From "traction bronchiectasis" to honeycombing in idiopathic pulmonary fibrosis: A spectrum of bronchiolar remodeling also in radiology?

The diagnostic and prognostic impact of traction bronchiectasis on high resolution CT scan (HRCT) in patients suspected to have idiopathic pulmonary fibrosis (IPF) is increasing significantly

Obstetric near-miss cases among women admitted to intensive care units in Italy

Objective. Maternal near-miss defines a narrow category of morbidity encompassing potentially life-threatening episodes. The purpose of this study was to detect near-miss instances among women admitted to intensive care units or coronary units, analyze associated causes, and compute absolute and specific maternal morbidity rates in six Italian regions. Design. Observational retrospective study. Setting. Six Italian regions representing 49% of all resident Italian women aged 15-49 years. Population. The study population included all pregnant women aged 15-49 years admitted to intensive care units or coronary care units in the participating regions. Cases were defined as women aged 15-49 years resident in the participating regions, with one or more hospitalizations in intensive care for pregnancy or any pregnancy outcome between 2004 and 2005. Methods. Cases were identified through the Hospital Discharge Database. Enrolled cases were diagnosed according to the 9th International Classification of Diseases. Main outcome measure. Maternal near-miss rate (number of women experiencing an admission to intensive care units/all women with live or stillborn babies). Results. A total of 1259 near-miss cases were identified and the total maternal near-miss rate was 2.0/1000 deliveries. Seventy percent of the women were admitted to intensive care units or coronary units after a cesarean section. The leading associated risk factors were obstetric hemorrhage/disseminated intravascular coagulation (40%) and hypertensive disorders of pregnancy (29%). Conclusions. Monitoring of near-miss morbidity in conjunction with mortality surveillance could help to identify effective preventive measures for potentially life-threatening episodes

Fumarate Reductase Activity Maintains an Energized Membrane in Anaerobic Mycobacterium tuberculosis

Oxygen depletion of Mycobacterium tuberculosis engages the DosR regulon that coordinates an overall down-regulation of metabolism while up-regulating specific genes involved in respiration and central metabolism. We have developed a chemostat model of M. tuberculosis where growth rate was a function of dissolved oxygen concentration to analyze metabolic adaptation to hypoxia. A drop in dissolved oxygen concentration from 50 mmHg to 0.42 mmHg led to a 2.3 fold decrease in intracellular ATP levels with an almost 70-fold increase in the ratio of NADH/NAD+. This suggests that re-oxidation of this co-factor becomes limiting in the absence of a terminal electron acceptor. Upon oxygen limitation genes involved in the reverse TCA cycle were upregulated and this upregulation was associated with a significant accumulation of succinate in the extracellular milieu. We confirmed that this succinate was produced by a reversal of the TCA cycle towards the non-oxidative direction with net CO2 incorporation by analysis of the isotopomers of secreted succinate after feeding stable isotope (13C) labeled precursors. This showed that the resulting succinate retained both carbons lost during oxidative operation of the TCA cycle. Metabolomic analyses of all glycolytic and TCA cycle intermediates from 13C-glucose fed cells under aerobic and anaerobic conditions showed a clear reversal of isotope labeling patterns accompanying the switch from normoxic to anoxic conditions. M. tuberculosis encodes three potential succinate-producing enzymes including a canonical fumarate reductase which was highly upregulated under hypoxia. Knockout of frd, however, failed to reduce succinate accumulation and gene expression studies revealed a compensatory upregulation of two homologous enzymes. These major realignments of central metabolism are consistent with a model of oxygen-induced stasis in which an energized membrane is maintained by coupling the reductive branch of the TCA cycle to succinate secretion. This fermentative process may offer unique targets for the treatment of latent tuberculosis

Open-system orchestration as a relational source of sensing capabilities: Evidence from a venture association

Research on innovation networks has highlighted the pivotal role that actors with more prominence and power, such as hub firms, may play in orchestrating the activities of other network members along a collective innovation effort. Our study examined the undertheorized, but no less important, type of orchestration that characterizes other organizations, such as business incubators and venture associations, who seek to support the dispersed entrepreneurial efforts of network members. We refer to this type as ‘open-system’ orchestration, as opposed to the commonly studied ‘closed-system’ type performed by hub firms. Our findings reveal how the processes of open-system orchestration differ markedly from those of closed-system orchestration, and detail how these processes influence the micro-foundations of network members’ sensing capabilities. By doing so, we also offer empirical substantiation and theoretical elaboration to the idea that dynamic capabilities might not reside exclusively inside firms, but could be co-created relationally with other parties in the business ecosystem