at which it is synthesized. This review provides new insights into the short‐ and long‐term effects of endogenous and exogenous NO in brain injury. ANN NEUROL 2013;73:442–448     

Association of RANTES G-403A gene polymorphism with increased risk of coronary arteriosclerosis

Aims Polymorphisms in the RANTES (G-403A), monocyte chemoattractantprotein-1 (MCP-1; A-2518G), stromal cell-derived factor-1ß(SDF-1ß; G801A), and C–C chemokine receptor-5(CCR5; 32) genes have been associated with functional effects.These chemokines have been implicated in leucocyte recruitmentto arterial lesions. In a case-control study, we explored relationsbetween these polymorphisms and coronary artery disease (CAD),with respect to angiographic abnormalities and acute coronarysyndromes (ACS). Methods and Results The LUdwigshafen Risk and Cardiovascularhealth (LURIC) cohort was genotyped by RFLP-PCR. Based on coronaryangiography, individuals were sub-divided into CAD cases and controls . RANTES-403 genotype frequencies were significantly different in cases and controls, as were A allele carrier frequencies (36.01% vs. 30.19%, OR=1.30 [95%-CI=1.06–1.60], ). By multivariate analysis, RANTES A-403 retained significantassociation with CAD . RANTES A-403 was associated with increased ACS prevalence (OR=1.36 [95%-CI=1.08–1.71],). MCP-1 G-2518, SDF-1ß A801, and CCR5 32 were not associated with CAD. Conclusions RANTES A-403 was associated with CAD independentlyfrom conventional risk factors and CRP or fibrinogen as inflammatorybiomarkers. The association was enhanced in smokers and ACS,conditions where platelet activation and inflammation predominate.RANTES A-403 may increase genetic susceptibility to CAD.     

Model-Based Determination of Effective Blood Concentrations of Cyclosporine for Neutrophil Response in the Treatment of Severe Aplastic Anemia in Children

Optimal immunosuppressive therapy in acquired severe aplastic anemia (SAA) remains to be refined, especially cyclosporine (CsA) use. Current recommendations state that CsA trough blood concentrations (TBC) should be maintained between 200 and 400 ng/mL despite the lack of supporting data. This study aimed at quantifying relationships between CsA exposure and neutrophil response and determining an effective range for CsA TBC. Twenty-three SAA patients treated with CsA were retrospectively analyzed. Nonlinear mixed effect modeling approaches were used to develop a pharmacokinetic-pharmacodynamic model. The pharmacokinetic model described the relationships between CsA doses and TBC. The pharmacodynamic model allowed to estimate boundaries for optimal CsA effects, neutrophils being used as biomarker of response. A time-to-event model linked effective concentration to time-to-therapeutic success. CsA TBC were adequately described by a two-compartment model with first-order absorption, a lag time, and a linear elimination. The efficient range of CsA TBC was estimated between 87 and 120 ng/mL. Model-based simulations and external validation in three additional patients confirmed these results. This original modeling approach was successful in describing the relationship between CsA TBC and neutrophil response in SAA patients. Although further evaluation of the model is necessary, this work suggests that an optimal CsA TBC target of 100 ng/mL would be associated with a better neutrophil response in children with SAA.KEY WORDS: aplastic anemia, cyclosporine, modeling, pharmacokinetics, regulatory T lymphocytes     

A Review of Neuroimaging Findings in Repetitive Brain Trauma

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease confirmed at postmortem. Those at highest risk are professional athletes who participate in contact sports and military personnel who are exposed to repetitive blast events. All neuropathologically confirmed CTE cases, to date, have had a history of repetitive head impacts. This suggests that repetitive head impacts may be necessary for the initiation of the pathogenetic cascade that, in some cases, leads to CTE. Importantly, while all CTE appears to result from repetitive brain trauma, not all repetitive brain trauma results in CTE. Magnetic resonance imaging has great potential for understanding better the underlying mechanisms of repetitive brain trauma. In this review, we provide an overview of advanced imaging techniques currently used to investigate brain anomalies. We also provide an overview of neuroimaging findings in those exposed to repetitive head impacts in the acute/subacute and chronic phase of injury and in more neurodegenerative phases of injury, as well as in military personnel exposed to repetitive head impacts. Finally, we discuss future directions for research that will likely lead to a better understanding of the underlying mechanisms separating those who recover from repetitive brain trauma vs. those who go on to develop CTE.     

Y-chromosome descent clusters and male differential reproductive success: young lineage expansions dominate Asian pastoral nomadic populations

High-frequency microsatellite haplotypes of the male-specific Y-chromosome can signal past episodes of high reproductive success of particular men and their patrilineal descendants. Previously, two examples of such successful Y-lineages have been described in Asia, both associated with Altaic-speaking pastoral nomadic societies, and putatively linked to dynasties descending, respectively, from Genghis Khan and Giocangga. Here we surveyed a total of 5321 Y-chromosomes from 127 Asian populations, including novel Y-SNP and microsatellite data on 461 Central Asian males, to ask whether additional lineage expansions could be identified. Based on the most frequent eight-microsatellite haplotypes, we objectively defined 11 descent clusters (DCs), each within a specific haplogroup, that represent likely past instances of high male reproductive success, including the two previously identified cases. Analysis of the geographical patterns and ages of these DCs and their associated cultural characteristics showed that the most successful lineages are found both among sedentary agriculturalists and pastoral nomads, and expanded between 2100 BCE and 1100 CE. However, those with recent origins in the historical period are almost exclusively found in Altaic-speaking pastoral nomadic populations, which may reflect a shift in political organisation in pastoralist economies and a greater ease of transmission of Y-chromosomes through time and space facilitated by the use of horses.