Low-dose CT was noninferior to standard-dose CT with respect to negative appendectomy rates in young adults with suspected appendicitis. (Funded by GE Healthcare Medical Diagnostics and others; ClinicalTrials.gov number, NCT00913380.).

No abstract

The lung is highly vulnerable during sepsis, yet its functional deterioration accompanied by disturbances in the pulmonary microcirculation is poorly understood. This study aimed to investigate how the pulmonary microcirculation is distorted in sepsis-induced acute lung injury (ALI) and reveal the underlying cellular pathophysiologic mechanism.Using a custom-made intravital lung microscopic imaging system in a murine model of sepsis-induced ALI, we achieved direct real-time visualisation of the pulmonary microcirculation and circulating cellsin vivo. We derived the functional capillary ratio (FCR) as a quantitative parameter for assessing the fraction of functional microvasculature in the pulmonary microcirculation and dead space.We identified that the FCR rapidly decreases in the early stage of sepsis-induced ALI. The intravital imaging revealed that this decrease resulted from the generation of dead space, which was induced by prolonged neutrophil entrapment within the capillaries. We further showed that the neutrophils had an extended sequestration time and an arrest-like dynamic behaviour, both of which triggered neutrophil aggregates inside the capillaries and arterioles. Finally, we found that Mac-1 (CD11b/CD18) was upregulated in the sequestered neutrophils and that a Mac-1 inhibitor restored the FCR and improved hypoxaemia.Using the intravital lung imaging system, we observed that Mac-1-upregulated neutrophil aggregates led to the generation of dead space in the pulmonary microcirculation that was recovered by a Mac-1 inhibitor in sepsis-induced ALI.

No abstract

BackgroundStudies have shown that long‐term exposure to air pollution such as fine particulate matter (≤2.5 μm in aerodynamic diameter [PM 2.5]) increases the risk of all‐cause and cardiovascular mortality. To date, however, there are limited data on the impact of air pollution on specific cardiovascular diseases. This study aimed to evaluate cardiovascular effects of long‐term exposure to air pollution among residents of Seoul, Korea.Methods and ResultsHealthy participants with no previous history of cardiovascular disease were evaluated between 2007 and 2013. Exposure to air pollutants was estimated by linking the location of outdoor monitors to the ZIP code of each participant's residence. Crude and adjusted analyses were performed using Cox regression models to evaluate the risk for composite cardiovascular events including cardiovascular mortality, acute myocardial infarction, congestive heart failure, and stroke. A total of 136 094 participants were followed for a median of 7.0 years (900 845 person‐years). The risk of major cardiovascular events increased with higher mean concentrations of PM 2.5 in a linear relationship, with a hazard ratio of 1.36 (95% confidence interval, 1.29–1.43) per 1 μg/m3 PM 2.5. Other pollutants including PM 2.5–10 of CO, SO 2, and NO 2, but not O3, were significantly associated with increased risk of cardiovascular events. The burden from air pollution was comparable to that from hypertension and diabetes mellitus.ConclusionsThis large‐scale population‐based study demonstrated that long‐term exposure to air pollution including PM 2.5 increases the risk of major cardiovascular disease and mortality. Air pollution should be considered an important modifiable environmental cardiovascular risk factor.

The prognostic performance of the L/A ratio was superior to that of a single lactate measurement for predicting 28-day mortality of critically ill sepsis patients. L/A ratio can be a useful prognostic factor regardless of initial lactate level and the presence of hepatic or renal dysfunction.

No abstract

mice. Together, our findings suggest that the interaction between the dopaminergic system and leptin signaling in hypothalamus is important in control of energy homeostasis.Dopamine is the main catecholamine in the brain. It serves important regulatory roles in many neural functions, including the control of locomotion, neuroendocrine hormone release, cognition, emotive behavior, reward, and memory (1). Dopamine is also a critical neurotransmitter in the control of feeding behavior. It is generally accepted that the dopaminergic pathway is primarily involved in the regulation of reward-related behaviors, including feeding behaviors. Dopamine regulates these behaviors through the mesolimbic dopaminergic pathways, which project from the ventral tegmental area (VTA) 4 to the limbic region, including the nucleus accumbens. Dopamine signaling in these reward-related circuits seems to control for different reward values, including food rewards (2, 3).The cellular and molecular mechanism by which dopamine controls food intake through these dopaminergic mesolimbic pathways remains largely unknown. Recent findings propose that hormones regulating energy homeostasis, such as leptin and insulin, can modulate the midbrain dopaminergic system to regulate feeding behavior (4, 5). However, it is not known if the action of these hormones in VTA regions of the midbrain would be physiologically relevant, because there are very few functional receptors of leptin or insulin in this region (3-5). Dopamine is presumed to regulate feeding via hypothalamic circuits in the brain (6 -10). Dopaminergic neurons project to the arcuate nucleus and to the median eminence of the hypothalamus. These projections may influence the function of hypothalamic neurons involved in ingestive behaviors. Pharmacological studies using D 1 -and D 2 -like receptor agonists and antagonists demonstrated that modulation of dopamine receptor activity in the hypothalamus could regulate food intake (11-16). However, the mechanism by which dopaminergic neurotransmission in the hypothalamus regulates food intake has yet to be defined. Different reports on the role of dopamine on food intake have yielded contradictory results. Contradictions may be due to the differential actions of dopamine on different hypothalamic areas or the involvement of different receptor subtypes.Binding of dopamine to the dopamine D 2 receptor is crucial for the regulation of diverse physiological functions, such as the control of locomotor activity, reward-related behavior, and the *